Forum Médical Suisse Forum Medico Svizzero Schweizerisches Medizin

Transcription

Forum Médical Suisse
Forum Medico Svizzero
Schweizerisches Medizin-Forum
17.5.2013
Supplementum 60
Online-Publikation
auf www.medicalforum.ch
Swiss Medical Forum
81. Jahresversammlung
der Schweizerischen Gesellschaft für Allgemeine Innere Medizin
81e Assemblée annuelle
de la Société Suisse de Médecine Interne Générale
81a Riunione annuale
della Società Svizzera di Medicina Interna Generale
81st Annual Meeting
of the Swiss Society of General Internal Medicine
Basel, 29.–31. Mai 2013
Editores Medicorum Helveticorum
Offizielles Fortbildungsorgan der FMH www.medicalforum.ch
Organe officiel de la FMH pour la formation continue www.medicalforum.ch
Bollettino ufficiale per la formazione della FMH www.medicalforum.ch
Inhalt / Sommaire
FM 105 - FM 107
S. 5 - 7
Presidential Symposium SGH
FM 222 – FM 225
S. 8 - 10
Freie Mitteilungen SGIM - Infektiologie / Immunologie
Communications libres SSMI - Infectiologie / Immunologie
FM 226 – FM 229
S. 11 - 13
Freie Mitteilungen SGIM - Allgemeine Innere Medizin 1
Communications libres SSMI - Médecine interne générale 1
FM 230 – FM 233
S. 14 - 16
Freie Mitteilungen SGIM - Notfallmedizin
Communications libres SSMI – Urgences
FM 234 – FM 237
S. 17 - 19
Freie Mitteilungen SGIM - Communications libres SSMI 2
Allgemeine Innere Medizin - Médecine interne générale 2
FM 238– FM 241
S. 20 - 22
Freie Mitteilungen SGIM - Communications libres SSMI
Kardiologie / Pneumologie - Cardiologie / Pneumologie
FM 242– FM 245
S. 23 - 26
Allgemeine Innere Medizin 3 - Médecine interne générale 3
FM 246– FM 248
S. 27 - 28
Bluthochdruck - Hypertension artérielle
FM 249– FM 252
S. 29 - 31
Endokrinologie - Endocrinologie
FM 253– FM 258
S. 32 - 36
Beste Freie Mitteilungen – Meilleur Communication libres
1
FM 259– FM 262
S. 37 - 39
Multimorbidität - Multimorbidité
FM 263– FM 270
S. 40 - 44
Freie Mitteilungen SGH - Communications libres SSH
Experimental Hematology - Experimental Hematology
FM 271 - FM 278
S. 45 - 49
Freie Mitteilungen SFGG - Communications libres SPSG
FM 279– FM 284
S. 50 - 53
Hemostasis, Vascular Biology and Transfusion Medicine
FM 285 – FM 292
S. 54 - 62
Clinical Hematology
P 293 – P 302
S. 63 - 68
Beste 10 Poster SGIM –
Meilleur 10 posters SSMI
P 303 – P 310
S. 69 - 75
Postesession 1 - Session des posters 1
P 311 - P 318
S. 76 - 80
P 319 - P 326
S. 81 - 88
Allgemeine Innere medizin 3 - Médecine interne générale 3
P 327 - P 334
2
S. 89 - 96
P 335 - P 342
S. 97 - 104
P 343 - P 350
S. 105 - 109
Onkologie – Notfallmedizin / Psychiatrie / Neurologie
Oncologie - Urgences / Psychiatrie - Neurologie
P 351 – P 359
S. 110 - 116
Psychiatrie / Neurologie - Arterieller Bluthochdruck – Endocrinologie - Diabetik
Psychiatrie / Neurologie - Néphrologie / Hypertension artérielle Endocrinologie
- Diabétologie
P 360 – P 367
S. 117 - 121
Infektiologie - Immunologie - Rheumatologie /
Infectiologie - Immunologie - Rhumatologie
P 368 – P 375
S. 122 - 127
Allgemeine Innere Medizin - Infektiologie / Immunologie / Rheumatologie Médecine interne générale - Infectiologie/Immunologie/Rhumatologie
P 376 – P 384
S. 128 - 135
Kardiologie - Pneumologie - Gastroenterologie 1 /
Cardiologie - Pneumologie - Gastroentérologie 1
P 385 – P 392
S. 136 - 142
Cardiologie / Pneumologie / Gastroentérologie 2
P 393 – P 394
S. 143 - 144
Postersession SFGG - Session des posters SPSG
P 395 – P 402
S. 145 - 153
3
P 403 – P 410
S. 154 - 160
P 411 – P 419
S. 161 - 165
P 420 – P 428
S. 166 - 172
P 429 – P 437
S. 173 - 178
P 438 – P 443
S. 179 - 182
Postersession SGH - Session des posters SSH
Hemostasis, Vascular Biology and Transfusion
P 444 – P 464
S. 183 - 197
Clinical Hematology
Autorenliste / Liste des auteurs
4
S. 198 - 213
Presidential Symposium SGH
Presidential Symposium SSH
105
Imetelstat rapidly induces and maintains substantial haematologic and
molecular responses in patients with essential thrombocythaemia (ET) who are
refractory or intolerant to prior therapy: preliminary phase II results
Gabriela Baerlocher*, Elisabeth Oppliger Leibundgut, Christina Ayran, Martha Blaney, Bart Burington,
Dianne Morfeld, Olatoyosi Odenike, Oliver Ottman, Anita Reddy, Alexander Roeth, Gary Spitzer,
Monic Stuart, Srdan Verstovsek, David Snyder
Hematology, University Hospital Bern (Bern, CH); Geron Corporation (Menlo Park, CA, US); University
of Chicago (Chicago, IL, US); Hematology, University Hospital of Frankfurt (Frankfurt, DE);
Hematology, University Hospital Essen (Essen, DE); Upstate Oncology Associates (Greenville, SC,
US); University of Houston (Houston, TX, US); Hematology and HCT, City of Hope (Duarte, CA, US)
Background: Myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), are
driven by neoplastic progenitor cells (NPC). The JAK2 V617F mutation is detected in approx. 50% of
patients (pts) with ET, and its burden can be used to measure the treatment-induced molecular
response (MR). Telomerase is upregulated in NPC and sustains indefinite replication. Imetelstat (Imet)
is a first in class, potent, specific inhibitor of telomerase which selectively distributes to bone marrow
and inhibits thrombopoiesis.
Methods: A phase II study enrolled pts with ET who had failed or were intolerant to at least one prior
therapy, or who refused standard therapy. Pts were treated with Imet 7.5 mg/kg or 9.4 mg/kg IV
weekly. After attainment of best platelet (plt) response in the induction phase, maintenance therapy
(MT) with Imet was commenced with dosing based upon plt count. Primary endpoint was best overall
hematologic response (HR) with complete response (CR) defined as plt count <400 x 10^3/µl
maintained for at least 4 consecutive weeks in the absence of new thromboembolic events. A key
secondary endpoint was rate of MR in pts with JAK2 V617F. JAK2 V617F allele burden was measured
by allele-specific qRT-PCR. CFU-Meg growth and tolerability were also assessed.
Results: As of October 10th, 2012, 14 pts were treated. Median (md) age was 60 yrs with a md of 2
prior treatments. Md years since initial diagnosis were 5.8 and md initial plt count was 788 x 10^3/µl.
Best overall HR was 100%, with 13 of 14 pts achieving a confirmed CR after a md of 6.1 weeks.
Thirteen of 14 pts remain on MT. Six pts have reached 1 year of therapy and continue to be treated
with ongoing HR. Dosing frequency on MT was reduced with time. A substantial decrease in JAK2
V617F allele burden (mean allele burden reduction of 82%) was demonstrated in all 7 JAK2 V617Fpositive pts. A reduction in CFU-Meg was also observed. Common adverse events reported were mild
to moderate gastrointestinal toxicities, reductions in neutrophil counts, and fatigue.
Conclusions: Imet rapidly induces and maintains HR in pts with ET who have failed or are intolerant to
conventional therapies. Importantly, substantial MR is observed in all JAK2 V617F-positive pts and
inhibition of CFU-Meg is demonstrated. These results suggest that Imet has a relatively selective
inhibitory effect on the growth of the neoplastic clone(s) which drive ET and has the potential to modify
the underlying biology of MPNs.
106
Hereditary thrombocytosis caused by a novel germ-line mutation in the
gelsolin gene
Annalisa Pianta*, Pontus Lundberg, Kun Liu, Hui Hao-Shen, Renate Looser, Robert Kralovics,
Takafumi Shimizu, Amy Shapiro, Radek Skoda
Department of Biomedicine (Basel, CH); CeMM Research Center for Molecular Medicine (Vienna,
AT); Indiana Hemophilia Thrombosis (Indianapolis, US)
Introduction: Hereditary thrombocytosis (HT) is a familial myeloproliferative disorder characterized by
an elevated platelet count in peripheral blood. Activating mutations in the thrombopoietin (THPO) gene
and the gene for the THPO receptor, MPL, account for approximately 10% of HT. However, in about
90% of HT the disease-causing gene remains unknown. Here we study a large family with 12 affected
family members in 5-generations with HT. Disease transmission is autosomal dominant with high
penetrance.
Methods: Mutations in MPL and THPO were excluded by capillary sequencing. Genome-wide linkage
analysis was performed on DNA from 21 family members using microsatellites and single nucleotide
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polymorphism arrays. All genes within the co-segregating region were sequenced by classical DNA
sequencing and by Next Generation Sequencing. Computational analysis, platelet-biogenesis in vitro
assay and transgenic mice were used to prove the function of the mutation.
Results: Linkage analysis defined a single co-segregating region on chromosome 9 with a LOD score
of 4.3 (a LOD score of >3.3 is considered proof for linkage). Sequencing of all exons and splice
junctions within this chromosomal interval revealed a candidate mutation. The alteration, a C/T
transversion resulting in a Gly to Cys amino acid change, was observed in the gene encoding for
gelsolin. Computational predictions of the protein structure showed that this single amino acid change
is very likely to affect protein function since the alteration is located at the interface where gelsolin
interacts with actin. Platelet-biogenesis in vitro assays showed that the candidate alteration increased
the release of platelets-like particles in DAMI cell line stably transfected with the mutant gelsolin. To
study the in vivo role of the candidate mutation, transgenic mice expressing the human mutant gelsolin
were generated. These mice developed thrombocytosis and increased numbers of megakaryocytes.
Conclusion: We describe a familial isolated thrombocytosis caused by a mutation in gelsolin, a gene
not previously linked to any hematological disorder. Transgenic mice expressing mutant gelsolin
showed an increased platelet count and number of megakaryocytes, thus recapitulating the phenotype
observed in the family. The exact mechanism of how this newly identified genetic alteration leads to
increased megakaryocytopoiesis needs further investigation
107
Investigation into the role of protein S in platelets
Sara Calzavarini*, Francois Saller, Laurent Burnier, Monica Azevedo, Debora Sanches Rodrigues,
Anne Brisset, Jose Fernandez, John H Griffin, Anne Angelillo-Scherrer
Centre Hospitalier Universitaire Vaudois (Lausanne, CH); AP-HP, Hôpital Paré (Paris, FR); Molecular
and Experimental Medicine, The Scripps Research Institute, (La Jolla, US); DSM Nutritional Products
Ltd Branch Pentapharm (Basel, CH)
Background: Anticoagulant protein S (PS) is essential for maintaining the haemostatic balance. Our
previous characterization of PS deficiency in mouse models has shown similarities with the human
phenotypes: heterozygous PS-deficient mice had increased thrombotic risk whereas homozygous
deficiency in PS was incompatible with life. Most of the PS in plasma is thought to be synthesized by
hepatocytes, however the PS gene (ProS) is also expressed by several other cell types, including
megakaryocytes (MK). In particular, about 2.5% of PS is stored in platelets and released upon platelet
stimulation. So far, little is known about the functionality and importance of platelet PS (pltPS).
Methods and Results: Mice carrying a conditional protein S knockout allele in MK lineage were
established using the Pf4 promoter as Cre drivers (ProSLox/LoxPf4Cre+). ProSLox/Lox Pf4Cre+ mice
did not have detectable PS levels in platelet lysates (n=5) but normal levels in plasma (88.9±4.6%,
n=19), as assessed by antigenic assays. Comparative analyses of complete blood counts established
that these animals retained a normal blood cell profile. Platelets were tested for their functionality ex
vivo by Platelet Function Analyzer-200 (PFA-200) and by light transmission aggregometry using
6
collagen and ADP as agonists, without showing any difference compared to ProSLox/Lox mice.
Differently, tail clipping test showed a relevant decrease of bleeding time compared to ProSLox/Lox
mice (P=0.021). When challenged in a tissue factor-induced thromboembolism model, ProSLox/Lox
Pf4Cre+ (n=15) mice exhibited a notable thrombotic phenotype in vivo (survival rate 46.7% compared
to 85.8%, ProSLox/Lox mice, n=14; P<0.05).
Beside its role on activated protein C, PS acts as cofactor of tissue factor pathway inhibitor alpha
(TFPI alpha) in the inhibition of factor Xa (FXa). The complete deletion of ProS gene in MK lineage did
not affect TFPI alpha expression, as assessed by antigenic assay of platelet lysates. Preliminary data
on PS cofactor activity toward TFPI alpha indicate that the absence of PS in platelet lysates abolish
the capacity of TFPI alpha to inhibit FXa, as assessed by amidolytic activity assay.
Conclusions: All together these data suggest that pltPS is delivered at the site of thrombosis to
counterbalances procoagulant activities on platelets thus inhibiting thrombus growth. Upon release,
pltPS may function as an anticoagulant protein enhancing the TFPI-dependent anticoagulant pathway.
7
Infektiologie / Immunologie - Infectiologie / Immunologie
FM222
Increasing incidence and atypical presentation of tularaemia in Switzerland
Urs Karrer*, Jan Amort, Silke Polsfuss, Paola Pilo, Jacques Gubler, Guido Bloemberg
Cantonal Hospital of Winterthur (Winterthur, CH); University of Zurich (Zürich, CH); University of Bern
(Bern, CH)
Background: Tularemia has been a very rare disease in Switzerland with ~7 cases (range: 2-13)
annually from 2004 to 2009 despite mandatory reporting since 2004. Most cases presented as typical
arthropod bite associated (ulcero)glandular disease. The diagnosis was mainly confirmed by F.
tularensis serology, by molecular diagnostics (i.e. PCR) and only rarely by culture of F. tularensis. In
2010/11 we have seen a moderate increase of tularemia to 14 and 13 annual cases, respectively.
However, a total of 37 confirmed tularemia cases were reported to the national authorities in 2012.
Methods: We performed a retrospective epidemiological and clinical analysis of all confirmed cases of
tularemia in Switzerland between 2004 and 2012 (n=98). Detailed review of clinical data, molecular
diagnostics and management was performed for ~50% of cases since 2010.
Results: Incidence rates of tularemia have increased 10-fold between 2004 (0.04/100’000 inhabitants)
and 2012 (0.46/100’000). Maximal rates of up to 1 case/100’000 were noted in the cantons of Zurich,
Aargau and Lucerne. More detailed epidemiological analyses will be presented to indicate the
establishment of true ‘hot spots’.
Overall, the clinical pattern of tularemia has not significantly changed over time: 55% of patients
present with local (ulcero)glandular disease while 32% suffered from systemic disease, mostly
pneumonia. During the past decade, one patient with tularemia died and 60% were hospitalised. In
2012, 4 of our 6 patients presented with unusual disease manifestations, namely severe sepsis with
macrophage activation syndrome, empyema of a pneumonectomy cavity, perimyocarditis and local
tularemia secondary to a bussard attack. Molecular diagnostics allowed the timely diagnosis and
treatment of these patients. While a short course (5-10 days) of intravenous aminoglycoside combined
with oral Doxycyclin (14-42 days) was successful in all patients with systemic disease oral therapy
was usually sufficient for local disease. Nevertheless, surgical drainage was required in up to 50% of
patients with lymphadenitis.
Discussion: In certain areas of Switzerland, incidence of tularemia has increased to a level which is
relevant to the general practitioner. Epidemiological data are best explained by a true increase in
disease incidence and not just by a reporting bias. The broad clinical spectrum and appropriate
management of the disease will be discussed in light of the changing epidemiology.
FM223
Progressive proximal muscle weakness after cessation of statin use: a case of
statin-triggered autoimmunity
Laetitia Mauti*, Veronika Kana, Stephan Regenass, Cäcilia Reiner, Herbert Budka, Dominik Schaer,
Irene Studer
Universitätsspital Zürich (Zürich, CH); Universitätsspital Zürich (Zürich, CH); Universitätsspital Zürich
(Zürich, CH); Universitätsspital Zürich (Zürich, CH); Universitätsspital Zürich (Zürich, CH)
Introduction: Statins are a widely used for the treatment of dyslipidemia and secondary prophylaxis
after cardio-vascular events. While the major side effect of reversible statin-induced myopathy is well
known, a new kind of statin-induced myopathy has recently been described, which persists after
discontinuation of the drug.
Case Report: We report the case of a 73-year-old woman with gradually progressive, painless,
symmetrical proximal muscle weakness developing 3 years after the initiation of treatment with
atorvastatin. The highly elevated creatinine-kinase levels did not decline nor did symptoms improve
more than six weeks after discontinuation of the statin. MRI showed diffuse signal enhancement in all
proximal muscle groups and muscle biopsy yielded histological findings compatible with statin-induced
necrotizing auto-immune myopathy (NAM). ELISA for antibodies against HMGCR (3-Hydroxy-3Methylglutaryl-Coenzym-A-reductase) was positive. The patient was started on immunosuppressants
and symptoms improved along with a rapid reduction of creatinine-kinase levels.
Discussion: Recently, a new form of myopathy associated with statin use has been described. Statininduced necrotizing auto-immune myopathy is mediated by antibodies against HMGCR. This enzyme,
8
which is blocked by statins, seems to become up-regulated in regenerating muscle fibers after an
initial - possibly statin-induced - minor lesion. This statin-triggered auto-immune disease persists upon
discontinuation of statins and requires longtime immuno-suppressive treatment.
FM224
Simple and fast prediction of Legionella species in community-acquired
pneumonia. Validation of a prediction rule
Sebastian Haubitz*, Fabienne Hitz, Lena Graedel, Marcus Batschwaroff, Timothy Lee Wiemken,
Paula Peyrani Dicastelnuovo, Julio Ramirez, Christoph Fux, Beat Mueller, Philipp Schuetz
Kantonsspital Aarau (Aarau, CH); Universität Basel (Basel, CH); University of Louisville (Louisville,
US)
Introduction: Ruling out Legionella sp. in patients presenting with community acquired pneumonia
(CAP) besides the low prevalence is important due to differences in treatment regimens. Antigen tests
as well as blood cultures have low sensitivity and ofthen there is an important time delay making
empirical broad spectrum coverage necessary particularly in severe cases. Fiumefreddo et al. recently
proposed a clinical score based on 6 clinical and laboratory variables (fever, cough, sodium, lactatedehydrogenase, C-reactive protein, platelet count) which allowed assessing the likelihood of
Legionella[1]. Yet, this prediction tool needs validation in an independent patient cohort before
implementation into clinical routine.
Methods: We analyzed data from a large multinational database of patients with CAP (CAPO)[2]
between 2001 and 2012, includiung 8278 patients at the time of analysis. Patients were excluded if
less than 5 of the 6 variables were available. In the remaining 1046 patients we performed logistic
regression analysis and area under the receiver operating characteristics (ROC) curve to study the
association of these variables with the diagnosis of Legionella.
Results: The propagated score using 6 dichotomized variables shows good diagnostic performance
with an area under the ROC curve of 0.84. Performance increased markedly when the continuous
variables were applied in the regression equation utilizing the original coefficients, area under ROC
curve: 0.91.
Conclusions: This analysis validates the Legionella score in an independent sample and shows high
diagnostic accuracy. Interventional trials with adapted antibiotic regimes for non-inferiority in a real live
population are warranted.
References:
[1] Fiumefreddo R, Zaborsky R, Haeuptle J, et al. Clinical predictors for Legionella in patients
presenting with community-acquired pneumonia to the emergency department. BMC pulm medicine
2009; 9:4-4
[2] Ramirez JA. Fostering international multicenter collaborative research: the CAPO Project. Int J
Tuberc Lung Dis 2007; 11:1062-1065
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FM225
Measles vaccination in Switzerland: results of a population-based survey on
vaccination coverage and determinants in 2012
Monica Wymann*, Mirjam Mäusezahl-Feuz
Bundesamt für Gesundheit (Bern, CH)
Introduction: In December 2011 the Federal Council passed the National Strategy on Measles
Elimination 2011–2015. One of the goals is that in accordance with WHO guidelines 95% of all
children are vaccinated with 2 doses of measles vaccine by the age of 2. An essential factor for the
evaluation of this goal is the knowledge of the vaccination coverage. Since 1999 national data is
collected for 2-, 8- and 16-year-olds through the Swiss National Vaccination Coverage Survey
(SNVCS). In addition in 2012 the Federal Office of Public Health (FOPH) conducted a measles
baseline survey to collect vaccination coverage data, to assess reasons for and against vaccination
and knowledge and attitude towards measles vaccination and elimination.
Methods: Computer assisted telephone interviews were conducted with parents of 2 to16-year-olds
and with young adults (20 to 29-year-olds) by a professional provider. Following the telephone
interview, respondents were asked to send their or their child’s vaccination card to the FOPH. A total
of 3237 interviews were conducted, 1814 with parents of children (N=1535 vaccination cards received)
and 1423 with young adults (N=807 vaccination cards).
Results: Vaccination coverage was 95% for 1 dose and 89% for 2 doses in 2-year-olds; 95% for 1
dose and 90% for 2 doses in 3 to 16-year-olds; and 93% for 1 dose and 77% for 2 doses in 20 to 29year-olds. Main reasons to vaccinate children on time were their parents’ wish to protect them (58.5%)
and recommendation by the pediatrician/general practitioner (GPs) (48.2%). Late vaccinations (first
dose after 2nd birthday) had been in 20% of cases directly recommended by the pediatrician/GPs.
43% of the young unvaccinated adults and 34% of parents of unvaccinated children showed a
willingness to vaccinate themselves or their child in order to help reach measles elimination.
Knowledge about measles was, especially in young adults, marked by uncertainty.
Conclusions: The results on point vaccination coverage in this survey are congruent with the SNVCS
data. As in the SNVCS coverage with 2 doses in 2-year-olds is still clearly below the targeted 95%.
Pediatricians and GPs play a key role as motivators for parents to vaccinate their children on time, but
organizational problems as well as insufficient knowledge in the general public seem to be part of the
problem as well. Unified efforts on the structural as well as communicational level are needed to reach
the goal of measles elimination in Switzerland.
10
FM226
Polypharmacy is associated with an increased risk of bleeding in elderly
patients with venous thromboembolism
Waltraud Leiss*, Marie Méan, Andreas Limacher, Marc Righini, Kurt Jaeger, Hans-Jürg Beer, Joseph
Osterwalder, Beat Frauchiger, Christian M. Matter, Nils Kucher, Anne Angelillo-Scherrer, Jacques
Cornuz, Martin Banyai, Bernhard Lämmle, Marc Husmann, Michael Egloff, Markus Aschwanden,
Henri Bounameaux, Nicolas Rodondi, Drahomir Aujesky
Bern University Hospital (Bern, CH); University of Bern (Bern, CH); Geneva University Hospital
(Genève, CH); Basel University Hospital (Basel, CH); Cantonal Hospital of Baden (Baden, CH);
Cantonal Hospital of St. Gallen (St. Gallen, CH); Cantonal Hospital of Frauenfeld (Frauenfeld, CH);
University of Zurich and Zurich University Hospital (Zürich, CH); Lausanne University Hospital
(Lausanne, CH); University of Lausanne (Lausanne, CH); Cantonal Hospital of Lucerne (Luzern, CH);
Zurich University Hospital and University of Zurich (Zürich, CH)
Background: Venous thromboembolism (VTE) often affects multimorbid older patients who take
multiple concomitant drugs (polypharmacy). Although drug interactions with vitamin K antagonists are
a potential cause of excessive anticoagulation and bleeding, whether polypharmacy increases
bleeding risk in elderly patients with VTE is uncertain.
Methods: In a multicenter Swiss cohort study, we prospectively enrolled consecutive patients aged
>=65 years who received vitamin K antagonists for acute VTE between September 2009 and March
2012. The presence of polypharmacy, defined as the use of more than 4 different drugs, was
assessed at baseline. The outcome was the time to a first major bleeding, defined as fatal bleeding,
symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin >=20 g/L or leading to
the transfusion >=2 units of red blood cells. We assessed the association between polypharmacy and
the time to a first major bleeding using Cox proportional hazard analysis, adjusting for known bleeding
risk factors (age, gender, history of major bleeding, active cancer, chronic liver disease, chronic renal
disease, cardiac disease, thrombocytopenia, cerebrovascular disease, diabetes mellitus, anemia,
arterial hypertension, recent major surgery and presence of symptomatic pulmonary embolism).
Results: Of 830 enrolled patients, 413 (49.8%) had polypharmacy. The mean +-SD follow-up duration
was 17.8 +-9.3 months. The overall incidence of major bleeding was 6.4% per person-year. Patients
with polypharmacy had a significantly higher incidence of major bleeding than patients without (9.0%
vs. 4.1% per person-year; p=0.002). After multivariate adjustment, polypharmacy remained
significantly associated with major bleeding (hazard ratio 2.1, 95% confidence interval 1.2-3.5;
p=0.007). Patients with polypharmacy did not spend a higher percentage of time with an excessive
international normalized ratio (>3.0) than patients without (17.7% vs. 16.0%; p=0.18).
Conclusion: Polypharmacy is common in elderly patients receiving vitamin K antagonists for VTE, and
is an independent predictor of major bleeding. Further studies need to explore by which mechanism
polypharmacy increases the bleeding risk in elderly patients with VTE.
FM227
Physicians’ response to control of cardiovascular risk factors in Switzerland:
overtreatment, undertreatment or appropriate care?
Stefan Weiler*, Armin Gemperli, Tinh-Hai Collet, Douglas Bauer, Lukas Zimmerli, Jacques Cornuz,
Edouard Battegay, Jean-Michel Gaspoz, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi
Inselspital Bern (Bern, CH); CTU Bern (Bern, CH); University of Lausanne (Lausanne, CH); University
of California (San Francisco, CH); University Hospital of Zurich (Zürich, CH); University Hospitals of
Geneva (Genève, CH); University of Michigan (Ann Arbor, CH)
Background: Evaluating whether physicians respond appropriately to poor risk factor control better
reflects quality of care than measuring proportions in control. New measures of potential
overtreatment have been recently suggested. These quality measurements have mainly been
examined in US integrated healthcare systems and not in settings without systematic quality
monitoring.
Methods: We performed a retrospective cohort study of 1,002 randomly selected patients aged 50-80
years from four university primary care settings in Switzerland, a country without quality monitoring. In
regard to control of hypertension, dyslipidemia and diabetes, we assessed the proportion of patients in
11
poor control and defined “appropriate care” as a therapy modification or return to control without
therapy modification within 12 months. We also examined potential overtreatment of these conditions
and defined it as intensive treatment among low-risk patients who already have low target values.
Results: Within 12 months, 61% of patients experienced therapy modification for poor control of
hypertension, 33% for dyslipidemia, and 85% for diabetes. Increases in number of drug classes (2851%) and in drug doses (10-61%) were most common. 0-5% of poorly controlled conditions returned
to control without therapy modification. Patients with target organ damage and higher baseline values
were more likely to receive appropriate care. We found potential overtreatment among 2% of patients
for hypertension, 3% for diabetes and 4% for dyslipidemia.
Conclusions: High rates of appropriate care were observed for poorly controlled diabetes mellitus and
lower rates for hypertension and dyslipidemia. Overtreatment appears uncommon. Such measures
may provide a better picture of the quality of care than relying only on simple measures of proportions
in control.
FM228
Suspicion of heparin-induced thrombocytopenia in internal medicine: how
appropriate are anti-PF4 antibody tests?
Yan Beauverd*, Elena Tessitore, Françoise Boehlen, Eric Gerstel, Mathieu Nendaz, Arnaud Perrier,
Jean-Luc Reny
Hôpitaux Universitaires de Genève (Genève, CH)
Objective: To describe the clinical management of patients suspected of HIT and evaluate to what
extent the 4T’s score and the HEP score might safely decrease anti-PF4 antibodies testing in internal
medicine patients clinically suspected of type II heparin induced thrombocytopenia (HIT).
Methods: Internal medicine patients treated with unfractionated heparin (UFH), low molecular weight
heparin (LMWH) or fondaparinux in whom anti-PF4 were assayed were included. Non inclusion
criteria were absence of thrombocytopenia or fall of platelets count and transfer from another hospital.
Results: We included 74 patients over a 29-month period with a mean age of 68±16 years. 25 (34%)
were transferred from the intensive care Unit. 43 (58%) were treated with UFH, 31 (42%) with LMWH
and none with fondaparinux. Indication was thromboprophylaxis in 45 (61%) and therapeutic in 29
(39%). 11 patients (15%) tested positive for antiPF4 and 4 (5.4%) had confirmed HIT. Clinicians
documented the 4T’s score in only 10 (14%) patients and the HEP score was never used. The
retrospectively calculated 4T’s score was < 4 in 54 patients (73%) who would not have needed
antiPF4 testing (Table). HEP score was < 2 implying no antiPF4 testing was necessary in 34 patients
(46%, p<0.0001 compared to 4T’s). Both scores had a sensitivity of 100% (no patient with a score
below the cut-off had HIT). Specificity of 4Ts was 77% and that of HEP was 48%. Following anti-PF4
testing, clinicians stopped heparin in 48 patients (65%) among which 25 (34%) were switched to
fondaparinux while the remaining had either a transient or definitive anticoagulant arrest. In 3 patients,
a heparin-induced platelet aggregation (HIPA) test was performed (1 despite a 4T’s score <4). At three
months of follow-up none of the patients were readmitted for a HIT-related condition.
Conclusions: Validated and recommended scores for HIT were vastly underused in this internal
medicine population while they could have avoided 73% of the requested antiPF4 tests (4T’s) or 46%
(HEP) and have a high sensitivity and safety using the appropriate cut-offs.
12
FM229
International variation in GP treatment strategies for subclinical
hypothyroidism in older adults
Wendy P.J. den Elzen, Anne Lefèbre - van de Fliert, Vanessa Virgini*, Simon P. Mooijaart, Patricia
Kearney, Ngaire Kerse, Christian D. Mallen, Vera McCarthy, Christiane Muth, Peter Frey, Thomas
Rosemann, Audrey Russell, Henk Schers, David J. Stott, Margot W.M. de Waal, Alex Warner, Rudi
G.J. Westendorp, Nicolas Rodondi, Jacobijn Gussekloo
Leiden University Medical Center (Leiden, NL); Inselspital Bern (Bern, CH); Institute for Evidencebased Medicine in Old age (Leiden, NL); University College Cork (Cork, IE); The University of
Auckland (Auckland, NZ); Keele University (Keele, GB); Johann Wolfgang Goethe University
(Frankfurt, DE); BIHAM, Universität Bern (Bern, CH); Universitätsspital Zürich (Zürich, CH); Radboud
University Medical Center (Nijmegen, NL); University of Glasgow (Glasgow, GB); University College
London (London, GB)
Introduction: Since there is limited evidence about the impact of treatment of subclinical
hypothyroidism on clinical outcomes, especially in older persons, international consensus on the
management of subclinical hypothyroidism is lacking. We investigated the variation in treatment
strategies of GPs for older patients with subclinical hypothyroidism depending on patient
characteristics and country.
Methods: We assessed the treatment strategy of GPs (treatment yes/no, starting dose of thyroxine) for
eight cases presenting a woman with non-specific complaints and subclinical hypothyroidism. The 8
cases differed in patient characteristics age (70 vs 85 years), vitality status (vital vs. vulnerable) and
TSH concentration (6 vs. 15 mU/L). The NetQuestionnaire survey was emailed to GP networks in the
Netherlands, Germany, England, Ireland, Switzerland and New Zealand.
Results: A total of 524 GPs participated to the survey; 129 from the Netherlands, Switzerland n=262,
Germany n=61, England n=22, Ireland n=19, and New Zealand n=31. We found large variations
across countries, with % starting therapy going from 35% in the Netherlands, 54% in Switzerland to
75% in Germany. Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old
women (pooled OR, random effects model, 0.74 [95% CI 0.63-0.87]). Older women with TSH 15 mU/L
were more likely to get treated than women with TSH 6 mU/L (pooled OR 9.4 [95% CI 5.8-15.4).
Across countries, differences in treatment strategy were observed for each case, witth most
pronounced when TSH was 6 mU/L.
Discussion: GPs treatment strategies of older persons with subclinical hypothyroidism vary not only by
patient characteristics but also largely by country. This large variation underlines the need for
evidence about the effects of treatment of subclinical hypothyroidism by a good quality RCT targeting
clinical outcomes.
13
Notfallmedizin - Urgences
FM230
Frequent users of the emergency department in Switzerland: a prospective,
controlled, cross-sectional study
Patrick Bodenmann*, Fabrice Althaus, Stephanie Stucki, Corine Ansermet, Sophie Guyot, Katia
Iglesias, Sophie Paroz, Lionel Trueb, Olivier Hugli, Jean-Bernard Daeppen
Policlinique Médicale Universitaire (Lausanne, CH); Centre Hospitalier Universitaire Vaudois
(Lausanne, CH)
Introduction: A heterogeneous subgroup of patients account for a substantial proportion of all
emergency department (ED) visits. The aim of this study was to systematically describe frequent users
of the ED in Switzerland.
Methods: This prospective controlled cross-sectional study compared frequent users of the ED to nonfrequent users (control group), and was conducted from November 2009 to June 2010 at the
University Hospital of Lausanne. Frequent users were defined as patients with five or more visits to
the ED in the previous 12 months; they were compared to controls in terms of socio-demographic
characteristics, medical indicators, and health care use. Outcome measures were obtained through a
robust questionnaire using previously validated scales.
Results: During the study period, 24,277 patients attended the ED and 351 met the definition of
frequent user (1.4% of all ED patients). Frequent users made a total of 2,030 visits in the past year,
which represented 6.3% of the 32,441 visits made by all ED users during the same period. A total of
226 frequent users and 173 controls were interviewed. In a multivariate analysis, adjusted odds ratio
of being a frequent user was 23.2 (95% CI 9.1-59.2) for patients with three or more admissions to
hospital, 8.4 (95% CI 2.1-32.7) for patients who do not have a primary care practitioner (PCP), 4.4
(95% CI 2.1-9.0) for patients living close to the ED (less than 5 km), 4.3 (95% CI 2.0-9.2) for patients
with a household income lower than 3,000 Swiss Francs/month, 2.7 (95% CI 1.2-6.1) for patients who
had attended other EDs, 2.6 (95% CI 1.1-5.9) for patients having a moderate to severe tobacco use,
2.3 (95% CI 1.2-4.7) for patients having at least one mental problem (panic, anxiety, or mood
disorder), 1.2 (95% CI 1.1-1.4) with a change of one unit according to the Charlson Index (somatic comorbidities). The risk of being a frequent user was decreased by 74.8% (95% CI 0.1-0.5) for patients
with no admission to hospital, 72.5% (95% CI 0.1-0.9) for people attending for injuries, and 68.1%
(95% CI 0.1-0.7) for patients having a chronic somatic condition.
Conclusions: Frequent users of the ED are a socially and medically vulnerable population. These
results are helpful to better target the complex needs of frequent users of the ED: through better
connection with a PCP, availability of ED-based case management teams, and as also by informing
decisions about further services which should be provided to patients in the ED.
FM231
Evolution of some quality indicators after the opening of a 'fast track way'
(Notfallpraxis) in an emergency department
Mattia Lepori*, Massimo Trobia, Mario Lazzaro, Adriana Degiorgi
Ospedale Regionale (Bellinzona, CH); Ospedale Regionale (Lugano, CH)
Background: there are many quality indicators to evaluate the performance of an ED; some of them
are mainly addressed to the waiting times and the quickness of the take in charge of patients, often
influenced by the ED’s overcrowding, and causing patients’ dissatisfaction.
Aim: to evaluate the evolution of some quality indicators, before and after the opening of a “fast track
way” (FTW) in the ED of a regional hospital, for the least serious cases.
Methodology: we studied the evolution of 4 quality indicators related to to the waiting times and the
quickness of the take in charge of patients, comparing the data for two periods before (March-August
2011) and after (March-August 2012) the FTW’s opening.
Results: during the two observed periods, the number of patients was very similar, being of 11148
(2011) vs 11678 (2012), (P=NS). The measurement of the following indicators showed a favourable
evolution:
•
Take in charge of patients in less than 30 minutes: 86.4% vs 74.3% (P < 0.05)
•
Patients with waiting time higher than 90 minutes: : 4.4% vs 12.3% (P < 0.05)
•
Number of written complaints due to long waiting time: 0.7/month vs 7/month (P < 0.05)
14
•
Percentage of patients who left the ED before being visited: 0.87% vs 1.78% (P < 0.01)
Moreover, a survey (performed granting anonimity) among 500 FTW’s patients, showed a positive
appraisal (92%) of the services performed by this new unit.
Conclusion: the opening of a FTW for the least serious cases, improves the quality and the perception
of satisfaction of the ED’s patients.
FM232
Patient characteristics and patterns of intoxication: one-time and repeated use
of emergency ambulance services in Zurich
Nina Rosset, Barbara Holzer, Christoph Minder, Gabriela Schätti, Edouard Battegay, Stefan Müller,
Lukas Zimmerli*
UniversitätsSpital Zürich (Zürich, CH); Universität Zürich (Zürich, CH); Schutz und Rettung Zürich
(Zürich, CH)
Objective: Intoxication, whether from alcohol, drugs, or alcohol and drugs in combination, remains a
challenging burden on emergency services. The increasing alcohol consumption among adolescents
and young adults, particularly heavy episodic drinking, and the resulting increase in the use of health
care resources for alcohol intoxication has been a widely discussed topic.
The aim of this study was to investigate the utilization of ambulance services due to alcohol and drug
intoxication during 1 year in the greater metropolitan area of Zurich, Switzerland, with an emphasis on
characteristic differences between patients with one-time or repeated use.
Method: All ambulance services report forms filed in 2010 were systematically screened for
ambulance services utilizations where alcohol intoxication or intoxication due to consumption of illicit
or legal drugs was the chief complaint.
Results: The majority of the intoxicated patients recorded (92%, n=2156), used ambulance services
only once in 2010, whereas 8% of patients (n=185) were transported by ambulance services multiple
times. Men made up approximately 65% of the study population, for both one-time and repeated
users. Repeated users differed from persons with one-time use in their characteristics and patterns of
intoxication. On average, patients with repeated ambulance use were almost 8 years older and had a
different pattern of ambulance use over the course of the week with no clear peak on any specific day.
More than half of the one-time utilizations (64.3%) occurred on the weekend (Friday to Sunday), with a
clear peak on Saturday (Figure 1). The mean number of ambulance services in patients with repeated
use was 2.8 (SD = 1.517) in the 1-year study period: Repeated-users were less likely to be injured
than patients with one-time ambulance services use and more often showed aggression or
uncooperative behavior towards paramedics. All cases of death associated with intoxication involved
patients with one-time ambulance use.
Conclusions: The ambulance services users’ generally slight impairment of consciousness and the
high proportion of intoxicated patients without any injuries bring up the question of how many of these
patients could be adequately cared for in a sobering center. Sobering centers might relieve hospital
emergency units of patients not requiring acute emergency care and, in addition, could provide
intervention services to prevent relapses.
15
FM233
Unconsciousness, low oxygen saturation and myocardial infarction. Acute
methemoglobinaemia: beware of poppers!
Olivier Clerc*, Markus Schneemann, Hugo Kupferschmidt
Universitätsspital Zürich (Zürich, CH); Schweizerisches Toxikologisches Informationszentrum (Zürich,
CH)
Introduction: Acute methemoglobinemia following drug intoxication is an uncommon, but a challenging
and life-threatening condition.
Methods: Case report, pathophysiological and clinical discussion.
Results: A 37 years old man with HIV-infection treated with tenofovir, emtricitabin and nevirapine
presented to our emergency department after an unclear fall with unconsciousness, weakness,
dyspnea, left chest pain and headache. Oxygen saturation was 74% on room air and 90% with 10
l/min oxygen. The clinical examination was otherwise normal. ECG showed transitory negative T
waves in II, III, aVF and V2-6. Laboratory tests found increased troponin (0.028 ug/l) and prolactin
(38.8 ug/l). A full body CT showed no traumatic lesion, normal lungs and no pulmonary embolism. The
blood gas analysis under oxygen pointed out an oxygen partial pressure of 51 kPa (N 11-14),
saturated hemoglobin 91% (N 95-99%), oxyhemoglobin 52% (N 94-99%) and methemoglobin 43% (N
<1,5%)! It demonstrated an acute severe methemoglobinemia with typical symptoms. Methemoglobin
has hemes with iron in the oxidized state (Fe3+), unable to carry oxygen and increasing the oxygen
affinity of non-oxidized hemes. Both aspects cause tissue hypoxia, in our case myocardial infarction
and unconfirmed seizures. Pulse oximetry is inaccurate and blood gas analysis with co-oximetry is
necessary to diagnose this condition. The cause is rarely genetic and mostly drug-induced by nitrites
(nitric oxide, nitroglycerine, amylnitrite), local anesthetics, metoclopramide, sulfonamides, dapsone,
clofazimine, chloroquine, primaquine, paraquat, derivatives of benzene and aniline. If
methemoglobinemia is >30%, intravenous methylene blue 1-2 mg/kg is indicated to activate NADPH
methemoglobin reductase in red blood cells and restore hemoglobin. In severe cases, blood
transfusion and hyperbaric oxygen can be helpful. Our patient finally admitted having sniffed poppers
and injected ketamine. Nitrites such as amylnitrite and isobutylnitrite ("poppers") are vasodilators
abused for their aphrodisiac effects and cause methemoglobinemia. They were used to treat angina
pectoris, are cyanide antidotes, but now mostly recreational drugs. In the meantime, our patient’s
methemoglobin and arterial oxygen had returned to acceptable levels. No specific therapy was
needed.
Conclusion: Methemoglobinemia >30% is a serious condition which clinicians should consider in
medical and recreative drug users. Methylene blue is the treatment of choice.
16
FM234
REX: diagnostic radiation exposure of inpatients in a department of medicine
over the past two years
Markus F. Rütti*, Petra Ferrari Pedrini, Stefan Zechmann, Stephan Scheidegger, Rahel Kubik, Jana
Efe, Jürg H. Beer
Cantonal Hospital of Baden (Baden, CH); Zurich University of Applied Sciences (Winterthur, CH)
Background: Routine application of imaging methods using ionizing radiation are a cornerstone of
diagnostic medicine. Physicians are increasingly aware of both the effective doses applied and the risk
estimates associated with radiological investigations.
The aim of this study was the assessment of the number of diagnostic x-ray procedures as well as an
average radiation exposure; at the same time, we obtained the number of diagnostic MRI over a
period of two years in the internal medicine population at a Swiss teaching hospital. The data would
then set the basis for an optimal diagnostic quality at the expense of a minimal radiation exposure and
the evidence for teaching and further improvement.
Methods: We assessed the annual number of conventional radiographies, CT scans, fluoroscopies
and MRIs in 2011 and 2012. Using the ICRP (International Commisssion of Radiological Protection)60 and ICRP-103 data, we estimated the radiation exposure for each procedure and the average
radiation exposure of the medical inpatients in 2011 and in 2012.
Results: In 2011/2012 a total of 7490/7132 x-ray examinations were performed at the Department of
Medicine, which translates into an average radiation exposure of 3.35/3.03 mSv per patient. The 2
consecutive years show a trend to less radiation exposure while the MRIs applied increased slightly
(see table).
Conclusions: An inverse trend of radiation exposure and MRI exams can be observed over the past 2
years. Many factors may account for this finding, among them the ALARA principle (as low as
reasonably achievable) applied in many teaching sessions at both Departments of Medicine and
Radiology. This practice may increase the quality of care. The use of modern equipment with ever
lower radiation exposure helps to further enhance our goal of lowering the radiation dose applied per
patient. Further Work will analyze the effective individual dose/patient and the exposure of the 10
years before to support the conclusion.
17
FM235
Patient and physician gender concordance in preventive care in university
primary care settings
Simone Krähenmann-Müller*, Vanessa Virgini, Manuel Blum, Bruno da Costa, Tinh-Hai Collet, Stefan
Weiler, Yonas Martin, Jaques Cornuz, Edouard Battegay, Jean-Michel Gaspoz, Douglas Charles
Bauer, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi
Inselspital Bern (Bern, CH); University of Bern (Bern, CH); University Hospital of Lausanne (Lausanne,
CH); University Hospital of Zurich (Zurich, CH); University Hospital of Geneva (Genève, CH);
University of California (San Francisco, US); University of Michigan (Ann Arbor, US)
Background: The proportion of female physicians working in primary care medicine has increased for
several decades. Several studies have reported physician gender differences in preventive health care
received by patients, especially for gender-specific preventive services. However, limited data exist on
the role of patient and physician gender and gender concordance in the broad spectrum of preventive
care. Therefore, we assessed the association between physician gender, patient-physician gender
concordance, and the quality of preventive care in Swiss university primary care settings.
Methods: We performed a retrospective cohort study of 1001 randomly selected patients aged 50-80
years from four Swiss university primary care settings. We used indicators derived from RAND’s
Quality Assessment Tools indicators and calculated percentages of recommended preventive care
(such as behavioral counseling and cancer screening) according to physician and patient gender. We
used a hierarchical multivariate logistic regression, adjusting for patients’ age and occupation, and for
physicians’ age, function and centre (both as random factors).
Results: 1001 patients (mean age 63.5 years, 557 male) were followed by 189 physicians (mean age
34.2 years, 90 male, 94.7% residents). After multivariate adjustment, female patients received less
recommended preventive care than male patients (88.4% vs. 91.3%, p<0.001). Female physicians
provided significantly more preventive care than male physicians (p=0.04) to both female (88.8% vs.
87.7%) and male patients (91.6% vs. 90.7%). We found no evidence that preventive care differed
among gender concordant and discordant patient-physician pairs (p for interaction = 0.78). Female
physicians provided particularly more recommended cancer screening (colon cancer, breast cancer)
than male physicians (81.2% vs. 75.3%, p=0.01).
Conclusion: In Swiss primary care settings, female patients receive less preventive care than male
patients. Furthermore, female physicians provide significantly more preventive care than their male
colleagues, particularly for cancer screening. This study suggests that greater attention should be paid
to female patients in preventive health care. Further studies are needed to understand why female
physicians tend to provide better preventive care.
FM236
Reporting of randomized controlled trials that were discontinued: an
international multicentre empirical study
Benjamin Kasenda*, Erik von Elm, Anette Blümle, Yuki Tomonaga, John You, Mihaela Stegert,
Dominik Mertz, Theresa Bengough, Kelechi Kalu Olu, Matthias Briel on behalf of the DISCO-study
group
Background: Randomized controlled trials (RCTs) may be discontinued prematurely for reasons
including unanticipated adverse effects, apparent benefit, futility, or slow accrual. Discontinued trials
have ethical implications: (i) participants consent on the premise of contributing to new medical
knowledge, (ii) limited resources for research are wasted, and (iii) bias might be introduced to metaanalyses if data are not available. Currently little is known about the epidemiology and publication
history of discontinued RCTs.
Objectives and Methods: Our aims were to determine: (i) the prevalence of RCT discontinuation for all
reasons, (ii) differences between industry and investigator-initiated RCTs, (iii) risk factors for
termination due to slow accrual, and (iv) the probability for publication of discontinued RCTs. We
established a multicentre cohort of RCTs based on protocols approved by 6 research ethics
committees (RECs) from 2000 to 2003 in Switzerland, Germany, and Canada. From all included RCT
protocols we extracted data on trial characteristics (e.g. medical field, single- vs multicentre design,
length of follow-up) and on planned recruitment (sample size calculations, period, etc.). We
determined completion status and publications of trials by using information from REC files and
publications identified through literature searches, or by surveying investigators.
Results: We included 953 RCT protocols. Of these, 556 (58%) trials are known to be completed as
planned, 271 (28%) were stopped early for any reason. Industry initiated trials (N=546 [57%]) were
18
completed in 69% whereas investigator-initiated trials (N=405, [43%]) were completed only in 44%.
The completion status of 125 (13%) trials is still under evaluation. In total, 580 (61%) trials were
published, 199 (21%) were definitely not. Industry-initiated trials were published in 66% whereas
investigator-initiated trials were published in 54%. The publication status of 173 (18%) trials is still
under evaluation. At the conference we will present final results of our study.
Conclusions: Our study provides insights into the prevalence and reporting of discontinued RCTs.
Empirical data on these aspects may help further emphasize the need for reporting data from
discontinued trials in order to (i) meet the ethical obligations related to RCTs, (ii) prevent early RCT
discontinuation due to slow accrual, (iii) reduce the waste of limited resources, and (iv) prevent
potential bias in systematic reviews.
FM237
Differential effect of Charlson index and its components on in-hospital
mortality and health costs
Marco Martinuz*, Gérard Waeber, Pedro Marques-Vidal
CHUV (Lausanne, CH); IUMSP (Lausanne, CH)
Introduction: The Charlson index (Charlson, 1987) is a commonly used comorbidity index in outcome
studies. Still, the use of different weights makes its calculation cumbersome, while the sum of its
components (comorbidities) is easier to compute. In this study, we assessed the effects of 1) the
Charlson index adapted for the Swiss population and 2) the sum of its components (number of
comorbidities, maximum 15) on a) in-hospital deaths and b) cost of hospitalization.
Methods: Anonymous data was obtained from the administrative database of the department of
internal medicine of the Lausanne University Hospital (CHUV). All hospitalizations of adult (>=18
years) patients occurring between 2003 and 2011 were included. For each hospitalization, the
Charlson index and the number of comorbidities were calculated. Analyses were conducted using
Stata.
Results: Data from 32,741 hospitalizations occurring between 2003 and 2011 was analyzed. On
bivariate analysis, both the Charlson index and the number of comorbidities were significantly and
positively associated with in hospital death. Conversely, multivariate adjustment for age, gender and
calendar year using Cox regression showed that the association was no longer significant for the
number of comorbidities (table).
On bivariate analysis, hospitalization costs increased both with Charlson index and with number of
comorbidities, but the increase was much steeper for the number of comorbidities (figure). Robust
regression after adjusting for age, gender, calendar year and duration of hospital stay showed that the
increase in one comorbidity led to an average increase in hospital costs of 321 CHF (95% CI: 272 to
370), while the increase in one score point of the Charlson index led to a decrease in hospital costs of
49 CHF (95% CI: 31 to 67).
Conclusion: Charlson index is better than the number of comorbidities in predicting in-hospital death.
Conversely, the number of comorbidities significantly increases hospital costs.
19
Kardiologie / Pneumologie – Cardiologie / Pneumologie
FM238
Factors associated with exacerbation in the GP-based Swiss Chronic
Obstructive Pulmonary Disease (COPD) cohort
Nebal Abu Hussein*, Pierre-Olivier Bridevaux, Prashant Chhajed, Jean-William Fitting, Thomas
Geiser, Ladina Joos Zellweger, Malcolm Kohler, Sabrina Maier, David Miedinger, Salome Schafroth
Török, Robert Thurnheer, Michael Tamm, Jörg Daniel Leuppi
Universitätsspital Basel (Basel, CH); Hôpitaux Universitaires de Genève (Genève, CH); Centre
Hospitalier Universitaire Vaudois (Lausanne, CH); Inselspital Bern (Bern, CH); Claraspital (Basel, CH);
Universitätsspital Zürich (Zürich, CH); Kantonsspital Münsterlingen (Münsterlingen, CH)
Background: Patients with COPD often suffer from acute exacerbations, which can require
hospitalization. Frequent COPD exacerbations are related with higher mortality. Our objective was to
investigate predictors for exacerbation in a general practitioners’ (GP’s) based Swiss COPD cohort.
Methods: In questionnaire-based cohort, COPD patients from 23 Swiss cantons were screened and
enrolled into our cohort. Demographic data, medical treatment, spirometric parameters and
exacerbation history were collected and recorded for 24 months. The patients with presumed mild to
very severe COPD (GOLD stages I-IV) were seen by their GPs at least twice a year during the study
period.
Results: Among 139 GPs, 465 COPD patients (64% male, mean age 68 years) were analyzed. In the
study period of two years, 239 exacerbations occurred (57 patients with > 3 exacerbations, 182
patients with 1-2 exacerbations and 235 patients with no exacerbation. Chronic cough (Hazarad Ratio
HR 2.29, p =2.29), sputum production (HR 3.28, p =0) and severe to very severe dyspnea (HR 2.89,
3.96, p =0) were correlated with high exacerbations’ risk. Cardiovascular diseases (HR 1.45 p =0.02),
previous rehabilitation (HR 2.96, p =0), hospitalization (HR 1,709, p = 0.09) and a history of
exacerbation at baseline (HR 7.66 p =0) were significantly associated with a future exacerbation.
Conclusion: Exacerbations in the past and current severe symptoms such as sputum production,
dyspnea and cough seem to be predictors for future exacerbation in patients with COPD treated in
primary–care settings.
FM239
Predictive value of exhaled nitric oxide to predict exercise-induced
bronchoconstriction
Claudia Gregoriano*, Nebal Abu Hussein, Sabrina Maier, Stefanie Zogg, Daniela Margelli Hartmann,
David Miedinger, Jörg Daniel Leuppi
Universitätsspital Basel (Basel, CH)
Background: In fire brigade environments, there are lots of asthma-triggering and –aggravating
factors, which can lead to respiratory symptoms. Working with self-contained breathing apparatus
(SCBA) might cause bronchoconstriction in asthmatic patients, because of the dry and cool air
delivered by SCBA.
Methods: A prospective study of fire-fighters assigned to work with SCBA was carried out. Participants
completed self-administered questionnaires on respiratory symptoms. Fire-fighters of the University
Hospital Basel were exercise challenged by climbing up 46 floors of the St. Chrischona radio tower
wearing SCBA. Prior to the exercise, exhaled nitric oxide (FeNO) and forced expiratory volume in one
second (FEV1) were measured. Upon arrival on the top, FEV1 was assessed every minute during a
10-minute period.
Results: 18 fire-fighters aged 27 to 53 (89% male, age 42.7+/-7.1yrs) participated in this study.
Complete data were available from 13 participants, who were finally analysed. 8 subjects (62%) were
non-smoker and 3 (23%) had an established diagnosis of asthma. Mean measured FeNO was 13.9+/4.6ppb. No participant exceeded the limit value of 25ppb. Mean baseline FEV1 predicted was 3.8+/0.6l/min. 8 individuals (62%) showed a significant drop in FEV1 after this exercise challenge test: 5
individuals (39%) had a fall of >10%, 1 (8%) had a fall of >15% and 2 (15%) had a fall of >20% in
FEV1 after exercise. Those with a significant drop had a mean FeNO of 16+/-5 vs. 12+/-3ppb (p=ns).
All individual with a fall of >15% were current or ex-smoker. 2 out of 3 asthmatics had a significant
drop in FEV1 after exercise.
20
Conclusion: In this population of active fire-fighters, we found a high prevalence of smokers, selfreported asthma diagnosis and exercise-induced bronchoconstriction. Those individuals, who admitted
smoking or asthma, were more likely to have significant fall in FEV1 post exercise with SCBA.
Individuals with significant fall in FEV1 tended to have higher FeNO values.
FM240
Does EuroSCORE predict intensity of postoperative care and rehabilitation
parameters?
Volkhard Göber*, Uta Fäh, Dorothee Keller, Hugo Saner, Thierry Carrel, Lars Englberger
Inselspital Bern (Bern, CH)
Background: An increasing number of older and more multi-morbid patients undergo cardiac surgery
which results in increased postoperative morbidity, prolonged ICU length of stay (LOS) and higher
hospital costs. We aimed to evaluate the EuroSCORE model for the prediction of ICU LOS, hospital
LOS, required nursing effort, and type of cardiac rehabilitation.
Patients and methods: Prospective observational evaluation of 505 consecutive adult patients (mean
age 65.1±12.1 years, 25.7% female) who underwent cardiac and/or aortic thoracic surgery with
cardiopulmonary bypass (CPB).
Results: Median additive and logistic EuroSCORE was 5 (IQR 3-7) and 5.8 (IQR 2.6 - 14.1),
respectively. In univariate analysis additive and logistic EuroSCORE were significantly associated with
prolonged ICU LOS, prolonged hospital LOS, higher daily nursing effort, and type of rehabilitation (inpatient versus ambulant); p<0.001 for all correlations).
Multivariate analysis including other clinically relevant variables (CPB time, type of operation, age,
body mass index, urgency of surgery, left ventricular ejection fraction) showed higher additive
EuroSCORE and higher logistic EuroSCORE independently associated with prolonged ICU LOS,
prolonged hospital LOS, and higher daily nursing effort. However, EuroSCORE did not independently
predict the type of rehabilitation.
Conclusions: The EuroSCORE can be used to identify patients with elevated risk for prolonged ICU
stay, prolonged hospital LOS and higher intensity of postoperative care. This information may support
timely planning of ICU resources, hospital beds and postoperative nursing.
FM241
Acute kidney injury and worsening kidney function predict outcomes of acute
heart failure patients
Grégory Berra*, Nicolas Garin, Anne-Sophie Janot-Berthier, Arnaud Perrier, Pierre-Yves Martin,
Sébastien Carballo
Introduction: Renal function is a strong predictor of outcome in acute heart failure, but the prognostic
implication of a deterioration of renal function during hospital management is debated. We aimed to
test if worsening renal function during the first 7 days of hospital stay was independently associated
with prognosis.
Method: Retrospective cohort study of 646 heart failure inpatients followed until 365 days or death.
The primary endpoint was the hazard ratio (HR) of death or readmission. Acute renal failure (ARF)
was defined according to Acute Kidney Injury Network (AKIN). Worsening renal function (WRF)
presenting during hospital stay was classified according to AKIN, using the difference between the first
and the highest creatinine value during the first 7 days of hospital stay. We used Kaplan Meier survival
analysis and Cox proportional hazard model to test the association between clinical and biological
variables and the primary outcome.
Results: ARF, WRF, hemoglobin and creatinine levels at admission and use of loop diuretics before
admission were significantly associated with the primary outcome in univariate analysis (figure).Only
ARF and WRF remained significantly associated with the outcome in a multivariate model, with HRs
for death or readmission of 1.32 (95%CI 1.12-1.55, p=0.001) and 1.27 (95%CI 1.07-1.51, p=0.005)
respectively.
Conclusions: Worsening renal function during the first days of hospitalization is strongly associated
with a poor outcome. Strict monitoring of renal function during hospital stay is therefore warranted.
21
22
FM242
LUFTIBUS study: how the Swiss get weaker with ageing. Epidemiology of
muscle mass and strength
Paolo M. Suter*, Tina Sander, Alexander Turk, Otto Brändli
USZ (Zürich, CH); Lunge Zurich (Zürich, CH)
Introduction: The loss of muscle mass, i.e. the loss of the active metabolic tissue, is one of the most
important risk factors for the development of the chronic diseases of aging. The epidemiology of the
muscle mass and muscle strength at the population level in Switzerland is mostly unknown.
Method: In the setting of the COPD-Roadshow of Lunge Zürich (www.lunge-zuerich.ch) we assessed
from April 2010 to May 2012 at 42 locations in 9 different Swiss Cantons 8332 individuals (age range
7- 96 years, m/f=47.5/52.5%). The test battery included a standard pulmonary function test
(spirometry), body weight (kg), body height (cm), grip strength measurements (Jamar hyraulic handdynamometer) at the dominant & non-dominant arm and body composition by bioimpedance
measurements (Tanita BC-420MA; data on fat mass, muscle mass (MM)). Data from the preliminary
analysis of the 20-89 year old participants will be presented.
Results: The decline in MM with aging was significant in men and women (p < 0.0001). There was a
significant relationship between MM and the grip strength in women and men (r=0.45, p < 0.0001).
MM loss started early with an acceleration around the age of 40 years in men; in women the decline
was more gradual and continuous without acceleration at a certain age. The relation between age
and grip strength for the right arm in men and women are shown in Figure 1 (ANOVA for trend over
age p < 0.0001 for men & women).
Conclusion: The Luftibus Study is the first large scale study in Switzerland reporting the changes of
MM and grip strength in a population of free living subjects. The loss of muscle mass is a central
pathophysiologic drive for the development of most age related chronic diseases. In view of the large
variability of the MM in all age groups with a large fraction of the population with low grip strength
(proxy for low MM) preventive strategies to minimize muscle loss and maintain muscle function will be
critical for the maintenance of health and a good functional status with aging. Strategies to achieve
this will be discussed in the context of this unique epidemiologic data set.
23
FM243
Are biomarkers useful to identify heavy drinking among people with alcohol
dependence?
Nicolas Bertholet*, Michael Winter, Debbie Cheng, Jeffrey Samet, Richard Saitz
Service d'alcoologie, Centre hospitalier universitaire vaudois (Lausanne, CH); Boston University
(Boston, US)
Background: Managing patients with alcohol dependence includes assessment for heavy drinking,
often done by asking patients. Biomarkers have been recommended to detect heavy drinking but
evidence of their accuracy is limited.
Aim : We assessed the operating characteristics of disialo-Carbohydrate-Deficient Transferrin
(%dCDT), gamma-glutamyltransferase (GGT), %dCDT and GGT together, and breath alcohol for
identifying heavy drinking among people with dependence.
Methods: We used cross-sectional data from 402 adults with alcohol dependence and current heavy
drinking. Subjects were referred to primary care and assessed with biomarkers 6 months after
enrollment. For %dCDT a cutoff point of >=1.7% defined a positive test; a positive GGT was >=66 U/L;
the combination test was defined as positive if either individual test was positive; a positive breath
alcohol test was >0. We assessed biomarker performance for detecting three heavy alcohol use levels
over the past 30 days as determined using the Timeline Follow-back calendar method reference
standard in confidential research interviews : 1) any heavy drinking (>=4 drinks in a day or >7
drinks/week for women, >=5 drinks in a day or >14 drinks/week for men), 2) recurrent heavy drinking
(>=5 drinks in a day on at least 5 days) and 3) persistent heavy drinking (>=5 drinks in a day on at
least 7 consecutive days).
Results: By self-report reference standard, the prevalence of any heavy drinking, recurrent, and
persistent heavy drinking was 54%, 34%, and 17% respectively. The Table displays the performance
of each studied test (%dCDT, GGT, both, breath alcohol) for each of the three self-reported heavy
alcohol use levels over the past 30 days.
Conclusions: %dCDT alone yielded the best likelihood ratio positive for each alcohol use level,
however it was not adequately sensitive to detect any, recurrent, or persistent heavy drinking. A noninvasive breath alcohol test was comparable to GGT but neither of these two was sufficiently sensitive
24
(both tests missed 70-80% of the cases). Although biomarkers may provide useful information,
determination of their role and incremental value over self-report in clinical settings is needed.
FM244
Are rehospitalisation rates a reliable quality marker?
Adrian Bachofner*, Regina Classen, Werner Zimmerli
Kantonsspital Liestal (Liestal, CH)
Background. Rehospitalisation rates are proposed to be a marker of quality of care provided by
hospitals. In Switzerland, the ANQ (Nationaler Verein für Qualitätsentwicklung in Spitälern) is
generating such rates applying the patient classification software SQLape in order to detect
“potentially avoidable readmissions”. The SQLape algorithm is undisclosed to its end user. In this
algorithm, each rehospitalisation within 30 days which is linked to a previously established condition, is
classified as potentially avoidable.
Objectives. To pinpoint the causes of early rehospitalisation in order to extract the fraction of
potentially avoidable readmissions. To evaluate whether the ANQ algorithm can be used as reliable
quality marker.
Methods. According to the SQLape software (version 2011), 274 cases were identified as potentially
avoidable readmission to the Medical University Clinic Liestal in 2010. We established a set of 3 main
categories defining the reason for “potentially avoidable readmission”: (1) patient care during index
admission, (2) discharge planning, and (3) outpatient follow up. A 4th category included cases
considered as misclassified. The 274 pairs of discharge reports (index admission and
rehospitalisation) were analysed, in order to define the single leading cause of rehospitalisation.
Results. 18 of 21 cases in category 1, 23/26 in category 2, 6/15 in category 3 and 0/212 in category 4
have to be considered as potentially avoidable readmission. This corresponds to only 17% of all 274
patients who have been classified by the ANQ algorithm. Examples for misclassification as “potentially
avoidable readmission” were the following situations: Category 1. Self-discharge against medical
advice (n=3); category 2. Accurate instruction of an incompliant patient (n=3); category 3. Error in
outpatient treatment (n=5), direct consulting of Emergency Room instead of primary care physician
(n=4); and category 4. Transfer of patient to in-house geriatric ward (n=51) or readmission for chronic
progressive condition, adequately diagnosed and treated during index stay (n=96).
Conclusion. In only 17% (47/274) of the patients classified as “potentially avoidable readmissions” by
SQLape, readmission could have been avoided by providing a better quality. Thus, the classification
software SQLape 2011 of the ANQ cannot be used as quality marker of hospital care.
25
FM245
Potentially avoidable readmissions within 30 days: a retrospective analysis of
11074 admissions in a division of general internal medicine
Marc Uhlmann*, Olivier Lamy, Estelle Lécureux, Hong Dung Duong, Gérard Waeber, Anne-Claude
Griesser
CHUV (Lausanne, CH)
Introduction: Hospital readmission (RA) rate within 30 days after discharge is an inpatient quality of
care indicator highlighting too early discharge or suboptimal care and coordination. Some early RA are
deemed potentially avoidable (RAPA) vs non-avoidable (RANA). In the context of the Swiss quality
measures program launched by the National Quality Association (ANQ) it has become mandatory to
evaluate the RAPA by mean of the SQLape computerized algorithm from routine administrative data.
We aimed to analyze the patients’ and stays’ characteristics within RAPA and RANA for a 3 years
period in the division of general internal medicine (DGIM).
Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our 200 acute care beds DGIM were
analyzed. We defined 5 groups of index stays: 1) ended by death 2) followed by no early RA 3)
SQLape non-eligible, followed by early RA 4) SQLape eligible with RANA 5) SQLape-eligible with
RAPA. Patients discharged to home directly from the emergency room were excluded.
The SQLape definition of RAPA includes: not planned at discharge, caused by at least 1 active
diagnosis present during the index hospitalization. Patients who died or were transferred are SQLape
non-eligible.
Results: 11’074 admissions were analyzed. 93% came from home or long-term care facility. Mean age
72.0 +/- 16.8y (23.7 % > 85y), 50.3% females, Charlson comorbidity score 2.3 ± 2.3, 41% with
psychiatric and 20% with oncological comorbidities. The length of stay was 16 +/- 15 days, 49.7% had
been admitted at least once within 12 months before the index admission.
8.4% died, 64.8% returned at home or long-term care facility, 26.8% were transferred to other
hospitals. 77.4% were not early RA. Of the 1575 (14.2%) early RA, 385 (3.5%) were SQLape-non
eligible and RA, 410 (3.7%) SQLape-eligible RANA and 780 (7.0%) SQLape-eligible RAPA. The
median time from discharge to RA was 13 days for RAPA and 15.5 days for RANA. Pulmonary (incl.
Cancer, RAPA 24%, RANA 25%), cardiovascular (RAPA 21%, RANA 27%) and digestive (incl.
Cancer, RAPA 19%, RANA 15%) diseases account for two third of RA.
Conclusion: We observed a 30 days RA rate of 14.2%. Half of the RA were deemed RAPA according
to SQLape. Considering the burden and the cost of RA, 2 main measures are needed: 1) general
preventive measures (e.g. medication review) and 2) identification of high risk patients to implement
targeted preventive measures (e.g. discharge plan including the patient, family and caregivers).
26
Bluthochdruck - Hypertension artérielle
FM246
Relationship between copeptin and nocturnal blood pressure in young and
healthy adults
Tobias Schön*, Stefanie Aeschbacher, Stefanie Leib, Martin Risch, Lorenz Risch, David Conen
Universitätsspital - Innere Medizin (Basel, CH); Labormedizinisches Zentrum Dr Risch (Schaan, LI);
Private Universität im Fürstentum Liechtenstein (Triesen, LI)
Purpose: Copeptin is a vasopressin related stress hormone. We investigated whether copeptin is
associated with 24-hour ambulatory daytime and/or nighttime blood pressure levels in young and
healthy adults.
Method: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk
Factors (GAPP) study is a population based cohort study of healthy adults aged 25-41 years in the
Principality of Liechtenstein. Individuals with diabetes, BMI >35 kg/m^2 and prevalent cardiovascular
disease were excluded. Copeptin was assayed using an immunoluminometric assay (BRAHMS
GmbH). Ambulatory blood pressure monitoring was performed using a validated, fully automatic, noninvasive device (Schiller BR-102 plus).
Results: Of 1443 individuals included in this study, 53% were female. The median age was 38 years,
BMI was 24.2 kg/m^2, and 21% were active smokers. The median copeptin levels were 3.7
(interquartile range [IQR]: 2.5, 5.7) and 2.3 pmol/l (IQR: 1.6, 3.4) in men and women, respectively. In
multivariable linear regression models, log-transformed Copeptin was significantly associated with
systolic and diastolic blood pressure during sleep (systolic blood pressure: Beta= 0.84 (95%
confidence interval [CI]: 0.03, 1.66), p=0.04; diastolic blood pressure: Beta= 1.23 (95% CI: 0.60, 1.87),
p=0.0001), as shown in the Table. However, copeptin was not associated with daytime blood pressure
levels (systolic blood pressure: Beta= -0.09 (CI: -0.85, 0.68, p=0.83), diastolic blood pressure: Beta=
0.45 (CI: -0.17, 1.08, p=0.15). The relationship between copeptin and nighttime blood pressure
seemed to be stronger in men compared to women (p for interaction 0.005).
Conclusion: In this large population based study of young and healthy adults, the stress hormone
copeptin was significantly associated with elevated nighttime but not daytime blood pressure levels.
Our data therefore suggest that stress may be involved in blood pressure elevations during sleep.
27
FM247
Comparison of a wrist device with position sensor and an arm device to
measure blood pressure in elderly persons
Celine Guggiari*, Christophe Büla, Stephan Eyer, Katia Iglesias, Bernard Waeber
CHUV (Epalinges, CH)
Background: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and
has been shown feasible in older persons. Wrist manometers have been recently proposed for such
home BP measurement, but their accuracy has not been previously assessed in older patients.
Methods: Forty eight subjects (33 women and 15 men, mean age 81.3±8.0 years) had their BP
measured with a wrist device with position sensor and an arm device in random order in sitting
position.
Results: Average BP measures were systematically lower with wrist than arm device for systolic BP
(120.1±2.2 vs 130.5±2.2 mmHg, p<.001) and diastolic BP (69.7±1.3 vs 66.0±1.3 mmHg, p<.001)
(Figure). Moreover, a 10 mmHg or greater difference between arm and wrist device was observed in
54.2% and 18.8% of systolic and diastolic measures, respectively.
Conclusions: Compared to arm device, wrist device with position sensor systematically
underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant
and questions the use of wrist device to monitor BP in elderly persons.
FM248
Effects of weight on blood pressure at rest and during exercise
Andreas Schönenberger*, Renate Schoenenberger, Paolo Suter, Paul Erne
Inselspital (Bern, CH); Luzerner Kantonsspital (Luzern, CH); Universitätsspital Zürich (Zürich, CH)
Introduction: Body weight (BW) and blood pressure (BP) have a close relationship which has been
accounted for by hormonal changes. No previous study evaluated the effect of wearing an external
weight vest on BP to answer the question whether there is a simple mechanism between BW and BP.
Methods: Seventeen healthy volunteers underwent weight reduction (WR) by caloric restriction. Before
and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before
and after WR, exercise testing was performed twice with random allocation of a weight vest (10 kg) to
one of the tests. Linear regression was used to detect independent associations between BP and
weight vest, BW or body fat percentage.
Results: BW decreased from 89.4 ± 15.4 kg before to 79.1 ± 14.0 kg after WR (P<0.001). WR led to
significant decreases of BP at rest (from 130.0/85.9 mmHg to 112.5/77.8 mmHg, P<0.001 for systolic
and diastolic BP) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7
mmHg before and 125.8/84.6 mmHg after WR) and during exercise. Linear regression revealed
evidence for independent associations of weight vest with BP (P=0.006 for systolic and P=0.008 for
diastolic BP at rest).
Conclusion: This study shows that wearing of an external weight vest has immediate effects on BP at
rest and during exercise independent of BW or body fat. More research is needed to understand the
physiological mechanisms between weight and BP.
28
Endokrinologie - Endocrinologie
FM249
Bariatric surgery versus non-surgical treatment for obesity: a systematic
review and meta-analysis of randomized controlled trials
Viktoria Luise Gloy*, Matthias Briel, Deepak L. Bhatt, Sangeeta R. Kashyap, Philip R. Schauer,
Geltrude Mingrone, Heiner C. Bucher, Alain J. Nordmann
Universitätsspital Basel (Basel, CH); Brigham and Women's Hospital, and Harvard Medical School
(Boston, US); Cleveland Clinic (Cleveland, US); Università Cattolica S. Cuore (Rom, IT)
Introduction: The overall effects of bariatric surgery compared to non-surgical treatment for obesity are
unclear. We aimed at quantifying the effects of bariatric surgery compared to non-surgical treatment
for obesity.
Methods: We searched Medline, Embase, and the Cochrane Library from their inception to December
2012 regardless of language or publication status. Eligible studies were randomized controlled trials
(>=1 year follow-up) which included individuals with a BMI greater 30 kg/m2, compared current
bariatric surgery techniques to non-surgical treatment, and reported on body weight, cardiovascular
risk factors, quality of life, and/or adverse events. Two investigators independently abstracted data
and assessed risk of bias. Any disagreements were resolved by consensus.
Results: The meta-analysis included 7 studies with 508 individuals (mean BMI: 34 to 48 kg/m2).
Individuals allocated to bariatric surgery lost more body weight (mean difference [MD] -25 kg, 95%
confidence interval [CI] -31 to -20 kg) compared to non-surgical treatment, had a higher remission rate
of type 2 diabetes (relative risk 11.9, 95% CI 2.1 to 66.7) and metabolic syndrome, greater
improvements in quality of life and reductions in drug use (no pooled data). Triglycerides decreased
more (MD -0.5, 95% CI -0.7 to -0.3 mmol/L) and HDL-cholesterol increased more (MD 0.16, 95% CI
0.1 to 0.2 mmol/L). Changes in blood pressure, total cholesterol or LDL were not different. Serious
adverse events after bariatric surgery were relatively rare.
Conclusions: Bariatric surgery improves body weight, cardiovascular risk factors, and quality of life
more efficiently than non-surgical treatment. Results are limited because only 7 RCTs could be
included and apply only to younger individuals with a BMI greater 35 kg/m2.
FM250
Comparison of diabetes quality of care indicators as reported by patients and
primary care physicians
Tinh-Hai Collet, Patrick Taffé, Julie Bordet, Bernard Burnand, Isabelle Peytremann-Bridevaux*
Policlinique Médicale Universitaire & Service d'Endocrinologie, Diabétologie et Métabolisme
(Lausanne, CH); Institut Universitaire de Médecine Sociale et Préventive (Lausanne, CH)
Background: Patient self-report of care is pervasive in daily care and clinical research. We compared
reliability and agreement parameters between patient and physician reports of diabetes-related
processes and outcome of care.
Methods: We used self-reported data from a community-based survey including non-institutionalized
adults with diabetes living in the canton of Vaud. The following past 12 months diabetes processes of
care were documented: HbA1c, lipids, microabuminuria, blood pressure, weight, feet and eye exams.
Participants were also asked to provide current levels of HbA1c, height, weight, and blood pressure, if
known; corresponding data were collected from treating physicians.
For dichotomous variables, we assessed reliability by Cohen’s kappa (discrimination of two
dichotomous reports) and agreement by uniform kappa (measurement error and how close two
reports are). For continuous measures, we used Lin’s concordance correlation coefficient to evaluate
reproducibility and Bland & Altman’s 95% limits of agreement to assess measurement error.
Results: Out of 406 patients included in the survey, 210 presented both self-reported and physicianreported data. Mean age was 65 years, 40% were women, 51% had diabetes for >10 years and 49%
were treated with insulin.
Agreement between patient and physician report was good for past 12 months routine processes of
care, such as measurement of blood pressure (uniform kappa=0.94), HbA1c (0.93), weight (0.88), and
lipid profile (0.78); it was less satisfactory for procedures such as urine analysis, foot and eye exam
(all <0.50). Cohen’s kappa values were all low (<0.25). Comparisons of patient and physician report of
continuous variables showed high concordance correlation coefficients for height and weight (0.93 and
29
0.97, resp.) and smaller ones for HbA1c (0.72) and blood pressure (0.5-0.6). Limits of agreement were
large in all cases (height ±6 cm, weight ±10 kg, HbA1C ±2% and blood pressure ±25 mmHg).
Conclusions: Our results suggested good concordance between patient and physician reports of
routine dichotomous processes of care, with decreasing concordance for procedures such as urine
analysis, foot and eye exam, which may reflect difficulties for patients to figure out what these exams
truly represent. Patient and physician reports of continuous outcomes yielded less good results.
Evaluation of quality of care from self-reported indicators should be made cautiously.
FM251
Gynecomastia in an obese man: not always an insignificant finding
Lea Slahor*, Stefan Fischli, Christoph Henzen
Luzerner Kantonsspital (Luzern, CH)
Case report: A 48-year-old man was referred for surgical breast reduction, as the recent onset of
bilateral breast enlargement had been considered to be due to obesity. In our out-patient clinic further
medical history revealed sexual dysfunction. No medication, no co-morbidities. On physical
examination body mass index was 31.8 kg/m^2, blood pressure 140/90 mmHg, pulse rate 78/min,
palpable tender breast tissue (3 cm) beneath the areolae bilaterally, no galactorrhea, low-normal
bilateral testes volume. Thyroid, renal and hepatic disease dysfunction were excluded with laboratory
studies. Isolated hypogonadotropic (secondary) hypogonadism was confirmed (total serum
testosterone 4.69 nmol/l, reference range 5.76-28.12 nmol/l and LH 2.9 U/l, reference range 1.7-8.6
U/l), caused by severe hyperprolactinemia (7561 ug/l, reference range 4.0-15.2 ug/l). MRI of the
pituitary gland showed a 4.1 cm sellar mass, thus a macroprolactinoma was diagnosed. Suprasellar
extension and optic chiasm compression led to visual field defects(bitemporal hemianopsia). Under
dopamine agonist therapy (quinagolid, 225 ug daily) the prolactin level (31 ug/l) and tumor size (2.4
cm) decreased significantly within 3 months. Furthermore gonadal function was restored and
gynecomastia reduced.
Comment: Gynecomastia is caused by an androgen/estrogen imbalance, for instance as a result of
increased aromatization of androgens to estrogens in adipose tissue in obese men. Even though a
secondary hypogonadism is a common finding in obese men, a hyperprolactinemia has to be
excluded. Prolactinomas (lactotroph adenomas) are the most common hormone-secreting pituitary
tumors, whereat serum prolactin levels parallel tumor size.
Conclusion: New-onset of postpubertal gynecomastia may be the single clinical sign of an underlying
endocrine disorder. Even in obese men, exclusion of an androgen-deficiency is mandatory and in
case of marked hypogonadotropic hypogonadism secondary cases as hyperprolactinemia should be
evaluated.
30
FM252
Subclinical thyroid dysfunction and functional capacity among older adults: a
prospective cohort study
Vanessa Virgini*, Liselotte Wijsman, Nicolas Rodondi, Douglas Bauer, Jacobijn Gussekloo, Wendy
den Elzen, Patricia Kearney, Wouter Jukema, Rudi Westendorp, Ian Ford, David Stott, Simon
Mooijaart
Inselspital, Universitätspital Bern (Bern, CH); Leiden University Medical Center (Leiden, NL); San
Francisco University Center (San Francisco, US); University College Cork (Cork, IE); University of
Glasgow (Glasgow, GB); Institute for Evidence-Based Medicine in Old Age (Leiden, NL)
Background: Subclinical thyroid dysfunction is common among older adults and has been associated
with decreased functional capacity, but data are conflicting. Furthermore, there are no data on the
association between persistent subclinical thyroid dysfunction and functional capacity. We investigated
the association between subclinical thyroid dysfunction as well as persistent subclinical thyroid
dysfunction and functional capacity in an elderly population.
Methods: Men and women aged 70-82 years (n=5182) who participated to the Prospective Study of
Pravastatin in the Elderly at Risk (PROSPER) were included. Self-reported functional capacity was
examined using the Barthel Index (BI) and the Instrumental Activities of Daily Living (IADL) at baseline
and over a mean 3.2-year follow-up period. Thyroid function was assessed at baseline and after six
months. Participants were classified into three thyroid states groups: subclinical hyperthyroidism
(TSH<=0.45mIU/L), subclinical hypothyroidism (TSH>=4.5mIU/L, both with normal free T4 levels) and
euthyroidism (0.45-4.5mIU/L). Multivariate models were used to determine the relationship between
thyroid function as well as persistent thyroid function and functional capacity.
Results: At baseline, subclinical hyperthyroidism was present in 65 (1.3%) participants and subclinical
hypothyroidism in 173 (3.3%) participants. Compared to euthyroid participants (mean BI 19.77+/(standard error) 0.01, mean IADL 13.62+/-0.02), there was no difference in functional capacity for
participants with subclinical hyperthyroidism (mean BI 19.63+/-0.09, mean IADL 13.60+/-0.12, both pvalues>0.05) or subclinical hypothyroidism (mean BI 19.85+/-0.05, mean IADL 13.63+/-0.07, both pvalues>0.05) at baseline. Over a mean 3.2-year period, there was no association between thyroid
function and annual decline of either BI or IADL (all p-values>0.05). No association was found
between persistent subclinical thyroid dysfunction and functional capacity at baseline or during followup (all p-values>0.05).
Conclusion: In a large population of generally well-functioning community-dwelling older persons,
there is no evidence to support the relationship between subclinical thyroid dysfunction and selfreported functional capacity. These findings suggest that screening for subclinical thyroid dysfunction
might not be indicated in older adults with decreased functional capacity.
31
Beste Freie Mitteilungen – Meilleur Communication libres
FM253
Is multimorbidity coming into conflict with quality of care?
Sven Streit*, Stefan Weiler, Tinh-Hai Collet, Douglas Bauer, Lukas Zimmerli, Peter Frey, Jacques
Cornuz, Jean-Michel Gaspoz, Edouard Battegay, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi
Insitute of General Practice BIHAM (Bern, CH); Bern University Hospital, Bern (Bern, CH); Lausanne
University Hospital (Lausanne, CH); University of California San Francisco (California, US); University
Hospital of Zurich (Zurich, CH); Berner Institut für Hausarztmedizin BIHAM (Bern, CH); Lausanne
University Hospital (Lausanne, CH); University Hospitals of Geneva, and Faculty of Medicine
(Genève, CH); University of Michigan (Ann Arbor Michigan, US)
Introduction: Clinical trials often exclude patients with comorbidities, but caring for patients with
multimorbidity is very common for general internists. Data on the impact of multimorbidity on quality of
care are conflicting. We aimed to analyze the association of multimorbidity and quality of preventive
care.
Methods: In a random sample of 1002 patients attending four Swiss university primary care settings,
we abstracted medical charts over 2 years to build a retrospective cohort. The inclusion criteria were
patients aged between 50-80 years followed for >= 1 year. As published definitions of multimorbidity
are inconsistent, we derived a new set of comorbidities based on previous studies and added
comorbidities used for the Charlson index and psychiatric diseases as an important comorbidity, finally
leading to 17 comorbidities. To evaluate the quality of preventive care and care for cardiovascular risk
factors (CVRF), we searched medical charts for indicators from RAND's Quality Assessment Tool. We
calculated the percentage of provided care as recommended care divided by patients who where
eligible for each indicator. We calculated two aggregate scores of quality of preventive care and care
for CVRF.
Results: The mean age was 63.5 years, 44% were women. Participants had a mean of 2.6 (SD 1.9)
comorbidities, while only 7.6% had no comorbidities. The mean Charlson index was 1.8 points (SD
1.9). Overall, participants received 69% of recommended preventive care and 84% received
recommended care for CVRF. Quality of care remained stable with increasing number of comorbidities
both for prevention (Figure 1) and for CVRF. Results were similar in analyses limited to Charlson
index and after adjusting for age, gender, civil status, legal status, work, center and number of visits.
Among subgroups of diseases (cardiovascular disease, psychiatric disorders, chronic pulmonary
disease, cancer or depression), we found similar quality of care.
Conclusions: In university primary care settings in Switzerland, multimorbidity was very common and
less than 10% of participants had no comorbidities. Quality of care for preventive care as well as for
CVRF was independent of increasing number of comorbidities. These findings confirm the high
prevalence of patients with multimorbidity in primary care and demonstrate that a high level of
preventive care is possible despite multimorbidity.
32
FM254
Suboptimal adherence to initial processes of care in elderly patients with acute
venous thromboembolism
Anna Stuck*, Marie Méan, Andreas Limacher, Marc Righini, Kurt Jäger, Hans Jürg Beer, Joseph
Osterwalder, Beat Frauchiger, Christian Matter, Nils Kucher, Anne Angelillo-Scherrer, Jacques
Cornuz, Martin Banyai, Bernhard Lämmle, Marc Husmann, Michael Egloff, Markus Aschwanden,
Henri Bounameaux, Nicolas Rodondi, Drahomir Aujesky
Bern University Hospital and University of Bern (Bern, CH); University of Bern (Bern, CH); Geneva
University Hospital (Genève, CH); Basel University Hospital (Basel, CH); Cantonal Hospital of Baden
(Baden, CH); Cantonal Hospital of St. Gallen (St. Gallen, CH); Cantonal Hospital of Frauenfeld
(Frauenfeld, CH); Zürich University Hospital (Zürich, CH); Lausanne University Hospital (Lausanne,
CH); University of Lausanne (Lausanne, CH); Cantonal Hospital of Lucerne (Luzern, CH); Zürich
University Hospital and University of Zürich (Zürich, CH)
Background: Although venous thromboembolism (VTE) is common in elderly persons, limited data
exist on the quality of care in elderly patients with VTE, and it is unknown whether such patients
receive recommended processes of care in the early phase of VTE.
Methods: We prospectively studied consecutive in- and outpatients aged >=65 years with acute,
symptomatic VTE from all five Swiss university- and four non-university hospitals between September
2009 and March 2011. We systematically assessed whether the following five processes of care,
which are recommended by the American College of Chest Physicians, were performed in each
patient: (1) duration of parenteral anticoagulation for >=5 days; (2) start of oral anticoagulation on the
first treatment day; (3) continuation of parenteral anticoagulation until the international normalized ratio
[INR] is >=2 for >=24 hours; (4) use of low-molecular-weight heparin monotherapy in patients with
cancer; and (5) prescription of compression stockings in patients with symptomatic deep vein
thrombosis. We used multivariable logistic models to identify patient and hospital factors
independently associated with adherence to recommended processes of care.
Results: Our cohort comprised 950 patients with VTE (median age 75 years). Of these, 86.0%
(645/750) received parenteral anticoagulation for >=5 days, 46.7% (350/750) had oral anticoagulation
started on the first treatment day, and 36.5% (274/750) had an INR >=2 for >=24 hours before
parenteral anticoagulation was discontinued. Overall, 34.6% (53/153) of patients with cancer received
low-molecular-weight heparin monotherapy and 71.9% (304/423) of patients with symptomatic deep
vein thrombosis were prescribed compression stockings. In multivariable analysis, obesity (odds ratio
[OR] 0.68, 95% confidence interval [CI] 0.47-0.97), symptomatic pulmonary embolism (OR 0.61, 95%
CI 0.43-0.86), and hospital-acquired VTE (OR 0.32, 95% CI, 0.19-0.54) were negatively associated
with the initiation of oral anticoagulation on the first treatment day.
Conclusion: The adherence to most recommended processes of care was suboptimal in elderly
patients with VTE. Several patient characteristics were associated with lower rates of initiating oral
anticoagulation on the first treatment day. Further efforts are needed to improve quality of care in
elderly patients with VTE.
FM255
A high risk of falls is associated with an increased risk of medically-relevant
non-major bleeding in elderly patients receiving anticoagulants
Marie Méan*, Andreas Limacher, Pascal Kämpfen, Drahomir Aujesky
Inselpital (Bern, CH)
Introduction: We aimed to evaluate whether a high falls risk is associated with an increased risk of
bleeding in elderly pts receiving anticoagulants for acute venous thromboembolism (VTE).
Methods: In a multicenter prospective Swiss cohort, we prospectively enrolled consecutive pts aged
>=65 years who received anticoagulants for acute VTE between 09/2009 and 03/2012. We assessed
the falls risk by asking pt two validated questions: 1) "Did you fall during the last year? ", 2) "Did you
notice any problems with gait, balance or mobility? ". If at least one of these questions was answered
positively, the falls risk was considered high. The primary outcome was the occurrence of a first major
bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in
hemoglobin >=;20 g/L or leading to the transfusion >=2 units of red blood cells. The secondary
outcome was the occurrence of a first non-major bleeding requiring medical attention. To examine the
association between falls risk and bleeding, we used a Cox proportional hazards model, adjusted for
age, gender, history of major bleeding, anemia, thrombocytopenia, cardiac disease, diabetes mellitus,
arterial hypertension, cancer, chronic liver disease, chronic renal disease, overt pulmonary embolism,
33
surgery in the last 3 months, polypharmacy, concomitant treatment with antiplatelet agents, and
history of stroke or transient ischemic attack.
Results: Of 991 enrolled pts, 458 (46.2%) had a high risk of falls. The mean ±SD follow-up duration
was 17 ± 10 months. The overall incidence rate of major and medically-relevant non-major bleeding
was 7.9 events and 12.0 events per 100 person-years, respectively. Pts with a high falls risk had a
somewhat higher rate of major bleeding (9.6 vs. 6.6; p=0.06) and a significantly higher rate of
medically-relevant non-major bleeding (16.7 vs. 8.3; p<0.001) than pts with a low falls risk (Fig.). After
adjustment, a high falls risk was significantly associated with non-major bleeding (hazard ratio [HR]
1.67, 95% confidence interval [CI] 1.18-2.36; p=0.004) but not with major bleeding (HR 1.18, 95% CI
0.78 to 1.77; p=0.43).
Discussion: In this prospective cohort of elderly pts with acute VTE, pts at high falls risk had a
significantly increased risk of medically-relevant non-major bleeding. A high falls risk may be an
argument against prolonging anticoagulation duration beyond 3 months in such pts.
FM256
Vascular dysfunction and hypertension in offspring of RDP mice is associated
with insulin resistance
Agim Pireva*, Emrush Rexhaj, Stefano Rimoldi, Elise Bouillet, Claudio Sartori, Yves Allemann, Urs
Scherrer
Inselspital (Bern, CH); CHUV (Lausanne, CH)
Background: Epidemiological and experimental studies in humans suggest that environmental
influences acting early in life predispose to premature cardiovascular and metabolic disease. In line
with these concept we recently found that children born after a pregnancy complicated by
preeclampsia display vascular dysfunction. In mice restrictive diet during pregnancy (RDP, a model
mimicking preeclampsia in humans) induce vascular dysfunction in the offspring involving decreased
vascular nitric oxide bioavailability. There is abundant evidence that NO plays an important role in the
regulation of insulin sensitivity in animals and humans. We speculated that offspring of RDP mice are
insulin-resistant.
34
Methods: To test this hypothesis, we assessed insulin sensitivity (intraperitoneal glucose tolerance
test (IPGTT) and euglycemic-hyperinsulinemic clamp studies) in offspring of RDP and control mice fed
with high fat diet (HFD) for 8 wks. To test for the underlying mechanism we studied basal and insulin
stimulated glucose uptake in isolated skeletal muscles.
Results: The main new finding was that HFD induced more severe insulin resistance in offspring of
RDP than in control mice, as evidenced by a markedly smaller glucose infusion rate to maintain
euglycemia (77.4±10.7 vs. 96.7±12.2, P<.001) and a higher plasma glucose concentration during the
IPGTT(ANOVA<.01) in offspring of RDP than in control mice. Insulin resistance appeared not to be
related to an intrinsic defect of skeletal muscle because insulin stimulated glucose uptake was similar
in RDP and control mice (34.8±17.6 vs. 35.6±12.4, P=0.91).
Conclusion: We demonstrate for the first time that RDP causes insulin resistant in mice. In analogy to
other NO-deficient states, this problem may be related to vascular dysfunction resulting in impaired
insulin stimulation of blood flow and substrate delivery to skeletal muscle tissue. Preeclampsiainduced vascular dysfunction has also been found in humans. We speculate that preeclampsia
represents a novel risk factor facilitating diet-induced insulin resistance in humans.
Grant support: Swiss National Science Foundation and Swiss Society of Hypertension
FM257
Association of peripheral neuropathy with circulating advanced glycation endproducts, soluble receptor for advanced glycation end-products and other risk
factors in patients with type 2 diabetes
Carole Aubert*, Pierre-Louis Michel, Philippe Gilléry, Stéphane Jaisson, Michèle Fonfrède, Florence
Morel, Agnès Hartemann, Olivier Bourron
Hôpital Cantonal de Fribourg (Fribourg, CH); Hôpital de la Pitié-Salpêtrière (Paris, FR); Hôpital
universitaire de Reims (Reims, FR)
Introduction: Pathogenesis of diabetic peripheral neuropathy is not yet fully understood. Nonenzymatic
glycation is one of the contributing mechanisms. The aim of this study was to assess, in a population
of patients with type 2 diabetes, the respective relationship between glycation and peripheral
neuropathy, compared with other identified risk factors for peripheral neuropathy.
Methods: We included 198 patients with type 2 diabetes. Serum concentrations of 3 advanced
glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1 and pentosidine) and
of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the
neuropathy disability score and by the Semmes-Weinstein 10g-monofilament test. It was defined as
either an abnormal monofilament test and/or a neuropathy disability score >=6. We performed
multivariate regression analyses that we adjusted for potential confounding factors for neuropathy:
age, gender, diabetes duration, current smoking, systolic blood pressure, waist, height, peripheral
arterial occlusive disease, glycated haemoglobin and lipid profile.
Results: The prevalence of peripheral neuropathy was 20.7% (n=41). Table 1 shows factors
associated with neuropathy, in univariate and multivariate regression analyses. sRAGE was
independently and positively associated with the severity and the presence of peripheral neuropathy.
Carboxymethyllysine was independently and positively associated with an abnormal monofilament
test. No significant association was found between peripheral neuropathy and methyl-glyoxalhydroimidazolone-1 or pentosidine. Waist, height, current smoking, glycated haemoglobin and
peripheral arterial occlusive disease were independently associated with peripheral neuropathy.
Conclusion: Carboxymethyllysine and sRAGE were independently associated with peripheral
neuropathy. This study confirms the relationship between advanced glycation and peripheral
neuropathy, independently of other known risk factors for peripheral neuropathy, in patients with type
2 diabetes. Our results may help assessing the impact of hyperglycemia in the pathogenesis of
peripheral neuropathy, and have direct future therapeutic implications, as inhibition of advanced
glycation may slow down progression of peripheral neuropathy. But further studies are needed to
assess the cause-to-effect relationship between advanced glycation and peripheral neuropathy.
35
FM258
Post-traumatic stress disorder in relatives of patients with out-of-hospital
cardiac arrest
Marius Zimmerli*, Kai Tisljar, Gian-Marco Balestra, Wolf Langewitz, Stephan Marsch, Sabina Hunziker
Universität Basel (Basel, CH)
Introduction: Being a family member of an out of hospital cardiac arrest (OHCA) patient causes
substantial psychological stress which may put them at increased risk for development of
psychological and psychosomatic long-term consequences, such as post-traumatic stress disorder
(PTSD). Yet, frequencies and risk factors for PTSD in this population are unknown. To answer this
question, we performed a survey with relatives of OHCA patients hospitalized at the University
Hospital in Basel between January 2007 and August 2012.
Methods: This is a prospective observational study. Consecutive relatives of OHCA patients were
contacted by phone interview using structured questionnaires, such as the revised Impact of Event
Scale (IES-r) for assessing PTSD and the Family-Satisfaction with Care in the ICU (FS-ICU)
instrument to assess risk factors associated with ICU care.
Results: From a total of 101 included relatives (30% male, mean age 58 [SD ±12.1] years), 40 (39.6%)
had PTSD-related symptoms. In multivariate logistic regression analysis [odds ratio, 95% confidence
interval], several relative-related factors (female gender [3.3, 1.08-10.11], past history of depression
[3.63, 1.02-12.96]), patient-related factors (hypothermia treatment [2.86, 0.96-8.48]) and factors
associated with ICU care (long time-interval to receive prognostic information from ICU staff [2.11,
0.83-5.38], therapeutic measures not perceived as being sufficient [18.4, 1.52-224.22], conflict with
ICU staff [3.61, 0.71-18.4]) were predictors for PTSD. A model including these factors showed high
discrimination with an area under the curve of 0.77. Death of the patient was not associated with
PTSD [OR 0.71, 95%CI 0.31-1.60, p=0.40] nor was it an effect modifier (p=ns).
Conclusion: This is the first study systematically investigating long-term psychological burden of
relatives from OHCA patients. PTSD was found in a high proportion of relatives and was associated
with baseline factors, as well as relatives experience with initial ICU care and the interaction with the
treating team including sharing of prognostic information. Further research is needed to develop
preventive strategies in this population.
36
Multimorbidität - Multimorbidité
FM259
Therapeutic conflicts in patients with multimorbidity: a retrospective analysis
from an emergency department of a tertiary care hospital
Stefan Markun*, Roksana Rodak, Vladimir Kaplan, Claudia Wagner, Barbara Holzer, Edouard
Battegay, Lukas Zimmerli
UniversitätsSpital Zürich (Zürich, CH)
Objective: Multimorbidity, or multiple active conditions in one patient, is increasingly common,
particularly among the elderly. However, the applicability and feasibility of clinical practice guidelines
(CPGs) in multimorbid patients is unknown. The aim of the study was to identify and quantify potential
therapeutic conflicts in patients with multimorbidity assuming stringent adherence to CPGs for each
active condition.
Methods: We reviewed the medical documentation of all patients >=18 years with at least two active
conditions, admitted from the emergency department to the medical ward of the Division of Internal
Medicine at the University Hospital Zurich during January 2009. In individual patients we assumed
treatment as suggested by CPGs for each active condition and counted the number of therapeutic
conflicts that arouse. Therapeutic conflicts were classified as major or minor according to clinical
importance and severity. Absolutely contraindicated treatments were rated as major therapeutic
conflicts, whereas treatments that were applicable under precautionary measures were defined as
minor therapeutic conflicts.
Results: We analyzed 166 patients with a mean age (±SD) of 63 (±19) years, and a mean number of
active conditions (±SD) of 6.6 (±3.4). We found 239 therapeutic conflicts in 81 patients (49%). Major
therapeutic conflicts were found in 48 patients (29%), with the most frequent conflict situation
occurring in patients with an infectious disease and concurrent immunosuppressive therapy, mostly
due to an organ transplant. Minor therapeutic conflicts occurred in 68 patients (41%), with the most
frequent conflict situation consisting of use of diuretics, mainly due to heart failure, in severe acute or
chronic renal failure.
Conclusion: We found that therapeutic conflicts were common in multimorbid patients with one out of
two having minor, and one out of three having major therapeutic conflicts. Thus, applicability of CPGs
in these patients appears to be limited. Managing multimorbidity is a complex task for health care
professionals as well as patients. Alternative strategies need to be developed.
FM260
Prevalence of measured and self-reported multimorbidity in the Swiss-CoLaus
population-based study
Basile Pache*, Peter Vollenweider, Gérard Waeber, Pedro Marques-Vidal
Centre Hospitalier Universitaire Vaudois (Lausanne, CH); The Swiss Institute of social epidemiology
(Lausanne, CH)
Introduction: The prevalence of multimorbidity (MM) in hospitalized patients is increasing and
recognized as an important factor that may modify the strategies of treatment and increase the length
of stay. Little is currently known about the prevalence of MM in the general population and if measured
or self-reported diseases are different in the outpatient setting compared to hospitalized patients. The
objective of the study was, therefore, to assess the prevalence of self-reported and measured MM in
representative sample of the general population aged 35-75 years in Switzerland.
Method: Data were obtained from the population based CoLaus Study: 3712 participants (1965
women, 50±9 years). MM was defined as presenting >=2 morbidities according to a list of 27 items
(either measured or self-reported data, according to Barret et al.) or a Functional Comorbidity Index
(FCI) (18 items, measured only).
Results: The prevalence of MM according to these three definitions is summarized in the table 1. For
all definitions prevalence of MM was higher in women, elderly participants, those with lower education
levels, Swiss nationals, former smokers and obese participants. The prevalence of MM when
measured data were used was significantly higher than according to self-reported (p<0.001).
Multivariate analysis confirmed most of these associations, except that no difference was found for
educational level and for overweight participants.
37
Conclusion: The prevalence of MM is high in the general population, ranging from 13.8 and 50.3%
even in the younger age group. The prevalence is higher in women, and increases with age and
weight. The prevalence varies considerably according to the definition and is lower when using selfreported compared to measured data.
References:
1.
Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity
and implications for health care, research, and medical education: a cross-sectional study. Lancet.
2012;380(9836):37-43.
2.
Groll DL, To T, Bombardier C, Wright JG. The development of a comorbidity index with
physical function as the outcome. J Clin Epidemiol. 2005;58(6):595-602.
FM261
Living arrangements and informal care needs one-to-three years after stroke
rehabilitation
Heike Geschwindner*, Horst Rettke
Pflegezentren der Stadt Zürich (Zürich, CH); Universitätsspital Zürich, Zentrum Klinische
Pflegewissenschaft (Zürich, CH)
Introduction: Stroke is a major cause of persisting disabilities and long-lasting needs for daily care and
assistance. Rehabilitation aims at restoring functioning and community reintegration. Goal setting and
evaluation guides these processes. However, when being discharged an informal care setting has to
be established to maintain daily care and assistance for an indefinite time period.
Method: A cross-sectional study has been conducted with a sample (n=287) of first-ever stroke
patients one to three years post-discharge from inpatient neurorehabilitation.
Results: At discharge from rehabilitation, about 80% of all respondents (n=174) attained their shortterm goal set at admission. One to three years post-discharge they showed a lesser degree in
attaining their long-term goals. However, the majority was living at home with help, and 14% were
living in an institution. Most stroke survivors were limited in physical and cognitive functioning to some
extent. Also problems concerning communication skills were stated. Then again, limitations were not
necessarily related to the actual living arrangement. Even when assessed as living independently
stroke patients may need assistance in ‘instrumental activities of daily living’, e.g. household tasks.
The results show that even three years post-discharge a considerable number of stroke survivors
(17%) are in need of daily care and support. Informal care is frequently provided by partners or family
members. Depending on a stroke survivor’s limitations in physical or cognitive functioning as well as in
38
socio-cultural activities more persons had been involved. If limitations require constant support, care is
given by the partner and close family members. However, if care has to be provided only at specific
points in time, home care services might be called in. While immediately after discharge the partner or
a close family member is often the only caregiver, our study results point to a shift towards the
involvement of more persons in informal caregiving in the long term.
Conclusions:
The high proportion of non-attainment of long-term goals, the often times enduring demand for
personal support and care post-stroke and continuing involvement of informal caregivers require
attention. Already during inpatient rehabilitation health care professionals should address long-term
outcomes and consequences by carefully informing and educating of the individual stroke patient and
family members.
FM262
Polypharmacy in a division of general internal medicine: a retrospective study
of the number and types of medications prescribed
Marc Uhlmann*, Estelle Lécureux, Anne-Claude Griesser, Hong Dung Duong, Olivier Lamy
CHUV (Lausanne, CH)
Introduction: Adverse drug events (ADE) account for the majority of hospital-based adverse events
and are a frequent cause of readmission. As the risk of ADE increases with the number of
medications, polypharmacy is of major concern. This is particularly true for the majority of patients
hospitalized in a division of general internal medicine (DGIM) mostly elderly and/or polymorbide. We
retrospectively analyzed the amount and types of medications prescribed, the number of prescribers
and treatment modifications over a 3 year period in our DGIM.
Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our tertiary DGIM (200 acute care
beds) were analyzed. We extracted prescription data from the computerized physician order entry
program (CPOE). The CPOE was unavailable for 409 patients. Patients discharged to home directly
from the emergency room were excluded.
was 72.0 +/- 16.8y (52.8% > 75y, 23.7% > 85y), 50.3% were females, Charlson comorbidity score was
2.3 ± 2.3, 41% had psychiatric comorbidities. The length of stay was 16 +/- 15 days.
During one hospital stay one patient had (mean) 16.5 different medications prescribed, 26 prescription
interventions and 3.7 prescribers. The most frequent prescriptions were (% of patients):
benzodiazepines (BZ 66.7%), anticoagulants (AC 59.5%), NSAID and anti-platelets (NAP 48.1%),
opiates (OP 45.8%) diuretics (DI 44.0%), anti-depressants or neuroleptics (ADN 38.0%) and antidiabetics (AD 21.2%).
At discharge (N=7’747) the mean number of medications prescribed was 7.7; 2’690 patients (34.7%)
had > 10 different medications. The most frequent prescriptions were: NAP (39.2%), DI (38.5%), BZ
(37.7%) ADN (22.6%), AC (21.2%), AD (18.0%), OP (16.5%) and systemic steroids (9.6%).
Conclusion: As the definition of polypharmacy differs between “many” and over 5-10, our observation
of 34.7% patients being discharged with > 10 different medications is striking. The proportion of some
high-risk medicines used is also source of concern as they have been associated with increased ADE.
Balance between over- and underprescription is necessary but difficult to achieve. As a multifaceted
approach seems increasingly necessary to reduce ADE, especially for the elderly during transition of
care, a comprehensive medication review by the hospital prescribers is mandatory.
39
Experimental Hematology - Experimental Hematology
FM263
Endothelial cells are essential to sense lipopolysaccharide (LPS) in a Myd88dependent manner and to subsequently induce emergency myelopoiesis
Steffen Böttcher*, Ramin Radpour, Rahel Gerosa, Mathias Heikenwälder, Manfred Kopf, Markus
Manz
UniversitätsSpital Zürich (Zürich, CH); Technische Universität München (München, DE);
Eidgenössische Technische Hochschule (Zürich, CH)
Severe systemic infections evoke a well-characterized and tightly-regulated hematopoietic response
program to enhance myeloid cell output, a condition which is referred to as emergency myelopoiesis.
However, detailed information on the initial steps involving pathogen recognition and translation into
accelerated bone marrow (BM) myelopoiesis are still lacking. We have recently demonstrated that
LPS-induced emergency myelopoiesis depends on TLR4-expressing non-hematopoietic cells
(Boettcher et al., J Immunol. 2012 Jun 15;188(12):5824-8.). However, the precise identity and
localization of the non-hematopoietic cell type crucial for sensing gram negative infection-derived
lipopolysaccharide (LPS) have remained elusive to date.
We now have addressed this fundamental question using Cre-loxP recombination technology. In order
to specifically delete TLR-downstream signaling in various non-hematopoietic cells including BM
Nestin+ mesenchymal stem cells (MSCs) and their progeny, perivascular cells, endothelial cells, and
hepatocytes, we generated Nes-Cre;Myd88fl/fl, Pdgfrb-Cre;Myd88fl/fl, Tek-Cre;Myd88fl/fl, and AlbCre;Myd88fl/fl mice, respectively. We observed a normal increase in the frequency of BM CD11b+Gr1low immature myeloid precursors accompanied by a decrease of BM CD11b+Gr-1high mature
myeloid cells upon LPS stimulation characteristic for efficient emergency myelopoiesis in NesCre;Myd88fl/fl, Pdgfrb-Cre;Myd88fl/fl, and Alb-Cre;Myd88fl/fl mice as compared to control mice.
Furthermore, we measured highly-elevated plasma G-CSF levels in these mouse strains upon LPS
injection. Hence, intact TLR-signaling in mesenchymal stromal cells incl. Nestin+ MSCs, perivascular
cells as well as hepatocytes is dispensable for induction of emergency myelopoiesis. Strikingly, TekCre;Myd88fl/fl mice were completely non-responsive towards LPS stimulation as assessed by the
above-mentioned parameters. Furthermore, freshly isolated endothelial cells from various solid organs
expressed Tlr2, Tlr4 and Myd88 transcripts at similar to even higher levels than cDCs and pDCs.
Preliminary results showed the same effects when Tek-Cre;Myd88fl/fl mice were infected with E. coli.
Our results thus demonstrate a fundamental and unanticipated role of the endothelium for sensing of
systemically spread pathogens and subsequent stimulation of BM emergency myelopoiesis.
FM264
Engineering a bone marrow stem cell niche through endochondrial ossification
Hitoshi Takizawa*, Elia Piccinini, Celeste Scotti, Markus Manz, Ivan Martin
Hematology, University Hospital Zurich (Zürich, CH); 2) Departments of Surgery and of Biomedicine,
University Hospital Basel (Basel, CH); Departments of Surgery and of Biomedicine, University Hospital
Basel (Basel, CH)
Bone marrow (BM) is a primary hematopoietic organ where lifelong self-renewing and hematopoietic
stem cells (HSCs) produce millions of all blood lineage cells every day. Robust regenerative potential
of HSCs is maintained in a unique microenvironment, termed HSC niche that produces necessary and
sufficient regulatory factors for HSC homeostasis. The structural and functional establishment of this
privileged niche at the embryo stage critically depends on the developmental process of endochondral
ossification.
Through a ”developmental engineering” approach, we recapitulated the endochondral route by ex
vivo culture of human adult mesenchymal stromal cells (hMSC) on a collagen sponge under
chondrogenic and hypertrophic conditions. Implantation into C57BL/6 nude mice allowed the
cartilaginous template to undergo extensive remodeling with CD31+ vessel ingrowth, TRAP+/MMP13+
osteoclast activity, and formation of mineralized bony tissue, thus defining an ectopic ossicle (EO).
Flowcytometric analysis of the EO-derived cells after 6 month in vivo remodeling showed comparable
frequencies of phenotypic mouse HSCs and progenitor cells to control native femurs. To test their in
vivo functionality, total cells harvested from EOs were transplanted together with competitor BM cells
into lethally irradiated congenic mice. Peripheral blood analysis showed that EO-derived cells
40
engrafted and reconstituted all blood lineages similar to control BM cells. BM analysis of recipients
after 3.5 months confirmed the successful engraftment and maintenance of EO-derived HSCs,
indicating a functional hematopoietic hierarchy reestablished by HSCs in EO.
These findings demonstrate that during in vivo stromal tissue remodeling the engineered EO becomes
capable of allowing endogenous HSCs to home and produce functional hematopoiesis, supporting its
functional equivalence in HSC niche formation to control BM. The engineering of ectopic BM niches
with hMSC could serve as a model to investigate physiology and pathophysiology of HSC
maintenance and hematopoiesis. Moreover, understanding of niche mediated regulatory mechanisms
of normal and pathologic HSCs will open the perspective towards improving clinical outcome of HSCbased regenerative medicine as well as cancer stem cell targeting therapies.
FM265
Loss of STAT1 ameliorates the phenotype of essential thrombocytaemia and
exacerbates erythropoiesis in in vivo models of JAK2V617F-driven MPN
Adrian Duek*, Pontus Lundberg, Takafumi Shimizu, Jean Grisouard, Radek Skoda
University of Basel (Basel, CH)
Introduction. Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic progenitors,
and include chronic myeloid leukaemia (CML), polycythaemia vera PV), essential thrombocythaemia
(ET) and others. In 2005, several independent groups identified a recurrent mutation (V617F) in the
pseudokinase domain of JAK2 in most patients with PV, ET or PMF. Its presence has been shown
responsible for cytokine hypersensitivity, aberrant regulation of its kinase activity by SOCS proteins,
and downregulation of PRMT5 methyltransferase activity. However, the question is how a unique
mutation might give rise to at least three different diseases. Recent publications have stressed the fact
that STAT1 signaling is activated in ET but not in PV. STAT1 promotes megakaryopoiesis while
inhibiting erythropoiesis and thus contributes to the ET phenotype.
Methods. To test the hypothesis that STAT1 promotes megakaryopoiesis and represses
erythropoiesis in the context of JAK2V617F-driven MPN, we used our transgenic mice expressing the
human JAK2V617F gene activated by CRE-recombinase under the control of either Vav (ET mouse
model) or the Scl promoter (PV mouse model), and crossed them with germline STAT1 knock out
(STAT1-/-) mice.
Results. JAK2V617F/VavCre/STAT1-/- mice showed attenuated ET phenotype in peripheral blood
comparing to JAK2V617F/VavCre/STAT1+/+. However, the mice still displayed splenomegaly,
evidence of myeloproliferation and fibrosis in both bone marrow and spleen. Analysis of
megakaryopoiesis in hematopoietic tissues revealed arrest in megakaryocytic maturation and increase
of pSTAT3 and pSTAT5 levels. JAK2V617F/SclCre/STAT1-/- line revealed similar attenuation in
platelet counts along with an evident exacerbation of the PV phenotype in peripheral blood. Analysis
of erythropoiesis demonstrated marked increase of erythroid precursors in spleen. The phenotype was
reproducible in recipient animals upon bone marrow transplantation.
Conclusion: We show that STAT1 plays a central role in determining the phenotypic presentation of
JAK2V617F-driven MPN by promoting megakaryopoiesis and repressing erythropoiesis. Bone marrow
transplantation showed that the changes observed in transgenic mice were cell autonomous and not
due to the effect of STAT1 deficiency on the microenvironment. However, nullizygousity of STAT1 is
not enough to totally abrogate the ET phenotype.
41
FM266
Engraftment and homing of human lymphoma B-cells are controlled by
junctional adhesion molecule C
Carmen Doñate*, Christiane Ody, Beat A. Imhof, Thomas Matthes
Hôpitaux Universitaire de Genève (Genève, CH); Université de Genève (Genève, CH)
Introduction: The junctional adhesion molecules (JAMs) are a subgroup of the Immunoglobulin
superfamily. JAM members localize at endothelial tight junctions and have been involved in the
formation and maintenance of interendothelial junctions and in leukocyte transmigration. JAM-C is
also expressed in human B cells and this expression is tightly controlled during differentiation, allowing
the classification of JAM-Cpos and JAM-Cneg B-cell lymphomas. In the current study, we investigated
the role of JAM-C in the homing and engraftment of normal and malignant B cells.
Methods: Human B cells were isolated from peripheral blood of healthy donors and lymphoma
patients. To study the role of JAM-C in B cell migration, B cells were incubated with a polyclonal and
six different monoclonal anti-JAM-C antibodies and injected i.v. into NOD/SCID mice. Homing of cells
to lymphoid organs (bone marrow, spleen, lymph nodes) was analyzed one hour later by flow
cytometry. To identify the interactions of JAM-C on B cells, binding, adhesion, immunofluorescence
and surface plasmon resonance assays were performed. To investigate the role of JAM-C in
lymphoma dissemination, the JAM-C positive B-cell line Jeko-1 was used for long-term engraftment
assays. Jeko-1 cells were injected into NOD/SCID mice and animals were treated for three weeks with
anti-JAM-C antibodies. Tumor burden was evaluated in lymphoid organs on day 26.
Results: Treatment with the polyclonal and 2/6 monoclonal anti-JAM-C antibodies reduced the homing
of normal and JAM-Cpos lymphoma B cells to lymph nodes, bone marrow and spleen by 50-60%.
Adhesion and plasmon resonance studies identified JAM-B as the major ligand for JAM-C, and
immunofluorescence analysis demonstrated the expression of JAM-B on murine and human lymphatic
endothelial cells. Accordingly, anti-JAM-C antibodies reduced the adhesion of JAM-C expressing B
cells to the ligand JAM-B by 50% and inhibited the binding of soluble JAM-B to JAM-Cpos B cells.
Long-term administration of anti-JAM-C antibodies reduced significantly the engraftment of JAM-Cpos
Jeko-1 cells in the bone marrow (21%), spleen (94%) and lymph nodes (93%) of NOD/SCID mice.
Conclusions: Our results demonstrate a functional role of JAM-C in B cell homing and engraftment into
lymphoid organs. Anti-JAM-C antibodies could thus represent a potential therapeutic approach
preventing lymphoma B cells from reaching supportive lymphoid microenvironments in bone marrow,
lymph nodes and spleen.
FM267
Aberrant somatic hypermutation-dependent BCL2 mutations in B-cell
lymphomas and their involvement in the evolution of follicular lymphoma
Regula Burkhard*, Urban Novak
Universität Bern (Bern, CH); Inselspital (Bern, CH)
Somatic hypermutation (SHM) is active in germinal centers (GC) and randomly introduces mutations
in immunoglobulin heavy chain genes (IgH) of B cells. Unlike normal B cells, 50% of diffuse large B
cell lymphomas (DLBCL) have somatic mutations in several proto-oncogenes. The features of these
mutations are consistent with an aberrant activity of the SHM (ASHM) mechanism on non-Ig loci.
Recently, BCL2 was identified as a novel target of ASHM in DLBCL (Saito & Novak, 2009). In 90% of
follicular lymphoma (FL) and 35% of GC-derived DLBCL, BCL2 expression is deregulated due to the
translocation t(14;18) joining BCL2 to the Ig enhancer. Clinically, FL is characterized by an indolent
course, but multiple relapses and transformation into DLBCL. To investigate if BCL2 is targeted by
ASHM in B cell non-Hodgkin’s lymphomas (B-NHLs) other than DLBCL, a panel of 104 primary BNHLs was screened for BCL2 mutations (promoter, exon 1 and 2, intron) by direct sequencing. Clonal
BCL2 mutations with features similar to those reported for IgH were present in various t(14;18)
positive and negative B-NHLs, which defines them as ASHM-depend. In comparison to DLBCL, BCL2
mutation frequency was lower in t(14;18) positive FL (0.77 vs. 0.31%) whereas it was higher in
t(14;18) negative FL (0.08 vs. 0.03%). To determine the involvement of BCL2 mutations during the
progression of FL, 10 matched pairs of FL relapsing to FL or DLBCL in the follow-up were
investigated. The lymphomas were clonally related in 9/10 cases as assessed by IgH-fragment length
analysis. Examination of BCL2 mutations in paired samples revealed two different patterns of a
genomic evolution of FL: (i) A direct / linear evolution from the antecedent FL clone reflected by few
novel clonal mutations in the DLBCL compared to the FL biopsy. (ii) The evolution from a common
progenitor cell characterized by both shared and unique clonal mutations in the initial FL and the
42
relapsed or transformed FL counterpart. As expected, in the clonally unrelated samples from one
patient, the sequential FL biopsies displayed no common BCL2 mutations, suggesting that the second
FL clone reflects a novel tumor and not a relapse of the ancestral FL. In summary, ASHM-dependent
BCL2 mutations are not restricted to DLBCL, indicating a critical involvement in B-NHL. BCL2
mutational analysis in serial biopsies of relapsing or transforming FL revealed contrasting patterns of
genomic evolution mirroring the complexity of FL.
FM268
Microtubule-associated protein 1S (MAP1S) is a novel PU.1 transcriptional
target in neutrophil differentiation of acute promyelocytic cells
Aladin Haimovici*, Martin Fey, Mario Tschan
Hôpital de l'Ile (Bern, CH)
The development of mature neutrophils is a complex process that is controlled by transcription factors
such as the myeloid master regulator PU.1. Suppression of PU.1 by the oncogenic fusion protein
PML-RARA in acute promyelocytic leukemia (APL) plays a major role in blocking differentiation of
these leukemic cells. In addition to its role in myeloid development, PU.1 is implicated in cell survival
and proliferation. The latter novel function of PU.1 has scarcely been studied. In this study we focused
on PU.1 targets involved in autophagy, which is mainly considered as a cell survival mechanism. A
first candidate gene possibly linking PU.1 to autophagy is the microtubule-associated protein 1S
(MAP1S). Generally, microtubules are associated with autophagosomes, which will fuse with
lysosomes for degradation of their contents. MAP1S has been implicated in microtubule dynamics,
mitotic abnormalities and cell death. Absence of this protein may result in various neurodegenerative
disorders, heart disease and cancer. We found that MAP1S is downregulated (mean delta Ct = 0,64)
in primary AML patient samples (n=120) compared to mature myeloid cells of healthy donors (mean
delta Ct = 3,45). Accordingly, MAP1S expression is upregulated in APL cell lines upon all-trans
retinoic acid (ATRA)-induced neutrophil differentiation. Knocking down PU.1 in NB4 APL cells
significantly impaired MAP1S upregulation during ATRA-induced differentiation. Moreover, PU.1
binding to the MAP1S promoter was shown by chromatin immunoprecipitation. Using lentiviral vectors
expressing shRNAs targeting MAP1S, we observed significantly attenuated neutrophil differentiation in
NB4 MAP1S knockdown as compared to control cells. Furthermore, knocking down MAP1S also
attenuated ATRA-induced autophagy. Together, we identified MAP1S as novel transcriptional target of
PU.1 with low expression in AML and a function in neutrophil development of APL cells. As
hematopoietic cells undergo several changes in morphology, the cytoskeleton might play an important
role in this process. Therefore a tight regulation of these cytoskeleton-associated compounds is
needed. Overall, our data link PU.1 to the cytoskeleton indicate a novel function of this transcription
factor.
FM269
Mesenchymal stem cells inhibit T-lymphocytes after poly(I:C) stimulation
José Maria Rincon Garriz, Marie Luce Piallat, Thomas Laumonier, Vincent Kindler*
Geneva University Hospital (Genève, CH); Geneva Medical University Center (Genève, CH)
Introduction: Lymph nodes are disseminated structures located in privileged regions of the body where
they drain the afferent lymph. They play a key role in the maintenance of self tolerance in steady state
conditions, and they restrain inflammation to specific sites during the ongoing of the immune
response. They comprise cells from hematopoietic origin recognized as effectors of acquired
immunity, and a stromal compartment, composed of various mesenchymal cell types including
mesenchymal stem cells (MSC), follicular dendritic cells (FDC), and fibroblastic reticular cell (FRC)
cells. Whereas MSC and FDC have been identified as key regulators of T and B lymphocytes, the
function of FRC has been thought for a long time to be restricted to structural tasks. However recent
investigations have demonstrated that FRC also participate to T and B lymphocyte control. We
therefore investigated whether MSC derived from human bone marrow could differentiate in FRC in
vitro.
Methods: Human MSC were purified from femoral head remains and amplified in vitro. Their
phenotype and their metabolic activity under various culture conditions were assessed by FACS and
biochemical assays.
Results: Human MSC amplified in vitro in the presence of platelet supernatant exhibited a phenotype
resembling that of FRC (CD31-, CD54low, CD44+, CD146+, alpha SMA+) suggesting that they
spontaneously differentiated toward this lineage. When incubated with poly IC in vitro they showed
43
similar phenotypic alterations than murine FRC exposed to poly IC in vivo, namely an increase in
MHC-I, CD54 and B7-H1 expression. Moreover MSC incubated with poly IC or gamma-interferon
actively depleted the culture medium in L-tryptophan indicating that the indolamine 2,3 deoxygenase
was activated, and such media could not support T cell proliferation.
Conclusion: These observations suggest that the systemic anti-inflammatory effect exerted by MSC
when infused intravenously (as documented by their ability to control steroid-resistant graft versus
host disease) may reflect the physiological regulation that MSCs, or their progeny differentiated in
FRC exert in the lymph nodes when exposed to local inflammation.
FM270
New function for Dicer1 in differentiation of acute promyelocytic leukaemia
cells
Julian Wampfler*, Maritn F. Fey, Mario P. Tschan
Institute of Pathology, University of Bern (Bern, CH); Inselspital (Bern, CH)
MicroRNAs (miRNAs) are globally downregulated in cancer and often impact on cellular differentiation
programs. Dicer1, an RNAse III family member, plays a key role in miRNA maturation. Importantly,
Dicer1 mutations correlate with adverse prognosis in many human cancers including ovarian cancer,
lung carcinoma and malignant melanoma. We investigated if Dicer1 plays a role in the pathology of
acute myeloid leukemia (AML) that is characterized by a block of myeloid differentiation at different
stages. Firstly, we quantified Dicer1 mRNA expression in a large cohort of AML patient samples (n =
119). We found a significant downregulation of Dicer1 in AML blasts and normal CD34^+ progenitor
cells as compared to mature neutrophils from healthy donors. In line with these findings, PML-RARA
positive acute promyelocytic leukemia (APL) NB4 cells displayed a significant induction of Dicer1
mRNA expression upon all-trans retinoic acid (ATRA) induced neutrophil differentiation. Conversely,
NB4-R2 ATRA-resistant cells showed no induction of Dicer1 expression indicating that Dicer1
upregulation is not due to an unspecific ATRA-response. Next, to address the function of Dicer1 in
neutrophil differentiation, we generated two independent NB4 Dicer1 knockdown cell lines using
lentiviral vectors expressing small harpin (sh) RNA targeting Dicer1. Of note, inhibiting Dicer1 will
phenocopy a cancer-like low miRNA expression model based on its central role in miRNA maturation.
Dicer1 knockdown resulted in a significantly reduced induction of the neutrophil-specific miR-223
during neutrophil differentiation showing functionality of the implemented Dicer1 knockdown.
Generally, Dicer1 knockdown cells displayed attenuated neutrophil differentiation compared to control
shRNA cells as assessed by CD11b and granulocyte colony-stimulating factor receptor expression as
well as reduced autophagy activity as measured by LC3 dot formation on cytospin preparations.
Autophagy, a bulk degeneration process, was recently linked to PML-RARA degradation in APL. Our
results indicate that Dicer1 plays a significant new role in neutrophil differentiation and in autophagy of
APL cells. We observed Dicer1 downregulation in a large cohort of clinical AML patient samples and
CD34^+ progenitor cells indicating that low Dicer1 expression is associated with an immature myeloid
phenotype. Dicer1 and thus miRNA deficiency leads to multiple alterations of pathways important for
APL differentiation and autophagy.
44
Freie Mitteilungen SFGG - Communications libres SPSG
FM271
Variations in population health status: results from a survey addressing
inequalities in ageing in Switzerland
Christophe Luthy*, Catherine Ludwig, Christine Cedraschi, Anne-francoise Allaz, Francois Herrmann
hôpitaux universitaires de genève (Genève, CH)
Objectives: The present cross-sectional, nation-wide survey aims to describe Health Related Quality
of Life (HRQOL) of elderly people in Switzerland. Data focusing on these aspects are scarce.
However, the conceptualization and assessment of HRQOL are crucial to health policy and evaluation
research in this population.
Methods: Stratified random samples representative of the general population aged >65 (65-69, 70-74,
75-79, 80-84, 85-80, > 90), living in the community (N=2907). The survey was conducted in the 3
linguistic areas. The EQ-5D was used to assess HRQOL. This self-reported questionnaire investigates
5 dimensions: Mobility (MO), Self-Care (SC), Usual Activities (UA), Pain/Discomfort (PD), and
Anxiety/Depression (AD). Each dimension is subdivided into three categories (no problem, moderate
problem, extreme problem) and provides a global score (Visual Analogue Scale ranging from 0 to
100). Socio-demographic variables included gender and education, besides age and linguistic area.
Regression analyses were carried out on the scores of each 5 dimensions.
Results: Mean EQ-5D global score was 75 (SD=20) for the total sample, and decreased with age,
ranging from 79 (SD=19) in the younger group to 71 (SD=22) in the oldest. Twenty-five percent of the
sample reported difficulties in MO, ranging from 9% in the younger group to 59% in the oldest; 7%
reported difficulties in SC (from 1% to 26%); 14% reported difficulties in UA (6% to 40%); 51%
reported PD (42% to 62%); and 21% reported AD (18% to 23%). Interestingly, the evaluation of the
severity, i.e. 'moderate' or 'extreme' problem, of each dimension had an impact on the global VAS
score for PD and AD only; as for the functional items, i.e. MO, SC and UA, only the presence or
absence of problems played a role.
Regression analyses showed that the effect of age was significant on all measures, except AD.
Besides, age explained more than 10% of the variance, but in the functional dimensions only.
Linguistic areas, gender and education had a significant effect although they explained only a marginal
part of the variance (<5%).
Discussion: HRQOL in the elderly is overall good although it decreases with age. Interestingly,
functional dimensions are more affected by age than pain and emotional problems. There is a similar
trend for the global score. Taken together, these results suggest that functional dimensions play a
major role in determining self-reported HRQOL in the aging population.
FM272
Prevalence of polypharmacy and potentially inappropriate medication in the
older, community-dwelling population in Switzerland
Eva Blozik*, Roland Rapold, Jan von Overbeck, Oliver Reich
Schweizer Zentrum für Telemedizin Medgate (Basel, CH); Helsana (Zürich, CH); Helsana (Zürich, CH)
Introduction: Polypharmacy and potentially inappropriate medication (PIM) are associated with
adverse outcomes such as hospitalisation, loss of productivity, and death. This study evaluates the
prevalence of polypharmacy and PIM in the older, community-dwelling population in Switzerland.
Methods: The analysis is done based on claims data of community-dwelling persons aged older than
65 years insured with the Helsana health insurance group (>3 million person years in the years 20082010). We calculated the number of medications submitted for reimbursement, the proportion of
persons with polypharmacy, and the proportion of persons receiving PIM according to the updated
Beer’s criteria and the PRISCUS list. Additionally, we estimated cost for medications and PIM, and
identified the most prevalent groups of PIM according to the Anatomical Therapeutic Chemical
Classification System (ATC).
Results: Forty-one percent of the older population in Switzerland received 5 or more medications
which is one of the common definitions of polypharmacy, and over 23% had a PIM according to Beers
criteria or the PRISCUS list. The most prevalent PIM were psycholeptics, sex hormons,
antiinflammatory drugs, and psychoanaleptics.
45
Conclusion: The prevalence of polypharmacy and PIM in Switzerland seems to be alarmingly high and
is associated with considerable cost. A broad spectrum of interventions on the individual level as well
as on the population level is urgently needed.
FM273
Patients’ characteristics associated with opiate prescription at discharge in
post-acute rehabilitation: a pilot study
Simona Mateiciuc*, Mélanie Theodoloz, Noémie Marcoz, Rebecca Dreher
Ensemble Hospitalier de la Côte (Gilly, CH)
Objective: To investigate patients’ characteristics associated with opiate prescription at discharge in
post- acute rehabilitation. Opiates were defined using WHO criteria.
Method: Over 12 months, opiate prescription at discharge was recorded prospectively in 392 patients
( mean age 82.9 ± 6.4 years; 71.9 % women; 63% living alone) consecutively admitted to post acute
rehabilitation. Data on demographics, medical and functional status were collected upon admission
using standardised instruments.
Results: Overall 23,2% (91/392) of patients had opiates prescribed at discharge. Compared to
persons without opiates, those with opiates at discharge, had no statistically significant difference
regarding age (mean 81.4 ±6.2 vs 83.3 ±6.4 years; p= .53), sex (80.2% women vs 69.4% women,
p=.061); living alone (70.3% vs 60.8% , p=.23), functional status at discharge (Barthel score 74.3 ±25
vs 76.3 ±23.3 p=.53) . In multivariate analysis age (being younger) (p=.001) and living alone (p=.04)
were independent predictors for having opiates prescribed at discharge. Concomitant laxative
prescription occurred in 83.3% of cases.
Conclusions: In these real world conditions, opiate prescription was high, with nearly a quarter of
these elderly, frail persons being discharged from a post- acute rehabilitation with an opiate.
Interestingly, age and living alone were the only independent characteristics associated with opiate
prescription. Further, larger studies need to be undertaken to better determine further characteristics.
FM274
Predictors of revascularisation after acute coronary syndrome in elderly
patients
Christophe Graf*, Anne Auckenthaler, Francois Sarasin, Gabriel Gold, Francois Herrmann, Thierry
Chevalley
Hôpital des Trois Chêne (Thonex, CH); Hôpitaux Universitaires de Genève (Genève, CH)
Acute coronary syndrome (ACS) is a major health problem and leads to a high rate of mortality.
Therapeutic strategies include either conservative or invasive treatment like percutaneous coronary
intervention or coronary artery bypass grafting. Invasive treatment is superior to control symptoms.
However, as older patients are often excluded from randomized controlled trials, its benefit in this
population is not established. The choice of treatment is based on a risk-stratification using for
instance the TIMI score, but does not take into account the comorbidities or the functional status.
This study aims at evaluating whether the comorbidities or the functional status influence the choice of
treatment in older patients with ACS.
We performed a cross-sectional study at the Geneva University hospitals. Patients over 70 years
admitted to the emergency department for ACS were included over a 6 month period. Exclusion
criteria were dementia, terminal illness or cardiac intervention in the previous 6 months. Functional
status was assessed by the Barthel index. Active comorbidities, cardio-vascular risk factors (CVRF),
TIMI scores and biological measurement like creatinemia were collected.
103 patients were included (mean age (±SD) 83.4±5.9 years, 54% of females). 57 patients (55%)
underwent a revascularization. According to the Barthel index, 7 (7%) patients were severely
dependent, 56 (54%) moderately dependent, and 40 (39%) independent. The number of active
comorbidities were (median (±IQR)) 3±2, of CVRF 2±1, and TIMI scores 3±1. Mean creatinemia was
114±49 µmol/l. In univariate logistic regression models, age and creatinemia were associated with a
decreased rate of revascularization with odds ratio (OR) and 95% confident interval [95% CI] of 0.79
[0.72-0.87] and 0.98 [0.97-0.99], respectively. On the other hand, Barthel index was positively
associated with a higher rate of invasive procedure of 1.05 [1.01-1.09]. Sex, number of CVRF, number
of comorbidities, and TIMI scores were not associated with the choice of treatment. In the multiple
regression analysis, age, creatinemia, number of CVRF, and number of comorbidities explained 30%
of the model's variance.
46
After an ACS, the choice between conservative or invasive treatment is clearly influenced by the
patients' age. Nevertheless, our results suggest that the number of comorbidities as well as the
functional status have to be taken into account for this decision.
FM275
The Liverpool Care Pathway (LCP) in the Geriatrische Klinik St. Gallen.
Yesterday, today, tomorrow
Bozana Popovic Sesartic*, Gabriela Bischofberger, Thomas Münzer
Geriatrische Klinik (St. Gallen, CH)
The Liverpool Care Pathway (LCP) is a standardised instrument for symptom control in palliative care,
used to support dying patients and their families during the period of dying and beyond death. It was
introduced in 2006 as a pilot project in the Geriatric Clinic St. Gallen (GC) and is established there
since 2007. A project group responsible for the introduction of LCP developed new forms and
conducted intensive training with the medical staff. Between 2007 and 2012, 126 women and 98 men
with an average age of 84.5 years were induced in the LCP. The main reasons for inclusion were:
cancer, stroke, heart failure and pneumonia. The average treatment time was 4 days. A statistical
analysis of symptoms during the last days and hours before death (pain, agitation, bronchial
secretions, nausea/vomiting, dyspnoea) helped to improve the concept. Until now there was a lack of
experience with LCP in geriatrics. The question when an old person is dying, remains still
unanswered. Therefore the project “diagnosing dying” was initiated. “Diagnosing dying” is a
prospective multicenter observational study with the goal to develop and validate an instrument for the
improvement of care and the detection of indicators for dying during the last days and hours of life. It is
a part of the OPCARE9 project, which is funded by the FP7 programme of the European Commission
started in October 2012. Based on our retrospective data analysis the LCP has become a very useful
palliative care tool in acute geriatrics. The structured approach leads to a transparent and optimized
process for all involved, thus reducing the psychological pressure on the medical team and the
patient’s relatives. The self-determination of the patient and his or her autonomy is guaranteed, the
relatives are more involved and therefore happier and relieved. The excellent experience with LCP in
GC has led to the decision to extend the LCP procedure to the long term care unit of the “Competence
Centre for Health and Aging” in St. Gallen.
FM276
Patients admitted to post-acute rehabilitation following a hip fracture:
outcomes and related factors
Sylvain Frascarolo*, Christophe Büla, Laurence Seematter-Bagnoud
Centre Hospitalier Universitaire Vaudois (Lausanne, CH)
Introduction: Hospital admissions following hip fracture increase due to the growing number of oldestold persons. Information regarding the profile and outcome of older patients admitted to post-acute
rehabilitation after a hip fracture is still fragmentary. This study aimed to describe the characteristics of
these patients, as well as functional recovery and other outcomes at discharge.
Methods: Subjects were community-dwelling patients (N=665) aged 65+ years admitted to the
university rehabilitation center following a hip fracture. Within 48 hours of admission, each patient was
systematically evaluated by rehabilitation team members who collected information on sociodemographics, medical, functional, affective, and cognitive status.
Outcomes were functional gain on the Barthel scale, length of stay, and discharge destination.
Results: Patients were aged 84.1±7.0 years, 77.4% were female. Prior to hospitalization, 65.8% lived
alone, and 50.6% received formal home care. At admission, 33.3% of the subjects had cognitive
impairment and 16.1% had depressive symptoms, 7.7 % having both.
Overall, mean Barthel score increased from 52.1±18.0 at admission to 75.4±20.6 at discharge (mean
gain 23.3). Functional performance at discharge was strongly associated with cognitive and affective
status at admission and decreased gradually from patients cognitively intact without depressive
symptoms to those with both cognitive and depressive problems, who achieved the lowest functional
gain (See Figure).
Mean length of stay varied according to patients’ cognitive status, ranging from 25.7±13.5 days in
those cognitively intact to 29.7±13.8 days among cognitively impaired ones (p<.001). In contrast,
length of stay was similar among patients without and with depressive symptoms (26.9±13.5 vs
26.7±14.9, p=.855).
47
Overall, most patients were discharged back home (70.8%). However, this proportion gradually
decreased from 82.8% among cognitively intact patients without depressive symptoms to only 45.6%
in patients with both cognitive and depressive problems. In parallel, the proportion admitted to long
term care increased.
Conclusion: Overall, older persons admitted to post-acute rehabilitation following hip fracture show
significant recovery during their stay. However, patients with cognitive and/or depressive problems
show significantly poorer rehabilitation outcomes, suggesting that they might benefit from specific,
longer, or more intensive rehabilitation interventions.
FM277
Complications during inpatient geriatric rehabilitation following proximal
femoral fractures and rehabilitation outcome
Matthias Frank*, Annika Lanz, Christian Ritter, Norbert Suhm, Eveline Nonnenmacher, Yvonne
Zysset, Martin Conzelmann
Felix Platter Spital (Basel, CH); Universitätsspital (Basel, CH)
Background: Proximal femoral fractures (PFF) are the most common fractures above the age of 80
years. Medical and surgical complications are often observed during inpatient geriatric rehabilitation.
Methods: We retrospectively studied all patients entering geriatric inpatient rehabilitation following
surgery for a PFF (pertrochanteric or femoral neck) between January 2011 and May 2012. Data on
medical and surgical complications were extracted from the medical records. Baseline data included
sociodemographic variables and the results of the geratric assessment on admission. Complications
were classified according to a consensus paper on outcome parameters in orthogeriatric management
(Liem et al., submitted)
Results: 109 patients were identified. There were 57 pertrochanteric and 52 femoral neck fractures. 69
patients (63%) suffered from at least one complication. Urinary (29%) and cardiac (17%)
complications were observed most frequently. Surgical complications were less common (11%). 39
(35%) patients had more than one complication. On admission, patients with complications were
significantly older, showed weaker hand grip, were more dependent (Barthel Index 41.4±16.8 vs
53.9±14.9) and scored lower on the MMSE. During rehabilitation, gain in Barthel index was similar in
both groups (25.8±18.6 vs 27.7±14.2), but patients suffering from complications had a longer length of
stay (36.0±18.9 vs. 26.1±11.5 days) and were less likely to be discharged to their own home directly
(59.4% vs. 85.0%).
48
Conclusion: Geriatric rehabilitation in PFF is complicated by medical or - to a much lesser extent –
surgical problems in more than half of patients. Geriatric assessment on admission can identify
patients at higher risk for complications. Rehabilitation length of stay is prolonged considerably in
patients suffering from complications.
FM278
Teaching functional assessment to medical students: why not play games?
Philippe Huber*, Abdelmalek Saber, Yves Schnellmann, Gabriel Gold
Service de gériatrie (Genève, CH)
Introduction: Nowadays, most physicians take care of a growing aging population suffering from
multiple chronic diseases and disabilities. Therefore, a good knowledge of functional assessment is
required, and this topic should be addressed in the pregraduate medical curriculum.
Method: We report our 10-year experience with a seminar on functional assessment using an "aging
game" as a pedagogic vector. This seminar is organized by geriatricians, occupational therapists and
physiotherapists. First, medical students are exposed to various situations where they experiment
disabilities and try to elaborate compensatory strategies. Then, they reflect on a challenging discharge
project by analyzing a written clinical case. This written case gives the opportunity to reflect on
functional assessment, on the importance of a multidisciplinary approach, and on the implication of
various actors of the health care system in the community. Finally, students are introduced to the use
of validated functional assessment instruments.
Results: Evaluation indicated that this pedagogical approach is much valuated by the students and
foster the acquisition of knowledge in functional assessment.
Conclusion: This seminar shows a good efficacy in introducing medical students to the difficult concept
of functional assessment. Moreover, this seminar can easily be adapted to the training of other health
care professionals.
49
Hemostasis, Vascular Biology and Transfusion Medicine - Hemostasis,
Vascular Biology and Transfusion Medicine
FM279
Dietary alpha-linolenic acid reduces platelet clearance in spleen and liver
inducing an increased platelet count in ApoE-/- mice
Simona Stivala*, Christine Lohmann, Thomas Lüscher, Christian Matter, Hans Jürg Beer
Kantonsspital Baden (Baden, CH); Physiology Institute, University of Zurich (Zurich, CH); University
Hospital (Zurich, CH)
Introduction: We recently showed that the plant-derived n-3 fatty acid alpha-linolenic acid (ALA) has
cardioprotective effects by reducing experimental atherosclerosis and platelet-dependent thrombosis
in mice. We hypothesized that ALA might lead to a prolonged platelet survival in the circulation due to
a reduced platelet activation.
Methods: 8-week-old male ApoE-/- mice were fed a 0,21g% cholesterol diet containing either a high
(7,3g%) or low (0,03g%) ALA content for 16 weeks. Platelet counts were assessed monthly. Platelet
production was analyzed by reticulated platelet staining and megakaryocyte-CFU. Platelet turnover
was assessed by plasma glycocalicin (GC) concentration (ELISA), normalized to the platelet count
(the GC-Index). Platelet clearance in spleen and liver was determined by immunofluorescence
staining on frozen sections. GPIbalpha cleavage upon thrombin stimulation was assessed by flow
cytometry.
Results: After 16 weeks mice in the high-ALA group had significantly higher platelet counts compared
to the low-ALA group (1591±650x103/ µ l vs 1053±323x103 µ l, n=30, p=0.0002), without showing
different tail bleeding times (285±83 high-ALA vs 221±56 sec low-ALA, n=5, p=n.s.). Platelet
production was not different between the two groups as assessed by the reticulated platelet count
(72±34 x103/ µ l in the low ALA vs 55±47 x103/ µ l in the high ALA group, n=15, p=n.s.), and number
of megakaryocyte-CFU from bone marrow (12±4 vs 11±4, n=3). Plasma GC was significantly lower in
the high ALA group (25±15 vs 53±27 µ g/ml, n=17, p=0.0007), and the GC-Index was 6,6±3 vs 15±5,
n=17, p<0.0001. Platelet clearance in spleen and liver was significantly reduced in the high ALA group
(spleen CD41+ area: 143,482 um2 vs 94,724 um2, n=3, p=0.0049; liver: 54,095 um2 vs 33,224, n=3,
p=0.033). GPIbalpha cleavage upon thrombin stimulation was significantly reduced in platelets from
the high ALA mice (mean fluorescence intensity vs resting state: 64 ±5% high ALA vs 52 ±8% low
ALA, n= 6, p=0.01).
Conclusions: A diet rich in ALA increases the platelet count by reducing platelet clearance.
Mechanisms may include the inhibition of MAP kinase p38 phosphorylation and therefore reduced
platelet activation and a reduced GPIbalpha cleavage. The finding might be of clinical importance in
transfusion medicine.
50
FM280
Genotype and phenotype of a large series of patients with congenital
dysfibrinogenaemia
Alessandro Casini*, Françoise Boehlen, Marguerite Neerman-Arbez, Philippe de Moerloose
HUG (Genève, CH); CMU (Genève, CH)
Introduction: Congenital dysfibrinogenemias (CD) are characterized by biosynthesis of a structurally
abnormal fibrinogen molecule that exhibits reduced functional properties compared to level of
fibrinogen antigen. To date a large number of mutations have been identified in patients with CD,
although few are predictive of the clinical phenotype. In order to better understand the clinical
complications in relation to the genotypes, we report a survey of 65 CD diagnosed in our laboratory.
Method: Biological and clinical characteristics were recorded at reception of samples using a
standardized case report. After isolation of genomic DNA, exons and intron-exon junctions of the
fibrinogen genes were amplified by polymerase chain reaction (PCR) and sequenced.
Results: Between 2005 and 2012 we diagnosed 65 CD. Samples were sent to our laboratory
principally to perform a familial screening (n=23, 36%), before surgery (n=14, 21%), following
thrombosis (n=8, 12%) and for investigation of bleeding (n=7, 11%). The median age at time of DNA
analysis was 36 years (range 1 – 76 years). The median fibrinogen activity (Clauss method) was 0.66
g/l (range 0.1 – 2.3) and the median antigen fibrinogen was 3.5 g/l (range 1.4 – 5.3). Mutations were
identified in the coding sequences of fibrinogen genes in all 54/54 (100%) probands. Heterozygous
missense mutations in residues Arg35(Arg19) of FGA in exon 2, Arg301(Arg275) of FGG exon 8 and
surrounding residues accounted for almost 75% of CD (Table 1). Twenty-three patients (35%) had
mild bleeding episodes, easy bruising, epistaxis and menorrhagia being the most frequent. Thirteen
(20%) and 3 (5%) patients experienced at least one venous or arterial thrombosis, respectively. A total
of 30 pregnancies were reported, including 6 (20%) miscarriages. Deliveries were not associated with
bleeding complications.
Conclusions: Mutations in exon 2 of FGA and in exon 8 of FGG are the most frequent causes of CD.
At the time of diagnosis half of patients experienced mild bleeding or thrombotic events. CD is
associated with miscarriage. An ongoing trial is evaluating the long term follow-up of these patients in
order to better define the true incidence of bleeding complications and/or thrombotic events during the
course of disease.
51
FM281
Clinical outcome of haemophilia patients undergoing major orthopaedic
surgery without pharmacological thromboprophylaxis
Stefan Rinderknecht Graf*, Bernhard Gerber, Peter P. Koch, Brigitte Brand
Spital Bülach (Bülach, CH); Universitätsspital Zürich (Zürich, CH); Universitätsklinik Balgrist (Zürich,
CH)
Background: Hemophilia patients are generally considered at low risk for venous thromboembolism.
However, orthopedic surgery for hemophilic arthropathy exposes them to well established major risk
factors for venous thrombosis due to the procedure itself, long immobilization, and factor replacement
therapy. In contrast to non-hemophilia patients, pharmacological prevention of thromboembolism for
hemophilia patients is not well studied nor standardized and largely depends on local practice. A
multicenter European survey reported that 50% of centers are using anticoagulant prophylaxis. At our
center, in agreement between orthopedic surgeon and hematologist, no pharmacological prevention of
thromboembolism is given to patients undergoing orthopedic surgery.
Aim: The present study analyzes the safety and feasibility of this approach.
Methods: Retrospective analysis of all orthopedic operations performed in hemophilia patients of our
center between 1978 and 2012.
Results: A total of 166 major orthopedic operations were performed in 47 patients. 43 (91.5 %) had
hemophilia A and 4 (8.5%) hemophilia B. 31 (66%) patients suffered from severe, 14 (29.8%) from
moderate and 2 (4.3%) from mild disease, respectively. One patient (2.1%) had a combined
FVIII/Factor V deficiency. Median age was 44.9 years (IQR 34.9-55.0). Orthopedic interventions were
divided into surgery of the lower extremity (n=138, 83.1%%) and the upper extremity (n=21, 12.7%),
for 7 (4.2%) data are missing. Follow-up information 9 weeks after surgery could be obtained for 124
operations (74.7%). No clinical signs of venous thromboembolism were observed in all cases. One
(0.6 %) intervention in a mild hemophiliac was complicated by a life-threatening perioperative
myocardial infarction.
Data on factor consumption was available for 101 interventions (60.3%) with a total dose per
hospitalization of 45’000 IU (IQR 33’250-60’250) given to patients (mean body weight of 71.3 kg).
Transfusions of red blood cells were needed in 12.3% of all interventions.
Conclusions: In this cohort of hemophilia patients undergoing orthopedic surgery without
pharmacological prevention of thromboembolism followed over an overall period of 34 years, no
symptomatic deep venous thrombosis or pulmonary embolism was observed. Prospective trials
incorporating a systematic assessment for thrombosis are needed to confirm these encouraging data.
FM282
Insights into the role of protein S/growth arrest-specific gene 6 pathway in the
pathophysiology of purpura fulminans
Raja Prince*, Sara Calzavarini, François Saller, Monica Azevedo, Michael Racine, Anne AngelilloScherrer
Background: Currently, purpura fulminans (PF) pathophysiology involves a complete blood flow
blockade in dermal and subcutaneous vasculature, the blockade being of thrombotic or infectious
origin.
Both protein S (ProS) and growth arrest-specific gene 6 (Gas6) product are vitamin K-dependent
proteins. ProS is a natural anticoagulant. Its physiological importance is evident in PF and other lifethreatening thrombotic disorders typical of ProS deficient patients. ProS deficiency in mice has shown
similarities with the human phenotypes. In contrast to ProS, Gas6 displays a procoagulant effect,
amplifying platelet activation and upregulating tissue factor in the vasculature. In tissues, ProS and
Gas6 exert cellular functions by binding to and activating tyrosine kinase receptors of the Tyro3 family
(TAM) on the cell surface.
Methods and results: Mice with complete Gas6 or partial ProS deficiency did not develop spontaneous
PF. To study further the role of ProS, Gas6 and TAM receptors in PF pathophysiology, we generated
a model mimicking this disorder by exposing mice to warfarin, a vitamin K antagonist. Wild-type (WT)
mice, or mice deficient in ProS, Gas6 or in either one of the TAM receptors received warfarin for 5
days. Most of Gas6-/- mice and Gas-/-/ProS+/- mice succumbed to this challenge whereas most WT
mice survived (mortality rate: 85% in Gas6-/- and 87% in Gas6-/-/ProS+/- compared to 5% in WT
mice, p<0.05). Some mice deficient in TAM receptors also died during warfarin challenge. On warfarin,
part of the mice with ProS/Gas6 pathway deficiency developed skin lesions compatible with PF
52
involving ears, extremities and genital areas. Such lesions were never observed in WT. Early lesions
were erythematous with highly visible ear skin vessels, necrosis appearing in advanced lesions. Ear
skin histology of mice with PF showed vascular engorgement, intradermal edema and only rare
thrombosis in early lesions, whereas massive red blood cell extravasation, intra-epidermal
hemorrhagic blisters and necrosis were found in advanced lesions.
Conclusions: There was a prominent vascular involvement in PF lesions when the ProS/Gas6
pathway was deficient. Lack of Gas6 or TAM receptors being antithrombotic, the thrombotic process
might be less central in PF pathophysiology than currently admitted. Thus, the vasculature might
constitute the main target during PF development and the ProS/Gas6 pathway through the TAM
receptors in the endothelium appeared to be involved in the process.
FM283
Anti-idiotypic DARPin molecules: potential new treatment tools for acquired
thrombotic thrombocytopenic purpura (aTTP)?
Monica Schaller*, Sabine Hiltbrunner, Irmela Sulzer, Monique Vogel, Karim Kentouche, Bernhard
Lämmle, Johanna Kremer Hovinga
Inselspital Bern (Bern, CH); Friedrich Schiller Universität (Jena, DE)
Aim: The hallmark of aTTP is a severe ADAMTS13 deficiency resulting from autoantibodies (Abs)
neutralizing and/or accelerating ADAMTS13 clearance. Despite the success of plasma exchange the
risk of relapse is ~ 40%. A therapy using small molecules capable to neutralize inhibitory antiADAMTS13 Abs and to eliminate anti-ADAMTS13 specific memory B- and plasma cells would be
highly desirable.
Method: Two small protein libraries of Designed-Ankyrin-Repeat-Protein (DARPins, Molecular
Partners AG, Switzerland) coding for 2 (N2C, diversity of 1015) or 3 (N3C, 1023) randomized ankyrin
repeat modules were screened against an equimolar pool of 3 previously generated spleen-derived
inhibitory monoclonal anti-ADAMTS13 Abs holding 1 of 4 CDR3 motifs shared by two acquired TTP
patients (pat) using Ribosomal display. DNA sequence of selected anti-idiotypic single DARPin clones
from the fourth panning round were analyzed and DARPins purified to test their specificity and
neutralization potential towards the selecting and additional inhibitory Abs (n=5) holding the same
CDR3 motif by ELISA or FRETS assay. Furthermore the binding capacity of an equimolar pool of the
selected DARPins towards anti-ADAMTS13 Abs in plasma of 37 different aTTP Pat were tested by
ELISA.
Results: Nine unique, as revealed by their DNA sequence, anti-idiotypic DARPins were highly specific
for their targets. Preincubation with spleen-derived inhibitory anti-ADAMTS13 Abs (equimolar mAbs
pool) with a 10- fold molar excess of four 4 anti-idiotypic DARPins restored ADAMTS13 activity in
plasma in a dose-dependent manner as assessed by FRETS assay. Moreover, the four anti-idiotypic
DARPins bound anti-ADAMTS13 antibodies from plasma of 27/37 additional aTTP Pat and reduced
binding to immobilized recombinant ADAMTS13 by 70-95% when pre-incubated with Pat plasma
(n=5).
Conclusions: Using inhibitory anti-ADAMTS13 Abs of one Pat we were able to select 4 different highly
specific anti-idiotypic DARPins that not only bind to anti-ADAMTS13 Abs holding a similar CDR3 motif
than the selecting Abs, but also to a substantial proportion of anti-ADAMTS13 Abs in plasma of
randomly selected aaTTP Pat. Our results are promising and hint at a limited number of different antiidiotypic molecules necessary to neutralize inhibitory anti-ADAMTS13 Abs as a therapy. Affinity and
neutralizing analysis of all 9 selected anti-idiotypic DARPins are underway.
FM284
Acute coronary syndrome in persons with haemophilia
Philippe de Moerloose*, Peter Staritz, Roger Schutgens, G. Dolan on behalf of the Advance Working
Group
Introduction. As life expectancy in persons with hemophilia (PWH) increases, cardiovascular disease
management becomes more important. Currently, evidence based guidelines for antithrombotic
management in PWH are lacking. ADVANCE is an expert panel of European hemophilia centers
supported by an educational grant from Bayer Healthcare.
Methods. Using structured communication techniques and a 35 point questionnaire to establish
consensus, 15 ADVANCE members reviewed recent ESC guidelines for STEMI, NSTEMI and
myocardial revascularization with regard to hemophilia.
53
Results. Questions are shown with percentage of agreement in parenthesis. A hemophilia expert
should be consulted as soon as PWH present with an acute coronary syndrome (ACS) (100%). PWH
should be managed according to the ESC "high bleeding risk" patient category (100%). Treatment of
an ACS should be started immediately (33%) or delayed until replacement therapy is available based
on known factor levels (66%). Fibrinolysis is justified in replaced PWH when early PCI is not available
(100%). Target factor level should be >=30 (100%), >=50 (78%), >=80 (53%). Target peak level for
early PCI should be >=30 (100%), >=50 (93%), >=80 (80%). Bare metal stents are preferred over drug
eluting (93%). All patients should receive dual antiplatelet therapy (87%). Anticoagulants are not
advisable in non-replaced PWH (80%), but are acceptable in replaced PWH (100%) with a preference
for unfractionated heparin and enoxaparin. The trough level for PWH undergoing long term dual
antiplatelet therapy should be >=1% (100%); >=5% (87%); >=10% (40%); >=30% (33%).
Conclusions. In ACS and myocardial revascularization, hemophilia treaters have to deal with
controversial therapeutic aims such as clotting factor replacement and therapeutic standards,
including anticoagulation and antiplatelet therapy which is normally contraindicated in PWH. Complete
consensus was not achieved especially concerning dosage of clotting factors. Risks and benefits have
to be assessed for every situation. The results of our process could aid decision making when tailoring
therapy for each PWH and setting.
54
Clinical Hematology - Clinical Hematology
FM285
Very early onset of autoimmune thrombotic thrombocytopenic purpura in five
children of Polynesian origin, in four cases combined with immunodeficiency
Magnus Mansouri Taleghani*, Peter Bradbeer, Nyree Cole, George Chan, Bernhard Lämmle,
Johanna A. Kremer Hovinga
Bern University Hospital and the University of Bern (Bern, CH); Starship Children's Hospital (Auckland,
NZ); Auckland City Hospital (Auckland, NZ)
Background
Autoimmune thrombotic thrombocytopenic purpura (aTTP) is a rare disease characterized by
thrombocytopenia, microangiopathic hemolytic anemia with schistocytes on the peripheral blood
smear and a variable degree of endorgan ischemia. The high mortality if left untreated (80-90%) and a
relapsing course in 44% of survivors underline the seriousness of this disease. Underlying is a severe
ADAMTS13 deficiency (<5% of the normal) due to inhibitory autoantibodies preventing normal
processing of unusually large Von Willebrand factor multimers. First episodes of aTTP typically occur
in women between 20-40 years of age and are rarely seen in children.
Observation
Strikingly, over the last 7 years we observed frequently relapsing aTTP with severe acquired
ADAMTS13 deficiency and inhibitory autoantibodies in 5 children (aged 1-11 years) of Polynesian
origin. At least 4 of the 5 cases have additional signs and symptoms indicative of a common variable
immune deficiency (CVID).
Results
Case 1,2 and 3 have hypogammaglobulinaemia requiring regular intravenous immunoglobulin
infusions (IvIg) for at least 5 years now. While in case 1 hypogammaglobulinaemia and other
symptoms indicative of immunological dysregulation (eosinophilic colitis, asthma, excema…) had been
documented prior to the first aTTP episode, in cases 2 and 3 (siblings) this was noted after Rituximab
treatment for relapsing aTTP. A poor response to single vaccinations (Diphtheria and Tetanus,
Pneumococcus) was documented in case 1 and 2, a negative pneumococcal serology in case 4, as
well as recurrent invasive infections including pneumococcal pneumonia, meningitis and otitis media in
cases 1 and 3. Flowcytometry was done in 2 children revealing low CD4 (Case 1) and decreased
switched- and memory B-cell levels (case 3), respectively.
Conclusions
Although cytopenias such as idiopathic thrombocytopenia or Evans’ syndrome, both differential
diagnoses of aTTP, and various other autoimmune diseases have been reported in CVID, the
association with aTTP is novel (or underreported). The common Polynesian ethnicity and the shared
clinical phenotype with the unusual early onset of aTTP hints at a new genetic underlying mechanism.
Further detailed diagnostics to confirm CVID or similar according to standard criteria (www.esid.com),
family studies and the search for common underlying genetic aberrations are underway.
FM286
A novel disease entity characterised by idiopathic generalised seizures and Lferritin deficiency
Jeroen Goede*, Anna Cozzi, Paolo Santambrogio, Daniela Privitera, Vania Broccoli, Ida Luisa
Rotundo, Barbara Garavaglia, Rudolf Benz, Martina Muckenthaler, Sonia Levi
UniversitätsSpital Zürich (Zürich, CH); San Raffaele Scientific Institute (Milano, IT); Vita-Salute San
Raffaele University (Milano, IT); IRCCS Foundation Neurological Institute "C. Besta" (Milano, IT);
Kantonsspital Münsterlingen (Münsterlingen, CH); University of Heidelberg (Heidelberg, DE)
Introduction: Genetic ablation of the H-ferritin gene in animal models reveals its critical importance for
development, while the role of the L-ferritin gene in vertebrates has not been addressed. Here we
describe a case of a 23-year old female patient affected by a homozygous loss of function mutation in
the L-ferritin gene and idiopathic generalized seizures during infancy. The patient is hallmarked by a
up to now unpublished homozygous nucleotide substitution (G310T) in exon 3 of the L-ferritin gene,
which results in a stop codon at amino acid 104 (E104X), generating a peptide unable to fold in a
ferritin full cage.
55
Methods: We characterized parameters of iron homeostasis and oxidative status in primary fibroblasts
that were derived from a patient’s skin biopsy, as well as in dopaminergic neurons from reprogrammed
fibroblasts.
Results: We show that the L-chain ferritin in E104X fibroblasts is undetectable and that the ferritin
molecule is composed only of H-chains. In accordance with the enhanced capacity of the H-ferritin
homopolymer to incorporate iron, the labile iron pool is decreased (~ 4 fold), which may have caused
increased cellular iron uptake (~1.5 fold) via transferrin receptor 1 (~1.4 fold increase). Moreover
reduced iron availability caused cytosolic scavengers of reactive oxygen species (catalase and SOD1
protein were reduced by ~ 4 and ~ 2.5 fold, respectively). Despite cytosolic iron starvation, reactive
oxygen species (ROS) production was enhanced and higher levels of oxidized proteins were detected.
Furthermore, ferritin showed an accelerated degradation rate in E104X cells (half-life was ~ 5 h
compared to ~18 h in controls). The increase in reactive oxygen species and transferrin receptor 1
protein levels was further confirmed in reprogrammed dopaminergic neurons from E104X fibroblasts
that were obtained with an efficiency of about 10%.
Conclusion: Our results highlight for the first time the pathophysiological consequences of human Lferritin deficiency and contribute to the definition of a new disease entity characterized by the absence
of L-peptide in ferritin and idiopathic generalized seizure.
FM287
Anaemia in the elderly: a component of polymorbidity or quite a normal finding
when slight?
Corina Risch*, Pedro Medina, Martin Risch, Jean-François Lambert, Urs Nydegger, Lorenz Risch
Universität Triesen (Triesen, LI); labormedizinisches zentrum Dr. Risch (Liebefeld, CH); Zentrallabor
Kantonsspital Graubünden (Chur, CH); Service d'Hématologie, CHUV (Lausanne, CH)
The World Health Organization defines cut-offs at 120 g/L (women) and 130 g/L (men).
56
As yet, clinical experience points to slightly below WHO standard hemoglobin levels as a normal
consequence of aging, current laboratory cut-offs not accounting for the elderly.
The prevalence of clinically overt anemia in the elderly has been stratified into one-third to nutritional
deficiency, another-third to iron/hepcidin dysbalance and a last-third to inflammation. All by searching
for age-adapted reference intervals (RI) in our regional healthy elderly in Switzerland, we also wanted
to gain insights on an array of laboratory analytes possibly associated with hemoglobin levels.
The Seniorlabor study has so far recruited over 1600 subjectively healthy Caucasian inhabitants >60
yrs of age. Venous blood samples were drawn after an overnight fasting period. Hemoglobin was
assessed using an XE-5000 hematology analyzer (Sysmex-Digitana, Switzerland).
RIs were assessed according to the CLSI-guideline C28-A3.
Here we report on the results from 557 men and 722 women. Men had significantly higher median
hemoglobin levels than women (149 vs. 137 g/L; p<0.001), and there was a significant Spearman rank
correlation between age and hemoglobin level (r=-0.113; p<0.001).
Thus RIs were stratified according to age and gender. Double-sided 95% reference intervals for men
were: 129-168 g/L (age 60-69), 125 – 168 g/L (age 70-79) and 118-169 g/L (age >80). The respective
RIs for females were: 120-157 g/L (age 60-69), 116 – 156 g/L (age 70-79), 115-164 g/L (age >80). A
linear regression model incorporating age, female gender, testosterone, ferritin, CRP, ALAT,
cholinesterase, and total bilirubin as significant predictors (all p<0.01) of hemoglobin concentrations
accounted for 37.4% of hemoglobin concentration variance. Interestingly, in this model, we could not
observe a significant association between hemoglobin and kidney function (CKD-EPI eGFR), folate
concentrations, Holo-Transcobalamin concentrations, and T4 concentrations.
With progressive age, there is a considerable decline of the lower limits of hemoglobin
concentrations., which is more pronounced in men than in women and seems to converge above age
80. The WHO cut-offs seem to be valid at age 60, but tend to get too restrictive at older age. This may
cause overdiagnosis of anemia, and consequently, may perturbate an elderly persons’ wellbeing and
lead to unnecessary and costly follow-up investigations.
FM288
Is less chemotherapy detrimental in adults with Philadelphia chromosome (Ph)positive acute lymphoblastic leukaemia (ALL) treated with high-dose imatinib?
Results of the prospective, randomized GRAAPH-2005 study
Yves Chalandon*, Xavier Thomas, Sandrine Hayette, Jean-Michel Cayuela, Claire Abbal, Françoise
Huguet, Emmanuel Raffoux, Thibault Leguay, Stephane Lepretre, Martine Escoffre-Barbe, Sebastien
Maury, Céline Berthon, Emmanuelle Tavernier, Jean-François Lambert, Marina Lafage, Véronique
Lhéritier, Sylvie Chevret, Norbert Ifrah, Hervé Dombret GRAALL group (Group for Research on Adult
Acute Lymphoblastic Leukemia)
Aim: To compare a less intensive regimen based on high-dose imatinib (IM) to an intensive
IM/HyperCVAD regimen in adults with Ph+ ALL, in terms of early response and outcome after stem
cell transplantation (SCT).
Methods: Patients (pts) aged 18-60 years with previously untreated Ph+ ALL were eligible. After a
steroid prephase, cycle 1 differed between randomization arms. In arm A (IM-based), IM was given at
800 mg on d1-28, combined with vincristine-dexamethasone. In arm B (IM/HyperCVAD), IM was given
at 800 mg on d1-14, combined with adriamycin, cyclophosphamide, vincristine, dexamethasone. All
pts received a cycle 2 combining high-dose methotrexate and AraC with IM at 800 mg on d1-14,
whatever their response. Minimal residual disease (MRD) was done by quantitative RQ-PCR after
cycle 1 (MRD1) and cycle 2 (MRD2). Major MRD response was defined as BCR-ABL/ABL ratio
<0.1%. Then, all pts were to receive alloSCT using related or unrelated matched donor SC or
autoSCT if no donor and a major MRD2 response. IM/chemotherapy maintenance was planned after
autoSCT. In the absence of SCT, pts received alternating cycles 1 (as in arm B) and cycles 2 followed
by maintenance. The primary objective was non-inferiority of arm A in term of major MRD2 response.
Results: 268/270 pts were evaluable for this analysis (135 arm A, 133 arm B; median age, 47 yrs;
median fup, 40 mths). Main pt characteristics were well-balanced. Due to higher induction mortality in
arm B (9 vs 1 deaths; P=0.01), CR rate was higher in the less intensive arm A (98% vs 91%;
P=0.006). The rates of pts reaching major MRD2 response was 65% (66% arm A, 64% arm B;
P=0.79, non-inferiority primary endpoint thus demonstrated, P= 0.004). EFS at 3 yrs was 41% (95%
CI, 35-48) and OS 52% (95% CI, 45-58, Fig. 1) and no difference between both arms. 160 pts
received alloSCT and 34 autoSCT in CR1. Allo TRM was similar in both arms (29% vs 21% at 3 years;
P=0.46). MRD2 did not significantly influence post-allotransplant EFS and OS. When restricting the
comparison to pts achieving major MRD2 response, there was no difference after auto as compared to
alloSCT (Fig. 2).
57
Conclusions: We demonstrated here that chemotherapy intensity may be safely reduced when
associated with high-dose IM. Similar outcome after auto and alloSCT observed in MRD responders
validates MRD as an important early surrogate endpoint for treatment stratification and new drug
investigation in this disease.
58
FM289
Impact of mutated NPM1 reduction upon chemotherapy on overall survival in
acute myeloid leukaemia (AML) patients
Judit Bencze*, Stefan Balabanov, Kornelius Arn, Markus Manz, Jeroen Goede
Introduction: During the last years moleculargenetic alterations are increasingly recognized in their
important predictive role for outcome of AML patients with normal karyotype at diagnosis.
Approximately 50% of AML-patients with normal karyotype harbor a mutation of the nucleophosmingene (NPM1), which in absence of a FLT3-ITD-mutation indicates a favorable risk group regarding
relapse free and overall survival. However about 40% of NPM1-mutated AML patients carry a FLT3ITD mutation that worsens prognosis. Recently a study published by Krönke et al. demonstrated an
important prognostic value of quantitative PCR NPM1 mutation analysis during therapy.
Methods: We retrospectively analyzed the data of 78 AML patients with an NPM1 mutation (Type A or
B) at our division since the year 2007. 58 of these patients were treated with intensive chemotherapy.
Samples of bone marrow and/or peripheral blood from patients at diagnosis and at different follow-up
times were examined by sensitive RQ-PCR assays for NPM1. The follow-up time points were
regeneration after the first and the second induction chemotherapy cycle and after consolidation.
Consolidation consisted of a conventional third chemotherapy cycle (n=25), allogeneic hematopoietic
stem cell transplantation (allo-HSCT; n=18) or high dose chemotherapy with autologous stem cell
transplantation (n=1).
Results: From the 58 curatively treated AML-patients with a NPM1 mutation 35% (20) showed
coexistence of a FLT3-ITD mutation. In patients not treated with allogeneic stem cell transplantation
the presence of the FLT3-ITD mutation caused a significant decrease in overall survival. This
significant difference in patient survival is not visible if we include the patients that were treated with
allo-HSCT, namely 11 (29%) of the group with isolated NPM1 mutations and 10 (50%) of the FLT3ITD-group. In addition, patients with NPM1 mutations who achieved a >4 log reduction in NPM1
values after 2 induction therapies (n=16 with isolated NPM1 mutation and n=8 with additional FLT3ITD) had a significantly longer overall survival in contrast to those achieving <4 log reduction (n=9 with
isolated NPM1 mutation and n=5 with additional FLT3-ITD).
Conclusion: Our results confirm that the kinetics of clearance of NPM1 mutated cells has an important
impact on overall survival in NPM1-AML patients and should be used as prognostic tool regarding the
indication of allogeneic bone marrow transplantation in NPM1 mutated leukemias.
59
FM290
Effect of anti-fungal and anti-bacterial prophylaxis in intensive acute myeloid
leukaemia (AML) therapy: a single centre experience
Bernhard Gerber*, Jan Köppel, Michaela Paul, Gayathri Nair, Thi Dan Linh Ngyuen-Kim, Thomas
Frauenfelder, Urs Schanz, Markus G. Manz
UniversitätsSpital Zürich (Zürich, CH); Universität (Zürich, CH)
Background: Infections remain a concern in AML and the optimal strategy to reduce infection related
morbidity and mortality is a matter of debate. The efficacy might depend on local settings. At our
institution we did not use prophylaxis until March 2010, when an anti-infective chemoprophylaxis with
posaconazole, levofloxacin and trimethroprim/sulfamethoxazole was introduced to accompany
intensive chemotherapy.
Aims: To assess the impact of the newly introduced primary prophylaxis scheme on the incidence of
invasive fungal disease (IFD) and bacteremia.
Methods: Retrospective single-center study performed at the leukemia ward (normal ventilation) and
hematopoietic stem cell transplantation unit (air filtration and positive-pressure) of the University
Hospital Zurich between 2009 and 2011. All Patients >18 years with AML or high-risk MDS (IPSS
>1.5) receiving intensive chemotherapy were included. Statistical analysis compared the patient
cohorts before and after introduction of the prophylaxis scheme. IFDs were classified according to the
EORTC/MSG 2008 guidelines.
Results: The study comprised 88 patients receiving a total of 203 chemotherapy cycles. Baseline
characteristics were similar in the non-prophylaxis and the prophylaxis cohort and other treatment
regimens or locations were not changed during the study time. Median age of the study population
was 51.3 years (IQR 20.7), 45 (51%) were male. Five and 7 patients in the non-prophylaxis and
prophylaxis cohort were diagnosed with IFD before the start of chemotherapy and excluded from the
analysis. Adherence to the prophylaxis scheme was 81.7% for posaconazole and 69.5% for
levofloxacin. Overall survival at 100 days was 88.4% in the non-prophylaxis and 84.4% in the
prophylaxis period. IFD were more common in the non-prophylaxis period than in the prophylaxis
period (88.9% and 55.3%; p = 0.0032). In both groups IFD were classified as 'possible'
(EORTC/MSG) in the vast majority of all cases (93.5% and 81%). In multivariate analysis
chemoprophylaxis a well as treatment in the hematopoietic stem cell transplantation unit (n=39) both
led to a reduction in IFD (p<0.0001 and p = 0.0021, respectively). The incidence of bacteremia was
not significantly different in the non-prophylaxis and the prophylaxis group (32.6% vs. 34.6%).
Conclusions: Combined antifungal and antibacterial primary prophylaxis with posaconazole resulted in
a significant reduction of possible IFD but did not reduce the incidence of bacteremia.
60
FM291
Importance of microarray analysis as a prognostic clinical tool in chronic
lymphocytic leukaemia
Nolwen Prie*, Sandrine Bougeon, Naomi Esther Kramer, Laurence Etter, Ornella Bruzzese, Delphine
Ernst, Sarah Porter, Dominique Muehlematter, Jacqueline Schoumans
CHUV (Lausanne, CH)
Introduction: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy with a highly variable clinical
course. In addition to the mutational status of the immunoglobulin heavy chain, recurrent genomic
abnormalities are among the strongest prognostic markers. Specific aberrations of prognostic
significance are usually detected by interphase fluorescence in situ hybridization (iFISH). Array-based
genomic technologies allow genome-wide screening for genomic alterations. They have proved to be
effective in the detection of copy number abnormalities (CNA) and copy-neutral loss of heterozygosity
(CN-LOH) and have consequently enabled the identification of new recurrent abnormalities of clinical
relevance. The aim of this study was to assess the usefulness of array based comparative genomic
hybridization (CGH)+single nucleotide polymorphism (SNP) array as an alternative to iFISH for the
detection of genomic abnormalities in routine clinical use.
Methods: Peripheral blood samples of 70 CLL patients were analysed both by iFISH and CGH+SNP
arrays.
Results: Genomic abnormalities were detected by iFISH in 51 patients (72.8 %) and by array in 52
patients (74.3 %). A high degree of concordance was observed (97 %) between both methods. A
discrepancy was observed in two patients with low proportions of abnormal cells (< 10 %) that were
only detected by iFISH. Conversely, by array, additional acquired genomic abnormalities not included
in the FISH panel were detected in 25 patients. Some were recurrent abnormalities such as loss of 1q,
8p, 9p, 10q, 12p, 15q, 18p and gain of 2p, 4q, 8q, 17q which appear to be of prognostic significance.
Large stretches >10 Mb of CNLOH were detected in 6% of the cases and accurate size mapping of
clinically relevant genomic markers was obtained in 69% of abnormal cases by array analysis. Overall,
array analysis provided additional clinical relevant genomic data in 88% of abnormal cases.
In addition, allowing the precise identification of breakpoints, aCGH can determine deleted regions of
prognostic significance and identify candidate genes implicated in CLL of potential clinical relevance.
Conclusion: CGH+SNP array analysis is a robust, high resolution and sensitive screening method for
routine clinical use in CLL and is able to reliably detect abnormalities only present in 10% of the cells.
Array analysis shows clearly a higher diagnostic yield than iFISH.
FM292
Is there a difference in the disease risk index for outcome of patients
undergoing allogeneic haematopoietic stem cell transplantation after T-cell
depletion?
Yan Beauverd*, Eddy Roosnek, Yordanka Tirefort, Monika Nagy-Hulliger, Michael Bernimoulin, Olga
Tsopra, Vincent Kindler, Marc Ansari, Carole Dantin, Alessandro Casini, Anne-Pascale Grandjean,
Ekaterina Chigrinova, Stavroula Masouridi-Levrat, Yves Chalandon
Objective: We have investigated if the disease risk index, previously published by Armand et al. (Blood
2012;120:905-13), which is predictive of the outcome after allogeneic HSCT is also valid in our center,
where 63% of patients are transplanted with T-cell depleted grafts (TDEP).
Methods:
We have analyzed 416 patients with various hematological malignancies transplanted between
January 1998 and October 2012. Patient characteristics are described in the table. GVHD prophylaxis
consisted mostly of calcineurin inhibitors (CSA) ± MTX (MAC) or MMF (RIC).
Results: Overall survival (OS) and disease free survival at 4 years were 50.2±5% and 40.6±5%
respectively. Incidence of relapse, relapse death and treatment related mortality (TRM) were 37.2±5%,
34.7±5% and 23.2±5%. OS at 4 years for low, intermediate, high and very high overall risk was
82.1±12%, 51.6±7%, 31±10% and 33.7±30% respectively (p<0.0001). 4-year relapse incidence for
low, intermediate, high and very high risk was 11.5±10%, 35.3±6%, 49.2±10% and 59.7±30%
respectively (p<0.0001). For TDEP transplant patients, 4-year OS for low, intermediate and high
overall risk was 88.3±11%, 51±8% and 42.6±15% respectively (p<0.001) (very high risk patients were
too few to be taken in account into the analysis). 4-year TRM and relapse incidence for low,
intermediate and high overall risk were 8.6±10%, 23.4±7%, 20.4±14%, (p=0.048) and 8.6±10%,
37±8%, 55.8±14% (p<0.0001) respectively. In univariate analysis, there was a significant impact of
61
TDEP on the low and high overall risk group regarding OS (better OS p=0.011 (low risk) and p=0.038
(high risk)), but there was no impact on TRM, relapse incidence or relapse death. This was confirmed
in multivariate analysis with a HR=0.68 (0.50-0.92) for TDEP (p=0.015). Other factors that impacted
OS in multivariate analysis were disease risk and type of donor (p<0001). Patients who received
TDEP displayed a lower acute GvHD grade 2-4 incidence (21 vs 43%, p<0.0001) and severe chronic
GvHD was 11% vs 17%,p=0.22.
Conclusions: Our study confirms the prognostic value of the disease risk index as previously shown by
Armand et al. Interestingly, we found a significant impact of TDEP on OS. However results should be
taken with caution due to the low number of patients in the low risk and very high risk groups and to
the retrospective nature of the study. The disease risk index is an easy and feasible prognostic score
for HSCT and may help identify patients that would benefit from TDEP.
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Beste 10 Poster SGIM – Meilleur 10 posters SSMI
P293
Interpretation in the medical setting: between translation and mediation
Marina Sleptsova*
Background: Errors in translation may have a significant impact upon health care. There is no uniform
understanding of the role that a professional medical interpreter should adhere to. Models range from
the interpreter as a conduit that transfers meaning from one language to the other to the interpreter as
a cultural broker who helps establish a helpful relationship.
Aim: We tried to assess role understanding of interpreters in a cohort of health care providers (hcp;
N=387) and professional interpreters (N=365) from Switzerland.
Methods: We used the German version of the IPRI questionnaire (C. Angelelli, 2004; overall Cronbach
alpha: .70/.68 for hcp and interpreters, respectively) that lists 38 statements on the role of interpreters
that are responded to from completely disagree to completely agree on a 6 point Likert scale (dividing
line between 3: don’t agree and 4: agree). After removal of non-distinctive items it contains four
subscales that describe different functions of the interpreter (Trust: 8 items, Cronbach alpha .67/.70;
Align: 6 items, Cronbach alpha .71/.73; culture: 6 items, Cronbach alpha .70/.65; Affect, 8 items,
Cronbach alpha .72/.65 in hcp’s/interpreters, respectively).
Results: The establishment of a trustful relationship is seen as not important by both groups; both
strongly do not agree that it is the primary task of the interpreter to form a close alliance with the
patient: (1.80 ± 0.74 vs. 1.84 ± 0.66; p= n.s.). Interpreters rather support the importance of a culturally
sensitive interpretation (3.83 ± 0.84 vs. 3.60 ± 0.83 in hcp; p<0.001). Both groups agree that the
interpreter should not help express patient emotions beyond the correct translation of emotional
utterances (2.77 ± 0.77 vs. 2.78 ± 0.78; p= n.s.).
Conclusion: In both groups the idea that interpreters should serve as patients’ advocate is not
supported, establishing a trustful relationship and supporting the expression of emotions is also not
seen as a primary task of interpretation. This speaks in favour of a neutral role that more closely
resembles the conduit model of interpretation.
P294
Sepsis due to Candidatus neoehrlichia mikurensis: (still) rare in humans, but
not in ticks!
Daniela Bircher*, Florian P. Maurer, Guido V. Bloemberg, Urs Karrer, Jacques Gubler
Medizinische Poliklinik Kantonsspital Winterthur (Winterthur, CH); Institut für Medizinische
Mikrobiologie Universität Zürich (Zürich, CH)
Case: In January 2012, a 58 year old patient was referred to our outpatient clinic because of a 3
month-history of recurrent fever up to 40°C, chills, night sweats and weight loss of 5 kg. Six months
earlier, he had finished six cycles of R-CHOP chemotherapy (Rituximab, Cyclophosphamide,
Doxorubicin, Vincristin, Prednisolon) for a stage IV follicular lymphoma achieving complete remission.
At time of referral he was treated with Rituximab every 3 months. Multiple blood cultures and HIV-,
EBV- and CMV-serologies had excluded active infection. A PET-CT scan showed no signs of
recurrent lymphoma. The general condition of the patient was markedly reduced. He was underweight
(BMI 19 kg/m2), had a low blood pressure (95/60 mmHg) and tachycardia (100/min) but no fever (36.7
°C). Otherwise, the physical exam was completely unremarkable. Lab results: hemoglobin 93 g/l,
platelets 199 G/l, leucocytes 6.2 G/l, lymphocytes 0.22 G/l, ESR 94 mm/h, CRP 92 mg/l, normal liver
and renal parameters. Bone marrow biopsy indicated unspecific inflammation without lymphoma.
Broad-range 16S rRNA gene PCR of bone marrow and peripheral blood was positive and sequencing
of the amplicons identified the presence of Candidatus Neoehrlichia mikurensis. Oral antibiotic therapy
with doxycycline was initiated and fever subsided within days. After 2 weeks, 16S PCR from blood
was negative and the patient had gained 6 kg. Oral doxycycline was continued for 6 weeks and the
patient made a full recovery.
Discussion: Neoehrlichiosis caused by Ca. Neoehrlichia mikurensis is an emerging tick-borne disease.
Ca. Neoehrlichia mikurensis is a novel bacterial species belonging to the family of Anaplasmatacea
and was recently isolated in a surprisingly high proportion of ticks from the greater Zurich area (up to
8%). Since 2008, eight human cases of neoehrlichiosis have been described in Europe, three of them
in Switzerland, mostly affecting immunocompromised patients. The disease is associated with severe
systemic inflammation with fever, malaise and weight-loss. Ca. Neoehrlichia mikurensis -specific or
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broad range 16S rRNA gene PCR of blood or lymphoid organs is the preferred diagnostic method
since successful culture methods or serological tests are not available. The treatment of choice for
neoehrlichiosis is oral doxycyclin for six weeks. Neoehrlichiosis should be considered in
immunocompromised patients with inflammatory syndromes not responding to conventional
antimicrobial (beta-lactam) therapy.
P295
Beef it up: severe hypercalcaemia caused by parenteral self-administration of a
veterinary drug containing high dose vitamin A, D, and E
Henriette Heinrich*, Rahel Schwotzer, Dominik Schneider, Daniel Franzen
Universitätsspital Zürich (Zürich, CH)
Introduction: Fixation of modern society on physical appereances has led to increasing abuse of
performance enhancing substances as well as injection of muscle augmenting substances not only
among professional body builders. The side effects are widely known. Here, we present a case of
intoxication due to self-administration of a parenteral veterinary drug containing vitamin A, D, and E.
Case report: A previously healthy 19-year-old man was referred because of recurrent vomiting,
nausea and weight loss of 15 kg within the last 3 months. The patient’s history revealed dysthymia but
was otherwise noncontributory. Alcohol or ilicit drug abuse was denied. Three months ago, he had
moved from Brasil to Switzerland, where his father runs a gym. In Brasil, he was doing resistance
training, but had not achieved satisfying results from his personal point of view. For this reason, he
weekly self-administered a veterinary drug containing high dose vitamin A, D, and E over 3 months
into brachial, pectoral, and deltoid muscles. Normally, the applied veterinary compound (ADE
Labovet®) is applied in cattle production for vitamin supplementation.
Clinical examination was uneventful, but biceps, pectoral and deltoid muscles were palpably and
asymmetrically prominent. Laboratory studies revealed a raised total albumin-corrected calcium serum
level of 3.66mmol/l and phosphate level of 0.76mmol/l. TSH serum level, chest X-ray, and abdominal
ultrasound were normal. PTH serum levels were low ruling out hyperparathyroidism. Hence, vitamin D
intoxication was presumed. During the treatment with hydration, furosemide and zolendronat, his
calcium serum levels returned to normal values. Depressive symptoms did not recur.
Discussion: The assumed cumulative dose of self-injected substance was 400ml, whereas 100ml
contains 20000000 U vitamin A, 500000U vitamin D3 and 6800 U vitamin E. A quantity toxic to
humans remains undisputable. Intramuscular injection of high dose vitamins A, D, and E leads to
muscular pseudohypertrophy imitating a silicon like effect by causing muscle edema. But a synergistic
effect of absorbed vitamin A and D leads to the clinical picture of hypervitaminosis A and D with
vomiting, anorexia, weight loss and psychiatric abnomalities. The treatment is analogous to the one of
hypercalemia. There are only a few case reports originating from South America, which describe this
entity in amateur body builders. Once again, a proper patient‘s history is crucial!
P296
Antigen-specific functionality of anti-FAP re-directed CD8+ T-cells
Christoph Renner, Petra Schuberth, Christian Hagedorn, Alex Soltermann, Sandra Tomaszek, Rolf
Stahel, Walter Weder, Ulf Petrausch*
UniversitätsSpital Basel (Basel, CH); UniversitätsSpital Zürich (Zürich, CH)
Introduction: T cells can be re-directed by retro-viral transfer of chimeric antigen receptors (CAR) that
recognize tumor-associated antigens (TAA). Adoptive T cell therapy (ACT) with CAR re-directed T
cells represents a new branch of immunotherapy and has recently shown clinical responses in CLL.
However, in solid organ cancers ACT has to be intensively investigated since the efficacy of ACT has
not conclusively been shown so far. Malignant pleural mesothelioma (MPM) is considered an
incurable disease where new treatment options like ACT could be evaluated. Fibroblast activation
protein (FAP) is predominantly expressed on the surface of tumor-associated fibroblasts and on
particular cancer types. FAP is a promising target for ACT because of its expression in a wide
spectrum of malignant lesions.
Methods: Immunohistochemistry (IHC) was performed with the monoclonal antibody F19 in MPM and
healthy tissue. IFN gamma ELISA and cytotoxicity assays were performed to demonstrate in vitro
functionality. Immunodeficient mice (NSG) were co-injected with FAP positive tumor cells and redirected T cells to demonstrate protection against a tumor challenge in vivo. The model system
allowed in vivo imaging by measuring the bioluminescence of luceferin, because the tumor cells were
modified to express luciferase.
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Results: We demonstrated expression of FAP by IHC in epitheloid, sarcomatoid and bi-phasic MPM.
We evaluated FAP expression in healthy tissue, to estimate off-tissue/on-target toxicity of FAP-specific
T cells. By IHC significant FAP expression could be found in pancreatic tissue. FAP-specific redirected T cells were successfully generated by retro-viral transduction of an anti-FAP-F19CD28/CD3-CAR. Expression of the CAR was observed in 35-55% of CD8+ T cells. FAP-specific redirected T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigenspecific manner in vitro. In the mouse model FAP-specific re-directed T cells inhibited the growth of
xenografted FAP positive human tumor cells in the peritoneal cavity.
Conclusion: Our data indicate the functionality of anti-FAP re-directed CD8+ T cells. Because of the
FAP expression in MPM we will start a phase I ACT trial for patients with MPM (Figure 1A&B) in 2013.
Re-directed T cells will be transfered in the malignant effusion (Figure 1C) of patients with MPM not
accessible for surgery at the time point of screening.
P297
Delayed positivity of Legionella urinary antigen: apropos of two cases
Thierry Gigandet*, Robert Escher, Gabriel Waldegg, Markus Riederer, Martin Egger
Regionalspital Emmental AG (Burgdorf, CH)
Introduction: Legionella pneumophila urinary antigen test (LUAT) is a useful tool for rapid diagnosis of
Legionella pneumonia: Urine samples are easy to obtain, the analysis is simple to perform, and the
test has a short turnaround time. It has a high specificity (98-99%) but limited sensitivity (70-85%)
depending on the type of assay, Legionella serogroup, and the clinical situation. Whereas prolonged
positivity of the LUAT is well described, there is little information in the literature concerning delayed
positivity.
Case description: Case 1: A 67 year-old man with chronic lymphocytic leukemia, diagnosed 11 years
ago and untreated so far, presented with a 3-day history of fever up to 40°C, dry cough and moderate
headache. The chest X-ray showed a pulmonary infiltrate in the right lower lobe. LUAT was negative
and treatment with ceftriaxone was started. After clinical worsening necessitating intensive care a
LUAT on day 5 was positive. Legionella pneumonia was confirmed by PCR in bronchoalveolar lavage
fluid.
Case 2: After a 4-day history of chills and increasing dyspnea a 50 year-old smoker with chronic
obstructive pulmonary disease (COPD) GOLD III, presented with severe dyspnea, a temperature of
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37.7°C and atrial flutter. The chest X-ray showed a pulmonary infiltrate in the lingula. LUAT was
negative. Treatment with amoxicillin/clavulanic acid was started. After 3 days of clinical and
radiographic worsening with increasing C-reactive protein a repeat LUAT was positive. A positive
Legionella PCR from pleural fluid confirmed the diagnosis.
Both patients were treated with levofloxacin and left the hospital in good condition.
Discussion: Our cases illustrate that LUAT may turn positive only a few days into the clinical
manifestation of Legionella pneumonia. This observation pertains to the BinaxNOWTM Legionella test
used in our hospital and may not be applicable to other brands. Such cases may contribute to the
false negatives responsible for the limited sensitivity reported for LUAT. The observation has
implications for the empiric coverage for Legionella in treatment of community acquired pneumonia.
Chronic lymphocytic leukemia and severe COPD, respectively, could have cautioned to provide
coverage for Legionella in our patients despite negative LUAT.
Conclusion: Repeated testing for LUAT may be warranted before withholding or stopping antibiotics
against Legionella in moderately severe to severe community-acquired pneumonia.
P298
Pitfalls in the microbiological diagnosis of pneumococci: clinical relevance
Nadine Lippuner*, Reinhard Zbinden, Christlieb Haller
Case Report: A previously healthy 82 year old woman presented with a 9 day history of respiratory
tract infection, non-productive cough, fever and a respiratory rate of 22/min. Further investigation
revealed leucocytosis, a markedly increased concentration of C-reactive protein and a right upper lobe
infiltrate on the chest x-ray. The patient was hospitalized and treated empirically for communityacquired lobar pneumonia with intravenous amoxicillin/clavulanate. The clinical impression of
pneumococcal pneumonia was supported by gram-positive cocci in 4 of 4 blood culture bottles and a
positive pneumococcal antigen agglutination test directly from the blood cultures. The pneumococcal
antigen test in the urin however was negative. Eventually a streptococcus mitis group isolate was
reported in the blood cultures. This unexpected result prompted a thorough investigation of potential
foci of S. mitis bacteremia including a dental evaluation and echocardiography. The discharge from
the hospital was delayed for 2 days despite the rapid clinical response with resolution of the fever
within 24 hours. The patient was instructed to monitor her temperature, continue oral antibiotic
treatment and follow up as an outpatient.
Two weeks later the initial clinical diagnosis of pneumococcal bacteremia was confirmed by recA gene
sequencing, which definitively identified the isolated bacteria as pneumococci.
The technically challenging distinction between S. mitis and S. pneumoniae had caused some
difficulty in the interpretation of the results with further confusion because of the term “S. mitis group”.
Discussion: The differentiation between S. mitis and S. pneumoniae - both members of the S. mitis
group - with conventional methods can be challenging if colony morphology is not typical and bile
solubility is not clearly positive. Evidently this difficulty also exists for state of the art techniques like
MALDI-TOF fingerprinting, 16S PCR and Vitek2. In this patient the routine microbiology results led to
unnecessary tests, prolonged hospital stay and caused considerable anxiety to the patient.
Conclusion: Clinicians need to be aware of the pitfalls in the differentiation between some streptococci
within the S. mitis group (namely S. mitis and S. pneumoniae) even with modern laboratory methods.
In case of discrepancies between clinical and laboratory findings the direct communication between
laboratory and clinical physicians remains essential for optimal patient management.
P299
Introduction and outcome analysis of systematic semi-automated alerts
regarding metformin dose-adjustment in patients with renal impairment in a
Swiss university hospital
Regina Krattinger*, Guido Bucklar, Ludwig Perger, Gerd Kullak-Ublick, Edouard Battegay, Stefan
Russmann
Background: Lack of dose-adjustment in response to impaired renal function is an important and
avoidable cause of adverse drug reactions and additional costs in hospitalized patients. Today,
electronic drug prescription provides new opportunities for the identification and prevention of
prescribing errors, including those that involve wrong dosing. This study introduced and evaluated
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automated electronic surveillance of metformin therapy in patients with impaired renal function,
followed by manual expert dosing recommendations.
Methods: We developed an algorithm that automatically identified patients of a Swiss University
Hospital with an estimated glomerular filtration rate (eGFR) below 60 ml/min and prescriptions for
metformin. Real-time automated alerts were displayed to clinical pharmacologists, who then reviewed
electronic medical records and provided dosing recommendations to prescribing physicians based on
locally customized guidelines published by Lipska et al. (Diabetes Care 2011;34,1431-7).
Results: During the calendar year 2012 we identified 436 cases with an eGFR <60 ml/min and current
metformin therapy. Among those, guideline-based dose reduction or stop of therapy was
recommended in 123 cases. In 88 (92.6%) out of 95 cases with known follow-up, our
recommendations led to an according change of therapy. We did not observe consistent changes in
the number of necessary recommendations per month over time. Furthermore, we identified 2 patients
with lactic acidosis under metformin therapy that had not been adjusted for impaired renal function.
Conclusions: Automated detection followed by manual expert recommendations (“semi-automated
alerts”) was highly efficient and detected a considerable absolute number of metformin dosing errors.
Their clinical relevance was underlined by 2 cases of lactic acidosis, which is a possible adverse effect
of metformin therapy. Our specific semi-automated alerts achieved compliance above 90% among
physicians, which compares to a typical compliance of less than 5% for unspecific automated alerts.
There was no evidence for a lasting educative effect of alerts on metformin prescribing behaviour. Our
findings indicate that, along with other preventive measures, continued semi-automated alerts can
play an important role for the efficient and effective prevention of clinically and economically relevant
medication errors.
P300
Accuracy of four cardiovascular risk scores in a Swiss population-based
cohort
Julien Vaucher*, Pedro Marques-Vidal, François Bastardot, Didier Locca, Olivier Muller, Patrik Michel,
Gérard Waeber, Peter Vollenweider CoLaus Study
Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been
developed. However, their accuracy and comparability need to be evaluated in populations others
from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV
risk scores using data of a large population-based cohort.
Methods: Prospective cohort study including 4980 participants (2698 women, mean age± SD:
52.7±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two
end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk
scores were compared: original and recalibrated Framingham coronary heart disease scores (1998
and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA);
Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using
Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The
sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score
using the highest risk category ([20+ % at 10 years) as the "positive" test.
Results: Recalibrated and original 1998 and original 2001 Framingham scores show better
discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly
calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and
40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998,
PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk
category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects.
Conclusion: In this cohort, we see variations of accuracy between risk scores, the original
Framingham 2001 score demonstrating the best compromise between its accuracy and its limited
selection of subjects in the highest risk category. We advocate that national guidelines, based on
independently validated data, take into account calibrated CV risk scores for their respective countries.
P301
Allergy to chlorhexidine: rare but not to be ignored
Ewa Degenhardt*, Manuel Bubenhofer, Arthur Helbling, Ulrich Weber-Mani, M Fricker
Universitätsspital Bern (Bern, CH); Stadthofpraxis (Thun, CH); Zieglerspital (Bern, CH)
Background: The broad spectrum antimicrobial agent chlorhexidine (CHX) is widely used in medicine
for disinfection of skin and mucosal tissue, e.g., in dental hygiene, surgical procedures, central venous
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catheterization and urethral catheterization. It is part of daily health care and a component of
cosmetics. Allergic reactions to CHX have been reported only occasionally.
Objectives: The purpose of this study was to elucidate the circumstances of the occurrence of allergy
in subjects with a proven allergy to CHX.
Methods: The clinical records from the years 2005-2010 from both allergy units in Bern (Division of
Clinical Immunology and Allergology of University Hospital Bern and Allergy Unit of Clinic of Internal
Medicine, Zieglerspital, Spital Netz Bern) were searched for patients with CHX allergy. Allergy work up
including accurate history, skin tests, serological tests (e.g. ImmunoCAP, BAT), and eventually a
follow up by telephone was carried out in 20 patients (16 m, 4 w; mean age of 46 years (11-76y)) with
a history of CHX allergy.
Results: Of the 20 patients with CHX allergy, 16 (80%) had an IgE-mediated, and 4 a delayed type
reaction after exposure to CHX. Immediate type allergic reactions - all systemic - occurred during
dental/mouth cleaning (3), at the dentist office (4), during urological procedures (5), perioperatively (3)
and after topic use (1). Specific IgE was detected in 11/16 patients, ranging from 0.78-13.0 kU/l (RAST
classes 2-3). Two patients had a positive basophilic activation test. The 4 patients with eczematous
skin lesions used topical products such as Merfen. As concluded from the patient's history, they most
probably became sensitized to CHX by a previous invasive procedure. 6 patients had a coexisting
atopic constitution.
Conclusion: In this study, the majority of patients with an allergy to CHX showed an immediate type
reaction (IgE-mediated) following CHX contact. Allergic reactions to CHX are indeed rare, but may
have a life-threatening potential. Allergy to CHX can occur anywhere, where CHX is used. In the
Swiss Drug Compendium 55 products are listed, and 88 commonly known cosmetic brands on the
Swiss market contain CHX. Therefore, CHX is an ubiquitous substance and may be a cause for
anaphylaxis in hospitals, in dentist's surgery, or even at home.
P302
Chronology of extraintestinal manifestations relative to inflammatory bowel
disease (IBD) diagnosis in the Swiss Inflammatory Bowel Disease cohort
Stephan Vavricka*, Gerhard Rogler, Ekaterina Safroneeva, Alain Schoepfer
Stadtspital Triemli (Zürich, CH); Universitätsspital (Zürich, CH); CHUV (Lausanne, CH)
Background: Data on the frequency of extraintestinal manifestations (EIM) in inflammatory bowel
disease (IBD) are scarce. There is especially a paucity of data evaluating the chronology between IBD
diagnosis and the occurrence of the EIM.
Aim: To assess the type and frequency of EIM in IBD patients and to evaluate their chronologic
behavior.
Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which
collects data since 2005 on a large sample of IBD patients from hospitals and private practices across
Switzerland. Parametric data are demonstrated as mean ± SD, non-parametric data as median +
interquartile range (IQR).
Results: At total of 1,143 patients were analyzed (572 (50%) female, mean age 42.1 ± 14.4 years),
629 with Crohn’s disease (CD), 501 with ulcerative colitis (UC), and 13 with indeterminate colitis (IC).
Of these, 374 (32.7%) presented one to five EIM (65% with CD, 33% with UC, 2% with IC). Of those
patients suffering from EIM, 41.7% presented two, 12.4% three, 5.3% four, and 3.2% five EIM during
lifetime. The initial EIM presented with the following frequencies: peripheral arthritis (PA) 63.4%,
ankylosing spondylitis (AS) 8.1%, primary sclerosing cholangitis (PSC) 6%, uveitis 5.7%, oral
aphthosis 5.7%, erythema nodosum (EN) 5%, other 3.6%, pyoderma gangrenosum 1.8%, psoriasis
0.7%. In only 7.1% of cases, the EIM manifested before IBD diagnosis was made (median time 28
months before IBD diagnosis, IQR 7-60 months), in 92.9% EIM manifested after established IBD
diagnosis (median 72 months, IQR 9-147 months). When looking at all EIM occurring during lifetime in
IBD patients, the frequencies were as follows (total exceeds 100 due to potential presence of multiple
EIM): peripheral arthritis 69.3%, oral aphthosis 23%, ankylosing spondylitis 19.4%, uveitis 15.5%,
erythema nodosum 14.5%, PSC 7.8%, pyoderma gangrenosum 6%, psoriasis 2.8%.
Conclusion: EIMs are a frequent problem in IBD patients. The vast majority of EIM manifest after IBD
diagnosis is established. Peripheral arthritis, ankylosing spondylitis, and PSC represent the most
frequent first manifestations of an EIM. Peripheral arthritis, oral aphthosis, and ankylosing spondylitis
represent the most frequent EIM during lifetime of an IBD patient.
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P303
Recurrent falls: no pitfall
Raphael Butsch*, Markus Schneemann
A 56-year-old Swiss woman was in hospital in june 2012 for strumectomy. Our clinic was involved due
to mild hypertension during the hospital stay.
Her past medical history revealed recurrent falling on her knees once to four times a year for the
lastfour years. She reported no stumbling, no prodromal signs and no loss of consciousness.
Personal history was remarkable for hypertension, well controlled Graves’ disease, depression and
obesity. Her medication consisted of candesartan 4 mg and carbimazole 5 - 10 mg daily. Clinical
examination was unremarkable with exception of the knees. ECG, laboratory findings and an
orthostatic test were normal.
How should we call this patient’s condition? It is neither a syncope nor a seizure. Rather, it might be
called a “drop attack”.
Patients with drop attacks are rare and the differential diagnosis is limited. Drop attacks are mentioned
in patients with narcolepsy, atonic seizures, vertebrobasilar insufficiency and in patients with thyroid
hypofunction. Neither of these disorders was suspected in this woman.
, D. L. Stevens and W. B. Matthews wrote an article in the British Medical Journal about such a
disturbance in 1973 (1). They called it “cryptogenic drop attack”. In French it is referred to as “Maladie
des genoux bleus”, the reason is obvious (see figure of our patient).
Initially, they collected 54 patients complaining about drop attacks, thereof 51 were women. Cases
with an underlying disease promoting falls were excluded. Amongst these, all three men were out.
Subsequently, they started a deliberate search for women with similar complaints attending the
gynecological clinic.
This process resulted in a total of 40 female patients complaining about falls without warning, without
vertigo or other cephalic sensations, without evidence of any malfunction of the lower limbs and not
induced by change of posture or head movements. In 28 women follow up was successful.
Their mean age was 45 years. 26 out of 28 only fell forward, 27 only while walking, all of them suffered
injuries of their knees, some as well of injuries of wrists, nose, face or chest. 10 were aware of falling,
16 at least of crashing to the ground. 2 did not recall falling but stood up quickly and resumed walking.
And most important: In all of these cases it was impossible to find a causal factor. They are
cryptogenic drop attacks - to this date! Acknowledgment of this fact - and one look at the patient’s
knees - may prevent extensive investigations.
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P304
Pharmacologic treatment of persistent hiccup after brain stem ischaemia
David Muggli*, Florian Furrer, Anne Brausch, Simon Andreas Müggler
Stadtspital Waid - Medizinische Klinik (Zürich, CH)
Introduction: Persistent hiccup (singultus) can be caused by neurological disease, such as brain stem
ischemia. Quality of life is frequently impaired in these patients. No evidence-based therapy is
currently available, therefore pharmacological treatment is empiric.
Case presention: A 46-year old man was admitted with vertigo, slurred speech, gait ataxy, nausea and
vomiting. Neurological examination showed dysarthria and hoarseness, dysphagia, spontaneous
nystagmus, discrete left-sided Horner’s syndrome, palate deviation to the right side and impaired pain
and temperature sensation of the right arm, consistent with Wallenberg’s syndrome. CT and MRI scan
of the brain showed acute ischemia of the left-sided posterolateral medulla oblongata. Fiber
endoscopic evaluation of swallowing showed paresis of the left hypopharynx, with aspiration of fluid.
Despite improvement of the dysarthria after a few days, the patient complained about persistent
hiccup lasting for several days, disturbing him at night and impeding oral nutrition. A percutaneous
endoscopic gastrostomy was performed to provide nutrition. Therapy of the hiccup by physical
maneuvers and empiric medical treatment with metoclopramide and inhalative lidocaine brought no
relief. An attempt with haloperidol led at last to full regression of the afflicting hiccup within two days.
Conclusion: Persistent hiccup is defined as hiccup continuing longer than 48 hours and less than one
month. The exact mechanism of hiccup remains unclear. Several neural pathways make up the
putative hiccup reflex arc (Figure 1). The central connections for hiccups seem to involve an
interaction among the medulla oblongata and reticular formation of the brain stem, phrenic nerve
nuclei, and the hypothalamus. Dopamine and gamma-aminobutyric acid (GABA) are supposed to be
involved as neurotransmitters. Any physical and chemical irritants, inflammatory and neoplastic
conditions involving the hiccup reflex arc may cause hiccup.
Treatment of an underlying condition should be the first step in treatment of hiccup. Due to the lack of
controlled trials, pharmacologic treatment of hiccup is still empiric and mainly targets the
neurotransmitters dopamine and GABA. Table 1 shows empiric therapies of hiccup. Chlorpromazine,
a dopamine-receptor-blocker, is often used to treat hiccup and is the only approved drug by the US
Food and Drug Administration, but not available in Switzerland.
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P305
Screening for latent tuberculosis: confusion between skin test (Mantoux™) and
BCG vaccine
Jean-Philippe Aegerter*, Jean-Pierre Zellweger, Laurent Christin
Service de Médecine (Nyon, CH); Ligue Pulmonaire Vaudoise (Lausanne, CH)
A 34 year old female consults our emergency department (ED) 4 days after receiving a tuberculosis
(TB) screening skin test at her primary care physician’s office. She works as a kindergarten teacher
and is a bout to start a new job; a TB screening skin test is part of a standard pre-enrollment check up.
She is known for severe Crohn disease which has been very well controlled with inFLIXimab
injections. She received the BCG vaccine in 1981. A TB skin test (Mantoux™) is recorded as negative
in her vaccination record in 2004, just before initiating inFLIXimab treatment.
She comes to the ED complaining of severe pain at the site of injection. It is hot and red, firm, tender,
without lymphadenitis. The ED physician considers this as a booster effect and prescribes a topical
NSAID. She returns to the ER 48 hours later because of persisting pain and redness. The lesion is
very tender and fluctuant. An incision brings out purulent fluid. A Ziehl–Neelsen stain reveals acid-fast
bacilli; a PCR returns positive for Mycobacterium tuberculosis complex. A chest x-ray is normal. A
Quantiferon™ test returns negative.
Our investigations reveal that her physician’s assistant injected her with BCG vaccine instead of
Mantoux™ test.
Since inFLIXimab treatment could not be interrupted, we decided to put the patient on rifampicin and
isoniazid for 6 months. Her Crohn disease has remained well controlled. The lesion has completely
healed, leaving a frank scar.
Comment: decrease in use of TB screening skin tests favors the confusion between products (i.e.
Mantoux vs BCG), even more so that their packaging is quite similar. Since skin test has very poor
specificity for Mycobacterium tuberculosis and given this high risk of confusion, specific immunologic
blood tests to detect latent tuberculosis should be our first choice in such situations.
P306
The border of reproductive control: undocumented immigration as a risk factor
for unintended pregnancy in Geneva
Alejandra Casillas*, Patrick Bodenmann, Manuella Epiney, Laurent Gétaz, Olivier Irion, Hans Wolff
Hopitaux Universitaires de Genève (Genève, CH); Centre Hospitalier de Vaud, PMU (Lausanne, CH)
Background: Unintended pregnancies reflect health disparities, and an unmet need for family
planning. Using the only Swiss database to inquire about pregnancy intention, this study examined the
relationship between immigrant documentation and unintended pregnancy.
Methods: We used questionnaire data from pregnant women presenting to the public hospital in
Geneva from February 2005-October 2006; women were asked if their pregnancy was intended.
Using Chi-square tests, we compared unintended pregnancies between documented and
undocumented women. We used logistic regression to examine whether undocumented status was
associated with unintended pregnancy after adjusting for socio-demographics, family
interaction/presence, health-services utilization, reproductive history, drug use, violence exposure, and
psychological trauma. We present odds ratios with 95% confidence intervals of the adjusted analyses,
significant at the p<=0.05 level.
Results: 409 women were invited to participate and 394 accepted (96%). 161 were undocumented,
uninsured immigrants of which 84% were Latina. More undocumented women were younger,
employed, lived in a one-room apartment, used contraception at conception (including "insecure"
methods: condom-only, calendar, retraction) and never had a Pap smear. Less were married, had a
stable relationship with the baby's father, had family or children in Geneva, had knowledge of
emergency contraception, used medications, and ever used tobacco or any other substance.
Undocumented women had more unintended pregnancies (75.2% vs. 20.6%, p<0.001).
Undocumented status was associated with unintended pregnancy after adjustment (OR 6.2, 1.8-21.2),
as was a history of psychological problems (OR 4.1, 1.3-12.7). Stable relationship with baby's father
(OR 0.10, 0.02-0.60), history of abortion (OR 0.35, 0.12-0.997), and current psychiatric treatment (OR
0.03, 0.004-0.04) decreased odds. Contraception non-use was notably associated with lower odds of
unintended pregnancy (OR 0.013, 0.004-0.04).
Conclusions: Undocumented status increased the odds of unintended pregnancy. Factors linked to
domestic stability and health treatment were protective. Contraception non-use decreased odds of
unintended pregnancy-- likely reflecting a desire for pregnancy in this group. However, this also
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distributes some focus to the need for teaching of effective and correctly-utilized methods, among all
women, given the use of insecure contraception observed in the study.
P307
Validation of a French version of a low back pain questionnaire
Michel Kossovsky*, Christophe Luthy, Timothé Fontolliet, Christine Cedraschi, Anne-Françoise Allaz
Introduction: Annual prevalence of low back pain (LBP) in Switzerland is estimated to reach 20 to
30%. A standardized definition of LBP is therefore important in terms of comparison between studies.
This was the goal of the DELPHI DOLBaPP (DD) questionnaire, developed in English by a committee
of 28 experts from 12 countries following a Delphi method. This seven-question self-administered
questionnaire explores different domains related to LBP such as localization, associated limitations,
irradiation, frequency, duration and severity. This questionnaire was translated in French by a team
from Montreal, Quebec, Canada. Our purpose was to test whether this version was readily applicable
to a French-speaking Swiss population.
Method: The questionnaire was administered to 40 subjects suffering LBP. The comprehension of
each item of the DD was assessed on a 7-point scale, ranging from ‘incomprehensible’ to ‘very
understandable’. Then, each item was reformulated by the subjects in their own words. A semistructured interview guide helped investigators to identify words or expressions that could be
associated with comprehension problems. Three other validated questionnaires testing severity and
consequences of pain (Brief Pain Inventory; BPI), quality of life (EuroQol-5D) and disability (Oswestry
Disability Index; ODI) were administered in order to verify further construct validity.
Results: Only 1 DD item concerning the duration of LBP did not reach a comprehension level
considered as satisfactory: only 40% of the subjects succeeded in properly reformulating it. The same
item was significantly less understood on the 7-point scale than the other 6 (5.3 SD 1.9 vs. 6.9 SD 0.3;
p<0.001). The response to other questionnaires did reinforce the construct validity of the DD
questionnaire. Subjects who mentioned limitations on the DD questionnaire had a significantly higher
incapacity level according to the ODI questionnaire (56.1 % SD 17.4 vs. 37.3% SD 17.5; p= 0.004).
There was a strong correlation (0.73, p<0.001) between the pain intensity scale in the DD
questionnaire and the average pain level assessed by the BPI questionnaire.
Conclusion: The French version of the DD questionnaire can be used for studies in the French
speaking part of Switzerland. A reformulation of one of the 7 questions could improve its
comprehension among subjects with LBP.
P308
Head-to-head comparison of 'fee-for-service' and 'diagnosis-related groups'
hospitals in Switzerland: an observational study
Noemi Weissenberger*, Désirée Thommen, Philipp Schuetz, Beat Müller, Christoph Reemts, Thomas
Holler, Jürg Schifferli, Martin Gerber, Balthasar Hug
Universitätsspital Basel (Basel, CH); Universitätsspital Aarau (Aarau, CH)
Background: Reimbursement for inpatient treatment in Switzerland differed until 2012 among states
(cantons). Some hospitals used Diagnosis Related Groups (DRG) based reimbursement and others
fee-for-service (FFS). We compare length of hospital stay (LOS), patient satisfaction and quality of life
between the two systems before a nation- wide implementation of DRG.
Aim: To investigate differences in patient and hospital relevant outcomes between an AP-DRG and a
FFS hospital in Switzerland, as baseline before a nation-wide adaption of the DRG system.
Methods: In a prospective, two-center observational cohort study we identified from January to June
2011 all patients with a main diagnosis of either community-acquired pneumonia, exacerbation of
chronic pulmonary obstructive disease, acute heart failure or total prosthesis of the hip and performed
a systematic questionnaire survey 2-4 months after hospital discharge investigating the differences
between the two hospitals.
Endpoints: The primary endpoint of this study was LOS defined as hospital admission until discharge.
Secondary endpoints were hospital readmission rates and patients’ satisfaction with the discharge
procedure and quality of life.
Results: Of 1,093 hospitalized patients 450 were included (175 AP-DRG, 275 FFS). The median age
was 77 years (48% male). Patients in the FFS hospital were older (median age 78 vs. 74 years;
p<0.001) and suffered from more co-morbidities.
73
Mean LOS was 9 days and shorter in the AP-DRG hospital (mean 8.2 vs 9.5 days, p=0.04) in an
unadjusted analysis. After multivariate adjustment, no significant difference in LOS was found
(p=0.24). More patients from the FFS hospital were re-hospitalized for any reason (35% vs. 17.5%;
p=0.01), re-admitted to acute-care institutions (11.7% vs. 5.2%; p=0.014), not satisfied with the
discharge process (15.3% vs. 9.7%; p=0.02), had problems with self-care (93.8% vs. 88%; p=0.03)
and with usual activities (79.3% vs. 76%; p=0.02) 90 days after enrollment.
Discussion: Our data suggest that the AP-DRG hospital shows a higher patient satisfaction regarding
discharge, lower rehospitalization rates and shorter LOS, which, however, is partly explained by a
higher burden of comorbidities and disease severity in the FFS hospital. This study provides a solid
baseline for comparison after nation-wide DRG implementation.
Correspondence: PD Dr. B. Hug, MBA, MPH, Division of Internal Medicine, University Hospital Basel,
E-Mail: [email protected]
P309
Diagnosis and treatment of iron deficiency in medical inpatients in a Swiss
tertiary university referral hospital
Balthasar Hug*, André Tichelli, Pascal Benkert, Guido Stirnimann, Jürg Schifferli
Background: Iron deficiency anemia is common; a European study found iron deficiency (ID) in about
every fifth young female (17-38 years)(1). The prevalence of ID in hospitalized patients is not well
known and may be significantly higher among patients with severe or chronic illness.
Aim: To evaluate the prevalence and the current diagnostic and treatment of iron deficiency (ID) in
hospitalized patients at the division of internal medicine in a Swiss tertiary university referral center.
Methods: Design: single center, retrospective observational cohort study including all consecutive
inpatients of the division of internal medicine at a tertiary referral university hospital in northwestern
Switzerland. Study duration: from July1st to December 31st 2011. Definitions: ID either ferritin <15
µg/L or ferritin <50 µg/L and transferrin saturation <20%. Anemia: males <130 g/L, females <120 g/L.
Results: Within the observation period 2,251 unique patients (2,781 hospitalization cases) were
enrolled; 55.5% were male and mean age was 66.4 years. Of these 2,267 cases (81.5 %) had their
blood drawn; in 329 cases (14.5%) iron parameters (IP) were determined and 45 (13.7%, CI : [10.2% 17,8%]) cases/unique patients with ID were detected. In statistical estimation 103 cases (69.6%) with
ID were not diagnosed. In ID the most prevalent diagnosis was heart failure (I50.01; 24,4 %) of which
72.7% had hemorrhage facilitating drugs (aspirin, phenprocoumon, heparins) on hospital admission or
discharge. Two thirds of patients with laboratory proven iron deficiency received iron substitution (IS)
of any kind (66.6%). Of the 30 patients receiving IS, 80% received it by i.v. route, 16.6% orally and
one patient combined i.v. and p. os. ID was coded correctly in 60%.
Conclusion: Iron deficiency (ID) is common in internal medicine and up to two thirds of concerned
cases may not be diagnosed. Every seventh patient who had his iron parameters (IPs) analyzed was
iron deficient and two thirds of patients with ID were treated with intravenous iron. Based on these
results further studies using a prospective design in order to optimize diagnosis and treatment of
patients with ID are warranted.
Literature
1)Grondin MA, Ruivard M, Perreve A, et al. Prevalence of iron deficiency and health-related quality of
life among female students. J Am Coll Nutr 2008; 27(2): 337-41.
Correspondence: PD Dr. B. Hug, Division of Internal Medicine, University Hospital, Basel . E-Mail:
[email protected]
P310
Cholesterol pilot study
Claude Rothen*, Theodor Kaufmann
Rothen Medizinische Laboratorien (Basel, CH); Praxis Bündnerhof (Basel, CH)
Introduction and Background: Dyslipidemia requiring treatment is common. Often patients ask for an
alternative treatment instead of the established statin therapy, mostly due to the occurrence of
unpleasant side effects of this treatment.
Some patients report considerable decrease of the cholesterol concentration with a red yeast rice
treatment. Red yeast rice contains Monacolin a substance known to inhibit the HMG CoA reductase.
Monacolin K is also the active substance in the HMG CoA reductase inhibitor Iovastatin.
74
The aim of this study is to answer the following question: Are there alternative therapies to the statin
treatment with comparable main effects on the lipid profiles, potentially reduced side effects and at
lower costs?
Method: We asked 14 test persons to take over eight weeks 2X2 capsules of red yeast rice daily (2.4
gram)
At baseline, after eight weeks, and after sixteen weeks blood samples were taken for total cholesterol,
triglycerides, HDL, LDL, and the ratio Chol/HDL.
Drug: We used capsules with red yeast with a defined content of monacolin K by 4%
Analysis: The analysis were measured using a Beckman Coulter DxC
To document the costs, we compared the daily costs of a common therapy with standard therapeutic
drugs
Results: From baseline to eight weeks we found in all patients a significant decrease of cholesterol
from 6.26 mmol/l to 5.22 mmol/l (p=0.0012), for LDL from 3.97 mmol/l to 3.03 mmol/l (p=0.0016) and
for the ratio from 4.03 to3.32 (p=0.001). After another eight weeks there was again an increase in the
concentrations of cholesterol, LDL and the ratio observed. (Fig 1)
Occasional side effects were reported
The comparison of the costs shows that the cost of the natural treatment are about the same as the
conventional treatment.
Conclusions: Our small study showed a significant reduction of total cholesterol and LDL levels when
taking red yeast rice for about eight weeks.
In comparison to the statins, the competitive price and the low incidence of side effects indicate a
possible alternative to the existing statin treatment.
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P311
Interprofessional collaboration between residents and nurses on a simulated
general internal medicine ward: behaviours enhancing teamwork quality
Virginie Muller-Juge*, Stéphane Cullati, Katherine Blondon, Patricia Hudelson, Fabienne Maître, Nu
Vu, Geroges Savoldelli, Mathieu Nendaz
University of Geneva (Genève, CH); University Hospitals of Geneva (Genève, CH)
Introduction: Studies have shown that effective teamwork is necessary for optimal patient care.
However, there is insufficient understanding of interactions between physicians and nurses on Internal
Medicine wards as compared to intensive-care or reanimation settings. The aim of our study was to
describe residents’ and nurses’ behaviors that contribute to teamwork quality.
Methodology: A volunteer sample of 14 residents and 14 nurses was recruited from the General
Internal Medicine Division at the University Hospitals of Geneva, Switzerland. Resident-nurse pairs
were asked to manage one non-urgent and one urgent clinical case in a simulated Internal Medicine
ward, using a high-fidelity mannequin. After the simulation, participants attended a stimulated-recall
session during which they viewed the videotape of the simulation and explained their actions and
perceptions.
All simulations were transcribed, coded, and analyzed, using a qualitative method (template analysis).
During previous interviews with the study participants, we identified behaviors important to observe
during the simulations, which then constituted the basis for our codebook, as well as items of
published scales. A team of 3 researchers (consisting of an educationalist, a physician, and alternately
one of the following: nurse, anthropologist, sociologist, or medical education specialist) first coded the
videos independently and then compared and discussed coding differences until consensus was
reached. Overall quality of teamwork during the simulations was scored based on patient
management efficiency, shared management goals, and the general tone or atmosphere of the
interaction.
Results: Analyses were ongoing at the time of the abstract submission. Preliminary results suggest
that, more than individual performance, the ability of the pair members to compensate for each other’s
weaknesses (such as lack of experience or autonomy) was associated with enhanced teamwork
quality. Individual decision-making without dialogue, coordination, and communication was associated
with diminished teamwork quality. The clinical case (urgent versus non-urgent) also seemed to
influence participants’ teamwork behaviors.
Conclusion: Certain behaviors, similar to those observed in multimember reanimation teams, appear
to enhance resident-nurse pair teamwork and may also compensate for some individual weaknesses.
Such behaviors should be addressed in interprofessional training at the pre- and post-graduate levels.
P312
Hepatitis B and prison officer perceptions: health beliefs about HBV
transmission
Alejandra Casillas*, Maria Pfefferle, Hans Wolff, Laurent Gétaz
Hopitaux Universitaires de Genève (Genève, CH)
Background: It is important to examine the health beliefs of those in close contact with populations at
high risk of infectious diseases, as is the case with prison officers. Incorrect beliefs among prison
officers may affect the efficacy of risk reduction programs for all individuals. The goal of this study was
to assess officers’ perceptions about hepatitis B (HBV) in the prison setting.
Methods: This descriptive study included five prisons in western Switzerland. Officers’ demographics,
specific fears and knowledge regarding various infectious diseases were collected by anonymous
questionnaire in 2012. Focusing on questions addressing HBV, we present descriptive analyses about
transmission knowledge and protective behaviours, and the associations between fear of HBV
infection and incorrect health beliefs.
Results: 170 prison officers (96% participated) completed the survey: 88% male and 56% based at a
pre-trial prison. While the majority (85%) recognized that contaminated needles could spread HBV, a
lower proportion was aware of the risks from tattooing (72%), unprotected sexual intercourse (62%),
sharing razors (69%) and toothbrushes (49%. Handshaking, food, and coughing were recognized as
false modes by 70%, 36% and 30% of the prison officers, respectively.
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In terms of HBV protection, 43% of participants stated that they used gloves when intervening in a
fight. But only 46% of participants said they were vaccinated, 16% were unsure, while 38% definitely
did not know their HBV vaccine status. Sterile needles and condoms were identified as prevention
measures by 82% and 67% of prison officers, respectively.
Regarding perceived fear, 44% had a moderate/great fear of HBV infection. There were significantly
higher rates of false beliefs among prison officers with moderate/great fear of contracting HBV (ref:
little/no fear) when asked about handshaking (RR 2.2, 95%CI 1.3-3.6), coughing (RR 1.3, 95%CI 1.031.5), and sharing food (RR 1.4, 95%CI 1.1-1.8) as possible transmission risks.
Discussion: HBV knowledge and protection strategies are suboptimal among prison officers. As well,
fear of HBV infection is associated with incorrect health beliefs. Improving health beliefs can decrease
fears, and lead to useful health behaviours, like vaccination and glove use. As prison physicians rely
on staff for ancillary support, it is increasingly important to address and improve their knowledge, for
the benefit of vulnerable patients residing in the prison setting.
P313
Syphilis and HSV2: prevalence study in a Swiss prison
Alejandra Casillas*, Hans Wolff, Javier Barro, Laurent Gétaz
Background : Latent syphilis infection and recurrence of Herpes Type-2 (HSV2) may lead to systemic
patient complications, and predisposal for other STD’s, respectively. However, prevalence data in
correctional settings (where patients may be at higher risk given behavioral history and SES) are
lacking. This study aimed to estimate the prevalence of syphilis and HSV2 and associated risk factors,
among male inmates in Switzerland’s largest pre-trial prison, Champ-Dollon, in Geneva.
Methods: This cross-sectional study analyzed serological markers for syphilis and HSV2 in a
representative sample of detainees. Screening for syphilis (ELISA) was offered in 2009 and 2011;
confirmation and disease activity tests (TPHA and VDRL) were applied to positive cases. HSV2-IgG
screening was only offered to participants recruited in 2011. Using a standardized questionnaire, we
obtained socio-demographic characteristics and patient-recall of genital ulcer history.
Results: 270/278 detainees were included for the syphilis screen (participation rate: 97.2%). Syphilis
screening was positive among four patients (1.5%, 95%CI 0.5-3.5): one had a history of ulcer. Three
had a positive TPHA-- with one positive and two inconclusive VDRL tests.
156/164 detainees participated in the HSV2 screen (participation rate: 95.1%). HSV2-IgG was positive
among 35 participants (22.4%, 95%CI 16.1-29.8%). Among HSV2+, 15% (5/35) had recurrent genital
ulcers in their history. Inmates from sub-Saharan African or Latin America had a higher risk of infection
versus those from other origins (RR 2.3, 95%CI 1.3-4.1). Inmates with a primary school education or
less had a higher risk versus those with more education (RR 2.2, 95% CI 1.14-4.1). History of sexual
intercourse with prostitutes, number of sexual partners, and frequency of condom use were not
associated with infection.
Conclusions: Even though the observed syphilis prevalence among prisoners was higher than in the
general population, studies are needed to define the cost-benefit of systematic screening given such
rates, in this vulnerable population. HSV2 prevalence in this setting was more than two times higher
than the Swiss general population among men of similar age. Interestingly, factors related to sexual
risk history did not efficiently discriminate HSV2-infected inmates. Overall, we recommend
strengthening preventive strategies in correctional settings, especially among low-educated inmates
originating from countries known for HSV2 endemics.
P314
The SPAM Network of family physicians: towards a better understanding of
primary care in Switzerland
Nicolas Senn*, Pakize Palan, Roland Fischer, Jacques Cornuz
Policlinique Médicale Universitaire (Lausanne, CH)
Introduction: Primary care (PC) is evolving in Switzerland like elsewhere. In this context, it is important
to have an accurate understanding of the functioning of PC. Recent works have identified an important
lack of data in Switzerland, particularly with regard to the access, quality of care, satisfaction and
services provided. The SPAM program (Swiss Primary Health Care Active Monitoring) aims to fill
these gaps by creating a prospective monitoring tool. As no systematic data collection exists in
Switzerland, it is essential to identify representative general internists’ (GI) practices able to provide
77
first hand information on the performances of the PC system. Our objective is to describe the
representativeness of the SPAM Network of 200 GI’s.
Method: A random pre-selection of 2027 GI was drawn from more than 7000 members of the
combined lists of the Swiss Family Physicians and Paediatricians Association (MFE) & Swiss General
Internal Medicine Society (SSMI). The draws were stratified by canton. Afterwards, physicians for who
general internal medicine was not the main clinical activity were removed.
To investigate the representativeness, we draw for comparison a random sample of 200 GI’s from the
same list of 2027 members (comparative group). The age was not available; therefore the date of birth
was estimated from the FMH database by subtracting 25 years to the year of the federal diploma.
Results: 200 GI accepted to join the Network (response rate = 9.9%). 62% speak German, 35%
French and 4% Italian. In the comparative group, the prevalence rates were 76%, 23% and 1%
respectively (p=0.02). 23% are female in the SPAM Network compared to 21% in the comparative
group (p=0.63). Mean age in 2012 is 53.8 years (estimated age based on year of diploma) in the
SPAM group compared to 53.4 in the comparative (p=0.68). For 4 cantons the recruitment target was
reached (29 GP’s), 7 cantons contribute too much (88 GP’s, expected 52) and 12 cantons not enough
(83 GP’s, expected 119).
Conclusion: Based on these data, the SPAM network of general internists appears to be
representative of Swiss general internists at a national level and will provide a solid basis to
investigate performances of the PC system. During the meeting, further survey results will be
presented on the activities of Swiss family physicians.
P315
Improvement of adherence to daily oral vitamin D supplementation in a
rheumatologic population: a pre/post-study
Delphine Stoll*, Olivier Lamy, Didier Hans, Pascal Zufferey, Alexander So, Marc-Antoine Krieg,
Bérengère Aubry-Rozier
CHUV (Lausanne, CH)
Introduction: Vitamin D (Vit.D) reduces the risk of falls and fractures. Some experts recommend that
serum Vit.D levels should be >30ng/ml (75nmol/l) for high-risk patients. Low Vit.D (<30ng/ml) was
highly prevalent in our outpatient population (86% in 20091). Subsequent to Vit.D informational
campaign to both our physicians and their patients we have evaluated the Vit.D status in a similar
population 2 years later.
Method: it.D levels were measured in November 20091 and 2011 in all outpatients who attended our
clinic. 25-OH Vit.D level was categorized as deficient (<10µg/l), insufficient (10-30µg/l) or normal
(>30µg/l). Patients who had received a high dose of Vit.D3 (>200’000IU) 6 months before each
screening period were excluded. Patients not regularly seen at our clinic were also excluded.
Results: In 2011, 239 patients were included (230 in 2009). The mean Vit.D level was 23.8 µg/l (4-53)
(20.8ng/ml in 2009, p=0.0001). 4% had deficiency (8% in 2009), 68% insufficiency (79% in 2009), 28%
normal levels (13% in 2009). The same percentage of patients was on daily oral Vit.D in 2009 and
2011 (38%). Of these supplemented patients 51% had normal results in 2011 compared to 25% in
2009 (p<0.01). Among the non-Vit.D users, 13 % had normal results in 2011 compared to 6% in 2009
(p=0.04).
If we used the limit of 20ng/ml rather than 30ng/ml as recommended by many experts, 52% patients
had Vit.D levels >20 ng/ml in 2009 and 66% in 2011 (p=0.001).
During the two years of the study the number of 25-OH Vit.D testings (4875 in 2009 and 6896 in 2011)
and the prescription of high doses of Vit.D3 (116 in 2009 and 253 in 2011) increased substantially in
our hospital. These improvements could also be related to the increasing number of publications and
grand round sessions about Vit.D between 2009 and 2011 in Switzerland.
Conclusion: The prevalence of low Vit.D decreased in two years from 86% to 72%. These results were
mainly due to the higher number of normal 25-OH Vit.D levels observed in patients taking oral daily
Vit.D (increasing from 25% to 51%). These results may be explained by: 1) better adherence to oral
daily Vit.D in the supplemented patients; 2) better information of physicians about hypovitaminosis D;
3) more frequent screening of Vit.D level and 4) higher prescription of high doses of Vit.D if this is
deemed needed.
1.
Stoll, D., et al., High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient
population. Swiss medical weekly, 2011. 141: p. w13196.
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P316
Training clinical supervisors in how to teach communication skills: an
exploration of factors affecting transfer to practice
Noelle Junod Perron*, Stéphane Cullati, Patricia Hudelson, Mathieu Nendaz, Diana Dolmans, Cees
Van der Vleuten
Hôpitaux Universitaires de Genève (Genève, CH); Maastricht University (Maastricht, NL)
Introduction: A faculty development program was designed to increase supervisors’ ability to give
feedback on junior doctors’ communication skills (CS) in clinical practice. The program combined CS
and teaching skills training. The aim of this study was to explore supervisors’ perceptions of factors
that facilitated skills transfer post-training.
Methods: 28 clinical supervisors from two medical settings took part in the program at the Geneva
University Hospitals, Switzerland. Skills transfer was explored through a short pre-post survey and
semi-structured interviews. Interviews were audio taped, transcribed verbatim and analyzed
thematically.
Results: Transfer was reported by supervisors for both communication and teaching skills. Work
characteristics that facilitated transfer of teaching skills included having opportunities to practice new
skills, being involved in structured teaching activities, and the existence of supportive institutional
policies. In addition, the combination of communication skills and teaching skills training in the same
training program, a mixture of practice and reflective work, and a positive learning climate were found
to be beneficial. Participants who reported teaching communication skills in practice were generally
involved in structured communication skills teaching and expressed increased confidence and
motivation post-training.
Discussion: Opportunities to practice and systematic involvement of supervisors in communication
skills structured teaching activities may increase transfer of communication skills teaching, probably
because it reinforces practice, maintains motivation. It also helps supervisors join a community of
teachers where exchange of ideas and insights can take place.
P317
Does training improve clinical supervisors’ ability to identify residents’
communication skills and teach them interactively in clinical practice?
Noelle Junod Perron*, Mathieu Nendaz, Johanna Sommer, Martine Louis-Simonet, Anne Gut, Cees
Van der Vleuten, Diana Dolmans
Hôpitaux Universitaires de Genève (Genève, CH); Faculté de médecine (Genève, CH); Maastricht
University (Maastricht, NL)
Introduction: Observation of residents’ communication skills followed by feedback by clinical
supervisors is a key element of communication skills teaching in clinical practice. However, clinical
supervisors may not be competent in identifying and addressing communication skills effectively. The
aim of this study was to measure the impact of a training program in teaching communication skills on
clinical supervisors’ ability to identify residents’ good and poor communication skills and their ability to
address them in an interactive way during feedback sessions.
Method: We conducted a pre-post controlled study in a hospital based and an outpatient setting at the
Geneva University Hospitals. Clinical supervisors participated in a training program (9 hours in total)
on how to teach communication skills in clinical practice over a period of 6-9 months. Outcome
measures were the number and the type of communication skills identified by participants on three
videotaped resident-patient encounters and the number of communication skills discussed in an
interactive way during three feedback sessions made before and after intervention.
Results : 48 clinical supervisors (28 in the intervention and 20 in the control group) participated.
Trained participants did not identify a higher number of residents’ communication skills on videotaped
clinical encounters after the training. However, they taught a significantly higher number of
communication issues in an interactive way during the feedback sessions after the training (effect
sizes 1.36-1.77).
Discussion : The training program did not increase the number of poor or good communication skills
recognized by supervisors but was effective in increasing the number of communication issues
discussed in an interactive way. Further research is needed to explore the respective weight of
accurate identification of communication skills or effective teaching skills to make communication skills
teaching more effective in clinical practice.
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P318
Needle and syringe exchange programmes: acceptability and safety of
retractable syringes for intravenous drug users in the largest pre-trial prison in
Switzerland
Hans Wolff*, Javier Barro, Alejandra Casillas, Thierry Favrod-Coune, Anne François, Jean-Pierre
Rieder, Mariem Baroudi, Laurent Gétaz, Barbara Broers
Geneva University Hospitals (Genève, CH)
Background: Needle and Syringe Exchange Programs (NSP) are efficient to prevent infectious
diseases in prison settings, but less than 1% of prisons worldwide have NSP. One identified barrier is
organizational concern for needle stick injuries and use of soiled syringes as weapons among
inmates. We evaluated 1) incarcerated drug users’ experiences with retractable syringes in an NSP,
and 2) beliefs and knowledge about NSP among prison officers (PO) and healthcare staff (HS) in
prison.
Method: In 2010, we replaced usual (insulin-type) syringes with retractable needle devices as part of
the NSP in the prison of Champ-Dollon, Geneva; Switzerland. We examined the demographics,
clinical profiles for and NSP use among NSP participants, and asked about the ease and safety of the
retractable needle device use, in face-to-face interviews. We distributed 98 questionnaires to prison
officers and to healthcare staff (HS), surveying individuals on their knowledge and opinions regarding
drug use and harm reduction measures.
Results: 284 retractable syringes were distributed to 28 inmates, with a return rate of 70%. Twenty-six
of them accepted to participate in the study. Thirteen were selected for interview and 10 interviews
were completed. Most participants were male (96.4%); mean age was 32 years (SD 4.8). They had a
median of 2 previous incarcerations (range 1-45) with a median duration of 70.7 days (range 5-690).
Median duration of IV drug use was 54 months (0-324). Seropravelence of HIV was 3%, HBV 7.1%
and HCV 60.7%. The majority of participants expressed that retractable syringes were acceptable
alternatives, but complained about difficulties due to the weight of the syringe and needle quality, as
well as the difficulty to install and use the syringe filter. Of the 98 questionnaires distributed to PO and
HS, 70% of PO and 100% of the HS estimated harm reduction policies as an effective means to
reduce the risk of transmission of blood-borne infections. However, 90.3% of PO and 9.6 % of HS
were still concerned about the use of syringes as weapons.
Conclusion: This is the first study evaluating experiences with retractable syringes for NSP in a
correctional setting. NSP was perceived as an acceptable alternative for incarcerated IV drug users.
Acceptance may be increased by improving the quality and ease of use of the retractable device as
suggested by prisoners. Addressing PO and HS safety concerns are an important step towards more
disseminated NSP implementation.
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Allgemeine Innere medizin 3 - Médecine interne générale 3
P319
Comparing perceived cross-cultural skillfulness between physicians and
nurses at Lausanne University Hospital: does provider role make a difference?
Alejandra Casillas*, Sophie Paroz, Alexander Green, Hans Wolff, Patrick Bodenmann
Policlinique Medicale Universitaire, CHUV (Lausanne, CH); Policlinique Medical Universitaire, CHUV
(Lausanne, CH); Harvard Medical School (Boston, US); Hopitaux Universitaires de Geneve (Genève,
CH)
Background: As the diversity of the local population evolves, measuring providers' cultural competency
and understanding what contextual factors may influence this skillfulness is necessary. Given a lack of
information on provider role, this question is increasingly important, as Swiss nurse practitioners begin
to assume clinical responsibilities for vulnerable patients. We compared perceived skillfulness and
explanatory predictors between physicians and nurses working at a university hospital.
Methods: A 64-item questionnaire on cross-cultural care, including translated/back-translated items
from a validated American survey was mailed in November 2010 to residents, chief residents and
nurses. Using Student's t-tests, we compared physicians' and nurses' mean composite scores for the
nine perceived skillfulness items (4-point Likert-scale), and proportion of "3-good/4-very good"
responses using Chi-square tests. We used linear regression to examine how provider role (physician
vs. nurse) was associated with composite scores, adjusting for demographics (gender, non-French
dominant language), workplace (time at institution, work-unit "sensitized" to cultural-care), items on
reported cultural-competence training, and on cross-cultural care problem-awareness. We present
results significant at the p=0.05 level.
Results: Of 885 questionnaires, 371 (41.2%) returned the survey: 123 (33.6%) physicians and 239
(66.4%) nurses, reflecting institutional distribution of providers. Physicians had better mean composite
scores for perceived skillfulness than nurses (2.7 vs. 2.5, p=.0005), and significantly higher proportion
of "good/very good" responses for 4/9 items. After adjusting for explanatory variables, physicians
remained more likely to have higher skillfulness (beta = 0.13, p=.049). Among all, higher skillfulness
was associated with perception/awareness of problems in the following areas: inadequate crosscultural training (beta = 0.14, p=.012) and lack of practical experience caring for diverse populations
(beta = 0.11, p=.040).
Conclusions: Overall, perceived cross-cultural skillfulness among providers was low. Physicians had
higher skillfulness than nurses. However, problem-awareness about cross-cultural care was positively
associated with skillfulness among both groups. Thus, attuning providers' awareness to the
surrounding problems in cross-cultural patient-care, can improve skillfulness- especially among nurses
with rising responsibilities.
P320
Predictors of cross-cultural care preparedness among physicians and nurses
in Lausanne, Switzerland
Alejandra Casillas*, Sophie Paroz, Alexander Green, Hans Wolff, Patrick Bodenmann
Policlinique Médicale Universitaire, CHUV (Lausanne, CH); Harvard Medical School (Boston, US);
Background: The changing influx of migrant and at-risk patients into the safety net represents a
challenge for health providers. We evaluated health provider cross-cultural preparedness for
commonly encountered vulnerable patient profiles.
Methods: A 64-item questionnaire on cross-cultural care, including translated/back-translated items
from a validated American survey was mailed in November 2010 to residents, chief residents and
nurses. Preparedness items asked "How prepared do you feel to care for…?" referring to patientprofiles, such as "patients with distrust of the health care system" on an ascending 5-point Likert scale.
We examined proportions of "4-well/5-very well prepared," and the mean composite score for the eight
items. We used simple and multivariate linear regression to examine the effect of the following
variables on the composite: demographics (gender, non-French dominant language), work context
(provider role, institution time, unit "sensitized" to cultural-care), and items on reported culturalcompetence training, and cross-cultural care problem-awareness. We present results significant at the
p=0.05 level.
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Results: Of 885 questionnaires, 371 (41.2%) returned the survey: 123 (33.6%) physicians and 239
(66.4%) nurses, reflecting the distribution of providers. The mean composite score was 3.30 (SD 0.70)
with the highest proportion of "well/very well-prepared" responses for the item referring to patients with
"cultures different from your own" (67.2%) and the lowest for "whose religious beliefs affect treatment"
(21.9%). After multivariate adjustment, having a non-French dominant language (beta = 0.25, p=.012),
nurse provider role (beta = 0.221, p=.03), working in a sensitized department (beta;= 0.21, p=.007),
and having received training on the history/culture of a specific group (beta = 0.25, p=.03) remained
significantly associated with higher preparedness; as was problem-awareness about the lack of
practical experience caring for diverse populations (beta = 0.25, p=.004) and about inadequate crosscultural training (beta = 0.18, p=.04).
Conclusions: Preparedness among providers leaves room for improvement. However, we found
specific factors that can be incorporated into organizational strategies aimed at cross-cultural
preparedness. The findings emphasize the institution's role in creating a diverse and culturallysensitive work environment towards increasing health provider preparedness-- thus improving crosscultural care.
P321
Critical assessment of anticoagulant and antiplatelet agent prescription pattern
in the polymorbid rehabilitation population after stroke and hip or knee surgery
(CASAC Study)
Helen Schmidt*, Helen Schmidt, Felix Angst, Andreas Gantenbein, Susanne Lehmann, Andre
Aeschlimann, Hans Jürg Beer
RehaClinic Zurzach (Zurzach, CH); KSB (Baden, CH)
Background: The prescription pattern of anticoagulant (AC) and antiplatelet therapy (APT) is changing
rapidly with the advent of new oral anticoagulants (NOACs) and new antiplatelet agents (NAPAs).
Dual or triple anticoagulation therapy (ACT) carries a high bleeding risk and its indication and duration
requires careful assessment.
Aim of the study: To critically appraise the indication and duration of AC and APT in the vulnerable
population of a rehabilitation clinic after stroke and major orthopaedic surgery.
Methods: 118 consecutive patients on NOACs, low molecular weight heparin (LMWH), Vitamin K
antagonists (VKA) and/or APT were evaluated from March to October 2012 in this retrospective cohort
study. Inclusion criterion was hospitalization after knee or hip surgery or stroke with the indication for
AC. Demographics, diagnoses esp. renal function, atrial fibrillation (AF), co-medication, HAS-BLEDand CHA2DS2-VASc scores were obtained. Indications were critically reviewed according to the
ACCP-guidelines (American College of Chest Physicians 2012) by a group of independent experts not
involved in the treatment of the patients.
Results: Mean age was 82 (±4.5) years, 63% were female. Diagnostic categories were stroke in 22%,
hip replacement in 48% and knee replacement in 30%. Creatinine Clearance <50ml/min occurred in
30% of the cases. The table shows the distribution of the use of AC, heparin and APT alone and in
combination.
Combinations of APT and VKA/NOAC or LMWH were found in 38% (45/118), 62% of these patients
on this dual therapy (28/45) received PPIs. A HAS-BLED score of >=3 was found in 80% (94/118)
from whom 49% (46/94) were on dual anticoagulation therapy.
Conclusions: Our study shows that a) NOACs are prescribed at a high frequency and b) in more than
one third as dual ACT in the daily practice of a frail rehabilitation patient population with a large
number of comorbidities including renal failure. c) A prophylactic treatment with PPIs is lacking in a
substantial proportion on dual ACT. To reduce the high bleeding risk, it is necessary to critically
assess indication and duration of dual ACT.
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P322
Traditional medicine travels too: a rare cause of lead poisoning
Halima MÜLLER*, Simon Regard, Nicole Petriccioli, Omar Kherad
La Tour Hospital (Genève, CH)
Introduction: Lead poisoning is a multisystemic organ disease which can present with non-specific
symptoms such as fatigue, anorexia, arthralgia, myalgia, neurological disorders, anemia abdominal
pain and encephalopathy. The diagnosis may represent a pitfall and is based on clinician
consideration to order appropriate blood lead level and erythrocitic protoporphyrins.
Methods: We report the case of a 42-year old man from Bhutan, who was admitted to the emergency
departement of La Tour Hospital, with a 5-day history of abdominal pain, nausea and vomiting.
Examination revealed pain on palpation of the right upper abdominal quadrant with no sign of
peritonism. The patient resides in Geneva and frequently travels to his home country.
Results: Blood tests revealed a cholestatic liver abnormality and a hemolytic anemia with hemoglobin
level at 90 g/l. An abdominal ultrasound and a thoraco-abdominal CT scan proved normal.
Serologies for HIV, CMV, EBV and hepatitis A,B,C were negative. A blood smear was performed and
showed basophilic stippling highly evocative of a heavy metal poisoning. Blood and urinary lead levels
were high at 80.8 mcg/dl and 208.8 mcg/g of creatinine respectively. An increase in urinary
coproporphyrin III level up to 155.9 nmol/mmol was also noted. It was discovered that the origin of the
intoxication was due to the patient taking Bhutanese traditional medicines to treat a resolutive Bell’s
palsy a few months earlier. These medicines were made of paper with ink writings, hair of a deceased
local priest and an additional unidentified substance (cf figure 1). The analysis showed the presence of
high level of lead.
Conclusion: Lead exposure and poisoning is still a major health issue in developing countries. It has
been estimated as responsible of 8’955’000 disability-adjusted life years (DALY) in 2004.
Complementary and alternative medicines (CAM) have become more frequent causes of lead
poisoning in the past few decades even in Western countries as they become more popular and easily
available on Internet. Enhancing public awareness about potential harmful effect of CAM is a major
objective of health care prevention. Meanwhile, it remains the responsibility of physician to obtain a
detailed history of medications use, even in developed countries where lead exposure and poisoning
are also reported.
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P323
Quality of life after pulmonary embolism: validation of the French version of
the PEmb-QoL questionnaire
Mathilde Rochat*, Marie Méan, Olivier Hugli, Andreas Limacher, Drahomir Aujesky
CHUV (Lausanne, CH); Inselspital (Berne, CH)
Introduction: The PEmb-QoL is a validated 38-item questionnaire to quantify health-related quality of
life in patients having experienced pulmonary embolism (PE). It includes 6 health dimensions:
frequency of complaints, activities of daily living limitations, work-related problems, social limitations,
intensity of complaints, and emotional complaints. Originally developed in English, we sought to
prospectively validate the psychometric properties of a French version of the PEmb-QoL.
Methods: We performed a forward and backward translation of the English version of PEmb-QoL into
French. We screened all consecutive patients aged >18 years with an acute objectively confirmed PE
admitted at the emergency department of the Lausanne university hospital from August 1, 2009 to
September 30, 2011 using an electronic patient tracking system. We telephonically invited all
screened patients who survived the PE episode for study participation. Patients who refused to
participate or who had insufficient spoken language ability in French were excluded. Enrolled patients
received per mail a baseline PEmb-QoL and SF-36 questionnaire. Patients were asked to complete
and return both questionnaires using a stamped return envelope. In order to assess the reproducibility
of the PEmb-QoL, participants were mailed a second PEmb-QoL and SF-36 questionnaire 10 days
after the baseline evaluation. We assessed internal consistency, test-retest reliability, convergent
validity, and construct validity of the French PEmb-QoL.
Results: Of 242 patients screened, 102 (42.1%) fulfilled all eligibility criteria and were enrolled in the
study. Internal consistency (Cronbach’s alpha 0.7-0.95) and test- retest reliability (intra-class
correlation coefficients 0.85-0.96) were adequate. Assessment of correlations between the dimensions
of the PEmb-QoL questionnaire and other clinical measures (age, gender, obesity, cancer, central PE,
history of PE, cardiovascular comorbidities) supported the construct validity of the questionnaire.
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Correlations between the dimensions of the PEmb-QoL- and SF-36 questionnaires also supported
convergent validity.
Conclusion: We successfully validated the French version of the PEmb-QoL questionnaire in patients
with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of
life after PE in French speaking patients.
P324
Impact of diuretic therapy-associated electrolyte disorders present on
admission to the emergency department: a cross-sectional analysis
Spyridon Arampatzis, Georg Funk, Alexander Leichtle, Georg Fiedler, Christoph Schwarz, Heinz
Zimmermann, Aristomenis Exadaktylos, Gregor Lindner*
Inselspital (Bern, CH); Otto Wagner Spital (Wien, AT); Medizinische Universität Graz (Graz, AT)
Background: Diuretics are among the most commonly prescribed medications and, due to their
mechanisms of action, electrolyte disorders are common side effects of their use. We investigated the
associations between diuretics being taken and the prevalence of electrolyte disorders on admission
as well as the impact of electrolyte disorders on patient outcome.
Methods: In this cross sectional analysis, all patients presenting between 1 January 2010 and 31
December 2011 to the Emergency Department of the Inselspital, University Hospital Bern, Switzerland
were included. Data on diuretic medication, baseline characteristics and laboratory data including
electrolytes and renal function parameters were obtained from all patients. A multivariable logistic
regression model was performed to assess the impact of factors on electrolyte disorders and patient
outcome.
Results: 8.5% of patients presenting to the ER used one diuretic, 2.5% two, and 0.4% three or four.
4% had hyponatraemia on admission and 12% hypernatraemia. Hypokalaemia was present in 11%
and hyperkalaemia in 4%. All forms of dysnatraemia and dyskalaemia were more common in patients
taking diuretics. Loop diuretics were an independent risk factor for hypernatraemia and hypokalaemia,
while thiazide diuretics were associated with the presence of hyponatraemia and hypokalaemia. In the
Cox regression model, all forms of dysnatraemia and dyskalaemia were independent risk factors for in
hospital mortality.
Conclusions: Existing diuretic treatment on admission to the ER was associated with an increased
prevalence of electrolyte disorders. Diuretic therapy itself and disorders of serum sodium and
potassium were risk factors for an adverse outcome.
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P325
Etiology and symptoms of severe hypokalaemia in emergency department
patients
Grischa Marti, Christoph Schwarz, Alexander Leichtle, Georg Leichtle, Spyridon Arampatzis,
Aristomenis Exadaktylos, Gregor Lindner*
Inselspital (Bern, CH); Medizinische Universität Graz (Graz, AT)
Purpose: To investigate the prevalence, etiology and symptoms of severe hypokalemia in patients
presenting to the ED.
Materials & Methods: In this retrospective, cross-sectional analysis we included all patients who
received measurement of serum potassium between April 2008 and 31 March 2011 at the ED in order
to calculate the prevalence rate for hypokalemia. Of all patients with a serum potassium below 2.6
mmol/L (severe hypokalemia) we performed a detailed review of the patients' charts from the ED and
the chart of the following hospitalization. We identified ECG changes attributable to hypokalemia from
the ECGs performed in the ED.
Main findings: During the study period a total of 43.805 measurements of serum potassium were
performed. 11% of patients had hypokalemia (potassium <= 3.5 mmol/L) at presentation. 53 patients
with severe hypokalemia could be identified. 49% were symptomatic with weakness and muscle pain
being the most common symptoms. 69% of patients had ECG changes with presence of a U wave
followed by ST segment depression and ventricular extrasystoles. Malnutrition and use of diuretics
were the main causes of severe hypokalemia.
Conclusions: Hypokalemia is common in the ED. Severe hypokalemia is often symptomatic and more
than two-third of patients have ECG changes.
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P326
Hyperkalaemia in the emergency department: etiology, symptoms and outcome
of a life-threatening electrolyte disorder
Carmen Pfortmüller*, Christoph Schwarz, Alexander Leichtle, Georg Fiedler, Spyridon Arampatzis,
Aristomenis Exadaktylos, Gregor Lindner
Inselspital (Bern, CH); Medizinische Universität Graz (Graz, AT)
Aims: To determine the prevalence, symptoms, etiology and outcome of severe hyperkalemia in the
ED of a large university hospital.
Methods: In this retrospective analysis patients admitted to our ED between 01 January 2009 and 31
December 2010 with measurement of serum potassium were included. Dyskalemias and
dysnatremias were defined according to the reference range of our laboratory (normal range,
potassium 3.5-4.5 mmol/L; sodium 135-145 mmol/L).
Of all patients with severe hyperkalemia, (>= 6.0 mmol/L) patient charts were reviewed for information
on the symptoms and etiology of hyperkalemia.
Results: Of a total of 29.250 potassium measurements, 2.585 patients (8.8%) had hyperkalemia, and
3.252 (11%) had hypokalemia. 88 patients (3.4% and 0.3% of all patients) had severe hyperkalemia.
Age of patients was 65 years (SD 17) with 20 patients (23%) being female and 68 male (77%).
Potassium was 6.4 mmol/L (6.1-6.8) with a maximum of 10.9 mmol/L and creatinine was 192 umol/L
(124-360). 36 patients (41%) had concurrent hyponatremia and 1 patient (1%) hypernatremia.
Hyponatremia was significantly more common in patients with severe hyperkalemia than in
normokalemic patients (36 vs. 9%, p<0.0001). In the venous blood gas analysis pH was 7.25 (7.037.34), pCO2 38 mmHg (28-46), bicarbonate 15.8 mmol/L (9.7-19.7) and lactate 2.0 mmol/L (1.4-7.2).
30 patients (34%) had metabolic acidemia, 5 (6%) respiratory acidosis and 1 patient had respiratory
alkalosis, combined metabolic and respiratory acidosis or metabolic acidosis acidosis and respiratory
alkalosis, respectively. 26 patients (30%) had symptoms attributable to hyperkalemia. 17 patients
(65% of symptomatic and 19% of all) presented with arrhythmias as objectivated by ECG. General
muscular weakness was present in 9 patients (34%/10%). 28 patients (64%) had ECG changes
attributable to hyperkalemia. Renal insufficiency (40%), end-stage renal disease (23%), CPR (11%)
and metabolic acidosis (6%) were the leading causes of severe hyperkalemia.
Conclusion: Disorders of serum potassium are common in the ED with 1 in 5 patients presenting with
it. Renal failure and cardiopulmonary resuscitation were the most common causes of hyperkalemia in
our patients.
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P327
Communication by official statements of Swiss Health organisations during
debate of the federal smoking ban 2008-2012
Rainer Kaelin* Initiativkomitee Schutz vor Pasivrauchen
Background: The Swiss legislative process towards a national smoking ban in public places started in
2004 by the signature of the WHO framework convention on Tobacco control and the initiative of MP
F. Gutzwiller MD. By 10/2008 it had resulted in a federal Alibi “Gastro-boro- Law”, elaborated under
heavy pressure by lobbying, failing to meet WHO standards. Therefore the Swiss Lung League (SLL;
federation of cantonal lung leagues) launched a popular initiative aiming better legislation. The
initiative was backed by a large alliance of health organizations. Despite 120 000 signatures collected
by 2010, the law project was refused by national vote 9/2012, after heavy campaigning.
Aim/Method: Since media reporting on the subject was poor (only 10 % of articles on smoking bans
between 11/2009-02/2010 were in favour), the present work analyses official statements of health
organizations in order to detect communication flaws, that may have contributed to insufficient
information of media and public.
Results: A. The federation of Swiss physicians (FMH) first declined the initiative (letter 03/09), arguing
that backing of the prevention law debated in parliament was more important, but finally endorsed it
(01/10) after a vote of their delegates. B. The internists society’s president declined official public
positioning on passive smoke protection at the 2008 congress arguing that the congress wasn’t smoke
free and sponsors should be consulted first. The members assembly though endorsed the initiative
2010, but nevertheless no official public statement was issued. C: The SLL urged cantonal lung
leagues to collect signatures, but some did not (ZH, VD). The president of the Vaud League
disapproved the launch of the initiative (letter to SLL 12/08), but finally backed it by vote of the
committee 2010. D. The national tobacco-fighting organization AT, member of the initiative’s alliance,
proposed its withdrawal 6 month before the popular vote, based on a committee decision.
Conclusion: The refusal of the initiative’s law proposal for a federal smoking ban cannot be attributed
only to the influence of the tobacco lobby on media. Lack of coherent communication strategy of
health organizations contributed to disinformation of the public
P328
Progressive sporotrichoid and disseminated fish tank granuloma by
Mycobacterium marinum in an HIV-infected patient
Florian Kuss*, Jan Amort, Julia Sproedt, Urs Karrer, Jacques Gubler
Kantonsspital Winterthur (Winterthur, CH)
Case: In May 2012, a 45-year-old patient presented to our surgery department with a purulent ulcer
under the right thumb nail and multiple satellite lesions along the extensor muscles. Prompt secondary
healing was noted after surgical debridement of the lesions without the need for systemic antimicrobial
therapy. Surprisingly, microbiology was only positive for Candida ssp. Two months later, progressive
phlegmonous infection of the thumb involving the metacarpo-phalangeal joint had occurred. Moreover,
distant abscesses had formed at the left arm and leg. Meanwhile, the patients’ GP had diagnosed
advanced HIV-infection with Candida esophagitis and wasting syndrome and had initiated
antiretroviral therapy (ART) with Efavirenz, Emtricitabin and Tenofovir (Atripla®) in June 2012.
Considering the profound immunodeficiency of this fish tank owner, we suspected disseminated nontuberculous mycobacterial infection. Indeed, examination of material from several distant abscesses
revealed acid fast bacilli in high density, later identified as Mycobacterium marinum. We introduced
antimycobacterial therapy with Ethambutol, Rifampicin and Azithromycin and added adjunctive
Prednisolone due to clinical evidence for immune reconstitution inflammatory syndrome (IRIS)
involving several joints. Dosing of the antiretroviral therapy was adapted to the pharmacokinetic
interaction with Rifampicin. While the patient swiftly recovered concerning his general condition,
weight and immune status, the course of wound healing was protracted over months. In December
2012, Rifampicin and Prednisolone were stopped and Ethambutol and Azithromycine will be continued
at least until February 2013.
Discussion: This patient is a typical example of a ‘late-presenter’ negating his substantial risk of HIVinfection and obvious signs of deteriorating health. A HIV-Test was ordered only after endoscopy,
89
performed for evaluation of dysphagia and massive weight loss of ~15kg, had demonstrated Candida
esophagitis. Insufficient communication between different health care providers further delayed
appropriate management by 2-3 months leading to progressive sporotrichoid and disseminated M.
marinum infection including IRIS. Concomittant antimycobacterial and antiretroviral therapy must take
into consideration the potentially serious pharmacologic interactions.
P329
Natriuretic peptides for early prediction of acute kidney injury in communityacquired pneumonia
Albina Nowak*, Tobias Breidthardt, Sarah Dejung, Mirjam Christ-Crain, Roland Bingisser, Beatrice
Drexler, Christophe Meune, David Marono, Tamina Mosimann, Beat Müller, Christian Müller
Universitätsspital Zürich (Zürich, CH); Universitätsspital Basel (Basel, CH); Kantonsspital Aarau
(Aarau, CH)
Background: Community-acquired pneumonia (CAP) is common and associated with a considerable
risk of acute kidney injury (AKI).
Methods. We prospectively enrolled 341 patients presenting to the emergency department with CAP
(mean age 72, male 61%). Blinded measurements of three natriuretic peptides (NT-proBNP, MRproANP and BNP) were performed upon presentation. The primary endpoint was the accuracy of the
natriuretic peptides to predict AKI within 48 hours.
Results. AKI occurred in 24 patients (7.6%) within the first 48 hours. NPs and creatinine were
significantly higher in AKI compared with patients without AKI (NT-proBNP 9517 [2042-26792] vs 1177
[280-4167] pg/ml; MR-proANP 641 [196-1075] vs 182 [99-352] pmol/l; BNP 592 [230-1630] vs 160
[64-463] pg/ml; creatinine 166 [131-289] versus 100 [78-134] µmol/L, P<0.001 for each). Predictive
accuracy as quantified by the area under the receiver operating characteristics curve was moderate to
high: NT-proBNP 0.79 (95%CI 0.70-0.88), MR-proANP 0.78 (95%CI 0.67-0.88), BNP 0.74 (95%CI
0.63-0.85), creatinine 0.77 (95%CI 0.66-0.88). In multivariate logistic regression analysis, NPs
remained the only independent AKI predictors: NT-proBNP (increase of 200 pg/ml) OR=1.01, 95%CI
1.00-1.01, P=0.009; MR-proANP (increase of 100 pg/ml) OR=1.23, 95%CI 1.09-1.39, P=0.001; BNP
(increase of 100 pg/ml) OR=1.08, 95%CI 1.03-1.14, P=0.002.
Conclusions. NP levels are significantly elevated in CAP-patients experiencing early AKI. Their
potential to predict early AKI is comparable to serum creatinine and might be useful in cases of
diagnostic uncertainty.
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P330
Postgraduate competency-based (CB) curriculum in internal medicine (IM):
pilot study of clinicians’ definitions and perceptions of CanMEDS roles and
physicians’ competencies
Matteo Monti*, Raphael Bonvin, Nu Viet Vu
CHUV (Lausanne, CH); School of medicine and UDREM (Genève, CH)
CB education in the health profession has emerged as a priority for curriculum planners to align with
societal needs. Switzerland has introduced for the pre- and postgraduate training a new curriculum
largely inspired from the Canadian “CanMEDS framework”. Since controversy exists regarding
transferability of general competencies in different social and political settings, we undertook to
determine, in the Swiss French IM in-patient hospital setting, 1) how front-line clinicians define
competencies expected of residents at the end of their postgraduate training , 2) how they perceive
the different roles defined in the CanMEDS.
Methods: We conducted a mixed qualitative and quantitative study, among a purposive sample of
faculty, chief residents, and residents at two large urban IM departments in Switzerland. 33 physicians
(8 faculty, 10 chief residents and 15 residents) volunteered to participate in six semi-structured focus
groups. The groups were guided by a protocol which included unstructured time for comments, a
guided discussion and time to complete a questionnaire. All the activities were carried out to gather
insights regarding the participants’ definition of competence and views of the five different taxonomic
levels of the Canadian framework. Focus groups discussions were tape-recorded and transcribed.
Verbatim transcriptions were coded by two independent researchers and classifications are based on
the consensus between the two researchers. We used for the analysis a “Grounded theory” approach.
Descriptive statistics were used to analyse the questionnaires. Fisher’s exact test was used to
compare responses from the three categories of participants.
Results: In all 6 focus groups, participants’ definition of competence included statements amenable to
all seven CanMEDS roles. Nevertheless the “Medical Expert, Communicator, Collaborator,
Professional and Scholar” roles were seen as most relevant to an in-patient IM rotation. Conversely
the “Manager” and “Health Advocate” roles were judged as least relevant. Those findings were
consistent with both the qualitative and quantitative analyses, independently from the physician status.
Conclusions: Implementation in the Swiss context of a CB curriculum based on the seven CanMEDS
roles is feasible and appropriate. Nevertheless adjustments are needed in the description of some
91
roles and competencies in order to make them acceptable and understandable for both the trainees
and the clinical supervisors
P331
Electrocardiographic manifestations in moderate to severe hyperkalaemia
Noémie Rapin*, Katia Iglesias-Rutishauser, Etienne Pruvot, Gerard Waeber, Matteo Monti
Faculté de biologie et médecine (Lausanne, CH); Centre de Recherche clinique, Département de
formation et Recherche, FBM (Lausanne, CH); CHUV (Lausanne, CH)
Hyperkalaemia is a serious electrolyte disturbance, which in extreme cases can lead to death.
Classical ECG changes are: QT-shortening, tenting of T-waves, lengthening of the PR interval, onset
conduction disturbances (BB- or AV- block), disappearance of P wave, QRS widening and finally
asystole. While studies on healthy volunteers conducted in the '40s had suggested a good correlation
between the level of potassium and ECG changes, more recently, several studies have found that in
mild hyperkalaemia (< 7mmol/l) potassium levels did not correlate with the severity of ECG changes.
The aim of our study was to determine which factors are associated to the development of ECG
modifications in patients with moderate to severe hyperkalaemia. Secondary outcome was the
estimation of mortality.
Methods: We undertook a retrospective analysis of all cases of moderate to severe hyperkalaemia
(K=>7,0mmol/l) in adults, hospitalised at our institution between 2009 and 2010. Patients were
included if an ECG was available at the same time of the hyperkalaemic episode. ECG analysis were
performed by two investigators, according to heart rate, QRS and QTc duration, T and RS amplitude
and the presence of a conduction disturbance (brunch bundle- or AV-block and arrhythmia). Univariate
and multivariate analysis were performed to look for associations between ECG characteristics,
chemistry (K, Na, Ca, pH, HCO3, pO2, SatO2), co-morbidities and demographics.
Results: Of the 913 patients screened, 82 were eligible for analysis. Mean age was 69y, 20,7% had
ESRD, 23,1% an acute renal injury and 33,7% CKD. Mean K 7,46mmol/l (7,0 to 9,0). Mean pH 7,23
(6,71-7,46). No correlation was found between K levels and ECG changes or mortality. Conversely,
the severity of acidosis was the only element capable of predicting the development of “typical” ECG
changes as well as the probability of cardiac arrest (CA) or death. CA/mortality rate was 30,5% during
the hospitalisation, but only 8,5% could be directly attributable to hyperkalaemia.
Conclusions: ECG is not a reliable tool for estimating the degree of hyperkalaemia or to select patients
at risk of complications or death. In hyperkalaemic patients however the severity of metabolic acidosis
is clearly associated with an increase in the QRS duration, the development of conduction
disturbances and also with an increased mortality. People with a pH <7.2 concomitant to severe
hyperkalaemia has to be considered particularly at risk.
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P332
Complete hydatid mole in a perimenopausal women with a subsequent thyroid
storm
Maya Rutishauser*, Tobias Gonzenbach
Spital Bülach (Bülach, CH); Spital Buelach (Bülach, CH)
Introduction: GTD are a rare complication of a normal pregnancy and occur often at the beginning or
the end of the reproductive period. Most have an excellent prognosis, occasionally if the disease
persists chemotherapy is required.
A rare complication of gestational trophoblastic disease (GTD) is the development of a secondary
hyperthyroidism, often disappearing after curettage. The underlying cause are structural and receptor
analogies between humanic chorionic gonadotropin (HCG) and thyreotropic hormone (TSH). High
HCG values as observed in GTD can induce a secondary hyperthyroidism.
Case report: A 51-year-old perimenopausal patient (IV Gravida, III Para) presented to the emergency
department with vomiting, nausea, diarrhea and vaginal bleeding for 2 months. Clinical examination
showed a palpable mass in the abdomen. A CT scan demonstrated a 14x13x12cm non-invasive tumor
of the uterus without abdominothoracic metastasis. Following a positive pregnancy test in the urine
bHCG in the blood was analyzed, with a highly elevated value of 1618600 IU/L, leading to the
assumption of a gestational trophoblastic disease. Further laboratory studies revealed a distinct
hyperthyroidism (TSH < 0.008mU/L, fT4 87.7pmol/L, fT3 28.2pmol/L). During the hospital stay the
patient developed a congestive heart failure (multifocal atrial tachycardia, dilated jugular veins,
bilateral pretibial edema, pulmonary congestion), interpreted as a clinical manifestation of
hyperthyroidism. Treatment with diuretics and ACE-Inhibitor, as well as Neomercazol and Propanolol
was started, under which the clinical condition stabilized. The patient underwent a suction curettage.
In the macroscopical, histological and immunhistochemical findings a complete hydatid mole was
confirmed. During the follow-up with serological controls every 2 week initially a decrease of the HCG
values was observed, followed by a sudden increase after 6 weeks. Abdominothoracic CT scan was
repeated and multiple pulmonary nodules restrained to the left lung, consistent with metastatic disease
were found. Chemotherapy with Methotrexat was started.
Conclusion: The coincidence of a gestational trophoblastic disease and hyperthyroidism, sometimes
devolving into a lifethreatening thyroid storm has been described in several papers; frequency varies
between 7-10%. An early measurement of thyroid function, particularly before operations or CT scans
with iodinated contrast is highly important.
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P333
A legion appears sometimes not alone
Isabel Morales*, Markus Eichelberger
Case A 25-year-old otherwise healthy man was hospitalized due to dyspnea, cough, fever and
gastrointestinal symptoms. Clinical examination revealed a tachypneic patient with fever. Radiography
94
showed infiltrates in the middle and right lower lobe. Urinary antigen test was positive for L.
pneumophila. Under treatment with Levofloxacin the patient was discharged. 3 days later he was
again admitted with sudden onset of right-sided chest pain, hemoptysis and painful swelling of the
right leg. A chest CT scan showed multiple segmental bilateral pulmonary embolism. A totally
thrombosed proximal Vena femoralis of the right leg was detected by ultrasound. Localized lysis was
abandoned because of hemoptysis with risk of fatal bleeding. In absence of previous VTE and
negative family history for VTE tumour screening was performed which was negative. Anticoagulation
was started and antibiotic treatment with Levofloxacin was continued. In presence of extensive VTE
screening for inherited thrombophilia was done and the result showed a heterozygous Factor V
mutation.
Discussion L. pneumophila is an aerobic gram-negative bacteria and causes Legionnaires’ disease as
a syndrome of community-acquired pneumonia and gastrointestinal symptoms. The incidence
depends upon the degree of water reservoir contamination, the intensity of exposure to that water, and
the susceptibility of the host. Different serogroups exist and most of the cases belong to the L.
pneumophila serogroup 1. Urinary antigen testing for L. pneumophila serogroup 1 is the diagnostic
method of choice due to the fast availability of the result and the persistence of positive results after
administration of the antibiotic therapy. Effective antibiotics are quinolones and macrolides. VTE may
occur because of activation of tissue factor, a glycoprotein of the subendothelial component of the
vessel wall. Tissue factor is activated because it comes into contact with blood during septicaemia;
therefore the coagulation cascade is activated. Because of extensive manifestation of VTE despite of
initial low-risk, screening for inherited thrombophilia was done and revealed heterozygous Factor V
mutation. Retrospectively important risk factors of VTE was immobilization, heterozygous Factor V
mutation and probably L. pneumophila itself. The length of anticoagulation was defined for 3 months;
prophylactic anticoagulation is commonly recommended in potential high-risk situations.
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P334
Attitudes towards morphine use among Swiss nurses and physicians
Maria Ferreira, Henk Verloo, Margarida Vieira, Pedro Marques-Vidal*
Hopital de Sion (Sion, CH); University of Applied Sciences, Nursing, La Source (Lausanne, CH);
Universidade Católica (Lissabon, PT); IUMSP (Lausanne, CH)
Background: There is little information regarding risk perception and attitudes on morphine use in
Switzerland.
Objectives: We aimed at assessing such attitudes in a sample of health professionals in the Frenchspeaking part of Switzerland.
Study design: Cross-sectional study.
Setting: five non-university hospitals of the French-speaking canton of Valais, Switzerland.
Methods: 431 nurses and 40 physicians (age range: 20-63). Risk perception and attitudes towards
morphine use were assessed using a validated questionnaire.
Results: Over half of participants showed a negative attitude regarding most adverse events related to
morphine, while less than one third showed a similar attitude regarding other statements. On bivariate
analyses, participants working in geriatrics showed a more negative attitude towards use of morphine
than participants working in medicine and surgery. Non-Swiss participants also showed a more
negative attitude than Swiss regarding use of morphine. Conversely, no differences were found
between genders, profession (nurses or physicians), years of experience (<=14 and >14) and religion
(catholic vs. others/no religion). These findings were further confirmed by multivariate adjustment.
Limitations: possible selection bias due to responders only. Results limited to French speaking
participants.
Conclusion: Attitudes regarding morphine uses are mainly driven by its potential adverse effects and
vary according to specialty and nationality. Educational measures directed at health professionals
working in geriatrics or coming from abroad might reduce the high morphinophobia levels observed in
these groups.
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P335
Contribution of multimorbidity to overall mortality in the population-based
CoLaus study
Basile Pache*, Peter Vollenweider, Martin Preisig, Pedro Marques-Vidal, Gérard Waeber
Centre Hospitalier Universitaire Vaudois (Lausanne, CH); The Swiss Institute of social epidemiology
(Lausanne, CH)
Introduction: Multimorbidity (MM) is currently a major health concern for hospitalized patients but little
is known about the relative importance of MM in the general population. Accordingly we assessed
whether MM could be a good predictor of overall mortality.
Method: Data from the population based CoLaus Study: 3239 participants (1731 women, mean age
50+/-9 years) followed for a median time of 5.4 years (range 0.4 to 8.5 years). MM was defined as
presenting >=2 morbidities according to Barnett et al. (27 items, measured data). Survival analysis
was conducted using Cox regression.
Results: During follow-up, 53 (1.6%) participants died. Participants who died had a higher number of
morbidities (2.4 +/- 1.6 vs. 1.9 +/- 1.5, p<0.05) and had a higher prevalence of MM (69.8% vs. 55.9%,
p<0.05). On bivariate analysis, presence of MM (defined as a yes/no variable) was significantly related
with overall mortality: relative risk (RR) of 1.84, 95% confidence interval [1.02; 3.31], p<0.05 (see
figure), but this association became non-significant after adjusting for age, gender and smoking:
RR=1.68 [0.93; 3.04], p=0.09. Similar results were obtained when using the number of morbidities: RR
for an extra morbidity 1.22 [1.05; 1.44], p<0.02; after adjusting for age, gender and smoking, RR=1.16
[0.99; 1.37], p=0.07.
Conclusion: During a short 5 year observation period, measured MM in the general population is
associated with overall mortality. This association becomes borderline significant after multivariate
adjustment. These observations will have to be confirmed during a longer follow-up period. This
increased mortality in MM patients may require developing specific strategies of screening and
prevention.
Reference: 1. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of
multimorbidity and implications for health care, research, and medical education: a cross-sectional
study. Lancet. 2012;380(9836):37-43.
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P336
Severe vitamin D deficiency and fatigue in a patient from Africa
Katarzyna Keller*, Albina Nowak
Case history: A 39 years old otherwise healthy patient, born in Ethiopia, complained about fatigue and
weakness for several months.
Findings: The clinical examination of this slim patient was uneventful. The laboratory findings revealed
a 25-hydroxy vitamin D under the detection level, a severe hypophosphatemia and an elevated
parathyroid hormone serum level (Table 1).
Diagnosis: Severe vitamin D deficiency with secondary hyperparathyroidism due to lack of sun
exposure and dark skin pigmentation.
Therapy and results After vitamin D supplementation 15 000 units as drops once per week, the fatigue
improved, the patient felt stronger. The clinical improvement correlated with the increase of serum
vitamin D and phosphate levels along with decrease of serum parathyroid hormone levels after 4 and
6 weeks of supplementation (Table 1).
Discussion: As food contains insufficient amounts of vitamin D, its synthesis in the skin is the most
important source. Black people have a reduced synthesis capacity of vitamin D in the skin due to
pigmentation. Furthermore, there is an evidence of increased vitamin D degradation in the dark skin.
These phenomena function as a protection against vitamin D excess in areas with high sunlight
exposure. However, in the northern hemisphere, especially during the winter, this mechanism can be
a risk factor for vitamin D deficiency.
Conclusion: Dark-skinned persons with insufficient sun exposure are at high risk for vitamin D
deficiency. In such situations, the Vitamin D level should be measured, the Vitamin D deficiency
should be treated.
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P337
Prevalence of prediabetes in healthy adults using HbA1c versus fasting plasma
glucose: the GAPP study
Jonas Blum*, Stefanie Aeschbacher, Tobias Schoen, Katrin Pumpol, Martin Risch, Lorenz Risch,
David Conen
Universitätsspital Basel (Basel, CH); Labormedizinisches Zentrum Dr Risch (Schaan, LI)
Introduction: According to current guidelines, both hemoglobin A1c (HbA1c) (5.7-6.4%) and fasting
plasma glucose (FPG, 5.6-6.9mmol/l) can be used as a screening tool for prediabetes. However, the
correlation between HbA1c and FPG for the diagnosis of prediabetes or diabetes is not well studied,
especially among young and healthy adults.
Methods: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular
Risk Factors (GAPP) study is a population based cohort of healthy adults aged 25-41 years in the
Principality of Liechtenstein. Main exclusion criteria are a prevalent cardiovascular disease, a prior
diagnosis of diabetes mellitus and a body mass index (BMI) >35 kg/m2. FPG and HbA1c were
assayed using a Roche Cobas 6000 (F.Hoffmann – La Roche, Switzerland) and high-performance
liquid chromatography (Bio-Rad D-10), respectively. Prediabetes was defined according to the current
guidelines as FPG between 5.6 and 6.9 mmol/l and/or HbA1c between 5.7 and 6.4%.
Results: Of 1568 subjects who completed the baseline examination, 839 (53.5%) were women, mean
age was 36.4 +- 4.9 years and the mean BMI was 24.7 +- 3.7 kg/m2. Obesity (BMI >=30kg/m2) was
present in 156 (9.9%) participants. The correlation coefficient between HbA1c and FPG was 0.25
(p<0.0001). Overall, 476 (30.4%) had prediabetes (36.6% among men, 25.2% among women,
p<0.0001). A diagnosis of prediabetes was present in 427 (27.2%) by HbA1c criteria only, 98 (6.3%)
by FPG criteria only and 49 (3.1%) by both criteria. This difference in prevalence was greater in
women than in men (p<0.0001), as shown in the Table.
Conclusion: The prevalence of prediabetes among young and healthy adults is highly dependent on
the test used and is significantly higher using HbA1c criterion. This is especially true among women. If
confirmed, our findings will have important implications for screening recommendation in the
population.
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P338
Where is the fever ?
Erwin Grüter*, Hans-Ruedi Räz
Kantonsspital Baden (Baden, CH)
A 45 year old woman with dizziness, headache and a blood pressure of 180/120 mmHg was
hospitalized. Her history revealed a known untreated hypertension grad 1 and dysmenorrhea with
regular intake of ibuprofen, a non steroidal anti-inflammatory agent (NSAIA). 2006 she had a
gastroscopy (because of epigastric pain) without any pathological findings. Clinical examination
showed no relevant pathologic findings. There was no specific family history.
Surprisingly laboratory evaluation revealed severe renal failure with an eGFR of 25ml/min/1.73m2
according to the CKD-Epi-Formula. Proteinuria was 4g/day, sodium, potassium, calcium, phosphate,
cholesterol and triglycerides where in the normal range, albumin was low, 30g/l. ANA, anti-ds-DNA,
ANCA, C3,C4, circulating immune complexes and rheumatoid factor, they all were in the normal
range. Clinically, edema was completely absent. Ultrasound showed a hyperechogenic kidney
parenchyma, with normal length, a smooth kidney surface and no pyelo-urethral dilatation. Only the
spleen was slightly enlarged. A kidney biopsy was performed. The unexpected result was an AAamyloidosis of the kidney. The rheumatologic and cardiologic workup showed no pathologic results:
an osteoarthritis of the ankles was explained by the history of intensive and competitive ice-skating in
her youth. The myocardium was normal and showed no signs of amyloidosis. Gastroscopy was
normal, but histology proved presence of AA-amyloid in the submucosal vessels. To find the reason
for deposition of AA-amyloid, we once more turned to the personal history of the patient. She
originated from Georgia, so we considered the possible presence of Familial Mediterranean Fever
(FMF), although fever episodes and signs of inflammation (CRP 7mg/l) were absent. A genetic
examination revealed a compound heterozygotia for the MEFV- (= Mediterranean fever) gene.
Therefore, in this 45 year old lady without fever, we could confirm the presence of double
heterozygous mutation of MEFV with severe chronic kidney disease stage IV A3 because of AAamyloidosis.
Conclusions: FMF can cause AA-amyloidosis without fever or inflammation. A genetic testing of FMF
should be undertaken in any case of unexplained AA-amyloidosis
P339
Psychological adjustment in cancer patients hospitalised in a supportive care
unit
Christophe Luthy*, Angela Pugliesi, Christine Cedraschi, Elisa Rapiti, Anne-francoise Allaz
hôpitaux universitaires de genève (Genève, CH); registre genevois du cancer (Genève, CH)
Aim: Cancer patients develop various cognitive and emotional reactions in their attempts to adjust to
disease and illness. An active adjustment may be associated with less distress. We investigated the
association between their mental adjustment and the psychological impact of the disease.
Methods: 164 consecutive patients hospitalized in a supportive care unit responded to a questionnaire
including psychological dimensions investigated by the Hospital Anxiety and Depression Scale
100
(HADS), the Distress Thermometer (DT) a graphic scale rated from 0-10, and the Mental Adjustment
to Cancer index (MAC). Socio-demographic and clinical characteristics were also recorded, along with
functional aspects (Performance Status), and the Physician Global Clinical Impression (PGCI) a
numerical scale rated from 0-10 assessing the estimated survival prognosis at the admission.
Results: 67% of the patients were men; mean age was 65 years (SD=14). Median time since
diagnosis was 1.8 years (range=0.1-12.5 years). A wide range of cancer diagnoses were represented;
26% had primary local diseases, 41% had local recurrences, and 33% had metastatic diseases.
Anxiety and depression rating scores were moderate to high (mean HADS: 10.5±0.5 and 10±0.5,
respectively; mean DT score: 4.7±0.2). The results of linear correlation tests showed a statistically
strong and inverse association between the dimension referring to fighting spirit in the MAC and
anxiety and depression as measured by the HADS (p<0.001), by the DT (p<0.001), and by specific
subscales of the MAC (p<0.001). Fighting spirit was also significantly associated with a better
evaluation of patient’s Performance Status (p<0.01) as well as with a better PGCI (p<0.01).
Conversely, hopelessness/helplessness was associated with a worse PGI (p<0.05).
Conclusions: Cancer patients experienced a high impact of the disease in terms of anxiety and
depression. Mental adjustment seemed to play a buffering role as mental adjustment strategies
allowing for a sense of control was related to a better psychological well-being. Patients endorsing
such strategies also elicited better clinical prognostic evaluations in the physicians.
P340
Sweet syndrome: an association with acute calcific tendinitis?
Matthias Zellweger*, Sergio Compagnoni, Raphael Jeker
Kantonsspital Graubünden (Chur, CH)
Case report: A 69-year-old woman was presented with a history of neck stiffness and neck pain,
weakness of the arms since the day before. Furthermore she had pain and swelling in the left wrist.
No headaches, no pain when chewing, no fever. There was no history of trauma, upper respiratory
infection, or dental problems. The flexion of the neck was restricted, and the posterolateral portion of
the neck was tender at palpation. The examination of the oro- and nasopharynx was normal and the
neurological status was also normal.
In 2008, there was reported a non-traumatic desinsertion of the hip abductors.
Laboratoy findings showed a highly increased c-reactive protein (386 mg/l). Erythrocyte sedimentation
rate was 56 mm/h. Determination of anti nuclear-antibodies were slightly elevated (1:160), the anti
citrullin and anti neutrophil antibodies were not elevated. The radiography of the hand releaved signs
of a crystal arthropathy.
A cervical and thoracic magnetic reonance tomography showed markedly increased signal intensity
corresponding to an inflammation of the soft tissue anterior and posterior of the vertebral column.
Without suspicion of a bacterial infection we treated with corticosteroids (100 mg methylprednisolon iv)
and diclofenac.
A rapid improvement of symptoms and a decrease of the inflammatory markers were registered and
the corticosteroids were reduced to 40 mg orally.
One week later, the patient presented with fever (39° Celsius), weakness, and an palpable
exanthema. Skin biopsy releaved a neutrophilic dermatosis. The neutrophil count in the blood
releaved 36 000 granulocytes/ml. We diagnosed a Sweet-Syndrome and we treated with
methylprednisolone. The dermatosis disappeared and the patient had a good evaluation in the next 7
days.
Discussion: This case report is impressive for us because of two reasons. First the presentation of a
crystal arthropathy with such clinical and radiological signs. This presentation could be misdiagnosed
with retropharyngeal abscess, meningitis and infectious spondylitis.
Second reason: The appearance of a Sweet-Syndrome under the treatment with 40 mg of prednisolon
and the crystal arthropathy as the trigger disease for the Sweet-Syndrome. As a trigger for the SweetSyndrome we discuss also the treatment with diclofenac, which is known as a trigger.
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P341
An unusual case of sarcoidosis
Emily Pollock*, Irene Studer, Valentin Gisler, Panagiotis Samaras
Introduction: Sarcoidosis is an inflammatory granulomatous disease of unknown aetiology capable of
involving any organ, with a typical histological finding of non-caseating granulomas. The clinical
outcome is extremely variable: sarcoidosis may resolve within months or be chronic, requiring
systemic therapy. Annual follow-up is recommended.
Case report: A 42-year-old male patient with sarcoidosis, hepatitis C, COPD and previous substance
abuse attended routine follow-up at our clinic in May 2011. Sarcoidosis had been diagnosed in 2002
based on a clinical picture of weakness, relapsing fever, generalized lymphadenopathy, dyspnoea and
myalgia together with a lymph node biopsy showing typical granulomas. Tuberculosis had been
excluded. Previously, in March 2010, the disease had been stable with stationary findings of hilar
lymphadenopathy and reduced diffusion capacity.
At follow-up, the patient felt well but reported mild neck and shoulder pain for the past two months and
a new skin lesion on the left lateral chest wall. Chest x-ray showed numerous additional lesions up to
1.5 cm in diameter (figure 1). Computerised tomography confirmed multiple pulmonary nodules which
were consistent with, but not typical for, sarcoidosis.
Two weeks later the patient developed intense neck pain and mild tetraparesis. MRI showed a spaceoccupying lesion with destruction of the C2 vertebra and spinal cord compression (figure 2). Biopsy
revealed a diffuse large B-cell non-Hodgkin’s lymphoma stage IV AE, IPI risk score 3 (highintermediate). Following surgical decompression and six cycles of R-CHOP chemotherapy, the
weakness resolved and the patient remains lymphoma recurrence free one year later. His sarcoidosis
has never required treatment.
Conclusion:
•
Our patient with long-standing sarcoidosis developed a new diagnosis of diffuse large B-cell
lymphoma.
•
Sarcoidosis has previously been associated with a range of malignancies, above all Hodgkin’s
and non-Hodgkin’s lymophoma, but also several solid organ tumours [1, 2]. This predisposition is
thought to occur through immune dysregulation [1].
•
It has also been suggested that lymphoma acts as a predisposing factor for sarcoidosis [3].
•
It may be particularly difficult to recognize the coexistence of sarcoidosis and lymphoma
because both are fluorodeoxyglucose-avid and show an uptake in PET imaging [3].
•
Our case emphasizes the importance of obtaining a second tissue diagnosis when the clinical
course is unusual in either condition.
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P342
Challenges to patient-centred care in a general internal medicine context:
findings from an exploratory study
David Gachoud*, Mathieu Albert, Scott Reeves
Service de médecine interne, Centre Hospitalier Universitaire Vaudois & Unité pédagogique, Faculté
de Biologie et Médecine, Université de Lausanne (Lausanne, CH); University of Toronto (Toronto,
CA); University of California (San Francisco, US)
Introduction: If we are to promote more patient-centred approaches in care delivery, we have to better
characterize the situations in which being patient-centred is difficult to achieve. Data from
professionals in health and social care are important because they are the people charged with
operationalizing patient-centred care (PCC) in their daily practice. However, empirical accounts from
frontline care providers are still lacking, and it is important to gather experiences not only from doctors
but also from the other care providers. Indeed, experiences from different professions can help inform
our understanding of patient care, which is expected to be both patient-centred and collaborative.
Methods: This study was based on the following research question: What factors make the provision
of PCC difficult to achieve?
Sample and setting
A purposeful sampling technique was used, allowing for a series of choices about the participants and
their professional affiliation. Because patient-centredness is the focus, 3 professions appeared to be of
special interest: general internists, nurses and social workers. The study was undertaken in the
General Internal Medicine Division of a teaching hospital located in a North American context.
Data Collection: To answer the research question, a methodological approach based on a theory
called phenomenology was chosen. Accordingly, semi-structured interviews were used since they
generate understanding of the meanings different individuals have of their lived world. Interviews with
8 physicians, 10 nurses and 10 social workers were eventually conducted.
Data analysis
An inductive thematic analysis was employed to make sense of the interview data.
Results: The thematic analysis allowed identifying various types of challenges to PCC. Although most
of the challenges were perceived by all three groups of professionals, they were perceived to a
different degree across the professions, which likely reflected the scope of practice of each profession.
The challenges and their distribution across the professions are illustrated in Table 1. Examples of
challenges are provided in Table 2.
Discussion: There is a tension between what is supposed to be done – what stands in the philosophy
of patient -centredness – and what is currently done – the real life with all the challenges to PCC.
According to some participants’ accounts, PCC clearly risks becoming a mere illusion for health care
professionals on which too great pressures are imposed.
103
104
Onkologie – Notfallmedizin / Psychiatrie / Neurologie
Oncologie - Urgences / Psychiatrie - Neurologie
P343
Verlängerung der PSA-Kontrollintervalle bei Männern mit Initialem PSA-Wert
von 0-1.99
Marco Randazzo*, Daniel Seiler, Andreas Huber, Rainer Grobholz, Martin Baumgartner, Franz
Recker, Maciej Kwiatkowski
Kantonsspital Aarau (Aarau, CH)
Einleitung: PSA ist ein Risikostratifizierer für die zukünftige Entwicklung eines Prostatakarzinoms
(PCa). In der Screening-Kohorte des Kantons Aargau hatte ein Grossteil der Männer (75%) in der
ersten Runde PSA-Werte zwischen 0 - 1.99ng/ml. Die Kontrollintervalle in diesem Bereich sind jedoch
noch nicht definiert. Ziel unserer Studie war deswegen die Adaptation der PSA-Kontrollintervalle.
Patienten und Methoden: Von 08/1998 - 08/2003 wurden 10.311 Männer 1:1 in die Screening Gruppe
bzw. in die Kontrollgruppe randomisiert. Ab einem PSA-Wert von 3.0ng/ml sowie zwischen 1.0 und
3.0ng/ml und einer PSA-Ratio < 20% (nur während der 1. Runde) wurde die Indikation zur Biopsie
gestellt. Im Abstand von 4 Jahren erfolgten bis anhin 3 Screening-Runden. Im PSA-Bereich 0 - 1.99
wurde die Inzidenz aggressiver Prostatakarzinom-Inzidenz (Gleason >= 7a) detektiert.
Resultate: Insgesamt wurden in der 1. Runde n=4932 Männer dem PSA-Screening unterzogen, was
einer 96.1%igen Compliance rate entspricht. Innerhalb von 3 Screening-Runden wurden kumulativ
n=482 PCa detektiert. Das mediane Follow-up betrug 9.6 Jahre. Im Bereich 0 - 1.99 lagen n = 3745
Männer. Das mediane Alter der Patient betrug 60.0 (PSA 0 - 0.99) bzw. 61.1 (1.0 - 1.99) Jahre. Bei n
= 2308 betrug der PSA-Wert 0 - 0.99ng/ml und bei n = 1437 Männern 1 - 1.99ng/ml. An signifikanten
PCa (Gleason >= 7a) wurden im Bereich 0 - 0.99 gesamthaft 0.3% sowie im Bereich 1 - 1.99 0.53%
detektiert.
Schlussfolgerung: Anhand der geringen Inzidenz an signifikanten Prostatakarzinomen über fast 10
Jahre ist eine Verlängerung des PSA-Kontrollintervalls auf 6 - 8 für PSA-Werte von 0 - 0.99
vorstellbar. Demgegenüber erachten wir ein Kontrollintervall für 4 Jahre für den Bereich von 1 - 1.99
für durchaus gerechtfertigt.
P344
Acquired angioedema! Acquired angioedema?
Raphael Butsch*, Karla Chaloupka, Verena Niggemeier, Dominik Schaer, Daniel Franzen
A 31-year-old male was referred with sudden onset of rapidly progressive and painful facial oedema
beginning a few hours earlier in connection with fever, chills, nausea and vomiting. He denied itching
or exanthema. There was no history of allergy or (hereditary) angioedema. Aside from
immunosuppressive drugs (ciclosporine, mycophenolate mofetil and prednisone because of renal
transplantation due kidney aplasia), he only took bisoprolol and calcitriol, but no ACE-inhibitor. Clinical
examination revealed severe angioedema of both periorbital regions with firm consistence, which was
painful on palpation. The swelling of his eyelids precluded proper eye opening. The tongue and throat
were unremarkable. His vital signs and his breath sound were completely normal. Laboratory results
were significant for raised inflammatory markers and acute-on-chronic renal failure (leucocytes 14.1
G/l with the eosinophil count within the normal range, C-reactive protein 81 mg/l, glomerular filtration
rate 23 ml/min).
Assuming a first episode of acquired angioedema, the patient was treated with a plasma-derived C1
esterase inhibitor (Berinert®), tranexamic acid (Cyklokapron®) and fresh-frozen plasma, after the
initial treatment with corticosteroids and histamine 1- and 2-blockers were unsuccessful.
Simultaneously, an antibiotic medication with piperacillin/tazobactam (Tazobac®) for suspected
infection of unknown site was instituted. Since then, the angioedema was not progressive, and the
pain was slightly improving. However, the initial diagnosis was wrong!
Two days after, his C-reactive protein value began to rise significantly to 408 mg/l, while the
leucocytes count was falling. Blood cultures grew group A Streptococci. In the MRI of his head, the
diagnosis of periorbital necrotizing fasciitis was confirmed. His treatment was subsequently changed
to clindamycin and ceftriaxone and the patient recovered slowly. Delayed surgical debridement of his
eye lids was carried out in the course, and he could be discharged from hospital after 21 days.
105
Facial (or periorbital) fasciitis is are rare and potentially lethal differential diagnosis of acute
angioedema, in particular if accompanied by severe pain and/or fever. Knowledge on the appearance
of this disorder cannot be overemphasized, as only early recognition and immediate initiation of highdose antibiotics combined with tissue debridement help to decrease the mortality.
P345
Rheumatoid arthritis and malignant pleural mesothelioma: curse or blessing?
A case report
Peter Moosmann*
Kantonsspital (Aarau, CH)
Introduction: Inhibitors of pro-inflammatory cytokines have greatly changed rheumatoid arthritis (RA)
outcomes. They could also be beneficial in malignant pleural mesothelioma (MPM) since a cytokineinduced chronic inflammatory response apparently favors mesothelial cell transformation.
Case Report: A 55 year-old man with RA was treated with methotrexate from 2003-2006 (stopped due
to possible lung toxicity). Sulfasalazine was installed thereafter (till Oct ‘09). 2007 – 2009 he received
etanercept and leflunomide (from Dec ‘08). Only the start of tocilizumab (TCZ) in Jun ‘09 led to a
significant clinical improvement. TCZ was paused in Mar ‘10, when a right-sided pleural effusion
developed. Repeated diagnostic procedures were unsuccessful. The patient received rituximab twice
in Aug ‘10 (no improvement). Finally, epithelial MPM was diagnosed in Oct ‘10 (possible asbestos
exposure). A trimodality therapy was started with platin-pemetrexed combination chemotherapy.
However, the disease was progressive after 3 cycles. Because of side effects and a flare-up of the RA
the patient refused further antineoplastic treatment. When TCZ was resumed in Apr ‘11 symptoms
disappeared and the patient’s performance status (PS) returned to normal. A CT scan in Dec ’12
showed progressive disease.
Discussion: MPM remains an incurable disease even in patients with good PS and early stage
disease. The median survival time in treated pts is <12 months. First-line chemotherapy was
ineffective and surgical intervention not feasible in the reported case. Anti IL-6R directed therapy
improved RA-related symptoms. Tumor growth appears rather slow: the patient is alive and under
treatment 27 months after diagnosis. Did he profit from an antitumor effect of the IL-6R inhibitor?
Indeed, there is evidence that pro-inflammatory cytokines contribute to MPM pathogenesis and might
be rewarding targets for novel therapies. IL-6 induces cell growth in MPM cell lines that can be
suppressed by IL-6 blockage. Although tumor progression appears unusually slow in this patient, there
106
are long-term survivors in MPM, especially among patients with low-risk features. No neat tumor
response was documented in this case. It remains unclear whether TCZ was able to influence the
primary course of the malignancy, therefore. Perhaps, the progressive MPM simply secreted IL-6
facilitating the RA flare-up, and TCZ controlled the latter.
Conclusion: The case of a patient with RA and MPM is presented and put up for discussion.
P346
Do we overdose erlotinib in patients with non-small-cell lung cancer and
activating epidermal growth factor receptor mutation?
Sophie Bauer*, Marc Kueng, Luc Burdet, David Chabanel, Daniel Betticher
HFR Fribourg (Fribourg, CH); HIB Payerne (Payerne, CH)
Introduction: Tyrosine kinase inhibitors are today standard first line treatments for patients suffering
from stage IV non-small-cell lung cancer (NSCLC) with activating epidermal growth factor (EGFR)
mutation. Side effects in particular skin reactions and diarrhea are frequently responsible for therapy
interruption and/or dose reduction. The established erlotinib dose of 150 mg/day has been defined as
the maximal tolerated dose limited by toxicity. A retrospective study in 7 patients receiving erlotinib at
25 mg/day described response rates in 71% and a progression free survival of 17 months (6-35
months), (Yeo W et al. J Thorac Oncol. 2010, 5, 1048-1053). Toxicities were minimal with only two
patients suffering from rash and none experiencing diarrhea. We report here on a patient who had
erlotinib dose reduction at 25 mg/day after skin rash and has a high benefit from therapy.
Case presentation: 70-years old woman suffering from an adenocarcinoma in the upper right lung
lobe, stage II. She underwent lobectomy and mediastinal lymphadenectomy and received adjuvant
chemotherapy. Sixteen months later, relapse was diagnosed with pulmonary metastases. Since an
EGFR mutation, exon 19 deletions, was detected, we started erlotinib 100mg/day. Treatment was
stopped after 32 days because of grade 3 thoracic and cervical exanthema. Under 25mg/day, erlotinib
was well tolerated and led to a complete remission with disappearance of all lung metastases;
remission duration is presently 10 months. Treatment is ongoing.
Discussion: To our knowledge, this is the first presentation of a complete remission in a patient with
NSCLC stage IV disease on erlotinib at a 25 mg/day dose. We have today no data allowing us to
define the optimal dose of erlotinib in order to obtain best tumor response and lowest toxicity
incidence. Trials investigating different dose levels of erlotinib (25-100 mg/day) in patients with EGFR
mutated lung cancer are warranted.
Conclusion: This patient presentation together with previously reported cases indicate that lower dose
of erlotinib may be sufficient for patients with NSCLC harboring the activating EGFR mutation, thus
allowing to diminish erlotinib side effects.
P347
Complete remission of Castleman's disease and Kaposi's sarcoma in an HIVpositive patient: the importance of combined therapy
Vérène Dougoud-Chauvin*, Christian Chuard, Daniel Betticher, Marc Küng
HFR-Fribourg (Fribourg, CH)
Introduction: The multicentric Castleman’s disease (MCD) is a lymphoproliferative disorder associated
with HIV and human herpesvirus 8 (HHV-8). It is characterised by generalized lymphadenopathy, multi
organ involvement and systemic features. The prognosis of HHV-8 associated MCD is poor.
Chemotherapy such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) as well
as the anti-CD20 antibody Rituximab (R) have significant activity in the treatment of this rare disease.
Kaposi‘s sarcoma (KS) is a low-grade vascular tumor associated with infection with HHV-8 and HIV.
The primary treatment of HIV-associated KS is highly active antiretroviral therapy (HAART). Poor
response to local treatment and symptomatic visceral involvement are indications for systemic
chemotherapy such as liposomal anthracyclines.
Case presentation: We present here the follow-up at 5 years of a 51 years old black patient from
Congo who has been diagnosed HIV positive stage C3 in February 2007. A few months later a MCD
was diagnosed on an axillary biopsy performed because of fever, generalized lymphadenopathy,
splenomegaly and poor performance status. Because of a low CD4 count (177 cells/mm3) and a high
viral load (379'000 copies/ml) a HAART was initiated. Immunochemotherapy with R-CHOP resulted in
a very good partial response on the lymphadenopathy and the splenomegaly but KS lesions confirmed
by biopsy on the extremities and the tongue appeared. The chemotherapy was changed for liposomal
doxorubicin (PLD) and the KS improved after 3 cycles. After restart of R with chemotherapy we noted
107
a progression of the KS. PLD as monotherapy was given from December 2007 until March 2008 but
stopped because of fall of the CD4 count. After radiotherapy of some skin lesions, another 15 cycles
of PLD monthly from June 2008 until September 2009 led to a complete remission of the KS and of
the MCD that is still maintained until 2013. Under HAART the HIV disease is still under control with
undetectable viral load.
Conclusion: Both multicentric Castleman’s disease and Kaposi’s sarcoma in this patient were
responsive to PLD, the treatment of choice for KS. R was highly effective in controlling MCD in this
HIV positive patient but it appeared to exacerbate concomitant KS. The inhibition of HIV replication by
HAART leads to an immune reconstitution and a better control of the KS and the MCD.
P348
Intoxication with acetaminophen: a time-consuming story with happy end
Cyrill Buehlmann*, Marcus Laube
Spitalzentrum Biel (Biel, CH)
A 16-year-old patient was referred to our emergency room by the family doctor because of
dehydration owing to recurrent vomiting and decreased fluid intake for a week. He reported having
eaten freshly picked mushrooms a week ago. He was in a reduced general condition, afebrile (37.3
°C) and with normal hemodynamic values (BP 128/85 mmHg, pulse 87/min). The abdominal
examination was unremarkable, except a light epigastric tenderness. The lab results are revealing an
liver failure (Table). The story seemed odd and further exploration was done. Only after repeated
questioning, the patient admitted to have ingested 39g of acetaminophen a week ago in a suicide
attempt prompted by family problems. A therapy with acetylcysteine was initiated accordingly
Prescott’s treatment-scheme and silibinin (Legalon®) was administered transiently. The patient was
transferred to the intensive care unit and monitored according the King's College criteria with regard to
a possible livertransplantation. In this context there was an emergency psychiatric case conference
done to evaluate latent suicidality. Although that the serum acetaminophen level was below the limit of
detection (<6.6 pmol/l) the acetylcysteine was given for 5 days (intravenous and peroral). Silibilin
treatment was stopped after recapitulating the case history with the patient’s father. The patient
recovered and left the hospital after 7 days for home.
In our patient, repeated history by three physicians and the finding of empty blister packs by the father,
suggested delayed an intoxication with acetaminophen to be the cause of the liver failure. Without a
healthy suspiciousness and insistency a livesaving treatment would have been omitted in our patient.
Even without hundert per cent certitude it is crucial in an emergency situation to include other causes
dangerous to life and to start treatment for those affection as rapidly as possible. Afterwards
meticulous medical procedures has to be carried out including a recapitulation of the case history with
the patient and the relatives.
P349
Sweet syndrome in a patient with myelodysplastic syndrome (MDS) after
treatment with azacitidine
Linda Rüegg*, Andreas Erdmann, Paul Scheidegger, Gad Singer, Andrèe Friedl, Clemens Caspar
Kantonsspital Baden (Baden, CH); Allergie- und Hautpraxis Brugg (Brugg, CH)
Here we report a 84 year old female with newly diagnosed Myelodysplastic Syndrome (MDS) who
developed fever, malaise and papular skin lesions after antineoplastic treatment with azacitidine. The
patient was admitted to our hospital three weeks after start of the chemotherapy, she felt extremely
weak, CRP values were markedly elevated. Initially a pulmonary infection was suspected
radiologically and antibiotic therapy was started. However, the clinical condition did not improve and
fevers persisted. Further infectiological evaluations did not show evidence of any infectious focus; in
addition serological exams for Herpes simplex and Varizella zoster as well as Leishmania turned out
to be negative, we did not find any proof of the presence of atypical mycobacteria. A few days after
hospitalization multiple papular, nodular skin lesions appeared rather quickly at the neck, both arms
and in the face, measuring from 0.5cm to 3cm in diameter, without any itching. An acute neutrophilic
dermatosis (Sweet syndrome) was suspected and could be confirmed by histological evaluation. The
symptoms and skin lesions resolved rapidly, after initiating high-dose steroid therapy. The appearance
of Sweet syndrome has been described in the context of MDS and other malignancies, but only single
cases after exposure to azacitidine are reported in the literature. Since the bone marrow aspirate
108
showed improvement of the MDS, we decided to rexpose the patient to azactidine. After two weeks
the patient developed the same symptoms, without the skin lesions though, and the symptoms
resolved again with steroids. Hence, we postulate a azacitidine induced systemic inflammatory
response presenting as a Sweet syndrome
P350
Severe neurotoxicity after body packing
Christiane Buschbeck*, Heike Juch, Bernhard Zoller, Christoph A. Meier, Simon Ritter
Stadtspital Triemli Zürich (Zürich, CH); Universitätsspital Zürich (Zürich, CH)
Background: Cocaine toxicity usually causes agitation, tachycardia, hypertension and occasionally
self-limited seizures. We report a fatal case of unintentional cocaine overdose associated with
prolonged epileptic activity and refractory shock.
Case Report: A 28-year old man was admitted after successful resuscitation following a generalized
seizure and a subsequent short-period cardiac arrest. He presented unconscious with bilateral
mydriasis, a blood pressure of 78/27 mmHg, heart rate of 74/min, and temperature of 36.6°C. Arterial
blood gas analysis revealed lactic acidosis (pH 6.46, lactate 27 mmol/L) with a methemoglobin of
3.4%. Antidotes for possible cyanide poisoning were administered (hydroxocobalamin, sodium
thiosulfate) and hemodynamic instability improved thereafter. Computed tomography (CT) scan of the
head was normal and a CT scan of the abdomen showed six foreign bodies in the distal sigma and
rectum. All packets, of which one was damaged with visible leakage, were safely removed by
endoscopy shortly after admission. However, the patient remained in coma, while cocaine was
detected in the urine. Electroencephalography demonstrated a non convulsive status epilepticus
(Figure: Intermittent generalized spike-wave discharges and amplitude depression). Despite
antiepileptic therapy and total colectomy for ischemic colitis, the patient developed combined septic
and circulatory shock with multiple organ failure, including liver failure and severe rhabdomyolysis
(serum myoglobin >30’000 mcg/L). He died thirty-eight hours after presentation.
Discussion: Cocaine acts via blockade of the presynaptic reuptake of biogenic amines, leading to both
adrenergic crisis and pro convulsive effects. Internal concealment used by drug dealers to smuggle
cocaine can therefore be life-threatening in case of package leakage. However, accidental overdose
death following body packing is a rare condition. Systemic drug toxicity from a ruptured packet can
lead to severe neurotoxicity, such as ischemic stroke, or intracranial hemorrhage. Status epilepticus in
a body packer may result from prolonged cocaine release within the gastrointestinal tract. Immediate
removal of the packets is recommended, generally by surgery.
Conclusions: Smuggling illicit drugs by use of body packing can result in acute drug intoxication and
subsequent death due to rupture of the packages. Body packing and cocaine intoxication should be
considered in patients with unexplained coma and sustained seizures.
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Psychiatrie / Neurologie - Arterieller Bluthochdruck – Endocrinologie - Diabetik
Psychiatrie / Neurologie - Néphrologie / Hypertension artérielle Endocrinologie
- Diabétologie
P351
Hirnstamminfarkt, Infektion oder Neuropathie?
Jens Alexander Petersen*, Konstantin Burgmann, Ludwig Theodor Heuss
Spital Zollikerberg (Zollikerberg, CH)
Einleitung: Das Miller-Fisher-Syndrom (MFS) ist eine entzündliche Neuropathie mit typischer Trias aus
Ophthalmoplegie, Ataxie und Areflexie. Die Abgrenzung vom Hirnstamminfarkt Schwierigkeiten kann
bereiten.
Fallbeschreibung: Ein 66jähriger Mann präsentierte sich mit neu aufgetretener Gehunfähigkeit. Er
klagte über diffuse Gefühlsstörungen, es fielen eine Ophthalmoparese sowie eine ausgeprägte
Dysarthrophonie auf. Im MRI konnte eine akute zerebrale Ischämie ausgeschlossen werden, die
Symptome waren jedoch progredient. VitB12, Folat, ANA und ANCA waren normal, die Suche nach
HIV, Borrelien, FSME und Porphyrie negativ. Bei positivem Lues-Suchtest wurde eine Lumbalpunktion
durchgeführt, die den Verdacht auf Neurolues nicht bestätigte. Bei möglichem paraneoplastischen
Geschehen erfolgte eine Tumorsuche per CT und Proteinelektrophorese, die ohne pathologischen
Befund blieb. Schließlich wurde aufgrund positiver GQ1b-Antikörper im Serum die Diagnose eines
Miller-Fisher-Syndroms gestellt. Nach 14 Tagen besserten sich die Symptome spontan, der Patient
konnte praktisch beschwerdefrei nach Hause entlassen werden. Bei bisher unbehandelter Lues erhielt
er eine antibiotische Therapie.
Diskussion: Das MFS ist eine seltene, akut entzündliche, vorwiegend sensible und axonale
Polyradikuloneuropathie. Es ist Teil eines Spektrums entzündlicher Erkrankungen, das auch das
Guillain-Barré-Syndrom und die Bickerstaff-Hirnstammenzephalitis umfasst. Bei bis zu 90% der
Patienten werden GQ1b-AK im Serum nachgewiesen. Wahrscheinlich wird das MFS durch virale
Infekte getriggert („molecular mimikry“). Unser Patient berichtete von einer „Lebensmittelvergiftung“
wenige Tage vor Auftreten der Symptome, die retrospektiv eher als virale Gastroenteritis beurteilt
wurde.
Der Verlauf ist monophasisch und selbstlimitierend. Nach max. 4wöchiger Progredienz bilden sich die
Symptome zurück – nach 1 Jahr sind bei 80% der Patienten keine Residuen mehr vorhanden.
Komplikationen sind respiratorische Insuffizienz und autonome (kardiovaskuläre) Dysregulationen.
Intravenöse Immunglobuline oder Phlasmapheresen stellen die einzigen Therapieoptionen dar.
Schlussfolgerung: Bei Patienten mit Hirnstammsymptomen und Gangstörung sollte nach Ausschluss
akut behandlungsbedürftiger Erkrankungen (wie zerebraler Ischämie, Hämorrhagie und Infektionen)
das MFS differentialdiagnostisch in Erwägung gezogen werden.
P352
Remission of anti-PLA2R-positive membranous nephropathy after
transplantation: a case report
Inge Maria Schudel*, Andreas Pasch
Introduction: Membranous nephropathy is a major cause of nephrotic syndrome in adults. The M-type
phospholipase A2 receptor (PLA2R) has been identified as the major antigen in this disease, and
recent data indicate a causal role of anti-PLA2R autoantibodies. Current data indicate, that early
recurrences of membranous nephropathy may occur after transplantation in anti-PLA2R-positive
patients. However, the impact of post-transplantation immunosuppression on PLA2R serum titers is
currently not known.
Methods: We report a successful living donor kidney transplantation of a patient with end-stage renal
disease due to anti-PLA2R autoantibody positive idiopathic membranous nephropathy.
Results: Biopsy-proven membranous nephropathy was diagnosed in 1990 in a 53-year-old female
patient. Upon progression to end-stage renal disease, she received a renal allograft from a living
donor in 2012. Proteinuria before transplantation was 4.5 g/day. Upon transplantation, the patient
received an induction therapy with basiliximab. Postoperative immunosuppression consisted of
cyclosporine, mycophenolate mofetil, and glucocorticoids. The anti-PLA2R autoantibody titer was 1:80
3 weeks before transplantation, but returned to negative 6 weeks post transplantation. Consecutively,
110
and consistent with membranous nephropathy undergoing remission, proteinuria completely
disappeared 3 weeks post transplantation.
Conclusion: Renal transplantation may favorably influence disease activity and anti-PLA2R
autoantibody titers in membranous nephropathy. Elevated anti-PLA2R autoantibody titers should not
delay kidney transplantation.
P353
Posterior reversible encephalopathy syndrome after postinfectious
glomerulonephritis
Ayla Yalamanoglu*, Alexander Imhof, Thomas Künzi
SRO AG, Spital Langenthal (Langenthal, CH)
Introduction: Posterior reversible encephalopathy syndrome (PRES) is characterized by clinical
symptoms as headache, seizures, decreased level of consciousness, visual disturbances and focal
neurologic deficits. Sometimes, diagnosis is made by radiologic findings on MRI, especially cerebral
white matter edema of both occipital lobes. Mostly, PRES occurs in patients with high blood pressure,
e. g. due to renal diseases. But the development of PRES has also been contributed to vasculitis,
eclampsia, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome and HenochSchönlein purpura.
Case: A 16-year-old male was admitted to our hospital because of acute history of headache and
seizures. 14 days ago, a treatment with clarithromycin because of respiratory tract infection was
started.
At admission, the blood pressure was 180/100mmHg and the serum creatinine level was 128 umol/L.
Furthermore, proteinuria (urine proteine/creatinine 5825 mg/g) and erythrocyturia (>40
erythrocytes/hpf) were found. The MRI revealed edema of the posterior cerebral white matter. The
kidney biopsy showed an exsudative and membrano-proliferative glomerulonephritis with deposits of
IgG and C3c, a finding consistent with the diagnosis of postinfectious glomerulonephritis (PGN).
The diagnosis of a PRES due to hypertension because of PGN was made. A treatment with phenytoin
for one month and lisinopril plus amlodipine was initiated. There were no further seizures reported.
Discussion: The main cause of PRES may be a leakage of cerebral capillaries related to elevations of
blood pressure exceeding the autoregulatory capacity of the vasculature. This results in focal fluid
extravasation producing vasogenic edema. Alternatively, endothelial dysfunction may play a role in
patients with autoimmune disorders. The predilection of the changes in the posterior cerebral region is
probably due to the relative lack of sympathetic innervation of the vertebro-basilar circulation.
The treatment consists of blood pressure lowering, usually leading to rapid resolution of clinical and
radiologic manifestations without progression to chronic epilepsy.
Conclusion: We want to point out, that in young adults presenting with headache, seizures and
hypertension, PRES should be considered and underlying etiological factors should be analyzed.
Early recognition and appropriate treatment result mostly in complete clinical and radiological
remission.
P354
A seizure after meditation
Till Hauffe*, Claudine Meindl-Fridez, Paolo M. Suter, Urs Schwarz, Markus Schneemann
A 48 year old formerly healthy patient was admitted to the emergency room following a first time tonicclonic seizure after participating in a meditational event.
The patient was disoriented and had a highly elevated blood pressure up to 230/130 mmHg.
Otherwise, the physical examination and vital signs were normal.
The ECG showed ST-Segment depressions and a positive Sokolow-Lyon Index. The laboratory
studies showed a slightly elevated hs-Troponin and creatinine of 182 umol/l (GFR 37ml/min) combined
with a proteinuria and a serum hypokalemia of 2.8mmol/l. Serum-glucose was elevated with
12.0mmol/l.
Tentative diagnoses of an acute coronary syndrome, acute renal failure, diabetes mellitus, and a firsttime epileptic seizure were made.
A head CT scan revealed several smaller hypodensities bilaterally in the occipital lobes and in the
cerebellum. An additional MRI showed increased signal intensities in the T2-weighted and in the
FLAIR image sequences (Fig. 1) corresponding to the abnormalities in the CT-Scan.
111
To rule out meningoencephalitis or subarachnoid hemorrhage, a lumbar puncture was performed (1
cell/uL, glucose 10 mmol/L, lactate 3.6 mmol/L, protein 0.7 g/L).
Altogether, the diagnosis of a Posterior Reversible Encephalopathy Syndrome (PRES) due to
malignant hypertension was made.
Further investigations to rule out causes for secondary hypertension were done and a suspicious
laboratory constellation with elevated methoxytyramine was found (see poster by C. Meindl-Fridez et
al).
Summary: PRES is a neurological disorder with distinct neuroradiological findings:
1.) In T2- and FLAIR-weighted MR image sequences, areas of vasogenic edema are typically seen
bilaterally in the parietal and occipital lobes.
2.) The white-matter is always involved, yet additional cortical lesions are also frequent.
3.) Isolated lesions, e.g. in the brainstem or the cerebellum, are rare.
If the underlying cause is treated promptly, those lesions are mostly fully reversible.
Amongst many others, typical risk factors are hypertension, pregnancy, and calcineurin inhibitors.
The pathophysiology is not fully understood; failures in the regulation of cerebral blood flow and/or
endothelial dysfunction are discussed.
P355
Downstream hormonal changes in the kidneys after unilateral renal
denervation in the rat
Jürgen Bohlender*, Frédéric Birkhäuser, Jürg Nussberger, Eric Grouzmann, George Thalmann, Hans
Imboden
Hôpital cantonal fribourgeois (Fribourg, CH); Universität Bern (Bern, CH); Centre Hospitalier
Universitaire Vaudois (Lausanne, CH)
Objective: Catheter-based renal denervation provides an effective treatment for some patients with
resistant hypertension. It decreases also chronically blood pressure (BP) in animal models with
experimental hypertension or even normotension which is partially explained by increased natriuresis
and urinary volume. This effect may involve yet unknown downstream hormonal mechanisms
112
including the renin-angiotensin and kallikrein-kinin systems which may independently contribute to the
resetting of the kidneys' pressure-natriuresis relationship.
Methods: Left kidneys of 8 WKY rats were surgically denervated and 8 rats sham-operated. Six days
thereafter, kidney concentrations of bradykinin (BK), kallikrein (K), renin (R), angiotensin (Ang) I and II,
Ang(2-8), Ang(3-8), Ang(4-8), norepinephrine (NE), epinephrine (E), dopamine (D), and plasma R
concentration (PRC) were determined by HPLC, biochemically or by radioimmunoassays. The renal
innervation was studied immunohistologically using antibodies against tyrosine hydroxylase and
calcitonin-gene related peptide. mRNA expression was quantified by RT-PCR.
Results: PRC values showed no differences between treatment groups (p=NS). Catecholaminergic or
sensory nerve fibers were no longer detected in denervated kidneys. Left denervated kidneys showed
lower AngI (39.5%), AngII (35.1%, p=NS), R (30.2%), NE (99.2%), D (-30.4%) and BK (30.4%)
concentrations (p<0.05) vs. sham left kidneys; K, Ang fragments, and E were comparable (p=NS).
Right kidneys had lower BK (26.6%, p=NS), AngI (41.2%, p=NS), AngII (22.5%, p<0.05) and higher E
(46.4%, p<0.05) levels vs. sham right kidneys without differences for K, R, Ang fragments, NE or DA.
Intraindividually, left denervated kidneys had lower R (23.5%), Ang(2-8) (45.9%), D (28.6%), and NE
(99.2%) levels vs. right kidneys (p<0.05). mRNA levels of D-decarboxylase (DDC), D-betahydroxylase, eNO-synthase (eNOS) and transforming growth-factor beta (TGFb) were higher (2259%) in denervated vs. right (p=NS) or sham kidneys (eNOS, p<0.05; DDC, TGFb, p=NS); Angsubstrate and converting enzyme were unchanged (p=NS).
Conclusion: Unilateral renal denervation decreases ipsilateral kidney NE and bilateral AII and BK
levels by side-dependent mechanisms documenting the importance of downstream hormonal
adaptations that contribute to or modify the post-denervation natriuretic and blood-pressure lowering
effects.
P356
Diabetic patients who report receiving processes of diabetic care do not
express a better quality of life
Alejandra Casillas*, Katia Iglesias, Bernard Burnand, Isabelle Peytremann-Bridevaux
IUMSP (Lausanne, CH)
Background: Chronic disease management initiatives emphasize patient-centered care, and quality of
life (QoL) is increasingly considered a representative outcome in that context. In this study we
evaluated the association between receipt of processes of diabetic care and QoL.
Methods: This cross-sectional population-based study (2011) used self-reported data from noninstitutionalized, adult diabetics, recruited from randomly selected community pharmacies in Vaud.
Outcomes included the physical and mental composites of the SF-36 (PCS, MCS) and the diseasespecific Audit of Diabetes-Dependent QoL (ADDQoL). Main exposure variables were receipt of six
diabetes processes-of care in the past 12 months. We also evaluated whether the association
between care received and QoL was congruent with the chronic care model, when assessed by the
Patient Assessment of Chronic Illness Care (PACIC). We used linear regressions to examine the
association between process measures and the three composites of health-related QoL. Analyses
were adjusted for age, gender, socioeconomic status, living companion, BMI, alcohol, smoking,
physical activity, co-morbidities and diabetes mellitus (DM) characteristics (type, insulin use,
complications, duration).
Results: Mean age of the 406 diabetic patients was 64.4 years (SD 11.4), 58% were male and 72%
had a living companion; 87% reported type 2 DM, half of respondents required insulin treatment, 47%
had at least one DM complication, and about 50% had DM over 10 years. Crude overall mean QoL
scores were PCS: 44.0 (SD 10.3), MCS: 47.1 (SD 11.2) and ADDQoL: -1.60 (SD 1.7). There were no
significant PCS, MCS or ADDQoL differences among all process indicators, when comparing those
who did/did not receive each individual process in bivariate analyses. After adjustment in models
including all processes, receipt of influenza vaccine was associated with ADDQoL (?= -0.45, p=.01);
there were no other associations between process indicators and QoL composites. Findings were
similar even when more processes were reported with combined measures of processes of care.
PACIC score was associated only with the MCS (?= 1.38, p=.03).
Conclusions: Process indicators for diabetes care did not show an association with QoL. This may
represent an effect lag time between time of process received and quality of life; or that treatment may
be related with inconvenience and patient worry. Further research is needed to explore these
unexpected findings.
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P357
An unusual case of diabetes
Yann Coattrenec*, Andreas Ebneter, Vérène Dougoud-Chauvin, Enzo Fontana
HFR (Fribourg, CH)
Introduction: Type 2 diabetes represents the most frequent etiology of diabetes, followed by type 1.
Secondary forms of diabetes, mainly in hospital, can exist and result from pancreatic pathologies.
Other hormones excess can also be part of the origin of a diabetes manifestation.
Case report: We report on the case of a 57-year-old man not known for metabolic disease and in
particular without diabetes. He presented 2 months ago with small cell lung cancer (SCLC), extensive
disease with multiple liver metastases, for which a dose-adapted chemotherapy was started (Cisplatin
and Etopophos, half dose). During this treatment, he was admitted to the hospital because of
generalized weakness, asthenia, weight loss, polydipsia and polyuria. Potassium was 2.8 mmol/l, and
glucose was found at 24, 4 mmol/l and creatinin at 59 µmol/l. Liver function was severely impared.
Blood pressure was 145/90 mmHg and general appearance was much reduced and the skin appeared
gray-brown. The following work-up showed a high plasma cortisol up to 2751 nmol/l and an ACTH
resulting very elevated to 252 ng/L . Insulin treatment was started and the oncological treatment was
stopped because of the severe liver dysfunction. Two weeks later the patient died of his progressive
cancer disease
Discussion: The case here presents an extreme condition of diabetes secondary to a Cushing
syndrome caused by an ectopic source of ACTH due to a SCLC. This paraneoplasic syndrom often
presents with a metabolic alkalosis and hypokalemia and hyperglycemia consecutively of the
important adrenal cortisol production following a very elevated ACTH. Insulin and potassium are
mandatory in the supplied therapy with chemotherapy for the cancer.
Conclusion: In non-obese oncological patient, it is important to search a possible cause of diabetes
particularly an immunologic cause or other secondary origin. Indeed the therapy will be adapted
according to the etiology and the efficacy.
P358
Diagnose der subakuten Thyreoiditis
Till Hauffe*, Christina Gold, Kemal Budak
Einleitung: Eine subakute Thyreoiditis präsentiert sich praktisch immer mit einer schmerzhaften
Schilddrüse. Da eine klinisch manifeste Hyperthyreose nur in rund der Hälfte der Fälle auftritt, kann
die Diagnosestellung erschwert sein. Die farbkodierte Duplexsonographie kann dem Grundversorger
auch ohne profunde Ultraschallkenntnis bei der Diagnose helfen.
Fallbericht: Eine 46 Jahre alte Patientin präsentierte sich mit Müdigkeit, Herzrasen und Diarrhoe. 4
Wochen zuvor trat eine Episode mit antibiotikaresistenten Halsschmerzen auf. In der klinischen
Untersuchung zeigten sich eine druckschmerzhafte Schilddrüse sowie ein feinschlägiger Tremor.
Auswärtig wurde laborchemisch eine Hyperthyreose festgestellt und eine thyreostatische Therapie
(Carbimazol) begonnen.
Bei Erstkonsultation bei uns lag eine Hyperthyreose mit TSH 0.01mmol/l und fT3 23pmol/l und fT4
>100pmol/l vor. Bis auf leicht erhöhte Entzündungsparameter (CRP 21mg/l) und einer leichten Anämie
(Hb 10.9g/l) war das Labor unauffällig. In der farbkodierten Duplexsonographie zeigte sich keine
gesteigerte Perfusion (s. Abb. A). Zusammen mit der Infektanamnese und der zervikalen Druckdolenz,
liess dieser Befund an eine subakute Thyreoiditis denken. Es wurde eine symptomatische Therapie
mit NSAR begonnen und die thyreostatische Therapie bei fehlender Indikation abgesetzt. Angesichts
der ausgeprägten Müdigkeit wurde auf eine Betablockertherapie verzichtet. Die TSH-RezeptorAntikörper (TRAK) fielen negativ aus, die Schilddrüsenszintigraphie zeigte keine Anreicherung.
Verlauf: Im Verlauf der nächsten Wochen erholte sich die Patientin, die Entzündungswerte
normalisierten sich und laborchemisch zeigte sich eine subklinische Hypothyreose.
Schlussfolgerung:
Die Erschöpfung wird häufig mit der Hypothyreose assoziiert, kann allerdings auch bei Hyperthyreose
auftreten. V. a. protrahiert verlaufende Halsschmerzen sollten an die Differentialdiagnose der
subakuten Thyreoiditis denken lassen.
Die Diagnose der subakuten Thyreoiditis wird klinisch gestellt, am wichtigsten sind Anamnese und
Klinik. Ergänzend kann die Sonographie helfen, die Differentialdiagnosen einzugrenzen (Abb. 2,
Morbus Basedow) und mittels Labor zu verifizieren. Eine Biopsie ist meist nicht notwendig.
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Aufgrund der destruktiven Entzündungsreaktion treten Schilddrüsenhormone unkontrolliert aus den
Follikeln. Da es sich nicht um eine vermehrte Hormonproduktion handelt, therapiert man mit
entzündungshemmenden Medikamenten und nicht mit Thyreostatika.
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P359
How to use 24-hour ambulatory blood pressure measurement (ABPM) for
smoking cessation
Fabian Aigner*, Paolo Suter
Introduction: Smoking is one of the most important risk factors in the modern world. Physicians are
aware of the chronic effect of smoking in promoting lung cancer and arteriosclerosis. However, the
immediate noxious effects of smoking on sympathetic nervous stimulation and overactivity in the
setting of daily practice with consecutive immediate effects on blood pressure (BP), heart rate and
myocardial contractility is ignored in the follow-up and control of patients. Here we report a case to
raise awareness of the importance to consider exact smoking history and behavior before the
measurement of office BP.
Case: A 33-year-old man with primary hypertension (office BP 140/99 mmHg on perindopril 8 mg,
bisoprolol 5 mg and HCTZ 12.5 mg) without target organ damage showed in regular BP consultation a
very variable office BP ranging from (high-) normal to hypertensive grade I. Non-compliance was
suspected. The same pattern was observed by the patient in his BP self-measurements. The patient
reported that he observed a correlation between smoking (> 20 cigarettes/d) in relation to his BP selfmeasurement and the variability of the blood pressure values. The information of the patient was so
convincing that we performed two 24-hour ABPM on two days (with/without smoking but with identical
work, physical activity schedule and sleeping/rest schedule). Figure 1 shows the profiles with a mean
decrease due to smoking cessation in systolic/diastolic BP of 11/7 mmHg during daytime and of 7/7
mmHg during the night. These convincing data motivated the patient to stop smoking.
Conclusion: Smoking behavior is an important modulator for short and long term BP. Not only usual
smoking habits but also short term smoking behavior should be addressed when measuring BP in the
office and also for BP self-measurements. Further BP effects of smoking should be used to motivate
for smoking cessation.
Figure 1: 24-hour ABPM measurement on the smoking day (A) and the non-smoking day (B)
1.
Omvik P. How smoking affects blood pressure. Blood Press 1996;5: 71-77.
2.
Mann SJ, James GD, Wang RS, Pickering TG. Elevation of ambulatory systolic blood
pressure in hypertensive smokers. A. Jama 1991;265: 2226-2228.
3.
Groppelli A, Giorgi DM, Omboni S, Parati G, Mancia G. Persistent blood pressure increase
induced by heavy smoking. J Hypertens 1992;10: 495-499.
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Infektiologie - Immunologie - Rheumatologie /
Infectiologie - Immunologie - Rhumatologie
P360
Low numbers of community-acquired extended-spectrum beta-lactamases
(ESBL) in a district in central Switzerland
Rein Jan Piso*, Cornelia Haldemann, Jeanine Rotzetter, Ines Griesshammer, Stefano Bassetti
Kantonsspital (Olten, CH)
Objective: The prevalence of ESBL positive bacteria is increasing in most countries in Europe and
elsewhere. Reasons for this increase are not well understood. A rise in community acquired ESBL is
often proclaimed for the situation. We retrospectively analysed the medical history of 75 patients one
year before the first detection of ESBL producing bacteria.
Methods: Medical records of 75 consecutive patients with first detection of ESBL producing bacteria
from 11/09 till 11/12 where studied. The detection was based on clinical specimen; we did not perform
routine testing. We especially were interested in hospitalisation, antibiotic treatment and urinary
catheters in the year prior to the first detection of ESBL. In cases of uncertainty, the family doctor of
the patient was also questioned.
Results: ESBL positive bacteria were detected in 54/75 patients in urine (72 ± 10.16%), 9/75 (12 ±
7.3%) in blood cultures, 8/75 (11 ± 7.1%) in wounds and in 11/75 (14.7 ± 8%)in other specimen. 53/75
(71± 10.3 %) of our patients had been hospitalized in the year prior first detection of ESBL, 33/75 (41 ±
11 %) in medical department, 26/75 (35±10.8%) in surgical, 7/75 (9 ±6.5%) on urological and 14/75
(19 ± 8.9%) in a rehabilitation clinic. 21/75 (28 ± 10.2 %) had been in the ICU, and 13/75 (17 ± 8.5 %)
were urological patients. 13/75 (17 ± 8.5%) of the patients had received urinary catheter, and 47/75
(63 ± 11 %) had received antibiotic treatment in the year prior first detection of ESBL. Only in 15/75
(20±9%) of our patients, no risk factor could be detected in the year prior first detection of ESBL.
Conclusion: We found only a low number of true community acquired ESBL. Most patients had been
hospitalized, and almost 2/3 has received antibiotic treatment in the year prior first detection of ESBL.
P361
Pneumococcal spondylodiscitis and psoas abscess in a patient with bronchial
carcinoma and poststenotic pneumonia
Ines Griesshammer*, Rein Jan Piso, Stefano Bassetti, Markus Zuber, Tobias Schütz, Seiichi Erné,
David William Crook
Kantonsspital Olten (Olten, CH)
Introduction: S.pneumoniae is a common pathogen with high morbidity and mortality in humans in
case of invasive infection. Usually it causes pneumonia, otitis media, sinusitis and meningitis. Disease
patterns like spondylodiscitis and psoas abscess are uncommonly caused by S. pneumoniae.
Case report: A 60 year old patient was admitted with lumboradicular pain that had not responded to
his usual pain pills. He received palliative chemotherapy for a bronchial carcinoma with osseous
metastases one week before admission. Fever, increased coughing or sputum were denied. Clinical
examination revealed in- and exspiratory wheezing and pronounced lumbar back pain. CRP was
elevated (284 mg/l), leucocyte count was 6.4 G/l with a left shift of 20%. Conventional x-ray and MRI
showed evidence of new bone metastasis and initially no signs of spondylodiscitis.
On day 3 the lower back pain worsened and signs of a sepsis occurred. Blood cultures showed
Streptococcus pneumoniae. We postulated a pneumococcal pneumonia and changed antibiotic
treatment to Penicillin G 4 x 5 Mio units/d. The patients’ condition improved slightly but CRP remained
high. The thoracoabdominal CT-scan exposed the poststenotic pneumonia plus a psoas abscess
formation.
Abscess drainage was performed which reduced both symptoms and inflammatory parameters. S.
pneumonia was also detected in the psoas abscess. The control CT-scan 10 days later though
showed a recrudescence of the left psoas abscess, but new abscess collection in the right psoas and
now signs of a spondylodiscitis. A second surgery was accomplished.
Discussion: Various bacteria, including S. aureus and Streptococci have been reported as pathogens
of psoas abscess and spondylodiscitis. S. pneumoniae is a rare cause of spondylodiscitis. Prompt
diagnosis is difficult since symptoms are often non-specific. In this case, we propose that the primary
focus was a bacteremic pneumonia that caused spondylodiscitis which carried along the psoas
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abscess, even if the spondylodicitis was not visible in the primary MRI. In general, the prognosis of
pneumococcal psoas abscess is good when treated with immediate surgery and adequate antibiotic
treatment but can have disastrous outcomes without treatment. Therefore psoas abscess and
spondylodiscitis must be excluded in patients with pneumococcal bacteremia and suspicious focal
symptoms, even if primary focus has been determined.
P362
The "feverish granny syndrome": severe primary cytomegalovirus (CMV)
infection in an elderly woman
Julia Steinrücken*, Sylvia Mayr, Peter Graber
Kantonsspital Liestal (Liestal, CH)
Background: CMV is a common virus in humans with a highly variable seroprevalence, depending on
age and socioeconomic factors. Primary CMV infection is usually mild or even asymptomatic in
children or adolescents. However, CMV may cause severe disease in immunocompromized patients
either by reactivation or primary infection. Primary CMV infection is a cause of high fever in the
immunocompetent elderly without evident focus.
Case description: A 60-year-old previously healthy woman presented with a 3-day history of fever,
chills, myalgia, and weakness. On admission, fever (39.0°C), hemorrhagic conjunctivitis, aphthous
stomatitis, and a few abdominal skin blisters were present. Leukocyte counts were normal with 26%
bands and lymphocytosis (3.5 x 109 /l, 55%) with atypical forms. In addition, thrombocytopenia (66 x
109 /l) and elevated CRP (239 mg/l), procalcitonin (1.25 µg/l), transaminases (ASAT 94 U/l, ASAT 75
U/l), and LDH (936 U/l) were detected. Thoracoabdominal CT was normal. At day 5 of illness,
antibodies to CMV, HIV, Brucella and Q-fever were negative. Hematologic malignancy was excluded
by bone marrow aspiration. After one week, the patient’s condition slowly improved, and inflammatory
parameters decreased. On day 9, CMV serology was repeated, showing seroconversion with positive
IgM and low avidity IgG antibodies. CMV PCR in blood was negative. However, CMV PCR from a
stored serum sample taken on the 2nd day of hospitalization and from skin blister fluid were both
positive, confirming the diagnosis of CMV infection. After 10 days, the patient could be discharged.
Careful exposure history revealed that her daughter-in-law and her 8-month-old grandchild had
suffered from a mild viral illness during the same time period, which turned out to be acute CMV
infection after serologic testing.
Clinical relevance: Primary CMV may cause severe symptoms in the elderly. Seronegative seniors are
at risk to be infected by their grandchildren, causing the “feverish granny syndrome”. Unexplained
fevers and atypical lymphocytes should raise the suspicion of primary CMV infection in seronegative
elderly persons. Detection of CMV in blood or urine should be attempted by PCR to avoid
unnecessary and costly diagnostic procedures. CMV serology may not be helpful in the early phase of
illness, but is still important to establish the final diagnosis of acute CMV infection.
P363
Fluctuating headache with changes in personality: cerebral vasculitis
Beatrice Müller*, Stefano Bassetti, Susanna Frigerio
Kantonsspital Olten (Olten, CH)
Background / Case presentation: Isolated cerebral vasculitis may present neurological symptoms with
headache, cognitive deficits and invariably psychiatric signs without any other clinical manifestation.
We present a 63-year-old patient with new onset and severe holocephal headache. In personal history
a marginal zone B-cell non-Hodgkin lymphoma in 2009 is known, currently in complete remission.
Physical examination showed reduced general condition with hypertensive blood pressure (183/95
mmHg). Behavioural neurologic examination presented an agitated and disinhibited patient.
Initial Results: Laboratory results showed normal Leucocytes (9.6 G/L), C-reactive protein (1.9 mg/l)
and almost regular sedimentation rate (12 mm/h). Cerebrospinal puncture exhibited a discrete
increase of total protein to 0.57 g/l (standard 0.15-0.45), but no lymphocytic pleocytosis in CSF or
other pathology, especially cytological analysis revealed no suspicious malignant cells. Native cranial
CT exposed bihemispheric subcortical hypodensities. Due to progressive restlessness and increasing
fluctuating headache accompanied by qualitative disturbance of consciousness with changes in
personality the transfer to our ICU was necessary.
Clinical Course: Non convulsive Status epilepticus could be excluded by EEG showing bilateral
generalized slowing with frontal intermittent rhythmic delta activity (FIRDA). Anticonvulsant therapy
with levetiracetam was installed with 1000 mg BID. Cerebral MRI scans showed bihemispheric
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subcortical leucencephalopathy with subacute ischemic lesions in the left hippocampus and in the
right parietal lobe. MR angiography revealed impressing irregularity of vessel calibre in several
intracranial arteries. Our estimated diagnosis of cerebral vasculitis was confirmed by the cerebral
angiography (Inselspital Bern) that showed the typical picture with significant irregularities of calibre of
the intracerebral arteries. During treatment with high-dose corticosteroid therapy, monthly Endoxan®
pulse therapy as well as anticonvulsant therapy qualitative disorders of consciousness regressed and
the patient was almost completely free of headache.
Conclusion: Our case report supports that normal serum inflammation markers do not rule out cerebral
vasculitis and that constellation of headache accompanied with fluctuating changes in personality
should prompt the search for cerebral vasculitis as an important differential diagnosis of secondary
headache.
P364
Wolf and dog: first manifestation of systemic lupus erythematosus combined
with Capnocytophaga sepsis
Marco Etter*, Agnes Kneubühl, Christian Steffen
Spital Lachen (Lachen, CH)
Introduction: Systemic lupus erythematosus (SLE) and its treatment may alter immunologic response.
Infection may induce SLE or trigger relapse. Capnocytophaga spp. is a gram-negative rod found in
normal oral flora of dogs. Systemic infection in immune competent individuals is rare. Fatal sepsis may
occur especially in asplenic individuals or persons with hepatic disease.
Case Report: An 18-year-old patient was referred to our emergency department because of fever and
chills and polyarthralgia for two weeks. He had a skin rash and neutropenia was documented. On
admission he was in mild distress and febrile (39.2°C). Vital signs where within normal range.
Previous history was unremarkable. He lives with his parents and his brother, is an office employee,
has a pet dog without reported bites and no recent travel history. Clinical examination showed a
maculopapular scaling rash on the trunk, thighs and arms. On the second day of hospitalization a
malar rash developed. He had generalized arthralgia without signs of arthritis. Laboratory testing
revealed pancytopenia, elevated C-reactive protein and Creatinin. In addition complement factors C3
and C4 were low and antibodies against double-stranded DNA were elevated. One blood culture grew
Capnocytophaga spp.. Urin investigation showed haematuria without casts and mild proteinuria.
Treatment with co-amoxicillin was initiated. Later the Patient developed Libman Sachs endocarditis.
Hence prednison and plaquenil were started. Renal biopsy showed lupus nephritis class III (World
Health Organisation). After two months of treatment echo-cardiographic findings and renal function
were normal. Azathioprin was added and Prednison gradually tapered. After 16 months, the patient is
doing well.
Discussion: We diagnosed SLE with Libman Sachs endocarditis and concomittant Capnocytophaga
sepsis in this patient. It remains unclear, whether SLE’s associated immunodepression allowed
systemic Capnocytophaga infection or if the latter induced SLE.
Conclusion: Even if Occam’s razor may lead to a conclusive diagnosis such as SLE, in a febrile
patient searching for bacterial infection is still necessary.
P365
Life-threatening sepsis due to typhoidal tularaemia during infliximab therapy
Nina Lutz*
Case: In august 2012, a 31-year-old warehouse clerk was referred to our hospital due to fever and
coughing since three days. For Crohn’s disease he was under treatment with the TNF-antagonist
infliximab. The patient is of Turkish descent but grew up mostly in Winterthur. On presentation the
patient was febrile without any localising signs or symptoms. Chest-X-Ray and CT scan revealed a
large mediastinal (10x5cm) and several pleural masses (max. 5x5cm). Routine blood tests were
normal beside an elevated CRP (86 mg/l). Pleural biopsy demonstrated malignant thymoma type B3.
The PET-CT showed low intensity FDG-accumulation in thymus and pleural metastases. Moreover,
very intense FDG-uptake was noted in tonsils, in multiple cervical, mediastinal and abdominal
lymphnodes and in the enlarged spleen and liver raising the strong suspicion of additional disease.
Meanwhile, the patient had developed severe systemic inflammation, progressive respiratory failure
and cholestatic hepatitis with the following lab results: leucocytes 23x109/L, neutrophils 15.6x109/L,
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CRP 483 mg/l, Procalcitonin 0.11 ng/ml, Ferritin 10’044 ug/L, Bilirubin 117 umol/l, ALAT 170 U/L, AP
323 U/L, LDH 1138 U/L.
Biopsies of bone marrow, tonsil and mediastinal lymph node revealed necrotising lymphadenitis with
atypical granulomas and severe inflammation without overt hemophagocytosis or lymphoma.
Empirical treatment was started including high dose methylprednisolone and tuberculostatic therapy
with Rifampicin, Isoniazid, Pyrazinamid and Moxifloxacin. The latter was included to treat possible
alternative bacterial infections. Within days, the patient’s condition and lab results markedly improved.
Surprisingly, broad spectrum bacterial PCR from the lymph node was positive for Francisella
tularensis leading to the diagnosis of typhoidal tularemia with severe sepsis. Treatment was changed
to Tobramycin i.v. for 5 days and Doxycyclin orally for 14 days and the patient made a full infectious
recovery. Unfortunately, metastatic thymoma was unresponsive to chemotherapy and the patient was
transferred to thoracic surgery in December 2012.
Discussion: This patient developed life-threatening sepsis due to systemic infection with F. tularensis
(subspecies holarctica). His disease course was extraordinarily fulminant and most likely triggered by
anti-TNF therapy known to cause very inefficient Francisella control in mice. This case highlights the
infectious risk of anti-TNF therapy beyond tuberculosis.
P366
Rabbit fever
Christina Lyko*, Christian Chuard
Hôpital Cantonal Fribourg (Fribourg, CH)
Introduction : Tularemia, also called rabbit fever, is an infection caused by Francisella tularensis, a
zoonose transmitted to humans by contacts with infected animals or by vectors such as ticks. This
disease is rare in Switzerland, where approximately 7 cases are recorded each year since the
introduction of the mandatory declaration in 2004, but its incidence has recently increased.
Cases report : 1)
A 51-year-old woman, owner of an equestrian center, was sent to hospital in
June 2012 after a 4-week therapy with beta-lactams for a cutaneous umbilical ulceration following tick
bite with bilateral inguinal lymphadenopathy and malaise. The ulceration improved but the
lymphadenopathy grew up and became fluctuant. Tularemia was suspected and confirmed
serologically at the 21st day of illness. Doxycycline was administered for 3 weeks with clinical
improvement reached on the 2nd day of therapy and complete resolution after 4 weeks of therapy.
2)
A 58-year-old butcher presented in October 2012 with a skin lesion, flulike symptoms and
weight loss. Physical examination revealed a painless 7-cm red plaque with a suppurative central
ulceration on the upper chest wall. A tender, fluctuant, 3-cm lymph node was palpable in the ispilateral
axillary region. Despite treatment with oral beta-lactams, the symptoms did not improve. Because a
tick bite was possible, tularemia was suspected and a therapy with doxycycline was started. The
clinical condition improved, but the serology for tularemia made on the 7th day of illness was negative.
It was repeated 3 weeks later and finally confirmed the diagnosis.
Discussion and conclusion:
Clinical manifestations of tularemia are diverse, but the ulceroglandular disease is the most common
form.
Diagnosis is based on serology with antibody titer rise approximately 2 weeks after the onset of
illness. When the suspicion is high, the serology should be repeated if necessary.
Although this infection is rare, it should be part of the differential diagnosis in front of a clinical setting
of lymphadenopathy with cutaneous ulceration, especially when it follows a tick bite or if a therapy with
beta-lactams is not effective.
P367
Penicillium marneffei sepsis: first manifestation of HIV infection
Victor Speidel*, Stefanie Nicolaus, Madeleine Rothen
Introduction: Though rarely seen in immunocompetent patients, P. marneffei is one of the most
common HIV-associated opportunistic infections in Southeast Asia. The dimorphic fungus is endemic
in Southeast Asia, but only few imported cases have been reported in Switzerland.
Clinical findings in patients with systemic infection are unspecific and may include fever (93%), skin
lesions (83%), weight loss (59%), cough (50%), lymphadenopathy (40%) and diarrhea (27%).
Case: A 52-year-old Swiss man consulted his family doctor for loss of appetite, nausea, dysphagia,
fever, diarrhea and a weight loss of 10kg in 6 weeks. He had smoked about 40 packyears and had no
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medical history apart from a dengue fever and treated syphilis about 20 years ago. Living in
Switzerland, he had spent five months each year in Thailand for the last 20 years.
Clinical examination showed cachexia, hypotension, fever, oral candidiasis, generalized
lymphadenopathy and a non-pruritic papular rash on the head and trunk.
Following a positive HIV-antibody test, further testing revealed a high viral load of 1.2mio cop/ml and a
CD4 count of 26/µl.
Blood cultures turned out positive for P. marneffei and antifungal therapy with itraconazole was
initiated four days after start of antiretroviral therapy.
During the first few weeks of treatment the skin lesions became more severe before disappearing after
2 months of therapy with resolution of all clinical symptoms, while the CD4 count rose to > 400/mm^3
and viral load decreased steeply.
Conclusion: Late presentation of HIV-infection may vary and is not uncommon even in Switzerland.
Although there are no endemic P. marneffei infections in western countries, they have to be thought of
due to travelling and migration.
Treatment recommendations include amphotericin B for 2 weeks, followed by 10 weeks of oral
itraconazole, but alternatively itraconazole alone can be given for 12 weeks. Secondary prophylaxis
needs to be continued until immune reconstitution is achieved to prevent relapse.
Symptoms of P. marneffei infection may only present or worsen upon treatment with antiretrovirals
due to immune restoration. The unmasking effect of improved cellular immunity is known as immune
reconstitution inflammatory syndrome (IRIS).
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Allgemeine Innere Medizin - Infektiologie / Immunologie / Rheumatologie Médecine interne générale - Infectiologie/Immunologie/Rhumatologie
P368
Raubvogelangriff mit Folgen: Tularämie (Hasenpest)
Maria Trachsel*, Reinhard Imoberdorf, Jacques Gubler, Urs Karrer
Fall: Ein 43- jähriger Patient wurde uns wegen persistierendem Fieber mit Schüttelfrost sowie
zervikaler und nuchaler Lymphknotenschwellung zugewiesen. 14 Tage zuvor wurde er beim Joggen
von einem Raubvogel attackiert und erlitt am Kopf diverse Kratz- und Schnabelverletzungen. Eine
orale antibiotische Therapie mit Amoxicillin/Clavulansäure hatte keine Besserung gebracht. Die
Wunde am Kopf war klinisch nicht entzündet, nuchal und zervikal bestand eine ausgeprägte
druckdolente Lymphknotenschwellung ohne Rötung oder Fluktuation. Im Lymphknotenpunktat konnte
mittels bakterieller Breitspektrum-PCR und kulturell Francisella tularensis nachgewiesen werden. Die
Therapie mit Tobramycin intravenös (5 Tage), gefolgt von Doxycyclin peroral für 2 Wochen resultierte
in einer raschen Besserung mit Regredienz des Fiebers und der Lymphknotenschwellung.
Diskussion: Die Tularämie ist eine in der Schweiz bisher seltene meldepflichtige bakterielle Zoonose.
2012 wurde mit insgesamt 37 bestätigten Fällen ein deutlicher Anstieg der Erkrankungen festgestellt.
Die Übertragung erfolgt durch blutsaugende Arthropoden (insb. Zecken), Haut- oder
Schleimhautkontakte mit infektiösem Tiermaterial, kontaminiertes Fleisch und Wasser oder durch
Inhalation von infektiösem Material. Eine Übertragung von Mensch zu Mensch ist unbekannt. F.
tularensis ist hochinfektiös, bereits 10 bis 50 Bakterien können zur Infektion führen. Die Krankheit
beginnt nach kurzer Inkubationszeit von 3-5 Tagen (1-21 Tage) mit Allgemeinsymptomen gefolgt von
lokalen Lymphknotenschwellungen. Am häufigsten ist die ulcero-glanduläre oder glanduläre
Manifestation, je nach Eintrittspforte kommen seltener auch oropharyngeale, thyphoidale oder
pulmonale Formen vor. Diagnostisch ist die Kultur von F. tularensis anspruchsvoll und wird
zunehmend durch die PCR aus Gewebe (ev. Blut) ersetzt. Die Serologie ist zuverlässig, wird aber erst
in der 2. Krankheitswoche positiv. Therapeutisch sollten Aminoglykoside, Tetrazykline oder Chinolone
verwendet werden, denn Beta-Lactame sind unwirksam.
Bei unserem Patienten lag eine ulzero-glanduläre Tularämie mit höchst ungewöhnlicher
Ansteckungsart vor. Wir gehen davon aus, dass der Raubvogel vor kurzem ein infiziertes Nagetier
gerissen hatte und so die Bakterien auf unseren Patienten übertragen konnte. Während
Raubvogelattacken auf Jogger gerade in der Brutzeit regelmässig vorkommen, ist in der Literatur
lediglich ein Fall einer Tularämie nach Raubvogelkontakt beschrieben.
P369
Value of 18F-FDG-PET-CT in diagnosis of large vessel vasculitis with aortic
arch involvement: two cases with impressive findings
Daniel Portmann*, Jacques Gubler
Introduction: Large vessel vasculitis (LVV) with involvement of the arotic arch is potentially life
threatening and early detection can be crucial. Clinical signs and symptoms of LVV are nonspecific,
making diagnosis and differentiation from polymyalgia rheumatica (PM) or Giant Cell Arteriitis (GCA)
difficult. We report two cases of LVV where early diagnosis was made by PET-CT.
Case 1: A 61-year-old woman was admitted to our outpatient clinic with a two month history of fever,
drenching night sweats and weight loss of 5kg. Laboratory investigations suggested systemic
inflammation with an erythrocyte sedimentation rate of >110 mm/hour, a C-reactive Protein of 239mg/l
and normocytic anemia. An extensive diagnostic evaluation was performed to exclude an unknown
primary tumor or an infectious cause. Finally, a PET-CT revealed LVV affecting aorta, subclavian,
proximal brachial, common carotid and femoral arteries bilaterally (Fig 1).
Case 2: A 57-year-old woman presented with a history of proximal muscle weakness, general fatigue
and drenching night sweets. Her ESR was >100mm/h, her CRP 122mg/l. PET-CT revealed LVV
affecting the whole aorta, the supraaortal arterial branches and popliteal arteries bilaterally (Fig 2).A
temporal artery biopsy showed no signs GCA.
Both patients had no signs of ischemia, notably no arm or leg claudication.Treatment with prednisolon
and methotrexate (MTX)led to a rapid resolution of clinical symptoms and normalization of laboratory
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parameters.Recovery in both patients took more time than one might expect from classical PM or
GCA.
Discussion: In patients with a clinical presentation of PM or GCA and extensive systemic complaints,
the possibility of LVV should be evaluated. Beck et al. noted a different clinical pattern for patients
LVV. While headache, jaw claudicatio and visual changes were rare, arm claudicatio is seen more
often in patients with LVV compared to classical GCA (38% vs. 0%). Surprisingly, they found no
difference in the rate of systemic symptoms.
Inflammatory cell infiltration (revealed by PET) is likely to precede the development of edema of the
vessel wall (depicted by MRI), making PET-CT the investigation of choice for LVV, with a sensitivity of
77-92% and specificity of 89-100%. Because of the potentially life threatening complications of LVV,
an early diagnosis is crucial. While therapy of PM and GCA initially use steroids alone, patients with
LVV may need an additional immunosuppresive agent, with MTX as first choice.
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P370
Malta fever from South America
Silvan Meier*, Thomas Bregenzer
Spital Lachen AG (Lachen, CH)
Introduction: Brucellosis is the world’s most common bacterial zoonosis with more than half a million
new cases annually. The mortality rate is about 2 %, mainly due to endocarditis. If untreated,
osteoarticular and genitourinary complications may lead to severe sequelae. Only five to ten cases are
reported in Switzerland annually, mainly imported from the Mediterranean region. After an incubation
period of up to 60 days, undulating malaria-like fever is the most common symptom. Brucella is an
intracellular pathogen with world wide occurrence. Many farm animals are reservoirs. It is mainly
transmitted through breaks in the skin or ingestion of dairy products.
Case Report: A 62-year-old patient suffered from fever, night-sweat, weight loss and fatigue for two
months. He was referred by his general practitioner who excluded malaria. His previous history was
unremarkable. There was evidence of past EBV-infection and hepatitis A. He was preparing his
retirement and planned to relocate to a rural region in Brazil where his wife already emigrated to. She
is farming there sheep and goats. He was exhausted, anorectic and complained in particular about a
periodical, undulating fever up to 38° C mainly in the evening. Clinical examination was without
pathological findings, an infectious focus could not be identified. The laboratory results showed
increased inflammation parameters and elevated liver enzymes. Abdominal sonography revealed
splenomegaly with 13.9 x 4.6 cm, chest X-ray was normal. Serologic investigation was positive for
brucella spp. All blood cultures grew brucella melitensis. Combination therapy with doxycycline and
gentamicin for two weeks and doxycycline monotherapy for another four weeks was initiated. Clinical
improvement and declining signs of inflammation were documented within one week of treatment. The
patient is asymptomatic and doing well six months after treatment.
Discussion: Brucellosis is rare in Switzerland and usually associated with a travel history in the
Mediterranean region. However, B. melitensis occurs worldwide. Our patient may have acquired the
infection when he visited his wife in Brazil. The recommended treatment is doxycycline combined with
gentamicin although quinolones may yield similar efficacy.
Conclusion: In patients with prolonged fever and constitutional symptoms, Malta fever should
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P371
White Islands...Fever Islands...
Philipp Jent*, Simon Steiner, Drahomir Aujesky, Daniel Vogel
Division of General Internal Medicine, University Hospital Bern (Bern, CH); Division of Infectious
Diseases, University Hospital Bern (Bern, CH)
Introduction: Dengue is a self-limited systemic viral infection transmitted between humans by
mosquitoes (A. aegypti and A. albopictus). Due to an increase in travel and global mobility a growing
number of cases are also seen in Europe. This case report is an example showing the features of this
infection with a huge global burden.
Method: Case Report: A 42-year-old woman returned from a two month holiday trip to Peru, followed
by 10 days in Curaçao (Caribbean). She was admitted to our emergency room with fever, retro-orbital
headache, heavy myalgia and joint pain with an onset 3 days after returning home. The clinical
examination showed no specific infectious focus, the laboratory findings included leukopenia (1,5G/L)
and thrombocytopenia (31G/L). The CRP was 3mg/L and malaria tests negative. Further evaluations,
including blood and stool cultures as well as serology for viral hepatitis, also remained negative. 5
Days after onset of symptoms a bright red confluent macular rash of the lower limbs with „islands of
white“ (unaffected skin) appeared (Fig. 1). In parallel, an increase of serum aminotransferase levels to
12 x the upper normal level was observed, peaking 9 days after symptom onset and declining
thereafter (Fig. 2). The suspected diagnosis of dengue fever could be confirmed serologically. After 5
days the fever and pain stopped spontaneously. Hematocrit stayed stable and there were no signs of
capillary leakage, severe bleeding or severe organ involment. Thrombocytes and leukocytes returned
to normal.
Key Points / Discussion
- Consider dengue in patients returning from Southeast Asia, South Central Asia, the Caribbean and
South America with fever, muscle and joint pain (‚break bone fever’) and headache.
- Approximately 50% of the patients show a characteristic rash (‚islands of white in a sea of red’)
predominantly of the lower limb.
- Typical laboratory findings include thrombocytopenia and leukopenia. Aminotransfase level
elevations are common; in less then 5% > 10 x the upper norm, as in our case.
- In the period of defervescence (days 4-7) signs indicating severe dengue such as capillary leakage,
bleeding (decreasing thrombocytes and hematocrit), increasing aminotransferase levels and
neurological impairment must be monitored closely.
P372
A rare cause of chronic diarrhoea
Gabriela Keller*, Urs Karrer, Reinhard Imoberdorf, Stephan Bosshard
Case: A 61 year old patient was admitted to our clinic due to chronic diarrhea and weight loss of 10 kg
since 1 year. He did not report any fever, chills or sweating. His body mass index was 15 kg/m2. Stool
examination only showed evidence of intestinal spirochetes and blastocystis hominis. Endoscopic,
histologic and serologic investigations ruled out Whipple’s disease, coeliac disease, inflammatory
bowel disease and other causes of chronic diarrhea combined with malnutrition. Thoraco-abdominal
CT scan with subsequent biopsy showed a 6x7 cm thymoma without metastases of a mixed histologic
type (AB). Total immunoglobulin levels in the serum (IgA, IgG and IgM) were substantially reduced
indicating thymoma associated Good syndrome. With the presumptive diagnosis of opportunistic
infectious diarrhea antimicrobial therapy against spirochetes and blastocystis was initiated leading to
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prompt cessation of watery diarrhea. Hypogammaglobulinemia was substituted with intravenous
immunoglobulin. In the short-term follow up the patient could maintain his body weight and was
clinically without an infection.
Diagnosis: Good syndrome is a rare cause of acquired immunodeficiency that occurs in association
with thymomas. Due to hypogammaglobulinemia affected patients may suffer from severe
opportunistic and recurrent bacterial infections.
Discussion: Thymoma associated with hypogammaglobulinemia and profound susceptibility to
recurrent and serious infections was first reported by Robert Good in 1954. Chronic diarrhea
associated with thymoma is mostly seen in patients with hypogammaglobulinemia. However, chronic
diarrhea may also occur with normal immunoglobulin levels. Our case illustrates that paraneoplastic
disorders associated with thymoma may lead to progressive illness with wasting syndrome. In this
setting, malnutrition which is crucial for the overall outcome may become self-perpetuating even in
absence of detectable opportunistic infection. Survival of patients with Good syndrome is mainly
limited by infection, autoimmune disease and hematologic complications. Complete surgical resection
of the thymoma is the preferred treatment approach for these patients. However, despite thymectomy
hypogammaglobulinemia may persist mandating the life long substitution of immunoglobulins.
P373
Bilateral parotid swelling caused by? It`s written in the stars!
Katja Stürzebecher*, Kirsten Mertz, Franz Büttner, Elke Ullmer
Kantonsspital Baselland/ Liestal (Liestal, CH)
Background: Sarcoidosis (SD) is a multisystem disorder affecting the respiratory system in >90% of
patients. Extrapulmonary organs frequently involved are peripheral lymph nodes, skin, eyes, liver,
heart, and central nervous system. Parotid gland involvement is rare (<6%).
Case: A 24-year-old woman was admitted with non-tender swellings at both angles of the jaw. She
denied cough, dyspnea, nightsweats or fever. Sonography revealed bulky, inhomogeneous parotid
glands. Cervical lymph nodes were not enlarged. Laboratory findings were not conclusive. CT scan
showed mediastinal and hilar lymphadenopathy. Additionally, round and irregular marginated masses
were visible in the superior segment of both lower lobes. In 2002, Nakatsu et al. first described these
coalescent granulomatous lesions as sarcoid "GALAXY SIGN". Bronchoscopy showed endobronchial
cobblestone pattern, histologically containing non-caseating granulomas. BAL revealed lymphocytic
alveolitis and CD4/ CD8 ratio was augmented. Infectious agents could not be detected. SD stage II
with lung and parotid gland involvement was diagnosed. Systemic steroids were started (1mg/kg KG)
and tapered over 6 months.
Discussion: Bilateral parotid swelling may be caused by viral or bacterial infections, sialolithiasis,
tumors or autoimmune disorders, mainly Sjögren`s syndrome and SD. Parotid swelling due to SD,
combined with uveitis, fever, and bell`s palsy is called Heerfordt`s syndrome. Bihilar lymphadenopathy
is the most common radiological finding in patients with SD. Although small nodules along the
bronchovascular bundles, interlobular septa, and major fissures or in the subpleural regions are
frequently observed, large parenchymal nodules are less common, but also pathognomonic for SD.
Coalescent nodules in the center form larger, more dense nodules than the peripheral satellite-like
micronodules resembling a GALAXY. Histologically, these nodules correspond to interstitial
granulomas. Peribronchial arrangement may result in an air bronchogram mimicking alveolar
infiltration. Central cavitation may occur.
Conclusion: Bilateral parotid swelling may be the first manifestation of SD. Bihilar lymphadenopathy
and diffuse small nodules with perilymphatic distribution are typical radiological manifestations. In
about 15% of patients, large, irregular marginated nodules occur. This „GALAXY-SIGN” should raise
suspicion for thoracic SD. Tbc is the most important differential diagnosis and has to be ruled out.
P374
Immunomodulatory effects of low dose immunoglobulin replacement in
patients with primary antibody disorders
Peter Jandus*, Camilla Jandus, Lukas Jörg, Daniel Yerly, Werner Pichler, Arthur Helbling
Service d'Allergologei et d'Immunologie, Hôpitaux Univeristaires de Genève (Genève, CH); Ludwig
Center for Cancer Research, UNIL (Lausanne, CH); Departement Rheumatologie, Klinical
Immunologie und Allergologie, Allergische-Immunologische Poliklinik, Inselspital (Bern, CH);
Departement Rheumatologie, Klinical Immunologie und Allergologie, Allergische-Immunologische
Poliklinik, Inselspital (Bern, CH); CDepartement Rheumatologie, Klinical Immunologie und
Allergologie, Allergische-Immunologische Poliklinik, Inselspital (Bern, CH)
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Introduction: Understanding the mechanisms of action of high-dose intravenous immunoglobulins
(IVIg) in autoimmune and inflammatory disorders has kept investigators busy over the past 3 decades.
A number of mechanisms for immune modulationsand anti-inflammatory actions of high-dose IVIg
have been described. In contrast, the mechanisms of action of low-dose IVIg in primary antibody
disorders have not yet been thoroughly investigated.
Aim of the study: a) Assess the effect of low-dose IVIg on immunological parameters in patients with
primary antibody disorders, longitudinally during IVIg replacement.
b) Identify correlations between favorable effects on clinical symptoms and modulation of
immunological parameters during low-dose IVIg substitution.
Methods: Eight patients with primary antibody disorders (CVID, subclass deficiency) with recurrent
infections requiring immunoglobulin substitution were included in the study. Blood was withdrawn
before the first IVIg replacement, at 3-4, at 6 and at 10-12 months of treatment. PBMCs were isolated
and serum was collected stored at 80°C. Quantification of pro- and anti-inflammatory cytokines in the
serum is performed by ELISA, phenotypic and functional analyses of lymphocyte subsets and
dendritic cells are assessed by multi-color flow cytometry and in vitro assays.
Results: In preliminary experiments, we observed a significant increase in the concentration of a large
number of cytokines in all 8 patients tested during low-dose IVIg, albeit with different kinetics. While IL2, IL-4, IL-10, IL-13, IL-1 beta, INF-gamma levels already were significantly higher 3-4 months after
initiation of the replacement therapy than before, IL-5, IL-12p70, IL-17 showed a more delayed, yet
sustained increase over the treatment period.
Conclusion: Taken together, these preliminary analyses suggest a modulation of action of low-dose
IVIg on the immune system supporting the hypothesis that a beneficial effect of low-dose IVIg in
patients with primary antibody disorders cannot be explained only by the reconstitution of normal
circulating immunoglobulin levels upon treatment.
P375
Trends in the main diseases in an internal medicine ward, 2003-2011
Marco Martinuz*, Gérard Waeber, Pedro Marques-Vidal
CHUV (Lausanne, CH)
Introduction: Population aging leads to a considerable increase in the prevalence of specific diseases.
We aimed to assess if those changes were already reflected in an Internal Medicine ward.
Methods: Anonymous data was obtained from the administrative database of the department of
internal medicine of the Lausanne University Hospital (CHUV). All hospitalizations of adult (>=18
years) patients occurring between 2003 and 2011 were included. Infections, cancers and diseases
according to body system (heart, lung…) were defined by the first letter of the ICD-10 code for the
main cause of hospitalization. Specific diseases (myocardial infarction, heart failure…) were defined
by the first three letters of the ICD-10 codes for the main cause of hospitalization.
Results: Data from 32,741 hospitalizations occurring between 2003 and 2011 was analyzed.
Cardiovascular (ICD-10 code I) and respiratory (ICD-10 code J) diseases ranked first and second,
respectively, and their ranks did not change during the study period (figure). Digestive and endocrine
diseases decreased while psychiatric diseases increased from rank 9 in 2003 to rank 6 in 2011
(figure).
Among specific diseases, pneumonia (organism unspecified, code J18) ranked first in 2003 and
second in 2011. Acute myocardial infarction (code I21) ranked second in 2003 and third in 2011.
Chronic obstructive pulmonary disease with acute lower respiratory infection (code J44) ranked third in
2003 and decreased to rank 8 in 2011. Conversely, heart failure (code I50) increased from rank 8 in
2003 to rank 1 in 2011 and delirium (not induced by alcohol and other psychoactive substances, code
F05) increased from below rank 20 in 2003 to rank 4 in 2011. For more details, see table.
Conclusion: In less than 10 years, considerable changes occurred in the presentation of patients
attending an Internal Medicine ward. The changes in diseases call for adaptations in hospital staff and
logistics.
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Cardiologie - Pneumologie - Gastroentérologie 1
P376
Right cardiac obstruction in a healthy 76-year-old lady
Tobias Öttl*, Daniel Jauslin, Pirmin Häuptle, Marc Gutmann, Andreas Lohri
Kantonsspital Baselland, Liestal (Liestal, CH)
A 76-year-old woman was admitted because of orthopnea. She reported mild effort intolerance (NYHA
II) over the past 6 months, but had continued her usual active lifestyle. Shortness of breath started to
deteriorate 4 weeks earlier. She had a history of untreated hypertension and no immunosuppressive
therapy. On admission, her heart rate was 100/min, peripheral oxygen saturation was 80%. Physical
examination showed jugular venous distension and suspected bibasilar pleural effusions. Laboratory
findings included a NT-proBNP level of 1100ng/l (normal value <125ng/l) and a LDH of 496 U/l
(normal value <250 U/l), a chest X-ray confirmed bilateral pleural effusions.
Cardiologic work-up included an initial transesophageal echocardiogram (TEE) that showed a circular
pericardial effusion of 3cm, no valvular dysfunction and a normal systolic function. Unexpectedly, a
large mass of 6.4x4.4cm was seen in the right ventricle that led to a high pressure in the right atrium
with a right-to-left shunting through a patent foramen ovale (figure 1). Further imaging consisted of a
thoracic and abdominal CT scan without signs of malignant lymphadenopathy or primary tumor.
Neither diagnostic pericardiocentesis nor thoracentesis showed malignant cells. After intense
discussions, the definite diagnostic was obtained by endomyocardial biopsy.
Histologically, a myocardial infiltration by a diffuse large B-cell lymphoma (DLBCL) was found. For
further staging, a bone marrow exam and a PET scan was performed. It confirmed the large tumor in
the right heart and some activity in a single adjacent lymph node. Testing for HIV was negative.
Symptoms started to improve after initiation of steroids and rituximab, a monoclonal anti-CD20
antibody . Treatment was continued with a modified R-CHOP regimen containing cyclophosphamide,
mitoxantrone, vincristine and prednisone. An early CT scan of the heart showed a tremendous
regression of the cardiac mass (figure 2), which was confirmed by a TEE four weeks later. After a total
of 6 cycles of chemotherapy, the patient's condition was stable and she was oligosymptomatic.
Primary malignant cardiac lymphoma are extremely rare in non-immunocompromised patients. They
occur less frequently than sarcoma and respond favourably to chemotherapy. Nevertheless, few
patients are desribed who obtain durable complete remissions.
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P377
Association of ECG abnormalities and incident heart failure events
Baris Gencer*, Javed Butler, Douglas Bauer, Reto Auer, Andreas Kalogeropoulos, Perdro MarquesVidal, William Applegate, Suzanne Satterfield, Tamara Harris, Anne Newman, Eric Vittinghoff, Nicolas
Rodondi
Geneva University Hospital (Genève, CH); Emory University (Atlanta, US); University of California
(San Francisco, US); Lausanne University Hospital (Lausanne, CH); Wake Forest University Baptist
Medical Center (Winston Salem, US); University of Tennessee Health Science Center (Memphis, US);
National Institute on Aging (Bethesda, US); University of Pittsburgh (Pittsburgh, US); Bern University
Hospital (Bern, CH)
Background: With the aging of the population, the heart failure (HF) incidence and prevalence trends
are expected to significantly worsen unless concentrated prevention efforts are undertaken. ECG
abnormalities are common in the elderly but data are limited for their association with HF risk.
Objective: To assess whether baseline ECG abnormalities or dynamic changes are associated with an
increased risk of HF.
Method: A prospective cohort study of 2915 participants aged 70 to 79 years without a preexisting HF
followed for a median period of 11.4 (IQR 7.0-11.7) years from the Health Aging and Body
Composition study. The Minnesota Code was used to define major and minor ECG abnormalities at
baseline and at 4-year. Main outcome measure was adjudicated incident HF events. Using Cox
models, the (1) the association between ECG abnormalities and incident HF and (2) incremental value
of adding ECG to the Health ABC HF Risk Score, was assessed.
Results: At baseline, 380 participants (13.0%) had minor and 620 (21.3%) had major ECG
abnormalities. During follow-up, 485 (16.6%) participants developed incident HF. After adjusting for
the eight clinical variables in the Health ABC HF Risk Score, the hazard ratio (HR) was 1.27 (95%
confidence interval [CI] 0.96-1.68) for minor and 1.99 (CI 1.61-2.44) for major ECG abnormalities (P
for trend <0.001) compared to no ECG abnormalities. The association did not change according to
presence of baseline CHD. At 4-year, 263 participants developed new and 549 had persistent
abnormalities and both were associated with increased HF risk (HR = 1.94, CI 1.38-2.72 for new and
HR=2.35, CI 1.82-3.02 for persistent compared to no ECG abnormalities). Baseline ECG correctly
reclassified 10.6% of overall participants across the categories of the Health ABC HF Risk Score.
Conclusion: Among older adults, baseline ECG abnormalities and changes in them over time are
common; both are associated with an increased risk of HF. Whether ECG should be incorporated in
routine screening of older adults should be evaluated in randomized controlled trials.
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P378
Development of an aorto-left atrial fistula in a patient with ankylosing
spondylitis
Vera König*, Raphael Jeker, Felix Schönrath, Walter H. Reinhart, Piero O. Bonetti
Kantonsspital Graubünden (Chur, CH); Universitätsspital (Zürich, CH)
Introduction: Ankylosing spondylitis (M. Bechterew) is a chronic inflammatory disease involving the
spine, but also other organs such as the heart, lungs, eyes, kidneys and aortic root (aortitis).
Involvement of the aortic root may lead to a thickening and dilation of the aortic wall and thickening
and retraction of the aortic cusps with subsequent aortic regurgitation. We report on a patient with
ankylosing spondylitis, who developed a fistula from the aortic root to the left atrium.
Case report: A 49-year-old man with advanced ankylosing spondylitis was admitted for an
echocardiographic control 18 months after mechanical aortic valve replacement and mitral valve
reconstruction for severe aortic regurgitation and moderate mitral regurgitation, respectively, which
were thought to be due to inflammation associated with ankylosing spondylitis. The patient reported a
worsening of his condition with increasing weakness. Transthoracal/transesophageal
echocardiography was suggestive for a supravalvular abscess on the posterior part of the aortic root
with an aorto-atrial fistula between the sinus valsalvae and the left atrium. Assuming infective
endocarditis, an empiric antibiotic treatment with rifampicin, gentamycin and vancomycin was started.
Blood cultures withdrawn before initiation of antibiotic therapy and a Quantiferon test remained
negative. Given the echocardiographic findings and the lack of improvement of his clinical condition,
the patient underwent urgent surgery including mechanical mitral valve replacement, replacement of
the mechanical aortic valve with graft-replacement of the ascending aorta and reconstruction of the
aorto-mitral transition zone with closure of the left atrial roof by a pericardial patch. Because all tissue
samples and cultures taken during surgery remained negative for bacterial infection, antibiotics were
stopped after a total of 4 weeks. Instead, assuming ankylosing spondylitis-associated aortitis, a
systemic corticosteroid therapy with 50 mg prednisolone daily was initiated, which led to rapid clinical
improvement. 2 months postoperatively, a therapy with Infliximab (Remicade®) was initiated.
Discussion: Clinically evident aortic root or valvular disease is observed in less than 20% of patients
with ankylosing spondylitis. To our knowledge, this is the first report an aorto-atrial fistula as a
complication of aortitis associated with ankylosing spondylitis.
P379
Improvements in quality of care for patients discharged after acute coronary
syndrome over the last ten years
Reto Auer, Baris Gencer*, Lorenz Räber, Roland Klingenberg, David Carballo, Sebastian Carballo,
David Nanchen, Jacques Cornuz, John-Paul Vader, Pierre Vogt, Peter Jüni, Christian Matter, Stephan
Windecker, Thomas Lüscher, François Mach, Nicolas Rodondi
University of California (San Francisco, US); Geneva University Hospital (Genève, CH); Bern
University Hospital (Bern, CH); Zürich University Hospital (Zürich, CH); Lausanne University Hospital
(Lausanne, CH)
Background: Adherence to guidelines is associated with improved outcomes of patients with acute
coronary syndrome (ACS). We aimed at determining the improvement in the rate of prescription of
recommended treatment at discharge over the last ten years, taking into account reasons for nonprescription, and the rate of attendance to cardiovascular rehabilitation(CR).
Methods: We measured the rate of recommended treatment at discharge, and attendance to CR
among 1260 patients hospitalized for ACS in 4 academic centers in Switzerland in 2009-2010.
Reasons for non-prescription were systematically collected according to guidelines. Data were
compared to 577 patients hospitalized in 1999 who had their medical charts reviewed for reasons for
non-prescription. We identified factors associated with attendance to CR using multivariable logistic
regression adjusted for clustering by center.
Results: Hundred percent of patients discharged in 2009-2010 were prescribed aspirin compared to
91% of those discharged in 1999(p<0.001). Prescription rates for beta-blockers increased from 81% to
96% (p<0.001) and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers for
patients with left ventricular ejection fractions <=40% rose from 80% to 100% (p<0.001). 61.5% of
patients attended CR. Older age, not having a ST-segment elevation myocardial infarction and
previous coronary heart disease were associated with decreased odds of CR(all p<0.05).
Conclusions: We found a marked increase in adherence to ACS guidelines for drug prescriptions over
the last 10 years among academic centers in Switzerland. Pre-specification of reasons for non131
prescription within clinical registries permits to identify remaining gaps in quality of care. However,
barriers to attendance to CR need to be further explored.
P380
Pulmonary embolism D-dimer testing and clinical judgment: a cautionary tale
Joana Barbosa*, Panagiotis Antiochos, Amir Jaff, Raffaella Craighero, Jérôme Burnand, Uwe
Schiemann
Hôpital Cantonal de Fribourg - Site de Riaz (Riaz, CH)
Introduction: Although a frequent and potentially severe pulmonary embolism (PE) remains difficult to
a rapidly and accurately diagnose. Plasmatic D-Dimer testing is commonly used in the evaluation of
possible PE in the emergency department sparing patients unnecessary radiation. As everything in
medicine, D-Dimer testing has limitations, which are essential to understand in our practice.
Case Report: A 72 years-old woman presented to our emergency department with complaints of
dyspnea class III/IV and a sharp chest pain radiating to both arms, neck and back for the preceding
24h. Personal history was notable for pulmonary embolism, a bladder carcinoma diagnosed three
years ago and active smoking with 30 pack years. An electrocardiogram showed sinus rhythm with a
Q wave in DIII. D-Dimers were within normal limits (363ng/ml) with a calculated modified Geneva
score revealing ``moderate PE risk``. The patient was hospitalized in our critical care unit for rhythmic
and clinical surveillance. A ``triple rule-out`` chest CT scan was undertaken and demonstrated multibilateral segmental pulmonary embolism, and coronary artery disease with significant left anterior
descending (LAD) stenosis. Treatment with low molecular weight heparin was started and the patient
underwent coronary angioplasty of her LAD and first marginal arteries.
Conclusion: Several major clinical models have been published and tested to determine patients’ pretest probability of PE. D-Dimer testing is considered an appropriate method for the exclusion of PE in
low to moderate risk patients where it shows a negative predictive value of 95.7%. Nevertheless,
definition of low-risk is not consensual. As in our case, clinical presentation of PE can be variable and
misleading. A negative D-dimer testing even in the context of a “moderate risk`` patient group can lead
to missing underlying PE which should be considered especially in cases where alternative diagnoses
are unlikely. As our case proves once again, laboratory values have to be interpreted in the light of
clinical data et clinical exam. More specifically in the case of PE, an approach of keeping a high index
of suspicion for this eventually lethal disease plays a paramount role in patient care.
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P381
A case series of omalizumab in non-allergic (intrinsic), eosinophilic asthma
Lukas Jörg-Walther*, Carolina Diaz, Max Pfenninger, Werner Pichler, Arthur Helbling
Inselspital, University Hospital Bern (Bern, CH); Praxis M. Pfenninger (Olten, CH)
Background: Omalizumab is a humanized monoclonal antibody, that binds selectively to free IgE in
plasma and inhibits its binding to Fc-IgE receptors on the surface of mast cells and basophils. This
results in a reduced Fc-IgE receptor level, which may be related to lower mast cell stimulation. Today
it is approved for the treatment of moderate to severe persistent allergic asthma. In contrast, there are
only few reports concerning the effect of this recombinant antibody in non-allergic (intrinsic) asthma.
Objectives: To evaluate the effect of omalizumab in patients with non-allergic asthma.
Methods: We report a case series of 4 patients with the diagnosis of severe uncontrolled intrinsic
asthma, median age of 60.5 years (2 females), 3 in the context of a aspirin exacerbated respiratory
disease (AERD). All patients were treated with omalizumab, during the past 3 years with dosing and
treatment intervals according to the manufacturers’ recommendations.
Results: After the first 4 months with omalizumab, there was a significant improvement in median
forced expiratory volume in one second (FEV1, expressed in % of predicted value) [+ 40.8 %], disease
control, number of exacerbations and use of basal and rescue medication. One of our patients with a
positive inhalative provocation test with L-Acetylic acid (cumulative dose: 25 mg) showed a negative
provocation (cumulative dose: 100mg) 4 months after initiation of omalizumab treatment. No adverse
events occurred.
Conclusion: Some patients with severe asthma associated with AERD and polyposis nasi without
sensitization to any inhaled allergens cannot be controlled with standard asthma treatment. Therefore
recurrent or prolonged use of systemic and inhaled corticosteroids including leukotriene antagonists is
required. These patients representing a subgroup with AERD and an eosinophile-dominated airway
inflammation may benefit from treatment with anti-IgE. Further studies are needed to confirm these
findings.
P382
L’iléus biliaire, cause rare de l’ileus mécanique.
Mireille Nsangu Mampasi*
Hôpital Fribourgeois . (Riaz, CH)
L’iléus biliaire, cause rare de l’ileus mécanique.
Nsangu Mampasi M., Leukefack JB., Théodoloz C., Schiemann U., Mihai-Christian I.
Service de médecine, service de chirurgie, service de radiologie, Hôpital fribourgeois Riaz
Présentation du cas clinique : Il s’agit d’une patiente de 90 ans, sans antécédent chirurgical, qui
consulte les urgences pour des vomissements verdâtres, depuis la veille, accompagnée des 2
épisodes de malaise sans perte de connaissance. Elle signale des constipations alternant avec des
diarrhées post lavement depuis environ 2 semaines. A l’examen clinique, l’abdomen est légèrement
ballonné, indolore avec des bruits abdominaux. Le bilan biologique révèle un discret syndrome
inflammatoire avec la C- protéine réactive à 39 mg/L, une leucocytose à 12,7 G/L, les enzymes
hépatiques normales. La radiographie de l’abdomen à vide montre quelques anses grêles
moyennement dilatées, sans niveau hydro-aérique, avec un gros calcul dans la vésicule biliaire.
L’Oeso-gastro-duodénoscopie réalisée est peu contributive, car elle est interrompue à cause d’une
rétention alimentaire qui provoque un vomissement avec broncho- aspiration modérée. La
tomodensitométrie abdominale montre un iléus grêle biliaire avec une vésicule biliaire en porcelaine
fistulisant dans le duodénum avec la présence d’un gros calcul calcifié au niveau de l’iléon proximal.
Une entérotomie est pratiquée par laparotomie avec extraction des 3 calculs au niveau de l’iléon
proximal respectivement de 3,5 cm, 1,5 cm et 1 cm de diamètre, étalés sur une longueur 15 cm.
L’évolution clinque est favorable avec la reprise du transit intestinal au sixième jour post -opératoire.
Conclusion : L’iléus biliaire est une occlusion intestinale rare, lié au passage d’un calcul biliaire dans
l’intestin, le plus souvent à travers une fistule cholécysto-duodenale( rarement une fistule cholécystocolique ou gastrique) , soit par migration endo-luminale d’un calcul biliaire , soit après une
cholécystectomie , ou lors d’une sphincterotomie endoscopique. Le diagnostic doit être évoqué devant
toute occlusion intestinale mécanique chez la personne âgée (25 % à partir de 70 ans). Le diagnostic
souvent tardif se fait radiologiquement par la triade de RIGLER caractérisé par l’aérobilie,
l’obstruction de l’intestin grêle et la localisation ectopique des calculs biliaires (le plus souvent dans la
fosse iliaque droite). Le traitement est essentiellement chirurgical (entérotomie avec / ou sans
cholecystectomie).
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P383
Long diagnostic delay in Crohn’s disease is associated with a complicated
disease course and increased operation rate
Stephan Vavricka*, Gerhard Rogler, Ekaterina Safroneeva, Alain Schoepfer
Stadtspital Triemli (Zürich, CH); Universitätsspital (Zürich, CH); CHUV (Lausanne, CH)
Background and Aims: The impact of diagnostic delay (a period from appearance of first symptoms to
diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of
diagnostic delay affects disease outcome.
Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university
centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence
of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery at distinct intervals after
CD diagnosis (0 - < 2, 2 - < 6, >= 6 years) were compared for groups of patients with different length
of diagnostic delay.
Results: The data from a group of 200 CD patients with long diagnostic delay (> 24 months, 76th 100th percentile) were compared to those from a group of 461 patients with a short diagnostic delay
(within 9 months, 1st - 50th percentile). Treatment regimens did not differ between the two groups.
Two years following diagnosis, patients with long diagnostic delay presented more frequently with
bowel stenoses (25% vs. 13.1%, p = 0.044), internal fistulas (10% vs. 2%, p = 0.018), perianal fistulas
(20% vs. 8.1%, p = 0.023) and more frequently underwent intestinal surgery (15% vs. 5.1%, p = 0.024)
than patients with short diagnostic delay. Intestinal surgery was also more frequently performed >= 6
years after diagnosis in a group with long diagnostic delay (56.2% vs. 42.3%, p = 0.005) when
compared to a group with short diagnostic delay.
Conclusions: Long diagnostic delay is associated with the development of increased bowel damage,
necessitating increased number of operations in the years following CD diagnosis. Efforts should be
undertaken to shorten the diagnostic delay.
P384
Secondary prevention after acute coronary syndromes in hospitals with and
without coronary intervention facilities in the French-speaking part of
Switzerland
Joris Welker*, Reto Auer, Baris Gencer, Jacquez Cornuz, Pierre F. Keller, Pierre Vogt, Christian M.
Matter, Stefan Windecker, Thomas F. Lüscher, François Mach, Nicolas Rodondi, David Nanchen
University of Lausanne (Lausanne, CH); UCSF, San Francisco (Californien, US); University Hospital
Geneva (Genève, CH); University Hospital, Lausanne (Lausanne, CH); University Hospital Zurich
(Zürich, CH); University Hospital Bern (Bern, CH); University of Bern (Bern, CH)
Introduction: The quality of care for patients with acute coronary syndromes (ACS) might differ
according to the type of hospital. Particularly few data exist about secondary prevention for patients
with ACS discharged from hospitals without percutaneous coronary intervention (PCI) facilities. We
aimed to assess and compare secondary prevention in patients with ACS at hospital discharge
according to the type of hospital defined by the availability of PCI facilities.
Methods: We studied 353 men and women with ACS underwent coronary angiography with or without
PCI between July 10th 2009 and November 3rd 2010 in five peripheral hospitals without PCI facilities
and one referring hospital with PCI in the French-speaking part of Switzerland. All participants were
either discharged from the referring hospital or transferred within one day after coronary angiography
to one of the five peripheral hospitals without PCI facilities and discharged from there. All clinical
information was abstracted at baseline and at discharge from medical records in each hospital. We
recorded the prescription of recommended secondary prevention medication or mentioned contraindications, including aspirin, statin, beta-blocker and angiotensin-converting enzyme inhibitor (ACE)
or angiotensin-II receptors blocker (ARB), inclusion in cardiac rehabilitation program and in-hospital
smoking cessation intervention or mentioned contraindications.
Results: Among 353 ACS patients, 262 (74.2%) were discharged from the hospital with PCI facilities,
and 91 (25.8%) from hospitals without PCI facilities. The mean age (SD) was 64.1 (12.2) years and
75.6% were men. The prescription of drugs for secondary prevention was high at hospitals with and
without PCI facilities, summing up to 86.3% and 84.6%, respectively (p=0.698). By contrast, only
51.6% of ACS patients in the hospital with PCI facilities and 59.3% in hospitals without PCI were
enrolled in a cardiac rehabilitation program (see Figure). Higher age, low education level, and a history
134
of preexisting cardiac disease were negatively associated with cardiac rehabilitation enrollment in both
types of hospital. In-hospital smoking cessation interventions were performed in 31.1% of smokers
and exclusively at the referring hospital with PCI facilities.
Conclusions: We found no difference in a high prescription of drugs for secondary prevention after
ACS in patients discharged from hospitals with or without PCI facilities. However, there is room for
improvement given the low rates of participation in cardiac rehabilitation programs or in-hospital
smoking cessation counseling in the French-speaking part of Switzerland.
135
Cardiologie / Pneumologie / Gastroentérologie 2
P385
Effekte der pneumologischen Rehabilitation im Hochgebirge: Ergebnisse der
Einjahreskatamnese der Davoser-Outcome-Studie (DOS)
Udo Kaiser*, Rüdiger Nübling, Jürgen Schmidt, David Kriz
Hochgebirgsklinik Davos (Davos Wolfgang, CH); GFQG (Karlsruhe, DE)
Einleitung: Pneumologische / dermatologische Erkrankungen haben eine hohe Prävalenz und führen
bei den Betroffenen und auch der Volkswirtschaft zu hohen Belastungen. Zur umfassenden
Behandlung gehören neben der kurativen Versorgung rehabilitative Angebote, die vorwiegend
wohnortfern durchgeführt werden. Obwohl der Nutzen dieser Behandlungen heute als nachgewiesen
gilt (Kaiser 1994, 2003), werden die Angebote nicht in notwendigem Umfang genutzt.
Methode: Im Rahmen der Davoser-Outcome-Studie (DOS; vgl. Kaiser et al., 2011), einer mehrere
Messzeit-punkte (Aufnahme, Entlassung, 6-, 12-, 24-Monatskatamnese) und Datenquellen (Patienten,
Klinikärzte, ambulante Ärzte) umfassenden Programmevaluationsstudie, wurden somatische,
funktionale, psychosoziale, behandlungsbezogene, soziodemographische und
gesundheitsökonomische Parameter erhoben. Hierbei kamen patientenseitig u.a. HADS, FKV-LIS,
SF-12, IRES-24, SIBAR, PAREMO, SGQR, FLQZ, ZUF8, arztseitig u.a. GAF, BSS, SCORAD, PASI,
FEV-1, M-Score zum Einsatz. Dane-ben wurden in Adaption Teilaspekte aus Fragbögen der
Arbeitsgruppe aus früheren Studien (z.B. EQUA, Schmidt et al. 2003, Davoser Reha-Studie I und II,
Kaiser, 1994, 2003) integriert. Ziel der Studie ist u.a. die Abbildung kurz-, mittel- und langfristiger
Behandlungseffekte. Die 12-Monatskatamnese wurde im August 2012 abgeschlossen.
Ergebnis: Es liegen n=892 (Aufnahmemessung-A) Patientenfragebögen vor. Die Rücklaufquote für
K12 beträgt 70%. Es handelt sich um 45% Männer und 55% Frauen mit einem Durchschnittsalter von
49.3 Jahren (SD 13.1 Jahre) mit vorwiegend pneumologischen Erkrankungen (71%) bei chronischem
Krankheits-verlauf (80% Krankheitsdauer > 10 Jahre) und ausgeprägter Multimorbidität (MW 2.54
Diagnosen).
Tab. 1 zeigt im Vergleich Aufnahme bis K12 das Ausmaß der Veränderungen bei ausgewählten Outcomeparametern mit mittleren bis hohen Effektstärken:
Schlussfolgerung: Die Teilergebnisse der Einjahreskatamnese belegen die Effekte stationärer
Behandlungen in der Hochgebirgsklinik Davos in relevanten Outcomeparametern. In den nächsten
Auswertungsschritten wird versucht, durch differenzielle Auswertungsstrategien den Nutzen für
unterschiedliche Subgruppen bzw. Problemkonstellationen näher zu analysieren. Schon heute kann
aus den Ergebnissen abgeleitet werden, dass Massnahmen dieser Art gezielter, früher und häufiger
zum Einsatz kommen sollten. Nübling, 2010).
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P386
Asthma Monitor: a free application for the diagnosis and management of
asthma
Nebal Abu Hussein*, Katharina Gessler, Esther Helen Steveling, Sabrina Maier, Claudia Gregoriano,
Stefania Zogg, Selina Dürr, Emanuel Hediger, David Miedinger, Jörg Daniel Leuppi
Universitätsspital Basel (Basel, CH); Fachhochschule Nordwestschweiz (Windisch, CH)
Recording peak flow (PEF) is an easy and objective method to detect changes of lung function in
asthmatic individuals. PEF, respiratory symptoms and the asthma control test (ACT) results can be
used to determine asthma control status and their longitudinal changes. This can support the
assessment of treatment response. Monitoring of these parameters might provide a better control and
management of asthma. However, to achieve this graphical interpretation and calculations of indices,
a daytime variability calculation is needed, which is not possible with handwritten asthma diaries.
The Asthma Monitor application is a free and easy in use program, designed for Android smartphones
and tablet computers. It allows patients to monitor their asthma easily by recording their PEF,
symptoms, emergency medication and activities on a daily basis, in addition to the asthma control
status using the ACT-test. PEF limit values can be entered to help the instructed patient to selfmanage her/his asthma. The recorded data can be displayed as graphs on screen, converted into a
.pdf-document or stored as raw database file and sent to the treating physician.
This application is an easy in use tool that might help asthmatic patients to better self-manage their
asthma. It can be used to diagnose lung function variability in previously undiagnosed asthma or in
situations, where the effect of treatment changes needs to be evaluated.
P387
Single-balloon assisted colonoscopy: success rates in patients with previous
incomplete colonoscopy
Gian-Marco Semadeni*, Christa Meyenberger, Remus Frei
Kantonsspital St. Gallen (St. Gallen, CH)
Background: Cecal or ileal intubation is a well recognized measure of colonoscopy quality.
Infrequently, a complete examination is unsuccessful with the standard technique. Extensive
diverticulosis, history of abdominal surgery, female gender und low body mass index are factors
associated with incomplete colonoscopy. The use of single-balloon overtube assisted technique in
these situations has only been studied sparsely.
Methods: In a prospective single-center study, single-balloon overtube assisted colonoscopy was
performed in patients with previous incomplete colonoscopy in standard technique. The single-balloon
enteroscope SIF-Q180 of Olympus® and fluoroscopy were used.
Results: Between February 2008 and January 2013, 53 consecutive patients (mean age 67y, range
38-87, 32 females, 21 males,) were examined in single-balloon overtube assisted technique. The
cecum was reached in 96% (51 of 53). The passage of the sigmoid colon with the SIF-Q180
endoscope was not possible in two cases: in one female patient with peritoneal carcinosis and in one
male patient with extensive diverticulosis, both with a fixed, looped sigmoid colon.
There were no pathologic findings in four patients (8%), twenty-nine patients (55%) showed a marked
diverticulosis. In twenty-one patients (40%), there were one or several polyps found, all of which could
be removed. Other findings were Crohn’s colitis, diversion colitis, angiodysplasia in the ascending
colon and adenocarcinoma in the sigmoid colon.
Two complications (4%) occurred. There was one single mucosal defect as a consequence of a
polypectomy, which was treated successfully by clipping and prophylactic antibiotic therapy. A second
patient suffered from abdominal pain and hematochezia after a diagnostic single-balloon colonoscopy
without intervention. A perforation was excluded by CT scan. She had to be admitted in the hospital
for surveillance for four days.
Conclusions: Colonoscopy in single-balloon overtube assisted technique is a safe and effective
procedure in patients with a previous incomplete or failed standard colonoscopy.
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P388
Daily physical activity across the new combined COPD risk groups
Stefanie Zogg*, Selina Dürr, Sabrina Maier, Esther Helen Steveling, David Miedinger, Jörg Daniel
Leuppi
Background: To more precisely evaluate the impact of COPD, a combination of symptom estimation
and spirometer-based classification and/or risk of exacerbation is recommended. Symptoms are
assessed by COPD assessment test (CAT) or Modified Medical Research Council (mMRC) dyspnea
scale. Since patients with COPD are known to practice a sedentary lifestyle, the aim of the present
study was to examine physical activity (PA) across COPD risk groups based on CAT and mMRC.
Methods: In 2011, patients with stable COPD were recruited at the University Hospital Basel.
Participants were divided into the 4 risk groups A to D according to the revised GOLD guidelines of
December 2011 (Figure 1). Based on CAT, the distribution of patients was A (n=27), B (n=36), C (n=1)
and D (n=14). Using mMRC, patients were classified as A (n=10), B (n=47), C (n=0) and D (n=14).
Risk groups C and D were combined for statistical analysis. PA was measured by the SenseWear Mini
Armband on 7 consecutive days. Daily number of steps, time spent in PA above 3.0 METs (PA3),
activity-based energy expenditure (AEE) and PA level (PAL) were analysed.
Results: Complete data were available from 78 patients aged 44 to 90 (57.7% male, age 66.6+/9.7yrs, BMI 25.8+/-5.5kg/m^2, steps 4783.6+/-3337.6, PA3 94.6+/-84.9min, AEE 443.6+/-383.1cal,
PAL 1.3+/-0.3METs). The interrater agreement between CAT- and mMRC-based classification was
found to be k=0.73, indicating a good agreement. Based on CAT, steps (p=0.003) and AEE (p=0.007)
were shown to be significantly higher in COPD risk group A compared to B. In contrast, all PA
parameters, steps (p=0.015), PA3 (p=0.001), AEE (p<0.001) and PAL (p=0.006), were found to be
reduced in risk group B compared to A, using mMRC.
Conclusion: This study provides evidence that daily PA is significantly impaired in more severe COPD
risk groups compared to mild one. Moreover, mMRC dyspnea scale focusing on the impact of
dyspnea might be a good and shorter alternative to commonly used CAT.
138
P389
Procalcitonin-guided antibiotic therapy in patients with congestive heart failure
and suspicion of lower respiratory tract infection: results from a randomized
trial
Alexander Kutz*, Eva Marianne Grolimund, Sebastian Haubitz, Désirée Demann, Alaadin Vögeli,
Mirjam Christ-Crain, Robert Thomann, Werner Zimmerli, Claus Hoess, Christoph Henzen, Beat Müller,
Philipp Schuetz
Kantonsspital Aarau (Aarau, CH); Universitätsspital Basel (Basel, CH); Bürgerspital Solothurn
(Solothurn, CH); Kantonsspital Liestal (Liestal, CH); Kantonsspital Münsterlingen (Münsterlingen, CH);
Kantonsspital Luzern (Luzern, CH)
Introduction: Differentiation of acute heart failure from infection in patients with respiratory symptoms
and a history of congestive heart failure (CHF) is challenging due to overlap of clinical symptoms and
X-ray findings. The BACH Study found higher mortality rates if patients presenting with dyspnea were
treated with antibiotics and their procalcitonin (PCT) levels was low indicating absence of bacterial
infection. Yet, the BACH study was observational and causal inference cannot be drawn. Herein, we
analyzed the effects of PCT guided antibiotic stewardship in CHF patients from a previous trial
(ProHOSP).
Methods: This is a secondary analysis of a previous randomized trial of adult emergency department
(ED) patients with respiratory symptoms and a history of CHF. Patients were randomized to
administration of antibiotics based on a PCT algorithm (PCT group) or standard guidelines without
knowledge of PCT levels (control group). The primary endpoint of this analysis is the risk of adverse
outcome defined as death or intensive care unit (ICU) admission within 30 days after ED admission.
Results: A total of 233 patients met the inclusion criteria with 116 in the PCT guided group and 117 in
the control group (Table 1). In the subgroup of patients with low initial PCT levels <0.25 µg/L (n=110),
PCT guided patients had a significant reduction in antibiotic exposure (mean of 3.7 vs 6.5 days,
difference -2.8 [95%CI -4.4, -1.2], p<0.001). Furthermore PCT guided patients had a significant lower
risk for death and ICU admission (4% vs 20%, odds ratio 6.0 [1.3, 28.2], p=0.02) (Figure 1).
Discussion: In CHF patients with suspicion of respiratory infection, use of a PCT protocol resulted in a
significant decrease of antibiotic exposure and significantly improved outcomes in patients with low
PCT levels indicating absence of bacterial infection. Whether inadequate antibiotic therapy in these
CHF patients requiring diuretic treatment explains this difference in clinical outcomes needs
verification.
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P390
Impact of pre-hospital electrocardiography on ECG-to-balloon time in patients
with ST elevation myocardial infarction in a rural area
Georgia Mitropoulou*, Cristoph Kaiser, Serge Diotte, Jean-Luc Crevoisier
Hôpital de Delémont (Delémont, CH); Universitätsspital Basel (Basel, CH)
Introduction: Primary percutaneous coronary intervention is the preferred reperfusion strategy in
patients presenting a ST elevation myocardial infarction and should be performed within 90 minutes
from first medical contact, in order to improve patient outcome. This study aims to assess the impact
on ECG-to-balloon time, of pre-hospital diagnosis and direct referral to a PCI capable centre, when
compared to conventional triage through a regional hospital.
Method: Retrospective comparison of ECG-to-balloon times in patients with acute STEMI diagnosed
with pre-hospital electrocardiography and transferred to a PCI centre, with patients referred initially to
the Hospital of Delémont.
Results: From April 2010 through March 2012, a total of 219 patients received a pre-hospital 12 lead
ECG, transmitted by the EMS personnel in the field to a cardiologist, with a final diagnosis of STEMI in
24 patients. Of the latter, 16 patients were directly referred to a PCI centre, bypassing the emergency
department. During the same period, 77 patients were admitted to our emergency department with
final diagnosis of STEMI and 44 of them were urgently transferred to a PCI centre. The two groups
presented no significant difference in baseline characteristics (average age 66.56 years versus 63.6
years, p=0.41, percentage of female patients 37.5% versus 27.2%, p=0.44). The mean ECG-toballoon time decreased significantly in patients with pre-hospital ECG compared to patients diagnosed
with initial in-hospital ECG (112 min versus 145 min, p=0.021). Hazard ratio for in-hospital diagnosis
was 1.29, with confidence intervals 95% (1.04 to 1.60).
Conclusion: In patients presenting an acute ST elevation myocardial infarction, residing in rural areas
away from PCI capable centres, pre-hospital ECG and triage to appropriate centres helps reduce
system delay. More efforts need to be undertaken in order to meet the target of time to reperfusion of
less than 90 minutes.
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P391
Congestive heart failure related to antifungal therapy with itraconazole:
illustrative case report
René Vollenbroich*, Daniel Weilenmann
Kantonsspital St. Gallen (St. Gallen, CH)
Introduction: Only a few cases of congestive heart failure (CHF) suggesting the association with the
use of itraconazole, a synthetic antifungal agent, have been reported to the United States FDA
Adverse Event Reporting System. To the best of our knowledge, this is the first case report describing
this adverse effect in Europe.
Case Report: In June 2006, a 60 year-old man was admitted to the Kantonsspital St. Gallen for the
treatment of an acute myocardial infarction. Early percutaneous coronary intervention revealed a
severe three vessel coronary artery disease with a significantly decreased left ventricular ejection
fraction of 30%, and resulted in a good angiographic result. The patient underwent primary
prophylactic ICD implantation thereafter. During regular six-month checkups, his condition proved to
be stable under antiplatelet, beta blocker, ACE inhibitor, and diuretic therapy. Statin therapy was
refused by the patient.
In September 2012, he was diagnosed with dermatomycosis of his right lower leg and was
administered oral itraconazole (200mg daily) for 1.5 months. During this period, the patient’s dyspnea
worsened, his diuretic intake increased, and he stopped itraconazole therapy on his own. In early
December 2012, transthoracic echocardiography revealed an increase in systolic pulmonary artery
pressure from 35 to 65 mmHg. In addition, brain natriuretic peptide and serum creatinine increased
(BNP: 304 to 579 ng/l, SCR: 99 to 128 µmol/l), as did OptiVol® measurements. In January 2013, 1.5
months after stopping the antifungal treatment, all these parameters significantly improved again.
Discussion: Although labeling of itraconazole has been changed to alert health care professionals to
adverse cardiovascular events, the possible coherence is still controversially discussed. However, in
our case the patient’s stable cardiac situation for many years as well as the unchanged medical
therapy prior to the intake of itraconazole, closely suggest an underlying relationship. This suspicion is
supported by the fact that there has been a close temporal relation of antifungal treatment and
essential parameters of CHF.
Conclusion: Despite its undeniable efficiency in antifungal treatment, adverse effects of itraconazole to
the cardiovascular system might be more common than currently suspected. More research is needed
to fully understand the effects of triazoles in particular to patients who are at risk of cardiac
decompensation.
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P392
Cough and abdominal pain: pancreatitis due to codeine
Lukas Brylski*, Martin Schelling
Introduction: Drug-induced acute pancreatitis can be caused by a plurality of drugs. Codeine is an
opiate which is commonly used for its analgesic and antitussive effects. Although it is a rare side effect
and only a few cases have been reported, codeine ingestion provoked a pancreatitis in some persons.
We report on a patient with pancreatitis after codeine ingestion and positive reexposition.
Case report: A 33-year old women at our emergency department, complained of crampy abdominal
pain. The patient suffered from upper respiratory tract infection and concomitant dry cough. She had
taken a codeine-containing antitussive (Resyl Plus) for symptomatic treatment. Onset of abdominal
pain was 90 min after ingestion. There was no history of alcohol use or abdominal trauma. She had
undergone cholecystectomy six years previously. Physical examination was normal. Serum lipase was
elevated at 85 U/l. Liver function tests were moderately abnormal: AST 86 U/l, ALT 53 U/l. Her
symptoms resolved and she was discharged. A mild pancreatitis was diagnosed. Seven months later,
the patient again took a codeine-containing compound (Codein 50mg) for similar respiratory
symptoms and developed a belt like epigastric pain. Laboratory tests were comparable to the first
presentation. Physical examination again was normal. A diagnosis of beginning pancreatitis due to
codeine ingestion was made and the patient was advised to abstain from codeine. After overnight
observation and conservative treatment, the patient recovered fully. Therefore no further radiologic
evaluation has been made to confirm the diagnosis.
Discussion: The presented patient had two events of acute pancreatitis. In both cases she had taken
codeine before abdominal pain started. After exclusion of other possible causes and because of a
close temporal relationship between drug ingestion and onset of symptoms, we believe that codeine
was the trigger for the pancreatitis. As pathophysiological mechanism it has been suggested that
codeine causes rapid but transient spasm of the sphincter Oddi. Laboratory studies have shown that
codeine may cause a mild, transient hyperamylasemia. Furthermore our patient had a previous
cholecystectomy, which is a risk factor for secondary sphincter dysfunction.
Conclusion: This case demonstrates that ingestion of even low doses of codeine may cause acute
pancreatitis. Codeine should be considered as a possible cause of acute pancreatitis, especially in
cholecystectomized patients.
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Postersession SFGG - Session des posters SPSG
P393
Length of stay of elderly patients in a palliative care unit: influence of the day
of admission
Martin Schneider*
HUG (Collonge-Bellerive, CH)
Background: A stay in a palliative care unit should be well timed to allow rational use of resources.
Many factors influence the length of stay, but little is known about the role of the day of admission,
working day or weekend.
Methods: The length of stay of all patients admitted to the palliative care unit of the University
hospitals of Geneva between 1 December 2011 and 31 May 2012 was prospectively recorded. The
data were completed by demographic and medical information.
A Cox regression model was developed for the length of stay of patients over 65 years, taking into
account sex, diagnosis of cancer and the admission on a working or weekend day. Admissions on
holidays were coded as weekend.
Results: During the observation period, 116 (87%) patients over 65 years were admitted on working
days and 18 (13%) on the weekend. There were 74 (55%) women and 60 (45%) men; mean age was
81 (standard deviation [SD] 8) years.
Patients admitted on working days stayed on average for 20 (SD 20) days, those admitted on the
weekend 13 (SD 18) days. Patients admitted on a weekend had shorter stays with a hazard rate of
1.76 (95% confidence interval 1.03 – 3.00) in the Cox regression controlling for sex and presence of
cancer.
Conclusion: In this study, patients over 65 years admitted on a weekend had shorter stays than those
admitted on working days. This difference could be due to unplanned emergency hospitalisations. A
better anticipation of the course of the disease and outpatient palliative care offers might reduce the
need for unplanned hospitalisations.
P394
Geriatric inpatient rehabilitation in periprosthetic femoral fractures: outcome
compared to proximal femoral fractures
Matthias Frank*, Annika Lanz, Norbert Suhm, Christian Ritter, Yvonne Zysset, Eveline
Nonnenmacher, Martin Conzelmann
Felix Platter Spital (Basel, CH); Universitätsspital (Basel, CH)
143
Background: Periprosthetic femoral fractures are increasingly observed in recent years. Prolonged
periods of reduced weight-bearing are typically needed postoperatively. We wanted to know if long
immobilization and hospital stay affected the outcome in these patients.
Methods: We retrospectively studied all patients entering geriatric inpatient rehabilitation with a
diagnosis of periprosthetic femoral fracture between January 2011 and May 2012. The control group
consisted of all patients admitted after surgery for a proximal femoral fracture (pertrochanteric or
femoral neck). Baseline data included sociodemographic variables and the results of the geratric
assessment on admission. Data on medical and surgical complications were extracted from the
medical records.
Results: 16 patients were identified. There were 109 patients in the control group. 10 patients were
classified as B, 2 as A and 1 as C according to the Vancouver classification. 3 patients had distal
femoral fractures next to a knee prosthesis. Two patients were treated conservatively, 7 patients were
stabilized with an osteosynthesis (less invasive stabilizing system LISS), 7 were treated with a revision
of the femoral shaft. There were no significant differences in the baseline variables and assessment
between the groups (68.8 vs. 69.7% female patients, age 84.0±8.6 vs. 81.9±9.5 years, Barthel index
46.8±24.3 vs. 46.1±17.1, MMSE 23.9±7.9 vs. 23.1±5.9). Complications during inpatient rehabilitation
were similar between the groups. 68.8% of patients in both groups could be discharged home. No
differences in outcome could be detcted (similar gain in Barthel index, gait velocity, Tinetti test).
Patients with periprosthetic fractures stayed significantly longer in rehabilitation (50.8±19.2 vs.
32.4±17.2 days, p<0.001).
Conclusion: Periprosthetic femoral fractures are a specific subgroup of geriatric fracture patients. In
our small sample, they were comparable to proximal femoral fractures in terms of demographic
characteristics, baseline assessment and rehabilitation outcome. However, rehabilitation stays were
significantly longer due to delayed weight-bearing.
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P395
Are we adhering to current guidelines for blood transfusion in a Swiss
hospital?
Bernard Surial*, Esther Bächli, Andreas Burkhart
Spital Uster (Uster, CH)
Introduction: Transfusion practices vary widely. One of the problems is the lack of guidelines
implemented in hospitals. The optimal use should involve administering enough RBCs to maximize
clinical outcomes while avoiding unnecessary transfusions that increase costs and potential harm. The
latest guidelines 1 recommends adhering to a restrictive (Hb 7-8g/dl) transfusion strategy in
hospitalized, stable patients compared with a more liberal strategy.
Method: We registered RBC transfusions during eleven month and the hemoglobin level before
transfusion in our hospital. We compared the hemoglobin levels before RBC transfusion between
different wards (for instance Internal Medicine, Surgery, Intensive care unit (ICU), Emergency room
(ER) and Gynecology) using ANOVA analysis. The transfusion rates of the Clinic of Internal Medicine
were subdivided into the following groups: Oncology, Internal Ward and Ambulatory.
Result: In total 1514 RBC transfusions were performed. In 739 cases the hemoglobin level was
known. The mean level of hemoglobin (MLH) was 7,69g/dl. It showed a significant difference (p:
<0,0001) between the MLH before RBC transfusion between the departments and their subgroups.
The Gynecology (MLH: 7,44g/dl), the Internal Ward (MLH: 7,42g/dl) and the Oncology (MLH: 7,46g/dl)
had the lowest MLH compared to the Surgery (MLH: 7,85g/dl), ICU (MLH: 7,83g/dl) and ER (MLH:
7,80g/dl). The highest MLH was measured at the Ambulatory (MLH: 7,91g/dl).
Conclusion: All the wards in our analysis are following the current guidelines with their transfusion
strategies. At the same time, we were able to detect significant differences between wards. A likely
explanation for this finding is because of the characteristics of patient groups. Lack of data about
indications for transfusion of RBC limits the reach of our results at the moment.
1 Guidelines of the American Association of Blood Bank in 2012
P396
Hemiparesis and epileptic seizure after percutaneous coronary intervention
misdiagnosed as a subarachnoidal haemorrhage
Dragan Despotovic*, Raphael Jeker, Ladina Signorell, Thomas Böhm, Alexander Rieke
Case report: A 73-year-old man with known coronary heart disease with status after 3-fold coronary
artery bypass-operation and multiple cardiovascular risk factors such as arterial hypertension,
hypercholesterolemia, diabetes mellitus and nicotine abuse presented with acute chest pain irradiated
to the left arm. We diagnosed an acute NSTEMI with indication of a percoutaneous cornonary
intervention (PCI) with stenting. Three hours after the intervention the patient developped a
hemiparesis of the left-sided extremities. The computer tomography scan of the brain without contrast
media showed a brain edema on the right side and a hyperdense zone in the subarachnoid space
which was consistent with an acute subarachnoid hemorrhage (Fig. 1) and no thrombolytic therapy
was performed. Some hours later the patient had a focal epileptic seizure and he was treated with
antiepileptic drugs. At the ward the clinical signs didn’t match with the radiologic findings and we
performed a magnetic resonance tomography. A subarachnoidal hemorrhage was excluded, but a
small ischemic area in the zone of the right-sided corona radiata was discovered (Fig. 2).
Conclusions: We concluded the left sided hemiparesis was related to an acute ischemic stroke at the
time of the PCI, which caused a dysfunction of the blood-brain barrier. This enabled the outflow of
contrast media which was injected during the PCI. The hyperdense zone in the subarachnoidal space,
detected in the CT, was contrast media and not blood. Also the epileptic seizure must be considered
as symptomatic seizure of the stroke and the perifocal edema. In the further evaluation the patient
showed a complete recovery of the neurological symptoms. Finally this case report allows the
conclusion that clinical and radiological findings must not necessarily suit each other. In doubt the
clinical findings have a higher relevance and must therefore be judged as decisive factor in terms of
further diagnostic measures and final diagnosis.
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P397
Was there something in the soup? Differential diagnosis of increased
methoxytyramine
Claudine Meindl-Fridez*, Till Hauffe, Urs Schwarz, Markus Schneemann, Eric Grouzmann, Paolo
Suter
UniversitätsSpital Zürich (Zürich, CH); Centre hospitalier universitaire vaudois (Lausanne, CH)
Introduction: A 48 year old man was admitted to our emergency department with a hypertensive
emergency showing blood pressure up to 230/130mmHg. He was diagnosed with a posterior
reversible encephalopathy syndrome (PRES, see poster by T. Hauffe et al.). Secondary hypertension
(i.e., renal artery stenosis or primary hyperaldosteronism) was ruled out by corresponding
investigations. However, we found increased levels of (free and total) plasma normetanephrine and
methoxytyramine (MT) and its precursor dopamine (see Table 1). The MT remained elevated in followup visits of the patient despite an adequate hypertension therapy and well-controlled blood pressure.
According to the patient, the hypertensive emergency occurred immediately after a Zen-meditation
and subsequent consumption of a traditional genmai soup. An increased concentration of MT was
identified in the soup by chromatography.
Background: MT is the methoxylated product of dopamine by catechol-O-methyltransferase. MT is
found in dopamine-producing paragangliomas and is an independent marker of metastatic
pheochromocytomas. Other important differential diagnoses of increased MT are: Parkinson
therapeutic agents (L-DOPA), biogenic amines in food (e.g., nuts, cheese, tomatoes, chocolate), and
ingestion of certain cactuses (e.g., trichocereus pachanoi (San Pedro cactus), lophophora williamsii
(Peyote)). Slices of dried trichocereus are advertised in the internet. They may be consumed in
different ways (e.g., as ingredient in mind-expanding hallucinogenic soups). Table 1 summarizes the
patient’s catecholamine and MT test results.
Discussion: The disproportional increased MT, which remained elevated during the follow-up, was
suspicious. Although the patient assured that he only consumed the genmai soup, he was well versed
- much better than the medical staff- in the constituents and application of hallucinogenic cactuses.
We will discuss the differential diagnoses of increased MT as well as analytic and toxicological
aspects.
P398
Focal colitis and widespread intestinal venal thrombosis: a case report
Stéphanie Wagner*, Claudia Brun del Re, Madeleine Rothen, Jonas Rutishauser, Annette Winkler,
Rahel Wirth, Shpendin Nuredini
Clinical presentation: A 59-year old male presented with diarrhea, fever and abdominal pain. He was
diagnosed with E. coli sepsis, possibly associated with sigma diverticulitis, and received antibiotic
treatment for 18 days. On a CT scan obtained upon admission, thrombosis of the portal, superior and
inferior mesenteric veins was detected, prompting anticoagulation. Thrombocytosis of up to 1300 G/L
was noted. While maintaining the hypothesis of septic thrombosis, we evaluated underlying
hypercoagulable states. A mutation in the JAK-2 gene was detected. A bone marrow biopsy and
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aspiration revealed myeloproliferative disease, with a differential diagnosis of primary
osteomyelofibrosis or essential thrombocytosis with progression to osteomyelofibrosis.
7 days after termination of the antibiotic therapy the patient presented with relapsing abdominal pain
predominantly in the lower left quadrant. A repeat CT scan showed increased colon wall thickening
without progressive intestinal thrombosis. Colonoscopy revealed focal inflammation of the cecum and
sigma. In the biopsies inflammatory changes were found. The patient’s symptoms decreased
spontaneously.
Discussion: Few cases of septic thrombosis in relation to diverticulitis have been published. In our
patient, a hypercoagulable state resulted from myeloproliferative disease, associated with a JAK-2
V617F mutation and thrombocytosis. We surmise that bacterial sepsis and hypercoagulability favored
widespread intestinal thrombosis.
Conclusion: This case illustrates the importance of testing for hypercoagulability in patients presenting
with thrombosis at unusual sites. Even though associated acute disease may be present, the
diagnosis of an underlying myeloproliferative disorder should not be missed.
P399
Die Hypokalzämie, welche durch Magnesiumzufuhr korrigiert wurde
Maria Trachsel*, Cornelia Keller, Peter E. Ballmer
Fall: Eine 66 jährige Patientin stellte sich vor wegen Schwäche, Schwindel und Hypotonie sowie
Diarrhoe unter Langzeittherapie mit Tavanic wegen einer Hüftotalprothesen-Spätinfektion. Im Labor
präsentierte sich eine ausgeprägte Hypokalzämie (albuminkorrigiertes Kalzium 1.33 mmol/l) sowie
eine schwere Hypomagnesiämie (0.22 mmol/l). Das 25-OH-VitaminD lag bei 15 µ g/l, das
Parathormon bei 44 ng/l (Referenzbereich 12-72ng/l). Die Hypokalzämie war oligosymptomatisch: Es
bestand ein intermittierendes Kribbeln perioral und in den Fingerspitzen. Chvostek- und TrousseauZeichen waren positiv. Im EKG war keine QT-Zeit-Verlängerung zu sehen.
Als Ursache der Hypokalzämie gingen wir von einem funktionellen Hypoparathyroidismus (im
Vergleich zur Schwere der Hypokalzämie inadäquat tiefes Parathormon) infolge einer durch
protrahierten Durchfall verursachten, schweren Hypomagnesiämie aus.
Unter Magnesiumsubstitution, initial intravenös, dann peroral, und symptomatischer Therapie des
Durchfalls normalisierten sich sowohl Magnesium- als auch Kalzium-Werte rasch, die diskreten
Hypokalzämie-Symptome verschwanden.
Diskussion:
Die klinischen Symptome einer Hypokalzämie hängen vom Schweregrad und der
Entstehungsgeschwindigkeit der Hypokalzämie ab und reichen von diskreten Zeichen einer erhöhten
neuromuskulären Erregbarkeit (Parästhesien) über Muskelkrämpfe und Hypotonie bis zu tonischen
Krampfanfällen und Laryngospasmen in schweren Fällen. Zu typischen klinischen Zeichen gehören
das Chvostek-Zeichen (Kontraktion der Gesichtsmuskulatur beim Beklopfen des N. facialis) und das
Trousseau-Zeichen (Pfötchenstellung der Hand nach Aufpumpfen der Blutdruckmanschette über den
systolischen Blutdruck). Charakteristische Zeichen im EKG sind QT-Zeit-Verlängerungen und STStreckenveränderungen.
Die häufigsten Gründe einer Hypokalzämie sind ein PTH-Mangel, insbesondere nach Operationen im
Bereich der Schilddrüse, oder aber ein Vitamin D-Mangel. Eine schwere Hypomagnesiämie kann, wie
in unserem Fall, zu einer verminderten PTH-Sekretion und PTH-Resistenz mit konsekutiver
Hypokalzämie führen. In solchen Fällen sollte primär Magnesium und nicht Kalzium substituiert
werden. Parallel muss die Ursache des chronischen Magnesiummangels behandelt werden.
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P400
A 36 year-old man with an unusual kind of proctitis
Thomas Stöckli*, Christophe Petrig
Medizinische Klinik (Solothurn, CH); Gastroenterologiezentrum (Solothurn, CH)
Case report: A 36 year-old man was admitted in May 2012 with abdominal pain in the left lower
quadrant, loss of mucus and blood as well as pain upon defecation. He reported receptive anal
intercourse with a single male partner one month before admission.
He had a past medical history of syphilis in 2009, treated appropriately with penicillin. His last HIVserology was negative in 2010.
On physical examination he had abdominal pain in the left lower quadrant, no fever. Examination of
anus and genitals was unremarkable.
HIV-serology was negative, serology for syphilis showed evidence of past infection. Since the patient
had received one dose of ceftriaxone (2g) intravenously, no diagnostic test for rectal gonorrhea was
requested.
A colonoscopy with biopsies was performed. Macroscopically, inflammatory changes in the anal and
rectal mucosa with swelling and fibrinous erosions were observed (A). Colon and distal ileum
appeared normal. Rectal histology showed hyperplastic crypts and infiltration of leucocytes within the
lamina propria (B). Real-time PCR on a rectal biopsy sample for Chlamydia trachomatis was positive
for Lymphogranuloma venereum (LGV) serovar L2b.
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The patient was discharged with doxycycline 100mg po twice daily for three weeks and subsequently
made a full recovery.
Comment: Lymphogranuloma venereum (LGV) is a sexually transmitted disease caused by
Chlamydia trachomatis serovar L1, L2 and L3. The classical presentation in both sexes includes
genital ulcers or papules and inguinal lymphadenopathy. In its classical presentation, LGV is endemic
in Africa, India, South East Asia, Central and South America and the Caribbean.
In Europe, including in Switzerland, an increasing number of atypical cases of LGV presenting with
proctitis in men who have sex with men (MSM) have been described in recent years. A large
proportion of these patients have concomitant HIV-infection. Since rectal LGV can cause chronic
inflammation with formation of fistula and fibrosis, timely diagnosis and appropriate antibiotic treatment
is crucial. Most experts recommend treatment with doxycycline 100mg po twice daily for three weeks.
Real-time PCR is an elegant new tool for detecting Chlamydia trachomatis L1, L2 and L3. A specific
protocol was developed at the Institute of Clinical Microbiology, University Hospital of Basel. Clinical
samples can be submitted for research purposes and will be analysed free of charge (contact
information: Tel. 061 265 5805).
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P401
Therapeutic drug monitoring of daptomycin: a retrospective monocentric
analysis
Claudine Reiber*, Oliver Senn, Daniel Müller, Gerd A. Kullak-Ublick, Natascia Corti
University Hospital Zurich (Zürich, CH)
Objectives: Daptomycin is a lipopeptide antibiotic with rapid concentration-dependent bactericidal
action against Gram-positive organisms. Target daptomycin plasma concentrations have been
determined in animal models for some pathogens but data on optimal exposure in humans are still
lacking. Measurement of daptomycin plasma concentration is available at our institution since 2009
and is performed regularly. The aim was to assess variability of daptomycin plasma concentrations
and the main determinants influencing daptomycin exposure.
Methods: We retrospectively collected data in patients with at least one determination of daptomycin
plasma concentrations during the period of January 2009 to February 2012 at the University Hospital
of Zurich. Samples were analyzed by LC-MS/MS. As daptomycin is mainly eliminated by the kidneys,
exposure in patients with no renal replacement therapy (nRT), intermittent RT (iRT) and continuous
RT (cRT) was compared. A trough level (Cmin) of at least 10mg/l and a minimal peak level (Cmax) of
50mg/l were defined as optimal based on animal data.
Results: 90 patients were identified with a mean (SD) age of 59 ±16years and a mean body weight of
74 ±21kg with 15 (16%) patients having a BMI >30. The mean total daptomycin dose was 448mg ±
133mg (range 175 -1000mg). In 22% daptomycin was administered every 48 hours and in 1% every
36 hours. Mean Cmax was 66.2mg/l (n=247, range 20-236mg/l) and mean Cmin was 16.7mg/l
(n=116, range 2-68mg/l). Cmax and Cmin levels were significantly lower in cRT (52±20mg/l and
9.5±7mg/l, respectively) compared with nRT (75.6±42mg/l and 21.4 ±16mg/l, p<0.0001). Cmin below
10mg/l was found in 69% of cRT, in 35% of iRT and 26% of nRT and Cmax was below 50mg/l in 52%
of cRT, 8% of iRT and 27% of nRT. When controlling for plasma creatinine and albumin concentration,
dose interval, administered dose/kg and BMI, cRT remained significantly associated with an increased
risk of a Cmin level below 10mg/l (OR= 3.1, p= 0.001) compared to nRT. There was an inverse and
independent association between administered dose/kg and Cmax below 50mg/l (OR=2.0, p=0.003).
Trough levels >20mg/l were mainly seen in nRT patients with renal impairment with only two cases of
mild CK elevation.
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Conclusion: Daptomycin exposure is highly variable depending on renal function and renal
replacement therapy used. Patients undergoing cRT had the highest proportion of low daptomycin
exposure with the highest risk for possible under dosing.
P402
Influence of parenteral nutrition on blood rheology and platelet aggregation in
vitro
Sergio Compagnoni*, Thomas Schulzki, Walter H. Reinhart
Background: Parenteral nutrition is an all-in-one emulsion composed of 3 components: Glucose,
amino acids, and lipids. Because of its high osmolality, it must be delivered via a central venous
catheter. We have studied the influence of parenteral nutrition in vitro on red blood cell (RBC)
morphology, blood rheology, and platelet aggregation.
Methods: Blood was drawn from healthy volunteers. A plasma volume of 0, 4, 10, and 25% was
replaced by a same volume of NuTRIflex® Omega special (B. Braun Medical AG, Sempach,
Switzerland). In a second set of experiments, the isolated components of NuTRIflex® were tested,
namely glucose, amino acids, and lipids at plasma concentrations of 10, 10 and 5%, respectively
(corresponding to their concentration with 25% NuTRIflex®). Besides hematological analysis, viscosity
was measured (Contraves LS-30) and platelet aggregation was assessed with a platelet function
analyser PFA-100.
Results: Changes were concentration-dependent. The mean RBC volume (MCV) measured by an
electronic particle counter increased (89.1±3.3 fl and 96.9±6.4 fl for control and 25% NuTRIflex®,
respectively, p<0.05) due to a glucose uptake and consecutive RBC swelling. In contrast, the MCV
calculated from the centrifuged hematocrit decreased from 90.6±3.8 to 80.8±4.3 fl (p<0.05), indicating
that in reality the hyperosmolar amino acid solution caused RBC shrinkage. Whole blood viscosity at a
high shear rate of 69.5s-1 was 4.53±0.56 and 4.83±0.37 mPa.s for control and 25% NuTRIflex®,
respectively. At a low shear rate of 0.1s-1, viscosities were 43.2±9.5 and 15.8±5.2 mPa.s (p<0.05)
suggesting a decreased RBC aggregation, which was confirmed by the RBC sedimentation rate
(20.8±10.2 and 2.7±1.3 mm/2h, p<0.05). Plasma viscosity was 1.31±0.07 and 1.27±0.04 mPa.s. RBC
morphology revealed some degree of echinocytic shape transformation (20.7±19.1% versus 9.0±5.3%
echinocytes) with concomitant hemolysis (LDH 335±47 and 1036±208 U/l, respectively, p< 0.05).
Platelet aggregation was decreased: The pore closure time in the PFA-100 instrument was prolonged
already with 4% NuTRIflex® (from 190±33 to 256±38s, p<0.05) and was >300s for 10 and 25%. The
strongest platelet inhibition was seen with the lipid component.
Conclusions: The parenteral nutrition NuTRIflex® induced in vitro a concentration-dependent
decrease in RBC volume, an echinocytic shape transformation, and a decrease in RBC and platelet
aggregation. These changes may have clinical implications.
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P403
A 65 year-old man with a skin lesion on his neck and cervical
lymphadenopathy after collecting raspberries in a forest
Andreas Plate*, Thomas Stöckli
Bürgerspital Solothurn, Medizinische Klinik (Solothurn, CH); Bürgerspital, Medizinische Klinik
(Solothurn, CH)
Case report: A 65 year-old male patient was admitted in July 2012 with night sweats, fever up to 39°C,
loss of appetite and malaise since 3 days. One week earlier, he had been in a forest near Bätterkinden
(BE), collecting raspberries. He had noticed an insect bite on the back of his neck.
Physical examination showed a wound on the back of his neck with a small central ulcer, at the site of
the previous insect bite (A). In addition, cervical and nuchal lymphadenopathies on the left side were
found. At the time of admission, the patient was afebrile and in good condition. Laboratory tests
showed elevated markers of infection, such as Procalcitonin and C-reactive protein.
The patient was hospitalized and treated with intravenous Piperacillin/Tazobactam. During the next
three days, he had episodes of fever up to 39ºC. On day four, his condition seemed to improve. He
therefore was discharged with amoxicillin/clavulanic acid 1g po twice daily.
However, the patient continued to have fever and night sweats at home and was therefore referred to
our infectious diseases outpatient clinic for reevaluation one week later. The antibiotic treatment was
changed to doxycycline 100mg po twice daily. Further serological tests were requested. The
Microagglutination Assay for Franciscella tularensis came back highly positive for IgM (475 U/ml) as
well as IgG (139 U/ml). After treatment with doxycycline for a total of three weeks, the patient
recovered completely. Serological follow up three weeks later showed an increase of the IgG titer to
>300 U/ml, consistent with recent infection.
Comment: Tularemia is caused Franciscella tularensis, a gramnegative bacteria. It is primarily a
zoonotic disease affecting rabbits, rodents and occasionally other animals. Transmission to humans
occurs through insects, such as bites by ticks or flies, or contact with infected animals. Clinical
symptoms are highly variable, depending on the site of entry of the organism. The patient presented
here had an ulceroglandular form of tularemia. Presumably, the organism was introduced by an
infected insect. At the entry site on the neck, a typical skin lesion with a central ulcer was formed,
followed by cervical and nuchal lymphadenitis, fever and malaise. Betalactam antibiotics are not
effective against Franciscella tularensis, in contrast to doxycycline. This might explain the patients
initial treatment failure. In Switzerland, about 5 -10 cases of tularemia are reported every year.
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P404
This giggling does not freeze
Noémie Stähli*, Lea Aerne, Thomas Bregenzer
Introduction: Ethylene glycol (EG) as a frequent ingredient of antifreeze and other industrial products
is relatively nontoxic. But diagnostic and therapeutic delay in EG intoxication can result in severe
organ dysfunctions or death (lethal dosis: >= 1g/kg). After ingestion, EG levels peak at 2 - 3 hours. By
oxidizing EG (mainly hepatic Alcohol dehydrogenase (ADH)), glycolate, glyxylate and oxalate may
accumulate and cause severe end-organ damages (seizures, pulmonary edema, hypotension, renal
failure). The anion gap in metabolic acidosis proportionally correlates with the accumulation of toxic
metabolites. Immediate ADH inhibition with fomepizol is the treatment of choice. Ethanol may also be
used.
Case report: A 51 year old woman came to our emergency department (ED). Eight hours (h) earlier
she drunk some swallows from a soda drink bottle which she found in her car and thought it was a
multi-vitamin drink bought by her sister who used her car before. But it was an originally labeled
lemonade bottle filled with orange-colored antifreeze from her car mechanic. Dizziness, headache,
nausea and intermittent palpitation developed 3.5 h later. After inducing vomiting she went to bed.
When she called us, we recommended her to start treatment immediately by drinking ethanol (wine or
hard liquor) and come to the ED. When she arrived she was boozed and giggling with a blood alcohol
level of 0.9 0/00. BGA revealed mild respiratory alkalosis and pathological osmolal gap. Oral treatment
with ethanol was continued until the antidote fomepizol was available and administered according to
guidelines. The EG-level after 14 h of therapy was 29mg/l (nontoxic <200mg/l), and fomepizol was
stopped. All clinical and laboratory controls were normal except a mild transient hypocalcaemia. No
oxalate crystals were seen in urine analyses. The patient left the hospital without sequelae after 45 h
of treatment.
Discussion: A forensic testing of the orange liquid confirmed the presence of 50 % of EG in water.
Since there was no anion gap acidosis without treatment 8 h after ingestion, the initial EG blood level
(not available) must have been low. Osmolal gap may have been elevated due to EG and/or ethanol in
the serum. ADH inhibition therapy may have contributed to the favorable outcome.
Conclusion: Anion and osmolal gap may help to recognize EG intoxication in unclear metabolic
acidosis. Immediate ADH inhibition is crucial. Ethanol serves as empiric treatment until fomepizol is
available.
P405
Discontinuation of recommended therapies one year after an acute coronary
syndrome: results from a prospective cohort
Baris Gencer*, Nicolas Rodondi, Reto Auer, David Carballo, Lorenz Räber, David Nanchen, Pierre
Vogt, Sebastian Carballo, Philippe Meyer, Pierre-Frédéric Keller, Christian Matter, Stefan Windecker,
Thomas Lüscher, François Mach
Geneva University Hospital (Genève, CH); Bern University Hospital (Bern, CH); University of California
(San Francisco, CH); Lausanne University Hospital (Lausanne, CH); Groupe médical Ziggurat
(Porrentruy, CH); Zürich University Hospital (Zürich, CH)
Background: Adherence to recommended medication is a key factor to decrease the recurrence of
acute coronary syndrome (ACS), but very limited data exist about reasons of discontinuation. We
aimed at determining the prevalence and reasons of therapy discontinuation one year after ACS.
Method : We studied 1385 men and women from a prospective cohort study of consecutive patients
hospitalized for an ACS from July 2009 to December 2010 (18 months) in four Swiss academic
hospitals. We measured the rate and the pre-specified reasons of medication discontinuation for
aspirin, statins, beta -Blockers and Angiotensin Converting Enzyme Inhibitors/AngioTensin II receptor
blockers (ACEI/ATII)one year after ACS. We assessed medical adherence with Medical Adherence
Scale (MAS) questionnaires. With the use of logistic regression we identified factors associated with
medication discontinuation.
Results: Among 1385 patients with ACS followed-up during one year, the discontinuation rate of
prescribed treatment one year after hospital discharge was 2.9% for aspirin, 6.5% for statins, 16.5 %
for beta -blockers and 15.6% for ACEI/ ATII(7.9% if heart failure was documented). More than 70% of
patients reported that treatment was stopped by their physician, while potential side effects were an
uncommon reason, except for statins (45.4%) and ACEI/ATII (32.5%). The preexisting use of any
medication, the diagnosis of ST-segment elevation ACS, an attendance to rehabilitation program and
155
a reported complete medication adherence (Medication Adherence Scale <1) were all negatively
associated with the one year cardiovascular medication discontinuation.
Conclusion: Adherence to medication after an ACS differs according to therapeutic drug classes with
the highest rate of discontinuation for beta -blockers. An attendance to rehabilitation program
decreased cardiovascular discontinuation at one year. Interestingly, patients attributed the reasons of
therapy discontinuation to the treating physicians' decision. These results indicate that there is a need
to better inform and educate both patients and physicians.
P406
Impact of extensive reform of discharge letter on general practitioners, resident
work and management
Antoine Garnier*, David Gachoud, Mariangela Gagliano, Géraldine Gilliot, Milva Cappai, Claudio
Sartori, Gérard Waeber, Marco Martinuz
Background: Communicating medical information is a major challenge because of the number of
health providers and increasing cutting edge medical care. Discharge letter(DL) is important but often
considered as a burden. In 2011, the Service of Internal Medicine, counting 173 beds, sent 4090 DL.
They were issued in an average of 41.2 days. Furthermore, electronic medical record (EMR) were
introduced in CHUV. Dictation has lost usefulness. Short medical report(faxmed), produced
electronically at the day of discharge, are duplicating DL but without validation of a supervisor. For the
chiefs residents and the head of service, it is time to initiate a reform. We must adapt to
computerization, maintain quality and reduce delays.
Method: A first task force met late 2011 and developed the concept: no more dictation; writing style
has to be telegraphic and synthetic.The DL is extracted from the list of problems build during the stay.
Comments are split in 3: background - discussion - proposal.The faxmed is abandoned. But difficulties
threaten the reform: resistance to the loss of prose, disagreement on structure and practical problems.
After problem identification, in July 2012, a new task force is created, more strictly coordinated and
interdisciplinary (physicians, administrator, secretary and IT support). Responsibilities are divided into
4 areas: EMR, content structure, layout, and standardization of procedures. General practitioners(GP)
are surveyed. Tests are conducted in a 25-beds unit.
Results: After 2 months, it appears that the reform induced cascades of changes in way of thinking,
working and documenting EMR throughout the stay.The secretariat's work is also redefine.EMR and
delays monitoring are improved.
Within the next 3 months, the process is extended to the six other units.Doctors have been specifically
trained and coached. Interaction between end-users and task force allowed further improvement.In
December 2012, the head of service endorses the reference document. Residents and GP are
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satisfied.The reflections of the DL shifted upstream of the stay. Although exciting, good synthesis isn't
so easy to do. Errors appear more evidently and supervisors still has an important work load.
December 31, the mean delay was 11 days.
Conclusion: Despite a large university service, a deep change has been achieved in less than 6
months. This success lies in a coordinated and interdisciplinary task force. The main medical benefit is
an upstream shift of the medical reflections.
P407
Lipid-lowering therapy modification and LDL-C goal achievement after an acute
coronary syndrome: a prospective Swiss cohort
Baris Gencer*, François Mach, Reto Auer, David Carballo, Lorenz Räber, David Nanchen, Pierre
Vogt, Sebastian Carballo, Philippe Meyer, Pierre-Frédéric Keller, Christian Schmied, Christian Matter,
Stefan Windecker, Thomas Lüscher, Nicolas Rodondi
Geneva University Hospital (Genève, CH); University of California (San Francisco, CH); Bern
University Hospital (Bern, CH); Lausanne University Hospital (Lausanne, CH); Groupe Médical
Ziggurat (Porrentruy, CH); Zürich University Hospital (Zürich, CH)
Background: Poorly controlled low-density lipoprotein cholesterol (LDL-C)levels after an acute
coronary syndrome ACS)are common. Although guidelines recommend an aggressive approach, no
study evaluated the lipid-lowering therapy modification performed by physicians to reach LDL levels
goals one year after an ACS.
Methods: We studied 924 men and women from a prospective cohort study of consecutive patients
hospitalized for ACS from July 2009 to December 2010 (18 months) in four Swiss academic hospitals.
We systematically collected data on lipid-lowering treatment and measured LDL-C levels at baseline
and after one year. We defined "appropriate care" as the continuation of the established therapy or the
switch to a high potency statins in those who did not reach the LDL-C goals. We measured adherence
with Medial Adherence Scale (MAS) questionnaires.
Results: Among 924 patients followed-up one year after an ACS, only 31.3% achieved the current
LDL-C goal of < 1.8 mmol/l. In patients taking high potency statins with complete medical adherence,
only 40.2% reached an LDL-C goal < 1.8 mmol/l. At one year, 94.4% of participants continued their
statins therapy, but only 57.1% had high potency statins and 38.5% of patients reported to have some
degree of non-adherence (MAS >= 1). Appropriate care of lipid-lowering therapy was delivered to
55.3% of patients with poorly controlled LDL-C.
Conclusion : Less than one third of patients achieved recommended LDL-C goal one year after ACS,
and appropriate care was delivered to 55% of patients with poorly controlled LDL-C. Although patients'
adherence and physicians' therapy modification should be improved, new therapeutic approaches are
needed to be able to reach the current LDL-C goals.
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P408
What are your patients searching on the internet while hospitalised?
Ameena Jesaimani*, Christophe Luthy, Natalia Pletneva, Michel Kossovsky, Anne-Françoise Allaz,
Christine Cedraschi, Valérie Piguet
HUG (Genève, CH); Health on the Net (Genève, CH)
Objective: Cross-sectional study assessing Internet use in hospitalized patients in a division of general
medical rehabilitation (GMR) at the Geneva University Hospitals.
Methods: The survey was carried out one day/week from July-December 2012. A questionnaire
investigating various aspects of Internet use was given to patients hospitalized at the GMR during this
time period.
Results: 245 patients were contacted; from the 159 (65%) included, 101 (64%) never used Internet
(group A); 36 (23%) used it at home only (group B) and 22 (14%) at home and at the hospital (group
C). Patients in group A were significantly older, less educated and had a higher chronic medication
intake (Table 1). Groups B and C displayed no significantly different sociodemographic characteristics,
but more patients in group C were on chronic medications (82% vs group B 67%; p=.03). Group C
reported a higher everyday access to Internet (81% vs group B 50%; p=.001) through mobile devices,
and 86% came to the GMR with at least one device (Table 2). Online activities were similar in both
groups, but more patients in group C searched for health information which concerned their own
health (73% vs group B 24%; p=.000); these patients were also eager to share health information with
relatives or health professionals and to get better, individualized and interactive health information.
Conclusions: Only few patients stayed connected to Internet when hospitalized, but they may well be
representative of future patients, with increased requests for interactive health information.
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P409
Rectus sheath haematoma: a rare but dangerous cause of acute abdominal
pain
Lea Landolt*, Tobias Hoefflinghaus, Esther Bächli
Introduction: Rectus sheath hematoma (RSH) is a rare complication of anticoagulant therapy and can
be life-threatening. Our aim was to analyze clinical features, diagnosis, treatment and outcome of
these cases in a general hospital.
Case Report: During a period of 24 months, 8 cases of RSH were diagnosed (0.1% of all inpatients).
Mean age was 79,4 years (y, SD+/-14.1). 75% were female. 7 patients (pts) were on therapy with
vitamine K antagonists (VKA), 2 in combination with Aspirin (ASA), 4 had low molecular weight
heparin (LMWH) for bridging of VKA therapy. 4 pts had INR levels between 3.1–4.4. One pt with liver
cirrhosis and low platelet count had ASA and LMWH prophylactically. Five pts (63%) were coughing.
Main symptom was localized pain in 7 pts. One pt was incidentally diagnosed on a CT scan performed
for different reason. 7 pts had a palpable mass of the abdominal wall. 5 RSH were diagnosed with CT,
2 with ultrasound, 1 clinically. All pts were treated conservatively. In 7 pts vitamine K and Beriplex®
was substituted. 4 pts received blood transfusions (1-4 units). The mean drop of hemoglobine (Hb)
was 37g/l (SD+/- 22g/l). The renal function was chronically impaired in 7 pts (mean creatinine
clearance 51ml/min +/-12.4) and declined further. 3 out of 8 pts died (38%, age 90-92y, female). In
these patients the observed change in Hb was 42-58g/l, 2 pts had combination of VKA, LMWH and
ASA, 1 pt had VKA only.
Discussion: Our series shows a substantial mortality (38%) and morbidity of RHS - especially in
elderly female pts with VKA in combination with antiaggregation therapy. Coughing was present in
63% and is an accepted risk factor.
Our findings were comparable to a review with 126 cases of RSH published in 2006 , where 64% were
women, 69% were on VKA, 29% had a cough, 84% abdominal pain and 63% a palpable abdominal
mass. Mostly, diagnosis was made by CT. 86% were treated conservatively, 7.9% had surgery or
embolization of the bleeding vessel. Mortality was 1.6% but mean age was lower (67.9y).
Conclusion: Acute abdominal pain in pts under anticoagulant and/or antiaggregation therapy
combined with renal impairment should always raise suspicion about RSH. Extensive blood loss,
shock and aggravation of renal failure can be fatal. In majority of cases the hematoma is palpable and
should prompt a CT scan of the abdomen. It is crucial to normalize coagulation parameters and to
correct intravascular volume depletion to avoid shock and further decline of renal failure.
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P410
What do we know about online searches about medication? A review of the
literature
Ameena Jesaimani*, Victoria Rollason, Christine Cedraschi, Christophe Luthy, Marie Besson, Celia
Boyer, Jules Alexandre Desmeules, Valérie Piguet
University Hospital of Geneva (Genève, CH)
Background: Internet has become a global network easy to access from anywhere. One of the most
common reasons for accessing Internet is searching for health information (HI).
Objective: To examine the use of Internet for seeking HI among patients and the general population in
order to investigate who searches for HI on Internet and for what purposes, with a specific focus on
medication.
Method: We conducted an electronic search using: PubMed, Cochrane library, Banque de Données
en Santé Publique and Google scholar for studies published up to March 2012. Inclusion criteria were
: the general population or patients looking for HI and for medication information (MI) on the Internet,
aged between 15 to 80 years, not suffering from cancer or AIDS.
Results: Of the 102 retrieved studies, 67 met the inclusion criteria (with a focus on MI, n=23). The
majority of studies were conducted in North America (45%), followed by Europe (33%), Middle East
and Asia (13%) and Australia and New Zealand (9%). More than half of the studies included the
general population, and 42% evaluated outpatients. Most surveys were conducted by phone (n=26) or
internet (n=11) interviews/questionnaires (n=23) and by face-to-face interviews (n=9).
About half of the general population and 50-99% of adults suffering >=1 chronic disease used Internet
to search for HI, mainly about a specific disease, its treatment, exercise and diet. Regarding
medications, about half of the online HI seekers, whether patients or not, looked for MI concerning
side effects, drug safety, interactions, update on drugs currently consumed, new drugs, over-thecounter or alternate medications. Women, adults < 50 years, well educated, searched significantly
more frequently for MI as well as for HI. The reasons to search online for MI were convenience, broad
range of information and peers' opinions. The online searches for MI did not replace health
professionals' information, but offered additional information and also a crosscheck. Online MI could
reassure or be an incentive to ask questions to the treating physicians but also confuse.
Conclusion: Further studies should provide health professionals with more details on patients'
expectations about online MI. This knowledge should enable them to develop online quality MI,
including Internet interactive possibilities to improve MI, in particular for self-management of chronic
diseases.
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P411
Socioeconomic status and quality of care in a population-based sample of
diabetic patients in the canton of Vaud
Aline Flatz*, Bernard Burnand, Isabelle Peytremann Bridevaux
Institut universitaire de médecine sociale et préventive (Lausanne, CH)
Introduction: Low socioeconomic status (SES) is associated with an increase in the prevalence of
many diseases such as diabetes mellitus as well as with worse outcomes. Further, associations have
been found between low SES and worse quality of care. In this study we aimed to explore this
relationship in the Swiss context.
Methods: We used data from a population-based random survey performed among 406 adult diabetic
patients living in the canton of Vaud. Data on patients' and diabetes characteristics, processes of care,
diabetes outcomes, use of health services and quality of life were collected with a self-administered
questionnaire. Dependent variables included 6 processes of care received during the previous 12
months: HbA1C, lipid, microalbuminuria, fundoscopy, feet examination and influenza vaccination. We
assessed the relationship between education level (primary, secondary and tertiary) and quality of
care as measured by processes of care as well as between income and quality of care using
regression analysis. Adjustment was made for age, gender and presence of co-morbidities.
Results: Mean age was 64.4 years, 40.6% were women; 68.5% reported type 2 DM, 12.8% type 1 DM
and in 18.7% the type was undetermined. Most patients had secondary education (55.6%), 19.1% had
primary and 25.3% tertiary education. Statistically significant results of adjusted regressions showed
that compared to patients with primary education, patients with a secondary or tertiary education were
more likely to get a fundoscopy (OR 2.1 95% CI 1.2-3.7, OR 2.6 95% CI 1.3-5.0, respectively) and
also more likely to get a feet examination by a physician (OR 1.8 95% CI 1.0-3.1; OR 2.5 95% CI 1.35.1, respectively). When using composite indicators of processes of care we observed that patients
with secondary or tertiary education were more likely to receive ?5/6 PoC (OR 2.23; 95%CI 1.23-4.04,
OR 2.83; 95%CI 1.42-5.61, respectively) compared to patients with primary education.
No associations were found between income and quality of care.
Conclusion: Diabetic patients with low education were less likely to have received the recommended
annual fundoscopy and feet examination than better educated patients. These data are in line with the
results of other studies performed in various countries and provide some more evidence for the
presence of health disparities in Switzerland.
P412
Treatment with intravenous immunoglobulin G (IVIgG) of unspecific myositis
with features of inclusion body myositis (IBM)
Florence Vallelian*, Ulf Petrausch, Dominik Schaer
Introduction: IBM is characterized by parallel autoimmune inflammation and muscle degeneration and
results in proximal and distal weakness of the legs and arms. One of the serious complications is
dysphagia. Histological features include typical intramuscular vacuoles, amyloid accumulation and
infiltration of CD8 positive T cells. However, vacuoles can be absent in the early phase of this disease.
In general, response to any treatment is poor. A possible treatment is the combination of methotrexate
or azathioprine with steroids. IVIgG was used in some patients resulting in clinical response. However,
placebo-controlled studies have failed show significant benefit.
Patient: We saw in 2010 a 73 years old male patient with progressive proximal weakness and pain of
both legs and difficulties to swallow. To further evaluate the weakness muscle biopsy of M. vastus
lateralis was performed showing T cell infiltration. Due to missing vacuoles the diagnosis of IBM could
not established formally. As sign of inflammation the MRI showed enhancements in M. sartorius, M.
vastus intermedius on both sides and in the corpus breve of M. biceps femoris on the left side. At that
time the creatine kinases (CK) was 2033 U/l.
Therapy: Therapy was started with working diagnosis of unspecific myositis with features of IBM. The
patient received azathioprine (1.5mg/Kg BW) and prednisone (1mg/kg BW). After 3 month the
immunomodulation resulted in improved muscle strength and reduced dysphagia. The CK dropped to
214 U/l. Prednisone was tapered to a dose of 10 mg daily. At that time the patient started to complain
161
about pain and weakness in the proximal muscles of the arms and legs which could not be controlled
by increased prednisone and azathioprine (2mg/Kg BW). As second line therapy IVIgG with 5 mg
prednisone daily was initiated after measuring base line muscle strength. For 3 times every 4 weeks
on 4 consecutive days 40g VIgG were infused (3x1.5g/Kg BW) with no side effects. After this therapy
the muscle strength again was measured showing a significant improvement. The nadir of the CK was
reached 8 weeks after stopping IVIgG with continued low dose prednisone. The most recent CK
values are indicating a relapse suggesting temporal efficacy of IVIgG to control myositis.
Conclusion: The case indicates that IVIgG with low dose steroids can induce an objective response as
second line treatment option in a patient with unspecific myositis.
P413
Lime Tree Project: health promotion by intersectorial action within a
community-campus-local authority partnership
Sandrine Motamed*
Université de Genève et HUG (Genève, CH)
The Lime Tree Project is a 10 year old partnership of a Swiss community, its local authority and the
university. Its aim was to help the residents to identify and express their own health needs and to meet
the challenges that were mainly socio-economic and psycho-social in nature. The inhabitants drew
together to develop, across many sectors, a more just society which over the years has resulted in a
novel concept of healthy living.
Meinier is a county near the city of Geneva. Following an initial study undertaken by students of the
University of Geneva (Institute of Social and Preventive Medicine, ISPM) aiming to identify its
residents' health needs, the local authority formally engaged the ISPM to try to resolve the problems
disclosed, which were of socio-economic and psycho-social nature. Numerous meetings of the
inhabitants gradually allowed dialogue within the community to develop, leading them to precisely
define their requirements.
Old people felt isolated and wished to remain in the village, even when they lost their autonomy, rather
than enter a nursing home elsewhere. Young families could not get established because of a lack of
available housing, the financial burden and nonexistent day care facilities for children. Social links
between people had diminished, especially between the generations. Further difficulties arose from
poor mobility, both for work and leisure. Given these findings the inhabitants drew together to develop
a more equitable society, in a partnership between the authorities and our Institute. A participative
intersectorial approach allowed a global program to be put together, which particularly united housing,
urbanism, ecology and mobility. An architectural competition brought this first, 5 year long, phase to a
close. The project, driven completely by community participation, is in its tenth year, its 40 million
dollar budget adopted by community vote. One prominent aspect is the new village center, with its
sheltered housing for the elderly, affordable accommodation for young families, child day care, a
games library, shops and a restaurant as well as an intergenerational park and living space.
The learning and experience gained in terms of community participation and of behavioral and social
health determinants has been very important for all concerned. The Lime Tree Project demonstrates
that a collaborative approach to implementing effective intersectorial health promotion works at county
level in Switzerland.
P414
Cooperation between Hospice Ticino and Cardiocentro Ticino for terminal
patients with cardiovascular pathologies
Augusto Bernasconi*, Stefanos Demertzis, Nicola Ferrari, Marianne Lang, Bea Marx, Monica Ranzi,
François Regoli, Claudio Benvenuti, Tiziano Moccetti
Hospice Ticino (Lugano, CH); Cardiocentro Ticino (Lugano, CH); SUPSI (Lugano, CH)
Introduction: On the hypothesis that some patients with heart complaints can benefit from palliative
care, a cooperation project between Hospice Ticino (HT), home medical and nursing organization, and
Cardiocentro Ticino (CCT) was initiated. Cardiology has developed instruments for patients whose
condition in the end is symptomatic of their illness. Palliative care is readily available for patients who
are suffering from oncological disease and only 4% of patients followed by HT have strictly
cardiovascular diagnoses. The aim was to offer a taking in charge for terminally-ill patients with heart
complaints and the objectives were to define the mutual responsibilities of the CCT and HT medicalnursing teams, to identify needs and offers of care and criteria of inclusion, and to propose operational
procedure.
162
Methods: A working group consisting of five doctors and two nurses met once a month. Professional
expertise was shared along with literature and brief experiences of their mutual activity. The principal
problems were acknowledged and enabled the identification of the criteria for inclusion. Regarding the
procedure for taking patients in charge, it meant discussing the operational instructions of
announcement to HT and the procedure of communication to be adopted to update all the professional
figures involved during the course of the patients’ illness.
Results: Five papers were drafted: shared papers; medical criteria for taking in charge into palliative
therapy; the needs of the terminally-ill patient with heart complaint from the nursing point of view;
criteria for inclusion (specifically of patients suffering from cardiovascular pathologies); communication
between care providers, patients and family. Since 26th July 2012, five patients have been discussed
and followed.
Conclusion: The first piece in the creation of an integrated system, between hospitals and local area,
of all the doctors and care providers involved in the consultation and in the palliative care of patients
suffering from chronic heart diseases.
P415
Effect of the GABAA ligands clobazam and clonazepam on the modulation of
pain transmission in humans
Marie Besson*, Alain Matthey, Youssef Daali, Pascal Vuillemier, Michele Curatolo, Pierre Dayer,
Zeilhofer Hanns Ulrich, Jules Desmeules
Hopitaux Universitaire de Genève (Genève, CH); Insel Spital (Bern, CH); Insel spital (Bern, CH);
University of Zurich (Zürich, CH)
Background: Facilitation of spinal GABAergic inhibition with benzodiazepines (BZD) reverses pain
sensitization in rodents. In human, the use of BZD in pain is limited by their sedative effect. We
previously demonstrated the antihyperalgesic effect of clobazam, a 1,5-BZD, in mice and its lack of
sedation at effective doses. Hence we designed a pharmacokinetic-pharmacodynamic study to
explore the effect of antihyperalgesic effect of BZD in healthy volunteers.
Methods: Randomised double blind cross over controlled study in 25 healthy volunteers comparing
clobazam 20mg to clonazepam 1 mg (positive control) and tolterodine 1,37mg (active placebo) two
weeks apart. The primary outcome was the effect on the size of secondary hyperalgesia elicited by the
UVB irradiation of the skin of the forearm (sun burn model). Quantitative sensory testing, nociceptive
flexion reflex and the cold pressor test were also performed. Sedation was measured by a visual
analog scale (VAS), the digit substitution symbol test (DSST) and saccadic eye movements (SEM)
recording. Blood samples were taken to determine the pharmacokinetic of clobazam.
Results : we observed a reduction of the area of the secondary hyperalgesia with clobazam and
clonazepam. The maximum of the effect was seen at t= 2h [median of the difference between t=2 and
baseline (MOD2-0) (+/-CI) vs placebo: 19.2 cm2 (-2.7-37.9) p=0.07 for clobazam and 29.6 cm2 (2.055.1), p=0.03, for clonazepam], in line with the expected Tmax of the compounds.
Regarding sedation, at t=2h, we saw an effect of the two active compounds on the VAS [MOD2-0 (+/CI) vs placebo: 14 mm (1.0-21.5), p=0.03 for clobazam and 26 mm (14.0-37.5), p<0.001 for
clonazepam] and on the peak velocity of the SEM [MOD2-0 (+/-CI) vs placebo: 30.8 deg./s. (6.6-60.6),
p<0.01 for clobazam and 55.2 deg./s.(24.5-85.0), p<0.01 for clonazepam]. The DSST was only
impaired by clonazepam [MOD2-0 (+/-CI) vs placebo: 11.0(5.0-18.0), p=0.03]. These effects
disappeared at t=8h except that clonazepam still impaired SEM [median of the difference between t=8
and baseline (+/-CI) vs placebo: 28.3 deg./s. (5.3-52.7), p=0.01].
Conclusion: clobazam and clonazepam decreased the area of secondary hyperalgesia in the sunburn
model, which suggests that GABAA receptor ligands are involved in the modulation of pain
sensitisation in human. Clobazam was less sedative than clonazepam and therefore a suitable “tool
compound” to assess the role of GABAergic pathways in human.
P416
Human immunodeficiency virus (HIV) screening in the emergency department:
patients’ perspectives
Olivier Hugli*, Timothée Favre-Bulle, Dimitri Baudat, Katharine Darling, Matthias Cavassini
CHUV (Lausanne, CH)
Introduction: Blood tests are frequently performed when a patient is admitted in the emergency
department (ED) or before surgery. A study at our institution demonstrated the following: 38% of
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patients who had had an operation believed that a screening HIV test was systematically part of the
preoperative blood work-up; of those, 96% interpreted the lack of information regarding the test result
as a proof of a negative HIV test; 80% of patients were in favor of a systematic HIV test (1). The goal
of our study is to assess among ED patients, a) the proportion of patients with the same erroneous
belief and, b) the proportion of patients in favor of a systematic HIV screening test.
Methods: Patients who were admitted to the ED of our hospital (50,000 patients / year) and had blood
drawn were asked 2 questions: 1) Did they believe that an HIV screening test was part of their blood
work-up? 2) Would they agree with a systematic HIV screening test. Exclusion criteria were: refusal to
participate; age =< 16 years or > 70 years; patients admitted > 12 hours or who left before being
interviewed; clinical instability; transfer from another hospital; dementia, psychosis or any other cause
that precluded informed consent; intoxication; known HIV+ status, and prisoner.
Results: 472 patients were screened, and 84% excluded based mainly on age > 70 years (48%), no
blood drawn (19%), or who had left before being interviewed (10%). Of the 121 eligible patients, 104
(86%) were included in the analysis. Their mean age was 44±16 (SD) years; 52% were women; 90%
Europeans; 26% believed to have been screened for HIV, without significant differences across age or
by gender or origin; 79% were in favor of a systematic HIV test in the ED.
Conclusion: In our sample of middle-age European patients, a quarter believed erroneously that HIV
screening is part of a standard blood work-up in the ED. Age or gender are not associated with this
belief. Our study confirms the results previously obtained in a group of patients who were operated on.
Our results suggest that there is a need for better information regarding the policy governing HIV
screening in our hospital. As the vast majority of patients support systematic HIV screening in the ED,
the question of a generalized opt-out strategy appears justified in this setting.
(1) Albrecht E et all. An analysis of patients' understanding of 'routine' preoperative blood tests and
HIV screening. Is no news really good news? HIV Med.2012;13:439-43
P417
Successful treatment of extended-spectrum beta-lactamases (ESBL)-producing
Escherichia coli-prostatitis with ceftriaxone
Flann Benjamin Postert*, Thomas Bregenzer
Introduction: Prostatitis with quinolone and co-trimoxazole resistant enteobacteriaceae is difficult to
treat. If there is an additional extended spectrum betalactamase (ESBL), usually reported as resistant
to all cephalosporins, there are no established treatment options since tissue penetration of antibiotics
with activity against ESBL-producing gram-negatives is low.
Case report: A 87-year-old patient in remission after transurethral resection of urothelial cancer
suffered from recurrent septic urinary tract infections (UTI). He was referred to our emergency
department with a third episode of bacteremic UTI with E. coli resistant to amoxicillin, co-trimoxazole
and quinolone, susceptible to cephalosporins and aminoglycosides. E. coli-prostatitis was diagnosed
clinically with the same resistance pattern. The patient recovered completely after a ten days course of
ceftriaxone. New symptoms of UTI and prostatitis occurred one week later. We initiated an
intravenous six weeks course with ceftriaxone once daily at our outpatient clinic while waiting for
results of a new urine culture. Resistance test results were available four days later. The patient was
already asymptomatic. However the E. coli now was identified as an ESBL-producing strain.
Ceftriaxone treatment was continued as scheduled. Repeated urine cultures during 3 months after
treatment remained sterile. When the patient had transurethral prostatectomy for obstructive prostate
hyperplasia no infectious complications occurred. During a follow-up of 12 months no UTI occurred
and repeatedly performed urine cultures remained sterile.
Discussion: Despite ESBL production the treatment with ceftriaxone was clinically successful and
there was no relapse during 12 months of follow-up. ESBL-producing enterobacteriaceae in urin
cultures do not mean that cephalosporins are clinically inactive. In children with acute pyelonephritis it
has been shown that empiric therapy with ceftriaxone is equally effective in those with and without
ESBL-producing E. coli.
Conclusion: UTI with ESBL-producing E.coli may respond to treatment with ceftriaxone. According to
the 2010 EUCAST recommendations it may be valuable to report resistance results in ESBLproducing enterobacteriaceae “as found”.
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P418
Alcohol intoxication in the Oberaargau district: a ten year trend
Alexander Imhof*, Peter Schott
medizinische Klinik, SRO AG (Langenthal, CH)
Background: Many authors reported an increase in alcohol intoxication, particularly in large cities.
However, there are only few clinical data about alcohol intoxication in hospitals in a rural part of an
industrial country. The aims of this study were trends over time in the numbers of alcohol intoxications
and trends with respect to gender and age distributions of intoxicated patients.
Methods: We conducted a retrospective study over a 10-year period in patients admitted to our
emergency department. Patient details and blood alcohol levels were obtained from the laboratory
information system for all samples sent from the emergency department.
Results: During the study period, 3527 alcohol tests were sent to the laboratory. The median age of all
patients with alcohol tests was 43.7 years (range: 13.2-93.9). 66.7% of the patients were male. The
median alcohol level was 11 mg/100ml (0-7.3). In 1946 (55.2%) patients the alcohol level was
>80mg/100ml and the median age in these patents was 40.9 years (13.2-92.9). The median of annual
increase of patients with a level >80mg/100ml was 9.1% (-7.0% (2008/2009) to 29.3% (2002/2003). A
significant increase of alcohol intoxication was found in all age groups. However, the age distribution
of our intoxicated patients showed a peak in the age group 40-55, followed by patients under 25 years
of age.
Conclusion: In our population, episodic drinking is not only a problem of young persons; it also
concerns the age group between 40-55 years. Preventive measures should not only be limited to
younger adults.
P419
Access to healthcare for undocumented people in Switzerland: differences
between cantons and clinical issues
Marius Besson*, Monica Varcher, Patricia Hudelson Consultation ambulatoire mobile de soins
communautaires (CAMSCO)
Background: Between 100’000-250’000 undocumented people (referred to as “sans-papiers” in
Switzerland) are estimated to live in Switzerland, mainly in urban areas. This population generally lives
in precarious conditions with poor access to health care and health insurance, but barriers to care vary
greatly between Swiss cantons. We describe and discuss intercantonal differences in access to care
for this vulnerable population in Switzerland.
Methods: The national platform, “Health care for undocumented migrants” was created in 2006. Its
members include Swiss health structures involved in providing health care to undocumented migrants,
and its main objective is to promote exchange about about health practices across the different
cantons. We obtained informations from the platform on socio-medical structures existing in 12 Swiss
cantons, with the aim of describing the challenges faced in providing convenient access to health care
for undocumented migrants.
Results: Two main approaches to providing health care to undocumented migrants were identified. In
the cantons of Geneva and Vaud, we have specifics programs dedicated to this population, organized
around primary care consultations and interdisciplinary teams (nurses, social workers, doctors). These
structures belong to the public health system and work closely with the public hospital and emergency
services. Collaboration and partnership with private networks of institutions working with vulnerable
populations are also well developed.
In the other cantons we find mainly private initiatives dedicated to help undocumented people in
needed of medical care. These structures vary in size and, and may include social workers, nurses
and private doctors. Collaboration with the public health system is more complex and at times difficult.
Conclusion: the Swiss health care system provides varied responses to the need for access to health
care for undocumented migrants. The quality, size and clinical efficiency of care differ greatly between
cantons. From a clinical, public health and ethical perspective, we believe that an approach based on
active involvement of public authorities and public health structures along with close collaboration with
private socio-medical sector is the best option for respecting the right to health care for undocumented
migrants.
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P420
A brief assessment tool for the early diagnosis of geriatric syndromes in
primary care: the AGE programme
Nicolas Senn*, Jacques Cornuz, Pakize Palan, Christophe Büla, Stéfanie Monod
Policlinique Médicale Universitaire (Lausanne, CH); centre hospitalier universitaire vaudois
(Lausanne, CH)
Introduction:
The ageing of the population associated to the increase of prevalence of chronic diseases and
functional dependency are major public health challenges. Early diagnosis and management of
geriatric syndromes has been shown to delay functional decline, decrease the risk of
institutionalization, and improve quality of life in older persons. However, geriatric syndromes are often
underdiagnosed by primary care physicians what delays their adequate management. This is partly
due to the lack of adapted efficient tools to comprehensively assess old patients for major geriatric
syndromes in primary care. The AGE (Active Geriatric Evaluation) program is a collaborative project
between a primary care institution and a specialised geriatric unit that aims at developing a brief
assessment tool adapted to the primary care setting. We describe here the development of this
program.
Method: The brief geriatric exam assesses nine geriatric syndromes: 1) cognitive impairment; 2) mood
disorder; 3) functional impairment; 4) urinary incontinence; 5) malnutrition; 6) gait and balance
impairment; 7) osteoporosis; 8) hearing impairment; 9) visual impairment. The AGE program is
developed along 3 phases: 1) Validation of the geriatric consultation as gold standard; 2) investigation
of the performances of the brief geriatric exam; 3) assessment of the effectiveness of the brief geriatric
exam in routine primary care practices.
Results: Phase 1 (validation of the geriatric consultation) will be completed in February 2013. A
convenience sample (N=19) of patients from geriatric ambulatory consultations and home visits have
been evaluated by two independent geriatricians. Phase 2 will start in February 2013 with a small pilot
study that will establish the feasibility of the brief geriatric exam in primary care practice. Further
results will be presented during the meeting.
Conclusion: This program is designed to develop a brief geriatric exam to be used by primary care
physicians aiming at improving early diagnosis of geriatric syndromes. This original 3-phase project
guarantees the continuity and homogeneity in the development of the intervention and could serve as
an example of research collaboration between specialists and primary care physicians. Furthermore,
this program has the potential for developing new model of care for elderly people in primary care.
P421
Prediction of potentially avoidable readmission risk in a division of general
internal medicine: developing a locally predictive model from retrospective
data.
Marc Uhlmann*, Anne-Claude Griesser, Olivier Lamy, Hong Dung Duong, Estelle Lécureux
CHUV (Lausanne, CH)
Introduction: The rate of readmissions (RA) potentially avoidable within 30 days after discharge
(RAPA) is an inpatient quality of care indicator. Considering the burden and cost of RA, many models
have been developed to screen high risk patients in order to implement preventive measures.
Unfortunately the predictive value of these models is often disappointing, especially when applied in
another setting. The LACE index (Length of stay (LS), Acuity of admission, Charlson comorbidity
score (CCS) and number of Emergency department (ED) visits in the previous 6 months) is the best
validated. We tested the LACE index in our population and derived retrospectively our own model.
Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our 200 acute care beds division of
general internal medicine were analyzed. Our model was derived from several data including:
demographic data, entry mode, LS, CIM10 diagnosis, CCS, any surgical intervention during stay
(CHOP), DRG severity, number of admissions during previous 6 and 12 months, laboratory values,
number and types of medications.
was 72.0 +/- 16.8y, 50.3% were females. 14.2% were readmitted of which half were classified RAPA.
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Patients with early RA were more often <=73y, men, with oncological diagnosis, received more
medications (diuretics, steroids, opiates) and had more often laboratory abnormalities (p<0.0001 for
each item).
The LACE index had an AUC of 0.611 to predict RAPA. 6729 stays fulfilled all criteria to derive our
model to predict RAPA (versus not readmitted). This multivariate logistic regression model includes 5
variables: number of admissions during previous 12 months >= 1 (OR:1.96, z=8.1), oncological
diagnosis with metastases (OR:2.81, z= 7.3), sodium <135 mmol/l (OR:2.15, z=5.6), CCS>1 (OR:1.46,
z=3.9), and LS > median value (11 days, OR:1.36, z=3.7). Our model has an AUC of 0.696.
Conclusion: The low predictive value of the LACE index in our population to predict early RA is not
surprising. There are major differences between the Canadian and Swiss setting. For example,
admission rate through the ED (58% vs 93%) as well as median LS. Building a predictive model
derived from local data is necessary. In order to implement targeted preventive measures, it should
aim high risk patients for RAPA and be easily applicable. Nevertheless, our model needs further
development and validation with the 2012 data.
P422
Pregnancy-associated cardiomyopathy: a very rare case of severe
cardiomyopathy in a patient with a twin pregnancy
Maude Grueber*, Marco Macinetti, Daniel Hayoz
Hôpital cantonal Fribourgeois (Fribourg, CH)
Introduction:In the western population peripartum cardiomyopathy is an infrequent and serious
condition. Non-compaction cardiomyopathy is a rare genetic disease, sharing the morphologic
features of hypertrophic and dilated cardiomyopathies. It occurs from the embryonic arrest of
myocardial maturation altering the compaction of myocardial fibres. Clinical manifestations are early
heart failure (HF), systemic embolization, atrial and ventricular arrhythmias which can lead to sudden
cardiac death. Familial forms represent up to 18% of cases, usually with a dominant autonomic
transmission.
Case report:We report the case of a 28 years old woman in previously good condition, presenting in
the emergency department on Christmas-eve in acute respiratory distress. The patient is close to the
term of a twin pregnancy, reported as normal during the routine follow-up consultations. The history of
the patient is characterized by an increasing dyspnoea associated to a foamy cough. Following
evaluation, we diagnosed an acute pulmonary oedema. The ECG showed signs of left ventricular
hypertrophy. Due to pre-eclampsia caesarean delivery was rapidly performed. After delivery, the
clinical status improved under medical therapy for heart failure. The first echocardiography showed a
severe reduction of the left ventricular (LV) function (15%) with a dilated LV, with an image of hypertrabeculation. A cardiac-MRI confirmed the elevated trabeculated mass of the LV with a ratio of noncompacted/compacted myocardium of 3.2. After 2 weeks of medical treatment, we observed a
significant clinical improvement as well as a LV ejection fraction of 36%. The twins are presently in a
good general status and they have been referred to paediatric cardiologist for further evaluation.
Discussion:Echocardiography is the most frequently used imaging modality to establish the diagnosis
of non-compaction cardiomyopathy, followed more recently by cardiac MRI. Different diagnostic
criteria exist based on the myocardial anatomy observed on the images. Treatment focuses on the
correction of heart failure and the prevention of arrhythmic events. Systemic cardioembolic events are
associated with the disease and anticoagulation must be individualized based on a risk/benefit
analysis. Medical devices are considered for heart support according to the guidelines for HF
treatment and heart transplantation should be considered when HF is refractory to optimal medical
and device therapies.
P423
Vertebral fracture discrimination by bone mineral density (BMD), microarchitecture estimation (TBS), and FRAX in stand-alone, combined or adjusted
approaches: the OsteoLaus study
Olivier Lamy*, Marc-Antoine Krieg, Delphine Stoll, Bérengère Aubry-Rozier, Marie Metzger, Peter
Vollenweider, Gerard Waeber, Martin Preisig, Didier Hans
University Hospital of Lausanne (Lausanne, CH)
Introduction: Trabecular Bone Score (TBS), a novel grey-level measurement derived from lumbar
spine DXA image texture, is related to microarchitecture (MA) and fracture risk independently of Bone
167
Mineral Density (BMD). FRAX estimates the 10-year probability of hip and major osteoporotic fracture
(MOF) using clinical risk factors (CRF) and femoral neck BMD. An adjustment of FRAX probability
according to lumbar spine TBS was recently proposed. The aim of the study is to compare the
performance of FRAX versus TBS adjusted FRAX to better identify women at high fracture risk.
Material and Method: The OsteoLaus cohort (a sub- study of Colaus; women 50 to 80 years living in
Lausanne) started in 2010. CRF for OP, FRAX, lumbar spine and hip BMD, vertebral fracture (VF)
assessment by DXA and MA evaluation by TBS were recorded. Sensitivity and specificity in regard to
VF grade 2&3 has been calculated for all bone modalities as stand-alone or combined approaches.
The adjustment of FRAX by TBS has been applied as proposed by Leslie WD et al. Integrated
discrimination index and net reclassification improvement have also been investigated.
Results: We included 911 women: mean age 65.2±7.9 y, BMI 25.7±4.4, mean lumbar spine BMD
0.931±0.163 (T-score -1.04 SD), TBS 1.289±0.100. As expected, correlation between BMD and site
matched TBS is low (r2=0.16). Prevalence of VFx grade 2/3 and MOF are 7.5% and 15.0%
respectively. Spine BMD (-2.5 T-score threshold)Se 29.4%, Sp 82.7%; Lowest BMD (-2.5 T-score
threshold)Se 35.3%, Sp 80.9%; Spine TBS (-1.200 threshold) Se 51.5%, Sp
77.1%; FRAX MOF
(20% threshold) Se 38.2%, Sp 94.8%; Lowest BMD or TBS thresholds Se 64.7%, Sp 65.4%; Spine
TBS or FRAX MOF (20%thresholds) Se 63.2%, Sp 74.4%; TBS adjusted FRAX All fracture (20%
threshold)Se 50.0%,Sp 89.9%.
When used to reclassify fracture risk, this gave a significant increase in integrated discrimination index
for VFx (+2.5%, P<0.001), with net reclassification improvement +7.6% for VFx (P<0.001).
Conclusion: While the optimal threshold for TBS should be investigated, an incremental improvement
in fracture identification was seen by using lumbar spine TBS in combination with FRAX. If validated in
prospective cohorts, lumbar spine TBS may become clinically useful for enhancing fracture prediction
from FRAX. Such simple way to take TBS into account would allow the use of current medical society
recommendations regarding osteoporosis management with only minor adaptation.
P424
Severe agranulocytosis induced by metamizol, a case report
Marisa Kälin*, Bernard Surial, Natascia Corti, Georg Tscherry, Esther Bächli
Spital Uster (Uster, CH); Universitätsspital Zürich (Zürich, CH)
Introduction: Metamizol is a highly potent second-line medication for the treatment of pain and fever,
which are unresponsive to Paracetamol or non-steroidal anti-inflammatory drugs. Due to several large
studies showing a possible association with agranulocytosis after long-term intake, its usage has been
discussed controversially, and is therefore restricted in many countries. We report a case of severe
neutropenia induced by Metamizol.
Case presentation: An 81-year-old female patient presented to our emergency department with a
history of fever, malaise and sore throat and perianal pain for 3 days. The clinical examination was
normal except for oral ulcers. Due to a chronic pain syndrome she was taking Paracetamol, Metamizol
and transdermal Fentanyl within the last months. Laboratory analysis showed inflammation (C reactive protein level 332 mg/l) and severe agranulocytosis (neutrophil count 100/ul) with otherwise
normal blood values. A chest radiograph showed no infiltrate, urine and blood culture were negative. A
peripheral blood smear showed no evidence for hematologic malignancy. A presumptive diagnosis of
drug-induced agranulocytosis due to Metamizol was made and its administration was discontinued.
After treatment with piperacilline/tazobactam and granulocyte colony-stimulating factor,
agranulocytosis, fever and mucous eruptions resolved on day 6 after admission.
Discussion: Neutropenic fever syndrome represents a rare, but potentially lethal complication of longterm treatment with Metamizol. Despite of this fatal side effect, Metamizol is increasingly being used in
Switzerland. In our hospital with 10’000 inpatients being treated yearly, we have been using 52’045
grams of Metamizol in 2012 compared to 97’566 grams of Paracetamol and 18’300 grams of
Ibuprofen. With only 5 cases being reported to Swissmedic between 1997 and 2005, underreporting
and/or under-recognition of this condition seem likely. To date, no conclusive incidence rates are
available, and its prevalence can only be estimated with the use of case reports. Therefore, complete
blood count must be performed in every patient who presents with fever under chronic treatment with
Metamizol, and its administration must be stopped. In studies, patients treated with hematopoietic
growth factor had shorter duration of neutropenia and a lower rate of infectious or fatal complications,
so its use should be considered in patients with agranulocytosis and/or life-threatening infectious
conditions.
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P425
Should a ‘prosthetic device’ be a major Duke criterion?
Seraina von Moos*, Christina Gold, Isabelle Kunz, Joachim Thöne
Introduction: The Duke criteria for endocarditis are well known, including major criteria (2 positive
blood cultures, positive echocardiography with vegetations) and minor criteria (predisposition, fever,
septic emboli, immunological reactions). Nevertheless, there is often a diagnostic delay.
Case presentation: In september 2012, a 54 year old man, was referred to the university hospital
Zurich with repeated episodes of fever and chills since easter 2012; after a surgical intervention for a
trivial thumb injury. In June he was diagnosed with right sided lung emboli in a peripheral hospital and
anticoagulation was started. At that time a diagnostic work-up for fever of unknown origin including
several blood cultures remained negative. Similarly, a transoesophageal echocardiography performed
end of august did not show any vegetation. In the personal history a sick sinus syndrome was known,
treated in 1987 with a pacemaker, changed in 1998.
At the emergency visit in September the patient reported progressive dyspnea. Clinical exam revealed
right basal crackles and conventional radiography showed suspicion of a right sided infiltrate.
Subsequent antibiotic treatment led to transient symptom amelioration. A new deterioration motivated
accomplishment of a 18-FDG PET-CT showing novel left sided lung infiltrates, in the differential
diagnosis described as new emboli. Repeated blood cultures (in totally 12) always remained without
growths even for the HACEK group. A PCR and Serology was negative, too. As fever episodes were
accelerating, a novel transoesophageal echocardiography was performed begin of January, showing a
3 cm thrombus adherent to the pacemaker electrode together with several tricuspidal vegetations.
Pacemaker cultures were positive for coagulase negative staphylococcus. Under a medical tri-therapy
and surgical removal of the pacemaker the patient recovered.
Discussion: Here we report a classical right heart endocarditis associated with repetitive fever and
septic lung emboli in a patient with a pacemaker. There was a considerable diagnostic delay, as major
Duke criteria remained negative. Nevertheless suspicion of endocarditis needs to be kept high in
patients with predisposition. Could inclusion of ‘prosthetic device’ in the major Duke criteria accelerate
the diagnosis of endocarditis?
P426
Communication strategy by adversaries to health protection during debate of
the federal smoking ban, 2008-2012
Rainer Kaelin* on behalf of Initiativkomitee Schutz vor Passivrauchen
Background: The swiss legislative process towards a national smoking ban in public places started in
2004 by the signature of the WHO framework convention of tobacco control and the initiative of MP F.
Gutzwiller MD. By 10/2008 it had resulted in a federal Alibi"Gastro-boro"Law, elaborated under heavy
pressure of lobbying, failing to meet WHO standards and passed by the national council (NC)with just
89 yes/88no. Therefore the Swiss lung league (SLL, federation of cantonal lung leagues)launched a
popular initiative aiming the law proposal of the NC's health commission that originally was backed by
the federal council. Despite 120 000 signatures collected by 2010 and the support of a large alliance
of health organizations, the initiative was refused by 66% in a popular vote 9/2012 after heavy
campaigning. Since 2008 the "economy's alliance for moderate prevention policy" was founded by
USAM (defending economy's interest), with the Tobacco industry and political parties as
members/supporters, the links between politicians and industry might have favored efficient
desinformation of the public.
Aim/Method: Analysis of official statements, their timing with media reports.
Results:A.The highly respected director of the federal office of health Prof.Zeltner was denigrated in
the USAM's journal as "health Taliban"; this was regularly repeated in media articles reporting on
preventive issues. In the right wing journal Weltwoche, Prof. Stadler, Universitiy professor of
immunology, wrote about the decline of coronary syndromes as false and disqualified the passive
smoke issue as an invention. B. The initiative was refused in the NC by 130 yes/60no,indicating far
more support of the federal law than by its adoption. Despite of its original position, the federal council
described the initative as extreme, suggesting that a general smoking ban was its aim.C. During the
campaign before the vote, publicity and media reports repeated these statements
Conclusion: During the elaboration of the federal smoking ban and the subsequent public debate of
the law proposal of the initiative, politicians, economy and media diffused coherently the same
message: prevention is generally controversial, prevention specialists are zealotes,the actual law
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works at satisfaction, the proposed improvement is an absolute smoking ban. The efficient
communication strategy suggests efficienbt links in the USAM's network, in the interest of the Tobacco
industry.
P427
Polyneuropathie als Frühkomplikation eines Diabetes mellitus Typ 1
Paula Rosegger*, Philippe Rochat, Beat Frauchiger
Kantonsspital Frauenfeld (Frauenfeld, CH)
Einleitung: Bei einem 32-jährigen Patient mit Diabetes mellitus Typ 1 (DM1) wurde bereits 2 Monate
nach der Diagnose eine kardiovaskuläre und gastrointestinale autonome und periphere
Polyneuropathie (PNP) festgestellt. Das frühe Auftreten dieser Komplikation im Krankheitsverlauf ist
ungewöhnlich. In der Literatur sind nur Einzelfälle beschrieben und sie ist mit einer schlechten
Überlebensprognose verbunden.
Fall: Die Zuweisung erfolgte wegen rezidivierenden Synkopen, postprandialen Bauchschmerzen und
Fussbrennen. Bei Eintritt war der Patient kachektisch, die Achillessehnenreflexe fehlten bds,
Vibrationssinn malleolär je 6/8. Der Blutzucker war 20 mmol/l, das HbA1c 9,1%. Positive Anti-GADund -IA2-AK bestätigten den vor 2 Monaten diagnostizierten DM1. Neurographisch (EMG) bestand
eine sensomotorische, beinbetonte, demyelinisierende, axonale PNP. Ewing- und Schellong-Test
[Tab] zeigten Zeichen der autonomen PNP (Herzfrequenz- und Blutdruckvariabilität bei
Provokationsmanövern pathologisch, persistierende Ruhetachykardie). Die Magendarmpassage
zeigte eine Gastroparese mit klinischer Besserung unter Motilium, nicht aber unter Erythromycin. Die
Suche nach weiteren PNP-Ursachen blieb negativ (Porphyrie, Bleispiegel, Hypothyreose, Alkohol
unregelmässig, normales CDT, Vitamin B12, Folat, BSR, CRP, ANA, ANCA, RF,
Proteinelektrophorese, Neoplasie [Abdomen-CT, obere und untere Endoskopie], Borrelien, EBV,
TPHA, HIV, HBV, HCV). Es bestanden keine Hinweise auf eine chronische inflammatorische
demyelinisierende PNP (Lumbalpunktion, EMG). Ein Synacthentest war normal. Wir hatten keine
sicheren Hinweise auf weitere diabetische Spätfolgen (Niere, Augen, Pulse). Wegen arterieller
Hypertonie Verzicht auf Fludrocortison und Midodrine.
Betablocker besserten die invalidisierende Orthostase nur gering. Die anschliessende stationäre
Neurorehabilitation blieb ohne wesentlichen Erfolg. Die Blutzuckerwerte sanken unter Insulin auf 59mmol/l. Die Parästhesien besserten sich schliesslich unter Gabapentin.
Schlussfolgerung: Die PNP tritt beim DM1 in Abhängigkeit der Blutzuckereinstellung und der
Krankheitsdauer typischerweise erst nach Jahren bis Jahrzehnten auf. Dieser Fall zeigt die mögliche,
seltene Frühmanifestation der PNP inklusive Befall des autonomen Nervensystems bereits 2 Monate
nach Erstdiagnose eines schlecht eingestellten DM1 nach sorgfältigem Ausschluss der
Differentialdiagnosen. Primäres Therapieziel ist die Euglykämie. Die medikamentöse
Symptomlinderung ist schwierig.
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P428
Evaluation of ankle-brachial index measurements performed by medical
students
Matteo Monti*, Luca Calanca, Adriano Alatri, Lucia Mazzolai
Centre Hospitalier Universitaire Vaudoise (Lausanne, CH)
Introduction: Ankle-brachial index (ABI) is a relatively simple, inexpensive, and non-invasive test used
by angiologists for diagnosis of peripheral artery disease (PAD). ABI is also a predictor of
cardiovascular (CV) events and mortality in PAD patients. ABI measurements performed by
angiologists show good accuracy and reproducibility with a sensitivity and specificity of 89-95% and
95-100%, respectively. ABI measurement could be a valuable tool for general and internal medicine
physicians for patients screening and CV morbidity evaluation. In the present study we evaluated
accuracy of ABI measurements, performed in hospitalized patients, by 6th year medical students after
a short training period.
Methods: Consecutive hospitalized patients (> 60 years) with at least one CV risk factor (diabetes,
hypertension, dyslipidemia, previous cardiac- or cerebro-vascular disease myocardial, active or past
smoking) were recruited.
ABI's were measured according to standard method (highest ankle systolic pressure over highest
humeral systolic pressure) using a hand held Doppler probe. ABI values were calculated separately
for each limb. All participating students received a short training period (3 hours) by an experimented
angiologist before study start. Sensitivity, specificity, negative predictive value (NPV), positive
predictive value (VPP), and Kappa test weighted were calculated according to results obtained in
patients with or without PAD (as assessed by the angiologist).
171
Results: Fifty-nine consecutive patients (27 women) were recruited. In 2 patients, for technical reasons
(leg ulcers), ABI was calculated in one leg only therefore, a total of 116 ABI's were available for
analysis.
According to the reference group ABI resulted: normal (>0.9-1.4) in 62.1% of cases, abnormal (>1.4)
in 18.1%, mild PAD (0.9-0.7) in 7.8%, moderate PAD (0.69-0.5) in 10.3%, and severe PAD (<0.5) in
1.7% of cases.
Overall, sensitivity, specificity, VPN, and VPP were 75.0%, 87.5%, 85.1% and 78.6%, respectively.
Resulting kappa test weighted was of 0.5854 (moderate agreement). In 5 cases, students were not
able to determine ABI. Among CV risk factor, only blood pressure was significantly higher in PAD
(p<0.001) compared to non PAD patients.
Conclusions: ABI measurements require well trained personnel and a short training period is not
sufficient to guarantee adequate accuracy and reproducibility.
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P429
Not in the right space: left lateral cardiac displacement due to an unusual
cause
Niels Holm*, Esther Bächli, Tobias Hoefflinghaus
Case report: A 69 year old male patient was admitted to the intensive care unit because of septic
shock of unknown cause. The patient’s history was remarkable for alcoholic liver disease with cirrhosis
and lung emphysema. The chest X-ray (CXR) revealed an enlarged and displaced cardiac silhouette
of atypical shape without signs of congestive heart failure. Electrocardiogram (ECG) showed right axis
deviation, leftward displaced transition zone in the precordial leads and significant changes of QRS
axis and R wave amplitude between admission and follow-up. Echocardiographic images were hard to
obtain, atypical lateral views were required. Computed tomography of the chest revealed cardiac
displacement into the left thoracic cavity. Congenital absent pericardium (CAP) was assumed. Shortly
after, the patient died of lung failure. Autopsy confirmed pneumonia as cause of death and incidentally
revealed a complete isolated absence of the pericardium and a displaced heart to the left.
Discussion: CAP was first described by Colombo (1559). The etiology of this anomaly is an incomplete
development of the transversal septum and the pleuropericardial folding in the early embryonic stage.
The prevalence is unknown; various authors have described isolated forms in surgical or pathological
series of 0.0001% to 0.044%. One third of all cases were associated with other cardiac lesions, like
atrial septal defect, bicuspid aortic valve and tetralogy of Fallot. Patients can present asymptomatic or
with atypical chest pain, largely nonexertional and with postural dependency. Partial defects can lead
to cardiac herniation with shock or sudden death. Clinical examination may show lateral displacement
of the heart. ECG often displays a partial right bundle block pattern and a deviated transition zone to
the left. CXR can show a levoshift with loss of the right heart border. Often lung tissue is interposed
between main pulmonary artery and aorta. Echocardiographic examination requires unusual views
and is difficult to interpret because of cardiac hypermobility leading to abnormal swinging and
ventricular septal motion. CXR combined with magnetic resonance imaging are key to establish the
diagnosis. In patients with debilitating symptoms pericardial reconstruction is a curative option.
Conclusion: Isolated CAP is a rare congenital anomaly and may cause acute chest pain, shock and
sudden death. However, in our case it was an incidental finding and not related to the outcome of this
patient.
P430
Striving for perfect laboratory values might cause harm
Teresa Stelzer*, Ludwig Theodor Heuss, Konstantin Burgmann
Spital Zollikerberg (Zollikerberg, CH)
Introduction: Statins are lipid-lowering drugs, well established in secondary and primary prevention of
cardiovascular events. The major side effect is myotoxicity, which can lead to life threatening renal
failure. Case report: A 55 year-old woman, suffering from type-1 diabetes and hypertension, was
admitted to our emergency unit for generalised myalgia. Her daily medication consisted of amlodipin,
telmisartan, hydrochlorothiazide, atorvastatin and insulin. Laboratory findings were: ASAT 1674U/l,
ALAT 1371U/l, CK 40096U/l, Na+ 125mmol/l. Other values, including differential blood count,
creatinine, CRP and TSH were normal. A1c-level was 5.6%. The patient was transferred to the ICU for
acute rhabdomyolysis, and intravenous hydration according to guidelines was performed. Within few
days, CK normalised and symptoms disappeared. Renal function was not impaired. Two weeks
before, the patient received telephone advice from her general practitioner after obtaining laboratory
results showing a LDL-level of 2mmol/l despite statin therapy: She was told to double the dose,
meaning 160mg of atorvastatin per day (max. daily dose 80mg). Discussion: Statin-induced myopathy
is rare and its pathophysiological mechanism is poorly understood. Nevertheless, myotoxicity is clearly
dose-dependent and, since most statins are metabolised via CYP450-enzymes, various drug
interferences can occur. Other comorbidities such as diabetes, hypothyreosis and impaired renal or
hepatic function further increase the risk of myotoxicity. Statin-induced hepatopathy is also well
known. In primary and secondary prophylaxis of cardiovascular events, target LDL-level <2.6mmol/l is
widely recognised. For individuals at high risk, as in macrovascular disease, LDL-level should be even
173
lower, <1.8mmol/l. Whether this strict goal also applies to diabetic patients (so-called “high-risk
equivalent”), is not clear. Obviously, the general practitioner was not aware that the patient was
already taking the maximum daily dosage of atorvastatin. Conclusion: In our case, rhabdomyolysis
seems to be clearly due to a statin overdosage. Furthermore, elevated ASAT/ALAT-levels and
hyponatremia are likely correlated to drug-related side effects (statin, thiazide). We conclude that the
prescription of drugs should always be considered weighing the risks posed to the individual. Aiming
for too ambitious metabolic control should be avoided, especially as LDL-targets in primary prevention
are not clearly established.
P431
More than honey: honey consumption followed by bradycardia and syncope in
the emergency department
Gonca Suna*, Sarah Schatzmann, Hans Jürg Beer
Kantonsspital Baden (Baden, CH)
Background: Consumption of honey is generally thought to have multiple health benefits. However,
honey contaminated with grayanotoxins can lead to severe hypotension and bradycardia.
Case description: In this case report, we present a 46-year old patient with severe hypotension and
bradycardia after the intake of turkish honey. Following a period of malaise the patient developed
nausea, vomiting and collapsed from hypotension. In the E.R., bradycardia of <40/min and a blood
pressure of 70/40mmHg were found. The patient was subsequently treated with intravenous saline
and metoclopramide and after an uneventful overnight stay he was discharged the following morning.
The patient had known arterial hypertension and a positive family history for coronary heart disease,
but there was no history of bradycardia or sick sinus syndrome. The relevant detail of his history was
the consumption of turkish honey half an hour prior to the onset of his symptoms.
Discussion: Hypotension and bradycardia are common findings in an emergency department.
However, a very uncommon reason for these symptoms is intoxication from grayanotoxincontaminated honey, also called “mad honey”. This toxin is found in honey produced from the nectar
of some species of rhododendron and other plants of the Ericaceae family, growing in the black sea
region of Turkey, as well as in Brazil, Japan, Nepal and Northern America. The target of grayanotoxins
are neuronal voltage-gated sodium-channels, increasing their sodium permeability. The cells remain in
a state of depolarisation and therefore in an activated state. The resulting peripheral vagal stimulation
is suggested to be the mechanism of bradycardia. Intoxication is characterized by nausea, vomiting,
hypotension and bradycardia, but severe complications such as complete atrioventricular block III and
consecutive syncope have also been described. History of honey intake is the key to diagnosis and
treatment is managed with saline infusions and atropine. In rare cases it is necessary to implant a
temporary pacemaker.
Conclusion: Grayanotoxin-induced bradycardia, hypotension and syncope after ingestion of honey
derived from pollen of certain rhododendron species can be added to the rare differential diagnoses of
syncope in the emergency room.
P432
Detoxification of gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL)dependence with pharmaceutical GHB: a case study
Barbara Broers*, Juan Garcia Martinez, Karim Bendjelid, Cor de Jong
Hôpitaux Universitaires Genève (Genève, CH); NISPA (Nijmegen, NL)
Introduction: Gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL) are used
recreationally for their (dose-dependent) euphoric, relaxing, aphrodisiac and anti-anxiety effects. The
prevalence of these easily available drugs may be increasing, and with it problems related to
intoxication, tolerance and dependence. In case of dependence, withdrawal is often characterized by
severe autonomic instability, and by agitation, confusion, life-threatening delirium and seizures.
Symptoms can be uncontrollable, even with to high dosages of benzodiazepines (GABA-A ergic),
while GHB activates GABA-B and GHB-specific receptors. Symptoms can last up to 2 weeks and
patients often need intensive care. A Dutch group developed a tapering scheme using pharmaceutical
GHB (in CH available as Xyrem®, UCB-Pharma SA, Bulle) and published a case-series on controlled
withdrawal within one week, without complications and low level of medical care 1.
Method: case study
Result: a 32 years old male patient presented with a GBL dependence (consuming at least every 2 hr
for up to 16-20 gr daily), and benzodiazepine dependence (100 mg chlorazepate/day). He gave
174
informed consent for off-label use of Xyrem® if benzodiazepines would not allow control of withdrawal
symptoms. Withdrawal symptoms started within 2 hours after last intake of GLB. Despite 100 mg
chlorazepate and 20 mg of lorazepam over 7 hr, he developed severe hypertension, agitation and
confusion, also not calmed by intravenous perfusion of 10 mg/hr of lorazepam. He was transferred to
the IC and sedated with propofol (50mg/hr intravenous perfusion). The next morning, still agitated, the
patient received 1.5 gr oral Xyrem©. Within 15' the patient calmed down, agitation and confusion
disappeared, and iv benzodiazepines could be stopped. The patient received Xyrem® every 3 hours in
digressive doses (0.25 g/dose/day) and was fully detoxified in 6 days without any complication.
Conclusion: GHB and GBL withdrawal symptoms are potentially life threatening despite high dosage
benzodiazepines. Applying of a general principle in addiction medicine, using a simile, controlled
tapering under clinical control with a pharmaceutical brand GHB (Xyrem®) appears safe, efficacious
and feasible in a case series, warranting further clinical research.
1 Eur Addict Res 2012;18:40-45
P433
Is the restriction of tobacco products sales to minors associated with different
modes of tobacco consumption among young Swiss men?
Carole Clair*, Roland Fischer, Gerhard Gmel, Jacques Cornuz
Policlinique Médicale Universitaire (Lausanne, CH); Centre de traitement en alcoologie (Lausanne,
CH)
Introduction: Tobacco control measures are effective to prevent the harms caused by tobacco
consumption. Some measures such as restriction of tobacco products sales to minors have the
potential to decrease the prevalence of cigarette smoking, among young people whose smoking
habits are not strongly implemented. However, young people might adopt other modes of tobacco
consumption, not legally obtained, to replace cigarette smoking. We aimed to describe the association
between legislation on tobacco products sales to minors and cigarette smoking as well as other form
of tobacco consumption such as smokeless tobacco and waterpipe, which are usually not legally
obtained.
Methods: We did a cross sectional analysis of the baseline data of a Cohort Study on Substance Use
Risk Factors (C-SURF). All young men at the national Swiss army recruitment centers were invited to
participate in this study. Participants filled out a computer based questionnaire on socio-professional
background and substance use. Descriptive statistics and multivariable-adjusted logistic regression
were performed.
Results: We included 5,990 participants, mean age was 19.5 years and 55% were French speaking.
Self-reported smoking prevalence was 47% (26.1% daily smokers, 21.3% occasional smokers),
consumption of smokeless tobacco during the last 12 months was 26.8% and of waterpipe 36.2%.
Regarding tobacco products sales to minors, 24% lived in cantons where there was no legislation,
43% in cantons where sales were forbidden to people < 16 years old and 33% in cantons where sales
were forbidden to people < 18 years old. Restriction of sales to minor did not influence significantly
cigarette smoking but it was significantly associated with smokeless tobacco and waterpipe
consumption. Living in cantons where sales were forbidden < 16 was significantly associated with
consumption of smokeless tobacco (multi-adjusted OR 1.49, 95% CI 1.23-1.80) compared with living
in cantons without legislation and living in cantons were sales were forbidden < 18 was associated
with consumption of smokeless tobacco (multi-adjusted OR 1.26, 95% CI 1.05-1.52). Similarly, living
in cantons where sales were forbidden (< 16 or < 18) was associated with waterpipe consumption
compared with living in cantons without legislation (multi-adjusted OR 1.25, 95% CI 1.05-1.48 or 1.28,
95% CI 1.08-1.51, respectively).
Conclusion: Restriction of sales to minor is associated with consumption of smokeless tobacco and
waterpipe.
P434
Patient characteristics of adult primary immunodeficiencies in Bern
Michaela Bitzenhofer-Grüber*, Peter Jandus, Urs Steiner, Werner Pichler, Arthur Helbling
Inselspital, 3010 Bern (Bern, CH); Hôpitaux Universitaires de Genève (Genève, CH); Spital Tiefenau
(Bern, CH)
Background: Primary immunodeficiencies (PID) constitute a large group disease, including at least
176 conservatively defined hereditary disorders affecting the development and function of the immune
system. The number of known PIDs has increased considerably over the last 20 years. The European
175
Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and
research data on patients with PID.
Methods: Clinical and biological features of 64 adults (> 18 years) with PID were registered in ESID
online patient registry by the allergy-immunology outpatient clinic at the University Hospital of Bern to
illustrate the clinical characteristics and distinctions of our patients.
Results: We present preliminary data of 64 adult patients, all with defined antibody immunodeficiency.
Subclass deficiencies (n= 25, 39%) were the most common category followed by the common variable
immunodeficiency (n= 23, 36%), unclassifiable hypogammaglobulinemia (n= 14, 24%), and selective
antibody deficiencies (n= 2, 3%). CVID patients showed frequently a non allergic bronchial
hyperresponsiveness (n= 7, 30%) and bronchiectasis (n= 9, 39%). 15 of 23 CVID patients were
substituted with immunoglobulins, 12 of 23 CVID patients showed complications not directly related to
infections: sarcoid like lesions (n= 3), autoimmune disease (n= 6) and lymphoma (n= 3). Patients with
subclass deficiencies had more atopic diseases and skin infections. Flow cytometric evaluations of
CD4, CD8, and B-cells revealed lower levels in CVID group than in other groups. No significant
difference was found for B-cell subpopulations.
Conclusion: All over Europe, the number of patients with PID is still unknown. In our center devoted to
adult medicine, the vast majority of patients have predominant antibody deficiencies, although some
patients with CVID have low T-cell numbers and functions. CVID patients have more noninfectious
complications, which need to be followed to prevent morbidity and mortality. The collection of data
allows to find warning signs because of the growing knowledge of clinical manifestation of PID in
adults for a better diagnosis and lower diagnostic delay.
P435
Should doctors tell their patients of the cardioprotective treatment effects of
antihypertensive medications and lipid-lowering drugs? The implementation of
the concept of shared decision making
Vladimir Sibalic*, Silke Henzen, Daniel Reuss, Guy Bourgeois, Marcel Schai, Sandra Simic, Aida
Karajkovic, Georg Stoffel
Private University in the Principality of Liechtenstein (Triesen) (St. Gallen, CH); Collegium for
Research in Primary Care (Sevelen, CH); Collegium for Research in Primary Care (Arbon, CH); Praxis
(St. Gallen, CH); Collegium for Research in Primary Care (Winterthur, CH)
Introduction: Physicians hesitate to discuss with patients the expected treatment effect of
cardiovascular agents. They are afraid of disappointing the patients and to reduce the therapeutic
adherence. Shared decision making is characterized by the interaction of patient’s individual
preferences and the professional medical contribution of the physicians. For clinical decision making, it
is meaningful to use the measure "number needed to treat", to explain the patients the potential
treatment effect.
Methods: This ongoing interrogation takes place in six primary-care offices in the Swiss Cantons
St.Gallen, Thurgau and Zurich. The study question addresses the patient’s wishes to learn more about
the treatment effect of drugs. It tests the readiness to take medications despite the lack of certainty for
the intended positive result.
The key-study question is as follows: “Would you take a newly developed drug that has shown to
prevent a myocardial infarction in 1 out of 50 patients (or 100-thousand out of 5-million patients) within
5 years? The remaining 49 patients would have taken the drug for 5 years without any benefit,
because they wouldn’t have had a myocardial infarction anyway. In other words, 49 patients would
have had taken the drug quasi without sense“. All patients over the age of 18 were asked to
participate. The patient-comorbidities were noted. The preliminary results of the first week studyperiod are shown.
Results: 102 patients were asked to participate. 92 filled out the questionnaire. 50% were male. Mean
age was 52 years (SD 18.9) (SEM 1.99). 21.7% had cardiovascular comorbidity. 41% were not
chronically ill. 53.3% of all would agree to take the pill. 31.5% would refuse. 15.2% were irresolute.
75% of cardiovascular patients would agree to swallow the drugs. 0% did not understand the question.
55.5% were disappointed by the treatment effect. 77.2% wanted to learn more about drug-effects.
37% felt well after the interrogation. 31.5% felt indisposed or surprised. None were frightened. 30.4%
showed no emotions. 89.1% found this interrogation reasonable.
Conclusion: The patients seem to know better how to deal with uncertainty than physicians might
expect. The physicians should consider telling the patients the whole story about the expected
treatment effect of prophylactic cardiovascular medications, because patients on higher cardiovascular
risk are known to profit most from treatment and they are very likely to agree the therapy.
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P436
Drug-related problems in a general internal medicine service
Bertrand Guignard*, Caroline Samer, Arnaud Perrier, Pascal Bonnabry, Pierre Dayer, Jules
Desmeules
Introduction: Some patients admitted to internal medicine wards receive a large number of drugs and
are at risk of drug-related problems (DRPs) that may be associated with morbidity and mortality. The
aim of the present study was to detect suboptimal drug use in 2 pilot wards of a general internal
medicine service and to offer a pharmacological and pharmaceutical evaluation to improve drug
prescription.
Method: This was a prospective study conducted during 6 months in 2 internal medicine wards in a
2’000-bed university hospital. Physician rounds were attended once every other week in each ward by
a clinical pharmacist and a clinical pharmacologist. All patients met during the physician rounds were
included. Prescriptions were analyzed through an assessment grid to detect DRPs. Treatment
optimizations were suggested to prescribers during the round. The main outcome measures were:
(1) most frequent DRPs and involved drugs or drug classes;
(2) types of intervention required: no intervention, verbal suggestion of treatment optimization, or
specialized written consultation;
(3) acceptance rate by prescribers.
Results: 145 patients (mean age 68 (21-99); 48% female) were included with 1523 prescriptions
(mean of 10.6 (0-21) prescriptions per patient). 383 DRPs were identified (mean of 2.6 (0-12) DRPs
per patient). The most frequently identified DRPs were: (a) drug interactions (21%), (b) untreated
indications (18%), (c) overdosage (16%) and (d) drug used without a valid indication (10%). The most
frequently involved drugs or drug classes were (a) for drug interactions: tramadol, antidepressants and
acenocoumarol; (b) for untreated indications: calcium-vitamin D, statins and aspirin; (c) for
overdosage: proton pump inhibitors and paracetamol; (d) for drug used without a valid indication:
proton pump inhibitors and aspirin.
51% of the identified DRPs were considered as clinically not relevant and were not reported to the
prescribers, 42% were reported with a verbal suggestion of treatment optimization, and 7% were
considered as complex and triggered a specialized written consultation by a clinical pharmacologist.
Suggestions of treatment optimization were accepted by prescribers in 84% of cases. Accepted
suggestions were applied by physicians in 64% of cases.
Conclusion: The most frequently identified DRPs were drug interactions. Half of the identified DRPs
required a suggestion of treatment optimization, which was accepted and applied by prescribers in
most cases.
P437
Depister le VIH ? Oui mais pas sans pouvoir offrir un traitement
Sophie Durieux-Paillard*, Alexandra Calmy, Marius Besson
Programme santé migrants, HUG (Genève, CH); consultation maladies infectieuses, HUG (Genève,
CH); consultation ambulatoire mobile de soins communautaires HUG (Besson, CH)
Introduction: Depuis 7 ans, en Suisse, dans le cadre de la lutte contre le VIH/sida, l'Office fédéral de la
santé publique promeut une stratégie de "VCT" (voluntary counselling and testing) auprès des
populations les plus à risque. Les migrants sont l'une de ces cibles. Parallèlement au developement
d'un concept de VCT adapté aux caractéristiques des migrants(recours aux interprètes, discours
adapté au niveau d'éducation, formulation culturelle adéquate), s'est posée la problématique éthique
de dépister des migrants sans statut légal alors que ces personnes ne peuvent pas accéder à une
thérapie antirétrovirale (TARV), faute de moyens pour le financer. Le cout des TARV et le caractère
chronique de ces traitements, rendaient inenvisageables leur prise en charge par un financement
institutionnel. Enfin, ne pas traiter des patients VIH précocement les exposent à des complications
sévères, dangereuses et également coûteuses.
Methode: recherche de fonds afin de financer les cotisations de caisse-maladie, pour une durée
maximale d'un an, aux patients dépistés positifs pour le VIH et nécessitant un traitement, si aucune
alternative n'est possible. Durant cette année d'assistance financière, une équipe psycho-sociale
assure un travail de soutien afin de permettre au patient, soit de retrouver une capacité de travail lui
permettant d'être autonome, soit d'obtenir un statut administratif lui donnant accès à l'aide sociale, soit
de bénéficier d'une aide au retour si la TARV est accessible dans son pays.
177
Resultats: un financement de 60'000 FS a été trouvé, dans le cadre d'un partenariat public/privé.
Pendant une durée de 18 mois, 30 situations de patients migrants précaires ont été examinées et 10
personnes ont été elligibles pour un appui par le fonds. La durée moyenne du soutien financier a été
de 7.8 mois. 6 patients ont récupéré une capacité de travail leur permettant d'être autonome bien que
sans statut légal, 1 a obtenu un permis de sejour stable, 2 sont retournés dans leur pays d'origine et
un dans un pays tiers. Aucun n'a nécessité d'hospitalsiation durant la période de suivi.
Conclusion: il est éthiquement inacceptable de promouvoir le dépistage du VIH/sida si les patients
dépistés positifs n'ont pas accès à une TARV. Dans le système de santé suisse actuel, une projet
comme le notre constitue une solution pragmatique permettant de promouvoir le dépistage auprès des
populations les plus à risque, tout en assurant aux patients une qualité des soins adéquate.
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Hemostasis, Vascular Biology and Transfusion
P438
Alpha-linolenic acid decreases platelet storage lesions (PSL) in platelet
concentrates: pilot study
Simona Stivala, Sara Meyer, Martin Reiner*, Thomas Lüscher, Andreas Buser, Hans Jürg Beer
Cantonal Hospital of Baden (Baden, CH); Blood transfusion Center, Division of Hematology, University
Hospital Basel (Basel, CH); Cantonal Hospital Baden (Baden, CH); Department of Cardiology,
University Hospital (Zürich, CH); Department of Internal Medicine, Cantonal Hospital Baden (Baden,
CH)
Background: PSL comprises deleterious effects on platelets during storage in platelet concentrates
(PCs) and pathogenic contaminations. The latter is prevented by the application of “Intercept Blood
System (IBS)”. We previously demonstrated that the plant-derived omega-3 fatty acid alpha-linolenic
acid (ALA) reduces platelet activation and aggregation, furthermore arterial thrombosis and increases
platelet survival by reducing its clearance in mouse models.
Aim: Addition of ALA to PCs a) reduces platelet baseline activation and b) preserves
function/activatability during storage in IBS-treated and untreated PCs.
Methods: 8 PCs were obtained from 4 healthy volunteers and divided in an IBS-treated (n=4) and
untreated (n=4) group. Each group was subdivided and incubated with ALA (30 uM, n=2) or vehicle
(ethanol, n=2). Bags were stored for 10 days and samples were analyzed daily by aggregometry,
platelet aggregation on collagen and adhesion to VWF under shear stress. Receptor
expression/activation/cleavage was determined by flow cytometry.
Results: At day 10, platelet aggregation on collagen was increased in both IBS-treated (covered area:
68.848 um2 vs 39.243 um2) and untreated PCs (102.779 um2 vs 68.729 um2) in addition adhesion to
vWF was higher. ALA augmented Thrombin-induced (0.5 U/ml) aggregation in bags exposed to IBS
(AUC: 59±51 vs 15±11) as well as in untreated PCs (AUC: 27±14 vs 14±7) at d10. GPIb cleavage
from the platelet surface was diminished by ALA in untreated bags (d1=100%, d10= 69±10% vs
63±7%) but was comparable when exposed to IBS treatment at d10. ALA further decreased
spontaneous P-selectin expression in PCs with and without IBS treatment. At day 1, ALA inhibited
platelet aggregation in response to thrombin (0.5 U/ml) and additionally platelet aggregation on
collagen.
Conclusions: ALA inhibits spontaneous platelet activation and preserves platelet function during
storage in IBS-treated and untreated PCs. However, effects of IBS treatment on platelets need further
investigation.
P439
Congenital fibrinogen disorders: unexpected clinical phenotypes associated
with two novel missense mutations
Alessandro Casini*, Françoise Boehlen, Marguerite Neerman-Arbez, Philippe de Moerloose
HUG (Genève, CH); CMU (Genève, CH)
Introduction: Despite the important increase of knowledge in molecular assessment of fibrinogen
disorders, relationship between genotype and phenotype are not completely established. We report
here a new mutation of FGA in an asymptomatic dysfibrinogenemic patient and a new mutation of
FGB in an afibrinogenemic patient that experienced severe bleeding and thrombosis.
Method: After isolation of genomic DNA, exons and intron-exon junctions of the fibrinogen genes were
amplified by polymerase chain reaction (PCR) and sequenced.
Results: Patient 1. A 52 years old Caucasian female was referred for low fibrinogen activity (0.8 g/L)
detected on preoperative screening (antigen 3.5 g/L). She reported no notable bleeding, even after
various tooth extractions and a surgery for varicose veins. Proband's father, sister and two children
also had low levels of fibrinogen activity and are asymptomatic. DNA analysis showed heterozygous
missense mutation at residue 17 of the exon 2 of FGA encoding the fibrinogen alpha-chain: FGA: c.
107 G>A (GGC>GAC, p.Gly36Asp, numbering from the initiator Met or Gly17Asp in the mature alphachain minus the signal peptide). This dysfibrinogenemia is associated with a delayed polymerization
as result of the abnormal structure of the knob A site. Mutations in this region are usually associated
with a bleeding phenotype.
179
Patient 2. A 30 years old Algerian male, diagnosed with afibrinogenemia (no fibrinogen and indefinitely
prolonged coagulation times) in early childhood, was hospitalized for a pulmonary embolism. He
reported a severe bleeding phenotype with prolonged bleeding after circumcision and massive
hemoptysis. Proband's parents were consanguineous. DNA analysis showed homozygous missense
mutation in exon 6 of FGB encoding the fibrinogen beta-chain: FGB: c. 895 T>C (TAT>CAT,
p.Tyr299His, numbering from the initiator Met or Tyr269His in the mature beta-chain minus the signal
peptide). This mutation is located in the sequence of globular C terminal domain which is crucial for
the expression of viable protein since evidence suggests that the supply of the B beta -chain is a ratelimiting factor in either assembly or secretion of the fibrinogen hexamer. Missense mutations reported
in this region are associated with bleeding phenotype. No thrombotic events in patients with mutation
in this region have been reported so far.
Conclusion: We report two new mutations causing fibrinogen disorders with unusual clinical
phenotypes.
P440
Impact of haemophilia on cancer detection and management: a retrospective
study
Philippe de Moerloose*, Christine Biron, Roseline D'Oiron, Hervé Chambost, Jean-François Schved,
Cedric Hermans
Hôpitaux Universitaires de Genève (Genève, CH); Hôpital St Eloi (Montpellier, FR); Kremlin Bicêtre
(Paris, FR); La Timone (Marseille, FR); Hôpital St Luc (Bruxelles, BE)
Introduction. Lymphoma and hepatocarcinoma secondary to blood-borne transmitted diseases are
well known malignancies in persons with hemophilia (PWH). However with increasing life expectancy
more PWH are confronted with other malignancies such as prostate or colorectal cancers, requiring a
close collaboration between oncologist and the haemophilia specialist.
Aim and Methods. The aim of present study was to collect retrospectively in the last 10 year-period
cases of cancer that occurred in PWH in five European hemophilia treatment centers (Brussels,
Geneva, Marseille, Montpellier and Paris) from three countries and to analyze the impact of
haemophilia on cancer detection and its management.
Results. A total of 46 malignancies occurred in 1267 PWH during the observation period. Eighteen
tumors were fatal (39%). The most common types of malignancy were hepatocellular carcinoma
(12/46) and urogenital tract tumors (9/46). Bleeding revealed a neoplasia in 4 patients and a change in
bleeding pattern in relation with cancer was observed in 2 patients. No bleeding was associated with
chemotherapy or radiotherapy but some bleeding complications occurred with surgical procedures in
spite of adequate clotting factor substitution. After cancer diagnosis, five patients switched from on
demand to prophylaxis substitution (either for a short or for a long term period). In the majority of
cases the treatment protocol was not modified because of hemophilia.
Conclusion. Our study emphasizes that in adults PWH a change in bleeding should raise the suspicion
of malignancy and also that a PWH should benefit from the same oncologic treatment as other
persons with cancer but no hemophilia.
P441
Albumin reverses echinocytosis induced by metabolic depletion and storage of
erythrocytes
Sophie A. Reinhart*, Thomas Schulzki, Walter H. Reinhart
Background: In vitro incubation of red blood cells (RBCs) and RBC storage for transfusion purposes
leads to a time-dependent echinocytic shape transformation of RBCs. We have recently observed that
albumin can restore to a great extent a normal discocytic shape of these RBCs. In the present study
we have investigated this phenomenon in more detail.
Methods and Results: Blood from healthy volunteers, anticoagulated with either heparin, citrate or
EDTA, was incubated at temperatures of 5°, 22° or 37°C for 0, 24, and 48h, respectively. A
temperature- and time-dependent decrease of glucose and ATP, increase of lactate and LDH,
erythrocytes swelling and echinocytic shape transformation were observed, irrespective of the
anticoagulant, indicating a calcium-independent mechanism. The morphology was analysed on wet
preparations of glutaraldehyde-fixed RBCs. The degree of echinocytic shape transformation correlated
with the increase in high shear blood viscosity. Echinocytosis was partially reversible when RBCs
were resuspended in a large volume of buffer containing 0.2% human serum albumin, which was
180
specific for albumin, since molecules with a similar molecular weight (dextran 70, heat shock protein,
protein C) had no effect. This effect of albumin was further studied by a systematic variation of the
concentration (0.05-3.2%), hematocrit (0.05-64%) and incubation time (1s-3h36min). The shape
restoring effect of albumin was concentration-dependent with a threshold level around 0.1%, it
correlated inversely with the hematocrit and showed the time-dependence with a marked shape
recovery already after 1s and a further gradual recovery over 1min. RBCs stored under blood banking
conditions for 7 weeks underwent a more marked echinocytosis. Nevertheless, RBC resuspension in
0.2% albumin led to a rapid shift towards a discocytic shape, which was seen even for the most
severe forms of echinocytosis. The lower the hematocrit of the suspension, the better the shape
recovery. Adding albumin to stored RBC units to reach a hematocrit of 40% induced a concentrationdependent shape recovery. When stored RBCs were resuspended in fresh-frozen plasma and mixed
with fresh blood, a partial shape recovery was found.
Conclusions: Human serum albumin has a capacity to reverse echinocytosis that occurs during
metabolic depletion and storage of RBCs. These observations may have an impact on transfusion
medicine and have the potential to improve the outcome of blood transfusions.
P442
Underestimation of positive Anti-PF4-Antibodies (HIT IgG) in patients with
myeloproliferative neoplasia and thrombocytosis: effect on vascular
complications
Eva Steinmann*, Thomas Lehmann, Patricia Muesser, Lukas Graf, Dimitrios Tsakiris
University Hospital Basel (Basel, CH)
Introduction: Heparin induced thrombocytopenia (HIT) is a thrombotic syndrome triggered by
autoantibodies against platelet factor 4 (PF4), a protein released from the alpha-granules of platelets.
There is suggestive evidence that a higher turn-over in platelets is associated with higher incidence of
HIT antibodies. Thus patients with myeloproliferative neoplasias (MPN) might be at risk for developing
HIT which can be masked by high platelet counts.
Patients and methods: We retrospectively reviewed clinical records of 130 patients with MPN (51 with
essential thrombocythemia, 76 polycythemia vera (PV) and 3 unclassifiable). Number and localization
of thrombosis were recorded from diagnosis of disease by duplex ultrasonography or spiral CT.
Laboratory parameters (blood cell counts and JAK2-allele burden were registered at the time of
diagnosis. Specific Anti-PF4-IgG antibodies were tested by ELISA (ZYMUTEST) in deep frozen serum
samples taken at time of diagnosis or later.
Results: Patients with MPN showed higher platelet and leucocyte counts (average 759 and 11.0 G/L).
Further 67/130 (52%) had splenomegaly, 91/130 (70%) had positive JAK2V617F, and 55/130 (42%)
had developed thrombotic complications during the course of disease. The most common thrombotic
events were stroke or venous thrombosis.
Most patients (65%) with thrombotic complications had higher leucocytes than 10.0 G/L. HIT
antibodies were detected in 22 patients (17%) by the qualitative screening assay for IgG, IgM and IgA
isotypes. Specific HIT IgG antibodies, were detected in 7 (5.4%) patients. Only 4 of these 7 patients
developed thrombotic complications, a non-significant result. Unfortunately state of positivity was not
known at time of the thrombotic events. All patients with HIT IgG had PV. All had splenomegaly and
were JAK2 V617F or JAK2 Exon 12 positive, 6/7 (86%) had leukocytes higher than 10.0 G/L. Two
patients had thrombocytopenia (140 and 73 G/L) at time of HIT IgG detection, but both patients had
never developed thrombotic complications.
Conclusions: Vascular events are one of the most common complications of MPN. Specific HIT IgG
antibodies seem to have a higher prevalence in patients with MPN compared to historical controls
without MPN, but positive HIT IgG antibodies are probably not associated with more frequent
thrombosis in this group. Thrombosis in MPN is probably a multifactorial event.
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P443
Impact of changes in haematocrit level and platelet count on
thromboelastometry parameters
Michael Nagler*, Silvio Kathriner, Lucas Bachmann, Walter Wuillemin
Inselspital University Hospital (Berne, CH); Luzerner Kantonsspital (Luzern, CH); medignition Inc.
(Zug, CH)
Introduction: To what extent haematocrit levels (Hct) and platelet counts (PLT) influence the
measurement of parameters of thromboelastometry when assessed with the ROTEM® device is
unclear. We investigated to what extent thromboelastometry measurements depend on Hct and PLT.
Methods: Whole blood samples were taken for in-vitro preparations of mixtures with three different
levels of PLT and a varying Hct. Maximum clot firmness (MCF), clotting time (CT), clot formation time
(CFT) and alpha angle for INTEM, EXTEM, FIBTEM and APTEM was recorded.
Results: Measurements depended substantially on Hct and PLT. MCF readings were systematically
lower with increasing Hct (0.2 vs. 0.4: -7.8 (-8.3 to -7.2); p<0.001, 0.2 vs. 0.55: -14.5 (-17.3 to -14.3);
p<0.001) but higher with increasing PLT (50 vs. 125x109/l: 8.2 (4.2 to 12.3); p=0.005, 50 vs.
250x109/l: 12.0 (7.2 to 16.8); p=0.002). CT readings were systematically higher with increasing Hct
(0.2 vs. 0.4: 9.2 (6.2 to 12.1); p=0.001, 0.2 vs. 0.55: 38.2 (21.5 to 54.9); p=0.003) while increasing PLT
had no influence. CFT readings were also systematically higher with increasing Hct (0.2 vs. 0.4: 83.8
(40.2 to 127.6); p=0.006, 0.2 vs. 0.55: 226.2 (110.7 to 341.7); p=0.006) but systematically lower with
increasing PLT (50 vs. 125x109/l: -144.0 (-272.3 to -15.6); p=0.036, 50 vs. 250x109/l: -189.2 (-330.4
to -48.0); p=0.02); readings of the alpha angle showed a similar pattern.
Conclusions: Our results suggest that readings of thromboelastometry parameters need to be
adjusted by Hct and PLT to avoid potential confounding and miss-interpretations in clinical practice.
182
Clinical Hematology
P444
Efficacy of azacitidine in acute myeloid leukaemia: a retrospective study
Cornelia Gemünden*, Rudolf Benz, Oliver Senn, Jeroen S. Goede, Markus G. Manz, Bernhard Gerber
UniversitätsSpital Zürich (Zürich, CH); Kantonsspital Münsterlingen (Münsterlingen, CH); Universität
Zürich (Zürich, CH)
Background: Treatment for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy
is challenging. Given its activity in myelodysplastic syndrome, Azacitidine is thought to be a potential
therapeutical alternative to low-dose Cytarabin in this patient population.
Methods: We retrospectively analyzed all patients with AML treated with Azacitidine at the University
Hospital Zurich or the Kantonsspital Münsterlingen. Treatment schedule: Azacitidine 100mg/m2
subcutaneously on days one to five or Azacitidine 75mg/m2 subcutaneously on days one to seven of a
28 day cycle. Observation period: September 2004 to February 2012. End of follow-up: 31st of May
2012. Primary end-point: Overall-survival. Secondary end points: Hospitalization days and transfusion
independency.
Results: Forty patients were included in the analysis of whom 22 (55%) had de novo AML, 15 (38%)
AML relapse, and 3 (7%) underwent a bridging therapy prior to allogeneic stem cell transplantation.
The median age was 67 years, 21 (52%) patients were female, 19 (48%) patients were transfusion
dependent and the median bone marrow blast count was 43% (interquartile range 26-80). According
to the HOVON/SAKK 102 risk stratification patients were classified in a good-risk, intermediate-risk,
poor-risk or very-poor risk group in 6 (15%), 8 (20%), 18 (45%) and 6 (15%), respectively. For two
(5%) patients these data are lacking. Median overall-survival was 591 (337-824) days in the whole
treatment group and 403 (232-683) days in patients with de-novo AML. After censoring for the
hospitalization days during the first treatment cycle, patients had to be hospitalized for a median of 6
(0-21) days (whole treatment group) and 5 (0-15) days (de novo AML), respectively. Transfusion
independency occurred in 3 (16%) patients. No serious adverse events related to Azacitidine were
noted.
Conclusion: Treatment with Azacitidine is safe for AML patients unfit for intensive chemotherapy.
Once the outpatient treatment was established, only few hospitalization days were needed. However,
only a minor effect on transfusion dependency was seen. Large randomized trials (e.g.
NCT01074047) will have to address the question whether Azacitidine is superior to the standard of
care in this patient population.
P445
Favourable long-term outcome in patients with 13q deletion and severe
aplastic anaemia
Andreas Holbro*, Martine Jotterand, Jakob Passweg, Andreas Buser, André Tichelli, Jörg Halter,
Dominik Heim, Martin Stern, Alicia Rovó
University Hospital Basel (Basel, CH); University of Lausanne (Lausanne, CH)
Introduction: The prognostic significance of cytogenetic abnormalities in aplastic anemia (AA) are
controversial. Del(13q) has been reported to occur in patients with MDS and other hematologic
malignancies. Additionally, cases of patients with bone marrow failure syndrome with del(13q), who
showed good response to immunosuppressive therapy have been reported.
Methods: We retrospectively analyzed outcome of patients diagnosed as AA with del(13q) at our
institution.
Results: For 86/353 (24%) patients cytogenetic analysis at any time during the disease course was
available. We identified six patients (7%) with del(13q). Table 1 shows patients characteristics. Median
age at diagnosis was 50.5 years (range: 22-71 years), half were male. One patient was diagnosed
with very severe AA, three patients with severe AA and two with AA. Del(13q) was detected at
diagnosis in four patients. One patient (UPN 936) had a normal karyotype at diagnosis and developed
del(13q) after a first course of antithymocyte globuline (ATG), and cyclosporine A (CYA). Two years
later this patient relapsed and received a second course of ATG and CYA with disappearance of the
del(13q) clone. She reached a partial response (PR) and remains under immunosuppression with
CYA, free of transfusions 86 months after last ATG. One patient diagnosed in 1987 with SAA (UPN
410) was treated with ATG in 1990, cytogenetics at diagnosis were not available. She reached a
183
complete response with persisting macrocytic anemia. Del(13q) was documented 10 years after ATG.
She remained hematologically stable for 276 months until her death in a car accident. In two patients,
del(13q) was no longer detectable at last follow-up. All patients except one are still alive after a
median follow-up of 105 months (range: 84-276 months). None of the patients showed progression to
acute myeloid leukemia or MDS.
Conclusion: Patients with bone marrow failure without dysplasia and isolated del(13q) should be
classified as AA and treated accordingly as they represent a subgroup of patients with favorable
outcome.
P446
Herpes zoster is a frequent event following autologous transplantation and
associated with favourable prognosis in myeloma patients
Christine Kamber*, Stefan Zimmerli, Marion Bleckmann, Thomas Pabst
Universitätsspital (Bern, CH)
Background: Herpes Zoster (HZ) is reported to occur in 17-50% of patients after allogeneic stem cell
transplantation. In contrast, only few data are available on the incidence of HZ following autologous
transplantation (ASCT). Consequently, evidence-based guidelines for prophylaxis against HZ are
widely missing for ASCT.
Methods: We analyzed all consecutive patients (n=380) with multiple myeloma, lymphomas, or AML
undergoing ASCT between January 2005 and March 2012 at the University Hospital of Berne,
Switzerland for the occurrence of HZ. After leukocyte recovery, patients received no routine antiviral
prophylactic treatment. Clinical records verifying HZ were assessed in all patients. In addition, patients
alive (n=274) were also investigated using a standardized questionnaire.
Results: Information on the incidence of HZ was obtained from 100% of the patients undergoing ASCT
in this period, and the questionnaire was obtained from all patients alive. We found that 100 of the 380
patients (26.3%) of our cohort had a HZ. 75 patients (19.7%) developed HZ after ASCT, and 25
(6.6%) patients had HZ during induction chemotherapy before transplantation. 54 of the 75 (72%)
patients with HZ after ASCT had the event within the first year after transplantation, peaking at five
months after ASCT. 63% of the patients with HZ considered the burden of HZ to be high or rather
high, and 70.7% reported significant post herpetic neuropathy. Finally, we found that the occurrence of
HZ in myeloma patients was an independent factor predicting better overall survival (p=0.034). A
similar trend for improved survival was observed in lymphoma patients with HZ (p=0.072).
Conclusion: HZ is a frequent event following autologous transplantation with significant morbidity and
it is associated with a more favorable course in myeloma patients. Our data provide the rationale for
subsequent prospective studies evaluating prophylactic strategies against HZ for patients undergoing
ASCT.
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P447
A single centre cohort of systemic light chain AL-amyloidosis patients: highdose chemotherapy with autologous stem cell transplantation is associated
with a more favourable outcome than conventional chemotherapy
Joelle Raschle*, Yara Banz, Thomas Pabst
Background: High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has
been reported to confer favourable outcome in systemic light chain AL-amyloidosis, a rare clonal
plasma cell disorder. However, data on treatment and outcome of AL-amyloidosis patients in
Switzerland are missing so far. The aim of this study was to establish a single centre cohort of light
chain amyloidosis patients and to compare the outcome of amyloidosis patients treated with
conventional chemotherapy versus HDCT with ASCT. Such a cohort may later be extended to
establish a Swiss cohort of amyloidosis patients.
Methods: Patients with biopsy confirmed immunoglobulin light chain AL-amyloidosis diagnosed
between January 1995 and December 2012 were included in this single centre retrospective analysis.
We comprehensively determined clinical characteristics and stratified the population into two groups:
patients treated with conventional chemotherapy or with HDCT and ASCT.
Results: 63 patients with systemic light chain AL-amyloidosis were identified. 50 patients were treated
with conventional chemotherapy and 13 patients with HDCT and ASCT. After a median follow-up of 31
months, one death occurred in the HDCT/ASCT group and 23 deaths in the conventional
chemotherapy group (P=0.0116). Patients undergoing HDCT and ASCT had a trend for better overall
survival (OS) compared to patients treated with conventional chemotherapy regimens (P=0.0651).
Whereas the group of patients with HDCT and ASCT did not yet reach the median OS, patients
treated with conventional chemotherapy had a median OS of 53 months. The median time to
progression (TTP) of the entire study population was 19 months, with a median TTP not yet reached in
the HDCT/ASCT group and with 15 months in the conventional therapy group (P=n.s.). Patient
characteristics between the two groups differed for the age of the patients (59 years for patients
treated with HDCT/ASCT versus 69 years; P=0.0006) and the Troponin-T value (0.015 versus 0.08
µg/l; P=0.0279).
Conclusion: To our knowledge, this is the first study in Switzerland aiming to comprehensively
characterize patients with systemic amyloidosis. Our results suggest that light chain AL-amyloidosis
patients which are considered fit enough to ultimately undergo HDCT and ASCT have a better
outcome than patients treated with conventional chemotherapy.
P448
Analysis of haemoglobin by top-down mass spectrometry
Pierre Lescuyer*, Didia Coelho Graça, Adelina Acosta Martin, Lorella Clerici, Yury Tsybin, Ralf
Hartmer, Markus Meyer, Denis Hochstrasser, Kaveh Samii, Alexander Scherl
Hôpitaux Universitaires de Genève (Genève, CH); Faculté de Médecine de Genève (Genève, CH);
Ecole Polytechnique Fédérale de Lausanne (Lausanne, CH); Bruker Daltonics (Bremen, DE)
Introduction: Mass spectrometry (MS)-based methods have the potential for changing dramatically the
way proteins are analyzed in clinical laboratories. In particular, MS offers new opportunities for
targeting protein modifications. In order to critically evaluate these possibilities in the context of a
clinically relevant application, we developed MS-based assays for qualitative and quantitative analysis
of normal hemoglobin chains and hemoglobin variants. We present a top-down MS approach with
electron transfer dissociation (ETD) for the identification of sequence variants and the precise
quantification of globin chains.
Method: EDTA blood samples were obtained from patients suffering from various hemoglobin
disorders and healthy controls. Hemoglobin was recovered in aqueous solution after washing and lysis
of red blood cells. A reverse-phase nanoscale liquid chromatography hyphenated to an ion trap with
ETD capabilities (Amazon Speed ETD, Bruker Daltonics) was used for top-down analysis. Selected
Reaction Monitoring with ETD was used for the identification of hemoglobin variants. For quantification
of globin chains, specific chains and charge states were isolated in the ion trap and ejected without
activation. Relative quantification between the globin chains was performed on the direct
measurement of these signals.
Results: ETD provided specific fragments covering more than 70% of the beta globin sequence.
Variants such as hemoglobin S, C, and E could thus be identified. Although hemoglobin D and O were
not analyzed by today, specific fragments surrounding these mutations were present indicating that
185
these variants could be detected as well. Quantification of the hemoglobin A2 delta chain was
achieved over a concentration range spanning from 3% to 18% of total hemoglobin with coefficients of
variation below 10%. Preliminary data suggests that similar analytical performances can be obtained
for the quantification of hemoglobin F and glycated hemoglobin (HbA1c). This MS method could then
be applied for the quantification of HbA1c in patients carrying hemoglobin variants or in the presence
of elevated concentrations of modified hemoglobin, such as carbamylated hemoglobin.
Conclusion: The presented method could be an alternative for the direct, rapid and comprehensive
analysis of various clinically relevant hemoglobin variants and post-translational modifications.
P449
The use of multiplex ligation-dependent probe amplification (MLPA) for the
diagnosis of large deletions in haemoglobinopathies (Hbpathies) and
thalassaemic syndromes
Tonguy Araud*, Frédéric Guerry, Pierre-Alain Menoud, Georgios Georgiou, Kaveh Samii, Lorella
Clerici, Regis Darbellay, Diego Andrey, Photis Beris
Unilabs Suisse (Genève, CH); Hôpitaux Universitaires de Genève (Genève, CH); Hôpitaux
Universitaires de Genève (Genève, CH)
Introduction: MLPA (Multiplex Ligation-dependent Probe Amplification) technique is a powerful method
that can be used for detection of genomic deletions. Although well-characterised deletions and
amplifications can be detected by PCR, the exact breakpoint site of most deletions is unknown.
Southern blot analysis was used in the past to investigate such cases but will not always detect small
deletions and is not ideal for routine. We applied this technology to diagnose cases with thalassemia
where a deletion was highly suspected. We present here our experience with two such cases.
Patients and methods: Case 1: A 35 years old male with Russian and French origins, was investigated
because of microcytic anemia (Hb 136g/l; MCV 67.8fl). HbA2 2.2%; HbF 7.8% and HbA 78.4%. No
abnormal Hb was found in IEF. Alpha2 (HBA2), alpha1 (HBA1) and beta (HBB) globin genes were
sequenced in an automated sequencer after amplification of the DNA with appropriate primers. A
deletion in the b-globin cluster (region 5´-HBE1 to HBB-3’) was looked by using MLPA technology
(MRC-Holland, P102-B2). Case 2: A 30 years old lady from Kenya was found to have HbS 66%, HbF
15.2%, an abnormal Hb 10.3% and HbA2 0.7%. Hb 100g/l; MCV 60.1fl. Iron status was normal.
Common deletions in the a-globin cluster were analysed by PCR, and Sanger sequencing. Deletions
in the b-globin cluster were looked by using MLPA technology.
Results: Case 1: No mutation has been detected in alpha1 and alpha2 genes as well as in beta gene.
MLPA analysis of the b-cluster, revealed the Mediterranean /SE-Asian form of (delta-beta)thalassemia, heterozygous state. The exact type of deletion is under investigation. Case 2: Alpha
globin analysis revealed a-globin triplication in one chromosome 16. Analysis of the whole b-cluster
showed a 22.5kb deletion starting at Agamma (HBG1) and finishing in the b-gene. This deletion
creates a fusion Agamma-beta gene known as Hb Kenya.
Comments and conclusions: These two cases illustrate the utility of this MLPA in the diagnosis of
Hbpathies and thalassemia syndromes secondary to deletions. This technique is particularly useful
when investigating cases of the deletional form of HPFH (Hereditary Persistance of Fetal
Hemoglobin)and cases of microcytosis secondary to non-common a-thalassemic deletions. The
existence of a commercial kit for investigation of both alpha and beta globin clusters in chromosomes
16 and 11 respectively, makes this technology affordable to all Hbpathies laboratories
P450
A surprising cause of Coombs-negative haemolytic anaemia
Rahel Schwotzer*, Brigit Brand, Abraham Licht, Beat Müllhaupt, Kornelius Arn
A 16-year old female of greek origin was referred with a three week history of diffuse abdominal pain
and two days history of nausea, vomiting and intermittent fever. The patient did not take any drugs
and travelled to Greece for a vacation two months ago. Physical examination revealed jaundice and
an abdomen tender to palpation.
Laboratory work-up was remarkable for anemia (Hb 98 g/l at presentation, 72 g/l after 12 hours), a
platelet count of 153 G/l and a reticulocyte count of 128 G/l, with elevated LDH (1023 U/l) and bilirubin
(256 mcmol/l), and an undetectable haptoglobin. The transaminases were only slightly elevated. Direct
Coombs test was negative and the coagulation assay showed an INR of 2.3. At that time we
discussed the differential diagnosis of a microangiopathic haemolytic anemia (TTP/HUS), an
186
erythrocyte enzyme defect, or a leptospirosis (travel to Greece) as possible causes of the haemolytic
anemia. The peripheral blood smear did not reveal any fragmentocytes, no evidence for Malaria on a
thick-smear preparation. 16 hours after presentation haemoglobin concentration dropped to 61 g/l
making red blood cell transfusions necessary, and the coagulation assays deteriorated including a low
factor V (minimal 35%). Serological testing for viral hepatitis and HIV were negative. Upon
hepatologist consultation acute Wilson’s disease was suspected and evaluation for urgent liver
transplantation was initiated. Elastographic examination of the liver (FibroScan) showed elevated liver
stiffness compatible with cirrhosis and the serum coeruloplasmin was below 200 mg/L, while the 24hour urinary copper excretion was elevated (49.2 mcmol). A slit lamp examination did not show
Kayser-Fleischer rings. Treatment with the copper chelator trientine dihydrochloride was initiated at a
dose of 1500 mg per day. Transjugular liver biopsy confirmed the diagnosis of Wilson’s disease with
1355 mcg/g copper per dry weight.
Chelation therapy ameliorated the liver function, thus liver transplantation became unnecessary. The
hemolytic activity stabilized with spontaneous rise of the haemoglobin concentration.
The diagnostic evaluation of acute onset coombs-negative hemolytic anemia can be a challenge.
While not a common finding, it may be the initial presentation of acute Wilson’s disease, with direct
copper toxicity as suggested mechanism. In our case the concomitant hepatopathy lead to the
diagnosis, in addition the age of onset and the ethnicity are quite typical.
P451
International registry for patients with hereditary thrombotic thrombocytopenic
purpura (TTP): Upshaw-Schulman syndrome
Magnus Mansouri Taleghani*, Yoshihiro Fujimura, James N. George, Ingrid Hrachovinova, Paul
Knoebl, Bernhard Lämmle, Petter Quist-Paulsen, Reinhard Schneppenheim, Johanna A. Kremer
Hovinga
Bern University Hospital and the University of Bern (Bern, CH); Nara Medical University (Nara, JP);
University of Oklahoma Health Sciences Center (Oklahoma City, US); Institute of Hematology and
Blood Transfusion (Prag, CZ); Medical University of Vienna (Wien, AT); St. Olavs Hospital Trondheim
University Hospital (Trondheim, NO); University Medical Center Eppendorf (Hamburg, DE)
Introduction: Hereditary TTP, also called Upshaw-Schulman syndrome (USS), is a rare, and
recessively inherited disorder, due to homozygous or compound heterozygous mutations in the
ADAMTS13 gene. Clinical presentation varies from mild thrombocytopenia to severe recurrent TTP
episodes leading to end organ damage or death. The first occurrence of USS ranges from neonatal
period up to older age. Due to the rareness of USS evidence based guidelines on prophylaxis with
fresh frozen plasma (FFP) and knowledge of long-term outcome are lacking, which emphasizes the
need of a multicenter cooperation.
Method: An electronic database system for USS patients and their interested family members
(www.ttpregistry.net, ClinicalTrials.gov NCT01257269) has been established to gather baseline and
long-term follow-up data. They contain the clinical courses and performed laboratory investigations in
order to identify yet unknown TTP episode triggers and factors influencing the clinical course,
eventually leading to improved therapy and better understanding of this disease.
Eligibility criteria are:
- ADAMTS13 activity <=10% on two separate occasions at least 1 month apart
and
- Absence of a functional ADAMTS13 inhibitor
and
- >=2 ADAMTS13 gene mutations and/or a positive infusion trial (full recovery and plasma half life of
2-3 days of infused plasma)
or
- Being a family members of a confirmed patient
Information is collected retrospectively up to enrollment as well as prospectively every 12 months and
when TTP episodes occur. Analysis of ADAMTS13 related parameters including molecular analysis of
the ADAMTS13 gene are offered free of charge for patients and family members.
Results: Today, 30 participants from 7 different countries (CH, CRO, CZ, NOR, PL,TU, USA) have
been entered into the database and another 8 countries (AUT, CAN, D, DAN,FIN, IND, IL, JP) have
confirmed their participation with 1 to over 40 patients per study site with data acquisition in progress.
A first point of interest is the investigation of episodes of thrombocytopenia during infections or
pregnancies in a number of obligatory or confirmed heterozygotes, so far generally reported as being
asymptomatic.
Conclusion
187
Establish an international network and knowledge platform to exchange information and experience on
USS will help to improve diagnosis, treatment and prevention of acute episodes for affected patients.
All Physicians are invited to contact us for diagnostics and enrollment of their patients with USS.
P452
Design and establishment of a biobank for a multicentre and interdisciplinary
prospective cohort enrolling elderly patients with venous thromboembolism
(SWITCO65+)
Marie Méan*, Drahomir Aujesky, Bernhard Lämmle, Christiane Gerschheimer, Sven Trelle, Anne
Angelillo-Scherrer
Inselpital (Bern, CH); CHUV (Lausanne, CH)
Introduction : In the field of haemostasis, many preanalytical variables influence the results of
coagulation assays and may affect the quality of the subsequent results. Methods to limit these results
variations should be foreseen when building a biobank in the field of haemostasis.
Our description of the biobank of the Swiss Cohort of Elderly Patients with Venous Thromboembolism
(SWITCO65+) is intended to facilitate set-up of other biobanks in the field of haemostasis.
Methods: SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients (pt)
aged >= 65 years with VTE at nine Swiss hospitals from 09/2009 to 03/2012. The pt will be followed
up until December 2013. The cohort includes a biobank with biological material from each participant
taken at baseline and after twelve months of follow-up. Whole blood from all participants was assayed
with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one
PAXgene Blood RNA System tube and one whole blood sample were also collected at baseline for
RNA/DNA extraction. Blood samples were processed and vialed within one hour of collection and
transported in batches to a central laboratory where they were stored in ultra-low temperature
archives. Use of barcoding and electronic databases ensured efficient management of the biobank. All
analyses of the same type were performed in the same laboratory in batches. Using multiple core
laboratories increased the speed of sample analyses and reduced storage time.
Results : Of the 1003 enrolled pt, 905 (90.2%) had a blood collection at baseline. Only a small minority
of pt refused to provide blood samples for genetic analyses (6.5%). The SWITCO65+ RNA/DNA
depository was designed to permit both genome wide association and replication studies, with the
single limitation that 99.8% of the patients were Caucasians. After an average follow-up time of 512
days, 799 (80.1%) pt were still participating, 150 (15.0%) had died, 1 (0.1%) was lost to follow-up, 47
(4.7%) patients had withdrawn their consent, but only 6 (0.6%) pt did not allow us the use of their data
and blood samples. By November 2012, 20,802 vials were stored in the central SWITCO65+ biobank
and 7,852 vials had already been sent for subsequent analyses in one of the participating laboratories.
Discussion : After recruiting, processing and analyzing the blood of 905 pt, we determined that the
adopted methods and technologies were fit-for-purpose and robust.
P453
Association of (delta-beta)-thalassaemia with the T>C; 12nts 5´ to the poly A
site mutation, confirms that the later constitutes a beta-silent thalassaemia
state
Kaveh Samii*, Lorella Clerici, Regis Darbellay, Frédéric Guerry, Tonguy Araud, Georgios Georgiou,
Pierre-Alain Menoud, Photis Beris
Hôpitaux Universitaires de Genève (Genève, CH); Hôpitaux Universitaires de Genève (Genève, CH);
Unilabs Suisse (Genève, CH)
Introduction: Silent b-thalassemia is defined when the simple carrier has normal hemogram without
the b-thalassemic markers: normal HbA2 and HbF; normal MCV and MCHC. Such cases are
diagnosed because when associated with the classical b+ or b0 thalassemias, they create a
phenotype close to thalassemia intermedia and always more severe of the known classical bthalassemia state. Here we provide evidence that the c.*+96T>C (rs34029390); 12nts 5´to the poly A
site mutation, constitutes a silent b-thalassemia state.
Patients and methods: The propositus, a 5 years old male child with Russian, French, German and
Polish origins, was investigated because of microcytic anemia (Hb 103g/l; MCV 65 fl). HbA2 2.6%;
HbF 18.6%; HbA 68.2%. Iron status was normal. His father has slight anemia with severe microcytosis
(Hb 136g/l; MCV 67.8 fl) with HbA2 2.2%; HbF 7.8% and HbA 78.4%. His mother besides a slight
anemia (Hb 114g/l), has normal MCV, HbA2 and HbF (87.6fl; 2.4%; 0.7% respectively). No abnormal
188
Hb was found in IEF of Hbs of all members of the family. Alpha2, alpha1 and beta globin genes were
sequenced in an automated sequencer after amplification of the DNA with appropriate primers. A
deletion in the b-globin cluster was looked by using MLPA technology.
Results: No deletion or point mutation was found in both a-globin genes in all members of the family.
In the father one chromosome 11 has the beta CD2 C>T polymorphism (c.[9C>T], p.His3His) while the
other chromosome carries the Mediterranean form of (delta-beta)-thalassemia. In the mother one bgene is normal. The other is carrying the T>C; 12nts 5´ poly A site mutation. The propositus is found
double heterozygous for the (delta-beta)-thalassemia of his father and for the T>C; 12nts 5´ poly A
mutation of his mother.
Comments and conclusions: The T>C substitution at nucleotide +1570 of the b-globin gene was first
described in 1992 by Cai et al as a novel typical b-thalassemia mutation (Blood 1992). Later the same
authors revised their communication by reporting data indicating that this mutation represents a
polymorphism. We now show that this mutation constitutes a silent b-thalassemic trait. In fact
combination with (delta-beta)-thalassemia creates a rather severe anemia not seen in the simple
heterozygous state, with highly increased HbF values. Further more, in the simple heterozygous state
hemogram, HbA2 and HbF values are normal. How this point mutation decreases beta mRNA
expression or stability is not known.
P454
Identification of the SF3B1 mutation in two cases with refractory anaemia with
ring sideroblasts with high platelet count (RARS-T) and one with refractory
anaemia with ring sideroblasts (RARS)
Georgiou Georgios*, Michael Franceschi, Jean-Luc Mandier, Pierre-Alain Menoud, Photis Beris
Unilabs Suisse (Genève, CH)
Introduction: Approximately 20% of Refractory Anemia with Ring Sideroblasts (RARS) present with
high platelet count (RARS-T). They belong to the provisional entity of the MDS/MPNs clonal myeloid
neoplasms according to WHO classification. Recently massive parallel sequencing technology
identified recurrent somatically acquired mutations in SF3B1 in RARS and RARS-T patients. We
present 2 cases of RARS-T and one RARS with three different mutations in SF3B1 gene.
Patients and methods: Case 1: Mr C. M. born on 1945. Hb 98g/l; MCV 108fl; GB 6G/l; Plt 468G/l.
Serum iron 39.6umol/l; transferine saturation 82%; ferritine 536ug/l; B12 1’164pmol/l; folates 90nmol/l;
Epo 114U/l. Bone marrow: 75% ring sideroblasts; blasts ~2%. Caryotype: 46, XY. Case 2: Mr F.A.
born on 1950. Hb 112g/l; MCV 104fl; GB 8.1G/l; Plt 1.125G/l. Serum iron 19.9umol/l; transferine
saturation 34%; ferritine 238ug/l; Bone marrow: 55% ring sideroblasts; blasts <2%. Caryotype: 46, XY.
Case 3: Mr Z.M. born on 1932. Hb 114g/l; MCV 105fl; GB 5.3G/l; Plt 291G/l. Serum iron 17umol/l;
transferine saturation 29%; ferritine 623ug/l; Bone marrow: 65% ring sideroblasts; blasts ~1%.
Caryotype: 46, XY, del(20)(q11;q13). We screened the three patients for the presence of JAK2 V617F
mutation (peripheral blood DNA extraction and pyrosequencing) and for SF3B1 mutations (direct
Sanger sequencing of exons 11-16). After peripheral blood RNA extraction and reverse transcription
to cDNA, an amplicon of 1kb was generated using the primers 5`-TGACCAGCCATCTGGAAATC-3`
(forward, exon 10) and 5`-CACCATCTGTCCCACAACAC-3` (reverse, exon 17).
Results: Patient 1 had the SF3B1 K700E mutation and was JAK2 V617F positive; patient 2 was found
to have the SF3B1 R625C mutation and patient 3 the SF3B1 K666R. The last two patients were JAK2
V617F negative.
Comments and conclusions: SF3B1 is a gene encoding an RNA-splicing factor. In recent studies, 79%
of RARS patients and 66.7% of RARS-T patients were found to carry different mutations in this gene.
(Papaemmanuil E et al N Eng J Med 2011). All our patients were positif for a previously described
mutation within SF3B1 gene. Preliminary data indicate a favourable clinical predictor of this mutation
(Malcovati L et al Blood 2011). One of our three patients has a survival of >15 years. We believe that
mutations at SF3B1 should be looked in every new case of RARS /RARS-T to confirm the better
clinical outcome of these patients which certainly will have an impact in therapeutic decisions.
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P455
Iron absorption test in iron deficiency
Petra Fellmann*, Mario Bargetzi
Kantonsspital Aarau (Aarau, CH)
Introduction: In earlier days the iron absorption test (IAT) was used as a diagnostic tool for iron
deficiency, but became less important since there are other parameters to define iron deficiency like
ferritin and the soluble transferrin receptor. The aim of our study was to see, whether the IAT could be
used for disorders, that lead to decreased iron absorption.
Methods: We retrospectively analyzed medical records of 131 patients, who had been referred to our
center with the diagnosis „iron deficiency“ between 2005 and 2010. The IAT was performed the
following way: 200mg of iron (Fe++) were administered per os, the serum iron concentration was
measured before, 2 and 4 hours after the iron intake. A normal test result was defined as increase of
serum iron concentration of 50-200% after 2 or 4 hours. An absolute value over 35micromol/l was
defined as an increased absorption. A low iron level at the beginning with an increase <50% was
defined as malabsorption (Fig. 1).
Results: Mean age of all patients was 50 years (range 16-90y), 86% were female. An IAT was
performed in 24% (n=32). 69% (n=22) showed an increased absorption, 25% (n=8) had normal values
and 6% (n=2) had a decreased absorption. Half of the patients with IAT had an upper endoscopy. 40%
(n=6) of patients with normal or increased absorption in the IAT had a normal endoscopy, in 60%
(n=9) there were abnormal findings. Patients with decreased iron absorption in the test had equal
distribution of normal and abnormal findings (Fig. 2). 60% (n=19) of patients with IAT were currently
taking an iron pill and had a low ferritin despite anamnestically adequate oral iron substitution. Only
one of these patients had a decreased absorption in the IAT, the other 18 patients had a normal or
increased iron absorption test. 16% (n=5) of the patients with IAT were taking a proton pump inhibitor
(PPI), 3 of them had a normal or increased iron absorption, 2 hat a decreased absorption.
Conclusions: The IAT is not reliable in order to indicate an iron malabsorption (lack of sensitivity). But
it is probable, that the IAT can indicate poor drug complicance regarding the fact, that patients with
insufficient increase of ferritin during oral iron substitution had (except one patient) a normal/increased
iron absorption test (good specificity). The intake of PPIs might have influenced the iron absorption in
the IAT in this study.
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P456
A case of chronic eosinophilic leukaemia with translocation t (8; 9) (p22; p24)
and PCM1-JAK 2 fusion gene
Mihaela Precup*, Paul Pugin, Valerie Parlier, Esther Garamvölgyi, Marc Kueng, Jacqueline
Schoumans, Yves Chalandon, Daniel Betticher, Emmanuel Levrat
Hôpital Cantonal Fribourg (Fribourg, CH); CHUV (Lausanne, CH); Promed (Marly, CH); HUG
(Genève, CH)
Introduction: Translocations involving the gene JAK2 (janus-activated kinase) are found in a wide
range of myeloproliferative disorders. One of the translocations rarely described to date and
considered as bad prognostic factor is the translocation t (8; 9) (p22;p24) with fusion of genes PCM1
(pericentriolar material 1) and JAK2, morphologically resulting in a myeloproliferation with eosinophilia
and myelofibrosis. We report on a case with this fusion transcript PCM1-JAK2 in the framework of a
chronic eosinophilic leukemia not otherwise specified (CEL-NOS).
Clinical case: A 47-year old patient with a history of a bipolar disorder has been investigated for a skin
infiltration on the anterolateral side of the right leg associated with palmo-plantar pustulosis. Night
sweats and fatigue lasted for several months .The CT scan showed hepatosplenomegaly without
significant lymphadenopathy. Complete blood count: leukocytosis 16.0 G/l, neutrophils 1,6 G/l,
eosinophils 4 G/l, lymphocytes 2,3 G/l, myelocytes 1,6 G/l , no blasts or erythroblasts; hemoglobin 112
g/l, platelets 150 G/l. The bone marrow (BM) biopsy revealed a hypercellularity , with hyperplasia and
atypia of myelopoiesis together with marked eosinophilia, normal megacaryopoiesis, atypia of
erythropoiesis and slight reticulinc fibrosis (MF1) without blast excess. BM cytogenetic showed
translocation t(8;9)(p22;p24) in 20/22 analyzed metaphases.The interphase FISH confirmed the
PCM1-JAK2 rearrangement in 129 (64.5%) nuclei studied. The skin biopsy revealed an eosinophilic
dermatosis with few immature myeloid elements. Based on these results the diagnosis of CEL-NOS
was made.
We started a therapy of Interferon-Alpha 2a (3 million units 3 x/wk) and Prednisone (1mg/kg/day,
progressively tapered to 5 mg/day over 3 months). We observed a significant regression of skin
lesions and disappearance of the peripheral eosinophilia. The BM biopsies after 5 and 12 months of
treatment demonstrated the persistence of the above described morphological and cytogenetic
changes, but an increased reticulinic fibrosis (MF2).
Conclusion: our case demonstrates a hematological favorable evolution under IFN alpha 2a
/prednisone therapy for a CEL–NOS with PCM1-JAK2 fusion gene, entity rarely described so far,
without however cytogenetic response. We intend to introduce ruxolitinib, a JAK2 inhibitor which has
been shown to induce complete cytogenetic remission in a similar situation.
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P457
Lenalidomid-induced pneumonitis
Rania Mohamed*, Monika Nagy Hulliger, Gregoire Gex, Christian Juillet, Yves Chalandon
Hopital du Valais (Sion, CH); Hopital Cantonal de Geneve (Genève, CH)
Background : Lenalidomide is an immunomodulatory agent, more potent than thalidomide and also a
less toxic analog of it, approved for use in myelodysplastic syndrome. In combination with
dexamethasone it’s widely used for refractory or relapsed multiple myeloma. Myelosuppression is the
most severe known side effect of lenalidomide, although pulmonary toxicity is probably underreported. The exact mechanism of lenalidomide-induced interstitial pneumonitis is unknown, but
inhibition of prostaglandin E(2) secretion by lenalidomide is supposed, as well as promoting
proliferation of fibroblast cells and collagen synthesis.
Case: We report here a clinical case of pulmonary toxicity without pulmonary symptoms. A 59 years
old patient was treated in the frontline setting with bortezomib/dexamethasone for an IgA lambda type
myeloma diagnosed in March 2012. Because of life threatening side effects of bortezomib (severe
paralytic ileus and serious perturbation of hepatic tests), without sign of pulmonary toxicity (normal
chest X-ray), the treatment was changed and lenalidomid introduced. After his sixth cycle of
lenalidomid the patient was hospitalized for a febrile agranulocytosis in September 2012. He
presented neither dyspnea, nor cough nor expectoration. Classical workup didn’t identify infection and
broad spectrum antibiotic was rapidly introduced. Chest examination revealed bibasal fine crackles. A
thoracic CT scan showed focal ground-glass attenuation. After four weeks, the patient remained
asymptomactic, without fever. A new thoracic CT showed persistence of ground glass attenuation and
new parenchymal bands.
The patient was not taking any drug with known pulmonary toxicity and denied any inhalation
exposure to toxins or allergens. A bronchoalvolar lavage was performed. Extensive cultures and
PCRs were all negative and the differential cell count showed increased number of lymphocytes
(63%), without monoclonality in flow cytometry. Lenalidomid treatment was interrupted. 2 months later,
a new thoracic CT revealed total resolution of aforementioned infiltrates.
Conclusion: Although pulmonary infection is a frequent complication of multiple myeloma treatment,
physicians should be aware of lenalidomid pulmonary toxicity, particularly among patients presenting
with atypical radiologic infiltrates not responding to antibiotics.
P458
Characteristics of the diagnostic approach of patients investigated for mild
bleeding disorders in two university hospitals
Françoise Boehlen*, Anne Angelillo-Scherrer, Gabrielle Martin, Françoise Bonfils, Rachel SpycherElbes, Linda Guida, Valérie Leclair-Rezbach, Nicolas von der Weid, Pierre Fontana
Hôpitaux Universitaires de Genève (Genève, CH); Centre Hospitalier Universitaire Vaudois
(Lausanne, CH)
192
Introduction: The diagnosis of mild bleeding disorders (MBD) is often a challenge, partly due to the
lack of standardisation in the diagnostic approach. We aimed to evaluate the characteristics of the
clinical and biological diagnostic procedures performed in patients referred for a suspicion of MBD in
two university hospitals (Geneva and Lausanne).
Methods: We performed a retrospective analysis of consecutive patients referred to both pediatric and
adult haemostasis/hematology outpatient clinics of the university hospitals of Geneva and Lausanne
between January 2009 and December 2010 for investigation of a putative bleeding disorder. We
collected the characteristics of the patients as well as the clinical and biological evaluation that were
performed.
Results: Up to now, 218 charts were included (109 in each centre, including 37 children). Mean age
was 42.4 ± 17.3 years with 70% of female patients in adults and 9.7 ± 4.1 years with 46% of female
patients in children. Characteristics of patients in Lausanne and Geneva did not differ in terms of age
and sex ratio. Patients were referred for a biological anomaly in 16%, a relative screening for a familial
history of MBD in 12% or for a personal bleeding history in 72% of cases. A standardized bleeding
questionaire was used in 14% of cases in Lausanne and in 91% of cases in Geneva (p<0.001). A
standardized assessment of menses was performed in 2% of adult women in Lausanne and 77% in
Geneva (p<0.001). The proportion of platelet function tests, dosage of coagulation or von Willebrand
factors was similar in both centres but the agonists used to evaluate platelet function were different.
Conclusion: The diagnostic approach of patients referred for investigation of a putative MBD differed
significantly in Geneva and Lausanne mainly regarding the initial clinical assessment and the platelet
function evaluation. The ongoing standardisation of this approach in both hospitals may help in
identifying patients at risk for a bleeding event.
P459
Splenic infarction in a young man: blood smear as clue to the underlying cause
Marcelo Caballero*, Lorenzo Alberio, Pascal Kämpfen, Drahomir Aujesky, Bernhard Lämmle
Inselspital, Universitätsspital Bern (Bern, CH); Inselspital, Bern University Hospital and University of
Bern (Bern, CH)
We report the case of a 26-year-old man admitted to our hospital for abdominal pain and fever. He
had been well until 5 days before admission when he felt feverish and developed acute left-sided
upper abdominal pain. Clinical examination showed reduced general health, the temperature was 39
°C, the left upper abdomen was tender to palpation. and the spleen was palpable at the left costal
boarder. There was no lymphadenopathy. Computed tomography showed a hypodense lesion of the
inferior part of the spleen consistent with a splenic infarction (Fig. 1). Our initial differential diagnosis
included a cardioembolic splenic arterial occlusion, a myeloproliferative or lymphoproliferative
neoplastic disease, or paroxysmal nocturnal hemoglobinuria.
On the first hospital day, paroxysmal nocturnal hemoglobinuria, and lymphoproliferative neoplastic
disease were excluded by flow cytometric immunophenotyping, and Lupus anticoagulant and
anticardiolipin antibodies were negative. Visual inspection of the blood smear showed many highly
atypical lymphocytes (Fig. 2) and subsequent EBV and CMV serology testing revealed an acute CMV
infection. The patient was treated with analgesic medication and recovered within a few days.
Acute CMV or EBV infection may rarely be associated with arterial splenic infarction. In some cases,
an accompanying thrombophilic defect, such as transient or permanent antiphospholipid antibodies,
protein C deficiency or an underlying spherocytosis with mild splenomegaly, have been reported. Our
patient was an immunocompetent man with no preexisting health problems. The blood smear hinted to
acute viral infection, and, therefore, foreseen echocardiography, bone marrow examination and
screening for JAK2 V617F or bcr-abl mutation were canceled. This case highlights the importance of
examining the blood smear in order to avoid unnecessary and costly tests in a patient with splenic
infarction.
193
P460
Thrombosis of palmar and interdigital arteries in hypereosinophilic syndrome
Cristina Gallardo*, Marco Mancinetti, Daniel Périard, Daniel Hayoz
HFR Fribourg Hôpital Cantonal (Fribourg, CH)
Introduction: Hypereosinophilic syndrome (HES) can be identified by three diagnostic criteria: blood
eosinophilia (> 1500/mm3) for longer than 6 months (or shorter in the presence of symptoms requiring
treatment), no other evident reason for the eosinophilia, signs/symptoms of organ involvement.
Case report:: A 69 years old male patient presented to the emergency department with a history of
painful and cyanotic fingers bilaterally, evoking ischemic injury. We performed a duplex
ultrasonography which demonstrated a thrombosis of both superficial palmar arches and several
interdigital arteries. Anticoagulation was introduced and the patient was admitted to our medical
department for further investigations. He reported a history of multiple organ damages (skin, lung,
gastrointestinal, vascular involvement) associated with hypereosinophilia evolving since three months.
Allergic tests, FAN, ANCA and RAST for aspergillus fumigatus were normal. A thoracic scan
194
demonstrated emphysema. The bronchoscopy with BAL showed eosinophilia but neither vasculitis nor
aspergillosis. A cutaneous biopsy demonstrated dermatitis with presence of eosinophils in the derm
without vasculitis. The gastroscopy showed a chronic inactive gastritis with rare eosinophils.
Echocardiography and stress test were both normal. We performed a bone marrow aspiration and
biopsy showing no specific findings. We retained the diagnosis of idiopathic hypereosinophilic
syndrome, without PDGFRA, PDGFRB, FGFR1 rearrangements and absence of FIP1L1-PDGFRA
chromosomal fusion. We introduced a corticosteroid therapy which was followed by a fast decrease of
the eosinophilic count.
Discussion: Thrombotic events are known as one of the most serious complications of
hypereosinophilic syndrome but digital damage is rarely described. In hypereosinophilic syndrome,
occlusion of intermediate- to large-sized arteries frequently causes peripheral ischemia and even
digital gangrene. Involvement of smaller vessel can also occur. Systemic corticosteroid remains the
first-line treatment of HES when specific mutations aren’t identified. It seems that thromboembolic
disease associated with HES is particularly difficult to control and anticoagulation is not usually
initiated empirically in the absence of a previous event.
P461
Primary germ cell tumor-associated acute megakaryoblastic leukaemia
Karolina Polchlopek*, Monika Nagy Hulliger, Nhu Nam Tran Thang Ducommun, Pierre-Yves Dietrich,
Yves Chalandon
Hopital Cantonal de Geneve (Genève, CH)
Background: The association between primary germ cell tumors (GCT) of the mediastinum and
hematologic malignancies is a known entity, but there are only few cases described in the literature.
We report a case of a young male with mediastinal GCT and acute megakaryoblastic leukemia.
Case: A 22-year-old man, previously in good health condition, was admitted to the emergency room
for epistaxis and fatigue. Full blood count showed severe thrombopenia (16 G/l). Chest X rays
revealed a mass in the anterior mediastinum. Lactate dehydrogenase were highly elevated (4668 U/l)
and alpha-fetoprotein level was mildly elevated (45 ug/l). The blood film showed very rare
megakaryoblasts. The imprints and the histopathology of the biopsy revealed a massive infiltration by
maturing dysplastic megakaryocytes with platelet glycoproteins CD41 (glycoprotein IIb/IIa) and CD61
(glycoproteine IIIa) expression. The histology of the mediastinal mass showed a GCT combined with
leukemia components. The diagnosis of acute megakaryoblastic leukemia (M7 according to the
French-American-British classification) associated with mediastinal germ cell tumour was identified.
The cytogenetic analysis showed a characteristic karyotype for this entity with an isochromosome 12p
(i12p).
After the first cycle of induction chemotherapy consisting of cisplatin, etoposide, mitoxantrone and
cytarabine to have combined activity against both types of tumor, the serum levels of AFP and LDH
decreased to normal range, the thrombopenia improved. The immunohistochemistry of bone marrow
biopsy indicated a leukemia free state. The patient is actually being treated with a fourth cycle of
chemotherapy including only cisplatin and etoposide targeting the germ cell tumor due to poor
hematopoiesis recovery. An allogeneic hematopoietic stem cell transplantation with a mismatched
unrelated donor is planned due to known very poor prognosis. All patients described to date with this
kind of combined germ cell tumor with leukemia, except a case of a child that received cord blood
transplant after 6 cycles of chemotherapy including cytarabine, mitoxantrone, idarubicin, etoposide
and cisplatine, died. (H Hiramatsu et al. BMT 2008;41:907-908).
Conclusion: This rare type of mediastinal germ cell tumor associated with hematologic malignancy
has a dismal prognosis. Combining chemotherapy aimed at targeting both tumors followed by
allogeneic hematopoietic stem cell transplantation may offer the only possibility of cure.
P462
Clinical course in a young man with severe haemolytic anaemia due to severe
pyruvate kinase deficiency
Anelia Siderow*, Roland A. Ammann, Nasser Semmo, Franziska Demarmels, Bernhard Lämmle
University Hospital, Inselspital and University of Bern (Bern, CH); Inselspital and University of Bern
(Bern, CH); Department of Visceral Medicine and Surgery, University Hospital, Inselspital and
University of Bern (Bern, CH)
Congenital non-spherocytic hemolytic anemias are rare enzymatic defects leading to a defective
erythrocyte stability and constitutional hemolytic anemia of variable severity.
195
We report on a now 18-year-old man with severe, probably homozygous or double heterozygous
pyruvate kinase deficiency (PKD). In the neonatal period he was anemic, showed a bilirubin up to 500
umol/l and needed exchange transfusions. Red blood cell (RBC) transfusions were then given every 4
weeks, together with iron chelation. At the age of 13 years a partial splenectomy together with
cholecystotomy for bilirubin stones was performed and greatly improved hemolytic activity. Bilirubin
decreased from about 220 to 20-40 umol/l, hemoglobin increased from 70-80g/l (with frequent RBC
transfusion requirement) to 80-95 g/l and RBC transfusions were needed only twice yearly. Iron
chelation could be withdrawn and despite a steady increase of hemolytic activity associated with
progressive hypertrophy of the remnant spleen, hemoglobin remained > 80g/l. In November 2012, at
an age of 17 years, severe upper gastrointestinal hemorrhage from isolated cardiac varices resulted in
a hemoglobin fall to 53 g/l. No generalized portal venous hypertension was found and a suspected
(partial) splenic vein thrombosis could neither be proven nor excluded. In January 2013 hemoglobin
has stabilized at 88g/l, hemolytic activity is high with 30% reticulocytes (750 G/l), bilirubin of 280 umol/l
and lactate dehydrogenase of 1400 U/l. Given the clear benefit of earlier partial splenectomy in this
patient, total splenectomy, after completion of the necessary vaccinations, is planned. At the same
time, splenectomy will reduce the risk of rebleeding from cardia varices, thus killing two birds with one
stone.
This case is presented to draw the attention of hematologists, pediatricians and internists to this rare
constitutional hemolytic enzymopathy.
P463
Intravascular large B-cell lymphoma: diagnostic pitfalls and therapeutic
recommendations
Martin D. Berger*, Yara Banz, Thomas Pabst
Background: IVLBCL is a rare type of extra-nodal large B-cell lymphoma characterized by the growth
of malignant lymphoid cells within the lumina of small blood vessels, predominantly capillaries. The
clinical manifestation may vary, but is typically associated with an aggressive course. Delay during
diagnostic work-up, mainly due to the unexpected histological presentation, is the prominent cause of
the usually unfavourable outcome of this lymphoma type.
Case presentation: A 48 year old male patient was admitted because of fatigue, poor exercise
tolerance, weight loss and progressive dyspnoea. His clinical condition further deteriorated and the
patient was referred to the ICU because of hemodynamic instability. Laboratory tests revealed
bicytopenia (haemoglobin 11g/dl and platelets 31 x 109/L, with normal leukocytes of 5.2 x 109/L). Creactive protein (157mg/l), lactate dehydrogenase (7’059 U/l) and liver enzymes (ALAT 155 U/l, ASAT
340 U/l) were elevated. Computed tomography indicated pleural and peritoneal effusions, whereas no
enlargement of lymph nodes or hepatosplenomegaly were detectable. Blood, stool and urine cultures
showed no growth.
Bone marrow biopsy revealed slightly elevated megakaryopoiesis, whereas erythro- and myelopoiesis
were considered normal. Small clusters of medium- to large-sized blastic cells were identified with
slightly course nuclear chromatin and prominent nucleoli, exhibiting CD20, CD79a, Pax-5 and MUM-1
as well as lambda light chain restriction. There was no expression of CD138, cyclin D1, CD10, BCL-6,
CD5, CD3 and the myeloid markers. These malignant lymphoid cells appeared “aligned” and were
found almost exclusively within the lumina of sinusoids of the bone marrow. These findings suggested
the diagnosis of intravascular large B-cell lymphoma (IVLBCL).
The patient was treated with six cycles of R-CHOP chemo-immunotherapy, and he was consolidated
in first remission with R-BEAM high-dose chemotherapy conditioning and autologous stem cell
transplantation (ASCT). Ten months after ASCT, the patient is in continuing first complete remission.
Discussion: This case illustrates key features of this rare type of extra-nodal large B-cell lymphoma.
With regards to the usually dismal prognosis of IVLBCL, such patients may benefit from early
consolidation with ASCT in first complete remission.
196
P464
A rare case of association of primary cutaneous follicle centre lymphoma
presenting as a giant tumor of the scalp and essential thrombocythaemia
Yordanka Tirefort*, Xuan-Cuong Pham, Michael Bernimoulin, Crista Prins, Begonia Cortes, Yves
Chalandon, Kaveh Samii
University Hospital of Geneva (Genève, CH)
Introduction:The concomitant diagnosis of essential thrombocythemia(ET) and lymphoproliferative
disorder(LPD) is extremely rare event.We describe exceptional case of primary cutaneous follicle
center lymphoma(PCFCL) in patient presenting with giant tumor of the scalp and with concomitant
ET.Case description:56-year-old man with unremarkable medical history developed multinodular mass
on the scalp 19x16x4cm over 18 months.Skin biopsy showed dense infiltrate throughout the dermis
and the subcutis consisted of large lymphocytes with focal nodular growth pattern,CD20+ and
BCL6+,BCL2,IRF4,CD10 negatives.Staging procedures revealed only one suspicious spinal lymph
node.According to ISCL/EORTC classification of cutaneous lymphomas, the diagnosis of
PCFCL,stage T2bN1M0 was made.In parallel,laboratory investigations showed platelet count
772x10^9/L without other blood film anomalies,normal LDH values and no splenomegaly.The bone
marrow(BM) biopsy found moderately hypercellular BM with marked proliferation of mature
megakaryocytes with hyperlobulated nuclei,sometimes in loose clusters,without increase of reticulin
fibres.The JAK2/V617F mutation was present and helped to exclude reactive thombocytosis.Because
of the exceptional size of the tumor,its location and possible nodal involvement,the patient received
systemic chemotherapy with 4 cycles of R-CHOP-21 followed by consolidation radiotherapy.After 2
courses of chemotherapy,there was 90% reduction of tumor mass.The patient was still in remission 18
months after last treatement.The chemotherapy received for PCFCL did not induce remission of the
ET and the platelet count remained between 500x10^9/L and 600x10^9/L without any clinical
feature.He was considered low risk ET and aspirin was started.Conclusion:PCFCL is cutaneous B-cell
lymphoma with excellent prognosis.Despite the impressively large size of tumor,we observed
spectacular response to treatment.This case is also exceptional in its concomitant presentation with
ET.Although the outcome for both diseases was favourable in this case,coexistence of ET and LPD
might raise concerns about long-term prognosis of these patients,due to the possibility of more
aggressive natural history of either one or both of the hematologic malignancies.Local recurrences can
occur in PCFCL.ET is considered a relatively benign disorder but the evolution may be influenced by
hemorrhagic or thrombotic complications or by disease transformation.A long term follow-up is thus
mandatory.
197
Autorenliste / Liste des Auteurs
Name
Programmnummer
Abbal, Claire
Abu Hussein, Nebal
Acosta Martin, Adelina
Aegerter, Jean-Philippe
Aerne, Lea
Aeschbacher, Stefanie
Aeschlimann, Andre
Aigner, Fabian
Alatri, Adriano
Alberio, Lorenzo
Albert, Mathieu
Allaz, Anne-Françoise
Allemann, Yves
Althaus, Fabrice
Ammann, Roland A.
Amort, Jan
Andrey, Diego
Angelillo-Scherrer, Anne
FM288
FM238, FM239, P386
P448
P305
P404
FM246, P337
P321
P359
P428
P459
P342
FM271, P307, P339, P408
FM256
FM230
P462
FM222, P328
P449
107, FM226, FM254, FM282, P452,
P458
P321
FM292
FM230
P380
P377
P324, P325, P326
P449, P453
FM289, P450
FM226, FM254
FM257
P315, P423
FM274
P377, P379, P384, P405, P407
FM226, FM227, FM235, FM253, FM254,
FM255, P323, P371, P452, P459
105
107, FM282
Angst, Felix
Ansari, Marc
Ansermet, Corine
Antiochos, Panagiotis
Applegate, William
Arampatzis, Spyridon
Araud, Tonguy
Arn, Kornelius
Aschwanden, Markus
Aubert, Carole
Aubry-Rozier, Bérengère
Auckenthaler, Anne
Auer, Reto
Aujesky, Drahomir
Ayran, Christina
Azevedo, Monica
Bächli, Esther
Bachmann, Lucas
Bachofner, Adrian
Baerlocher, Gabriela
Balabanov, Stefan
Balestra, Gian-Marco
Ballmer, Peter E.
Banyai, Martin
Banz, Yara
Barbosa, Joana
Bargetzi, Mario
Baroudi, Mariem
Barro, Javier
Bassetti, Stefano
Bastardot, François
Batschwaroff, Marcus
Battegay, Edouard
Baudat, Dimitri
Bauer, Douglas
198
P395, P409, P424, P429
P443
FM244
105
FM289
FM258
P399
FM226, FM254
P447, P463
P380
P455
P318
P313, P318
P360, P361, P363
P300
FM224
FM227, FM232, FM235, FM253, FM259,
P299
P416
FM227, FM235, FM252, FM253, P377
Name
Programmnummer
Bauer, Sophie
Baumgartner, Martin
Beauverd, Yan
Beer, Hans Jürg
P346
P343
FM228, FM292
FM226, FM234, FM254, FM279, P321,
P431, P438
FM289
P432
FM236
P309
P414
FM286, P444
P463
P449, P453, P454
P414
FM292, P464
FM241
FM243
FM288
P410, P415
P419, P437
P346, P347, P456
FM249
P329
P294
P355
P440
FM275
P434
105
P446
FM222, P294
P311
FM272
P337
FM235
FM236
FM230, P306, P319, P320
FM228, FM280, P439, P458
P355
P396
P378
P458
P436
P330
FM250
P372
FM263
FM291
FM256
FM226, FM254
P435
FM257
P410
FM285
FM281, P450
FM242
P304
P370, P404, P417
P329
FM238
FM236, FM249
Bencze, Judit
Bendjelid, Karim
Bengough, Theresa
Benkert, Pascal
Benvenuti, Claudio
Benz, Rudolf
Berger, Martin D.
Beris, Photis
Bernasconi, Augusto
Bernimoulin, Michael
Berra, Grégory
Bertholet, Nicolas
Berthon, Céline
Besson, Marie
Besson, Marius
Betticher, Daniel
Bhatt, Deepak L.
Bingisser, Roland
Bircher, Daniela
Birkhäuser, Frédéric
Biron, Christine
Bischofberger, Gabriela
Bitzenhofer-Grüber, Michaela
Blaney, Martha
Bleckmann, Marion
Bloemberg, Guido V.
Blondon, Katherine
Blozik, Eva
Blum, Jonas
Blum, Manuel
Blümle, Anette
Bodenmann, Patrick
Boehlen, Françoise
Bohlender, Jürgen
Böhm, Thomas
Bonetti, Piero O.
Bonfils, Françoise
Bonnabry, Pascal
Bonvin, Raphael
Bordet, Julie
Bosshard, Stephan
Böttcher, Steffen
Bougeon, Sandrine
Bouillet, Elise
Bounameaux, Henri
Bourgeois, Guy
Bourron, Olivier
Boyer, Celia
Bradbeer, Peter
Brand, Brigitte
Brändli, Otto
Brausch, Anne
Bregenzer, Thomas
Breidthardt, Tobias
Bridevaux, Pierre-Olivier
Briel, Matthias
199
Name
Programmnummer
Brisset, Anne
Broccoli, Vania
Broers, Barbara
Brun del Re, Claudia
Bruzzese, Ornella
Brylski, Lukas
Bubenhofer, Manuel
Bucher, Heiner C.
Bucklar, Guido
Budak, Kemal
Budka, Herbert
Buehlmann, Cyrill
Büla, Christophe
Burdet, Luc
Burgmann, Konstantin
Burington, Bart
Burkhard, Regula
Burkhart, Andreas
Burnand, Bernard
Burnand, Jérôme
Burnier, Laurent
Buschbeck, Christiane
Buser, Andreas
Butler, Javed
Butsch, Raphael
Büttner, Franz
107
FM286
P318, P432
P398
FM291
P392
P301
FM249
P299
P358
FM223
P348
FM247, FM276, P420
P346
P351, P430
105
FM267
P395
FM250, P356, P411
P380
107
P350
P438, P445
P377
P303, P344
P373
Caballero, Marcelo
Calanca, Luca
Calmy, Alexandra
Calzavarini, Sara
Cappai, Milva
Carballo, David
Carballo, Sebastian
Carrel, Thierry
Casillas, Alejandra
P459
P428
P437
107, FM282
P406
P379, P405, P407
FM241, P379, P405, P407
FM240
P306, P312, P313, P318, P319, P320,
P356
FM280, FM292, P439
P349
P416
FM288
FM271, P307, P339, P408, P410
P346
FM288, FM292, P457, P461, P464
P456
P344
P440
FM285
FM243
FM274
FM288
FM238
FM292
P329, P389
P305
P347, P366
P433
FM244
FM233
P448, P449, P453
P357
Casini, Alessandro
Caspar, Clemens
Cavassini, Matthias
Cayuela, Jean-Michel
Cedraschi, Christine
Chabanel, David
Chalandon, Yves
Chalandon, Yves
Chaloupka, Karla
Chambost, Hervé
Chan, George
Cheng, Debbie
Chevalley, Thierry
Chevret, Sylvie
Chhajed, Prashant
Chigrinova, Ekaterina
Christ-Crain, Mirjam
Christin, Laurent
Chuard, Christian
Clair, Carole
Classen, Regina
Clerc, Olivier
Clerici, Lorella
Coattrenec, Yann
200
Name
Programmnummer
Coelho Graça, Didia
Cole, Nyree
Collet, Tinh-Hai
Compagnoni, Sergio
Conen, David
Conzelmann, Martin
Cornuz, Jacques
Cortes, Begonia
Corti, Natascia
Cozzi, Anna
Craighero, Raffaella
Crevoisier, Jean-Luc
Crook, David William
Cullati, Stéphane
Curatolo, Michele
P448
FM285
FM227, FM235, FM250, FM253
P340, P402
FM246, P337
FM277, P394
FM226, FM235, FM227, FM253, FM254,
P314, P379, P384, P420, P433
P464
P401, P424
FM286
P380
P390
P361
P311, P316
P415
D'Oiron, Roseline
da Costa, Bruno
Daali, Youssef
Daeppen, Jean-Bernard
Dantin, Carole
Darbellay, Regis
Darling, Katharine
Dayer, Pierre
de Jong, Cor
de Moerloose, Philippe
de Waal, Margot W.M.
Degenhardt, Ewa
Degiorgi, Adriana
Dejung, Sarah
Demann, Désirée
Demarmels, Franziska
Demertzis, Stefanos
den Elzen, Wendy P.J.
Desmeules, Jules
Despotovic, Dragan
Diaz, Carolina
Dietrich, Pierre-Yves
Diotte, Serge
Dolan, G.
Dolmans, Diana
Dombret, Hervé
Doñate, Carmen
Dougoud-Chauvin, Vérène
Dreher, Rebecca
Drexler, Beatrice
Duek, Adrian
Duong, Hong Dung
Durieux-Paillard, Sophie
Dürr, Selina
P440
FM235
P415
FM230
FM292
P449, P453
P416
P415, P436
P432
FM280, FM284, P439, P440
FM229
P301
FM231
P329
P389
P462
P414
FM229, FM252
P410, P415, P436
P396
P381
P461
P390
FM284
P316, P317
FM288
FM266
P347, P357
FM273
P329
FM265
FM245, FM262, P421
P437
P386, P388
Ebneter, Andreas
Efe, Jana
Egger, Martin
Egloff, Michael
Eichelberger, Markus
Englberger, Lars
Epiney, Manuella
Erdmann, Andreas
Erne, Paul
P357
FM234
P297
FM226, FM254
P333
FM240
P306
P349
FM248
201
Name
Programmnummer
Erné, Seiichi
Ernst, Delphine
Escher, Robert
Escoffre-Barbe, Martine
Etter, Laurence
Etter, Marco
Exadaktylos, Aristomenis
Eyer, Stephan
P361
FM291
P297
FM288
FM291
P364
P324, P325, P326
FM247
Fäh, Uta
Favre-Bulle, Timothée
Favrod-Coune, Thierry
Fellmann, Petra
Fernandez, Jose
Ferrari, Nicola
Ferrari Pedrini, Petra
Ferreira, Maria
Fey, Maritn F.
Fiedler, Georg
Fischer, Roland
Fischli, Stefan
Fitting, Jean-William
Flatz, Aline
Fonfrède, Michèle
Fontana, Enzo
Fontana, Pierre
Fontolliet, Timothé
Ford, Ian
Franceschi, Michael
François, Anne
Frank, Matthias
Franzen, Daniel
Frascarolo, Sylvain
Frauchiger, Beat
Frauenfelder, Thomas
Frei, Remus
Frey, Peter
Fricker, M
Friedl, Andrèe
Frigerio, Susanna
Fujimura, Yoshihiro
Funk, Georg
Furrer, Florian
Fux, Christoph
FM240
P416
P318
P455
107
P414
FM234
P334
FM268, FM270
P324, P326
P314, P433
FM251
FM238
P411
FM257
P357
P458
P307
FM252
P454
P318
FM277, P394
P295, P344
FM276
FM226, FM254, P427
FM290
P387
FM229, FM253
P301
P349
P363
P451
P324
P304
FM224
Gachoud, David
Gagliano, Mariangela
Gallardo, Cristina
Gantenbein, Andreas
Garamvölgyi, Esther
Garavaglia, Barbara
Garcia Martinez, Juan
Garin, Nicolas
Garnier, Antoine
Gaspoz, Jean-Michel
Geiser, Thomas
Gemperli, Armin
Gemünden, Cornelia
Gencer, Baris
George, James N.
Georgios, Georgiou
P342, P406
P406
P460
P321
P456
FM286
P432
FM241
P406
FM227, FM235, FM253
FM238
FM227
P444
P377, P379, P384, P405, P407
P451
P454
202
Name
Programmnummer
Georgiou, Georgios
Gerber, Bernhard
Gerber, Martin
Gerosa, Rahel
Gerschheimer, Christiane
Gerstel, Eric
Geschwindner, Heike
Gessler, Katharina
Gétaz, Laurent
Gex, Gregoire
Gigandet, Thierry
Gilléry, Philippe
Gilliot, Géraldine
Gisler, Valentin
Gloy, Viktoria Luise
Gmel, Gerhard
Göber, Volkhard
Goede, Jeroen S.
Goede, Jeroen
Gold, Christina
Gold, Gabriel
Gonzenbach, Tobias
Graber, Peter
Graedel, Lena
Graf, Christophe
Graf, Lukas
Grandjean, Anne-Pascale
Green, Alexander
Gregoriano, Claudia
Griesser, Anne-Claude
Griesshammer, Ines
Griffin, John H
Grisouard, Jean
Grobholz, Rainer
Grolimund, Eva Marianne
Grouzmann, Eric
Grueber, Maude
Grüter, Erwin
Gubler, Jacques
Guerry, Frédéric
Guggiari, Celine
Guida, Linda
Guignard, Bertrand
Gussekloo, Jacobijn
Gut, Anne
Gutmann, Marc
Guyot, Sophie
P449, P453
FM281, FM290, P444
P308
FM263
P452
FM228
FM261
P386
P306, P312, P313, P318
P457
P297
FM257
P406
P341
FM249
P433
FM240
P444
FM286, FM289
P358, P425
FM274, FM278
P332
P362
FM224
FM274
P442
FM292
P319, P320
FM239, P386
FM245, FM262, P421
P360, P361
107
FM265
P343
P389
P355, P397
P422
P338
FM222, P294, P328, P368, P369
P449, P453
FM247
P458
P436
FM229, FM252
P317
P376
FM230
Hagedorn, Christian
Haimovici, Aladin
Haldemann, Cornelia
Haller, Christlieb
Halter, Jörg
Hanns Ulrich, Zeilhofer
Hans, Didier
Hao-Shen, Hui
Harris, Tamara
Hartemann, Agnès
Hartmer, Ralf
Haubitz, Sebastian
P296
FM268
P360
P298
P445
P415
P315, P423
106
P377
FM257
P448
FM224, P389
203
Name
Programmnummer
Hauffe, Till
Häuptle, Pirmin
Hayette, Sandrine
Hayoz, Daniel
Hediger, Emanuel
Heikenwälder, Mathias
Heim, Dominik
Heinrich, Henriette
Helbling, Arthur
Henzen, Christoph
Henzen, Silke
Hermans, Cedric
Herrmann, Francois
Heuss, Ludwig Theodor
Hiltbrunner, Sabine
Hitz, Fabienne
Hochstrasser, Denis
Hoefflinghaus, Tobias
Hoess, Claus
Holbro, Andreas
Holler, Thomas
Holm, Niels
Holzer, Barbara
Hrachovinova, Ingrid
Huber, Andreas
Huber, Philippe
Hudelson, Patricia
Hug, Balthasar
Hugli, Olivier
Huguet, Françoise
Hunziker, Sabina
Husmann, Marc
P354, P358, P397
P376
FM288
P422, P460
P386
FM263
P445
P295
P301, P374, P381, P434
FM251, P389
P435
P440
FM271, FM274
P351, P430
FM283
FM224
P448
P409, P429
P389
P445
P308
P429
FM232, FM259
P451
P343
FM278
P311, P316, P419
P308, P309
FM230, P323, P416
FM288
FM258
FM226, FM254
Ifrah, Norbert
Iglesias, Katia
Iglesias-Rutishauser, Katia
Imboden, Hans
Imhof, Alexander
Imhof, Beat A.
Imoberdorf, Reinhard
Irion, Olivier
Jaeger, Kurt
FM288
FM230, FM247, P356
P331
P355
P353, P418
FM266
P368, P372
P306
FM226
Jaff, Amir
Jäger, Kurt
Jaisson, Stéphane
Jandus, Camilla
Jandus, Peter
Janot-Berthier, Anne-Sophie
Jauslin, Daniel
Jeker, Raphael
Jent, Philipp
Jesaimani, Ameena
Joos Zellweger, Ladina
Jörg, Lukas
Jörg-Walther, Lukas
Jotterand, Martine
Juch, Heike
Juillet, Christian
Jukema, Wouter
Jüni, Peter
P380
FM254
FM257
P374
P374, P434
FM241
P376
P340, P378, P396
P371
P408, P410
FM238
P374
P381
P445
P350
P457
FM252
P379
204
Name
Programmnummer
Junod Perron, Noelle
P316, P317
Kaelin, Rainer
Kaiser, Cristoph
Kaiser, Udo
Kälin, Marisa
Kalogeropoulos, Andreas
Kalu Olu, Kelechi
Kamber, Christine
Kämpfen, Pascal
Kana, Veronika
Kaplan, Vladimir
Karajkovic, Aida
Karrer, Urs
Kasenda, Benjamin
Kashyap, Sangeeta R.
Kathriner, Silvio
Kaufmann, Theodor
Kearney, Patricia
Keller, Cornelia
Keller, Dorothee
Keller, Gabriela
Keller, Katarzyna
Keller, Pierre F.
Kentouche, Karim
Kerr, Eve
Kerse, Ngaire
Kherad, Omar
Kindler, Vincent
Klingenberg, Roland
Kneubühl, Agnes
Knoebl, Paul
Koch, Peter P.
Kohler, Malcolm
König, Vera
Kopf, Manfred
Köppel, Jan
Kossovsky, Michel
Krähenmann-Müller, Simone
Kralovics, Robert
Kramer, Naomi Esther
Krattinger, Regina
Kremer Hovinga, Johanna A.
Krieg, Marc-Antoine
Kriz, David
Kubik, Rahel
Kucher, Nils
Kueng, Marc
Kullak-Ublick, Gerd A.
Küng, Marc
Kunz, Isabelle
Künzi, Thomas
Kupferschmidt, Hugo
Kuss, Florian
Kutz, Alexander
Kwiatkowski, Maciej
P327, P426
P390
P385
P424
P377
FM236
P446
FM255, P459
FM223
FM259
P435
FM222, P294, P328, P368, P372
FM236
FM249
P443
P310
FM229, FM252
P399
FM240
P372
P336
P384, P405, P407
FM283
FM227, FM235, FM253
FM229
P322
FM269, FM292
P379
P364
P451
FM281
FM238
P378
FM263
FM290
P307, P408
FM235
106
FM291
P299
FM283, FM285, P451
P315, P423
P385
FM234
FM226, FM254
P346, P456
P299, P401
P347
P425
P353
FM233
P328
P389
P343
Lafage, Marina
Lambert, Jean-François
Lämmle, Bernhard
FM288
FM287, FM288
FM226, FM254, FM283, FM285, P451,
P452, P459, P462
205
Name
Programmnummer
Lamy, Olivier
Landolt, Lea
Lang, Marianne
Langewitz, Wolf
Lanz, Annika
Laube, Marcus
Laumonier, Thomas
Lazzaro, Mario
Leclair-Rezbach, Valérie
Lécureux, Estelle
Lefèbre - van de Fliert, Anne
Leguay, Thibault
Lehmann, Susanne
Lehmann, Thomas
Leib, Stefanie
Leichtle, Alexander
Leichtle, Georg
Leiss, Waltraud
Lepori, Mattia
Lepretre, Stephane
Lescuyer, Pierre
Leuppi, Jörg Daniel
Levi, Sonia
Levrat, Emmanuel
Lhéritier, Véronique
Licht, Abraham
Limacher, Andreas
Limacher, Andreas
Lindner, Gregor
Lippuner, Nadine
Liu, Kun
Locca, Didier
Lohmann, Christine
Lohri, Andreas
Looser, Renate
Louis-Simonet, Martine
Ludwig, Catherine
Lundberg, Pontus
Lüscher, Thomas
Luthy, Christophe
Lutz, Nina
Lyko, Christina
FM245, FM262, P315, P421
P409, P423
P414
FM258
FM277, P394
P348
FM269
FM231
P458
FM245, FM262, P421
FM229
FM288
P321
P442
FM246
P324, P325, P326
P325
FM226
FM231
FM288
P448
FM238, FM239, P386, P388
FM286
P456
FM288
P450
FM226, FM254, FM255
P323
P324, P325, P326
P298
106
P300
FM279
P376
106
P317
FM271
106, FM265
FM279, P379, P384, P405, P407, P438
FM271, P307, P339, P408, P410
P365
P366
Mach, François
Macinetti, Marco
Maier, Sabrina
Maître, Fabienne
Mallen, Christian D.
Mancinetti, Marco
Mandier, Jean-Luc
Mansouri Taleghani, Magnus
Manz, Markus
Marcoz, Noémie
Margelli Hartmann, Daniela
Markun, Stefan
Marono, David
Marques-Vidal, Pedro
P379, P384, P405, P407
P422
FM238, FM239, P386, P388
P311
FM229
P460
P454
FM285, P451
FM263, FM264, FM289, FM290, P444
FM273
FM239
FM259
P329
FM237, FM260, P300, P334, P335,
P375, P377
FM258
P325
P458
Marsch, Stephan
Marti, Grischa
Martin, Gabrielle
206
Name
Programmnummer
Martin, Ivan
Martin, Pierre-Yves
Martin, Yonas
Martinuz, Marco
Marx, Bea
Masouridi-Levrat, Stavroula
Mateiciuc, Simona
Matter, Christian
FM264
FM241
FM235
FM237, P375, P406
P414
FM292
FM273
FM226, FM254, FM279, P379, P384,
P405, P407
FM266
P415
P294
FM288
FM225
FM223
P362
P428
FM229
P323, FM226, FM254, FM255, P452
FM287
P350
P370
P354, P397
P449, P453, P454
FM236
P373
P423
P329
P387
P448
P405, P407
P438
P300
FM257
FM238, FM239, P386, P388
FM232
FM249
P390
P414
P457
P420
P330, P331, P428
FM229, FM252
P345
P333
FM257
105
P329
P413
FM286
FM291
FM224
P442
P304
P304
P363
P308, P329, P389
P329
P401
P322
P300
Matthes, Thomas
Matthey, Alain
Maurer, Florian P.
Maury, Sebastien
Mäusezahl-Feuz, Mirjam
Mauti, Laetitia
Mayr, Sylvia
Mazzolai, Lucia
McCarthy, Vera
Méan, Marie
Medina, Pedro
Meier, Christoph A.
Meier, Silvan
Meindl-Fridez, Claudine
Menoud, Pierre-Alain
Mertz, Dominik
Mertz, Kirsten
Metzger, Marie
Meune, Christophe
Meyenberger, Christa
Meyer, Markus
Meyer, Philippe
Meyer, Sara
Michel, Patrik
Michel, Pierre-Louis
Miedinger, David
Minder, Christoph
Mingrone, Geltrude
Mitropoulou, Georgia
Moccetti, Tiziano
Mohamed, Rania
Monod, Stéfanie
Monti, Matteo
Mooijaart, Simon P.
Moosmann, Peter
Morales, Isabel
Morel, Florence
Morfeld, Dianne
Mosimann, Tamina
Motamed, Sandrine
Muckenthaler, Martina
Muehlematter, Dominique
Mueller, Beat
Muesser, Patricia
Müggler, Simon Andreas
Muggli, David
Müller, Beatrice
Müller, Beat
Müller, Christian
Müller, Daniel
Müller, Halima
Muller, Olivier
207
Name
Programmnummer
Müller, Stefan
Muller-Juge, Virginie
Müllhaupt, Beat
Münzer, Thomas
Muth, Christiane
FM232
P311
P450
FM275
FM229
Nagler, Michael
Nagy Hulliger, Monika
Nair, Gayathri
Nanchen, David
Neerman-Arbez, Marguerite
Nendaz, Mathieu
Newman, Anne
Ngyuen-Kim, Thi Dan Linh
Nicolaus, Stefanie
Niggemeier, Verena
Nonnenmacher, Eveline
Nordmann, Alain J.
Novak, Urban
Nowak, Albina
Nsangu Mampasi, Mireille
Nübling, Rüdiger
Nuredini, Shpendin
Nussberger, Jürg
Nydegger, Urs
P443
FM292, P457, P461
FM290
P379, P384, P405, P407
FM280, P439
FM228, P311, P316, P317
P377
FM290
P367
P344
FM277, P394
FM249
FM267
P329, P336
P382
P385
P398
P355
FM287
Odenike, Olatoyosi
Ody, Christiane
Oppliger Leibundgut, Elisabeth
Osterwalder, Joseph
Öttl, Tobias
Ottman, Oliver
105
FM266
105
FM226, FM254
P376
105
Pabst, Thomas
Pache, Basile
Palan, Pakize
Parlier, Valerie
Paroz, Sophie
Pasch, Andreas
Passweg, Jakob
Paul, Michaela
Perger, Ludwig
Périard, Daniel
Perrier, Arnaud
Petersen, Jens Alexander
Petrausch, Ulf
Petriccioli, Nicole
Petrig, Christophe
Peyrani Dicastelnuovo, Paula
Peytremann-Bridevaux, Isabelle
Pfefferle, Maria
Pfenninger, Max
Pfortmüller, Carmen
Pham, Xuan-Cuong
Piallat, Marie Luce
Pianta, Annalisa
Piccinini, Elia
Pichler, Werner
Piguet, Valérie
Pilo, Paola
Pireva, Agim
P446, P447, P463
FM260, P335
P314, P420
P456
FM230, P319, P320
P352
P445
FM290
P299
P460
FM228, FM241, P436
P351
P296, P412
P322
P400
FM224
FM250, P356, P411
P312
P381
P326
P464
FM269
106
FM264
P374, P381, P434
P408, P410
FM222
FM256
208
Name
Programmnummer
Piso, Rein Jan
Plate, Andreas
Pletneva, Natalia
Polchlopek, Karolina
Pollock, Emily
Polsfuss, Silke
Popovic Sesartic, Bozana
Porter, Sarah
Portmann, Daniel
Postert, Flann Benjamin
Precup, Mihaela
Preisig, Martin
Prie, Nolwen
Prince, Raja
Prins, Crista
Privitera, Daniela
Pruvot, Etienne
Pugin, Paul
Pugliesi, Angela
Pumpol, Katrin
P360, P361
P403
P408
P461
P341
FM222
FM275
FM291
P369
P417
P456
P335, P423
FM291
FM282
P464
FM286
P331
P456
P339
P337
Quist-Paulsen, Petter
P451
Räber, Lorenz
Racine, Michael
Radpour, Ramin
Raffoux, Emmanuel
Ramirez, Julio
Randazzo, Marco
Ranzi, Monica
Rapin, Noémie
Rapiti, Elisa
Rapold, Roland
Raschle, Joelle
Räz, Hans-Ruedi
Recker, Franz
Reddy, Anita
Reemts, Christoph
Reeves, Scott
Regard, Simon
Regenass, Stephan
Regoli, François
Reiber, Claudine
Reich, Oliver
Reiner, Cäcilia
Reiner, Martin
Reinhart, Sophie A.
Reinhart, Walter H.
Renner, Christoph
Reny, Jean-Luc
Rettke, Horst
Reuss, Daniel
Rexhaj, Emrush
Rieder, Jean-Pierre
Riederer, Markus
Rieke, Alexander
Righini, Marc
Rimoldi, Stefano
Rincon Garriz, José Maria
Rinderknecht Graf, Stefan
Risch, Corina
P379, P405, P407
FM282
FM263
FM288
FM224
P343
P414
P331
P339
FM272
P447
P338
P343
105
P308
P342
P322
FM223
P414
P401
FM272
FM223
P438
P441
P378, P402, P441
P296
FM228
FM261
P435
FM256
P318
P297
P396
FM226, FM254
FM256
FM269
FM281
FM287
209
Name
Programmnummer
Risch, Lorenz
Risch, Martin
Ritter, Christian
Ritter, Simon
Rochat, Mathilde
Rochat, Philippe
Rodak, Roksana
Rodondi, Nicolas
Roeth, Alexander
Rogler, Gerhard
Rollason, Victoria
Roosnek, Eddy
Rosegger, Paula
Rosemann, Thomas
Rosset, Nina
Rothen, Claude
Rothen, Madeleine
Rotundo, Ida Luisa
Rotzetter, Jeanine
Rovó, Alicia
Rüegg, Linda
Russell, Audrey
Russmann, Stefan
Rutishauser, Jonas
Rutishauser, Maya
Rütti, Markus F.
FM246, FM287, P337
FM246, FM287, P337
FM277, P394
P350
P323
P427
FM259
FM226, FM227, FM229, FM235, FM252,
FM253, FM254, P377, P379, P384,
P405, P407
105
P302, P383
P410
FM292
P427
FM229
FM232
P310
P367, P398
FM286
P360
P445
P349
FM229
P299
P398
P332
FM234
Saber, Abdelmalek
Safroneeva, Ekaterina
Saitz, Richard
Saller, Francois
Samaras, Panagiotis
Samer, Caroline
Samet, Jeffrey
Samii, Kaveh
Sanches Rodrigues, Debora
Sander, Tina
Saner, Hugo
Santambrogio, Paolo
Sarasin, Francois
Sartori, Claudio
Satterfield, Suzanne
Savoldelli, Geroges
Schaer, Dominik
Schafroth Török, Salome
Schai, Marcel
Schaller, Monica
Schanz, Urs
Schätti, Gabriela
Schatzmann, Sarah
Schauer, Philip R.
Scheidegger, Paul
Scheidegger, Stephan
Schelling, Martin
Scherl, Alexander
Scherrer, Urs
Schers, Henk
Schiemann, Uwe
Schifferli, Jürg
FM278
P302, P383
FM243
107, FM282
P341
P436
FM243
P448, P449, P453, P464
107
FM242
FM240
FM286
FM274
FM256, P406
P377
P311
FM223, P344, P412
FM238
P435
FM283
FM290
FM232
P431
FM249
P349
FM234
P392
P448
FM256
FM229
P380
P308, P309
210
Name
Programmnummer
Schmidt, Helen
Schmidt, Jürgen
Schmied, Christian
Schneemann, Markus
Schneider, Dominik
Schneider, Martin
Schnellmann, Yves
Schneppenheim, Reinhard
Schoen, Tobias
Schoenenberger, Renate
Schoepfer, Alain
Schön, Tobias
Schönenberger, Andreas
Schönrath, Felix
Schott, Peter
Schoumans, Jacqueline
Schuberth, Petra
Schudel, Inge Maria
Schuetz, Philipp
Schulzki, Thomas
Schutgens, Roger
Schütz, Tobias
Schved, Jean-François
Schwarz, Christoph
Schwarz, Urs
Schwotzer, Rahel
Scotti, Celeste
Seematter-Bagnoud, Laurence
Seiler, Daniel
Semadeni, Gian-Marco
Semmo, Nasser
Senn, Nicolas
Senn, Oliver
Shapiro, Amy
Shimizu, Takafumi
Sibalic, Vladimir
Siderow, Anelia
Signorell, Ladina
Simic, Sandra
Singer, Gad
Skoda, Radek
Slahor, Lea
Sleptsova, Marina
Snyder, David
So, Alexander
Soltermann, Alex
Sommer, Johanna
Speidel, Victor
Spitzer, Gary
Sproedt, Julia
Spycher-Elbes, Rachel
Stahel, Rolf
Stähli, Noémie
Staritz, Peter
Steffen, Christian
Stegert, Mihaela
Steiner, Simon
Steiner, Urs
Steinmann, Eva
Steinrücken, Julia
Stelzer, Teresa
P321, P321
P385
P407
FM233, P303, P354, P397
P295
P393
FM278
P451
P337
FM248
P302, P383
FM246
FM248
P378
P418
FM291, P456
P296
P352
FM224, P308, P389
P402, P441
FM284
P361
P440
P324, P325, P326
P354, P397
P295, P450
FM264
FM276
P343
P387
P462
P314, P420
P401, P444
106
106, FM265
P435
P462
P396
P435
P349
106, FM265
FM251
P293
105
P315
P296
P317
P367
105
P328
P458
P296
P404
FM284
P364
FM236
P371
P434
P442
P362
P430
211
Name
Programmnummer
Stern, Martin
Steveling, Esther Helen
Stirnimann, Guido
Stivala, Simona
Stöckli, Thomas
Stoffel, Georg
Stoll, Delphine
Stott, David J.
Streit, Sven
Stuart, Monic
Stuck, Anna
Stucki, Stephanie
Studer, Irene
Stürzebecher, Katja
Suhm, Norbert
Sulzer, Irmela
Suna, Gonca
Surial, Bernard
Suter, Paolo
P445
P386, P388
P309
FM279, P438
P400, P403
P435
P315, P423
FM229, FM252
FM253
105
FM254
FM230
FM223, P341
P373
FM277, P394
FM283
P431
P395, P424
FM242, FM248, P354, P359, P397
Taffé, Patrick
Takizawa, Hitoshi
Tamm, Michael
Tavernier, Emmanuelle
Tessitore, Elena
Thalmann, George
Theodoloz, Mélanie
Thomann, Robert
Thomas, Xavier
Thommen, Désirée
Thöne, Joachim
Thurnheer, Robert
Tichelli, André
Tirefort, Yordanka
Tisljar, Kai
Tomaszek, Sandra
Tomonaga, Yuki
Trachsel, Maria
Tran Thang Ducommun, Nhu Nam
Trelle, Sven
Trobia, Massimo
Trueb, Lionel
Tsakiris, Dimitrios
Tschan, Mario
Tscherry, Georg
Tsopra, Olga
Tsybin, Yury
Turk, Alexander
FM250
FM264
FM238
FM288
FM228
P355
FM273
P389
FM288
P308
P425
FM238
P309, P445
FM292, P464
FM258
P296
FM236
P368, P399
P461
P452
FM231
FM230
P442
FM268, FM270
P424
FM292
P448
FM242
Uhlmann, Marc
Ullmer, Elke
FM245, FM262, P421
P373
Vader, John-Paul
Vallelian, Florence
Van der Vleuten, Cees
Varcher, Monica
Vaucher, Julien
Vavricka, Stephan
Verloo, Henk
Verstovsek, Srdan
Vieira, Margarida
P379
P412
P316, P317
P419
P300
P302, P383
P334
105
P334
212
Name
Programmnummer
Virgini, Vanessa
Vittinghoff, Eric
Vogel, Daniel
Vogel, Monique
Vögeli, Alaadin
Vogt, Pierre
Vollenbroich, René
Vollenweider, Peter
von der Weid, Nicolas
von Elm, Erik
von Moos, Seraina
von Overbeck, Jan
Vu, Nu Viet
Vuillemier, Pascal
Waeber, Bernard
Waeber, Gérard
Wagner, Claudia
Wagner, Stéphanie
Waldegg, Gabriel
Wampfler, Julian
Warner, Alex
Weber-Mani, Ulrich
Weder, Walter
Weilenmann, Daniel
Weiler, Stefan
Weissenberger, Noemi
Welker, Joris
Westendorp, Rudi G.J.
Wiemken, Timothy Lee
Wijsman, Liselotte
Windecker, Stefan
Winkler, Annette
Winter, Michael
Wirth, Rahel
Wolff, Hans
Wuillemin, Walter
Wymann, Monica
FM229, FM235, FM252
P377
P371
FM283
P389
P379, P384, P405, P407
P391
FM260, P300, P335, P423
P458
FM236
P425
FM272
P311, P330
P415
FM247
FM237, FM245, FM260, P300, P331,
P335, P375, P406, P423
FM259
P398
P297
FM270
FM229
P301
P296
P391
FM227, FM235, FM253
P308
P384
FM229, FM252
FM224
FM252
P379, P384, P405, P407
P398
FM243
P398
P306, P312, P313, P318, P319, P320
P443
FM225
Yalamanoglu, Ayla
Yerly, Daniel
You, John
P353
P374
FM236
Zbinden, Reinhard
Zechmann, Stefan
Zellweger, Jean-Pierre
Zellweger, Matthias
Zimmerli, Lukas
Zimmerli, Marius
Zimmerli, Stefan
Zimmerli, Werner
Zimmermann, Heinz
Zogg, Stefanie
Zoller, Bernhard
Zuber, Markus
Zufferey, Pascal
Zysset, Yvonne
P298
FM234
P305
P340
FM227, FM232, FM253, FM259
FM258
P446
FM244, P389
P324
FM239, P388, P386
P350
P361
P315
FM277, P394
213

Forum Médical Suisse Forum Medico Svizzero Schweizerisches Medizin

Transcription

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