2011 - Amphia Ziekenhuis

Transcription

Telefoon 076 595 50 00
www.amphia.nl
Breda/Oosterhout
Locatie Pasteurlaan
Pasteurlaan 9
4901 DH Oosterhout
–
Locatie Molengracht
Molengracht 21
4818 CK Breda
Vierde wetenschapsboek van het Amphia Ziekenhuis
Locatie Langendijk
Langendijk 75
4819 EV Breda
Vierde
wetenschapsboek
van het
Amphia Ziekenhuis
Breda/Oosterhout
Vierde Wetenschapsboek van het Amphia Ziekenhuis Breda/Oosterhout
Vierde wetenschapsboek
van het
Amphia Ziekenhuis
Breda/Oosterhout
Voorjaar 2012
© 2012 Amphia Ziekenhuis Breda Oosterhout
Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een
geautomatiseerd gegevensbestand, of openbaar gemaakt, in enige vorm of op enige wijze, hetzij elektronisch,
mechanisch, door fotokopieën, opnamen, of enige andere manier, zonder voorafgaande toestemming van de
uitgever. Voor zover het maken van kopieën uit deze uitgave is toegestaan op grond van artikel 16B Auteurswet
1912 jo het Besluit van 20 juni 1974, St.b. 351, zoals gewijzigd bij Besluit van 23 augustus 1985, St.b. 471 en
artikel 17 Auteurswet 1912, dient men de daarvoor wettelijk verschuldigde vergoedingen te voldoen aan de
Stichting Reprorecht. Voor het overnemen van gedeeltae(n) uit deze uitgave in bloemlezingen, readers en andere
compilatie- of andere werken (artikel 16 Auteurswet 1912), in welke vorm dan ook, dient men zich tot de
samenstellers/uitgever te wenden.
De inzichten in de geneeskunde en wetenschap zijn voortdurend aan verandering onderhevig als gevolg van
onderzoek en ervaring. De auteurs en uitgever zijn uiterst zorgvuldig te werk gegaan, om ervoor te zorgen dat
de in dit boek verstrekte informatie, in overeenstemming is met de huidige kennis van zaken. Dit ontslaat de
gebruiker van het boek echter niet van de verplichting om aan de hand van bestaande richtlijnen, protocollen en
wetenschappelijke informatie te controleren of de daar verstrekte informatie afwijkt van de gegevens in dit boek
en daarmee vast te stellen of de inhoud nog in overeenstemming is met de huidige stand van zaken ten aanzien
van kennis en handelen.
Ondanks alle aan de samenstelling van deze uitgave bestede zorg, zullen noch de samenstellers, noch de uitgever
aansprakelijkheid aanvaarden voor eventuele schade die zou kunnen voortvloeien uit enige fout die in deze
uitgave zou kunnen voorkomen.
Woord vooraf
Afgelopen jaar verscheen, in opdracht van de
branchevereniging STZ (Stichting samenwerkende
Topklinische Ziekenhuizen) een studie naar de
wetenschappelijke prestaties van de aangesloten
ziekenhuizen. Tot onze grote vreugde behaalden de
wetenschappelijke publicaties van het Amphia Ziekenhuis
een hoge impact factor. Daarmee behoren we in Nederland
tot de groep ziekenhuizen die bovengemiddelde
wetenschappelijke prestaties leveren. Bijzonder is daarbij
dat het aantal publicaties niet opvallend hoog is, maar de
wetenschappelijke relevantie van de publicaties des te meer.
De resultaten van dit onderzoek geven aardig weer waar
dr. J.J. (Hans) Meij
het Amphia Ziekenhuis staat en waar het voor staat. Het
Amphia Ziekenhuis wil op wetenschappelijk gebied een relevante bijdrage leveren aan
de geneeskunde in al haar facetten. De omvang van onze patiëntenpopulatie maakt
een dergelijke bijdrage mogelijk. Deze – soms omvangrijke – patiëntengroepen maken
het mogelijk om, samen met universitaire centra snel resultaten te boeken. Daarbij zijn
diepgang en relevantie voor ons belangrijker dan publicatie-frequentie.
Ook het afgelopen jaar is er in ons ziekenhuis weer op veel terreinen onderzoek verricht.
De resultaten hiervan zien wij terug in dit vierde Wetenschapsboek. Opvallend is dat
het aantal promoties dat in ons ziekenhuis is voorbereid snel toeneemt. Ons promotiestimulatiebeleid, waarin wij ook jonge talentvolle arts-assistenten en andere medewerkers
tijd en ruimte geven voor promotieonderzoek, werpt zijn vruchten af.
Woord vooraf
5
Wij hopen dat de gebundelde resultaten van de onderzoeken, alsmede de interviews met
auteurs en onderzoekers ook anderen stimuleren tot het verkennen van blinde vlekken
der geneeskunde en het ontdekken van het onbekende.
Namens het Directiecomité
dr. J.J. (Hans) Meij MBA
Directeur Innovatie
6
Vierde wetenschapsboek van het Amphia Ziekenhuis Breda/Oosterhout
De Wetenschapsraad kanaliseert
en coördineert
Het Amphia Ziekenhuis hecht veel belang aan wetenschappelijk onderzoek.
Directeur Innovatie dr. J.J. Meij legt uit waarom eind 2011 de Wetenschapsraad
is opgericht: “Om de wetenschappelijke activiteiten van alle specialismen en
specialisten in kaart te brengen en waar gewenst of nodig te coördineren.”
Een deel van de Wetenschapsraad 2011 v.l.n.r.:
dr. J. (Joachim) Aerts, mw. dr. A.A.P.H. (Anja) Vaessen dr. L. (Lijckle) van der Laan, dr. M.H.M. (Marc) Thelen,
dr. N.J.M. (Nardo) van der Meer, mw. drs. M. (Mariska) Bot, dr. J.J.E. (Hans) Meij, mw. dr. B.(Bouchra) Lechkar,
N.E. (Nils) van ‘t Veer, dr. G.L. (Giorgio) Porro, D.K.G. (Deric) van der Schoot
De Wetenschapsraad kanaliseert en coördineert
7
De eerste bijeenkomst van de Wetenschapsraad vond plaats op 20 december 2011.
Wetenschappelijk onderzoek is belangrijk voor het behoud van de topklinische functie
van het Amphia Ziekenhuis. Zowel voor de profilering naar patiënten en verzekeraars toe
(het bieden van kwalitatief hoogstaande zorg) als naar personeel en medisch specialisten
toe (het werven van topmedewerkers). Directeur Meij heeft naast innovatie ook onderwijs,
opleiding en onderzoek als zijn aandachtsgebieden. Hij is initiatiefnemer van de
Wetenschapsraad. “Van alle disciplines die onderzoek verrichten is een vertegenwoordiger
opgenomen in de raad. Zo kunnen we ook gezamenlijke onderzoeksgebieden definiëren.
Zonder verplichtingen te stellen, ontstaat een mogelijkheid om aan te schuiven bij
onderzoek dat bij de speerpunten van het ziekenhuis past.”
Beleid
8
Als voorbeeld van een onderzoekslijn noemt Meij het onderzoek naar veroudering. “Dat
is voor het hele ziekenhuis belangrijk. Weten wij al hoe we ouder wordende patiënten
behandelen? Velen hebben meerdere aandoeningen tegelijk en dat maakt de behandeling
steeds complexer. Bovendien is leeftijd meestal niet meer de beste indicator voor de
lichamelijke conditie en is bij ouderen een afwachtend beleid in bepaalde situaties beter
dan direct ingrijpen.” Genoeg facetten voor onderzoek. Na het uitzetten van een centrale
onderzoekslijn kunnen alle disciplines zich desgewenst aansluiten.
Opleidingsziekenhuis
Het Amphia Ziekenhuis is lid van de Stichting Topklinische opleidingsZiekenhuizen (STZ),
een status die belangrijk is voor het verkrijgen, behouden en uitbreiden van opleidingen.
“De onderzoeken die het Amphia Ziekenhuis initieert of waarin het participeert, hebben
een hoge kwaliteit, zo blijkt uit tellingen. De kwantiteit kan nog een tandje hoger en daar
zet de Wetenschapsraad zich voor in”, aldus Meij. Onderzoeksactiviteiten bevorderen de
kwaliteit van de zorgverlening en leveren vaak kostenbesparingen op. Bovendien zijn ze
goed voor de profilering richting collega-ziekenhuizen.
Aantal publicaties
De directeur geeft aan dat de Wetenschapsraad een regisserende functie heeft die voor
veel medewerkers meer op de achtergrond plaatsvindt. “Onderzoekers hoeven niet meer
individueel de wetenschapsweg te zoeken, maar kunnen leren van elkaars kennis. De
impact die wij als Wetenschapsraad wensen, zal onder meer blijken uit een toename van
het aantal publicaties.”
De wetenschapsraad kent de volgende samenstelling:
• dr. J. (Joachim) Aerts (Longgeneeskunde)
• mw. dr. A. (Annechien) Beumer (Orthopedie)
• mw. drs. M. (Mariska) Bot (Wetenschapscoördinatie)
• M.R. (Michel) Ju (Psychiatrie)
• prof. dr. J.A.J.W. (Jan) Kluytmans (Laboratorium voor Microbiologie en
Infectiepreventie)
• dr. L. (Lijckle) van der Laan (Chirurgie)
• mw. dr. B. (Bouchra) Lechkar (Reumatologie)
• dr. N.J.M. (Nardo) van der Meer (Anesthesiologie, Intensive care)
• dr. J.J.E. (Hans) Meij (directeur Innovatie)
• M. (Martijn) Meuwissen (Cardiologie)
• dr. M.A.W.M. (Marc) van Milligen de Wit (Interne geneeskunde en MDL)
• dr. D.N.M. (Dimitri) Papatsonis (Gynaecologie)
• dr. G.L. (Giorgio) Porro (Oogheelkunde)
• dr. B.P. (Bart-Pieter) van Putte (Cardiothoracale chirurgie)
• D.K.G. (Deric) van der Schoot (Urologie)
• dr. M.H.M. (Marc) Thelen (Klinische chemie)
• mw. dr. A.A.P.H. (Anja) Vaessen (Kindergeneeskunde)
• N.E. (Nils) van ’t Veer (Klinische farmacie)
De Wetenschapsraad kanaliseert en coördineert
9
Inhoud
Anesthesiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Apotheek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Cardiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Cardiothoracale chirurgie. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Chirurgie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Dermatologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Geriatrie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Gynaecologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Interne geneeskunde en Maag- darm- levergeneeskunde . . . . . . . 79
Kaakchirurgie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Kindergeneeskunde. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Klinisch Chemisch Hematologisch Laboratorium (KCHL) . . . . . . 105
Klinische fysica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Laboratorium voor Microbiologie en Infectiepreventie . . . . . . . . 117
Longgeneeskunde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Neurologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Nucleaire geneeskunde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Oogheelkunde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Orthopedie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Pathologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Radiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Reumatologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Seksuologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Urologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Inhoud
11
Publicaties Medisch Specialisten 2011 . . . . . . . . . . . . . . . . . . . 183
Publicaties Arts-assistenten 2011 . . . . . . . . . . . . . . . . . . . . . . 205
Publicaties Medewerkers 2011 . . . . . . . . . . . . . . . . . . . . . . . . 209
12
Anesthesiologie
Een helikopterblik op anesthesiologie
In 2010 promoveerde anesthesioloog B.M. (Bas) Gerritse op een onderzoek dat twee
wetenschappelijke prijzen won. Klinisch perfusionist D.M. (Dorien) Kimenai doet
zeer praktisch onderzoek naar de priming van hart-longmachines bij extracorporale
circulatie.
mw. dr. D.M. (Dorien) Kimenai en dr. B.M. (Bas) Gerritse
De maatschap Anesthesiologie heeft bijna elk jaar een promovendus en heel de zorgkern
profiteert van de nieuwe onderzoekskennis. Bas Gerritse werkt sinds 2008 in het Amphia
Ziekenhuis en is gespecialiseerd in cardio-anesthesiologie: “Maar de maatschap schoof
Anesthesiologie
13
mij naar voren voor dit interview vanwege een ander onderzoek dat ik eerder in Nijmegen
deed rond traumahelikopters.” Daarnaast begeleidde Gerritse het afstudeeronderzoek van
klinisch perfusionist Dorien Kimenai, die drie jaar bij het Amphia Ziekenhuis werkt en half
februari 2012 afstudeerde.
Twee prijzen
14
Anesthesioloog Gerritse won met zijn onderzoek de prijs voor het beste artikel
(‘Prehospitale echografie bij kinderen’) van een anesthesioloog van de Nederlandse
Vereniging voor Anesthesiologie. Hij ontving ook de Catharine Pijls Proefschriftprijs
(Universiteit van Maastricht) voor multidisciplinair, maatschappelijk relevant en excellent
onderzoek. Het onderzoek waarop Gerritse promoveerde bij de Radboud Universiteit
Nijmegen, heet ‘Prehospitale medische zorg bij kinderen door een helikopter Mobiel
Medisch Team’. Voor dit onderzoek volgde hij gedurende een periode van acht jaar 891
kinderen waarvoor de traumahelikopter in actie kwam. Daarbij keek hij naar meldingen,
gemaakte keuzes en ingezette behandelingen. Via een zorgvuldige registratie en
gevalideerde meetsystemen (psychomotorische en psychosociale vragenlijsten met in
totaal 90 vragen) ontstond een beeld van de gevolgen van een traumabehandeling voor
de jeugdige patiënt. De resultaten van de vragenlijsten zijn vergeleken met vergelijkbare
kinderen in dezelfde leeftijdscategorie waarbij een dergelijke behandeling niet plaatsvond.
“Veel kinderen doen het slechter dan je zou verwachten, zelfs in vergelijking met kinderen
na bijvoorbeeld hersenchirurgie of met ernstige juveniele reuma. Sommige kinderen zijn
overleden”, zegt Gerritse ernstig. “Ook daar kun je veel van leren. Bij kinderen die in
leven bleven, keken we naar de eventuele gevolgen. Na vijf jaar bezocht ik de betrokken
families weer om te kijken hoe het op dat moment ging. Ik moest voorzichtig te werk
gaan, want ik beschikte niet altijd over de volledige dataregistratie – als arts van de
traumahelikopter ben je geen directe behandelaar – en ik wist vaak niet of een kind nog
in leven was of niet. In het laatste geval was het oprakelen van het gebeurde natuurlijk
niet prettig voor ouders.”
Zo veel mogelijk van leren
Gerritse legde complete patiëntendossiers aan, met honderden velden per kind,
inclusief laboratoriumuitslagen et cetera. Deze werkwijze resulteerde in een gigantische
hoeveelheid data, die de anesthesioloog statistisch verwerkte met hulp van de afdeling
biomedische wetenschappen in Nijmegen. “We hebben zo veel mogelijk vastgelegd,
gemeten en geregistreerd, om er zo veel mogelijk van te leren. Wat zijn de redenen om
de traumahelikopter in te schakelen? Waar verrichten we de meeste levensreddende
handelingen? Dat begint met mislukte thuisbevallingen en daarna komen aangeboren
hartafwijkingen, hersenvliesontstekingen, geweldsmisdrijven, brandwonden, verstikkingen
en reanimaties om allerlei redenen. Bij sommige kinderen is de helikopter meerdere
keren geland om in te grijpen op hun vitale functies. Uit onderzoek blijkt dat dit soms
te relateren is aan sociale klasse, bijvoorbeeld bij brandwonden zie je dat heel duidelijk.
Kinderen raken eerder gewond als ze al een internistisch probleem hadden dat soms tot op
dat moment niet geconstateerd was, waardoor ze bijvoorbeeld net iets trager zijn. Soms
volgen ze al speciaal onderwijs.”
Welke lessen zijn er zo te leren uit de dagelijkse praktijk van de traumahelikopter?
Gerritse: “Een belangrijke les was dat kinderen geen kleine volwassenen zijn. Een halskraag die bij volwassenen prima voldoet, kan ongeschikt zijn voor een kind. Ook zagen we
dat bepaalde handelingen van het ambulancepersoneel – die bij volwassenen goed gaan –
bij kinderen vaak misgingen. Bijvoorbeeld het aanbrengen van een beademingsbuisje, dat
kan beter niet door ambulancepersoneel worden gedaan, want dat ging in dertig procent
van de gevallen mis.”
Praktisch en preventief
De onderzoeker geeft aan dat met deze bevindingen een algemene verbetering van de
ambulancezorg kan plaatsvinden. “Het onderzoek was uniek in zijn soort en leidde
onder meer tot de conclusie dat er gewoonweg nog te weinig onderzoek is gedaan naar
het reanimeren van kinderen. Dit was eigenlijk het eerste onderzoek in Nederland
dat keek naar kinderreanimatie buiten het ziekenhuis.” Ook waren er verbeteringen
in individuele situaties: toen bij twee kinderen uit hetzelfde gezin een onontdekte
hartafwijking werd geconstateerd, is ook de rest van de familie hierop onderzocht. Uit
de ervaring van Bas Gerritse komen ook praktische adviezen voort: zo bleek dat er veel
letsel plaatsvindt als mensen hun barbecue aansteken met aanmaakvloeistof in plaats
van blokjes. “Mensen spuiten dat in die barbecue en wie staat er vooraan? Het kind. Zo’n
constatering maakt preventie mogelijk van ongevallen op dit gebied, haal die vloeistof
toch uit de handel!” Op basis van de verzamelde data hebben meerdere publicaties
plaatsgevonden: over de geschiedenis van het vitaal bedreigde kind, de meldstructuur
per regio, aankomsthandelingen, echo-onderzoek op locatie, wel of niet opereren, beloop
op de IC, het opvolgingstraject et cetera. Gerritse was twaalf jaar actief met het Mobiel
Medisch Team, met soms vier tot tien inzetten op een dag. Op de vraag of het niet ‘saai’ is
om daarna te werken op een anesthesieafdeling, schudt Gerritse lachend zijn hoofd. “Nee
hoor, al vlieg je in een helikopter, het was ook gewoon werk. Hier doen we weer andere
dingen. Cardiochirurgie is absoluut niet saai. Bovendien heb ik veel praktijkervaring die ik
bij kinderen maar ook bij hartoperaties van volwassenen kan inzetten.”
Priming hart-longmachine
Half april is volgens planning ook het onderzoek van Kimenai afgerond. Dit is een
praktisch onderzoek, dat kijkt naar het effect op de stolling van het bloed door de vulling,
de zogenaamde priming, van hart-longmachines bij extracorporale circulatie. “Om de
Anesthesiologie
15
patiënt op de hart-longmachine te kunnen aansluiten, ontstollen we het bloed volledig
en leiden het daarna naar de hart-longmachine”, legt Kimenai uit. “Bij openhartchirurgie
leggen we het hart van de patiënt stil.” Ze toont het multifunctionele apparaat, dat
tijdelijk de hart- en longfunctie van de patiënt overneemt. Het bloed wordt met
misschien wel een derde verdund. Ondertussen worden op meerdere schermen exact de
omstandigheden gemonitord. Kimenai licht toe: “Na de operatie dient het bloed terug te
gaan naar de patiënt, waarna het nu juist weer van belang is de stolling zo veel mogelijk
te optimaliseren. Om het effect op de stolling van het bloed te meten gebruiken we naast
de klassieke stollingstesten ook een klinische point-of-caretest, de ROTEM®. Gewoonlijk
gebruiken we bij de afdeling extracorporale circulatie een priming op basis van gelatine
terwijl veel andere specialismen priming op basis van zetmeel gebruiken.” Kimenai
vervolgt dat gelatine een groot nadeel heeft, namelijk dat het rundercollageen bevat,
hetgeen allergische reacties op kan roepen. “Daarom zijn patiënten erbij gebaat als we de
priming op zetmeelbasis ook hier toepassen. Bovendien is het kostenbesparend als we het
ziekenhuisbeleid op dit gebied kunnen harmoniseren.”
16
Opvulling literatuurhiaat
De Duitse anesthesioloog Joachim Boldt legde de basis van het onderzoek, maar heeft
niet goed gehandeld met de ethische commissie. Een groot deel van zijn artikelen is
teruggetrokken uit de literatuur. “Daardoor is er een hiaat gevallen in de literatuur
op dit gebied, dat we met dit onderzoek willen opvullen”, legt Kimenai uit. De pilot
is nu afgerond en daarbij is vooral gekeken naar de uitvoerbaarheid. “Die is goed. Nu
hopen we binnen twee maanden de laatste zeventien van in totaal zestig patiënten te
includeren en dan ronden we af. Uit de resultaten van de pilot blijkt dat er geen nadelige
verschillen zijn op het effect van de stolling van het bloed tussen priming op gelatine- of
op zetmeelbasis. In afwachting van de hoofdstudie zou dat betekenen dat we inderdaad
het minder allergene product ziekenhuisbreed kunnen gaan toepassen.” Gerritse vult
aan dat dit onderzoek bijdraagt aan het overkoepelende doel: bloedbesparend werken.
“Collega Rosseel deed veel onderzoek naar bloedbesparing en optimale stolling. Verloren
bloed wassen we en we bewaren de cellen.” Gerritse eindigt met een boodschap voor het
hele Amphia Ziekenhuis. “We moeten niet te bescheiden zijn als ziekenhuis. Goed, netjes
opgezet onderzoek is belangrijk. Alleen al om methoden en technieken te gebruiken die
slimmer en handiger zijn voor de patiënt.”
Kerngegevens zorgkern Anesthesiologie
• 29 anesthesiologen: mw. A. (Anna) Besselink-Lobanova, S.F. (Sjoerd) de Boer, H.P.
(Henk) van Driel, M.J.P.G. (Maarten) van Eerd, P.A.V. (Peter) Frietman, F.E.A. (Ferd)
Geisler, G. (Gerhard) van Gelder, dr. B.M. (Bas) Gerritse, dr. V.L.H. (Vincent) Hoffmann,
L.H. (Lode) Jacobs, A. (Aad) van Keeken, J.D.L. (Johan ) Konings, A.Q. (Ahn) Le,
P.J.F. (Frank) de Loos, E.B. (Edmund) Lachitjaran, P.P.M. (Paul) Maas, dr. N.J.M. (Nardo)
van der Meer MBA, R.J. (Robert) Meulemans, F.X. (Frank) O’Connor, T.A. (Tom) Rijpstra,
dr. P.M.J. (Peter) Rosseel, dr. T.V. (Thierry) Scohy, C.M.P. (Clemens) Theunissen,
G. (Gilbert) Tjiang, dr. W.A. (Anton) Visser, mw. J. (Jacqueline) van Vliet, M.A.J.
(Michael) Voets, dr. E. (Erik) Winters, mw. S.I.M. (Simone) van Zijll Langhout-Kokke
• 8 arts-assistenten
• 10 assistenten niet in opleiding
• subspecialismen: cardio-anesthesiologie, pijnbestrijding, algemene anesthesiologie,
intensive care
Overzicht lopende onderzoeken
• Invasieve behandeling van degeneratieve nekklachten (promotieonderzoek Maarten van
Eerd)
• Bloedbesparende technieken bij cardiochirurgie
• Het effect op de stolling van plasmavervangers Gelofusin en Hydroxyethyl Starch 130/0.4
in combinatie met Ringerslactaat
• Prospectief onderzoek naar klinische waarde van routine-X-thorax bij patiënten op de
intensive care
• Intra-ossale toediening van medicijnen en infuusvloeistof bij medische noodsituaties
• Cardiac-outputmeting via innovatieve en weinig invasieve methodes
Samenvattingen gepubliceerde artikelen
Jansen NE, van Leiden HA, Haase-Kromwijk BJ, van der Meer NJ, Kruijff EV, van der
Lely N, van Zon H, Meinders AJ, Mosselman M, Hoitsma AJ. Appointing ‘trained donation
practitioners’ results in a higher family consent rate in the Netherlands: a multicenter
study. Transpl Int. 2011 Dec;24(12):1189-97. Epub 2011 Sep 8.
The consent process for organ and tissue donation is complex, both for families and
professionals. To help professionals in broaching this subject we performed a multicenter
study. We compared family consent to donation in three hospitals between December 2007
and December 2009. In the intervention hospital, trained donation practitioners (TDP) guided
66 families throughout the time in the ICU until a decision regarding donation had been
reached. In the first control hospital, without any family guidance or training, 107 families
were approached. In the second control hospital ‘hostesses’, who were not trained in donation
questions, supported 99 families during admittance. A total of 272 families were requested to
donate. We primarily compared consent rates, but also asked families about their experiences
through a questionnaire. Family consent rate was significantly higher in the intervention
hospital: 57.6% (38/66), than in the control hospitals: 34.6% (37/107) and 39.4% (39/99).
The 69% response rate to the questionnaire - 5 months after death - showed no confounding
Anesthesiologie
17
variables that could have influenced the consent rate. Appointing TDPs in the intervention
hospital to guide families during admittance and the donation decision-making process, results
in higher family consent rates. © 2011 The Authors. Transplant International © 2011 European
Society for Organ Transplantation.
PMID: 21902727
Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; Dutch SOD-SDD Trialists Group* [ Meer
NJ et al.]. The role of intestinal colonization with gram-negative bacteria as a source for
intensive care unit-acquired bacteremia. Crit Care Med. 2011 May;39(5):961-6.
OBJECTIVE: Selective digestive tract decontamination aims to eradicate gram-negative bacteria
in both the intestinal tract and respiratory tract and is combined with a 4-day course of
intravenous cefotaxime. Selective oropharyngeal decontamination only aims to eradicate
respiratory tract colonization. In a recent study, selective digestive tract decontamination and
selective oropharyngeal decontamination were associated with lower day-28 mortality, when
compared to standard care. Furthermore, selective digestive tract decontamination was associated
18
with a lower incidence of intensive care unit-acquired bacteremia caused by gram-negative
bacteria. We quantified the role of intestinal tract carriage with gram-negative bacteria and
intensive care unit-acquired gram-negative bacteremia. DESIGN: Data from a cluster-randomized
and a single-center observational study. SETTING: Intensive care unit in The Netherlands.
PATIENTS: Patients with intensive care unit stay of >48 hrs that received selective digestive tract
decontamination (n = 2,667), selective oropharyngeal decontamination (n = 2,166) or standard
care (n = 1,945). INTERVENTIONS: Selective digestive tract decontamination or selective
oropharyngeal decontamination. MEASUREMENTS AND MAIN RESULTS: Incidence densities
(episodes/1000 days) of intensive care unit-acquired gram-negative bacteremia were 4.5, 3.0,
and 1.4 during standard care, selective oropharyngeal decontamination, and selective digestive
tract decontamination, respectively, and the daily risk for developing intensive care unitacquired gram-negative bacteria bacteremia increased until days 36, 33, and 31 for selective
digestive tract decontamination, standard care, and selective oropharyngeal decontamination
and was always lowest during selective digestive tract decontamination. Rectal colonization
with gram-negative bacteria was present in 26% and 71% of patient days during selective
digestive tract decontamination and selective oropharyngeal decontamination, respectively
(p < .01). Irrespective of interventions, incidence densities of intensive care unit-acquired
gram-negative bacteremia was 4.5 during patient days with both intestinal and respiratory
tract gram-negative bacteria carriage. These incidence densities reduced with 33% (to 3.1)
during days with intestinal gram-negative bacteria carriage only and with another 45% (to 1.0)
during days without gram-negative bacteria carriage at both sites. CONCLUSIONS: Respiratory
tract decolonization was associated with a 33% and intestinal tract decolonization was
associated with a 45% reduction in the occurrence of intensive care unit-acquired gram-negative
bacteremia. *Collaborators (31): Kalkman CJ, Joore HJ, Leverstein-van Hall MA, Blok HE,
Kluytmans JA, van der Meer NJ, Mascini EM, Kaasjager K, Bosch FH, Benus RF, van der Werf TS,
van der Hoeven JG, Pickkers P, Sturm PD, Voss A, Bernards AT, Kuijper EJ, Harinck HI, Bindels
AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH,
van Iterson M, Thijsen SF, Kluge GH, de Vries JW, Kaan JA.
Comment in: Crit Care Med. 2011 May;39(5):1202-3.
PMID: 21283008 [PubMed - indexed for MEDLINE]
Scohy TV, Golab HD, Egal M, Takkenberg JJ, Bogers AJ. Intraoperative glycemic control
without insulin infusion during pediatric cardiac surgery for congenital heart disease.
Paediatr Anaesth. 2011 Aug;21(8):872-9. Epub 2011 Apr 4.
BACKGROUND: Many studies are reporting that the occurrence of hyperglycemia in the
postoperative period is associated with increased morbidity and mortality rates in children after
cardiac surgery for congenital heart disease. This study sought to determine blood glucose levels
in standard pediatric cardiac anesthesiological management without insulin infusions. METHODS:
The study population consisted of 204 consecutive pediatric patients aged from 3 days to
15.4 years undergoing open cardiac surgery for congenital heart disease between June 2007
and January 2009. Glucose-containing fluids were not administrated intraoperatively, and all
patients received high dose of opioids (sufentanil 10 mcg·kg(-1) ) and steroids (30 mg·kg(-1)
methylprednisolone) iv. Glucose levels were measured before CPB, 10 min after initiation
of CPB, every hour on CPB, post-CPB, and on arrival at intensive care unit (ICU). RESULTS:
Intraoperatively, only one patient had a glucose level <50 mg·dl(-1) (=34.2 mg·dl(-1)), 57/204
patients (27.9%) had at least one intraoperative glucose >180 mg·dl(-1) , but only 12 patients
(5.8%) had a glucose level >180 mg·dl(-1) at ICU arrival. Thirty-day mortality was 1.5%
(3/204). Younger age, lower body weight, and lower CPB temperature were associated with
hyperglycemia at ICU arrival, as were higher RACHS and Aristotle severity scores. CONCLUSION:
A conventional (no insulin, no glucose) anesthetic management seems sufficient in the vast
majority of patients (96.5%). Special attention should be paid to small neonates with complex
congenital heart surgery, in whom insulin treatment may be contemplated. © 2011 Blackwell
Publishing Ltd.
Scohy TV, Lüthen C, McGhie J, Oei F. Three-dimensional transesophageal
echocardiography: diagnosing intraoperative pulmonary artery thrombus. Interact
Cardiovasc Thorac Surg. 2011 May;12(5):840-1. Epub 2011 Feb 5.
A 61-year-old patient with the diagnosis of acute heart failure based on severe mitral valve
insufficiency due to chordae rupture was scheduled for surgery. Intraoperatively, a standard
Anesthesiologie
19
two-dimensional transesophageal echocardiogram (2D-TEE) examination, revealed severe mitral
valve regurgitation due to a prolaps with chordal rupture and an echo dense structure in the
pulmonary artery (PA). Because it was not possible to visualize this echo dense structure fully
with 2D-TEE we performed a three-dimensional transesophageal echocardiogram (3D-TEE).
On the basis of the clear demonstration on 3D-TEE of an at least 6-cm thrombus in the PA we
decided to remove the thrombus prior to proceeding with the mitral valve repair. We conclude
that 3D-TEE can alter surgical management and provide more valuable information on PA
thrombus than that obtained by 2D-TEE.
Comment in: Interact Cardiovasc Thorac Surg. 2011 May;12(5):841-2.
Lipszyc M, Winters E, Engelman E, Baurain M, Barvais L. Remifentanil patient-controlled
analgesia effect-site target-controlled infusion compared with morphine patient-controlled
analgesia for treatment of acute pain after uterine artery embolization. Br J Anaesth. 2011
May;106(5):724-31. Epub 2011 Mar 25.
20
BACKGROUND: Post-procedural pain control after uterine artery embolization (UAE) of urethral
leiomyomata remains a major problem. METHODS: This double-blind, randomized study tested
the possibility to obtain a quicker onset of analgesia by using effect-compartment controlled
remifentanil patient-controlled analgesia (remifentanil TCI-PCA) than by using i.v. morphine
PCA. Both systems were connected to an i.v. catheter. Active drug or matching placebo
administration was activated by a single push-button. Pain was assessed using a numerical
rating scale (NRS) from 0 to 10. RESULTS: NRS values were lower in the remifentanil group
(with a possible difference from two to seven points on the scale) during the initial 4 h
post-embolization. After the fourth hour, the NRS values were identical between the groups.
No major respiratory or haemodynamic side-effect was observed. CONCLUSIONS: Remifentanil
PCA-TCI with a slow and progressive adapted algorithm without any associated premedication or
co-medication is feasible in young healthy women undergoing UAE.
Complete publicatielijst
De Vogel J, Heydanus R, Mulders AG, Smalbraak DJ, Papatsonis DN, Gerritse BM. lifesaving
intraosseous access in a patient with a massive obstetric hemorrhage. Am J Perinatol
Rep. 2011; 1(2): 119-122.
Jansen NE, van Leiden HA, Haase-Kromwijk BJ, van der Meer NJ, Kruijff EV, van der Lely
N, van Zon H, Meinders AJ, Mosselman M, Hoitsma AJ. Appointing ‘trained donation
Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; Dutch SOD-SDD Trialists Group* [Meer
NJ et al... ]. The role of intestinal colonization with gram-negative bacteria as a source
for intensive care unit-acquired bacteremia. Crit Care Med. 2011 May;39(5):961-6.
Scohy TV. Perioperative Anesthestic Innovations during Pediatric Cardiac Surgery.
Rotterdam: Optima Grafische Communicatie, 2011. Proefschrift Erasmus Universiteit
Rotterdam.
Geniets B, van de Ven CP, Maat AP, Scohy TV. Intraoperative transesophageal
echocardiography for mediastinal mass surgery improves anesthetic management in
pediatric patients. Paediatr Anaesth. 2011 Dec;21(12):1276-8.
analgesia effect-site target-controlled infusion compared with morphine patientcontrolled analgesia for treatment of acute pain after uterine artery embolization.
Br J Anaesth. 2011 May;106(5):724-31. Epub 2011 Mar 25.
Anesthesiologie
21
Apotheek
Wetenschap in opbouw: publicaties in press
Je kunt als afdeling druk bezig zijn met onderzoeksactiviteiten, in afwachting van
publicaties. De apotheek van het Amphia Ziekenhuis is zo’n voorbeeld. Het verhaal
van ziekenhuisapotheker Nils van ’t Veer schetst hoe zo’n ‘prepressfase’ eruitziet.
N.E. (Nils) van ’t Veer
Apotheek
23
“De voorgaande jaren hadden we telkens twee of drie publicaties, als auteur of
medeauteur”, vertelt Van ’t Veer. “We zijn een iets afwijkende ziekenhuisafdeling.
We kennen nog geen directe patiëntencontacten en we richten ons op farmaceutische
ondersteuning en productie van geneesmiddelen. Tegelijkertijd zien we natuurlijk het
belang van onderzoek en bovendien zijn onderzoeksactiviteiten van belang voor de
ziekenhuisapothekers die we opleiden.” Bij de opleidingsvisitatie in 2010 bleek dat
de zaken goed op orde zijn. Er is een derde opleidingsplaats bijgekomen, maar die is
niet ingevuld wegens een landelijke instroombeperking. Wel kwam uit de visitatie de
aanbeveling voort om voor 2015 meer onderzoeksactiviteiten te ontplooien. “Dat belang
zagen we zelf ook in. Daarom zijn we volop onderzoek aan het ontwikkelen,
in samenwerking met anderen in dit ziekenhuis.”
Onderzoek naar aandoening met iatrogene oorzaak
24
Samen met Longgeneeskunde startte de apotheek een onderzoek naar aandoeningen
met iatrogene oorzaak, een belangrijk aandachtsgebied in het Amphia Ziekenhuis.
De ziekenhuisapotheker legt uit dat de therapieën voor longkanker steeds intensiever
en krachtiger worden. Bij een kleincellig longcarcinoom vindt zowel chemotherapie als
bestraling plaats en die bestralingen nemen toe in intensiteit. “Dan ontstaat vaak een
mucositis (slijmvliesontsteking) en ook een ontsteking van de oesophagus en dat is
het gebied waar we interesse in hebben. Nu testen we of toepassing van een specifieke
elektrolytoplossing een preventieve werking heeft en oesofagitis voorkomt. Wellicht
kan dit de kwaliteit van leven van longkankerpatiënten verbeteren.” Er is nu een
conceptprotocol en de studie start in 2012. Vanwege de benodigde populatiegrootte is er
contact gelegd met andere ziekenhuizen voor samenwerking. “Wellicht komt er zelfs een
promotie uit voort.”
Wetenschapsklimaat
Een groot deel van de toekomstige publicaties zal de vorm krijgen van case reports.
Daarnaast is het streven om ten minste één onderzoek per jaar te starten. In de
ziekenhuisapotheek is voor Van ’t Veer wel tijd vrijgemaakt voor onderzoek. “Maar ik heb
niet veel minder taken”, glimlacht hij. Hij is blij met de Wetenschapsraad die in oprichting
is in het Amphia Ziekenhuis. “Het is fijn dat er een stimulerend klimaat heerst, met
initiatiefnemers als Joachim Aerts die je enthousiast maken. Dan ontstaat een groeimodel,
want je hebt de ondersteuning van anderen nodig.” Alle zeven ziekenhuisapothekers
hebben eigen aandachtsgebieden. Een taak van Van ’t Veer is het opleiden van ziekenhuisapothekers in opleiding.
Onderzoek met microbiologie en gynaecologie
Een tweede onderzoek dat Van ’t Veer noemt, vindt plaats in samenwerking met
microbiologie. “We hebben een lange historie met deze afdeling. We doen regelmatig
onderzoek naar het effect van interventies.”
Verder heeft de ziekenhuisapotheek geparticipeerd in het landelijke ‘Apostel III’onderzoek van de Zorgkern gynaecologie. Dit is een onderzoek naar weeënremming
met nifedipine bij dreigende vroeggeboorte. “We keken naar de farmacokinetiek bij
verschillen in dosis en gebruiksduur. Het onderzoek is afgesloten en een publicatie is
in voorbereiding.” Het is een multicenteronderzoek, waaraan het Amphia Ziekenhuis
bijdraagt vanwege het grote aantal klinische bevallingen dat hier plaatsvindt.
Onderzoek met ICU en Anesthesiologie
Bij de ICU is het onderzoek naar dosisaanpassing van antibiotica bij nierinsufficiëntie
actueel. “Er was een vraag vanuit de intensivisten om een praktisch doseerschema zonder
dosisaanpassing te onderbouwen met farmacokinetisch onderzoek. Belangrijk is dat bij
verschillende stadia van verminderde nierfunctie de juiste hoeveelheid medicatie wordt
toegediend terwijl de uitscheiding van de nier is verminderd. Bij dialyse is die uitscheiding
maar twintig procent van wat de nieren gewoonlijk doen, dus dan moet je sturen. Maar
bij ernstig zieke patiënten wil je ook niet onderbehandelen. Stel je bent ernstig ziek en je
hebt een bloedvergiftiging, hoeveel antibioticum doseer je? Sommige antibiotica hebben
een geringe toxiciteit. Ga je bij nierinsufficiëntie de dosis halveren, of toch die honderd
procent doseren?” Dit wordt onderzocht voor cefotaxim.
Met Anesthesiologie is een onderzoek gedaan naar postoperatieve nausea en vomiting
na buik-OK’s. “Bij een buik-OK ontvang je morfine als pijnstilling. Daarvan kun je, net als
van de operatie zelf, misselijk worden. In dit onderzoek voegden we droperidol toe aan
de pijncassette. Onze hypothese is bevestigd in een dubbelblind onderzoek, waardoor we
toekomstig beleid kunnen aanpassen. Publicaties zijn in voorbereiding.”
Nu zaaien, straks oogsten
Voor de toekomst ziet Van ’t Veer een innovatieve rol weggelegd voor het elektronisch
voorschrijfsysteem van EPIC. Dit kan de medicatiebewaking verbeteren door
koppelingen met bijvoorbeeld laboratoriumgegevens en biedt naar verwachting
betere mogelijkheden tot uitkomstenonderzoek. Ook de op te richten poliklinische
apotheek biedt aanknopingspunten. De ziekenhuisapotheker is content met de gestarte
onderzoeksactiviteiten: “Mooi van deze wetenschappelijke inspanningen is dat het
ziekenhuis en de apotheek hierbij hand in hand kunnen gaan. Onderzoek verbindt de
apotheek met het ziekenhuis en resulteert in onderzoekslijnen. Voor onze afdeling geldt
daarbij: we zaaien nu onderzoek, om straks te oogsten.”
Apotheek
25
Kerngegevens Apotheek
• 7 ziekenhuisapothekers: P.R.M. (Paul) van Hattum, mw. V.S (Victorine) Koster,
C.H.P. (Chris) Pellicaan, P.A.O. (Peter) Smithuis, N.E. (Nils) van ’t Veer, mw. R.R.E.C.M.
(Relin) Verzijl-Zeegers, mw. M.F.G. (Marjolein) Winters
• 2 assistenten in opleiding
• 1 project apotheker
• verwerkte recepten per jaar: 480.000
26
Cardiologie
Kerngegevens zorgkern Cardiologie
• 14 cardiologen: dr. A.M.W. (Marco) Alings, dr. B.J.L. (Ben) van den Branden,
W.A.J. (Wim) Bruggeling, H.M.A. (Huub) Corbeij, dr. P.H.J.M. (Peter) Dunselman,
H.P.J. (Henry) de Haan, dr. P. (Peter) den Heijer, dr. M. (Martijn) Meuwissen,
S.G (Sander) Molhoek, J.A.M. (Hans) te Riele, dr. T.A. (Tim) Simmers, dr. S. (Sipke)
Strikwerda, dr. J. (Jeroen) Vos, dr. R.P. (Rob) Wielenga
• 1 chef de clinique
• subspecialismen: algemene cardiologie (hart- en vaatziekten in brede zin),
beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stenten dotterbehandelingen, vervanging hartklep), congenitale cardiologie (aangeboren
hartgebreken) en elektrofysiologie (behandeling van hartritmestoornissen)
Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, Atar D, Avezum Á,
Blomström P, Borggrefe M, Budaj A, Chen SA, Ching CK, Commerford P, Dans A, Davy JM,
Delacrétaz E, Di Pasquale G, Diaz R, Dorian P, Flaker G, Golitsyn S, Gonzalez-Hermosillo
A, Granger CB, Heidbüchel H, Kautzner J, Kim JS, Lanas F, Lewis BS, Merino JL, Morillo
C, Murin J, Narasimhan C, Paolasso E, Parkhomenko A, Peters NS, Sim KH, Stiles MK,
Tanomsup S, Toivonen L, Tomcsányi J, Torp-Pedersen C, Tse HF, Vardas P, Vinereanu D,
Xavier D, Zhu J, Zhu JR, Baret-Cormel L, Weinling E, Staiger C, Yusuf S, Chrolavicius S,
Afzal R, Hohnloser SH; PALLAS Investigators*. Dronedarone in high-risk permanent atrial
fibrillation. N Engl J Med. 2011 Dec 15;365(24):2268-76. Epub 2011 Nov 14.
Cardiologie
27
BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death
in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has
antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that
dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.
METHODS: We assigned patients who were at least 65 years of age with at least a 6-month
history of permanent atrial fibrillation and risk factors for major vascular events to receive
dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction,
systemic embolism, or death from cardiovascular causes. The second coprimary outcome was
unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment
of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome
occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29;
95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular
causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00
to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively
(hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the
dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88;
28
P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group
and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS:
Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in
patients with permanent atrial fibrillation who were at risk for major vascular events. Our data
show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS
ClinicalTrials.gov number, NCT01151137.). * Collaborators (550) Erratum in: N Engl J Med. 2012
Feb 16;366(7):672.
Comment in: N Engl J Med. 2011 Dec 15;365(24):2321-2; Nat Rev Cardiol. 2012 Jan;9(1):5.
PMID: 22082198[PubMed - indexed for MEDLINE]
Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G,
Reilly PA, Yang S, Yusuf S, Wallentin L, Connolly SJ; RE-LY Investigators. Risks for stroke,
bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in
relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med.
2011 Nov 15;155(10):660-7, W204.
BACKGROUND: CHADS(2) is a simple, validated risk score for predicting the risk for stroke in
patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the
risk for thrombotic and bleeding complications according to the CHADS(2) score in patients
receiving anticoagulant therapy. OBJECTIVE: To evaluate the prognostic importance of CHADS(2)
risk score in patients with atrial fibrillation receiving oral anticoagulants, including the
vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran. DESIGN: Subgroup
analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600)
SETTING: Multinational study setting. PATIENTS: 18 112 patients with atrial fibrillation who were
receiving oral anticoagulants. MEASUREMENTS: Baseline CHADS(2) score, which assigns 1 point
each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus
and 2 points for stroke. RESULTS: Distribution of CHADS(2) scores were as follows: 0 to 1-5775
patients; 2-6455 patients; and 3 to 6-5882 patients. Annual rates of the primary outcome of
stroke or systemic embolism among all participants were 0.93% in patients with a CHADS(2)
score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6.
Annual rates of other outcomes among all participants with CHADS(2) scores of 0 to 1, 2, and
3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial
bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001
for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and
vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS(2)
score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily,
and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than
those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS(2)
scores. LIMITATION: These analyses were not prespecified and should be deemed exploratory.
CONCLUSION: Higher CHADS(2) scores were associated with increased risks for stroke or systemic
embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants.
Primary Funding Source: Boehringer Ingelheim.
Comment in: Ann Intern Med. 2011 Nov 15;155(10):714-5, W218.
PMID: 22084332 [PubMed - in process]
Groenveld HF, Crijns HJ, Van den Berg MP, Van Sonderen E, Alings AM, Tijssen JG, Hillege
HL, Tuininga YS, Van Veldhuisen DJ, Ranchor AV, Van Gelder IC; RACE II Investigators. The
effect of rate control on quality of life in patients with permanent atrial fibrillation: data
from the RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) study. J Am Coll
Cardiol. 2011 Oct 18;58(17):1795-803.
OBJECTIVES: The aim of this study was to investigate the influence of rate control on quality
of life (QOL). BACKGROUND: The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation
II) trial showed that lenient rate control is not inferior to strict rate control in terms of
cardiovascular morbidity and mortality. The influence of stringency of rate control on QOL is
unknown. METHODS: In RACE II, a total of 614 patients with permanent atrial fibrillation (AF)
were randomized to lenient (resting heart rate [HR] <110 beats/min) or strict (resting HR
<80 beats/min, HR during moderate exercise <110 beats/min) rate control. QOL was assessed
in 437 patients using the Medical Outcomes Study 36-item Short-Form Health Survey (SF36) questionnaire, AF severity scale, and Multidimensional Fatigue Inventory-20 (MFI-20) at
baseline, 1 year, and end of study. QOL changes were related to patient characteristics. RESULTS:
Median follow-up was 3 years. Mean age was 68 ± 8 years, and 66% were males. At the end of
Cardiologie
29
follow-up, all SF-36 subscales were comparable between both groups. The AF severity scale was
similar at baseline and end of study. At baseline and at end of study there were no differences
in the MFI-20 subscales between the 2 groups. Symptoms at baseline, younger age, and less
severe underlying disease, rather than assigned therapy or heart rate, were associated with
QOL improvements. Female sex and cardiovascular endpoints during the study were associated
with worsening of QOL. CONCLUSIONS: Stringency of heart rate control does not influence QOL.
Instead, symptoms, sex, age, and severity of the underlying disease influence QOL. (Rate Control
Efficacy in Permanent Atrial Fibrillation; NCT00392613). Copyright © 2011 American College of
Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Comment in: J Am Coll Cardiol. 2011 Oct 18;58(17):1804-6.
30
Smit MD, Crijns HJ, Tijssen JG, Hillege HL, Alings M, Tuininga YS, Groenveld HF, Van den
Berg MP, Van Veldhuisen DJ, Van Gelder IC; RACE II Investigators. Effect of lenient versus
strict rate control on cardiac remodeling in patients with atrial fibrillation data of the
RACE II (RAte Control Efficacy in permanent atrial fibrillation II) study. J Am Coll Cardiol.
2011 Aug 23;58(9):942-9.
OBJECTIVES: The aim of this study was to evaluate echocardiographic remodeling in permanent
atrial fibrillation (AF) patients treated with either lenient or strict rate control. BACKGROUND:
It is unknown whether in permanent AF, lenient rate control is associated with more adverse
cardiac remodeling than strict rate control. METHODS: Echocardiography was conducted at
baseline and at follow-up in 517 patients included in the RACE II (RAte Control Efficacy in
permanent atrial fibrillation II) trial. Echocardiographic parameters were compared between
patients randomized to lenient rate control (n = 261) or strict rate control (n = 256). RESULTS:
Baseline echocardiographic parameters were comparable between patients randomized to lenient
and strict rate control. Between baseline and follow-up, significant adverse atrial or ventricular
remodeling was not observed in either group. There were also no significant differences in atrial
and ventricular remodeling between patients who continuously had heart rates between 80 and
110 beats/min and patients who continuously had heart rates <80 beats/min during followup. Lenient rate control was not independently associated with changes in echocardiographic
parameters: mean adjusted effect on left atrial size was 1.6 mm (p = 0.09) and 1.1 mm on left
ventricular end-diastolic diameter (p = 0.23). Instead, female sex was independently associated
with adverse remodeling: mean adjusted effect on left atrial size was 2.4 mm (p = 0.02) and
6.5 mm on left ventricular end-diastolic diameter (p < 0.0001). CONCLUSIONS: Female sex, not
lenient rate control, seemed to be associated with significant adverse cardiac remodeling in
patients with permanent AF such as those enrolled in the RACE II study. (RAte Control Efficacy
in Permanent Atrial Fibrillation [RACE II]; NCT00392613). Copyright © 2011 American College of
Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Comment in: J Am Coll Cardiol. 2011 Aug 23;58(9):950-2; Nat Rev Cardiol. 2011 Nov;8(11):608.
Van den Broek KC, Tekle FB, Habibovic M, Alings M, van der Voort PH, Denollet J.
Emotional distress, positive affect, and mortality in patients with an implantable
cardioverter defibrillator. Int J Cardiol. 2011 Sep 29. [Epub ahead of print]
BACKGROUND: Little is known about the relationship between emotional distress and mortality
in patients with an implantable cardioverter defibrillator (ICD). Our aim was to examine the
predictive value of general negative and positive affect, and depressive symptoms (including
its components somatic symptoms and cognitive-affective symptoms) for mortality. METHODS:
ICD patients (N=591, 81% male, mean age=62.7±10.1years) completed the Global Mood Scale
to measure the independent dimensions negative and positive mood, and the Beck Depression
Inventory to measure depressive symptoms. Covariates consisted of demographic and clinical
variables. RESULTS: During the median follow-up of 3.2years, 96 (16.2%) patients died. After
controlling for covariates, negative affect was significantly related to all-cause mortality
(HR=1.034, p=0.002), whereas positive affect was not (HR=1.007, p=0.61). Depressive symptoms
were also independently associated with an increased mortality risk (HR=1.031, p=0.030) and
somatic symptoms of depression in particular (HR=1.130, p=0.003), but cognitive-affective
symptoms were not associated with mortality (HR=0.968, p=0.29). When entering both
significant psychological predictors in a covariate-adjusted model, negative mood remained
significant (HR=1.039, p=0.009), but somatic symptoms of depression did not (HR=0.988,
p=0.78). Similar results were found for cardiac-related death. Of covariates, increased age,
CRT, appropriate shocks were positively related to death. CONCLUSIONS: Negative affect in
general was related to mortality, but reduced positive affect was not. Depression, particularly
its somatic symptoms, was also related to mortality, while cognitive-affective symptoms were
not. Future research may further focus on the differential predictive value of emotional distress
factors, as well as on mechanisms that relate emotional distress factors to mortality.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PMID: 21963213 [PubMed - as supplied by publisher]
Habibovic M, van den Broek KC, Theuns DA, Jordaens L, Alings M, van der Voort PH,
Pedersen SS. Gender disparities in anxiety and quality of life in patients with an
implantable cardioverter-defibrillator. Europace. 2011 Dec;13(12):1723-30. Epub 2011
Aug 6.
AIMS: A paucity of studies in implantable cardioverter-defibrillator (ICD) patients has examined
gender disparities in patient-reported outcomes, such as anxiety and quality of life (QoL). We
investigated (i) gender disparities in anxiety and QoL and (ii) the magnitude of the effect of
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gender vs. New York Heart Association (NYHA) functional class (III/IV), ICD shock, and Type D
personality on these outcomes. METHODS AND RESULTS: Implantable cardioverter-defibrillator
patients (n = 718; 81% men) completed the State-Trait Anxiety Inventory (STAI) and the ShortForm Health Survey 36 (SF-36) at baseline and 12 months post-implantation. The magnitude
of the effect was indicated using Cohen’s effect size index. Multivariate analysis of covariance
for repeated measures showed no differences between men and women on mean scores of
anxiety (F((1,696)) = 2.67, P = 0.10). Differences in QoL were observed for only two of the
eight subscales of the SF-36, with women reporting poorer physical functioning (F((1,696)) =
7.14, P = 0.008) and vitality (F((1,696)) = 4.88, P = 0.028) than men. With respect to anxiety,
effect sizes at baseline and 12 months for gender, NYHA class, and ICD shocks were small. A
large effect size for Type D personality was found at both time points. For QoL, at baseline and
12 months, the effect sizes for gender were small, while the influence of NYHA class and Type
D personality was moderate to large. CONCLUSIONS: Men and women did not differ on mean
anxiety or QoL scores, except for women reporting poorer QoL on two domains. The relative
influence of gender on anxiety and QoL was less than that of NYHA functional class and Type D
personality.
32
Versteeg H, van den Broek KC, Theuns DA, Mommersteeg PM, Alings M, van der Voort
PH, Jordaens L, Pedersen SS. Effect of cardiac resynchronization therapy-defibrillator
implantation on health status in patients with mild versus moderate symptoms of heart
failure. Am J Cardiol. 2011 Oct 15;108(8):1155-9. Epub 2011 Aug 6.
Indications for cardiac resynchronization therapy (CRT) have expanded to include patients with
mild congestive heart failure (CHF) symptoms (New York Heart Association [NYHA] functional
class II) because of a demonstrated morbidity reduction in this subset of patients. However,
little is known about postimplantation changes in their self-reported health status compared to
patients with more severe CHF. The aim of this study was to examine the influence of baseline
NYHA functional class on health status changes in the first 12 months after implantation of
a CRT with defibrillator (CRT-D). Patients with first-time CRT-D (n = 169, 75% men, mean age
62.1 ± 10.7 years) were recruited from 3 Dutch hospitals. All patients completed the SF-36
Health Survey at the time of implantation and at 12 months after implantation. Mildly (NYHA
functional class II; n = 54) and moderately (NYHA functional class III; n = 115) symptomatic
CHF patients showed improved health status in several SF-36 domains at 12 months after CRT-D.
When adjusting for baseline health status, the groups did not differ with respect to their health
status improvement over time, but after adjustment for demographic and clinical factors, the
mildly symptomatic patients reported relatively more improvement in general health (B = 10.15,
SE = 3.31, p = 0.003) and social functioning (B = 10.64, SE = 3.74, p = 0.005). In conclusion,
NYHA functional class II patients reported equal, and in some domains even more, improvement
in health status compared to NYHA functional class III patients at 12 months after CRT-D.
Hence, CRT not only prevents clinical adverse events in patients with mild CHF symptoms but
also improves health status. Copyright © 2011 Elsevier Inc. All rights reserved.
Habibovic M, van den Broek KC, Alings M, Van der Voort PH, Denollet J. Posttraumatic
stress 18 months following cardioverter defibrillator implantation: Shocks, anxiety, and
personality. Health Psychol. 2011 Aug 1. [Epub ahead of print].
OBJECTIVE: Posttraumatic stress disorder (PTSD) has been observed in cardiac patients, but
little is known about PTSD in implantable cardioverter defibrillator (ICD) patients. We examined
the prevalence and predictors (clinical variables, personality, and anxiety) of PTSD in ICD
patients. METHOD: Three hundred ninety-five ICD patients (20.1% female; mean age = 62.8 ±
10.3 years) from two Dutch referral hospitals completed the 14-item Type D scale (DS14) and
the State-Trait Anxiety Inventory to assess Type D (distressed) personality (high negative
affect with social inhibition) and anxiety (on the State Anxiety Inventory) at the time of
implantation. Logistic regression analysis was performed to identify independent predictors of
PTSD at 18 months postimplantation. RESULTS: At 18 months postimplantation, 30 patients
(7.6%) qualified for a PTSD diagnosis. Of these patients, 55% (n = 16) had a Type D personality,
83% (n = 25) experienced anxiety at baseline, and 24% (n = 7) had experienced shocks during
follow-up. Both Type D personality (odds ratio [OR] = 3.5) and baseline anxiety (OR = 4.3) were
significant predictors of posttraumatic stress at 18 months postimplantation, independent of
shocks and other clinical and demographic covariates. Shocks were not significantly associated
with PTSD. CONCLUSION: A significant group of ICD patients is at risk of posttraumatic stress
18 months postimplantation, especially Type D patients and patients with increased levels of
baseline anxiety. Identification of patients with Type D personality and anxiety at the time of
implantation may be warranted to prevent PTSD in ICD patients. (PsycINFO Database Record (c)
2011 APA, all rights reserved).
Bogale N, Priori S, Gitt A, Alings M, Linde C, Dickstein K; Scientific Committee, National
coordinators, and investigators*. The European cardiac resynchronization therapy survey:
patient selection and implantation practice vary according to centre volume. Europace.
2011 Oct;13(10):1445-53. Epub 2011 Jun 28.
AIMS: The European cardiac resynchronization therapy (CRT) survey is a joint initiative
taken by the Heart Failure Association and the European Heart Rhythm Association of the
European Society of Cardiology with the primary objective of describing current European
practice associated with CRT implantations. The results demonstrated that a substantial
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number of implantations took place in patients without conventional guideline indications. We
investigated whether the volume of implants per centre was a determinant of the propensity
to use devices for ‘off-label’ indications. METHODS AND RESULTS: One hundred and forty-one
centres from 13 European countries contributed data from consecutive patients successfully
implanted with a CRT-P or CRT-D device between November 2008 and June 2009. Centres were
categorized into low volume (LVol; = 120 implantations/year) and high volume (HVol; >120
implantations/year) based on median implantable cardioverter-defibrilator implantation the
previous year. No differences were noted with regard to sex, age, or peri-procedural and devicerelated complications. High-volume centres implanted CRT devices in significantly more patients
with mild symptoms and a narrow QRS width. The procedure and fluoroscopy times were
substantially longer at LVol centres and devices were more frequently implanted by surgeons and
interventional cardiologists. Patients stayed longer in hospital in LVol centres with a median of
4 (2-9) vs. 2 (2-6) days. CONCLUSIONS: High-volume centres explore newer indications in their
CRT practice and implant devices more frequently in patients with mild symptoms and narrow
QRS durations. Electrophysiologists dominate implantation practice at HVol centres and duration
of hospitalization is substantially shorter at these centres. *Collaborators (50): Dickstein K,
34
Priori S, Auricchio A, Bogale N, Brugada J, Cleland JG, Derumeaux G, Gitt A, Gras D, Komajda
M, Linde C, Morgan J, van Veldhuisen DJ, Fruhwald F, Strohmer B, Goethals M, Vijgen J, Trochu
JN, Gras D, Kindermann M, Stellbrink C, McDonnald K, Keane D, Ben Gal T, Glikson M, Metra M,
Gasparini M, Maass A, Jordaens L, Alings M, Larsen AI, Færestrand S, Delgado J, Mont L, Persson
H, Gadler F, Brunner-La Rocca HP, Osswald S, Squire I, Morgan J, Brant J, Gadler F, Linde C,
Andresen D, Butter C, Gonska B, Jung W, Kuck KH, Senges J, Stellbrink C.
Rónaszéki A, Alings M, Egstrup K, Gaciong Z, Hranai M, Király C, Sereg M, Figatowski
W, Bondarov P, Johansson S, Frison L, Edvardsson N, Berggren A. Pharmacological
cardioversion of atrial fibrillation–a double-blind, randomized, placebo-controlled,
multicentre, dose-escalation study of AZD1305 given intravenously. Europace. 2011
Aug;13(8):1148-56. Epub 2011 May 11.
AIM: AZD1305 is a combined ion channel blocker developed for the treatment of atrial
fibrillation (AF). The aim of this study was to determine whether AZD1305 was effective
in converting AF to sinus rhythm (SR). METHODS AND RESULTS: Patients with AF episodes
of duration 3 h to 3 months were randomized in a 3:1 ratio to receive a maximum 30 min
intravenous infusion of AZD1305 or matching placebo. The primary efficacy endpoint was the
proportion of patients converting within 90 min of the start of infusion, after which patients
who had not converted were to undergo direct current (DC) cardioversion. Four ascending
AZD1305 dose groups were assigned sequentially, with dose rates of 50, 100, 130, and 180
mg/h. A total of 171 patients were randomized. Pharmacological conversion was achieved in
0 of 43 patients (0%) in the placebo group, and in 2 of 26 (8%; P= 0.14 vs. placebo), 8 of 45
(18%; P= 0.006), 17 of 45 (38%; P< 0.001), and 6 of 12 patients (50%; P< 0.001) in AZD1305
dose groups 1-4, respectively. Maximum QTcF (QT interval corrected according to Fridericia’s
formula) generally increased dose-dependently up to a plateau, although there was wide
variation between patients. Two patients experienced torsade de pointes (TdP): one patient
without symptoms in dose group 3, and one patient requiring DC defibrillation in dose group 4.
Both patients recovered without sequelae. CONCLUSIONS: AZD1305 was effective in converting
AF to SR, but was associated with QT prolongation and TdP. The benefit-risk profile was judged
as unfavourable and the AZD1305 development programme was discontinued. Clinical trial
registration: http://clinicaltrials.gov identifier NCT00915356.
Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S,
Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J,
Yusuf S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and
younger patients with atrial fibrillation: an analysis of the randomized evaluation of
long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011 May 31;123(21):2363-72.
Epub 2011 May 16.
BACKGROUND: Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke
prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding
in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. METHODS AND
RESULTS: The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice
a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median
follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated
with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg
twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32).
There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day
compared with warfarin was associated with a lower risk of major bleeding in patients aged <75
years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged =75 years (4.43% versus
4.37%; P=0.89; P for interaction <0.001), whereas dabigatran 150 mg twice a day compared
with warfarin was associated with a lower risk of major bleeding in those aged <75 years (2.12%
versus 3.04%; P<0.001) and a trend toward higher risk of major bleeding in those aged =75 years
(5.10% versus 4.37%; P=0.07; P for interaction <0.001). The interaction with age was evident
for extracranial bleeding, but not for intracranial bleeding, with the risk of the latter being
consistently reduced with dabigatran compared with warfarin irrespective of age. CONCLUSIONS:
In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with
warfarin have lower risks of both intracranial and extracranial bleeding in patients aged
<75 years. In those aged =75 years, intracranial bleeding risk is lower but extracranial bleeding
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35
risk is similar or higher with both doses of dabigatran compared with warfarin. CLINICAL TRIAL
REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
Comment in: Ann Intern Med. 2011 Sep 20;155(6):JC3-3.
Alings M, Vireca E, Bastian D, Wardeh AJ, Nimeth C, Tukkie R, Trinks S, Kainz W, Delaney
C, Kaltofen G; AUTOMATICITY Study Investigators*. Clinical use of automatic pacemaker
algorithms: results of the AUTOMATICITY registry. Europace. 2011 Jul;13(7):976-83. Epub
2011 Mar 21.
AIMS: Follow-up of the ever-increasing numbers of patients with implantable cardiac devices
places a heavy burden on clinical departments. Device automaticity may alleviate the followup burden by minimizing the time for physician involvement. The aim of the prospective,
multicentre AUTOMATICITY registry was to examine the performance of a subset of programmed
automatic algorithms during patient follow-up and their acceptance by implanting physicians.
METHODS AND RESULTS: The clinical use of automatic algorithms from the Insignia pacemakers
36
(PM; Boston Scientific, St Paul, MN, USA) was evaluated: atrial and ventricular AutoSense
(sensitivity adjustment), ventricular Automatic Capture (threshold verification and output
setting), AutoLifeStyle (sensor settings adjustment). The objective of the study was to
assess the reprogramming rates within 12 months of implant, the reasons for reprogramming
and relationship to adverse events. A total of 960 patients were enrolled in the study. The
proportion of patients free from any algorithm reprogramming at 12 months was 86.1%. A total
of 2736 algorithms were activated at enrolment, with 156 (5.7%) being reprogrammed in 115
patients at 12 months for any reason. Forty-nine reprogrammings (1.8%) were unintentional or
related to changes in device settings such that the algorithm was no longer available, 33 (1.2%)
were due to suspected sensing issues, and 22 (0.8%) were assumed related to the algorithm.
The individual 12-month reprogramming-free rates were: ventricular AutoSense 94.3%, Atrial
AutoSense 93.3%, AutoLifeStyle 93.9%, and Automatic Capture 95.9%. CONCLUSION: The results
of the AUTOMATICITY registry show that automatic measurement of key settings and automatic
adjustment to optimal programming is feasible and safe. The simplicity of PM follow-up and
avoidance of frequent reprogramming may contribute to a more effective use of hospital time
and resources. *Collaborators (63): Alings M, Bloch-Thomsen PE, Cihalik C, Lawo T, Agraou B,
Deutsch P, Bazin P, Guyomar Y, Bobillier M, Defaye P, Amiel A, Lazarus A, Guenoun M, Le Franc
P, Oei FL, Nicastia D, Hoenen S, de Porto AE, Vontobel H, Robles de Medina R, Kainz W, Brunner
P, Alzueta J, Santos JA, Navarro AB, Hie C, Kautzner J, Ammann-Kardiol P, Kaltofen G, Tukkie
R, Zeindlhofer E, Nimeth C, Frömmel M, Brachmann J, Göhl K, Trinks S, van der Meer P, Zenker
G, Gebetsberger F, Unger T, Ruiter JH, Ramanna H, Hadj KB, Lang A, Predel D, Schnabel A,
Martinek M, Cheng CW, Ward K, Jensen G, O’Nunain S, Jiang S, Terpstra WF, Budschedl E, van
Doorn DJ, Marenne F, Wahlers T, Zeus T, Osswald S, Engby B, Christensen PD, Junbo G, van der
Veen M.
Pedersen SS, den Broek KC, Theuns DA, Erdman RA, Alings M, Meijer A, Jordaens L,
Denollet J. Risk of chronic anxiety in implantable defibrillator patients: a multi-center
study. Int J Cardiol. 2011 Mar 17;147(3):420-3. Epub 2009 Nov 6.
BACKGROUND: Little is known about the prevalence of chronic anxiety in patients with an
implantable cardioverter defibrillator (ICD). In a multi-center, prospective study, we examined
1) the prevalence of chronic anxiety (i.e., patients anxious at implantation and 12 months),
and 2) predictors of chronic anxiety. METHODS: ICD patients (N=284; 21.1% women) anxious
(cut-off = 40 on the State Trait Anxiety Inventory (STAI)) at the time of implantation qualified
for inclusion in the current study. Patients completed the Type D Scale at baseline and the
STAI (state measure) at baseline and 12 months. RESULTS: Of 284 patients anxious at baseline,
53.9% (153/284) remained anxious at 12-month follow-up. Diabetes (OR:2.49; 95%CI:1.16-5.36),
cardiac resynchronization therapy (CRT) (OR:2.03; 95%CI:1.02-4.05), and Type D personality
(OR:1.87; 95%CI:1.09-3.19) were independent predictors of 12-month anxiety, adjusting for
demographic and clinical variables including ICD therapy during follow-up. Shocks (both
appropriate and inappropriate during follow-up) were not associated with chronic anxiety at
12 months (OR:0.94; 95%CI:0.42-2.12). The prevalence of chronic anxiety in the 96 patients
with no risk factors was 34.4% and 63.8% in the 120 patients with either diabetes, CRT, or Type
D personality. CONCLUSIONS: More than 50% of ICD patients anxious at the time of implantation
were still anxious at 12 months, indicating a high level of chronicity. Diabetes, CRT, and
Type D personality were independent predictors of chronic anxiety. ICD patients anxious at
implantation should be closely monitored and offered adjunctive psychosocial intervention if
symptoms do not remit spontaneously in order to prevent adverse health outcomes.
Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
Vokó Z, de Brouwer S, Lubsen J, Danchin N, Otterstad JE, Dunselman PH, Kirwan BA.
Long-term impact of secondary preventive treatments in patients with stable angina.
Eur J Epidemiol. 2011 May;26(5):375-83. Epub 2011 Feb 19.
We assessed the independent effects of beta blockers, calcium antagonists, lipid-lowering drugs,
angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), antiplatelet drugs, vitamin K antagonists, percutaneous coronary intervention (PCI) and coronary
artery by-pass grafting (CABG) on mortality and on the composite endpoint of death, myocardial
infarction, stroke or heart failure in patients with stable angina pectoris. We estimated the
Cardiologie
37
effects of the interventions used at baseline by multivariate Cox regression and during follow-up
by G-estimation in 7,665 patients followed for a mean of 5 years in the ACTION trial. Adjusted
hazard ratios (95% confidence intervals) comparing all cause mortality among users during
follow-up to non-users were 1.01 (0.91, 1.09) for beta blockade, 0.82 (0.75, 0.89) for ACEIs or
ARBs, 0.93 (0.87, 0.98) for calcium antagonists, 0.54 (0.49, 0.62) for lipid-lowering drugs, 0.49
(0.42, 0.53) for anti-platelet drugs, 0.74 (0.69, 0.78) for PCI, and 0.91 (0.82, 0.98) for CABG.
Effects on the composite endpoint were less marked. This observational study confirms that
ACEIs or ARBs, lipid-lowering and anti-platelet drugs as used in the everyday management of
stable angina have independent secondary preventive effects. Calcium antagonists, PCI and
CABG also appear to improve outcome.
Cohen DJ, Van Hout B, Serruys PW, Mohr FW, Macaya C, den Heijer P, Vrakking MM, Wang
K, Mahoney EM, Audi S, Leadley K, Dawkins KD, Kappetein AP. Synergy between PCI with
Taxus and Cardiac Surgery Investigators. Quality of life after PCI with drug-eluting stents
or coronary-artery bypass surgery. N Engl J Med. 2011 Mar 17;364(11):1016-26.
38
BACKGROUND: Previous studies have shown that among patients undergoing multivessel
revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous
coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal
stents, results in greater relief from angina and improved quality of life. The effect of PCI with
the use of drug-eluting stents on these outcomes is unknown. METHODS: In a large, randomized
trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to
undergo either CABG (897 patients) or PCI with paclitaxel-eluting stents (903 patients). Healthrelated quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the
Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health
Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the
SAQ (on which scores range from 0 to 100, with higher scores indicating better health status).
RESULTS: The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and
12 months than at baseline in both groups. The score on the angina-frequency subscale of the
SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P=0.04
and P=0.03, respectively), but the between-group differences were small (mean treatment effect
of 1.7 points at both time points). The proportion of patients who were free from angina was
similar in the two groups at 1 month and 6 months and was higher in the CABG group than in
the PCI group at 12 months (76.3% vs. 71.6%, P=0.05). Scores on all the other SAQ and SF-36
subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two
groups throughout the follow-up period. CONCLUSIONS: Among patients with three-vessel or left
main coronary artery disease, there was greater relief from angina after CABG than after PCI at
6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific;
ClinicalTrials.gov number, NCT00114972.).
Comment in: Internist (Berl). 2012 Jan;53(1):108-10; Ann Intern Med. 2011 Jul 19;155(2):JC1-10.
Damman P, Beijk MA, Kuijt WJ, Verouden NJ, van Geloven N, Henriques JP, Baan J, Vis
MM, Meuwissen M, van Straalen JP, Fischer J, Koch KT, Piek JJ, Tijssen JG, de Winter
RJ. Multiple biomarkers at admission significantly improve the prediction of mortality in
patients undergoing primary percutaneous coronary intervention for acute ST-segment
elevation myocardial infarction. J Am Coll Cardiol. 2011 Jan 4;57(1):29-36.
OBJECTIVES: We investigated whether multiple biomarkers improve prognostication in STsegment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous
coronary intervention. BACKGROUND: Few data exist on the prognostic value of combined
biomarkers. METHODS: We used data from 1,034 STEMI patients undergoing primary
percutaneous coronary intervention in a high-volume percutaneous coronary intervention
center in the Netherlands and investigated whether combining N-terminal pro-brain natriuretic
peptide, glucose, C-reactive protein, estimated glomerular filtration rate, and cardiac troponin
T improved the prediction of mortality. A risk score was developed based on the strongest
predicting biomarkers in multivariate Cox regression. The additional prognostic value of the
strongest predicting biomarkers to the established prognostic factors (age, body weight,
diabetes, hypertension, systolic blood pressure, heart rate, anterior myocardial infarction,
and time to treatment) was assessed in multivariable Cox regression. RESULTS: During followup (median, 901 days), 120 of the 1,034 patients died. In Cox regression, glucose, estimated
glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were the strongest
predictors for mortality (p < 0.05, for all). A risk score incorporating these biomarkers
identified a high-risk STEMI subgroup with a significantly higher mortality when compared
with an intermediate- or low-risk subgroup (p < 0.001). Addition of the 3 biomarkers to
established prognostic factors significantly improved prediction for mortality, as shown by the
net reclassification improvement (0.481, p < 0.001) [corrected] and integrated discrimination
improvement (0.0226, p = 0.03) [corrected]. CONCLUSIONS: Our data suggest that addition of a
multimarker to a model including established risk factors improves the prediction of mortality in
STEMI patients undergoing primary percutaneous coronary intervention. Furthermore, the use of
a simple risk score based on these biomarkers identifies a high-risk subgroup. Copyright © 2011
American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Erratum in: J Am Coll Cardiol. 2011 Apr 19;57(16):1717-9.
Comment in: J Am Coll Cardiol. 2011 Jan 4;57(1):37-9.
Cardiologie
39
Engström AE, Sjauw KD, Baan J, Remmelink M, Claessen BE, Kikkert WJ, Hoebers LP,
Vis MM, Koch KT, Meuwissen MM, Tijssen JG, De Winter RJ, Piek JJ, Henriques JP. Longterm safety and sustained left ventricular recovery: long-term results of percutaneous
left ventricular support with Impella LP2.5 in ST-elevation myocardial infarction.
EuroIntervention. 2011 Feb;6(7):860-5.
AIMS: Mechanical left ventricular (LV) unloading may reduce infarct size when combined with
primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial
infarction (STEMI). The Impella LP2.5 is a novel percutaneous left ventricular assist device.
Although the short-term safety and feasibility of this device have been demonstrated, the
long-term effects are unknown. The purpose of the current study was to evaluate the long-term
effects of the Impella LP2.5 support on the aortic valve and left ventricular ejection fraction
(LVEF). METHODS AND RESULTS: In 2006, 10 patients with anterior STEMI received 3-day support
with the Impella LP2.5 after PCI. The control group consisted of 10 comparable patients, treated
according to routine care. For the current study, echocardiography was performed and adverse
events were recorded. Mean duration of follow-up was 2.9±0.6 years in the Impella group and
40
3.0±0.3 years in the control group. No differences in aortic valve abnormalities and LVEF were
demonstrated between the groups; nevertheless, LVEF increase from baseline was significantly
greater in Impella-treated patients (23.6±8.9% versus 6.7±7.0%, P=0.008). CONCLUSIONS: Threeday support with the Impella LP2.5 is not associated with adverse effects on the aortic valve
at long-term follow-up. LVEF was similar in both groups; however, recovery was significantly
greater in the Impella group.
Erratum in: EuroIntervention. 2011 Jun;7(2):289. [multiple author names corrected]
Delewi R, Remmelink M, Meuwissen M, van Royen N, Vis MM, Koch KT, Henriques JP,
de Winter RJ, Tijssen JG, Baan J Jr, Piek JJ. Acute haemodynamic effects of accelerated
idioventricular rhythm in primary percutaneous coronary intervention. EuroIntervention.
2011 Aug;7(4):467-71.
AIMS: Accelerated idioventricular rhythm (AIVR) is very frequently observed in primary
percutaneous coronary intervention (PCI), however knowledge of the haemodynamic effects
is lacking. METHODS AND RESULTS: We studied an ST-segment elevation myocardial infarction
cohort of 128 consecutive patients (aged 62±11 years) in whom AIVR occurred following
reperfusion during primary PCI. Mean systolic blood pressure (SBP), diastolic blood pressure
(DBP) and heart rate were determined during periods of AIVR and sinus rhythm. We grouped
patients according to the infarct-related artery and the site of the coronary occlusion. AIVR
caused an immediate reduction in SBP (130±27 vs. 98±22 mmHg, p<0.001) and DBP (80±19
vs. 69±16 mmHg, p<0.001) and a small increase in heart rate (78±12 vs. 83±11 bpm, p<0.001)
as compared to sinus rhythm, irrespective of infarct-related artery. Both absolute as well as
relative reduction in SBP were more pronounced in distal than proximal left coronary artery
(LCA) occlusions (36±16 vs. 27±12 mmHg, p<0.01, respectively 25±9 vs. 20±8%, p<0.05). These
haemodynamic differences between proximal and distal occlusion sites were not observed in
the right coronary artery. CONCLUSIONS: AIVR following reperfusion is associated with marked
reduction in both SBP and DBP, irrespective of infarct-related artery. These haemodynamic
effects are accompanied by only a very modest increase in heart rate during AIVR. Patients with
a culprit lesion in the proximal LCA showed a smaller reduction in systolic blood pressure than
distal LCA lesions.
Comment in: EuroIntervention. 2011 Aug;7(4):415, 417, 419.
Verouden NJ, Kramer MC, Li X, Meuwissen M, Koch KT, Henriques JP, Baan J, Vis MM,
Piek JJ, van der Wal AC, Tijssen JG, de Winter RJ. Histopathology of aspirated thrombus
and its association with ST-segment recovery in patients undergoing primary percutaneous
coronary intervention with routine thrombus aspiration. Catheter Cardiovasc Interv.
2011 Jan 1;77(1):35-42.
BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing
primary percutaneous coronary intervention (PCI) with thrombus aspiration, the histopathology
of aspirated thrombus was previously related to long-term mortality. In this study, we sought
to investigate the association between histopathology of aspirated thrombus and ST-segment
recovery, a marker of microvascular dysfunction, immediately at the end of the PCI procedure.
METHODS: We included 892 STEMI patients who underwent primary PCI with routine thrombus
aspiration and for whom combined data on histopathology of aspirated thrombus and STsegment recovery were available. Patients were categorized according to histopathology of
aspirated thrombus: fresh only (<1 day), older (>1 day), or no material aspirated. ST-segment
recovery was defined as incomplete if <50%. RESULTS: Incomplete ST-segment recovery
occurred in 134 of 363 patients (37%) with fresh thrombus, in 104 of 238 patients (44%)
with older thrombus, and in 142 of 291 patients (49%) with no material. Unadjusted odds
ratios for incomplete ST-segment recovery of patients with older thrombus and no material,
when compared with patients with fresh thrombus, were 1.33 (95% CI, 0.95-1.85; P = 0.097)
and 1.63 (95% CI 1.19-2.23; P = 0.002), respectively. Both associations were unchanged after
multivariable adjustment for clinical predictors of ST-segment recovery. ST-segment recovery
was a strong predictor of long-term mortality, independent of the histopathology of aspirated
thrombus. CONCLUSIONS: This study shows that ST-segment recovery immediately at the end
of the PCI procedure was a significant prognosticator, independent of the histopathology of
aspirated thrombus. We found that the histopathology of aspirated thrombus (fresh, older, no
Cardiologie
41
material) was associated with ST-segment recovery in STEMI patients undergoing primary PCI
with thrombus aspiration. Copyright © 2010 Wiley-Liss, Inc.
Comment in: Catheter Cardiovasc Interv. 2011 Jan 1;77(1):43-4.
42
Blomström P, Borggrefe M, Budaj A, Chen SA, Ching CK, Commerford P, Dans A, Davy
JM, Delacrétaz E, Di Pasquale G, Diaz R, Dorian P, Flaker G, Golitsyn S, GonzalezHermosillo A, Granger CB, Heidbüchel H, Kautzner J, Kim JS, Lanas F, Lewis BS, Merino
JL, Morillo C, Murin J, Narasimhan C, Paolasso E, Parkhomenko A, Peters NS, Sim KH,
Stiles MK, Tanomsup S, Toivonen L, Tomcsányi J, Torp-Pedersen C, Tse HF, Vardas P,
Vinereanu D, Xavier D, Zhu J, Zhu JR, Baret-Cormel L, Weinling E, Staiger C, Yusuf S,
Chrolavicius S, Afzal R, Hohnloser SH; PALLAS Investigators*. Dronedarone in high-risk
permanent atrial fibrillation. N Engl J Med. 2011 Dec 15;365(24):2268-76. Epub 2011
Nov 14.
Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G, Reilly
PA, Yang S, Yusuf S, Wallentin L, Connolly SJ; RE-LY Investigators. Risks for stroke,
bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin
in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern
Med. 2011 Nov 15;155(10):660-7, W204.
Groenveld HF, Crijns HJ, Van den Berg MP, Van Sonderen E, Alings AM, Tijssen JG,
Hillege HL, Tuininga YS, Van Veldhuisen DJ, Ranchor AV, Van Gelder IC; RACE II
Investigators. The effect of rate control on quality of life in patients with permanent
atrial fibrillation: data from the RACE II (Rate Control Efficacy in Permanent Atrial
Fibrillation II) study. J Am Coll Cardiol. 2011 Oct 18;58(17):1795-803.
Berg MP, Van Veldhuisen DJ, Van Gelder IC; RACE II Investigators. Effect of lenient
versus strict rate control on cardiac remodeling in patients with atrial fibrillation data
of the RACE II (RAte Control Efficacy in permanent atrial fibrillation II) study. J Am
Coll Cardiol. 2011 Aug 23;58(9):942-9.
cardioverter defibrillator. Int J Cardiol. 2011 Sep 29. [Epub ahead of print].
Aug 6.
coordinators, and investigators*. The European cardiac resynchronization therapy
survey: patient selection and implantation practice vary according to centre volume.
Europace. 2011 Oct;13(10):1445-53. Epub 2011 Jun 28.
cardioversion of atrial fibrillation--a double-blind, randomized, placebo-controlled,
Aug;13(8):1148-56. Epub 2011 May 11.
Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings
M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf
S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and
long-term anticoagulant therapy (RE-LY) trial. Circulation.
2011 May 31;123(21):2363-72. Epub 2011 May 16.
algorithms: results of the AUTOMATICITY registry. Europace. 2011 Jul;13(7):976-83.
Epub 2011 Mar 21.
K, Mahoney EM, Audi S, Leadley K, Dawkins KD, Kappetein AP. Synergy between PCI
with Taxus and Cardiac Surgery Investigators. Quality of life after PCI with drug-eluting
stents or coronary-artery bypass surgery. N Engl J Med. 2011 Mar 17;364(11):1016-26.
Damman P, Beijk MA, Kuijt WJ, Verouden NJ, van Geloven N, Henriques JP, Baan J, Vis MM,
Meuwissen M, van Straalen JP, Fischer J, Koch KT, Piek JJ, Tijssen JG, de Winter RJ.
Multiple biomarkers at admission significantly improve the prediction of mortality in
Cardiologie
43
44
Engström AE, Sjauw KD, Baan J, Remmelink M, Claessen BE, Kikkert WJ, Hoebers LP,
Vis MM, Koch KT, Meuwissen MM, Tijssen JG, De Winter RJ, Piek JJ, Henriques
JP. Long-term safety and sustained left ventricular recovery: long-term results of
percutaneous left ventricular support with Impella LP2.5 in ST-elevation myocardial
infarction. EuroIntervention. 2011 Feb;6(7):860-5.
Delewi R, Remmelink M, Meuwissen M, van Royen N, Vis MM, Koch KT, Henriques
JP, de Winter RJ, Tijssen JG, Baan J Jr, Piek JJ. Acute haemodynamic effects of
accelerated idioventricular rhythm in primary percutaneous coronary intervention.
EuroIntervention. 2011 Aug;7(4):467-71.
Verouden NJ, Kramer MC, Li X, Meuwissen M, Koch KT, Henriques JP, Baan J, Vis MM, Piek
JJ, van der Wal AC, Tijssen JG, de Winter RJ. Histopathology of aspirated thrombus and
its association with ST-segment recovery in patients undergoing primary percutaneous
2011 Jan 1;77(1):35-42.
Meuleman VG, Schinkel AF, Vos J. Electrocardiographic abnormalities caused by acute
pancreatitis. Neth Heart J. 2011 Mar;19(3):137-9.
Cardiothoracale chirurgie
De ultieme samenwerkers van het ziekenhuis
Nieuwe operatietechnieken in de cardiothoracale chirurgie verlagen de mortaliteit,
maar het valideren van de nieuwe methodes door onderzoek blijkt lastig. Een goede
database en casecontrolstudies bieden uitkomst, legt dr. Bart P. van Putte uit.
dr. B.P. (Bart Pieter) van Putte
“We werken zeer nauw samen met de interventiecardiologen”, opent Van Putte. “We
hebben dagelijks overleg als hartteam, waarin we alle lopende patiënten bespreken.” Met
ruim 1.550 hartoperaties per jaar heeft het Amphia Ziekenhuis kwantitatief een gedeelde
tweede plaats in Nederland. De cardiothoracaal chirurg licht toe: “We zijn groter dan de
academische ziekenhuizen, in aantal maar vooral ook in operatiespectrum en casemix.”
Hij hoeft niet lang na te denken over wat de vakgroep kenmerkt: “Ten eerste dat de
45
ontwikkelingen in ons vak enorm hard gaan en ten tweede dat ons vak zo complex is.
Qua techniek, maar vooral omdat we in een ketenzorgspecialisme zitten. We werken
nauw samen met de cardiologen, anesthesiologen, intensive care en longartsen. Wij zijn
de ultieme samenwerkers van dit ziekenhuis. Er zijn dus veel variabelen. Daarbij wil ik
benadrukken dat we hier in Breda heel goed zijn in minimaal invasieve ingrepen.”
Nieuwe operatietechnieken
Van Putte licht toe dat zijn afdeling veel nieuwe operatietechnieken heeft binnengehaald
die alle gekenmerkt worden door ‘minimal access’ (kleine incisie). Hij noemt de mini-AVR
(aortaklepvervanging via een incisie van 5 cm), de mini-MPL (mitralisklepplastiek via een
incisie van 5 cm) en de mini-maze (chirurgische behandeling van boezemfibrilleren via
een kijkoperatie). Andere belangrijke ontwikkelingen zijn er op het gebied van percutane
aortaklepimplantaties (via de liesslagader, de schouderslagader of de punt van het hart
onder röntgendoorlichting). En dan vinden er sinds enige tijd de VATS-gerelateerde
ingrepen (Video Assisted ThoracScopie) plaats voor het plaatsen van pacemakerdraden,
voor het maken van pericardluikjes en voor de longchirurgie.
46
Vergelijkend onderzoek
Van al deze nieuwe/doorontwikkelde operatietechnieken wordt gedacht dat ze de
mortaliteit verlagen. De incisies zijn kleiner en dus minder belastend voor de patiënt.
Bovendien maken ze operaties mogelijk bij patiënten die anders mogelijk inoperabel
zouden zijn. Toch moeten de methodes gevalideerd worden via onderzoek. De nieuwe
technieken moeten aantoonbaar minimaal net zo goed werken als de gouden standaard.
“Maar juist dat onderzoeken is heel lastig”, geeft Van Putte aan. “Want vind maar eens
patiënten en verwijzers die – ter vergelijking – voor de oude, meer invasieve methode
willen gaan, terwijl de nieuwe methode duidelijk minder belastend is. Daarom doen
we vooral casecontrolstudies. Dat betekent dat we bij te opereren patiënten in onze
database een patiënt terugzoeken die qua leeftijd en omstandigheden vergelijkbaar
is en nog via de oude methode is geopereerd. Die twee casussen zetten we tegenover
elkaar. Dat is tijdrovend, maar heel zinvol onderzoek.” Volgens de cardiothoracaal chirurg
is de opgebouwde database met operatieve gegevens uniek door de grote hoeveelheid
variabelen, de compleetheid en het zeer lange tijdsinterval waarop het betrekking heeft.
Afgelopen jaar zijn de resultaten van redontherapie bij mediastinitis (geïnfecteerd
borstbeen na hartchirurgie) vergeleken met een ander Nederlands hartcentrum. Dit artikel
is ingediend voor publicatie.
Nog geen publicaties
De lopende onderzoeken zijn nog volop in gang en er zijn nog geen publicaties. “In die
fase zitten we nog niet, maar dat gaat natuurlijk het komende jaar wel komen. Voor de
mini-AVR en -MPL zijn we nu bezig om controlepatiënten op te zoeken. De mini-maze is
een ander verhaal, want dat is een behandeling voor een ritmestoornis waar eerder een
grote hartoperatie voor gedaan moest worden.” De methode bestaat pas kort, Van Putte
beschreef deze voor het eerst in 2008 met enkele collega’s in Nieuwegein, waar hij tot
eind 2010 werkte. “Bijna negentig procent van de patiënten is na de ingreep vrij van
boezemfibrilleren. Deze ingreep willen we als chirurgen bovendien nog gaan combineren
met de katheterisatietechniek van de cardiologen. Meer samenwerking dus.”
Toekomstambitie
Dit jaar start hopelijk ook een nieuwe behandeling voor longmetastasen in het
Amphia Ziekenhuis: de geïsoleerde longperfusie, het onderwerp waar Van Putte in
2004 op promoveerde. Een methode die veel betere resultaten lijkt op te leveren dan
chemotherapie of een operatie alleen. “Daar zijn we nu mee bezig. We zijn inmiddels
een trainingscentrum geworden voor nieuwe devices voor minimaal invasieve ingrepen.
Voor nieuwe producten zoals kleppen en andere devices zet de industrie ons graag in als
testcentrum vanwege onze expertise en onze operatievolumina.”
Nieuw is ook de aortapoli die Van Putte per 1 februari heeft opgestart voor thoracale
aortopathologie. Als copromotor van een Italiaanse collega (Malvindi) met een proefschrift ‘Reoperaties aan de aorta ascendens’ onderschrijft hij het belang van een levenslange opvolging bij patiënten met aortapathologie. Als laatste inspanning noemt de
cardiothoracaal chirurg de inzet om een opleidingsziekenhuis te worden. “De B-opleiding
gaat er komen, in samenwerking met het AMC. De vraag is alleen of dat dit jaar nog gaat
lukken.”
Kerngegevens zorgkern Cardiothoracale chirurgie
• 6 cardiothoracaal chirurgen: M. (Mohamed) Bentala, mw. C.A. (Connie) Boot,
P.A.E. (Peter) Hiddema, dr. B.P. (Bart Pieter) van Putte, M.M. (Ries) Vrakking,
J. (Jan) Witkop.
Lopende onderzoeken:
• Primary closure using Redon drains as a treatment of post-sternotomy mediastinitis.
Dit onderzoek evalueert de effectiviteit van primaire sluiting van het borstbeen over
hoogvacuümredondrains in geval van mediastinitis.
• Evaluation of left ventricular pacemaker lead implantation by VATS. Dit onderzoek
beschrijven en vergelijken we de implantatietechniek via VATS met de open
chirurgische procedure en met de transveneuze-kathetertechniek.
47
• Mini-mitral surgery compared with open surgery: a case control study. In dit onderzoek
vergelijken we de resultaten van minimaal invasieve mitralisklepchirurgie met de ‘oude’
sternotomiebenadering.
• Evaluation of aortic valve replacement by minimal access. In deze studie vergelijken we
de resultaten van de mini-AVR met die van de klassieke sternotomie.
Van Putte BP, Ozturk S, Siddiqi S, Schepens MA, Heijmen RH, Morshuis WJ. Early and late
outcome after aortic root replacement with a mechanical valve prosthesis in a series of
528 patients. Ann Thorac Surg. 2012 Feb;93(2):503-9. Epub 2011 Dec 24.
BACKGROUND: Aortic root replacement with a mechanical valve prosthesis is a widely accepted
surgical technique. This study aims to evaluate short-term and long-term outcomes of this
approach and to identify predictors of 30-day mortality. METHODS: We retrospectively analyzed
a consecutive series of 528 patients (mean age, 54 ± 13 years) who underwent aortic root
replacement for aneurysm (83%), acute type A dissection (15%), or endocarditis (2%) in the
48
period between 1974 and 2008. The mean time of follow-up was 9.0 ± 7.0 years (range, 0 to
36years). Concomitant aortic surgery was performed in 71%, coronary revascularization in 18%,
and mitral valve surgery in 3%. Selective antegrade cerebral perfusion was applied in 25% and
deep hypothermic circulatory arrest in 28% of patients. RESULTS: Overall 30-day mortality was
3.2% to 2.5% for elective surgery and 6.5% for urgent surgery. Morbidity included resternotomy
for bleeding or tamponade (19%), pacemaker implantation (3.6%), myocardial infarction (4.0%),
and neurologic damage (4.2%). Multivariate analysis revealed myocardial infarction (p < 0.001)
and the lack of glue use (p = 0.018) as independent predictors of 30-day mortality. Subanalysis
of the selective antegrade cerebral perfusion patients and the deep hypothermic circulatory
arrest patients revealed infarction (p = 0.005) and coronary artery disease (p = 0.45) for selective
antegrade cerebral perfusion and wrapping (p = 0.035) for deep hypothermic circulatory arrest
as independent risk factors. The survival rate was 87%, 73%, and 29% after 5, 10, and 25 years,
respectively. CONCLUSIONS: Aortic root replacement with a mechanical valve prosthesis can
be performed safely with low mortality and acceptable morbidity. Perioperative myocardial
infarction is the strongest independent risk factor of 30-day mortality. Copyright © 2012
The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Yilmaz A, van Putte BP, Van Boven WJ. Closed chest lobectomy with subxyphoid
retraction. Interact Cardiovasc Thorac Surg. 2011 Dec;13(6):549-51. Epub 2011 Sep 16.
An important disadvantage of the video-assisted thoracoscopic surgery (VATS) lobectomy
technique remains the minithoracotomy for specimen removal resulting in some degree of
traction on the ribs even without the usage of a rib retractor. We describe a new technique
of VATS lobectomy in supine position consisting of complete lymph node dissection and
subxyphoidal removal of the lobe(s) preventing any degree of rib traction.
Comment in: Interact Cardiovasc Thorac Surg. 2011 Dec;13(6):551.
Malvindi PG, van Putte BP, Leone A, Heijmen RH, Schepens MA, Morshuis WJ. Aortic
reoperation after freestanding homograft and pulmonary autograft root replacement.
Ann Thorac Surg. 2011 Apr;91(4):1135-40. Epub 2011 Feb 25.
BACKGROUND: Human allografts and pulmonary autografts offer many advantages as an
aortic valve and root substitute. The progressive degeneration of the aortic allograft and
the pulmonary autograft has been seen as an important disadvantage, and the need for a
reoperation has been perceived as challenging and risky for the patients. METHODS: Between
March 1992 and October 2009, 53 consecutive patients (mean age 50 ± 13 years; 38 male),
who had a previous aortic root replacement, underwent redo surgery for failure of the aortic
homograft (n = 42) or the pulmonary autograft (n = 11). The median follow-up (available
for 47 of 51 patients) was 44 months. RESULTS: Structural valve deterioration was the main
indication for reoperation on the homograft (86%), with an earlier presentation in patients who
received homografts from donors more than 55 years old. Failure of the pulmonary autograft
occurred primarily because of severe aortic regurgitation predominantly due to dilation of the
autograft (n = 5) and autograft valve prolapse (n = 5). The total in-hospital mortality was 3.8%
(n = 2). No deaths occurred among patients who previously underwent a Ross procedure. The
course was complicated in 25 cases (48%). The cumulative 1-year, 5-year, and 8-year survival
rates were 92%, 90%, and 77%, respectively. No late deaths were encountered after reoperation
on the pulmonary autograft (maximum follow-up 218 months). Freedom from reoperation
(excluding early in-hospital operation) for recurrent aortic valve or root pathology was 97%
at 8 years. CONCLUSIONS: Reoperation after freestanding homograft and pulmonary autograft
root replacement can be accomplished safely. The total postoperative morbidity rate is still
high. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights
reserved.
K, Mahoney EM, Audi S, Leadley K, Dawkins KD, Kappetein AP. Synergy between PCI with
Taxus and Cardiac Surgery Investigators. Quality of life after PCI with drug-eluting stents
or coronary-artery bypass surgery. N Engl J Med. 2011 Mar 17;364(11):1016-26.
49
BACKGROUND: Previous studies have shown that among patients undergoing multivessel
revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous
coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal
stents, results in greater relief from angina and improved quality of life. The effect of PCI with
the use of drug-eluting stents on these outcomes is unknown. METHODS: In a large, randomized
trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to
undergo either CABG (897 patients) or PCI with paclitaxel-eluting stents (903 patients). Healthrelated quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the
Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health
Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the
SAQ (on which scores range from 0 to 100, with higher scores indicating better health status).
RESULTS: The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and
12 months than at baseline in both groups. The score on the angina-frequency subscale of the
SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P=0.04
and P=0.03, respectively), but the between-group differences were small (mean treatment effect
of 1.7 points at both time points). The proportion of patients who were free from angina was
50
similar in the two groups at 1 month and 6 months and was higher in the CABG group than in
the PCI group at 12 months (76.3% vs. 71.6%, P=0.05). Scores on all the other SAQ and SF-36
subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two
groups throughout the follow-up period. CONCLUSIONS: Among patients with three-vessel or left
main coronary artery disease, there was greater relief from angina after CABG than after PCI at
6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific;
ClinicalTrials.gov number, NCT00114972.).
Comment in: Internist (Berl). 2012 Jan;53(1):108-10; Ann Intern Med. 2011 Jul 19;155(2):JC1- 10.
Chirurgie
Kerngegevens zorgkern Chirurgie
• 15 chirurgen: R.M.P.H. (Rogier) Crolla, H.G.W. (Hans) de Groot, dr. G.H. (Gwan)
Ho, dr. L. (Lyckle) van der Laan, dr. E.J.T. (Ernest) Luiten, dr. J.K.S. (Hans)
Nuytinck, dr. E.J.H. (Eric) van Rhede van der Kloot, dr. A.M. (Arjen) Rijken,
P.J.H.J. (Piet) Romme, G.P. (George) van der Schelling, dr. E.J. (Eelco) Veen,
mw. D.I. (Dagmar) Vos, dr. J.P.A.M. (Jos) Vroemen, J.C.H. (Jan) van der Waal,
dr. J.H. (Jan) Wijsman.
• subspecialismen: maag-, darm-, oncologische chirurgie, traumatologie, vaatchirurgie,
longchirurgie, algemene chirurgie
Te Slaa A, Dolmans DE, Ho GH, Mulder PG, van der Waal JC, de Groot HG, van der Laan
L. Prospective randomized controlled trial to analyze the effects of intermittent pneumatic
compression on edema following autologous femoropopliteal bypass surgery. World J Surg.
2011 Feb;35(2):446-54.
BACKGROUND: Patients who undergo autologous femoropopliteal bypass surgery develop
postoperative edema in the revascularized leg. The effects of intermittent pneumatic
compression (IPC) to treat and to prevent postreconstructive edema were examined in this
study. METHODS: In a prospective randomized trial, patients were assigned to one of two groups.
All patients suffered from peripheral arterial disease, and all were subjected to autologous
femoropopliteal bypass reconstruction. Patients in group 1 used a compression stocking (CS)
above the knee exerting 18 mmHg (class I) on the leg postoperatively for 1 week (day and
night). Patients in group 2 used IPC on the foot postoperatively at night for 1 week. The lower
Chirurgie
51
leg circumference was measured preoperatively and at five postoperative time points.
A multivariate analysis was done using a mixed model analysis of variance. RESULTS: A total of
57 patients were analyzed (CS 28; IPC 29). Indications for operation were severe claudication
(CS 13; IPC 13), rest pain (10/5), or tissue loss (7/11). Revascularization was performed
with either a supragenicular (CS 13; IPC10) or an infragenicular (CS 15; IPC 19) autologous
bypass. Leg circumference increased on day 1 (CS/IPC): 0.4%/2.7%, day 4 (2.1%/6.1%), day
7 (2.5%/7.9%), day 14 (4.7%/7.3%), and day 90 (1.0%/3.3%) from baseline (preoperative
situation). On days 1, 4, and 7 there was a significant difference in leg circumference between
the two treatment groups. CONCLUSIONS: Edema following femoropopliteal bypass surgery occurs
in all patients. For the prevention and treatment of that edema the use of a class I CS proved
superior to treatment with IPC. The use of CS remains the recommended practice following
femoropopliteal bypass surgery.
PMCID: PMC3017305
52
Van Schaik DE, Dolmans DE, Ho G, Geenen GP, Vos L, van der Waal JC, de Groot HG, van
der Laan L. Ruptured abdominal aortic aneurysm: endovascular or open approach in a
Dutch general hospital. J Cardiovasc Surg (Torino). 2011 Jun;52(3):363-9.
AIM: We compared the outcomes of 56 patients with a ruptured abdominal aortic aneurysm
(RAAA) who underwent either open repair or emergency endovascular aneurysm repair (eEVAR)
in a general hospital. It seems feasible that the availability of eEVAR for treatment of RAAA
could lead to a decrease in hospital mortality. METHODS: We analyzed all admitted patients with
a RAAA, between January 2006 and April 2008, eEVAR is compared to open repair. We studied
30 days mortality, intensive care unit stay, hospital stay, total blood loss and complications.
RESULTS: Fifteen eEVAR procedures (26.8%) were performed. Mortality in the eEVAR-group
was 26%, in the open repair-group 46%. Mean intensive care unit stay was 3.9 days and 4.8
days in the eEVAR-group and open repair-group, respectively. Mean hospital stay was 13 days
and 10.5 days. The average blood loss was 210cc and 2760cc. The amount of blood products
for transfusion was significantly higher in the open repair. Overall complication rate was not
significantly different in both treatment groups. CONCLUSION: Treatment in a Dutch general
hospital of a RAAA with an eEVAR procedure has a lower mortality in comparison to the open
repair. Therefore, whenever possible the eEVAR is the preferred treatment method.
Donker JM, Ho GH, Te Slaa A, de Groot HG, van der Waal JC, Veen EJ, van der Laan
L. Midterm results of autologous saphenous vein and ePTFE pre-cuffed bypass surgery in
peripheral arterial occlusive disease. Vasc Endovascular Surg. 2011 Oct;45(7):598-603. Epub
2011 Jul 14.
INTRODUCTION: The graft of choice in lower limb bypass surgery is the autologous saphenous
vein (ASV). However, a prosthetic graft is needed in the absence of an ASV. In such situations,
we used an expanded polytetrafluoroethylene (ePTFE) pre-cuffed Dynaflo graft as supragenicular
bypass or Distaflo graft as infragenicular or femorocrural bypass. In respect to the expanding
possibilities of percutaneous transluminal angioplasty (PTA), the indication for bypass surgery
moved toward patients with advanced stages of peripheral arterial occlusive disease. For this
reason, this study analyzed the current performances of these ePTFE grafts and ASV grafts with
special attention to limb salvage. METHODS: In a retrospective study all patients who underwent
peripheral bypass surgery between 2004 and 2008 were included. Kaplan-Meier curves were
used to express primary patency, secondary patency, and limb salvage rates at 1 and 3 years.
Log-rank tests were performed to compare graft types. RESULTS: A total of 272 grafts (ePTFE/
ASV: 110/162) were performed in lower limb bypass surgery. The mean follow-up was 20.3
months. The secondary 3-year patency rates were for (n=78) supragenicular grafts (ePTFE/
ASV: 45%/94%)*, for (n=124) infragenicular grafts (24%/74%), and 70 for femorocrural grafts
(26%/52%). Limb salvage after 3 years was 59% in the ePTFE group versus 78% in the ASV group
(P < .05). CONCLUSION: In the current population of vascular patients where no PTA is possible
and a peripheral bypass is necessary, the ASV remains the graft of first choice. However, the precuffed ePTFE graft is a good alternative, especially in cases of critical limb ischemia, in respect
to an acceptable limb salvage rate.
Te Slaa A, Tetteroo E, Mulder PG, Ho GH, Vos LD, Moll FL, van der Laan L. Magnetic
resonance imaging reveals edema-like changes not only subcutaneously, but also in muscle
tissue after femoropopliteal bypass surgery. Ann Vasc Surg. 2012 Feb;26(2):233-41. Epub
2011 Nov 1.
BACKGROUND: The pathophysiological mechanisms that induce postrevascularization edema
after femoropopliteal bypass surgery are not completely understood. Reperfusion-associated
injury to revascularized tissue and damage to lymphatic structures are both likely to play a role.
Aim of this study was to study edema formation after peripheral bypass surgery with magnetic
resonance imaging. MATERIALS AND METHODS: Nine patients suffering from severe peripheral
arterial occlusive disease were subjected to magnetic resonance imaging scans before and 1 week
after autologous femoropopliteal or femorocrural bypass surgery. RESULTS: A 12% increase
in volume of the upper legs and an 11% increase in volume of the lower legs were measured
in patients postoperatively. The increase of volume was largely due to expansion of the
subcutaneous compartments: a 35% increase in the upper legs and a 41% increase in the lower
legs. Edema in the upper legs was predominantly located medially at the site of the surgical
wound. In contrast, edema in the lower legs was homogenously distributed around the entire
leg circumference. The muscle compartment showed no significant change of volume. However,
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53
in the majority of patients, edema-like changes were seen in selected muscles as well after a
peripheral bypass reconstruction. CONCLUSION: Swelling of the subcutaneous compartments
is mainly responsible for the volume increases in upper and lower legs similar to lymphatic
edema. In addition, in a majority of patients, edema-like changes in selected muscles were seen
especially in the upper legs. Reperfusion-associated injury as a cause of these changes cannot
be ruled out. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All
rights reserved.
Oztürk C, Te Slaa A, Dolmans DE, Ho GH, de Vries J, Mulder PG, van der Laan L. Quality
of life in perspective to treatment of postoperative edema after peripheral bypass surgery.
Ann Vasc Surg. 2011 Nov 5. [Epub ahead of print]
BACKGROUND: To examine the effects of peripheral bypass surgery on patients’ quality of life
(QoL) as well as to compare two treatment modalities to reduce postoperative edema with regard
to patients’ QoL. METHODS: This was a randomized controlled trial set in the department of
54
vascular surgery in a nonacademic teaching hospital. Ninety-three patients (mean age, 70 years;
33% Rutherford 5-6), enrolled between August 2006 and September 2009, who underwent
peripheral bypass surgery (autologous 57, polytetrafluoroethylene 36). Patients were assigned
to intermittent pneumatic compression (n = 46) or to compression stockings (n = 47). The
main outcome measure was QoL, measured with the World Health Organization Quality of Life
assessment instrument (short form: WHOQOL-BREF). RESULTS: QoL improved on the domain of
Physical Health by 7.18 points (p < 0.001 [range, 0-100]) after 2 weeks and by 10.03 points
(p < 0.001) after 3 months. Patients who received a polytetrafluoroethylene bypass scored 0.45
points (p = 0.0008 [range, 1-5]) lower at baseline on Global QoL than patients who received an
autologous bypass. Type of bypass or edema treatment method did not affect the improvements.
Edema did not correlate with QoL. CONCLUSION: Improvement in QoL on the domain Physical
Health following femoropopliteal bypass surgery was found as soon as 2 weeks after surgery.
Improvement in QoL domains was not influenced by the type of bypass reconstruction. No
specific effects of edema on QoL were detected. Copyright © 2011 Annals of Vascular Surgery
Inc. Published by Elsevier Inc. All rights reserved.
Azizi F, Reichman BL, de Groot HG, van der Laan L. Primary aortoduodenal fistula in
combination with aortoiliac occlusive disease: report of a rare case. J Cardiovasc Surg
(Torino). 2011 May 10. [Epub ahead of print].
Most of the cases of aortoenteric fistula are due to aneurysm of the aorta, although infection,
tumor, radiotherapy, gastric ulcers and foreign body ingestion have also been described in the
literature. We report the case of a 62-year-old woman presenting with massive gastrointestinal
bleeding with hematemesis and melaena. This case is unique in that the primary aortoduodenal
(PADF) fistula formed as a result of complex atherosclerotic disease of the abdominal aorta and
both iliacal arteries, also known as Leriche’s syndrome, and not primarily due to an aneurysm.
We will give a brief summary of the difficulties and challenges which the surgeon faced during
the operation and a surprisingly uneventful postoperative course.
Dolmans DE, de Borst GJ, te Slaa A, Remmers MJ, Verbiest HB, Hol M, Moll FL, van der
Laan L. Tijdverlies van beroerte tot carotisendarteriëctomie. [Time lost between stroke
and carotid endarterectomy]. Ned Tijdschr Geneeskd. 2011;155(32):A3300.
OBJECTIVE: To establish whether measures taken to shorten the interval of time between a
stroke and carotid endarterectomy (CEA) procedure at two Dutch hospitals had any effect.
DESIGN: Retrospective and descriptive. METHOD: Data were gathered on all patients with
symptomatic narrowing of the carotid artery from a non-academic teaching hospital (Amphia
Ziekenhuis in Breda) as well as from a university clinic dedicated to carotid abnormalities
(University Medical Center Utrecht, UMCU). ‘Pass-through’ intervals were analysed from 2006
and 2007 and compared with those from 2010 when the sequence of hospital care had been
improved in terms of time interval from stroke up to and including CEA. The time interval
between the first symptoms of stroke and the first visit to the outpatient clinic specialist was
determined, as well as the time interval between the stroke and CEA procedure. RESULTS:
After the hospitals had taken measures to shorten the time interval between a stroke and an
operation, the percentage of patients who had undergone surgery within 2 weeks in 2010 was
34% at Amphia Ziekenhuis and 21% at the UMCU, as opposed to 5.5% (2006) and 10.5% (2007),
respectively. The median time between first symptoms and surgery had decreased from 40 to
19 days at Amphia Ziekenhuis and from 57 to 36 days at the UMCU. CONCLUSION: At both the
non-academic clinic and the university centre dedicated to carotid abnormalities, the majority
of symptomatic patients had not undergone surgery within 2 weeks of a stroke in 2010. A CEA
must therefore become a semi-acute operation instead of a semi-elective one in order to meet its
associated performance criteria in the near future.
Kimman ML, Dirksen CD, Voogd AC, Falger P, Gijsen BC, Thuring M, Lenssen A, van der
Ent F, Verkeyn J, Haekens C, Hupperets P, Nuytinck JK, van Riet Y, Brenninkmeijer SJ,
Scheijmans LJ, Kessels A, Lambin P, Boersma LJ. Economic evaluation of four follow-up
strategies after curative treatment for breast cancer: results of an RCT. Eur J Cancer.
2011 May;47(8):1175-85. Epub 2011 Jan 21.
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55
BACKGROUND: An economic evaluation was performed alongside a randomised controlled trial
(ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead
of hospital visits, and of a short educational group programme (EGP) in the first year after breast
cancer treatment. METHOD: This economic evaluation (n = 299) compared the one-year costs and
the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone followup; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were
measured using cost diaries and hospital registrations. Quality-adjusted life years (QALYs) were
measured using the EQ-5D. Outcomes were expressed in incremental cost-effectiveness ratios
(ICERs) and cost-effectiveness acceptability curves. RESULTS: Hospital follow-up plus EGP yielded
most QALYs (0.776), but also incurred the highest mean annual costs (€4914). The ICER of this
strategy versus the next best alternative, nurse-led telephone follow-up plus EGP (0.772 QALYs
and €3971), amounted to €235.750/QALY. Hospital and telephone follow-up without EGP both
incurred higher costs and less QALYs than telephone follow-up plus EGP and were judged inferior.
Hospital follow-up plus EGP was not considered cost-effective, therefore, telephone follow-up
plus EGP was the preferred strategy. The probability of telephone follow-up plus EGP being costeffective ranged from 49% to 62% for different QALY threshold values. Secondary and sensitivity
56
analyses showed that results were robust. CONCLUSION: Nurse-led telephone follow-up plus
EGP seems an appropriate and cost-effective alternative to hospital follow-up for breast cancer
patients during their first year after treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID: 21257305 [ PubMed - indexed for MEDLINE]
Ent F, Verkeyn J, Haekens C, Hupperets P, Nuytinck JK, van Riet Y, Brenninkmeijer SJ,
Scheijmans LJ, Kessels A, Lambin P, Boersma LJ. Nurse-led telephone follow-up and an
educational group programme after breast cancer treatment: results of a 2 × 2 randomised
controlled trial. Eur J Cancer. 2011 May;47(7):1027-36. Epub 2011 Jan 13.
OBJECTIVE: To investigate whether frequent hospital follow-up in the first year after
breast cancer treatment might partly be replaced by nurse-led telephone follow-up without
deteriorating health-related quality of life (HRQoL), and whether a short educational group
programme (EGP) would enhance HRQoL. PATIENTS AND METHODS: A multicentre pragmatic
randomised controlled trial (RCT) with a 2×2 factorial design was performed among 320 breast
cancer patients who were treated with curative intent. Participants were randomised to followup care as usual (3-monthly outpatient clinic visits), nurse-led telephone follow-up, or the
former strategies combined with an educational group programme. The primary outcome for
both interventions was HRQoL, measured by EORTC QLQ-C30. Secondary outcomes were role
and emotional functioning and feelings of control and anxiety. RESULTS: Data of 299 patients
were available for evaluation. There was no significant difference in HRQoL between nurseled telephone and hospital follow-up at 12 months after treatment (p = 0.42; 95% confidence
interval (CI) for difference: -1.93-4.64) and neither between follow-up with or without EGP
(p = 0.86; 95% CI for difference: -3.59-3.00). Furthermore, no differences between the
intervention groups and their corresponding control groups were found in role and emotional
functioning, and feelings of control and anxiety (all p-values > 0.05). CONCLUSION: Replacement
of most hospital follow-up visits in the first year after breast cancer treatment by nurse-led
telephone follow-up does not impede patient outcomes. Hence, nurse-led telephone follow-up
seems an appropriate way to reduce clinic visits and represents an accepted alternative strategy.
An EGP does not unequivocally affect positive HRQoL outcomes. Copyright © 2010 Elsevier Ltd.
All rights reserved.
Van Hooft JE, Bemelman WA, Oldenburg B, Marinelli AW, Holzik MF, Grubben MJ, Sprangers
MA, Dijkgraaf MG, Fockens P; collaborative Dutch Stent-In study group* [Rijken AM et
al...]. Colonic stenting versus emergency surgery for acute left-sided malignant colonic
obstruction: a multicentre randomised trial. Lancet Oncol. 2011 Apr;12(4):344-52.
BACKGROUND: Colonic stenting as a bridge to elective surgery is an alternative for emergency
surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We
aimed to establish whether colonic stenting has better health outcomes than does emergency
surgery. METHODS: Patients with acute obstructive left-sided colorectal cancer were enrolled
from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic
stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was
computer generated with permuted blocks and was stratified by centre; treatment allocation
was concealed by use of a web-based application. Investigators and patients were unmasked to
treatment assignment. The primary outcome was mean global health status during a 6-month
follow-up, which was assessed with the QL2 subscale of the European Organisation for Research
and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by
intention to treat. This study is registered, number ISRCTN46462267. FINDINGS: Between March
9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients)
or emergency surgery (n=51). Two successive interim analyses showed increased 30-day
morbidity in the colonic stenting group, with an absolute risk increase of 0.19 (95% CI -0.06 to
0.41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of 32
receiving emergency surgery), and an absolute risk increase of 0.19 (-0.01 to 0.37) in analysis
of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice of the data
safety monitoring committee, the study was suspended on Sept 18, 2009, and ended on March
12, 2010. At the final analysis of 98 patients, mean global health status during follow-up was
63.0 (SD 23.8) in the colonic stenting group and 61.4 (SD 21.9) in the emergency surgery group;
after adjustment for baseline values, mean global health status did not differ between treatment
groups (-4.7, 95% CI -14.8 to 5.5, p=0.36). No difference was recorded between treatment
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groups in 30-day mortality (absolute risk difference -0.01, 95% CI -0.14 to 0.12, p=0.89), overall
mortality (-0.02, -0.17 to 0.14, p=0.84), morbidity (-0.08, -0.27 to 0.11, p=0.43), and stoma
rates at latest follow-up (0.09, -0.10 to 0.27, p=0.35). However, the emergency surgery group
had an increased stoma rate directly after initial intervention (0.23, 0.04 to 0.40, p=0.016) and
a reduced frequency of stoma-related problems (between-group difference -12.0, -23.7 to -0.2,
p=0.046). The most common serious adverse events were abscess (three in the colonic stenting
group vs four in the emergency surgery group), perforations (six vs none), and anastomotic
leakage (five vs one), and the most common adverse events were pneumonia (three vs one)
and wound infection (one vs three). INTERPRETATION: Colonic stenting has no decisive clinical
advantages to emergency surgery. It could be used as an alternative treatment in as yet
undefined subsets of patients, although with caution because of concerns about tumour spread
caused by perforations. FUNDING: None. *Collaborators: 53
Erratum in: Lancet Oncol. 2011 May;12(5):418.
Comment in: Nat Rev Clin Oncol. 2011 Jun;8(6):318; Lancet Oncol. 2011 Apr;12(4):314-5; Lancet
Oncol. 2011 Jul;12(7):621; author reply 621-2.
58
Van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ahmed Ali U, Schrijver AM,
Boermeester MA, van Goor H, Dejong CH, van Eijck CH, van Ramshorst B, Schaapherder
AF, van der Harst E, Hofker S, Nieuwenhuijs VB, Brink MA, Kruyt PM, Manusama ER, van
der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de
Wit RJ, Houdijk AP, Cuesta MA, Wahab PJ, Gooszen HG; Dutch Pancreatitis Study Group*.
A conservative and minimally invasive approach to necrotizing pancreatitis improves
outcome. Gastroenterology. 2011 Oct;141(4):1254-63. Epub 2011 Jul 8.
BACKGROUND & AIMS: Treatment of patients with necrotizing pancreatitis has become more
conservative and less invasive, but there are few data from prospective studies to support the
efficacy of this change. We performed a prospective multicenter study of treatment outcomes
among patients with necrotizing pancreatitis. METHODS: We collected data from 639 consecutive
patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data
were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome.
RESULTS: Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%),
with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An
intervention was performed in 242 patients (38%), with 27% mortality; this included early
emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times
between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days,
26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for
infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first
intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary
catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003).
Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only
peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and
mortality (20% vs 9%, P<.001). CONCLUSIONS: Approximately 62% of patients with necrotizing
pancreatitis can be treated without an intervention and with low mortality. In patients with
infected necrosis, delayed intervention and catheter drainage as first treatment improves
outcome. Collaborators (81): Boermeester MA, Bollen TL, Dejong CH, van Eijck CH, van Goor H,
Gooszen HG, Hofker HS, Laméris JS, van Leeuwen MS, Schaapherder AF, Timmer R, Nieuwenhuijs
VB, van Dam RM, Rutten JP, Stoot JH, Keulemans Y, Vliegen R, Roeterdink A, Zeguers V, Ahmed
Ali U, Rijnhart HG, Cirkel GA, van Erpecum KJ, Vleggaar FP, van Baal M, Akkermans LM, van
Leeuwen MS, Wiezer MJ, Weusten BL, Biemond HD, Ploeg RJ, Buitenhuis HT, van Vliet SU,
Ramcharan S, van Dullemen HM, van Ruler O, Laméris W, Gouma DJ, Busch OR, Fockens P,
Haasnoot A, Veenendaal R, Witteman BJ, Pierie JP, Spoelstra P, Dol JA, Gerritsen RT, Lange JF,
Wijffels NA, van Walraven LA, Coene PP, Kubben FJ, Wijsman JH, Crolla RM, van Milligen de Wit
AW, Rijk MC, Stassen LP, Buscher H, Heisterkamp J, van Oostvogel H, Grubben MJ, Tan A, van
der Wal JB, Morak MJ, Hermans JJ, Kuipers EJ, Poley JW, Bruno M, Jansen JB, Strijk SP, Lips
D, Olsman JG, van Munster IP, Kolkman JJ, Huisman AB, Tuynman HA, Wiarda BM, Consten EJ,
Schwartz MP, van der Peet DL, Mulder CJ. Copyright © 2011 AGA Institute. Published by Elsevier
Inc. All rights reserved.
Lemmens VE, Bosscha K, van der Schelling G, Brenninkmeijer S, Coebergh JW, de Hingh
IH. Improving outcome for patients with pancreatic cancer through centralization.
Br J Surg. 2011 Oct;98(10):1455-62. doi: 10.1002/bjs.7581. Epub 2011 Jun 29.
BACKGROUND: High-volume institutions are associated with improved clinical outcomes for
pancreatic cancer. This study investigated the impact of centralizing pancreatic cancer surgery
in the south of the Netherlands. METHODS: All patients diagnosed in the Eindhoven Cancer
Registry area in 1995-2000 (precentralization) and 2005-2008 (implementation of centralization
agreements) with primary cancer of the pancreatic head, extrahepatic bile ducts, ampulla of
Vater or duodenum were included. Resection rates, in-hospital mortality, 2-year survival and
changes in treatment patterns were analysed. Multivariable regression analyses were used
to identify independent risk factors for death. RESULTS: Some 2129 patients were identified.
Resection rates increased from 19·0 to 30·0 per cent (P < 0·001). The number of hospitals
performing resections decreased from eight to three, and the annual number of resections per
hospital increased from two to 16. The in-hospital mortality rate dropped from 24·4 to 3·6 per
cent (P < 0·001) and was zero in 2008. The 2-year survival rate after surgery increased from
38·1 to 49·4 per cent (P = 0·001), and the rate irrespective of treatment increased from 10·3
to 16·0 per cent (P < 0·001). There was no improvement in 2-year survival in non-operated
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patients. After adjustment for relevant patient and tumour factors, those undergoing surgery
more recently had a lower risk of death (hazard ratio 0·70, 95 per cent confidence interval
0·51 to 0·97). Changes in surgical patterns seemed largely to explain the improvements.
CONCLUSION: High-quality care can be achieved in regional hospitals through collaboration.
Centralization should no longer be regarded as a threat by general hospitals but as a chance to
improve outcomes in pancreatic cancer. Copyright © 2011 British Journal of Surgery Society Ltd.
Published by John Wiley & Sons, Ltd.
Bosma E, Veen EJ, Roukema JA. Incidence, nature and impact of error in surgery.
Br J Surg. 2011 Nov;98(11):1654-9. Epub 2011 Jun 27.
BACKGROUND: Adverse events occur in 3·8-17 per cent of hospital admissions. The purpose of
this study was to analyse the incidence of medical errors and assess the feasibility of an error
registry for quality improvement programmes. METHODS: Errors were recorded prospectively in a
complication registry between 1 June 2005 and 31 December 2007. Events were coded according
60
to the Trauma Registry of the American College of Surgeons; the nature of events was recorded
and the severity graded using the 1992 Clavien system. Recorded events were discussed by the
medical staff on a daily basis and, if by consensus judged to be errors, were saved to the registry
database. RESULTS: Of 12,121 patients admitted to the surgical ward during the study interval,
2033 (16·8 per cent) had a complication and 735 (6·1 per cent) had an error documented
in the registry. Of 873 recorded errors, 607 (69·5 per cent) were of little or no consequence
(Clavien grade I) and 220 (25·2 per cent) required therapeutic intervention (Clavien grade
IIa and IIb). Errors leading to permanent injury (Clavien grade III) occurred in 41 instances
(4·7 per cent) and five patients (0·6 per cent) died (Clavien grade IV). CONCLUSION: This study
shows that errors are common in surgery, and that near misses are more frequent than errors
with serious consequences. It is hypothesized that registration of near misses might prevent
errors with serious consequences and thus improve quality of care. Copyright © 2011 British
Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Ritchie ED, Veen EJ, Olsman J, Bosscha K. A case of bowel entrapment after penetrating
injury of the pelvis: don’t forget the omentumplasty. Scand J Trauma Resusc Emerg Med.
2011 Jun 10;19:34.
Bowel entrapment within a pelvic injury is rare and difficult to diagnose. Usually, it is diagnosed
late because of concomitant abdominal injuries. It may present itself as an acute intestinal
obstruction or, more commonly, as a prolonged or intermittent ileus. Therefore, one should be
aware of this late complication and primarily take measures for avoiding bowel entrapment.
This report describes an unusual case of bowel entrapment within a pelvic fracture after a
penetrating injury, and discusses options for preventing such a complication. PMID: 21663625
[PubMed - indexed for MEDLINE] PMCID:PMC3123199 Gorter EA, Vos DI, Sier CF, Schipper IB.
Implant removal associated complications in children with limb fractures due to trauma. Eur
J Trauma Emerg Surg. 2011 Dec;37(6):623-627. Epub 2011 Mar 17. PURPOSE: The purpose of
this study was to analyze the number and type of complications that occurred after fracture
implant removal and to investigate whether implant removal should be performed routinely
in children. METHODS: In a retrospective study, patient records were used for the analyses
of patient characteristics, surgery reports, and complications. Children under the age of 16
years with a limb fracture due to trauma, treated with either Kirschner wires (K-wires), elastic
stable intramedullary nails (ESIN), or screw fixation between 2000 and 2007, were included.
Exclusion criteria were as follows: refracture, pathological fracture, fracture of the hands and
feet, or polytrauma patients (Injury Severity Score [ISS] > 15). RESULTS: Three-hundred and
nine fractures were analyzed. All K-wires (173) and ESIN (96) were removed as per standard
procedure, resulting in 17/173 and 7/96 complications after removal, respectively. In 19/40
patients with screw fixation treatments, it was decided to remove the material after fracture
consolidation, resulting in 4/19 complications. The decision in 21 treatments to leave the screw
in situ led to four complications. No significant difference in complication rates could be found
for the three groups after removal surgery (17/173, 7/96, and 4/19) or between hardware
removal (4/19) and retention (4/21) in the case of screw fixation. CONCLUSIONS: The removal of
K-wires, ESIN, and screws is considered to be a safe procedure in children and is, by definition,
indicated for K-wires and ESIN after fracture healing.
PMID: 22207879 [PubMed]
PMCID:PMC3232347
Stegeman SA, de Jong M, Sier CF, Krijnen P, Duijff JW, van Thiel TP, de Rijcke PA, Soesman
NM, Hagenaars T, Boekhoudt FD, de Vries MR, Roukema GR, Tanka AF, van den Bremer J,
van der Meulen HG, Bronkhorst MW, van Dijkman BA, van Zutphen SW, Vos DI, Schep NW,
Eversdijk MG, van Olden GD, van den Brand JG, Hillen RJ, Frölke JP, Schipper IB. Displaced
midshaft fractures of the clavicle: non-operative treatment versus plate fixation (SleutelTRIAL). A multicentre randomised controlled trial. BMC Musculoskelet Disord.
2011 Aug 24;12:196.
BACKGROUND: The traditional view that the vast majority of midshaft clavicular fractures heal
with good functional outcomes following non-operative treatment may be no longer valid for
all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of
non-union and identified speciic limitations of the shoulder function in subgroups of patients
with these injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will be
conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder
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function after either non-operative treatment with a sling or a plate fixation. METHODS/DESIGN:
A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated
midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will
be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad
view). Secondary outcome will be the functional outcome, measured using the Constant Score.
Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2).
Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm,
Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data
on complications, bone union, cosmetic aspects and use of painkillers will be collected with
follow-up questionnaires. The follow-up time will be two years. All patients will be monitored
at regular intervals over the subsequent twelve months (two and six weeks, three months and
one year). After two years an interview by telephone and a written survey will be performed
to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an
intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: This trial will
provide level-1 evidence for the comparison of consolidation and functional outcome between
two standardised treatment options for dislocated midshaft clavicular fractures. The gathered
62
data may support the development of a clinical guideline for treatment of clavicular fractures.
TRIAL REGISTRATION: Netherlands National Trial Register NTR2399.
PMCID:PMC3175212
Verdam FJ, Dolmans DE, Loos MJ, Raber MH, de Wit RJ, Charbon JA, Vroemen JP. Delayed
primary closure of the septic open abdomen with a dynamic closure system. World J Surg.
2011 Oct;35(10):2348-55.
BACKGROUND: The major challenge in the management of patients with an infected open
abdomen (OA) is to control septic peritonitis and intra-abdominal fluid secretion, and to
facilitate repeated abdominal exploration, while preserving the fascia for delayed primary
closure. We here present a novel method for closure of the infected OA, based on continuous
dynamic tension, in order to achieve re-approximation of the fascial edges of the abdominal
wall. METHODS: Eighteen cases with severe peritonitis of various origin (e.g., gastrointestinal
perforations, anastomotic leakage) were primarily stabilized by laparostomy, sealed with
either the vacuum-assisted closure abdominal dressing or the Bogotá bag. After hemodynamic
stabilization and control of the sepsis, the Abdominal Re-approximation Anchor System (ABRA;
Canica Design, Almonte, Ontario, Canada) was applied. This system approximates the wound
margins through dynamic traction exerted by transfascial elastomers. Before ABRA application,
5/18 patients had a grade 2B, 2/18 a grade 3, and 11/18 a grade or 4 status according to
the open abdomen classification of Björck. RESULTS: In this severely ill population the mean
time before ABRA system application was 12 days (range: 2-39 days). Two of 18 patients died
of non-ABRA-related causes within three weeks. In 14 of the remaining 16 patients (88%)
primary abdominal closure of the midline was accomplished in 15 days (range: 7-30 days). The
other two patients needed a component separation technique according to Ramirez to reach
closure. However, secondary wound dehiscence occurred in both these patients. Two thirds of
patients (12/18) developed pressure sores to the skin and/or dermis, but all healed without
further complications. During outpatient clinic follow-up, 4/14 successfully closed patients
still developed a midline hernia. CONCLUSIONS: Delayed primary closure of OA in septic patients
could be achieved in 88% with this new approximation system. However, the risk of hernia
development remained. We consider this system a useful tool in the treatment of septic patients
with an open abdomen.
PMCID:PMC3170463
Kaas L, van Riet RP, Turkenburg JL, Vroemen JP, van Dijk CN, Eygendaal D. Magnetic
resonance imaging in radial head fractures: most associated injuries are not clinically
relevant. J Shoulder Elbow Surg. 2011 Dec;20(8):1282-8. Epub 2011 Sep 16.
63
BACKGROUND: Recent studies report that magnetic resonance imaging (MRI) shows a high
incidence of associated injuries in patients with a radial head fracture. This retrospective study
describes the clinical relevance of these injuries. MATERIALS AND METHODS: Forty patients
with 42 radial head fractures underwent a MRI scan after a mean of 7.0 days after trauma
and were reviewed after a mean of 13.3 months. RESULTS: MRI showed 24 of 42 elbows had a
lateral collateral ligament (LCL) lesion, 1 had a medial collateral ligament (MCL) and LCL lesion,
16 had an injury of the capitellum, 1 had a coronoid fracture, and 2 had loose osteochondral
fragments. Clinical evaluation after a mean of 13.3 months showed that 3 elbows had clinical
MCL or LCL laxity, of which 2 elbows had no ligamentous injuries diagnosed with MRI. One
elbow with a loose osteochondral fragment showed infrequent elbow locking. The mean Mayo
Elbow Performance Scale was 97.5 (range, 80-100) after a mean of 13.3 months after trauma,
with no significant difference between patients with and without associated injuries (P =
.8). CONCLUSION: Most injuries found with MRI in patients with radial head fractures are not
symptomatic or of clinical importance in short-term follow-up. Copyright © 2011 Journal of
Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.
L. Prospective randomized controlled trial to analyze the effects of intermittent
pneumatic compression on edema following autologous femoropopliteal bypass surgery.
World J Surg. 2011 Feb;35(2):446-54.
Chirurgie
64
Donker JM, Ho GH, Te Slaa A, de Groot HG, van der Waal JC, Veen EJ, van der Laan L.
Midterm results of autologous saphenous vein and ePTFE pre-cuffed bypass surgery in
peripheral arterial occlusive disease. Vasc Endovascular Surg. 2011 Oct;45(7):598-603.
Epub 2011 Jul 14.
Franken JM, de Groot HGW, Geenen GPJ, van der Laan L. Leriche syndrome in
combination with a pelvic kidney. Chirurgia. 2011 April;24(2):93-4.
World J Surg. 2011 Feb;35(2):446-54.
Epub 2011 Jul 14.
Van Dijck RA, Ho GH, Haans HA. Het thoracic-outletsyndroom bij de orthopedisch chirurg.
Ned Tijdschr Traumatol 2011;2:38-41.
resonance imaging reveals edema-like changes not only subcutaneously, but
also in muscle tissue after femoropopliteal bypass surgery. Ann Vasc Surg. 2012
Feb;26(2):233-41. Epub 2011 Nov 1.
Oztürk C, Te Slaa A, Dolmans DE, Ho GH, de Vries J, Mulder PG, van der Laan L. Quality of
life in perspective to treatment of postoperative edema after peripheral bypass surgery.
World J Surg. 2011 Feb;35(2):446-54.
Helleman JN, Vos DI, van der Laan L. Pseudoaneurysm of the deep femoral artery after
pertrochanteric hip fracture: A case report. Vasc Dis Man. 2011;8(6):e119-e120
Zeeland MLP, van der Laan L. Late complications following aortic aneurysm repair. In:
Diagnosis, Screening and Treatment of Abdominal, Thoracoabdominal and Thoracic
Aortic Aneurysms / Grundmann RT [ed]. [s.l.] : Intech, 2011. Chapter 2; 9-34.
ISBN 978-953-307-466-5.
Epub 2011 Jul 14.
Mahmoodi BK; Nijsten, M; Wijsman J, Matthews AG, van der Laan L. ABO-blood groups
and risk of abdominal aortic aneurysm and peripheral obstructive arterial disease: two
sides of the same coin. Thromb Res. 2012 Jan;129(1):89-90. Epub 2011 Oct 19.
Spelt D, Frima H, van der Laan L. Bareback equestrian trauma: pubic symphysiolysis and
abdominal arterial hemorrhage. Surgical Science. 2011;2:493-495.
resonance imaging reveals edema-like changes not only subcutaneously, but also in
muscle tissue after femoropopliteal bypass surgery. Ann Vasc Surg.
2012 Feb;26(2):233-41. Epub 2011 Nov 1.
Kimman ML, Dirksen CD, Voogd AC, Falger P, Gijsen BC, Thuring M, Lenssen A, van der Ent
F, Verkeyn J, Haekens C, Hupperets P, Nuytinck JK, van Riet Y, Brenninkmeijer SJ,
2011 May;47(8):1175-85. Epub 2011 Jan 21.
Ent F, Verkeyn J, Haekens C, Hupperets P, Nuytinck JK, van Riet Y, Brenninkmeijer
SJ, Scheijmans LJ, Kessels A, Lambin P, Boersma LJ. Nurse-led telephone follow-up
Chirurgie
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66
and an educational group programme after breast cancer treatment: results of a 2 × 2
randomised controlled trial. Eur J Cancer. 2011 May;47(7):1027-36. Epub 2011 Jan 13.
Schreinemakers JM, Rijken AM. Een losse tand. Ned Tijdschr Heelkunde
2011;20(8):309-310.
obstruction: a multicentre randomised trial. Lancet Oncol.
2011 Apr;12(4):344-52.
AF, van der Harst E, Hofker S, Nieuwenhuijs VB, Brink MA, Kruyt PM, Manusama ER,
van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha
K, de Wit RJ, Houdijk AP, Cuesta MA, Wahab PJ, Gooszen HG; Dutch Pancreatitis Study
Group*. A conservative and minimally invasive approach to necrotizing pancreatitis
improves outcome. Gastroenterology. 2011 Oct;141(4):1254-63. Epub 2011 Jul 8.
Epub 2011 Jul 14.
injury of the pelvis: don’t forget the omentumplasty. Scand J Trauma Resusc Emerg
Med. 2011 Jun 10;19:34.
Gorter EA, Vos DI, Sier CF, Schipper IB. Implant removal associated complications
in children with limb fractures due to trauma. Eur J Trauma Emerg Surg. 2011
Dec;37(6):623-627. Epub 2011 Mar 17.
Stegeman SA, de Jong M, Sier CF, Krijnen P, Duijff JW, van Thiel TP, de Rijcke PA,
Soesman NM, Hagenaars T, Boekhoudt FD, de Vries MR, Roukema GR, Tanka AF, van
den Bremer J, van der Meulen HG, Bronkhorst MW, van Dijkman BA, van Zutphen SW,
Vos DI, Schep NW, Eversdijk MG, van Olden GD, van den Brand JG, Hillen RJ, Frölke
JP, Schipper IB. Displaced midshaft fractures of the clavicle: non-operative treatment
versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial. BMC
Musculoskelet Disord. 2011 Aug 24;12:196.
primary closure of the septic open abdomen with a dynamic closure system. World J
Surg. 2011 Oct;35(10):2348-55.
World J Surg. 2011 Feb;35(2):446-54.
Epub 2011 Jul 14.
Franken J, Wijsman J. Neusmaagsonde. Medisch Contact 2011 sep 9;66(36):2136.
Chirurgie
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Dermatologie
Kerngegevens zorgkern Dermatologie
• 7 dermatologen: mw. A. (Angelina) Barentsen-Erceg, dr. A.Y.R.L. (Annick) Bracke,
mw. S.J. (Sarah) Caers, W.J.A. (Wim) de Kort, dr. J.E.M. (John) Körver, mw. dr. D.I.M.
(Danielle) Kuijpers, mw. F.J.A.M. (Francoise) van Neer
• subspecialismen: allergologie, flebologie, dermato-oncologie
Samenvatting gepubliceerd artikel
Holterhues C, Cornish D, van de Poll-Franse LV, Krekels G, Koedijk F, Kuijpers D, Coebergh
JW, Nijsten T. Impact of melanoma on patients’ lives among 562 survivors: a Dutch
population-based study. Arch Dermatol. 2011 Feb;147(2):177-85.
OBJECTIVE: To assess the impact of melanoma on the health-related quality of life of patients
from the general population up to 10 years after diagnosis and its determinants. DESIGN:
A cross-sectional Dutch population-based postal survey among patients with melanoma for
the years 1998 to 2008 using the Eindhoven Cancer Registry. MAIN OUTCOME MEASURES: The
36-Item Short-Form Health Survey (SF-36), Impact of Cancer (IOC) questionnaire and specific
melanoma-related questions. The SF-36 scores of the cases were compared with normative
data. Multiple linear regression models were used to identify associated factors of SF-36 and
IOC scores. RESULTS: The response rate was 80%. The mean age of the 562 respondents was
57.3 years; 62% were female, and 76% had a melanoma with a Breslow thickness of less than
2 mm. The SF-36 component scores of patients with melanoma were similar to those of the
normative population. In a multiple linear regression model, stage at diagnosis, female sex, age,
and comorbidity were significantly associated (P<.05) with the physical and mental component
scores. Women were significantly more likely to report higher levels of both positive and
Dermatologie
69
negative IOC. Time since diagnosis, tumor stage, and comorbidity were significant predictors
of negative IOC scores. Women seemed to adjust their sun behavior more often (54% vs 67%;
P<.001) than men and were more worried about the deleterious effects of UV radiation (45% vs
66%; P<.001). CONCLUSION: The impact of melanoma seems to be specific and more substantial
in women, suggesting that they may need additional care to cope with their melanoma
optimally. ©2011 American Medical Association. All rights reserved.
Comment in: Arch Dermatol. 2011 Feb;147(2):186.
Van Wijk-Tiemes DEM, Körver JEM, Bos WH, Seyger MMB. Seniele gluteale dermatose
veroorzaakt door frictie. Ned Tijdschr Dermatol Venereol. 2011;21(4):231-233.
population-based study. Arch Dermatol. 2011 Feb;147(2):177-85.
70
Geriatrie
Kerngegevens zorgkern Geriatrie
• 4 geriaters: mw. D.C. (Dominique) Berendschot- de Lange, M.Th. (Theo) Feitsma,
R.A.M. (Richard) de Jonckheere, K.R (Remco) Pameijer
• 1 haio
• 1 vaio
Jobse IC, Feitsma Th. Klinische presentatie van het chronisch subduraal hematoom bij
ouderen. Tijdschr Gerontologie en Geriatrie. 2011;42 (3):139-143.
Feitsma MTh, Pameijer R, van den Bosch-Eland A, Slappendel R. Valpreventie zonder
onrustband. Medisch Contact 2011 sep 23;66(38):2305-2307.
Geriatrie
71
Gynaecologie
Kerngegevens Gynaecologie
• 16 gynaecologen: J. (Jeroen) van Bavel, dr. P.F.J. (Peter) van Bommel,
mw. M.G.K. (Marja) Dijksterhuis, dr. H.W.H. (Harry) Feijen, dr. D.A. (Dirk) Gietelink,
dr. D.J. (Dave) Hendriks, dr. R. (Roger) Heydanus, mw. J.C.M (Anneke) Jeurgens-Borst,
G.J.A. (Gerhard) Knol, mw. A.L.M. (Angela) Kok, mw. dr. M.S. (Simone) Lunshof,
dr. D.N.M. (Dimitri) Papatsonis, mw. M.F.M. (Mariska) Shekary-Moonen,
mw. D.J.C. (Ineke) Smalbraak, mw. M.C.S. (Ellen) Vermeer, dr. H.J. (Henk) Vonsée
• 1 chef de clinique: mw. drs. A. (Aagje) Bais
• 1 baios
• 2 fertiliteitsartsen
• 1 Prenetale Diagnostiek arts
• subspecialismen: algemene gynaecologie, prenetale diagnostiek, fertiliteit,
bekkenbodem, oncologie, psychosomatiek, zwangerschap en verloskunde
Jozwiak M, Oude Rengerink K, Benthem M, van Beek E, Dijksterhuis MG, de Graaf IM, van
Huizen ME, Oudijk MA, Papatsonis DN, Perquin DA, Porath M, van der Post JA, Rijnders
RJ, Scheepers HC, Spaanderman ME, van Pampus MG, de Leeuw JW, Mol BW, Bloemenkamp
KW; PROBAAT Study Group*. Foley catheter versus vaginal prostaglandin E2 gel for
induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial.
Lancet. 2011 Dec 17;378(9809):2095-103. Epub 2011 Oct 24.
Gynaecologie
73
BACKGROUND: Induction of labour is a common obstetric procedure. Both mechanical (eg,
Foley catheters) and pharmacological methods (eg, prostaglandins) are used for induction of
labour in women with an unfavourable cervix. We aimed to compare the effectiveness and
safety of induction of labour with a Foley catheter with induction with vaginal prostaglandin
E2 gel. METHODS: We did an open-label, randomised controlled trial in 12 hospitals in the
Netherlands between Feb 10, 2009, and May 17, 2010. We enrolled women with a term singleton
pregnancy in cephalic presentation, intact membranes, an unfavourable cervix, an indication
for induction of labour, and no prior caesarean section. Participants were randomly allocated
by an online randomisation system to induction of labour with a 30 mL Foley catheter or
vaginal prostaglandin E2 gel (1:1 ratio). Because of the nature of the intervention this study
was not blinded. The primary outcome was caesarean section rate. Secondary outcomes were
maternal and neonatal morbidity and time from intervention to birth. All analyses were done
on an intention-to-treat basis. We also did a meta-analysis that included our trial. The trial
was registered with the Dutch trial registry, number NTR 1646. FINDINGS: 824 women were
allocated to induction of labour with a Foley catheter (n=412) or vaginal prostaglandin E2 gel
(n=412). Caesarean section rates were much the same between the two groups (23%vs 20%, risk
74
ratio [RR] 1·13, 95% CI 0·87-1·47). A meta-analysis including our trial data confirmed that a
Foley catheter did not reduce caesarean section rates. We recorded two serious maternal adverse
events, both in the prostaglandin group: one uterine perforation and one uterine rupture.
INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with a
Foley catheter is similar to induction of labour with prostaglandin E2 gel, with fewer maternal
and neonatal side-effects. FUNDING: None. Collaborators (8): Doornbos H, Drogtrop A, de Groot
C, Huisjes A, Kleiverda G, van Meir C, van der Salm P, Schuitemaker N. Copyright © 2011 Elsevier
Ltd. All rights reserved.
Comment in: Lancet. 2011 Dec 17;378(9809):2054-5.
Van de Poll-Franse LV, Nicolaije KA, Vos MC, Pijnenborg JM, Boll D, Husson O, Ezendam NP,
Boss EA, Hermans RH, Engelhart KC, Haartsen JE, Pijlman BM, Feijen HW, Mertens HJ,
Nolting WE, van Beek JJ, Roukema JA, Kruitwagen RF. The impact of a cancer Survivorship
Care Plan on gynaecological cancer patient and health care provider reported outcomes
(ROGY Care): study protocol for a pragmatic cluster randomized controlled trial. Trials.
2011 Dec 5;12:256.
BACKGROUND: There is a need for improvement of information provision and post-treatment
care for cancer survivors. A Survivorship Care Plan (SCP) is recommended by the American
Institute of Medicine and the Dutch Health Council, which is a summary of patients’ course
of treatment as a formal document, and includes recommendations for subsequent cancer
surveillance, management of late effects, and strategies for health promotion. Until now,
evidence on the effects of implementing the SCP in clinical practice is lacking. The rationale and
study design of a pragmatic cluster randomized trial, aiming to assess the impact of SCP care
in routine clinical practice, is presented. METHODS/DESIGN: A web-based patient registration
system ‘Registrationsystem Oncological GYnecology’ (ROGY) is used by gynecologists in the
South of the Netherlands since 2006. A personalized SCP can automatically be generated out
of ROGY. In this pragmatic cluster randomized controlled trial, 12 hospitals are randomized
to either ‘usual care’ or ‘SCP care’. In patients with ‘usual care’, the gynecologist provides care
as usual. In patients with ‘SCP care’, information about the tumor stage and treatment is
personally discussed with the patient and a document is handed to the patient. Prospectively,
all patients diagnosed with endometrial or ovarian cancer in the participating hospitals will
be approached for study participation. Patients will complete questionnaires after surgery,
and before additional treatment, and after 6, 12, 18 and 24 months. In addition, health care
providers will be asked their opinion about implementation of SCP care. Primary outcome is
defined as patient satisfaction with information provision and care. Secondary outcomes are
illness perception, health-related quality of life, health care use, prevalence, course and referral
rate of survivors with psychosocial distress, and health care providers’ evaluation of SCP care.
DISCUSSION: The ROGY Care trial will help to gain insight into the impact of SCP care on patient
reported outcomes, and on the evaluation of cancer survivors and health care providers of the
different elements of the SCP. Therefore, results will contribute to efforts to improve quality of
care for cancer survivors. TRIAL REGISTRATION: Trial Registration: http://www.ClinicalTrials.gov.
Identifier: NCT01185626Medical Research Ethics Committee Reference Number: NL33429.008.10
Grant Reference Number: UVT2010-4743.
PMCID:PMC3286432
Vollebregt A, Fischer K, Gietelink D, van der Vaart CH. Primary surgical repair of anterior
vaginal prolapse: a randomised trial comparing anatomical and functional outcome
between anterior colporrhaphy and trocar-guided transobturator anterior mesh. BJOG.
2011 Nov;118(12):1518-27. doi: 10.1111/j.1471-0528.2011.03082.x. Epub 2011 Aug 22.
OBJECTIVE: To compare anterior colporrhaphy with a trocar-guided transobturator mesh
procedure (Avaulta(®) anterior). DESIGN: Randomised, controlled trial. SETTING: Three teaching
hospitals. POPULATION: Women with a symptomatic cystocele at least stage II requiring primary
surgical correction. METHODS: A total of 125 women were assessed at baseline and 1-year follow
up. A sacrospinous hysteropexy or posterior colporrhaphy was performed when indicated. MAIN
OUTCOME MEASURES: The primary outcome was the difference in anatomical cure (defined as
Pelvic Organ Prolapse-Quantification <stage II cystocele). Secondary outcomes were complications,
self-reported urogenital symptom severity, and quality of life, as measured with validated
questionnaires. RESULTS: In all, 64 women were allocated to the anterior colporrhaphy group and
Gynaecologie
75
61 to the mesh group; 58/64 women versus 56/61 completed 12 months of follow-up analysis.
Compared with the anterior colporrhaphy group, the mesh reduced the risk of anatomical failure
at 12 months follow up from 59 to 9% (risk reduction 50.3%, 95% CI 35.5-65.1). Only three (5%)
re-operations for anatomical failure in the anterior colporrhaphy group were performed versus
0% in the mesh group. Functional outcome improved significantly at 12 months on almost all
domains, with similar results between groups. Mesh exposure occurred in two (4%) women.
Baseline dyspareunia disappeared significantly more often after an anterior colporrhaphy (80%)
than in the mesh group (20%). There was a trend towards more de novo dyspareunia in the mesh
group (15% versus 9%). CONCLUSIONS: Primary cystocele repair with trocar-guided transobturator
mesh resulted in a statistically significant better anatomical outcome compared with the anterior
colporrhaphy. However, functional outcome was similar between groups. © 2011 The Authors
BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.
76
Vollebregt A, Fischer K, Gietelink D, van der Vaart CH. Effects of vaginal prolapse surgery
on sexuality in women and men; results from a rct on repair with and without mesh.
J Sex Med. 2012 Feb 9. [Epub ahead of print]
INTRODUCTION: In pelvic organ prolapse (POP) repair, the use of synthetic mesh is not only
increasing but also a subject of discussion. The focus shifts from anatomical toward functional
outcome, with sexual function being an important parameter. One of the concerns with mesh
usage in POP surgery is the possible negative effect on sexual function. AIM: To compare and
assess sexual function in women and men after primary cystocele repair with or without trocarguided transobturator mesh. Methods. One hundred twenty-five women with a symptomatic
cystocele stage = II were included in this multicenter randomized controlled trial and assessed
at baseline and 6-month follow-up. MAIN OUTCOME MEASURES: Female sexual function was
measured by the Female Sexual Function Index (FSFI) and male sexual function by the Male
Sexual Health Questionnaire. A subgroup analysis of women with a participating partner was
performed. RESULTS: In the mesh group, 54/59 women vs. 53/62 in the anterior colporrhaphy
group participated. In men, 29 vs. 30 participated. After surgery, FSFI scores were comparable
for both treatment groups. However, within group analysis showed significant improvement
on the domains pain (effect size = 0.5), lubrication (effect size = 0.4), and overall satisfaction
(effect size = 0.5) in the colporrhaphy group. This improvement was not observed in the mesh
group. A subgroup of women with a participating partner reported significantly higher baseline
domain scores as compared with other women and did not report a significant improvement of
sexual functioning irrespective of treatment allocation. Worsening of baseline sexual function
was reported by 43% of women in the mesh group compared with 18% in anterior colporrhaphy
group (P = 0.05). Male sexual functioning did not change in either group. CONCLUSIONS: Women
after an anterior colporrhaphy report a significant and clinically relevant improvement of their
sexual functioning, whereas women after a mesh procedure did not. © 2012 International
Society for Sexual Medicine.
Jozwiak M, Oude Rengerink K, Benthem M, van Beek E, Dijksterhuis MG, de Graaf IM,
van Huizen ME, Oudijk MA, Papatsonis DN, Perquin DA, Porath M, van der Post JA,
Rijnders RJ, Scheepers HC, Spaanderman ME, van Pampus MG, de Leeuw JW, Mol BW,
Bloemenkamp KW; PROBAAT Study Group*. Foley catheter versus vaginal prostaglandin
E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised
controlled trial. Lancet. 2011 Dec 17;378(9809):2095-103. Epub 2011 Oct 24.
Boss EA, Hermans RH, Engelhart KC, Haartsen JE, Pijlman BM, Feijen HW, Mertens
HJ, Nolting WE, van Beek JJ, Roukema JA, Kruitwagen RF. The impact of a cancer
Survivorship Care Plan on gynecological cancer patient and health care provider
reported outcomes (ROGY Care): study protocol for a pragmatic cluster randomized
controlled trial. Trials. 2011 Dec 5;12:256.
on sexuality in women and men; results from a RCT on repair with and without mesh.
J Sex Med. 2012 Feb 9. [Epub ahead of print]
De Vogel J, Heydanus R, Mulders AG, Smalbraak DJ, Papatsonis DN, Gerritse BM. Lifesaving
intraosseous access in a patient with a massive obstetric hemorrhage.
Am J Perinatol Rep. 2011; 1(2): 119-122.
De Vogel J, Heydanus R, Mulders AG, Smalbraak DJ, Papatsonis DN, Gerritse BM.
Lifesaving intraosseous access in a patient with a massive obstetric hemorrhage.
Gynaecologie
77
Interne geneeskunde en
Maag- darm- levergeneeskunde
Kerngegevens Interne geneeskunde en Maag- darm- levergeneeskunde
• 21 internisten: dr. R.C. (René) Bakker, mw. R.S. (Rinske) Boersma,
mw. dr. P.W.G. (Peggy) du Buf – Vereijken, mw. T.T. (Nynke) Cnossen, mw.
S.A.M. (Simone) Ennecker-Jans, dr. J.W.J. (Joost) van Esser, dr. R.W. (Ronald) van
Etten, medisch manager , mw. A.M. (Astrid) van Gent, G.J. (Gerard) Goverde,
dr. C. (Coen) van Guldener, mw. J.B. (Joan) Heijns, mw. dr. M.H.W. (Mariëtte)
Kappers, mw. dr. M.A. (Marieke) van Leeuwen-Artz, O.J.L. (Olaf) Loosveld, F.J. (Frits)
Schuitemaker (internist-intensivist), dr. S.W. (Sjoerd) van Thiel, dr. A.J. (Bert-Jan)
ten Tije, B.F.E. (Bernard) Veldhuijzen, R.A.L. (Ruud) de Waal (internist-intensivist),
G.P. (Gerrit) Verburg, P. (Peter) van Wijngaarden
• 6 MDL-artsen: A.G.L. (Alexander) Bodelier, I.M. (Ivar) Harkema,
mw. M.J.(Marianne) van Heerde , dr. A.W.M (Marc) van Milligen de Wit,
dr. M.C.M. (Marno) Rijk, dr. T.C.J (Tom) Seerden
• subspecialismen: diabetes, endocrinologie, hematologie, infectieziekten, nefrologie,
oncologie, maag- darm- leverziekten
Stevens KN, Croes S, Boersma RS, Stobberingh EE, van der Marel C, van der Veen FH,
Knetsch ML, Koole LH. Hydrophilic surface coatings with embedded biocidal silver
nano particles and sodium heparin for central venous catheters. Biomaterials. 2011
Feb;32(5):1264-9. Epub 2010 Nov 19.
Interne geneeskunde en Maag- darm- levergeneeskunde
79
Central venous catheters (CVCs) have become indispensable in the treatment of neonates
and patients undergoing chemotherapy or hemodialysis. A CVC provides easy access to the
patient’s circulation, thus enabling facile monitoring of hemodynamic parameters, nutritional
support, or administration of (cytostatic) medication. However, complications with CVCs, such
as bacterial bloodstream infection or thromboembolism, are common. Bloodstream infections,
predominantly caused by Staphylococcus aureus, are notoriously difficult to prevent and
treat. Furthermore, patients receiving infusion therapy through a CVC are at risk for deepvein thrombosis, especially of the upper limbs. Several recent clinical trials have shown that
prophylactic anticoagulation (low-molecular-weight heparin or vitamin K antagonists) is not
effective. Here, we report on the systematic development of a new bifunctional coating concept
that can -uniquely- be applied to make CVC surfaces antimicrobial and antithrombogenic at
the same time. The novel coating consists of a moderately hydrophilic synthetic copolymer
of N-vinylpyrrollidinone (NVP) and n-butyl methacrylate (BMA), containing embedded silver
nanoparticles (AgNPs) and sodium heparin. The work demonstrates that the AgNPs strongly
inhibit adhesion of S. aureus (reference strain and clinical isolates). Surprisingly, heparin not
only rendered our surfaces practically non-thrombogenic, but also contributed synergistically to
80
their biocidal activity. Copyright © 2010 Elsevier Ltd. All rights reserved.
Creemers K, van der Heiden O, Los J, van Esser J, Newhall D, Djamin RS, Aerts JG.
Endoscopic ultrasound fine needle aspiration in the diagnosis of lymphoma. J Oncol.
2011;2011:785425. Epub 2011 Apr 10.
In recent years, endoscopic ultrasound techniques with Fine Needle Aspiration (FNA)
have become an increasingly used diagnostic aid in the differentiation of mediastinal
lymphadenopathy. Endobronchial ultrasound (EBUS) and endoesophageal ultrasound (EUS) are
now available for clinicians to reach mediastinal and paramediastinal masses using a minimally
invasive approach. These techniques are an established component for diagnosing and staging
lung cancer and their benefit in the diagnosis of lymphoma’s has been highlighted in a number
of case studies. However, the lack of tissue architecture obtained by cytological FNA specimens
decreases the diagnostic accuracy for benign causes of thoracic lymphadenopathies, lymphomas,
and histopathological subtyping of lung cancer. Accordingly, our study group have adapted the
FNA sampling technique, resulting in tissue fragments that can be used for histopathological
examinations. As an illustration, we report a case of follicular non-Hodgkin lymphoma,
diagnosed on tissue fragments obtained by adjusted EUS FNA. We believe that this relatively
simple adjustment to routine FNA sampling can help to overcome the diagnostic limitations
inherent in cytology obtained by routine FNA. PMID: 21559244 [PubMed] PMCID: PMC3087462
Verheijden N, Ermens TA, van Esser JW. Persisterende polyklonale B-cellymfocytose. [Persistent
polyclonal B-cell lymphocytosis]. Ned Tijdschr Geneeskd. 2011;155:A3149. BACKGROUND:
Persistent polyclonal B-cell lymphocytosis (PPBL) is a benign condition associated with
smoking. CASE REPORT: A 42-year-old woman was referred to an internist because of an
abnormal blood test outcome identified during routine sampling. She had no symptoms; she
had smoked for thirty pack years. Physical examination revealed no abnormalities. Laboratory
analysis showed absolute lymphocytosis. A blood smear identified binuclear (‘buttock’) cells.
The diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL) was made, with nicotine
abuse as the probable cause. The patient was advised to quit smoking. CONCLUSION: Polyclonal
B-cell lymphocytosis is a benign condition that is characterised by: (a) polyclonal increase of
B-lymphocytes in peripheral blood; (b) the presence of binuclear lymphocytes (buttock cells)
in microscopic differentiation; (c) polyclonal increase in IgM. Recognition is important for the
prevention of unnecessary diagnostic testing.
Van Durme CM, Kisters JM, van Paassen P, van Etten RW, Tervaert JW. Multiple endocrine
abnormalities. Lancet. 2011 Aug 6;378(9790):540.
Rayson D, Suter TM, Jackisch C, van der Vegt S, Bermejo B, van den Bosch J, Vivanco
GL, van Gent AM, Wildiers H, Torres A, Provencher L, Temizkan M, Chirgwin J, Canon
JL, Ferrandina G, Srinivasan S, Zhang L, Richel DJ. Cardiac safety of adjuvant pegylated
liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial.
Ann Oncol. 2011 Nov 4. [Epub ahead of print]
BACKGROUND: The cardiac safety of trastuzumab concurrent with pegylated liposomal
doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. PATIENTS
AND METHODS: Women with resected node-positive or intermediate-risk node-negative HER2
overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) * 55% were
randomized (1:2) to doxorubicin 60 mg/m(2) (A) + cyclophosphamide 600 mg/m(2) (C) every
21 days (q21d) for four cycles or PLD 35 mg/m(2) + C q21d + trastuzumab 2 mg/kg weekly (H)
for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m(2) with H for 12 weeks
followed by H to complete 1 year. The primary end point was cardiac event rate or inability
to administer 1 year of trastuzumab. RESULTS: Of 181 randomized patients, 179 underwent
cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to
cardiotoxicity was 18.6% [n = 11; 95% confidence interval (CI) 9.7% to 30.9%] with A + C → T
+ H and 4.2% (n = 5; 95% CI 1.4% to 9.5%) with PLD + C + H → T + H (P = 0.0036). All events,
except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean
absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P = 0.0014).
81
CONCLUSION: PLD + C + H → T + H is feasible and results in lower early cardiotoxicity rates
compared with A + C → T + H.
Haberkorn BC, Ermens AA, Koeken A, Cobbaert CM, van Guldener C. Improving diagnosis
of adult-type hypolactasia in patients with abdominal complaints. Clin Chem Lab Med.
2011 Sep 21. [Epub ahead of print]
BACKGROUND: Adult-type hypolactasia is caused by genetic lactase non-persistence. It is the
most common cause of lactose intolerance, which results in gastrointestinal symptoms after
ingestion of dairy products. Currently, lactose intolerance is investigated by the hydrogen breath
test (HBT), which is considered the preferred diagnostic test. Adult-type hypolactasia may also
be diagnosed by genotyping. The single nucleotide polymorphism -13910C>T, which is located
upstream of the lactase gene (LCT), is tightly associated with lactase persistence. Several other
variants, mostly in non-European populations, can also lead to lactase persistence. This study
investigated the accuracy of a mo-ified, recently proposed algorithm which includes genotyping
82
for the diagnosis of adult-type hypolactasia in a patient population with unexplained abdominal
complaints. METHODS: In 126 patients with unexplained abdominal symptoms or who were
suspected to have adult-type hypolactasia, LCT genotyping by melting curve analysis on a
LightCycler was performed. Those patients with CC(-13910) genotype (indicating loss of lactase
expression) were directly referred to a dietician for a lactose-free diet. Those identified as
CT(-13910) or TT(-13910) genotype underwent a HBT. Those who tested positive for hydrogen
were also referred to a dietician for a lactose-free diet. The response to diet modification
was recorded. RESULTS: Genotype prevalences were: CC(-13910): 43 (34.1%); CT(-13910):
48 (38.1%); TT(-13910): 33 (26.2%); TG(-13915): 2 (1.6%). Eleven of 48 (23%) patients
with CT(-13910)-genotype and 1/33 (3%) patients with TT(-13910)-genotype had a positive
hydrogen breath test. They all improved after a lactose-free diet. Four of 43 (9%) patients with
CC(- 13910)-genotype still had symptoms after a lactose-free diet. CONCLUSIONS: The results
show that lactase-genotype testing can be used as a first step to diagnose lactose intolerance
in a patient population with unexplained abdominal complaints. It accurately identifies the
group of patients sensitive to lactose, those who need further breath testing and those in whom
adult-type hypolactasia can be excluded with high probability without performing a HBT. This
algorithm would save hydrogen breath testing in more than 50% of the patients who present
with unexplained abdominal symptoms.
Kappers MH, de Beer VJ, Zhou Z, Danser AH, Sleijfer S, Duncker DJ, van den Meiracker
AH, Merkus D. Sunitinib-induced systemic vasoconstriction in swine is endothelin
mediated and does not involve nitric oxide or oxidative stress. Hypertension. 2012
Jan;59(1):151-7. Epub 2011 Nov 28.
Angiogenesis inhibition with agents targeting tyrosine kinases of vascular endothelial growth
factor receptors is an established anticancer treatment, but is, unfortunately, frequently
accompanied by systemic hypertension and cardiac toxicity. Whether vascular endothelial
growth factor receptor antagonism also has adverse effects on the pulmonary and coronary
circulations is presently unknown. In chronically instrumented awake swine, the effects of the
vascular endothelial growth factor receptor antagonist sunitinib on the systemic, pulmonary,
and coronary circulation were studied. One week after sunitinib (50 mg PO daily), mean aortic
blood pressure (MABP) had increased from 83±5 mm Hg at baseline to 97±6 mm Hg (P<0.05)
because of a 57±20% increase in systemic vascular resistance as cardiac output decreased. In
contrast, sunitinib had no discernible effects on pulmonary and coronary hemodynamics or
cardiac function. We subsequently investigated the mechanisms underlying the sunitinibinduced systemic hypertension. Intravenous administration of NO synthase inhibitor N(G)-nitrol-arginine increased MABP by 24±1 mm Hg under baseline conditions, whereas it increased MABP
even further after sunitinib administration (32±3 mm Hg; P<0.05). Reactive oxygen species
scavenging with a mixture of antioxidants lowered MABP by 13±2 mm Hg before but only
by 5±2 mm Hg (P<0.05) after sunitinib administration. However, intravenous administration
of the dual endothelin A/endothelin B receptor blocker tezosentan, which did not lower
MABP at baseline, completely reversed MABP to presunitinib values. These findings indicate
that sunitinib produces vasoconstriction selectively in the systemic vascular bed, without
affecting pulmonary or coronary circulations. The sunitinib-mediated systemic hypertension is
principally attributed to an increased vasoconstrictor influence of endothelin, with no apparent
contributions of a loss of NO bioavailability or increased oxidative stress.
Kappers MH, van Esch JH, Smedts FM, de Krijger RR, Eechoute K, Mathijssen RH,
Sleijfer S, Leijten F, Danser AH, van den Meiracker AH, Visser TJ. Sunitinib-induced
hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary
regression. J Clin Endocrinol Metab. Epub 2011 Aug 3.
CONTEXT: Anticancer treatment with the tyrosine kinase inhibitor sunitinib causes thyroid
dysfunction. OBJECTIVE: Our objective was to investigate the time course and underlying
mechanisms of sunitinib-induced thyroid dysfunction. DESIGN: Thyroid function tests of 83
patients on sunitinib were collected retrospectively for their total treatment duration between
January 2006 and November 2009 and prospectively in 15 patients on sunitinib for 10 wk.
Additionally, thyroid function and histology were assessed in rats on sunitinib (8 d; n = 10)
and after sunitinib withdrawal (11 d; n = 7) and compared with controls (n = 7). SETTING:
83
Patients were seen at a university outpatient oncology clinic. Patients and Animals: Patients
with metastatic renal cell carcinoma or gastrointestinal stromal tumors participated in the
clinical study and Wistar Kyoto rats were used in the rat study. Intervention: Sunitinib was
taken according to a 4 wk “on,” 2 wk “off” treatment regimen. Blood samples for measurement
of thyroid function were collected at baseline and at wk 4 and 10. In rats, blood, liver, and
thyroid were collected to assess thyroid hormones, deiodinase activity, and thyroid histology.
MAIN OUTCOME MEASURES: TSH and free T(4) levels, deiodinase activity, and thyroid histology
were assessed. RESULTS: Forty-two percent of patients in the retrospective study developed
elevated TSH levels. Prospective analysis showed increased TSH levels within 10 wk of treatment,
accompanied by a decreased T(3)/rT(3) ratio. In rats, serum T(4) and T(3) decreased, hepatic
type 3 deiodinase activity increased, and thyroid histology showed marked capillary regression,
which all but thyroid hormones reversed after sunitinib withdrawal. CONCLUSION: Sunitinib
induces hypothyroidism due to alterations in T(4)/T(3) metabolism as well as thyroid capillary
regression.
84
Kappers MH, Smedts FM, Horn T, van Esch JH, Sleijfer S, Leijten F, Wesseling S, Strevens
H, Jan Danser AH, van den Meiracker AH. The vascular endothelial growth factor receptor
inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin
system. Hypertension. 2011 Aug;58(2):295-302. Epub 2011 Jun 13.
Angiogenesis inhibition is an established treatment for several tumor types. Unfortunately, this
therapy is associated with adverse effects, including hypertension and renal toxicity, referred
to as “preeclampsia.” Recently, we demonstrated in patients and in rats that the multitarget
tyrosine kinase inhibitor sunitinib induces a rise in blood pressure (BP), renal dysfunction,
and proteinuria associated with activation of the endothelin system. In the current study we
investigated the effects of sunitinib on rat renal histology, including the resemblance with
preeclampsia, as well as the roles of endothelin 1, decreased nitric oxide (NO) bioavailability,
and increased oxidative stress in the development of sunitinib-induced hypertension and renal
toxicity. In rats on sunitinib, light and electron microscopic examination revealed marked
glomerular endotheliosis, a characteristic histological feature of preeclampsia, which was partly
reversible after sunitinib discontinuation. The histological abnormalities were accompanied by
an increase in urinary excretion of endothelin 1 and diminished NO metabolite excretion. In rats
on sunitinib alone, BP increased (6BP: 31.6±0.9 mm Hg). This rise could largely be prevented
with the endothelin receptor antagonist macitentan (6BP: 12.3±1.5 mm Hg) and only mildly
with Tempol, a superoxide dismutase mimetic (6BP: 25.9±2.3 mm Hg). Both compounds could
not prevent the sunitinib-induced rise in serum creatinine or renal histological abnormalities
and had no effect on urine nitrates but decreased proteinuria and urinary endothelin
1 excretion. Our findings indicate that both the endothelin system and oxidative stress play
important roles in the development of sunitinib-induced proteinuria and that the endothelin
system rather than oxidative stress is important for the development of sunitinib-induced
hypertension.
Verdonk K, Visser W, Steegers EA, Kappers MH, Danser AH, van den Meiracker AH. Nieuwe
inzichten in pathogenese van pre-eclampsie De rol van angiogeneseremmende factoren.
[New insights into the pathogenesis of pre-eclampsia: the role of angiogenesis-inhibiting
factors]. Ned Tijdschr Geneeskd. 2011;155:A2946.
The pathogenesis of pre-eclampsia is biphasic. The first phase is characterised by insufficient
placentation and the second phase by an increased placental release of 2 anti-angiogenic
factors, namely, soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng). Within
maternal circulation, sFlt-1 and sEng inhibit the effects of vascular endothelial growth factor
(VEGF) and transforming growth factor ß (TGFß). This results in endothelial cell activation and
inflammation, and eventually leads to the clinical syndrome of pre-eclampsia. The rise in plasma
concentrations of sFlt-1 and sEng precedes the development of pre-eclampsia with 6-8 weeks.
Whether elevations in the plasma concentrations of sFlt and sEng, combined with a decrease
in placental growth factor concentrations, can be utilised as a predictor for pre-eclampsia is
currently under investigation.
Venderbosch S, de Wilt JH, Teerenstra S, Loosveld OJ, van Bochove A, Sinnige HA,
Creemers GJ, Tesselaar ME, Mol L, Punt CJ, Koopman M. Prognostic value of resection
of primary tumor in patients with stage IV colorectal cancer: retrospective analysis
of two randomized studies and a review of the literature. Ann Surg Oncol. 2011
Nov;18(12):3252-60. Epub 2011 Aug 6.
BACKGROUND: In patients with metastatic colorectal cancer (mCRC) with an asymptomatic
primary tumor, there is no consensus on the indication for resection of the primary tumor.
METHODS: A retrospective analysis was performed on the outcome of stage IV colorectal cancer
(CRC) patients with or without resection of the primary tumor treated in the phase III CAIRO
and CAIRO2 studies. A review of the literature was performed. RESULTS: In the CAIRO and
CAIRO2 studies, 258 and 289 patients had undergone a primary tumor resection and 141 and 159
patients had not, respectively. In the CAIRO study, a significantly better median overall survival
and progression-free survival was observed for the resection compared to the nonresection
group, with 16.7 vs. 11.4 months [P<0.0001, hazard ratio (HR) 0.61], and 6.7 vs. 5.9 months
(P=0.004; HR 0.74), respectively. In the CAIRO2 study, median overall survival and progressionfree survival were also significantly better for the resection compared to the nonresection
85
group, with 20.7 vs. 13.4 months (P<0.0001; HR 0.65) and 10.5 vs. 7.8 months (P=0.014; HR
0.78), respectively. These differences remained significant in multivariate analyses. Our review
identified 22 nonrandomized studies, most of which showed improved survival for mCRC patients
who underwent resection of the primary tumor. CONCLUSIONS: Our results as well as data from
literature indicate that resection of the primary tumor is a prognostic factor for survival in stage
IV CRC patients. The potential bias of these results warrants prospective studies on the value of
resection of primary tumor in this setting; such studies are currently being planned.
Comment in: Ann Surg Oncol. 2011 Nov;18(12):3229-31.
PMCID:PMC3192274
Lalisang RI, Erdkamp FL, Rodenburg CJ, Knibbeler-van Rossum CT, Nortier JW, van
Bochove A, Slee PH, Voest EE, Wils JA, Wals J, Loosveld OJ, Smals AE, Blijham GH,
Tjan-Heijnen VC, Schouten HC. Epirubicin and paclitaxel with G-CSF support in first line
metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated
chemotherapy. Breast Cancer Res Treat. 2011 Jul;128(2):437-45. Epub 2011 May 17.
86
An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle
(dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter
randomized phase II study assessed the efficacy and safety of two different approaches:
epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin
75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF.
Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled
for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade =
3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dosedense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic)
cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194
and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose
intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm,
respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months,
respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time,
but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The
value of dose-densification over standard scheduled chemotherapy regimes yet needs to be
determined.
Hamberg P, Bos MM, Braun HJ, Stouthard JM, van Deijk GA, Erdkamp FL, van der SteltFrissen IN, Bontenbal M, Creemers GJ, Portielje JE, Pruijt JF, Loosveld OJ, Smit WM,
Muller EW, Schmitz PI, Seynaeve C, Klijn JG; Dutch Breast Cancer Trialists’ Group (BOOG).
Randomized phase II study comparing efficacy and safety of combination-therapy
trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel
alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast
cancer: HERTAX trial. Clin Breast Cancer. 2011 Apr;11(2):103-13. Epub 2011 Apr 11.
BACKGROUND: Because chemotherapy for metastatic breast cancer (MBC) is associated with
relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease
progression might be an attractive approach. METHODS: In a multicenter phase II trial, 101
patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were
randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and
sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel
alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was
progression-free survival (PFS) after completed sequential or combination therapy. RESULTS:
For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS
rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79%
vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively
(P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent
docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab
of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D
group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of
patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall
survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively).
CONCLUSION: First-line treatment in patients with MBC with H→D resulted in a similar PFS
compared with H+D, but the response rate was lower and the overall survival nonsignificantly
shorter. Copyright © 2011 Elsevier Inc. All rights reserved.
Lemmens VE, de Haan N, Rutten HJ, Martijn H, Loosveld OJ, Roumen RM, Creemers GJ.
Improvements in population-based survival of patients presenting with metastatic
rectal cancer in the south of the Netherlands, 1992-2008. Clin Exp Metastasis. 2011
Mar;28(3):283-90. Epub 2011 Jan 5.
We analysed population-based treatment and survival data of patients who presented with
metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal
cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of
diagnosis was divided into three periods (1992-1999, 2000-2004, 2005-2008) according to the
availability of chemotherapy type. We assessed treatment patterns and overall survival according
to period of diagnosis. The proportion of patients diagnosed with stage IV disease increased
from 16% in 1992-1999 to 20% in 2005-2008 (P < 0.0001). Chemotherapy use increased from 5%
87
in 1992 to 61% in 2008 (P < 0.0001). Resection rates of the primary tumour decreased from 65%
in 1992 to 27% in 2008 (P < 0.0001), while metastasectomy rates remained constant since 1999
(9%). Median survival increased from 38 weeks (95% confidence interval (CI) 32-44) in 19921999 to 53 weeks (95% CI 48-61) in 2005-2008. Among patients not receiving chemotherapy
median survival remained approximately 30 weeks. Multivariable analysis confirmed the lower
risk of death among patients diagnosed in more recent years. Increased use of chemotherapy
went together with improved median survival among patients with metastatic rectal cancer in
the last two decades. Stage migration as an effect of more effective imaging procedures is likely
to be partly responsible for this improved survival.
PMCID:PMC3040315
Delgado V, Biermasz NR, van Thiel SW, Ewe SH, Ajmone Marsan N, Holman ER, Feelders
RA, Smit JW, Bax JJ, Pereira AM. Changes in heart valve structure and function in
patients treated with dopamine agonists for prolactinomas, a 2-year follow-up study.
Clin Endocrinol (Oxf). 2011 Dec 23. [Epub ahead of print]
88
OBJECTIVE: The use of ergot-derived dopamine agonists (DA) to treat patients with
prolactinomas has not been associated with an increased risk of significant heart valve
dysfunction. Accordingly, the present study evaluated whether the long-term use of DA for
hyperprolactinaemia may be associated with increased risk of significant valvular heart disease.
METHODS: A total of 74 patients (mean age 48 ± 1.4 years, 23% male) with prolactinoma
treated with DA for at least 1 year were evaluated with 2-dimensional echocardiography at
baseline. After 2 years of follow-up, a repeat echocardiography was performed to evaluate
significant changes in valvular heart structure (thickening, calcifications and leaflet motion
abnormalities) and function (regurgitation or stenosis). Patients were classified according to
treatment: patients treated with cabergoline (group 1: n=45), and patients not treated with
cabergoline (group 2: n=29). RESULTS: At 2 year follow-up, no significant valvular stenosis was
observed in any patient. In addition, the prevalence of any significant valve regurgitation did
not change significantly (from 12% to 15%, P=NS). However, there was a significant increase in
the prevalence of valvular calcifications (from 48% to 58%, P=0.004) and, particularly, in the
prevalence of aortic valve calcifications (from 39% to 53%, P=0.002). In a per-treatment based
analysis, the group of patients treated with cabergoline had significantly higher prevalence
of aortic valve calcification at 2 years follow-up as compared to the group of patients not
treated with cabergoline (63% vs. 38%, P=0.016). CONCLUSIONS: The long-term therapy with
DA (cabergoline) of patients with prolactinoma is associated with an increased prevalence of
valvular calcification. However, these structural changes were not accompanied by an increased
prevalence of valvular dysfunction. © 2011 Blackwell Publishing Ltd.
Bökkerink GM, de Graaf EJ, Punt CJ, Nagtegaal ID, Rütten H, Nuyttens JJ, van Meerten E,
Doornebosch PG, Tanis PJ, Derksen EJ, Dwarkasing RS, Marijnen CA, Cats A, Tollenaar
RA, de Hingh IH, Rutten HJ, van der Schelling GP, Ten Tije AJ, Leijtens JW, Lammering
G, Beets GL, Aufenacker TJ, Pronk A, Manusama ER, Hoff C, Bremers AJ, Verhoef C, de
Wilt JH. The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum
followed by organ-sparing transanal endoscopic microsurgery. BMC Surg. 2011 Dec
15;11(1):34.
BACKGROUND: The CARTS study is a multicenter feasibility study, investigating the role of
rectum saving surgery for distal rectal cancer. METHODS/DESIGN: Patients with a clinical
T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant
chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal
Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative
treatment depending on the clinical response.Primary objective is to determine the number
of patients with a (near) complete pathological response after chemoradiation therapy and
TEM. Secondary objectives are the local recurrence rate and quality of life after this combined
therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to
ensure the feasibility of this treatment protocol. DISCUSSION: The CARTS-study is one of the
first prospective multicentre trials to investigate the role of a rectum saving treatment modality
using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.
gov (NCT01273051).
PMCID: PMC3295682
Kerckhoffs MC, Hoskam JA, ten Tije AJ. Miltruptuur zonder trauma. [Non-traumatic
rupture of the spleen]. Ned Tijdschr Geneeskd. 2011;155:A2935.
BACKGROUND: A non-traumatic rupture of the spleen is a rare, serious condition with a high
mortality rate. This sort of rupture can occur in a healthy patient or in patients with an
underlying disease such as an infection or a haematological disorder. CASE DESCRIPTION: Here
we describe a 52-year-old man who had Legionella pneumonia and suffered a spontaneous
rupture of the spleen. He had to undergo a splenectomy following an unsuccessful embolisation
of the lienal artery. He recovered. In the second patient, a 73-year-old man with monoclonal
gammopathy, rupture of the spleen was caused by amyloidosis of the spleen. CONCLUSION:
Rupture of the spleen can cause life threatening haemorrhage, so early recognition is important.
89
Geraedts MC, Troost FJ, De Ridder RJ, Bodelier AG, Masclee AA, Saris WH. Validation
of using chamber technology to study satiety hormone release from human duodenal
specimens. Obesity (Silver Spring). 2012 Mar;20(3):678-82. Epub 2011 May 12.
By developing novel screening technologies to test effects of food ingredients on hormone
release, which are comparable to the in vivo situation, fewer tests may have to be performed
using volunteers, whereas it still provides information that can be extrapolated to the human
situation. In an in vivo intervention study, 10 lean (BMI: 20-25 kg/m(2)) and 10 obese (BMI
>30 kg/m(2)) were recruited. All subjects randomly received pea protein (PP) solutions or
placebo, orally and intraduodenally. Cholecystokinin (CCK) and glucagon like peptide 1 (GLP-1)
release was measured over 2 h. During the oral interventions, gastrointestinal (GI) fluids were
retrieved. For the present ex vivo study, duodenal biopsies were taken and placed in Ussing
chambers. The luminal side was exposed to PP, placebo, intraduodenal fluid after oral PP-intake
and oral placebo-intake in vivo, and a commercial pea-hydrolysate for 2 h. CCK and GLP-1
levels were measured at the serosal side. After intraduodenal PP administration in vivo, the
area under the curve (AUC) for both CCK and GLP-1 was significantly increased in both lean
90
and obese subjects. In the ex vivo study, exposure to PP resulted in significantly elevated levels
of CCK and GLP-1 compared to all other test solutions. These results indicate that the ex vivo
Ussing chamber technology is a valid alternative for in vivo studies, and may therefore serve
as a suitable screening tool for studying the effects of nutritional compounds on the release of
satiety hormones.
MA, Dijkgraaf MG, Fockens P; collaborative Dutch Stent-In study group* [Milligen de
Wit A et al...]. Colonic stenting versus emergency surgery for acute left-sided malignant
colonic obstruction: a multicentre randomised trial. Lancet Oncol. 2011 Apr;12(4):344-52.
BACKGROUND: Colonic stenting as a bridge to elective surgery is an alternative for emergency
surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We
aimed to establish whether colonic stenting has better health outcomes than does emergency
surgery. METHODS: Patients with acute obstructive left-sided colorectal cancer were enrolled
from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic
stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was
computer generated with permuted blocks and was stratified by centre; treatment allocation
was concealed by use of a web-based application. Investigators and patients were unmasked to
treatment assignment. The primary outcome was mean global health status during a 6-month
follow-up, which was assessed with the QL2 subscale of the European Organisation for Research
and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by
intention to treat. This study is registered, number ISRCTN46462267. FINDINGS: Between March
9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients)
or emergency surgery (n=51). Two successive interim analyses showed increased 30-day
morbidity in the colonic stenting group, with an absolute risk increase of 0.19 (95% CI -0.06 to
0.41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of
32 receiving emergency surgery), and an absolute risk increase of 0.19 (-0.01 to 0.37) in
analysis of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice
of the data safety monitoring committee, the study was suspended on Sept 18, 2009, and
ended on March 12, 2010. At the final analysis of 98 patients, mean global health status during
follow-up was 63.0 (SD 23.8) in the colonic stenting group and 61.4 (SD 21.9) in the emergency
surgery group; after adjustment for baseline values, mean global health status did not differ
between treatment groups (-4.7, 95% CI -14.8 to 5.5, p=0.36). No difference was recorded
between treatment groups in 30-day mortality (absolute risk difference -0.01, 95% CI -0.14
to 0.12, p=0.89), overall mortality (-0.02, -0.17 to 0.14, p=0.84), morbidity (-0.08, -0.27 to
0.11, p=0.43), and stoma rates at latest follow-up (0.09, -0.10 to 0.27, p=0.35). However, the
emergency surgery group had an increased stoma rate directly after initial intervention (0.23,
0.04 to 0.40, p=0.016) and a reduced frequency of stoma-related problems (between-group
difference -12.0, -23.7 to -0.2, p=0.046). The most common serious adverse events were abscess
(three in the colonic stenting group vs four in the emergency surgery group), perforations
(six vs none), and anastomotic leakage (five vs one), and the most common adverse events
were pneumonia (three vs one) and wound infection (one vs three). INTERPRETATION: Colonic
stenting has no decisive clinical advantages to emergency surgery. It could be used as an
alternative treatment in as yet undefined subsets of patients, although with caution because of
concerns about tumour spread caused by perforations. FUNDING: None. *Collaborators: 53.
Erratum in: Lancet Oncol. 2011 May;12(5):418.
Comment in: Nat Rev Clin Oncol. 2011 Jun;8(6):318; Lancet Oncol. 2011 Apr;12(4):314-5; Lancet
Oncol. 2011 Jul;12(7):621; author reply 621-2.
Van der Meulen-de Jong AE, Morreau H, Becx MC, Crobach LF, van Haastert M, ten Hove
WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst
A, Tuynman HA, Vecht J, Verhulst ML, de Vos tot Nederveen Cappel WH, Walinga H,
Weinhardt OK, Westerveld BD, Witte AM, Wolters HJ, Vasen HF High detection rate of
adenomas in familial colorectal cancer. Gut. 2011 Jan;60(1):73-6. Epub 2010 Sep 9.
BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer
(CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current
guidelines recommend colonoscopic surveillance of such families. However, information about
the yield of surveillance is limited. The aim of the present study was to evaluate the outcome
91
of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND
METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects
aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with
CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel
disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the
selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456
remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid).
Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects
(8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have
an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group
B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic
surveillance in familial CRC is substantially higher than the yield of screening reported for the
general population.
92
Larghi A, Verna EC, Ricci R, Seerden TC, Galasso D, Carnuccio A, Uchida N, Rindi G,
Costamagna G. EUS-guided fine-needle tissue acquisition by using a 19-gauge needle
in a selected patient population: a prospective study. Gastrointest Endosc. 2011
Sep;74(3):504-10.
BACKGROUND: The ability to obtain tissue samples for histological examination during EUS has
theoretical advantages over cytology alone. OBJECTIVE: To prospectively evaluate the feasibility
and yield of EUS-guided fine-needle tissue acquisition (EUS-FNTA) with a large-gauge needle in
patients in whom we expected histology to be more useful than cytology to reach a definitive
diagnosis. DESIGN: Prospective cohort study. SETTING: Tertiary care academic medical center.
PATIENTS: Consecutive patients with subepithelial lesions, esophagogastric wall thickening,
mediastinal and abdominal masses/lymphadenopathy of unknown origin, or pancreatic lesions
after nondiagnostic FNA. INTERVENTIONS: EUS-FNTA with a 19-gauge needle. MAIN OUTCOME
MEASUREMENTS: Feasibility and yield of EUS-FNTA. RESULTS: A total of 120 patients with
a mean age of 61 ± 14.6 years and mean lesion size of 38 ± 25 mm (range 8-140 mm) were
enrolled. FNTA was successfully performed in all but 1 patient (98.9%), and adequate samples
for histological examination were obtained in 116 of the 119 patients (97.5%) in whom EUSFNTA was technically successful. A mean of 2.8 ± 0.8 passes per patient were performed. At
the time of current follow-up, a definitive diagnosis was available in 117 of the 120 patients
(97.5%), with only 8 false-negative results. The sensitivity, specificity, positive and negative
predictive values, and diagnostic accuracy of EUS-FNTA in the 117 patients with a definitive
diagnosis were 91.8%, 100%, 100%, 71.4%, and 93.2%, respectively. LIMITATIONS: Singlecenter study with limited power. CONCLUSIONS: EUS-FNTA by using a large-gauge needle has a
high yield and promising diagnostic accuracy and could be used when histology may be more
useful than cytology to reach a definitive diagnosis. Copyright © 2011 American Society for
Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.
Seerden TC, Larghi A. Staging of early adenocarcinoma in Barrett’s esophagus. Gastrointest
Endosc Clin N Am. 2011 Jan;21(1):53-66.
The main goal in the staging of patients with early neoplasia arising in the context of
Barrett’s esophagus (BE) is to identify individuals who are eligible for endoscopic therapy
and differentiate them from those who require surgical management. To make the proper
patient selection a combined staging strategy consisting of endoscopy evaluation, endoscopic
ultrasonography, and endoscopic mucosal resection is necessary. In this article, the authors
summarize the evidence behind each different staging modality in the setting of early BE
adenocarcinoma and propose a staging approach that helps to select patients who are suitable
for endoscopic therapy. Copyright © 2011 Elsevier Inc. All rights reserved.
93
Feb;32(5):1264-9. Epub 2010 Nov 19.
2011;2011:785425. Epub 2011 Apr 10.
Verheijden N, Ermens TA, van Esser JW. Persisterende polyklonale B-cellymfocytose.
[Persistent polyclonal B-cell lymphocytosis]. Ned Tijdschr Geneeskd. 2011;155:A3149.
Rayson D, Suter TM, Jackisch C, van der Vegt S, Bermejo B, van den Bosch J, Vivanco GL,
van Gent AM, Wildiers H, Torres A, Provencher L, Temizkan M, Chirgwin J, Canon JL,
Ferrandina G, Srinivasan S, Zhang L, Richel DJ. Cardiac safety of adjuvant pegylated
liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial. Ann
Oncol. 2011 Nov 4. [Epub ahead of print]
Kappers MH. Cardiovascular, renal and thyroid toxicity during angiogenesis inhibition:
a translational approach. [S.l. : s.n.], 2011. ISBN 9789461691323.
94
Jan;59(1):151-7. Epub 2011 Nov 28.
hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal
capillary regression. J Clin Endocrinol Metab. Epub 2011 Aug 3.
H, Jan Danser AH, van den Meiracker AH. The vascular endothelial growth factor
receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the
endothelin system. Hypertension. 2011 Aug;58(2):295-302. Epub 2011 Jun 13.
[New insights into the pathogenesis of pre-eclampsia: the role of angiogenesisinhibiting factors]. Ned Tijdschr Geneeskd. 2011;155:A2946.
Nov;18(12):3252-60. Epub 2011 Aug 6.
Lalisang RI, Erdkamp FL, Rodenburg CJ, Knibbeler-van Rossum CT, Nortier JW, van Bochove
A, Slee PH, Voest EE, Wils JA, Wals J, Loosveld OJ, Smals AE, Blijham GH, Tjan-Heijnen
VC, Schouten HC. Epirubicin and paclitaxel with G-CSF support in first line metastatic
breast cancer: a randomized phase II study of dose-dense and dose-escalated
Muller EW, Schmitz PI, Seynaeve C, Klijn JG; Dutch Breast Cancer Trialists’ Group
(BOOG). Randomized phase II study comparing efficacy and safety of combinationtherapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed
by docetaxel alone at progression as first-line chemotherapy in patients with HER2+
metastatic breast cancer: HERTAX trial. Clin Breast Cancer. 2011 Apr;11(2):103-13. Epub
2011 Apr 11.
Mar;28(3):283-90. Epub 2011 Jan 5.
Bökkerink GM, de Graaf EJ, Punt CJ, Nagtegaal ID, Rütten H, Nuyttens JJ, van Meerten E,
Doornebosch PG, Tanis PJ, Derksen EJ, Dwarkasing RS, Marijnen CA, Cats A, Tollenaar
RA, de Hingh IH, Rutten HJ, van der Schelling GP, Ten Tije AJ, Leijtens JW, Lammering
G, Beets GL, Aufenacker TJ, Pronk A, Manusama ER, Hoff C, Bremers AJ, Verhoef C,
de Wilt JH. The CARTS study: Chemoradiation therapy for rectal cancer in the distal
rectum followed by organ-sparing transanal endoscopic microsurgery. BMC Surg. 2011
Dec 15;11(1):34.
Van Wijngaarden P, Hoskam J, Koeken A, Boer JMA, Swinkels DW, Ermens AAM, Cobbaert
CM. Primaire hemochromatose door ferroportinegenmutaties: is er een plaats voor
hepcidine in de diagnostiek? Ned Tijdschr Klin Chem Labgeneesk. 2011; 36: 6-11.
Geraedts MC, Troost FJ, De Ridder RJ, Bodelier AG, Masclee AA, Saris WH. Validation of
using chamber technology to study satiety hormone release from human duodenal
MA, Dijkgraaf MG, Fockens P; collaborative Dutch Stent-In study group* [ Milligen
de Wit A et al...]. Colonic stenting versus emergency surgery for acute left-sided
malignant colonic obstruction: a multicentre randomised trial. Lancet Oncol. 2011
Apr;12(4):344-52.
Sep;74(3):504-10.
Mutignani M, Lim LL, Seerden T, Familiari P, Tringali A, Perri V, Costamagna G. Successful
off-label use of enteral stents in uncommon complicated biliary tract diseases.
Gastrointest Endosc. 2011 Apr;73(4):828-32.
95
Larghi A, Seerden TC, Galasso D, Perri V, Uchida N, Carnuccio A, Costamagna G. EUSguided cystojejunostomy for drainage of a pseudocyst in a patient with Billroth II
gastrectomy. Gastrointest Endosc. 2011 Jan;73(1):169-71. Epub 2010 Jul 3.
96
Kaakchirurgie
Kerngegevens zorgkern Kaakchirurgie
• 6 kaakchirurgen: dr. J.E. (Eelco) Bergsma, J.M.T. (Jan) van Gemert, dr. P.J.J (Peter)
Gooris, E. (Eric) van Hooft, dr. G. (Gertjan) Mensink, dr. A.B.E. (Bert) Voûte
• subspecialisme: implantologie
Van Gemert JT, van Es RJ, Rosenberg AJ, van der Bilt A, Koole R, Van Cann EM. Free
Vascularized Flaps for Reconstruction of the Mandible: Complications, Success, and Dental
Rehabilitation. J Oral Maxillofac Surg. 2011 Nov 11. [Epub ahead of print].
PURPOSE: To evaluate complications and success of mandibular reconstruction with free fibula
flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental
rehabilitation after these reconstructions. PATIENTS AND METHODS: Eighty-three patients with
segmental mandibular defects were included. Correlation analyses were used to determine
the relationship between reconstruction type and clinical parameters with recipient-site
complications and success. The dental rehabilitation was evaluated in successfully reconstructed
survivors. RESULTS: Multivariate analyses showed significant correlations between flap type
and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction.
Mandibular reconstruction with a free forearm flap and reconstruction plate was associated
with higher complication rates at the recipient site and higher failure rates compared with
reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors,
14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did
not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis.
CONCLUSIONS: Reconstruction of the mandible with a free vascularized bone flap is superior
Kaakchirurgie
97
to reconstruction with a free forearm flap with a reconstruction plate. Complete dental
rehabilitation was reached in fewer than half of the surviving patients. Copyright © 2011
American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights
reserved.
Verlinden CR, Gooris PG, Becking AG. Complications in transpalatal distraction osteogenesis: a retrospective clinical study. J Oral Maxillofac Surg. 2011 Mar;69(3):899-905.
Epub 2011 Jan 13.
PURPOSE: Transpalatal distraction osteogenesis is a bone-borne technique to expand the maxilla
and has become a routine method in treating patients with transverse maxillary hypoplasia.
Limited reports concerning treatment difficulties have been published. The purpose of this
study was to investigate and categorize the short- and middle-term incidence of peri- and
postoperative difficulties (categorized by the classification of Paley in problems, obstacles, and
complications). The signs of adverse dental and periodontal effects were established at least
98
1 year after removal of the distractor. PATIENTS AND METHODS: A total of 73 patients (27 male,
46 female; mean age: 28 years; range: 9-59) that underwent bone-borne SARPE in 3 centers
were retrospectively investigated. Clinical follow-up was performed in 63 patients after an
average period of 23.9 months (range: 6-63 months). RESULTS: Twenty-seven problems (mainly
appliance related), 10 obstacles (appliance-related and asymmetric maxillary expansion), and
1 complication (premature loss of the TPD-module, due to lack of space, in a cleft patient)
occurred. Clinical examination showed minimal periodontal damage (gingival recession on
15 sites and pocket depths 4-5 mm in 11 sites). In 28.6% of the incisors radiographic signs
of external apical root resorption were seen. CONCLUSION: Bone-borne SARPE is a reliable
technique with predictable outcomes. These results suggest that bone-borne SARPE is associated
with a low incidence of dental and periodontal damage. Nevertheless, further research,
preferably in randomized controlled design, is needed to evaluate the long-term effects and
stability. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published
by Elsevier Inc. All rights reserved.
Mensink G, Karagozoglu KH, Strackee SD, van Teeseling RA, Smeele LE, Becking AG.
Autotransplantation of two maxillary premolars in a free vascularized fibula reconstructed
mandible. Int J Oral Maxillofac Surg. 2011 Feb;40(2):219-21. Epub 2010 Sep 15.
A 10-year-old female patient with a fibula transplant in her left hemimandible due to
ameloblastoma treatment was referred for combined orthodontic and surgical planning and
treatment to observe and prevent expected asymmetric facial development and malocclusion,
because the premolars and molars on the left side of the mandible were missing. The patient had
an Angle Class II malocclusion and arch length discrepancy in the upper jaw. The two second
premolars in the maxilla were transplanted into the neomandible to create occlusion on the left
side and retention for orthodontic treatment. Clinical and radiological examination 3 months
postoperatively showed good integration of both premolars without pocket formation. After
4 months, active orthodontic treatment with fixed appliances was started to create sufficient
arch space in the upper jaw for both canines to erupt and to extrude and for the transplanted
premolars in the lower jaw to rotate and align into the planned positions. This case report
demonstrates that autotransplantation of premolars into a fibula transplant can be a successful
dental rehabilitation procedure. Copyright © 2010 International Association of Oral and
Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Buijs GJ. Biodegradable plates and screws in oral and maxillofacial surgery. [S.l. : s.n.];
Heerenveen: Drukkerij van der Eems, 2011. ISBN: 9789036749664. Proefschrift
Rijksuniversiteit Groningen.
vascularized flaps for reconstruction of the mandible: complications, success, and
dental rehabilitation. J Oral Maxillofac Surg. 2011 Nov 11. [Epub ahead of print].
Verlinden CR, Gooris PG, Becking AG. Complications in transpalatal distraction
osteogenesis: a retrospective clinical study. J Oral Maxillofac Surg. 2011
Mar;69(3):899-905. Epub 2011 Jan 13.
Mensink G, Karagozoglu KH, Strackee SD, van Teeseling RA, Smeele LE, Becking
AG. Autotransplantation of two maxillary premolars in a free vascularized fibula
reconstructed mandible. Int J Oral Maxillofac Surg. 2011 Feb;40(2):219-21. Epub 2010
Sep 15.
Kaakchirurgie
99
Kindergeneeskunde
Kerngegevens zorgkern Kindergeneeskunde
• 13 kinderartsen: mw. C.D. (Coranne) Aarts-Tesselaar, dr. R.H.T. (Ron) van Beek,
dr. A.R. (Anthon) Hulsmann, M.H. (Marc) Jonkers, J. (Jaap) Kooijman, M.C. (Maarten)
Küthe, mw. dr. S.A. (Stella) de Man, P.W.J. (Paul) van Mossevelde,
mw. S.M.H.B. (Saskia) de Pont, L. (Leo) Torn, mw. dr. A.A.P.H. (Anja) Vaessen-Verberne,
mw. E.J.M. (Esther) Veldkamp, dr. H.M. (Herbert) Wering
• 3 baios
• 1 tagio
Kuethe M, Vaessen-Verberne A, Mulder P, Bindels P, van Aalderen W. Paediatric asthma
outpatient care by asthma nurse, paediatrician or general practitioner: randomised
controlled trial with two-year follow-up. Prim Care Respir J. 2011 Mar;20(1):84-91.
AIMS: For children with stable asthma, to test non-inferiority of care provided by a hospitalbased specialised asthma nurse versus a general practitioner (GP) or paediatrician. METHODS:
Randomised controlled trial evaluating standard care by a GP, paediatrician or an asthma nurse,
with two-year follow-up. RESULTS: 107 children were recruited, 45 from general practice and
62 from hospital. After two years, no significant differences between groups were found for
airway responsiveness, FEV1, asthma control, medication, school absence or parental work
absence. In the general practice group there was a significantly lower frequency of regular
review visits (‘regular’ = at least one review per six months) compared to the paediatrician
and specialised asthma nurse group, both after one year [45.7% versus 87.9% and 94.3%,
respectively, (p<0.0005)] and after two years [26.5% versus 87.9% and 75.8%, respectively,
Kindergeneeskunde
101
(p<0.0005)]. We found no significant differences in unplanned visits. In most cases the asthma
nurse was able to provide care without consultation with the paediatrician. CONCLUSION: The
degree of disease control in stable childhood asthma managed by an asthma nurse is not inferior
to traditional management by primary or secondary care physicians. The results also suggest
that a lower review frequency does not detract from good disease control.
Comment in: Prim Care Respir J. 2011 Mar;20(1):9-10.
Ermens AA, van Beek RH. Een jongetje met icterus. [A boy with jaundice]. Ned Tijdschr
Geneeskd. 2011;155:A2020.
A 1-year-old Moroccan boy was referred because of jaundice. A peripheral blood smear showed
‘blister cells’. This finding is characteristic for haemolysis caused by glucose-6-phosphate
dehydrogenase deficiency. It appeared hemolysis occurred because the boy ate fava beans. PMID:
21447212 [PubMed - indexed for MEDLINE] Koolen BB, Pijnenburg MW, Brackel HJ, Landstra
AM, van den Berg NJ, Merkus PJ, Hop WC, Vaessen-Verberne AA. Comparing Global Initiative
102
for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control
Test (ACT). Eur Respir J. 2011 Sep;38(3):561-6. Epub 2011 Mar 15. Several tools are useful
in detecting uncontrolled asthma in children. The aim of this study was to compare Global
Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and
the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with
asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication
and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled
asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines,
asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children.
The area under the curve in the receiver operating characteristic curves for C-ACT and ACT
versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT
resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT
and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly
used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with
uncontrolled asthma as defined by GINA.
Koolen BB, Pijnenburg MW, Brackel HJ, Landstra AM, van den Berg NJ, Merkus PJ, Hop WC,
Vaessen-Verberne AA. Validation of a web-based version of the asthma control test and
childhood asthma control test. Pediatr Pulmonol. 2011 Oct;46(10):941-8. Epub 2011 Apr 1.
RATIONALE: Recent guidelines focus on adjusting asthma treatment to the level of asthma
control. The availability of a web-based asthma control questionnaire offers the possibility to
assess asthma control without the need of outpatient clinic visits. The aim of this study was to
evaluate the agreement between web-based and paper-based versions of the Asthma Control Test
(ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction
with both versions. METHODS: One hundred seventy-three children with stable asthma and a
normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT
(4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite
version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paperbased) 7 days later. RESULTS: Eighty-eight children filled in the C-ACT, 68 children filled in the
ACT. Intraclass Correlation Coefficient (ICC) for web-based versus paper-based C-ACT was 0.81
(95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For webbased and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and 0.75 (95%
CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paper-based versions
was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of
patients preferred the web-based version. CONCLUSION: The web-based version of the C-ACT and
ACT is reproducible and comparable with the paper-based version in assessing asthma control.
Most children and their parents prefer the web-based version. Copyright © 2011 Wiley-Liss, Inc.
Van Wering HM, Tabbers MM, Benninga MA. Are constipation drugs effective and safe
to be used in children? A review of the literature. Expert Opin Drug Saf. 2012
Jan;11(1):71-82. Epub 2011 Jul 29.
INTRODUCTION: Functional constipation is a common and often enduring problem in childhood.
Although functional constipation is well defined by the Rome III criteria, these criteria have not
always been integrated in general practice. Early diagnosis and treatment are key factors with
respect to successful long-term outcome, as chronic constipation has a negative effect on the
quality of life and is a burden for the public healthcare system. The safety of laxatives used for
paediatric-functional constipation is based on well-designed trials carried out mostly in adults.
Therefore, we conducted a review of the literature outlining the evidence for the efficacy and
safety of laxatives used in chronic paediatric-functional constipation. AREAS COVERED: This
review clearly shows a lack of large well-designed placebo-controlled trials in children with
constipation. Therefore, any interpretation with regards to the evidence for the effectiveness or
safety of laxatives used in children is difficult and we extended the search for side effects to the
adult literature. EXPERT OPINION: In adults, new promising drugs are on the virtue of breaking
through in the treatment of chronic constipation. Carrying out well-defined placebo-controlled
trials in children should be the next step before using these drugs.
Kindergeneeskunde
103
104
Geneeskd. 2011;155:A2020.
Hulsmann AR, Bruinenberg J, van Elburg RM. Reanimatie van de pasgeborene. A & I.
2011;3:41-5.
Oranje AP, Hulsmann A, de Waard-van der Spek FB. Skin care and dermatotherapy in
neonates and infants. Review. Treatment Strategies-Paediatrics 2011; 1,:60-7.
Vaessen-Verberne AA. Comparing Global Initiative for Asthma (GINA) criteria with the
Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT). Eur Respir J.
2011 Sep;38(3):561-6. Epub 2011 Mar 15.
Koolen BB, Pijnenburg MW, Brackel HJ, Landstra AM, van den Berg NJ, Merkus PJ, Hop
WC, Vaessen-Verberne AA. Validation of a web-based version of the asthma control
test and childhood asthma control test. Pediatr Pulmonol. 2011 Oct;46(10):941-8. Epub
2011 Apr 1.
Van Wering HM, Tabbers MM, Benninga MA. Are constipation drugs effective and
safe to be used in children? A review of the literature. Expert Opin Drug Saf. 2012
Jan;11(1):71-82. Epub 2011 Jul 29.
Klinisch Chemisch Hematologisch
Laboratorium (KCHL)
Onderzoek op het gebied van borst- en prostaatkanker
Het KCHL verricht laboratoriumonderzoek op lichaamsstoffen als bloed, liquor, urine
en ontlasting. Ook onderzoekt het KCHL de bloedspiegels van de medicijnen. Het
KCHL doet bij elke transfusie vooronderzoek en zorgt dat de juiste bloedproducten
worden uitgegeven. Daarnaast ontplooit het KCHL veel wetenschappelijke
onderzoeksactiviteiten. Een van de projecten betreft een onderzoekstraject samen
met Hogeschool Avans.
dr. ir. (Monique) J.M. de Groot
Klinisch Chemisch Hematologisch Laboratorium (KCHL)
105
Publiceren over endocrinologie en hematologie draagt voor het KCHL bij aan behoud
van de opleidingsbevoegdheid en voor het Amphia Ziekenhuis aan de STZ-status
(samenwerkende topklinische opleidingsziekenhuizen). Dr. ir. Monique J.M. de Groot
geeft aan dat het KCHL het belangrijk vindt dat alle onderzoek de Amphia-speerpunten
ondersteunt, daarom wordt bijvoorbeeld onderzoek ten behoeve van de oncologie verricht.
De Groot vertelt dat het KCHL ook veel energie steekt in het opleiden van de klinisch
chemici. “De opleidingsaanpak is nogal veranderd. Dat betekent dat we af moeten tasten
welke kennis al aanwezig is. Voor ons betekent de opleiding oude en nieuwe stijl dat we
op twee manieren moeten begeleiden.”
Aandachtsgebieden
106
Klinische chemie is een erg breed vak. Hoewel iedereen van alle aspecten op de hoogte
is, is er wel een onderverdeling gemaakt van aandachtsgebieden om zo verdieping te
kunnen creëren. De Groot beschrijft de aandachtsgebieden van de verschillende collega’s.
“Marc Thelen is onze medisch manager. Hij is verantwoordelijk voor de algemene chemie.
René Idema is sterk betrokken bij bloedstolling en de preanalyse van bloedafname, een
bijzonder kritische afdeling. Hij regelt onze automatisering en heeft een bijzondere taak
verricht in het elektronisch aanvragen in EPIC. Adriaan van Gammeren focust zich op de
bloedtransfusie, point-of-care testing en DNA-onderzoek. Ton Ermens is de hoofdopleider
en doet onderzoek naar bloedarmoede en leukemie.” Zelf is De Groot plaatsvervangend
opleider. Haar aandachtsgebieden zijn endocrinologie en auto-immuniteit. Verder bepaalt
ze medicijnspiegels in samenwerking met de apotheek. De Groot promoveerde zelf op
‘lipidenstofwisseling bij infarcten’. Nu richt ze zich voornamelijk op de endocrinologie.
“Ik ben ook nog bezig met een superspecialisatie. Daarvoor ga ik een dag per week naar
Nijmegen – waar een groot bijniercentrum zit – om te leren van specialisten. We bespreken
bijzondere patiëntencasuïstiek en diagnostiek.”
Oestradiol- en testosteronbepaling
Twee veel voorkomende vormen van kanker zijn borst- en prostaatkanker. Op deze
twee gebieden verricht het KCHL onderzoek, waarvoor een bijzondere constructie is
opgezet. “Dat komt zo”, legt De Groot uit. “Voor de oestradiolbepaling bij borstkanker
en de testosteronbepaling bij prostaatkanker is een LC-MS-apparaat nodig. Liquid
Chromatography Mass Spectrometry is een hoogwaardige, gevoelige techniek om
componenten te scheiden, te identificeren en te kwantificeren. Met deze techniek kun je
de manier waarop we tot nu toe werkten – met radioactieve labels – verlaten.” De LC-MStechniek is relatief duur en het KCHL werkt daarom samen met Hogeschool Avans, die
subsidie ontvangt voor innovatieonderzoek in het beroepenveld. “Nu staat de LC-MS bij
Avans en onze mensen doen daar onderzoek samen met Avans-studenten Labtechniek.
Ook het departement Farmaceutische Wetenschappen van de Universiteit Utrecht brengt
expertise in. Een prima oplossing toch?”
Blokkeren van receptoren
Het oestradiolonderzoek richt zich op de bepaling van oestradiol in humaan serum op
een zeer laag concentratieniveau voor verbetering van het monitoren van vrouwen
met borstkanker. “Daarop is de endocriene therapie gericht, op het voorkomen dat
tumorcellen groeien. Het is echter nog een uitdaging om dat lage niveau te bereiken.”
Het prostaatkankeronderzoek is vergelijkbaar, alleen gaat het hierbij om de bepaling van
lage concentraties testosteron bij mannen. (was bijna identieke zin als bij de vrouwen).
Omdat testosteron op een hoger concentratieniveau dan oestradiol ligt, zijn er minder
storende factoren. “De status van dit onderzoek is ook nog lopende, maar we kunnen het
meten en dat kan bij oestradiol nog niet. Nu gaan we valideren of we testosteron juist en
reproduceerbaar meten.”
Derde onderzoekslijn
Inmiddels loopt er een vooraanvraag voor een derde onderzoekslijn. De Groot: “We willen
onderzoeken of tamoxifen als vorm van medicatie bij borstkankerpatiënten bij iedereen
even effectief is.” Om tamoxifen om te zetten naar de metabolieten is een enzym nodig
dat niet bij alle patiënten goed werkt. “We willen een onderscheid maken tussen goede en
slechte responders aan de hand van het metabolietenprofiel en dit vervolgens relateren aan
hun genotype.” De klinisch chemicus ervaart dat het steeds moeilijker wordt om subsidies
te ontvangen. “Terwijl toch duidelijk is dat alle drie de onderzoekslijnen zeer van belang
zijn voor patiënten.” Bovendien zijn de Avans-studenten erg enthousiast zijn over hun
deelname in het onderzoek. “En als Amphia Ziekenhuis maken wij weer gebruik van de LCMS-ervaring van Avans. Toch hopen we in een volgende investeringsaanvraag de apparatuur
zelf aan te kopen. Avans kan dan nog steeds voorwerk doen en wij passen het toe.”
Hoogwaardig kwalitatief lab
Een rechtstreeks kwaliteitsonderzoek betreft het optimaliseren van het bloedtransfusiebeleid. Hiervoor is de 4-5-6-flexnorm ingevoerd en dit is omgezet in een aanvraagformulier.
De Groot legt uit dat het formulier helpt patiënten in te delen in categorieën. “Afhankelijk
van het Hb ga je eenheden bloed uitgeven. Want meer eenheden is niet altijd beter. Het is
een ideaal formulier, dat veel discussie en verspilling voorkomt. In 2011 leverde het een
significante reductie op in bloedverbruik bij patiënten.”
Verder is het KCHL betrokken bij internationale uniformerings- en kwaliteitsprojecten
en lopen er altijd onderzoeken rondom de diagnoses van bijzondere patiëntengroepen, wat
tot interessante resultaten en informatieve publicaties kan leiden, ook voor de mensen in
opleiding. Ten slotte vindt veel onderzoek in opdracht van derden plaats (bijvoorbeeld de
107
IC) voor het bepalen van de waarde van nieuwe toepassingen van biomarkers. Het KCHL
voelt zich als ondersteunende afdeling verantwoordelijk om ook de wetenschappelijke
inspanningen van andere afdelingen te ondersteunen. Wanneer de capaciteit in het geding
komt, wordt voorrang gegeven aan projecten die aansluiten bij de Amphia-speerpunten.
Om onderzoek te stimuleren krijgen onderzoekers wetenschapsdagen toegekend. Ze hebben
dan geen telefoondienst en kunnen zich echt concentreren op onderzoeksactiviteiten.
Over de wens voor de toekomst hoeft De Groot niet lang na te denken: “We streven naar
een hoogwaardig kwalitatief lab met steeds nieuwe technieken. Dat vergt investering,
maar dan ben je altijd innovatief bezig.”
Kerngegevens zorgkern Klinisch Chemisch Hematologisch Laboratorium
• 5 klinisch chemici: dr. ir. A.A.M. (Ton) Ermens, dr. A.J. (Adriaan) van Gammeren,
mw. dr. ir. M.J.M. (Monique) de Groot, dr. R.N. (René) Idema, dr. M.H.M. (Marc) Thelen
• 2 klinisch chemici in opleiding: mw. dr. I.J.M. (Ivon) van der Linden, mw. dr. ir.
A.M.C.P. (Annemiek) Joosen
108
Lopende onderzoeken
•
•
•
•
•
Oestradiol-onderzoek
Testosteron-onderzoek
Tamoxifen-onderzoek
Uniformerings- en kwaliteitsprojecten
Ondersteuning van diverse studies van andere specialismen naar nieuwe toepassing
van biomarkers
• Patiëntencasuïstiek
BACKGROUND: Adult-type hypolactasia is caused by genetic lactase non-persistence. It is the
most common cause of lactose intolerance, which results in gastrointestinal symptoms after
ingestion of dairy products. Currently, lactose intolerance is investigated by the hydrogen breath
test (HBT), which is considered the preferred diagnostic test. Adult-type hypolactasia may also
be diagnosed by genotyping. The single nucleotide polymorphism -13910C>T, which is located
upstream of the lactase gene (LCT), is tightly associated with lactase persistence. Several other
variants, mostly in non-European populations, can also lead to lactase persistence. This study
investigated the accuracy of a modified, recently proposed algorithm which includes genotyping
for the diagnosis of adult-type hypolactasia in a patient population with unexplained abdominal
complaints. METHODS: In 126 patients with unexplained abdominal symptoms or who were
suspected to have adult-type hypolactasia, LCT genotyping by melting curve analysis on a
LightCycler was performed. Those patients with CC(-13910) genotype (indicating loss of lactase
expression) were directly referred to a dietician for a lactose-free diet. Those identified as
CT(-13910) or TT(-13910) genotype underwent a HBT. Those who tested positive for hydrogen
were also referred to a dietician for a lactose-free diet. The response to diet modification
was recorded. RESULTS: Genotype prevalences were: CC(-13910): 43 (34.1%); CT(-13910):
48 (38.1%); TT(-13910): 33 (26.2%); TG(-13915): 2 (1.6%). Eleven of 48 (23%) patients
with CT(- 3910)-genotype and 1/33 (3%) patients with TT(-13910)-genotype had a positive
hydrogen breath test. They all improved after a lactose-free diet. Four of 43 (9%) patients with
CC(- 13910)-genotype still had symptoms after a lactose-free diet. CONCLUSIONS: The results
show that lactase-genotype testing can be used as a first step to diagnose lactose intolerance
in a patient population with unexplained abdominal complaints. It accurately identifies the
group of patients sensitive to lactose, those who need further breath testing and those in whom
adult-type hypolactasia can be excluded with high probability without performing a HBT. This
algorithm would save hydrogen breath testing in more than 50% of the patients who present
with unexplained abdominal symptoms.
Ermens AA, Hoffmann JJ, Krockenberger M, Van Wijk EM. New erythrocyte and
reticulocyte parameters on CELL-DYN Sapphire: analytical and preanalytical aspects.
Int J Lab Hematol. 2011 Dec 8. [Epub ahead of print]
INTRODUCTION: Extended RBC and reticulocyte parameters are useful in diagnosing functional
iron deficiency and various other clinical conditions. The newest software of the CELLDYN Sapphire measures extended RBC and reticulocyte parameters. The aims of the present
communication were to assess the analytical aspects of these parameters compared with the
Siemens Advia 120 analyzer, to study the effect of sample aging and to briefly explore their
clinical usefulness in patients with anemia. METHODS: Blood samples were obtained from the
routine workload of two hospital laboratories and were run on Siemens Advia and Abbott
CELL-DYN Sapphire analyzers in parallel. Data analysis was performed using standard statistics.
RESULTS: In total, 1416 patient samples were analyzed. There was close correlation in microcytic
and macrocytic RBC (r(2) > 0.97) with small bias. The hypo- and hyperchromic RBC showed
reasonable correlations, Advia 120 giving higher values. Reticulocyte MCV showed acceptable
agreement, with significant proportional bias (Advia 8-9% higher). CELL-DYN Sapphire MCHr
correlated rather well with Advia CHr (r(2) > 0.91) with significant absolute bias. Remarkably,
the correlation data differed significantly between the two laboratories. It was found that
aging of EDTA samples had significant effect on most of the RBC parameters. CONCLUSIONS: The
new RBC parameters of CELL-DYN Sapphire generally correlated well with those of Advia 120,
109
although significant systematic differences were present, particularly in reticulocyte MCH and
MCV. These differences necessitate instrument-specific reference ranges and clinical decision
values. To minimize preanalytical effects, these parameters should be measured in fresh blood
samples. © 2011 Blackwell Publishing Ltd.
Geneeskd. 2011;155:A2020.
A 1-year-old Moroccan boy was referred because of jaundice. A peripheral blood smear showed
‘blister cells’. This finding is characteristic for haemolysis caused by glucose-6-phosphate
dehydrogenase deficiency. It appeared hemolysis occurred because the boy ate fava beans.
110
BACKGROUND: Persistent polyclonal B-cell lymphocytosis (PPBL) is a benign condition associated
with smoking. CASE REPORT: A 42-year-old woman was referred to an internist because of an
abnormal blood test outcome identified during routine sampling. She had no symptoms; she
had smoked for thirty pack years. Physical examination revealed no abnormalities. Laboratory
analysis showed absolute lymphocytosis. A blood smear identified binuclear (‘buttock’) cells.
The diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL) was made, with nicotine
abuse as the probable cause. The patient was advised to quit smoking. CONCLUSION: Polyclonal
B-cell lymphocytosis is a benign condition that is characterised by: (a) polyclonal increase of
B-lymphocytes in peripheral blood; (b) the presence of binuclear lymphocytes (buttock cells)
in microscopic differentiation; (c) polyclonal increase in IgM. Recognition is important for the
prevention of unnecessary diagnostic testing.
Gammeren AJ, Haperen CV, Kuypers AW. The effect of acidification and oxalate
concentration on urine calcium measurements in EQAS materials and patient samples.
Clin Chem Lab Med. 2011 Sep 16. [Epub ahead of print]
BACKGROUND: An increase in urine calcium compared to the consensus value was observed
in some urine samples of the Dutch External Quality Assessment Scheme (EQAS). It appeared
that the increase was due to the addition of oxalate by the EQAS organizers and preanalytical
acidification of the samples by some of the participants. Because of this observation, the effect
of urine acidification on urine calcium level in EQAS and patient samples with added oxalate
was investigated. METHODS: Twenty-four EQAS urine samples and 20 patient urine samples
were subject to recovery measurements of urine calcium before and after addition of sodium
oxalate and acidification. RESULTS: Differences in urine calcium between acidified and nonacidified samples up to 30.9% have been observed in EQAS samples with added oxalate. Patient
samples show differences up to 80%. Differences between acidified and non-acidified samples
are minimal for low calcium oxalate levels but increase with higher levels. Samples without
added oxalate show equal urine calcium results between acidified and non-acidified samples.
CONCLUSIONS: Urine calcium results are decreased in non-acidified samples with an excess of
oxalate. In case of hyper-oxaluria, acidification of patient urine collections and EQAS samples is
recommended for correct urine calcium values.
Van der Linden IJ, de Groot MJ, de Jong NC, Bozkurt Z, Cobbaert CM The diagnostic
performance of allergen-molecules in comparison to allergen-extracts. Clin Chem Lab Med.
2011 Oct 6. [Epub ahead of print]
BACKGROUND: This study evaluated the diagnostic performance of naturally purified allergenmolecules compared to that of allergen-extracts for house dust mite, cat dander epithelium
and dog dander. METHODS: In vitro tests for allergen-specific IgE were performed on the
IMMULITE(®) 2000 in serum samples from 66 allergic patients. RESULTS: House dust mite:
specificity for the allergen-extract (D1) and the allergen-molecules (nDer p 1, nDer f 1, nDer p
2 and nDer f 2) is comparable. The allergen-extract has a significantly higher sensitivity (100%)
and total agreement (TA) (93%) relative to sensitivity (57%-70%) and TA (76%-81%) of the
individual allergen-molecules. Cat dander epithelium: sensitivity (90%), specificity (96%) and
TA (94%) of the allergen-molecule (nFel d 1) are comparable to those of the allergen-extract
(E1). Dog dander: The allergen-molecule (nCan d 1) and allergen-extract (E5) have comparable
specificity and TA. The allergen-extract has a lower sensitivity (52%) than the allergen-molecule
(71%), although not significant (p=0.125). CONCLUSIONS: There is no diagnostic benefit of
using allergen-molecules instead of allergen-extracts for initial allergy screening on cat dander
epithelium and dog dander. However, use of these allergen-molecules might contribute to better
standardization of the specific IgE tests. The studied allergen-molecules for house dust mite are
of minor diagnostic value, because of loss of sensitivity.
Albersen A, Kemper-Proper E, Thelen MH, Kianmanesh Rad NA, Hoedemaeker RF,
Boesten LS. A case of consistent discrepancies between urine and blood human chorionic
gonadotropin measurements. Clin Chem Lab Med. 2011 Jun;49(6):1029-32. Epub 2011
Mar 17.
111
BACKGROUND: Our laboratory was confronted with two successive urine samples from a single
patient which tested positive for human chorionic gonadotropin (hCG) when tested with
both qualitative and quantitative assays, combined with no detectable hCG in corresponding
plasma samples. METHODS: Serial dilution and recovery experiments were performed in order
to investigate the presence of interfering substances or a high-dose hook effect. The ovarian
cysts that were removed from this patient were immunohistochemically stained using polyclonal
anti-human hCG antibodies. Furthermore, a urine sample was sent to the USA hCG Reference
Service for hCG variant analysis. RESULTS: Dilution and recovery experiments in urine and
plasma samples were unremarkable. The biopsy stained negative for human hCG and free
ß-subunit. hCG isoform analysis in the urine sample revealed that approximately 87.5% of the
immunoreactive hCG lacked the ß-subunit C-terminal peptide (CTP). CONCLUSIONS: We report a
rare case in which two successive urine samples test positive for hCG whereas in corresponding
plasma samples hCG is undetectable. The majority of the total hCG contained a degraded form of
ß-subunit that lacks the CTP. This hCG variant, possibly of pituitary origin, is thought to have
an extreme fast clearance rate possibly explaining the discordance between the hCG results in
urine and plasma samples.
112
Geneeskd. 2011;155:A2020.
Van der Linden JM, Ligthart PC, Folman CC, van Driel MW, Ermens AA, van Gammeren AJ.
Anti-Landsteiner-Wiener (anti-LW) ‘in disguise’. Tijdschr Bloedtransfusie
2011;4(4):138-41.
2011;4(4):138-41.
performance of allergen-molecules in comparison to allergen-extracts. Clin Chem Lab
Med. 2011 Oct 6. [Epub ahead of print]
Albersen A, Kemper-Proper E, Thelen MH, Kianmanesh Rad NA, Hoedemaeker RF, Boesten
LS. A case of consistent discrepancies between urine and blood human chorionic
Mar 17.
113
Klinische fysica
Kerngegevens zorgkern Klinische fysica
• 3 klinisch fysici: mw. ir. A.N. (Anouk) de Jong, ir. E. (Egon) Scheepers,
dr. R.L. (Richard) Kamman
115
Tossici-Bolt L, Dickson JC, Sera T, de Nijs R, Bagnara MC, Jonsson C, Scheepers E, Zito
F, Seese A, Koulibaly PM, Kapucu OL, Koole M, Raith M, George J, Lonsdale MN, Münzing
W, Tatsch K, Varrone A. Calibration of gamma camera systems for a multicentre European
¹²³I-FP-CIT SPECT normal database. Eur J Nucl Med Mol Imaging. 2011 Aug;38(8):1529-40.
Epub 2011 Apr 6
PURPOSE: A joint initiative of the European Association of Nuclear Medicine (EANM)
Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of
[(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls.
This study describes the characterization and harmonization of the imaging equipment of the
institutions involved. METHODS: (123)I SPECT images of a striatal phantom filled with striatal to
background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute
ratios measured from aliquots. The images were reconstructed by a core lab using ordered
subset expectation maximization (OSEM) without corrections (NC), with attenuation correction
only (AC) and additional scatter and septal penetration correction (ACSC) using the triple
energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR),
was measured using the “Southampton” methodology that accounts for the partial volume
effect and compared against the actual values obtained from the aliquots. Camera-specific
recovery coefficients were derived from linear regression and the error of the measurements
was evaluated using the coefficient of variation (COV). RESULTS: The relationship between
measured and actual sSBRs was linear across all systems. Variability was observed between
Klinische fysica
different manufacturers and, to a lesser extent, between cameras of the same type. The NC
and AC measurements were found to underestimate systematically the actual sSBRs, while the
ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range
69-89%, ACSC range 87-116%). The COV improved from 46% (NC) to 32% (AC) and to 14%
(ACSC) (p < 0.001). CONCLUSION: A satisfactory linear response was observed across all cameras.
Quantitative measurements depend upon the characteristics of the SPECT systems and their
calibration is a necessary prerequisite for data pooling. Together with accounting for partial
volume, the correction for scatter and septal penetration is essential for accurate quantification.
116
Kamman RL. De ICT-afdeling als commandocentrum. In: De nieuwe ICT. [s.l.] : iSense.
2011:22-5.
Tossici-Bolt L, Dickson JC, Sera T, de Nijs R, Bagnara MC, Jonsson C, Scheepers E, Zito F,
Seese A, Koulibaly PM, Kapucu OL, Koole M, Raith M, George J, Lonsdale MN, Münzing
W, Tatsch K, Varrone A. Calibration of gamma camera systems for a multicentre
European ¹²³I-FP-CIT SPECT normal database. Eur J Nucl Med Mol Imaging. 2011
Aug;38(8):1529-40. Epub 2011 Apr 6
Laboratorium voor Microbiologie
en Infectiepreventie
Kerngegevens zorgkern Laboratorium voor Microbiologie en
Infectiepreventie
• 3 medisch microbiologen: prof.dr. J.A.J.W. (Jan) Kluytmans, J.H. (Jan) Marcelis,
P.H.J. (Peter) van Keulen, dr. G.J. (Jolanda) Hooydonk-Elving
• 2 consultants infectiepreventie: mw. drs. M.M.L. van Rijen, mw. dr. L.E. Willemsen
• 4 adviseurs infectiepreventie: H.P.M. Coertjens, mw. A.B. Moen, mw. Y.J.A.M. Hendriks,
mw. V.A.T.C. Weterings
• 1 adviseur infectiepreventie in opleiding: mw. C.M. van Leest
• 2 aos
Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. Transmissibility of
livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch
hospitals. Clin Microbiol Infect. 2011 Feb;17(2):316-9.
We quantified nosocomial transmission rates of sequence type (ST) 398 methicillin-resistant
Staphylococcus aureus (MRSA) (an emerging livestock-associated MRSA clone) and non-ST398
MRSA isolates in patients hospitalized without infection control measures in 51 Dutch hospitals.
Identification of 174 index patients initiated 139 post-exposure screenings of 9925 persons.
There were 65 genotype-confirmed secondary cases (three and 62 for ST398 and non-ST398
MRSA, respectively), yielding a relative transmission risk for ST398 MRSA of 0.28 (95% CI
0.09-0.90), which was not sensitive to adjustment for duration of hospitalization at time of
detection. Nosocomial transmission of ST398 MRSA is 72% less likely than that of non-ST398
Laboratorium voor Microbiologie en Infectiepreventie
117
MRSA strains. © 2010 The Authors. Journal Compilation © 2010 European Society of Clinical
Microbiology and Infectious Diseases. PMID: 20459436 [PubMed - indexed for MEDLINE] Verkade
E, Verhulst C, van Cleef B, Kluytmans J. Clinical evaluation of Bio-Rad MRSASelect™ medium
for the detection of livestock-associated methicillin-resistant Staphylococcus aureus. Eur J Clin
Microbiol Infect Dis. 2011 Jan;30(1):109-12. Bio-Rad MRSASelect™ medium was evaluated for
its ability to recover methicillin-resistant Staphylococcus aureus (MRSA) from nasal samples of
pig farmers and their household members. In total, 257 samples were inoculated on Bio-Rad
MRSASelect™ medium with and without broth enrichment and on bioMérieux MRSA ID with
broth enrichment. A sample was considered to be positive if at least one of the media grew
MRSA. The sensitivity of Bio-Rad MRSASelect™ medium without broth enrichment was 63.9%.
With broth enrichment, the sensitivity increased to 98.4%. The specificity was 95.4% both with
and without broth enrichment. In conclusion, Bio-Rad MRSASelect™ medium as well as MRSA
ID medium are reliable methods to detect MRSA carriage when used in combination with broth
enrichment. The directly inoculated MRSASelect™ medium was statistically significantly less
sensitive than the two media after broth enrichment.
118
PMCID: PMC2998642
Lackner M, De Man FH, Eygendaal D, Wintermans RG, Kluytmans JA, Klaassen CH, Meis JF.
Severe prosthetic joint infection in an immunocompetent male patient due to a therapy
refractory Pseudallescheria apiosperma. Mycoses. 2011 Oct;54 Suppl 3:22-7.
Prosthetic joint infections (PJI) are rarely due to fungal agents and if so they are mainly caused
by Candida strains. This case represents a PJI caused by a multi-drug resistant Pseudallescheria
apiosperma, with poor in vivo response to itraconazole and voriconazole. This case differs
also by the way of infection, since the joint infection did not follow a penetrating trauma. In
the majority of cases, Scedosporium extremity infections remain local in immunocompetent
individuals. We report a persistent joint infection with multiple therapeutic failures, and
subsequent amputation of the left leg. Detailed clinical data, patient history, treatment regime
and outcome of a very long-lasting (>4 years) P. apiosperma prosthetic knee infection in an
immunocompetent, 61-year-old male patient are presented with this case. The patient was
finally cured by the combination of multiple and extensive surgical interventions and prolonged
antifungal combination therapy with voriconazole and terbinafine. © 2011 Blackwell Verlag
GmbH.
Melsen WG, de Smet AM, Kluytmans JA, Bonten MJ; on behalf of the Dutch SOD-SDD
Trialists’ Group. Selective decontamination of the oral and digestive tract in surgical versus
non-surgical patients in intensive care in a cluster-randomized trial. Br J Surg.
2012 Feb;99(2):232-237. Epub 2011 Oct 24.
BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal
decontamination (SOD) are effective in improving survival in patients under intensive care. In
this study possible differential effects in surgical and non-surgical patients were investigated.
METHODS: This was a post hoc subgroup analysis of data from a cluster-randomized multicentre
trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical
and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of
mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and
bacteraemia rates were secondary outcomes. RESULTS: The subgroup analyses included a total of
2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios
(ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86
(95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095)
respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were
significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared
with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in
non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6
per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to
treat of 18. CONCLUSION: Subgroup analysis found similar effects of SDD in reducing mortality
in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical
patients. The hypothesis-generating findings mandate investigation into mechanisms between
different ICU populations. Copyright © 2011 British Journal of Surgery Society Ltd. Published by
John Wiley & Sons, Ltd. Copyright © 2011 British Journal of Surgery Society Ltd. Published by
John Wiley & Sons, Ltd.
Overdevest IT, Willemsen I, Elberts S, Verhulst C, Rijnsburger M, Savelkoul P, Kluytmans
JA. Evaluation of the DiversiLab typing method in a multicenter study assessing horizontal
spread of highly resistant gram-negative rods. J Clin Microbiol. 2011 Oct;49(10):3551-4.
Epub 2011 Aug 24.
The worldwide prevalence of highly resistant Gram-negative rods (HR-GNR) is increasing
rapidly. Reliable typing methods are needed to detect and control outbreaks and to monitor the
effectiveness of infection control programs in endemic situations. In this study, we investigated
the performance of the DiversiLab typing method in comparison with the amplified fragment
length polymorphism (AFLP) typing method. Six hundred fifty-three HR-GNR isolates, which
were obtained during a 6-month prospective survey in 18 Dutch hospitals, were typed by AFLP
and DiversiLab. Subsequently, the sensitivity and specificity of DiversiLab were calculated, using
119
AFLP as the reference method. In addition, results were compared by means of epidemiological
linkage, and Cohen’s kappa for agreement was calculated. DiversiLab considered significantly
more isolates (275) to belong to a cluster than AFLP (198) (P < 0.001). In direct comparison,
the sensitivity was 83.8%, and the specificity was 78.6%. When epidemiological linkage was
included in the analysis, DiversiLab considered eight isolates as secondary cases, which were
considered unique in AFLP. Only two secondary cases, according to AFLP, were missed by
DiversiLab. This results in a kappa for agreement of 0.985. In daily practice, a typing method
has to be used in combination with epidemiological information. When this was done, DiversiLab
was shown to be a reliable method for the typing of HR-GNR. This, in combination with the ease
of use and the speed, makes DiversiLab an appropriate method for screening in routine clinical
practice. When a cluster is suspected and the consequences of these findings are substantial, a
confirmatory analysis should be performed.
PMCID: PMC3187329
120
Bode LG, Wertheim HF, Kluytmans JA, Bogaers-Hofman D, Vandenbroucke-Grauls, CM,
Roosendaal R, Troelstra A, Box AT, Voss A, van Belkum A, Verbrugh HA, Vos MC. Sustained
low prevalence of meticillin-resistant Staphylococcus aureus upon admission to hospital in
The Netherlands. J Hosp Infect. 2011 Nov;79(3):198-201. Epub 2011 Jul 16.
The prevalence of meticillin-resistant Staphylococcus aureus (MRSA) carriage at hospital
admission in The Netherlands was 0.03% in 1999-2000. The aim of the present study was to
assess whether the prevalence of MRSA carriage in The Netherlands has changed over the last
few years. In five Dutch hospitals, 6496 unique patients were screened for nasal S. aureus
carriage at hospital admission by microbiological culture between 1 October 2005 and 7 June
2007. In total, 2036 of 6496 (31.3%) patients carried S. aureus in their nose, and seven of
6496 (0.11%) patients were nasal carriers of MRSA. Compared with 1999-2000, the prevalence
of MRSA carriage in the Dutch population at hospital admission has increased more than three
fold; however, this increase was not significant (P=0.06, Fisher’s exact test). This prevalence
is still among the lowest in the world, probably as a result of the stringent Dutch infection
control policy, and the restrictive use of antibiotics in The Netherlands. Copyright © 2011
The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Overdevest I, Willemsen I, Rijnsburger M, Eustace A, Xu L, Hawkey P, Heck M, Savelkoul P,
Vandenbroucke-Grauls C, van der Zwaluw K, Huijsdens X, Kluytmans J. Extended-spectrum
ß-lactamase genes of Escherichia coli in chicken meat and humans, The Netherlands.
Emerg Infect Dis. 2011 Jul;17(7):1216-22.
We determined the prevalence and characteristics of extended-spectrum ß-lactamase (ESBL)
genes of Enterobacteriaceae in retail chicken meat and humans in the Netherlands. Raw
meat samples were obtained, and simultaneous cross-sectional surveys of fecal carriage were
performed in 4 hospitals in the same area. Human blood cultures from these hospitals that
contained ESBL genes were included. A high prevalence of ESBL genes was found in chicken
meat (79.8%). Genetic analysis showed that the predominant ESBL genes in chicken meat
and human rectal swab specimens were identical. These genes were also frequently found in
human blood culture isolates. Typing results of Escherichia coli strains showed a high degree
of similarity with strains from meat and humans. These findings suggest that the abundant
presence of ESBL genes in the food chain may have a profound effect on future treatment
options for a wide range of infections caused by gram-negative bacteria.
Ammerlaan HS, Kluytmans JA, Berkhout H, Buiting A, de Brauwer EI, van den Broek PJ,
van Gelderen P, Leenders SA, Ott A, Richter C, Spanjaard L, Spijkerman IJ, van Tiel FH,
Voorn GP, Wulf MW, van Zeijl J, Troelstra A, Bonten MJ; MRSA Eradication Study Group.
Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness of a
national guideline. J Antimicrob Chemother. 2011 Oct;66(10):2409-17.
BACKGROUND: We evaluated the effectiveness of eradication of methicillin-resistant
Staphylococcus aureus (MRSA) carriage in the Netherlands after the introduction of a guideline
in 2006. The guideline distinguishes complicated (defined as the presence of MRSA infection,
skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage)
and uncomplicated carriage (not meeting criteria for complicated carriage). Mupirocin nasal
ointment and chlorhexidine soap solution are recommended for uncomplicated carriers and the
same treatment in combination with two oral antibiotics for complicated carriage. METHODS: A
prospective cohort study was performed in 18 Dutch centres from 1 October 2006 until 1 October
2008. RESULTS: Six hundred and thirteen MRSA carriers underwent one or more decolonization
treatments during the study period, mostly after hospital discharge. Decolonization was
achieved in 367 (60%) patients with one eradication attempt and ultimately 493 (80%)
patients were decolonized, with a median time until decolonization of 10 days (interquartile
range 7-43 days). Three hundred and twenty-seven (62%) carriers were treated according to
the guideline, which was associated with an absolute increase in treatment success of 20%
[from 45% (91/203) to 65% (214/327)]. CONCLUSIONS: Sixty percent of MRSA carriers were
successfully decolonized after the first eradication attempt and 62% were treated according to
the guideline, which was associated with an increased treatment success.
PMID: 21719473[PubMed - in process]
121
Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of
treatment failure. J Antimicrob Chemother. 2011 Oct;66(10):2418-24.
BACKGROUND: Using data from an observational study in which the effectiveness of a guideline
for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we
identified variables that were associated with treatment failure. METHODS: A multivariate logistic
regression model was performed with subgroup analyses for uncomplicated and complicated
MRSA carriage (the latter including MRSA infection, skin lesions, foreign-body material,
mupirocin resistance and/or exclusive extranasal carriage) and for those treated according to
the guideline (i.e. mupirocin nasal ointment and chlorhexidine soap solution for uncomplicated
carriage, in combination with two oral antibiotics for complicated carriage). RESULTS: Six
hundred and thirteen MRSA carriers were included, of whom 333 (54%) had complicated carriage;
327 of 530 patients (62%) with known complexity of carriage were treated according to the
122
guideline with an absolute increase in treatment success of 20% (95% confidence interval
12%-28%). Among those with uncomplicated carriage, guideline adherence [adjusted odds ratio
(OR(a)) 7.4 (1.7-31.7)], chronic pulmonary disease [OR(a) 44 (2.9-668)], throat carriage [OR(a)
2.9 (1.4-6.1)], perineal carriage [OR(a) 2.2 (1.1-4.4)] and carriage among household contacts
[OR(a) 5.6 (1.2-26)] were associated with treatment failure. Among those with complicated
carriage, guideline adherence was associated with treatment success [OR(a) 0.2 (0.1-0.3)],
whereas throat carriage [OR(a) 4.4 (2.3-8.3)] and dependence in activities of daily living [OR(a)
3.6 (1.4-8.9)] were associated with failure. CONCLUSIONS: Guideline adherence, especially
among those with complicated MRSA carriage, was associated with treatment success. Adding
patients with extranasal carriage or dependence in daily self-care activities to the definition of
complicated carriage, and treating them likewise, may further increase treatment success.
Hetem DJ, de Ruiter SC, Buiting AG, Kluytmans JA, Thijsen SF, Vlaminckx BJ, Wintermans
RG, Bonten MJ, Ekkelenkamp MB. Preventing Staphylococcus aureus bacteremia and
sepsis in patients with Staphylococcus aureus colonization of intravascular catheters:
a retrospective multicenter study and meta-analysis. Medicine (Baltimore).
2011 Jul;90(4):284-8.
Two previous studies in tertiary care hospitals identified Staphylococcus aureus colonization of
intravascular (IV) catheters as a strong predictor of subsequent S. aureus bacteremia (SAB), even
in the absence of clinical signs of systemic infection. Bacteremia was effectively prevented by
timely antibiotic therapy. We conducted this study to corroborate the validity of these findings
in non-university hospitals.Using the laboratory information management systems of the clinical
microbiology departments in 6 Dutch hospitals, we identified patients who had IV catheters from
which S. aureus was cultured between January 1, 2003, and December 31, 2008. Patients with
demonstrated SAB between 7 days before catheter removal and 24 hours after catheter removal
were excluded. We extracted clinical and demographic patient data from the patients’ medical
records. The primary risk factor was initiation of anti-staphylococcal antibiotic therapy within
24 hours, and the primary endpoint was SAB >24 hours after IV catheter removal. Subsequently,
we performed a systematic review and meta-analysis of all observational studies evaluating the
effect of antibiotic therapy for S. aureus IV catheter tip colonization.In the current study, 18 of
the 192 included patients developed subsequent SAB, which was associated with not receiving
antibiotic therapy within 24 hours (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.1-15.6)
and with documented exit-site infection (OR, 3.3; 95% CI, 1.2-9.3). When we combined these
results with results of a previous study in a university hospital, a third risk factor was also
associated with subsequent SAB, namely corticosteroid therapy (OR, 2.9; 95% CI, 1.3-6.3). We
identified 3 other studies, in addition to the present study, in a systematic review. In the metaanalysis of these studies, antibiotic therapy yielded an absolute risk reduction of 13.6% for
subsequent SAB. The number needed to treat to prevent 1 episode of SAB was 7.4. We conclude
that early initiation of antibiotic therapy for IV catheters colonized with S. aureus prevents
subsequent SAB.
Platteel TN, Stuart JW, Voets GM, Scharringa J, van de Sande N, Fluit AC, Leverstein-Van
Hall MA; ESBL national surveillance working group* [ Kluytmans J et al...] Evaluation
of a commercial microarray as a confirmation test for the presence of extended-spectrum
ß-lactamases in isolates from the routine clinical setting. Clin Microbiol Infect.
2011 Sep;17(9):1435-8.
Since the diagnostic characteristics of the Check-KPC ESBL microarray as a confirmation test
on isolates obtained in a routine clinical setting have not been determined, we evaluated the
microarray in a random selection of 346 clinical isolates with a positive ESBL screen test (MIC
>1 mg/L for cefotaxime or ceftazidime or an ESBL alarm from the Phoenix or Vitek-2 expert
system) collected from 31 clinical microbiology laboratories in the Netherlands in 2009. Using
sequencing as the reference method the sensitivity of the microarray was 97% (237/245),
the specificity 98% (97/99), the positive predictive value 99% (237/239) and the negative
predictive value 92% (97/105). *Collaborators (41): Andriesse G, Arends JP, Bakker LJ, Bernards
ST, Bonten MJ, Buiting AG, Cohen JW, van Dam AP, Diederen BM, Fleer A, Fluit AC, van
Griethuysen A, Grundmann H, Hendrickx BG, Horrevorts AM, Kluytmans JA, Leverstein-van Hall
MA, Mascini EM, Moffie BG, de Neeling AJ, Platteel TN, Sabbe LJ, van de Sande N, Schapendonk
CM, Scharringa J, Schellekens JF, Sebens FW, Stals FS, Sturm P, Thijsen SF, Verduin K, Verhoef L,
123
Vlaminckx BJ, Voets GM, Vogels WH, Vreede RW, Waar K, Wagenvoort HH, Wever PC, Wintermans
RG, Wolfhagen MJ. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European
Society of Clinical Microbiology and Infectious Diseases.
Willemsen I, Overdevest I, Al Naiemi N, Rijnsburger M, Savelkoul P, Vandenbroucke-Grauls
C, Kluytmans J; TRIANGLe Study Group. New diagnostic microarray (Check-KPC ESBL) for
detection and identification of extended-spectrum beta-lactamases in highly resistant
Enterobacteriaceae. J Clin Microbiol. 2011 Aug;49(8):2985-7.
The performance of a microarray for the detection of extended-spectrum beta-lactamases was
determined on a collection of 638 highly resistant members of the family Enterobacteriaceae
collected from patients in 18 hospitals in The Netherlands. The microarray had a significantly
higher specificity than the phenotypic assays. It also detects carbapenemases and characterizes
the resistance genes, providing epidemiological insight. Collaborators (14)*: Lommerse E,
Spanjaard L, Vlaminckx B, Voss A, Wulf M, Vos M, Wintermans R, Andriesse G, van Zeijl J, van
124
der Vorm E, Buiting A, Sturm P, Blok H, Troelstra A.
PMID:21653759 [PubMed - indexed for MEDLINE]
PMCID: PMC3147782
Wassenberg MW, Kluytmans JA, Bosboom RW, Buiting AG, van Elzakker EP, Melchers WJ,
Thijsen SF, Troelstra A, Vandenbroucke-Grauls CM, Visser CE, Voss A, Wolffs PF, Wulf MW,
van Zwet AA, de Wit GA, Bonten MJ. Rapid diagnostic testing of methicillin-resistant
Staphylococcus aureus carriage at different anatomical sites: costs and benefits of less
extensive screening regimens. Clin Microbiol Infect. 2011 Nov;17(11):1704-10.
Multiple body site screening and pre-emptive isolation of patients at risk for methicillinresistant Staphylococcus aureus (MRSA) carriage are considered essential for control of
nosocomial spread. The relative importance of extranasal screening when using rapid diagnostic
testing (RDT) is unknown. Using data from a multicentre study evaluating BD GeneOhm™
MRSA PCR (IDI), Xpert MRSA (GeneXpert) and chromogenic agar, added to conventional
cultures, we determined cost-effectiveness assuming isolation measures would have been based
on RDT results of different hypothetical screening regimes. Costs per isolation day avoided
were calculated for regimes with single or less extensive multiple site RDT, regimes without
conventional back-up cultures and when PCR would have been performed with pooling of
swabs. Among 1764 patients at risk, MRSA prevalence was 3.3% (n = 59). In all scenarios the
negative predictive value is above 98.4%. With back-up cultures of all sites as a reference, the
costs per isolation day avoided were €15.19, €30.83 and €45.37 with ‘nares only’ screening
using chromogenic agar, IDI and GeneXpert, respectively, as compared with €19.95, €95.77
and €125.4, per isolation day avoided when all body sites had been screened. Without back-up
cultures costs per isolation day avoided using chromogenic agar would range from €9.24 to
€76.18 when costs per false-negative RDT range from €5000 up to €50 000; costs for molecular
screening methods would be higher in all scenarios evaluated. In conclusion, in a low endemic
setting chromogenic agar screening added to multiple site conventional cultures is the most
cost-effective MRSA screening strategy. © 2011 The Authors. Clinical Microbiology and Infection
© 2011 European Society of Clinical Microbiology and Infectious Diseases.
Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J, Voets GM, van den Munckhof MP,
van Essen-Zandbergen A, Platteel T, Fluit AC, van de Sande-Bruinsma N, Scharinga J,
Bonten MJ, Mevius DJ; National ESBL surveillance group* [ Kluytmans JA et al..]. Dutch
patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains.
Clin Microbiol Infect. 2011 Jun;17(6):873-80.
Intestinal carriage of extended-spectrum beta-lactamase (ESBL) -producing bacteria in foodproducing animals and contamination of retail meat may contribute to increased incidences
of infections with ESBL-producing bacteria in humans. Therefore, distribution of ESBL genes,
plasmids and strain genotypes in Escherichia coli obtained from poultry and retail chicken
meat in the Netherlands was determined and defined as ‘poultry-associated’ (PA). Subsequently,
the proportion of E. coli isolates with PA ESBL genes, plasmids and strains was quantified in
a representative sample of clinical isolates. The E. coli were derived from 98 retail chicken
meat samples, a prevalence survey among poultry, and 516 human clinical samples from
31 laboratories collected during a 3-month period in 2009. Isolates were analysed using an
ESBL-specific microarray, sequencing of ESBL genes, PCR-based replicon typing of plasmids,
plasmid multi-locus sequence typing (pMLST) and strain genotyping (MLST). Six ESBL genes
were defined as PA (bla(CTX-M-1) , bla(CTX-M-2) , bla(SHV-2) , bla(SHV-12) , bla(TEM-20) ,
bla(TEM-52) ): 35% of the human isolates contained PA ESBL genes and 19% contained PA ESBL
genes located on IncI1 plasmids that were genetically indistinguishable from those obtained
from poultry (meat). Of these ESBL genes, 86% were bla(CTX-M-1) and bla(TEM-52) genes,
which were also the predominant genes in poultry (78%) and retail chicken meat (75%). Of the
retail meat samples, 94% contained ESBL-producing isolates of which 39% belonged to E. coli
genotypes also present in human samples. These findings are suggestive for transmission of
ESBL genes, plasmids and E. coli isolates from poultry to humans, most likely through the food
chain. *Collaborators (84): Andriesse G, Arends JP, Bernards ST, Bonten MJ, De Brauwer EI,
Buiting AG, Cohen Stuart JW, van Dam AP, Diederen BM, Dorigo-Zetsma JW, Fleer A, Fluit AC,
van Griethuysen A, Grundmann H, Hendrickx BG, Horrevorts AM, Kluytmans JA, Leversteinvan Hall MA, Mascini EM, Moffie B, de Neeling AJ, Platteel TN, Sabbe LJ, van de Sande N,
Schapendonk CM, Scharringa J, Schellekens JF, Sebens W, Stals FS, Sturm P, Thijssen SF, Tjhie
125
JT, Verhoef L, Vlaminckx BJ, Voets GM, Vogels WH, Vreede RW, Waar K, Wever PC, Wintermans
RG, Wolfhagen MJ, Leverstein-van Hall MA, Cohen Stuart JW, Fluit AC, Voets GM, Scharringa
J, Schapendonk CM, Platteel TN, Bonten MJ, van Dam AP, Andriesse G, Kluytmans JA, Vreede
RW, Sebens FW, Sabbe LJ, Schellekens JF, Arends JP, Grundmann H, Dorigo-Zetsma JW, Waar
K, Vlaminckx BJ, Horrevorts AM, Sturm P, Stals FS, Wintermans RG, Moffie BG, Hendrickx BG,
Buiting AG, Verhoef L, Tjhie HT, Wolfhagen MJ, Diederen BM, Thijssen SF, Mascini EM, van
Griethuysen A, Bosch D, Wever PC, Fleer A, De Brauwer EI, Bernards AT, Leverstein- van Hall MA,
de Sande-Bruinsma N, Grundmann H, de Neeling AJ. 2011 The Authors. Clinical Microbiology and
Infection; 2011 European Society of Clinical Microbiology and Infectious Diseases.
126
Willemsen I, Elberts S, Verhulst C, Rijnsburger M, Filius M, Savelkoul P, Kluytmans J,
Lommerse E, Spanjaard L, Vlaminckx B, Vos A, Wulf M, Vos M, Wintermans R, Andriesse
G, van Zeijl J, van der Vorm E, Buiting A, Sturm P, Blok H, Troelstra A, Kaiser A,
Vandenbroucke-Grauls C. Highly resistant gram-negative microorganisms: incidence
density and occurrence of nosocomial transmission (TRIANGLe Study). Infect Control Hosp
Epidemiol. 2011 Apr;32(4):333-41.
OBJECTIVES: The objectives of this study were to determine the incidence density and the
occurrence of horizontal spread of highly resistant gram-negative rods (HR-GNRs) in Dutch
hospitals. The factors that influence these outcome measures were also investigated. METHODS:
All patients with HR-GNRs, as determined by sample testing, who were hospitalized in 1 of
18 hospitals during a 6-month period (April through October 2007) were included in this study.
For all available isolates, the species was identified, susceptibility was determined (including
the presence of extended-spectrum ß-lactamases [ESBLs]), and molecular typing was performed.
On the basis of a combination of species identification, molecular typing, and epidemiological
data, the occurrence of nosocomial transmission was determined. RESULTS: The mean incidence
density of patients with HR-GNRs was 55 per 100,000 patient-days (cumulative incidence, 39 per
10,000 patients admitted). A facility being a university hospital was a statistically significant
(P = .03) independent determinant of a higher incidence of patients with HR-GNRs. The majority
of HR-GNR isolates were ESBL producers. The adjusted transmission index-the ratio between
secondary and primary cases-in the participating hospitals ranged from 0.0 to 0.2. The overall
adjusted transmission index of HR-GNRs was 0.07. No determinants for a higher transmission
index were identified. DISCUSSION: The nosocomial transmission rate of HR-GNRs was relatively
low in all hospitals where well-established transmission-based precautions were used. The
incidence density of patients with HR-GNRs was higher in university hospitals, probably due to
the patient population and the complexity of the care provided.
De Smet AM, Kluytmans JA, Blok HE, Mascini EM, Benus RF, Bernards AT, Kuijper EJ,
Leverstein-van Hall MA, Jansz AR, de Jongh BM, van Asselt GJ, Frenay IH, Thijsen SF,
Conijn SN, Kaan JA, Arends JP, Sturm PD, Bootsma MC, Bonten MJ. Selective digestive
tract decontamination and selective oropharyngeal decontamination and antibiotic
resistance in patients in intensive-care units: an open-label, clustered group-randomised,
crossover study. Lancet Infect Dis. 2011 May;11(5):372-80.
BACKGROUND: Previously, we assessed selective digestive tract decontamination (SDD) and
selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in
patients in intensive-care units. In this analysis, we aimed to assess effectiveness of these
interventions for prevention of respiratory tract colonisation and bacteraemia with highly
resistant microorganisms acquired in intensive-care units. METHODS: We did an open-label,
clustered group-randomised, crossover study in 13 intensive-care units in the Netherlands
between May, 2004, and July, 2006. Participants admitted to intensive-care units with an
expected duration of mechanical ventilation of more than 48 h or an expected stay of more
than 72 h received SOD (topical tobramycin, colistin, and amphotericin B in the oropharynx),
SDD (SOD antibiotics in the oropharynx and stomach plus 4 days’ intravenous cefotaxime), or
standard care. The computer-randomised order of study regimens was applied by an independent
clinical pharmacist who was masked to intensive-care-unit identity. We calculated crude odds
ratios (95% CI) for rates of bacteraemia or respiratory tract colonisation with highly resistant
microorganisms in patients who stayed in intensive-care units for more than 3 days (ie, acquired
infection). This trial is registered at http://isrctn.org, number ISRCTN35176830. FINDINGS: Data
were available for 5927 (>99%) of 5939 patients, of whom 5463 (92%) were in intensive-care
units for more than 3 days. 239 (13%) of 1837 patients in standard care acquired bacteraemia
after 3 days, compared with 158 (9%) of 1758 in SOD (odds ratio 0·66, 95% CI 0·53-0·82),
and 124 (7%) of 1868 in SDD (0·48, 0·38-0·60). Eight patients acquired bacteraemia with
highly resistant microorganisms during SDD, compared with 18 patients (with 19 episodes)
during standard care (0·41, 0·18-0·94; rate reduction [RR] 59%, absolute risk reduction [ARR]
0·6%) and 20 during SOD (0·37, 0·16-0·85; RR 63%, ARR 0·7%). Of the patients staying
in intensive-care units for more than 3 days, we obtained endotracheal aspirate cultures
for 881 (49%) patients receiving standard care, 886 (50%) receiving SOD, and 828 (44%)
receiving SDD. 128 (15%) patients acquired respiratory tract colonisation with highly resistant
microorganisms during standard care, compared with 74 (8%) during SDD (0·58, 0·43-0·78; RR
38%, ARR 5·5%) and 88 (10%) during SOD (0·65, 0·49-0·87; RR 32%, ARR 4·6%). Acquired
respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistinresistant pathogens was lowest during SDD. INTERPRETATION: Widespread use of SDD and SOD
in intensive-care units with low levels of antibiotic resistance is justified. FUNDING: None.
Copyright © 2011 Elsevier Ltd. All rights reserved.
127
Comment in: Lancet Infect Dis. 2011 May;11(5):337-8.
Verkade E, Ferket M, Kluytmans J. Clinical evaluation of Oxoid Brilliance MRSA Agar
in comparison with bioMerieux MRSA ID medium for detection of livestock-associated
meticillin-resistant Staphylococcus aureus. J Med Microbiol. 2011 Jul;60(Pt 7):905-8.
Oxoid Brilliance MRSA Agar and bioMérieux MRSA ID medium were evaluated for their ability
to identify meticillin-resistant Staphylococcus aureus (MRSA) in clinical samples. Nasal and
throat samples (n=629) were taken from veterinarians and their household members. The
sensitivities of Brilliance MRSA Agar and MRSA ID medium after 20 h of incubation were 63.6
and 64.5%, and the specificities were 94.1 and 99.4%, respectively. After an enrichment step,
the sensitivities increased to 96.3 and 97.2%, but the specificities decreased to 88.7 and
98.5%, respectively. Brilliance MRSA Agar and MRSA ID medium are both sensitive methods
for the screening of MRSA in combination with broth enrichment, but positive results require
confirmation. PMID: 21415201 [PubMed - indexed for MEDLINE] Van Cleef BA, Monnet DL, Voss
128
A, Krziwanek K, Allerberger F, Struelens M, Zemlickova H, Skov RL, Vuopio-Varkila J, Cuny C,
Friedrich AW, Spiliopoulou I, Pászti J, Hardardottir H, Rossney A, Pan A, Pantosti A, Borg M,
Grundmann H, Mueller-Premru M, Olsson-Liljequist B, Widmer A, Harbarth S, Schweiger A, Unal
S, Kluytmans JA. Livestock-associated methicillin-resistant Staphylococcus aureus in humans,
Europe. Emerg Infect Dis. 2011 Mar;17(3):502-5. To estimate the proportion of methicillinresistant Staphylococcus aureus (MRSA) isolates from humans that were sequence type (ST)
398, we surveyed 24 laboratories in 17 countries in Europe in 2007. Livestock-associated MRSA
ST398 accounted for only a small proportion of MRSA isolates from humans; most were from the
Netherlands, Belgium, Denmark, and Austria.
PMCID:PMC3166010
Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; Dutch SOD-SDD Trialists Group*
[Kluytmans JA et al...]. The role of intestinal colonization with gram-negative bacteria as
a source for intensive care unit-acquired bacteremia. Crit Care Med. 2011 May;39(5):961-6.
OBJECTIVE: Selective digestive tract decontamination aims to eradicate gram-negative bacteria
in both the intestinal tract and respiratory tract and is combined with a 4-day course of
intravenous cefotaxime. Selective oropharyngeal decontamination only aims to eradicate
respiratory tract colonization. In a recent study, selective digestive tract decontamination
and selective oropharyngeal decontamination were associated with lower day-28 mortality,
when compared to standard care. Furthermore, selective digestive tract decontamination
was associated with a lower incidence of intensive care unit-acquired bacteremia caused by
gram-negative bacteria. We quantified the role of intestinal tract carriage with gram-negative
bacteria and intensive care unit-acquired gram-negative bacteremia. DESIGN: Data from a
cluster-randomized and a single-center observational study. SETTING: Intensive care unit in
The Netherlands. PATIENTS: Patients with intensive care unit stay of >48 hrs that received
selective digestive tract decontamination (n = 2,667), selective oropharyngeal decontamination
(n = 2,166) or standard care (n = 1,945). INTERVENTIONS: Selective digestive tract
decontamination or selective oropharyngeal decontamination. MEASUREMENTS AND MAIN
RESULTS: Incidence densities (episodes/1000 days) of intensive care unit-acquired gramnegative bacteremia were 4.5, 3.0, and 1.4 during standard care, selective oropharyngeal
decontamination, and selective digestive tract decontamination, respectively, and the daily
risk for developing intensive care unit-acquired gram-negative bacteria bacteremia increased
until days 36, 33, and 31 for selective digestive tract decontamination, standard care, and
selective oropharyngeal decontamination and was always lowest during selective digestive tract
decontamination. Rectal colonization with gram-negative bacteria was present in 26% and 71%
of patient days during selective digestive tract decontamination and selective oropharyngeal
decontamination, respectively (p < .01). Irrespective of interventions, incidence densities of
intensive care unit-acquired gram-negative bacteremia was 4.5 during patient days with both
intestinal and respiratory tract gram-negative bacteria carriage. These incidence densities
reduced with 33% (to 3.1) during days with intestinal gram-negative bacteria carriage only and
with another 45% (to 1.0) during days without gram-negative bacteria carriage at both sites.
CONCLUSIONS: Respiratory tract decolonization was associated with a 33% and intestinal tract
decolonization was associated with a 45% reduction in the occurrence of intensive care unitacquired gram-negative bacteremia. *Collaborators (31): Kalkman CJ, Joore HJ, Leverstein-van
Hall MA, Blok HE, Kluytmans JA, van der Meer NJ, Mascini EM, Kaasjager K, Bosch FH, Benus
RF, van der Werf TS, van der Hoeven JG, Pickkers P, Sturm PD, Voss A, Bernards AT, Kuijper EJ,
Harinck HI, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te
Velde LF, Frenay IH, van Iterson M, Thijsen SF, Kluge GH, de Vries JW, Kaan JA.
Comment in: Crit Care Med. 2011 May;39(5):1202-3.
Van Cleef BA, Graveland H, Haenen AP, van de Giessen AW, Heederik D, Wagenaar JA,
Kluytmans JA. Persistence of livestock-associated methicillin-resistant Staphylococcus
aureus in field workers after short-term occupational exposure to pigs and veal calves.
J Clin Microbiol. 2011 Mar;49(3):1030-3.
The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in pig and veal
calf farmers in the Netherlands is estimated at 25 to 35%. However, no information is available
about MRSA carriage in humans after short-term occupational exposure to pigs or veal calves.
129
This study examines the prevalence and duration of MRSA acquisition after short-term intensive
exposure to pigs or veal calves for persons not exposed to livestock on a daily basis. The study
was performed with field workers who took samples from the animals or the animal houses in
studies on MRSA prevalence in pig and veal farms. They were tested for MRSA by taking nasal
samples before, directly after, and 24 h after they visited the farms. There were 199 sampling
moments from visits to 118 MRSA-positive farms. Thirty-four of these visits (17%) resulted in
the acquisition of MRSA. Thirty-one persons (94%) appeared negative again after 24 h. There
were 62 visits to 34 MRSA-negative farms; none of the field workers acquired MRSA during these
visits. Except for that from one person, all spa types found in the field workers were identical
to those found in the animals or in the dust in animal houses and belonged to the livestockassociated clone. In conclusion, MRSA is frequently present after short-term occupational
exposure, but in most cases the strain is lost again after 24 h.
PMCID:PMC3067751
130
Andriesse GI, Elberts S, Vrolijk A, Verhulst C, Kluytmans JA. Evaluation of a fourthgeneration latex agglutination test for the identification of Staphylococcus aureus.
Eur J Clin Microbiol Infect Dis. 2011 Feb;30(2):259-64.
In this study, we evaluated a fourth-generation agglutination assay (Staph Plus;
DiaMondiaL[DML]) for the rapid identification of Staphylococcus aureus. First, comparison
with three third-generation assays (Slidex Staph Plus, bioMérieux; Staphaurex Plus, Murex
Diagnostics; Pastorex Staph-Plus, Sanofi Diagnostics Pasteur) was performed on a predefined
strain collection: 265 coagulase-negative staphylococci (CNS), 266 methicillin-resistant S. aureus
(MRSA) and 262 methicillin-susceptible S. aureus (MSSA) strains (“strain study”). Second,
patient material-derived strains (883 CNS, 847 MSSA and 135 MRSA) were tested concurrently
with both the DML and Slidex assays (“daily practice study”). In the strain study, the overall
sensitivity and specificity of the DML, Slidex, Staphaurex and Pastorex assays were 99.2%
and 100%, 98.1% and 100%, 95.2% and 100%, and 98.2% and 98.8%, respectively. Using the
respective tests, the result was indeterminate in 0.0%, 0.6%, 0.4% and 1.5% of the strains.
Overall, the sensitivity of the DML and Slidex assays were comparable in both sub-studies.
However, in MRSA strains, the sensitivity of the DML assay was significantly lower than the
Slidex assay. The specificity of the Slidex assay was significantly higher than the DML assay.
However, the percentage of indeterminate results was much higher for the Slidex than the DML
assay. In conclusion, the presumptive identification of S. aureus by the DML assay proved to be
equal to third-generation latex agglutination assays.
PMCID: PMC3022149
Overdevest IT, Willemsen I, Elberts S, Verhulst C, Kluytmans JA. Laboratory detection
of extended-spectrum-beta-lactamase-producing Enterobacteriaceae: evaluation of two
screening agar plates and two confirmation techniques. J Clin Microbiol.
2011 Feb;49(2):519-22.
The worldwide prevalence of extended-spectrum-beta-lactamase-producing ESBL-producing
Enterobacteriaceae (ESBL-E) is increasing, making the need for optimized detection techniques
more urgent. In this study we investigated the performance of two ESBL-E screening and two
ESBL-E confirmation techniques. In accordance with the Dutch national guidelines (www.wip.nl),
a collection of 642 highly resistant Enterobacteriaceae strains, as identified by Vitek2, was used
to test the performances of two screening techniques (EbSA ESBL agar plate and ChromID ESBL
agar plate) and of two confirmation techniques (MIC-strip ESBL and Vitek2 ESBL test panel).
The individual test results were compared by using Etest, followed by a combination disk test if
Etest results were inconclusive. Among group 1 isolates (Escherichia coli, Klebsiella spp., Proteus
spp., Salmonella spp., and Shigella spp.) 291 (57.6%) were ESBL-E, versus 65 (47.4%) in group 2
(Enterobacter spp., Citrobacter spp., Morganella morganii, Serratia spp., and Providencia spp.).
The sensitivities of all four tests for group 1 were comparable (EbSA, 96.6%; ChromID, 97.3%;
MIC-strip, 99.6%; and Vitek2, 95.1%). The specificities of the EbSA and ChromID were the
same (93.9%). However, the confirmation techniques produced many inconclusive test results,
which reduces the applicability in routine laboratories. Only the two screening agar plates were
validated for ESBL testing of group 2 microorganisms. They showed comparable sensitivities;
however, the EbSA screening agar plate had a significantly higher specificity (78.6% versus
44.3%). In conclusion the screening agar plates performed better than the two confirmation
techniques. The EbSA agar plate had the best overall performance.
PMCID: PMC3043506
Störmer M, Arroyo A, Brachert J, Carrero H, Devine D, Epstein JS, Gabriel C, Gelber C,
Goodrich R, Hanschmann KM, Heath DG, Jacobs MR, Keil S, de Korte D, Lambrecht B,
Lee CK, Marcelis J, Marschner S, McDonald C, McGuane S, McKee M, Müller TH, Muthivhi
T, Pettersson A, Radziwon P, Ramirez-Arcos S, Reesink HW, Rojo J, Rood I, Schmidt
M, Schneider CK, Seifried E, Sicker U, Wendel S, Wood EM, Yomtovian RA, Montag T.
Establishment of the first international repository for transfusion-relevant bacteria
reference strains: ISBT working party transfusion-transmitted infectious diseases
(WP-TTID), subgroup on bacteria. Vox Sang. 2012 Jan;102(1):22-31. Epub 2011 Jul 7.
BACKGROUND: Bacterial contamination of platelet concentrates (PCs) still remains a significant
problem in transfusion with potential important clinical consequences, including death. The
International Society of Blood Transfusion Working Party on Transfusion-Transmitted Infectious
131
Diseases, Subgroup on Bacteria, organised an international study on Transfusion-Relevant
Bacteria References to be used as a tool for development, validation and comparison of both
bacterial screening and pathogen reduction methods. MATERIAL AND METHODS: Four Bacteria
References (Staphylococcus epidermidis PEI-B-06, Streptococcus pyogenes PEI-B-20, Klebsiella
pneumoniae PEI-B-08 and Escherichia coli PEI-B-19) were selected regarding their ability to
proliferate to high counts in PCs and distributed anonymised to 14 laboratories in 10 countries
for identification, enumeration and bacterial proliferation in PCs after low spiking (0·3 and
0·03 CFU/ml), to simulate contamination occurring during blood donation. RESULTS: Bacteria
References were correctly identified in 98% of all 52 identifications. S. pyogenes and E. coli
grew in PCs in 11 out of 12 laboratories, and K. pneumoniae and S. epidermidis replicated in
all participating laboratories. The results of bacterial counts were very consistent between
laboratories: the 95% confidence intervals were for S. epidermidis: 1·19-1·32 × 10(7) CFU/ml,
S. pyogenes: 0·58-0·69 × 10(7) CFU/ml, K. pneumoniae: 18·71-20·26 × 10(7) CFU/ml and E.
coli: 1·78-2·10 × 10(7) CFU/ml. CONCLUSION: The study was undertaken as a proof of principle
with the aim to demonstrate (i) the quality, stability and suitability of the bacterial strains
for low-titre spiking of blood components, (ii) the property of donor-independent proliferation
132
in PCs, and (iii) their suitability for worldwide shipping of deep frozen, blinded pathogenic
bacteria. These aims were successfully fulfilled. The WHO Expert Committee Biological
Standardisation has approved the adoption of these four bacteria strains as the first Repository
for Transfusion-Relevant Bacteria Reference Strains and, additionally, endorsed as a project the
addition of six further bacteria strain preparations suitable for control of platelet contamination
as the next step of enlargement of the repository. © 2011 The Author(s). Vox Sanguinis © 2011
International Society of Blood Transfusion.
Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. Transmissibility
of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch
Verkade E, Verhulst C, van Cleef B, Kluytmans J. Clinical evaluation of Bio-Rad
MRSASelect™ medium for the detection of livestock-associated methicillin-resistant
Staphylococcus aureus. Eur J Clin Microbiol Infect Dis. 2011 Jan;30(1):109-12.
Andremont A, Bonten M, Kluytmans J, Carmeli Y, Cars O, Harbarth S. Fighting bacterial
resistance at the root: need for adapted EMEA guidelines. Lancet Infect Dis. 2011
Jan;11(1):6-8.
Lackner M, De Man FH, Eygendaal D, Wintermans RG, Kluytmans JA, Klaassen CH, Meis
JF. Severe prosthetic joint infection in an immunocompetent male patient due to a
therapy refractory Pseudallescheria apiosperma. Mycoses. 2011 Oct;54 Suppl 3:22-7.
Trialists’ Group. Selective decontamination of the oral and digestive tract in surgical
versus non-surgical patients in intensive care in a cluster-randomized trial. Br J Surg.
2012 Feb;99(2):232-237. Epub 2011 Oct 24.
Kluytmans J, Harbarth S. Control of MRSA in intensive care units. BMJ. 2011 Oct
5;343:d5885.
JA. Evaluation of the DiversiLab typing method in a multicenter study assessing
horizontal spread of highly resistant gram-negative rods. J Clin Microbiol. 2011
Oct;49(10):3551-4. Epub 2011 Aug 24.
Roosendaal R, Troelstra A, Box AT, Voss A, van Belkum A, Verbrugh HA, Vos MC.
Sustained low prevalence of meticillin-resistant Staphylococcus aureus upon admission
to hospital in The Netherlands. J Hosp Infect. 2011 Nov;79(3):198-201. Epub 2011 Jul
16.
Overdevest I, Willemsen I, Rijnsburger M, Eustace A, Xu L, Hawkey P, Heck M, Savelkoul
P, Vandenbroucke-Grauls C, van der Zwaluw K, Huijsdens X, Kluytmans J. Extendedspectrum ß-lactamase genes of Escherichia coli in chicken meat and humans, The
Netherlands. Emerg Infect Dis. 2011 Jul;17(7):1216-22.
Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness
of a national guideline. J Antimicrob Chemother. 2011 Oct;66(10):2409-17.
Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants
of treatment failure. J Antimicrob Chemother. 2011 Oct;66(10):2418-24.
a retrospective multicenter study and meta-analysis. Medicine (Baltimore). 2011
Jul;90(4):284-8.
of a commercial microarray as a confirmation test for the presence of extendedspectrum ß-lactamases in isolates from the routine clinical setting. Clin Microbiol
Infect. 2011 Sep;17(9):1435-8.
133
134
C, Kluytmans J; TRIANGLe Study Group. New diagnostic microarray (Check-KPC ESBL)
for detection and identification of extended-spectrum beta-lactamases in highly
resistant Enterobacteriaceae. J Clin Microbiol. 2011 Aug;49(8):2985-7.
Wassenberg MW, Kluytmans JA, Bosboom RW, Buiting AG, van Elzakker EP, Melchers
WJ, Thijsen SF, Troelstra A, Vandenbroucke-Grauls CM, Visser CE, Voss A, Wolffs
PF, Wulf MW, van Zwet AA, de Wit GA, Bonten MJ. Rapid diagnostic testing of
methicillin-resistant Staphylococcus aureus carriage at different anatomical sites:
costs and benefits of less extensive screening regimens. Clin Microbiol Infect. 2011
Nov;17(11):1704-10.
Van Laren M, van Walree NC, Kluytmans JA. Multiple lung abscesses secondary to a
uterine empyema caused by an intrauterine device. Infection. 2011 Aug;39(4):385-7.
van Essen-Zandbergen A, Platteel T, Fluit AC, van de Sande-Bruinsma N, Scharinga
J, Bonten MJ, Mevius DJ; National ESBL surveillance group* [Kluytmans JA et al..].
Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids
and strains. Clin Microbiol Infect. 2011 Jun;17(6):873-80.
density and occurrence of nosocomial transmission (TRIANGLe Study). Infect Control
Hosp Epidemiol. 2011 Apr;32(4):333-41.
Leverstein-van Hall MA, Jansz AR, de Jongh BM, van Asselt GJ, Frenay IH, Thijsen
SF, Conijn SN, Kaan JA, Arends JP, Sturm PD, Bootsma MC, Bonten MJ. Selective
digestive tract decontamination and selective oropharyngeal decontamination and
antibiotic resistance in patients in intensive-care units: an open-label, clustered grouprandomised, crossover study. Lancet Infect Dis. 2011 May;11(5):372-80.
Verkade E, Ferket M, Kluytmans J. Clinical evaluation of Oxoid Brilliance MRSA Agar in
comparison with bioMerieux MRSA ID medium for detection of livestock-associated
meticillin-resistan Staphylococcus aureus. J Med Microbiol. 2011 Jul;60(Pt 7):905-8.
Van Cleef BA, Monnet DL, Voss A, Krziwanek K, Allerberger F, Struelens M, Zemlickova H,
Skov RL, Vuopio-Varkila J, Cuny C, Friedrich AW, Spiliopoulou I, Pászti J, Hardardottir
H, Rossney A, Pan A, Pantosti A, Borg M, Grundmann H, Mueller-Premru M, OlssonLiljequist B, Widmer A, Harbarth S, Schweiger A, Unal S, Kluytmans JA. Livestockassociated methicillin-resistant Staphylococcus aureus in humans, Europe. Emerg Infect
Dis. 2011 Mar;17(3):502-5.
[ Kluytmans JA et al...]. The role of intestinal colonization with gram-negative
bacteria as a source for intensive care unit-acquired bacteremia. Crit Care Med. 2011
May;39(5):961-6.
Kluytmans JAJW. MRSA in Nederland: het water stijgt, maar de dijken houden stand.
Infectieziekten Bulletin Themanummer MRSA 2011;22(B):4-5.
of extended-spectrum-beta-lactamase-producing Enterobacteriaceae: evaluation of
two screening agar plates and two confirmation techniques. J Clin Microbiol. 2011
Feb;49(2):519-22.
Van de Loo EEAJ, Oldenburg AW, Marcelis JH, van Oers JAH. Gegeneraliseerde tetanus bij
een 65-jarige man met slikklachten, pijn in de nek en trismus na stap in een spijker.
A&I. 2011;3(3):38-43.
Goodrich R, Hanschmann KM, Heath DG, Jacobs MR, Keil S, de Korte D, Lambrecht
B, Lee CK, Marcelis J, Marschner S, McDonald C, McGuane S, McKee M, Müller TH,
Muthivhi T, Pettersson A, Radziwon P, Ramirez-Arcos S, Reesink HW, Rojo J, Rood I,
Schmidt M, Schneider CK, Seifried E, Sicker U, Wendel S, Wood EM, Yomtovian RA,
Montag T. Establishment of the first international repository for transfusion-relevant
bacteria reference strains: ISBT working party transfusion-transmitted infectious
diseases (WP-TTID), subgroup on bacteria. Vox Sang. 2012 Jan;102(1):22-31. Epub 2011
Jul 7.
135
Longgeneeskunde
Kerngegevens zorgkern Longgeneeskunde
• 9 longartsen: dr. J.G.J.V. (Joachim) Aerts, J. (Jerryll) Asin, T.A. (Theo) Bantje,
H.N.A. (Huub) Belderbos, R.S. (Remco) Djamin, dr. M.J.J.H. (Marco) Grootenboers,
A.M. (André) Janssens, V.M.J. (Vic) Linsen, N.C. (Nico) van Walree
• 1 chef de clinique, dr. V. Nowé
• subspecialismen: astma/COPD, allergologie, interstitiële longziekten, longziekten,
longkanker, slaapapneu en niet invasieve (masker)thuisbeademing
2011;2011:785425. Epub 2011 Apr 10.
Longgeneeskunde
137
inherent in cytology obtained by routine FNA.
PMID: 21559244 [PubMed] PMCID: PMC3087462
Van der Leest C, Smit EF, Baas J, Versteijlen RJ, van Walree N, Hoogsteden HC, Aerts JG.
SUV(max) during 18FDG-PET scanning in small cell lung cancer: Similar information as in
non-small cell lung cancer? Lung Cancer. 2011 Oct 11. [Epub ahead of print].
In patients with non-small cell lung carcinoma (NSCLC) fluorine-18 fluorodeoxyglucose positron
emission tomography (18FDG-PET)-scanning is shown to be of prognostic value. Small cell lung
cancer (SCLC) is an aggressive tumor with poor prognosis. Limited results on the prognostic
and predictive value of the maximum standard uptake values (SUV(max)) obtained during
18FDG-PET scanning in SCLC are available. An observational study in 75 chemonaive patients
diagnosed with SCLC who underwent a 18FDG-PET scan was performed. SUV(max) values of
the primary tumor were related to the overall survival (OS) and the progression free survival
138
(PFS). Significant lower SUV(max) values of the primary tumor were observed in patients with
stage I-III disease compared to stage IV disease. SUV(max) did not discriminate for either OS
or PFS in the whole group of patients. In patients with stage IV disease and treatment with
chemotherapy, OS and PFS were significantly higher in patients with a high SUV(max). (p-value
0.005 and 0.002 respectively) compared to patients with a low SUV(max) value. In patients with
SCLC metabolic activity determined using 18FDG-PET (SUV(max)) differed between stage I-III
and stage IV diseases. Compared to NSCLC, the relationship between SUV(max) and prognosis
seems more complex. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Kerstjens HA, Disse B, Schröder-Babo W, Bantje TA, Gahlemann M, Sigmund R, Engel M,
van Noord JA. Tiotropium improves lung function in patients with severe uncontrolled
asthma: a randomized controlled trial. J Allergy Clin Immunol.
2011 Aug;128(2):308-14. Epub 2011 Jun 2.
BACKGROUND: Some patients with severe asthma remain symptomatic and obstructed despite
maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent,
might be an effective bronchodilator in such patients. OBJECTIVE: We sought to compare the
efficacy and safety of 2 doses of tiotropium (5 and 10 μg daily) administered through the
Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma
(Asthma Control Questionnaire score, = 1.5; postbronchodilator FEV1, = 80% of predicted
value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a
long-acting ß2-agonist. METHODS: This was a randomized, double-blind, crossover study with
three 8-week treatment periods. The primary end point was peak FEV1 at the end of each
treatment period. RESULTS: Of 107 randomized patients (54% female patients; mean, 55 years
of age; postbronchodilator FEV1, 65% of predicted value), 100 completed all periods. Peak
FEV1 was significantly higher with 5 μg (difference, 139 mL; 95% CI, 96-181 mL) and 10 μg
(difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001).
There was no significant difference between the active doses. Trough FEV1 at the end of the
dosing interval was higher with tiotropium (5 μg: 86 mL [95% CI, 41-132 mL]; 10 μg: 113 mL
[95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were
higher with both tiotropium doses. There were no significant differences in asthma-related
health status or symptoms. Adverse events were balanced across groups except for dry mouth,
which was more common on 10 μg of tiotropium. CONCLUSION: The addition of once-daily
tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting
ß2-agonist, significantly improves lung function over 24 hours in patients with inadequately
controlled, severe, persistent asthma. Copyright © 2011 American Academy of Allergy, Asthma
& Immunology. Published by Mosby, Inc. All rights reserved. PMID: 21636120 [PubMed - indexed
for MEDLINE] Van Laren M, van Walree NC, Kluytmans JA. Multiple lung abscesses secondary to
a uterine empyema caused by an intrauterine device. Infection. 2011 Aug;39(4):385-7.
2011;2011:785425. Epub 2011 Apr 10.
SUV(max) during 18FDG-PET scanning in small cell lung cancer: Similar information as
in non-small cell lung cancer? Lung Cancer. 2011 Oct 11. [Epub ahead of print].
Aerts JG, van den Borne B, Creemers G. [red.] Adviezen over het gebruik van bevacizumab
bij de behandeling van NSCLC : bijwerkingen-management en aandachtspunten.
[Wormer] : Ariez Publishing, 2011.
Aerts JGJV. Maligne pleuritiden. In: Het pulmonaal formularium : een praktische leidraad
/ Van den Bosch, JJM {et al...][red.]. Houten : Bohn Stafleu van Loghum, 2011.
ISBN 9789031386307.
Aerts JGJV. Mesothelioom. In: Het pulmonaal formularium : een praktische leidraad
/ Van den Bosch, JJM {et al...][red.]. Houten : Bohn Stafleu van Loghum, 2011.
ISBN 9789031386307.
asthma: a randomized controlled trial. J Allergy Clin Immunol. 2011 Aug;128(2):308-14.
Epub 2011 Jun 2.
Longgeneeskunde
139
2011;2011:785425. Epub 2011 Apr 10.
140
Neurologie
Van geheugenpoli tot rugstraat
Momenteel is de vakgroep neurologie hard aan het werk om de opleiding binnen te
halen, in samenwerking met de universiteit van Antwerpen. Het opleidingsklimaat
binnen de vakgroep is de laatste vijf jaar onder begeleiding van neuroloog dr. Jan
C.M. Zijlmans naar een hoger niveau getild.
dr. (Jan) C.M. Zijlmans
“We hebben acht opleidingsmomenten per week, dat is meer dan in veel A-opleidingsziekenhuizen, laat staan B-opleidingsziekenhuizen.” Neuroloog Zijlmans somt op
dat er elke maandag multidisciplinair overleg plaatsvindt met revalidatieartsen en
allerlei paramedici. Op dinsdag is er tijdens de lunch een boekbespreking of een
Neurologie
141
richtlijnbespreking met de assistenten. Dinsdagmiddag is er radioneurologiebespreking. Op
woensdag neuro-orthopediebespreking, op donderdag is er tijdens de lunch een coreferaat
met coassistenten en ’s middags een neurovasculaire bespreking. Elke vrijdag is er een
patiëntendemonstratie. Zijlmans: “Centraal staat de casuïstiek van een patiënt, er kunnen
aanvullende vragen gesteld worden – eerst door de coassistenten, dan door de assistenten
en daarna door de neurologen – en dan volgt een conclusie en bespreken we twee soorten
differentiaaldiagnoses, een topografische en een etiologische. Dat is altijd heel didactisch
en spannend.” Sinds januari is de stage neurologie in het kader van de geriatrie al binnen.
Patiëntenzorg
142
Voor de beste zorg voor de patiënt is een aantal poli’s ingericht. Er zijn geheugen-,
multiple sclerose- en beroertepoli’s. Ook is er een TIA-dagscreening. Er is ketenzorg in
samenwerking met verpleeghuisrevalidatie voor CVA-patiënten en er is een ‘straat’ voor
rugklachten. “Als er een vermoeden is van hernia dan kan de huisarts een formulier
faxen – zit het links of rechts –dan krijgt de patiënt eerst een MRI-scan en binnen een
week volgt een consult bij de neuroloog zodat we het heel snel kunnen afhandelen”, legt
Zijlmans uit. “Ook scoren we goed in het percentage trombolyses op de spoedeisende hulp.
We zijn ingebed in het ParkinsonNet met paramedici en ik zit in de commissie Gezond
Ouder Worden, die verbeteringen voor ouderen initieert.” De maatschap Neurologie bestaat
uit twaalf neurologen en er is ruimte voor twee nieuwe collega’s. Alle neurologen in het
Amphia Ziekenhuis werken in de breedte, wel hebben ze eigen aandachtsgebieden.
Mw. dr. J.F. de Rijk-van Andel (kinderneuroloog)
“Collega De Rijk-van Andel doet ten eerste veel onderzoek naar lissencefalie, een
aanlegstoornis van de hersenen”, zegt Zijlmans. Het is al meer dan vijftien jaar haar
aandachtsgebied en nog steeds publiceert ze daarover, net als over de langetermijnfollowup. Als tweede besteedt ze veel aandacht aan tyrosinehydroxylasedeficiëntie, een
heel dramatisch uitziende aandoening bij kinderen met een dopaminetekort (zoals bij
parkinson). Zijlmans: “Kinderen kunnen dan bijna niet lopen, maar als ze de dopamine
aanvullen, zijn ze ogenschijnlijk weer normaal. Op tijd ingrijpen is dus belangrijk. Zij
heeft dat als een van de eersten beschreven. Het werd toen zelfs even het De Rijk-van
Andelsyndroom genoemd. Ze publiceert hier nog steeds over, onder andere in Brain.”
Als derde heeft ze veel patiënten geïncludeerd voor onderzoek naar multiple sclerose bij
kinderen in samenwerking met de VU. Bovendien is ze enthousiast over haar publicatie
over fenotypes van paroxysmale dyskinesie.
Dr. J.E. Visser (gesubspecialiseerd in de ziekte van Parkinson)
“Collega Visser is gepromoveerd op balansproblemen bij de ziekte van Parkinson”,
vertelt Zijlmans. “Bijzonder is dat Visser ook bioloog is en dus op een iets andere manier
onderzoek doet. Zo kijkt hij naar de moleculaire achtergrond van door lichaamsbeweging
gestimuleerde plasticiteit van het brein in een diermodel van de ziekte van Parkinson.
Voor dit werk ontving hij een Veni-subsidie en dat is heel bijzonder voor een perifeer
werkende neuroloog. Hij werkt tachtig procent in het Amphia Ziekenhuis en twintig
procent in het Academisch Ziekenhuis in Nijmegen.” Bovendien doet Visser onderzoek naar
de moleculaire oorzaak van de ziekte van Lesch-Nyhan, een stofwisselingsziekte die leidt
tot ernstige bewegings- en gedragsstoornissen. Bij deze ziekte lijkt de neurogenetische
programmering van bepaalde neuronen spaak te lopen.
Dr. J.C.M. Zijlmans (gesubspecialiseerd in de ziekte van Parkinson)
Zelf is Zijlmans in 1996 gepromoveerd op onderzoek naar vasculair parkinsonisme.
Hij deed rond de millenniumwisseling twee jaar onderzoek op parkinsonpoli’s en de
parkinsonhersenbank (1.200 hersenen van mensen met deze ziekte) in Londen, het mekka
van de klinische neurologie.
Zijlmans verrichtte een vervolgonderzoek naar vasculair parkinsonisme, dat dezelfde
verschijnselen heeft als parkinson, maar veroorzaakt wordt door een doorbloedingsstoornis
in de hersenen en een andere aanpak vraagt. “Naar aanleiding van dat onderzoek bij de
hersenbank in Londen stelde ik de klinische criteria op voor vasculair parkinsonisme en
in een review in het Movement Disorders Journal wordt geadviseerd om bij onderzoek naar
deze aandoening voortaan de ‘Zijlmans-criteria’ te gebruiken.”
Kerngegevens zorgkern Neurologie
• 12 neurologen: R. (Ron) van Dijl, dr. P.M.M. (Paul) van Erven, R.J. (Robert-Jan) de
Graaf, mw. dr. I.A.W. (Irene) Kotsopoulos, H.B.M. (Hans) van Lieshout, M.J.M. (Michel)
Remmers, mw. dr. J.F. (Johanneke) de Rijk - van Andel, dr. E.A.C.M. (Evert) Sanders,
J.P.M. (Jan-Pieter) Stroy, H.B.C. (Henk) Verbiest, J.E. (Jasper) Visser, dr. J.C.M. (Jan)
Zijlmans
• 2 neurologen/kinderneurologen: mw. dr. I.A.W. (Irene) Kotsopoulos,
mw. dr. J.F. (Johanneke) de Rijk-van Andel
• subspecialisme: kinderneurologie
Lopende onderzoeken
• LEAP (vanuit AMC). Net diagnose parkinson, dan placebo/medicatie of alleen
medicatie.
• Artis (vanuit AMC). Onderzoek naar het gebruik van Ascal na trombolyse.
• Pass (vanuit AMC). Vergelijkend onderzoek antibioticum en placebo (preventie
infecties).
• Diagram (vanuit UMC Utrecht). Diagnostic angiography to find vascular malformations.
Neurologie
143
• Parkfit-onderzoek (vanuit UMC Nijmegen). Beter functioneren na gespecialiseerde
fysiotherapie (inclusies zijn niet meer mogelijk).
Elfferich P, Verleun-Mooijman MC, Maat-Kievit JA, van de Warrenburg BP, Abdo WF,
Eshuis SA, Leenders KL, Hovestadt A, Zijlmans JC, Stroy JP, van Swieten JC, Boon AJ,
van Engelen K, Verschuuren-Bemelmans CC, Lesnik-Oberstein SA, Tassorelli C, Lopiano L,
Bonifati V, Dooijes D, van Minkelen R. Breakpoint mapping of 13 large parkin deletions/
duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations.
Neurogenetics. 2011 Nov;12(4):263-71. Epub 2011 Oct 13.
Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin
(PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large
deletions or duplications. Although many different rearrangements have been found in parkin
before, the exact breakpoints involving these rearrangements are rarely mapped. In the present
study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13
144
patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe
Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain
reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests
were developed as a rapid and low cost tool to confirm MLPA results and to test family members
or patients with similar parkin deletions/duplications. Besides several different deletions, an
exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families.
Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be
distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion
of exon 4. These findings suggest common founder effects for distinct large rearrangements in
parkin.
PMCID: PMC3215878
Laan L. Tijdverlies van beroerte tot carotisendarteriëctomie. [Time lost between stroke and
carotid endarterectomy]. Ned Tijdschr Geneeskd. 2011;155(32):A3300.
OBJECTIVE: To establish whether measures taken to shorten the interval of time between a
stroke and carotid endarterectomy (CEA) procedure at two Dutch hospitals had any effect.
DESIGN: Retrospective and descriptive. METHOD: Data were gathered on all patients with
symptomatic narrowing of the carotid artery from a non-academic teaching hospital (Amphia
Ziekenhuis in Breda) as well as from a university clinic dedicated to carotid abnormalities
(University Medical Center Utrecht, UMCU). ‘Pass-through’ intervals were analysed from 2006
and 2007 and compared with those from 2010 when the sequence of hospital care had been
improved in terms of time interval from stroke up to and including CEA. The time interval
between the first symptoms of stroke and the first visit to the outpatient clinic specialist was
determined, as well as the time interval between the stroke and CEA procedure. RESULTS:
After the hospitals had taken measures to shorten the time interval between a stroke and an
operation, the percentage of patients who had undergone surgery within 2 weeks in 2010 was
34% at Amphia Ziekenhuis and 21% at the UMCU, as opposed to 5.5% (2006) and 10.5% (2007),
respectively. The median time between first symptoms and surgery had decreased from 40 to
19 days at Amphia Ziekenhuis and from 57 to 36 days at the UMCU. CONCLUSION: At both the
non-academic clinic and the university centre dedicated to carotid abnormalities, the majority
of symptomatic patients had not undergone surgery within 2 weeks of a stroke in 2010. A CEA
must therefore become a semi-acute operation instead of a semi-elective one in order to meet its
associated performance criteria in the near future.
Namavar Y, Barth PG, Kasher PR, van Ruissen F, Brockmann K, Bernert G, Writzl K,
Ventura K, Cheng EY, Ferriero DM, Basel-Vanagaite L, Eggens VR, Krägeloh-Mann I, De
Meirleir L, King M, Graham JM Jr, von Moers A, Knoers N, Sztriha L, Korinthenberg R;
PCH Consortium, Dobyns WB, Baas F, Poll-The BT. Collaborators (62): et al... [de Rijk van
Andel] Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.
Brain. 2011 Jan;134(Pt 1):143-56. Epub 2010 Oct 15.
Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with
prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy
of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable
neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA
splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated
with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA
arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We
studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106
patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order
to delineate the neuroradiological and clinical phenotype of patients with mutations in these
genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who
were negative on mutation analysis. We found a strong correlation (P < 0.0005) between TSEN54
mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the
cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared.
Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable
degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site
mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms,
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ventilator dependency and early death. In addition, we present ten new mutations in TSEN54,
TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with
elevated cerebrospinal fluid lactate may be caused by RARS2 mutations. Collaborators (62): Van
der Aa N, Arts WF, Ades LC, Bahi-Buisson N, Battini R, Bodamer O, Boltshauser E, Boycott K,
Brueton L, Brussel W, Chandler KE, Cowan FM, Crow Y, Debus O, Demir E, Hastanesi G, Eason J,
Ferrie CD, Fisher RB, Foulds N, Freeman JL, Gooskens R, Haeussler M, Hageman G, Hammersen G,
Horn D, Isidor B, van der Knaap MS, Kress W, Kroisel PM, Kyllerman M, Lachmeijer AM, Lunsing
RJ, McGillivray G, Möllmann S, Muntoni F, Nemeth AH, Neufeld-Kaiser W, van Nieuwenhuizen
O, Ouvrier R, Pálmafy B, Peeters EA, Phillips JJ, Price S, Rankin J, Régal L, de Rijk-van Andel
JF, Roelens F, Rutledge JC, Ryan MM, Seidl R, Sellerer NC, Shannon NL, Sival DA, Snoeck IN,
Straussberg R, Tijssen MA, Verloo P, de Vries LS, Wargowski D, Williams AN, Windpassinger C.
De Wit MC, de Rijk - van Andel J, Halley DJ, Poddighe PJ, Arts WF, de Coo IF, Mancini
GM. Long-term follow-up of type 1 lissencephaly: survival is related to neuroimaging
abnormalities. Dev Med Child Neurol. 2011 May;53(5):417-21. Epub 2011 Mar 17.
146
AIM: To evaluate survival, clinical, and genetic characteristics of all patients with classic or type
1 lissencephaly born between 1972 and 1990 in the Netherlands, who at the time were enrolled
in an observational study. METHOD: We re-evaluated 24 patients (11 males, 13 females) for
long-term follow-up and survival information. RESULTS: Mean length of follow-up was 14 years
(SD 9y 8mo). Eleven patients were alive at follow-up. All patients showed severe intellectual
disability, intractable epilepsy, and complete dependency on care. Life expectancy was related
to the severity of the lissencephaly on neuroimaging. Molecular analysis of the LIS1 gene was
not possible at the time of the original study and was now requested by eight parents. This
revealed a pathogenic nonsense mutation or deletion in seven patients. INTERPRETATION: Our
study provides information about the long-term course of lissencephaly and the relationship
between lissencephaly severity and prognosis. It also shows that renewed attention to genetic
counselling remains valued by families of patients with a severe congenital neurological disease.
© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.
Edgar C, Jongen PJ, Sanders E, Sindic C, Goffette S, Dupuis M, Jacquerye P, Guillaume
D, Reznik R, Wesnes K. Cognitive performance in relapsing remitting multiple sclerosis:
a longitudinal study in daily practice using a brief computerized cognitive battery.
BMC Neurol. 2011 Jun 7;11:68.
BACKGROUND: There is need for a cognitive test battery that can be easily used in clinical
practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In
order to conduct, in this patient group, a preliminary investigation of the validity and utility
of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally
assessed cognition in patients with relapsing remitting (RR) MS. METHODS: Forty-three mildly
disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol
Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores
derived from the CDR computerized cognitive test system (CDR System): Power of Attention,
Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed
of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability
Status Scale (EDSS) measured disability. RESULTS: The composite scores from the CDR battery
generally showed excellent test-retest reliability over the repeated assessments, though was
low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures.
The CDR measures tended to be highly correlated with other measures of cognition (DSST and
PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated
large impairments to visual information processing speed and attention (DSST, Cohen’s d 1.1;
Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a
moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex
information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and
episodic Memory]), when compared to normative data derived from healthy volunteers enrolled
in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and
episodic memory (Quality of Episodic Memory) were unimpaired. CONCLUSIONS: Preliminary
validation of the CDR System indicated that for most, but not all measures psychometric
properties were adequate and the measures were related to disability (EDSS and MSFC) and other
measures of cognition.
PMCID:PMC3128855
Jongen PJ, Sindic C, Sanders E, Hawkins S, Linssen W, van Munster E, Frequin S, Borm G;
Functional Composite and Quality of Life in Avonex-treated Relapsing Multiple Sclerosis
Patients Study Group*. Adverse events of interferon beta-1a: a prospective multi-centre
international ICH-GCP-based CRO-supported external validation study in daily practice.
PLoS One. 2011;6(10):e26568. Epub 2011 Oct 25.
BACKGROUND: Due to methodological shortcomings the available post-registration data on
the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to
adequately validate phase III data and only partially inform on safety in daily practice.
We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with
intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to
those in phase III trials. METHODS: A prospective, International Conference on Harmonization
(ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study
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in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During
24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs’ severity
(mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were
compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients
experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5%
were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of
the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial,
we found statistically significantly lower incidences for most of the common AEs: headache,
muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular
events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION:
Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatmentrelated AEs, most of these being mild. Our data externally validate the favorable phase III safety
profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less
than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially
hazardous AEs of IM INFb-1a. Collaborators (46): Driessen, Baard, Frequin, Hintzen, Hupperts,
Jongen, Linssen, Beyer M, Moll, van Munster, Den Bosch, Pratzsky, Sanders, Smits, van Walbeek,
148
Willems, Witjes, van Zuilen, Bartholomé, Braeckveldt, Van der Motte, Debruyne, Decoo, Dedeyn,
Engelborghs, Dupuis, Jacquerye, Van de Gaer, Guillaume, Reznik, Harmant, D’Hooghe, Klippel,
Willems, van Landegem, Strauven, de Noordhout M, Delavaux, Nagels, Seeldrayers, Vervonck,
Sindic, Goffette, El-Memar, Hawkins, de Diego.
PMCID:PMC3201962
Visser JE, Schretlen DJ, Bloem BR, Jinnah HA. Levodopa is not a useful treatment for
Lesch-Nyhan disease. Mov Disord. 2011 Mar;26(4):746-9. Epub 2011 Jan 31.
Lesch-Nyhan disease (LND) is characterized by dystonia, cognitive abnormalities, and selfinjurious behavior. No effective therapies are available. LND is associated with a presynaptic
dopaminergic deficit, but the reported effects of dopamine replacement therapy are conflicting.
The current prospective open-label study assesses the effects of levodopa on both neurological
and behavioral features of LND. All 6 study participants discontinued levodopa early, due to lack
of effect and sometimes worsening of motor function. The results provide important clues for
pathophysiological mechanisms and suggestions for future treatment options. Copyright © 2011
Movement Disorder Society.
Zijlmans JC. Vascular Chorea in Adults and Children. Handb Clin Neurol. 2011;100:261-70.
Chorea may occur as part of the symptomatology of acute stroke; it occasionally also may
be delayed or progressive. Patients with vascular-related chorea typically present with an
acute or subacute onset of chorea of one side of the body (hemichorea), contralateral to the
lesion. Cerebrovascular disease is the most common cause of sporadic chorea. Lesions are
most frequently found in the thalamus and lentiform nucleus, and less often in subthalamic
nucleus. The differential diagnosis of choreic syndromes relies not so much on differences in the
phenomenology of the hyperkinesia but the age at onset, mode of onset, time course, family
history, drug use, distribution of chorea in the body, and presence of accompanying neurological
findings. Magnetic resonance imaging is preferred to demonstrate the presence of strategic small
lesions in regions that are difficult to image with computed tomography, such as the globus
pallidus, thalamus, and subthalamic nucleus. Although the prognosis of hemichorea can be
benign, the long-term prognosis is not specifically determined by the hemichorea but by the
long-term prognosis of stroke patients. Symptomatic treatment with antichoreic drugs may be
necessary in the acute phase. Surgery is rarely indicated to treat vascular chorea. Copyright ©
2011 Elsevier B.V. All rights reserved.
149
Namavar Y, Barth PG, Kasher PR, van Ruissen F, Brockmann K, Bernert G, Writzl K, Ventura
K, Cheng EY, Ferriero DM, Basel-Vanagaite L, Eggens VR, Krägeloh-Mann I, De Meirleir
L, King M, Graham JM Jr, von Moers A, Knoers N, Sztriha L, Korinthenberg R; PCH
Consortium, Dobyns WB, Baas F, Poll-The BT. Collaborators (62): et al... [de Rijk van
Sanders EA. Monoclonale antilichamen voor de behandeling van relapsing remitting
multiple sclerose. In: Infocus, [s.l.] : [s.n.], 2011. ISBN: 9789085232193.
Moll JBW, Sanders EACM. Het verloop van progressieve multifocale leuko-encephalopathie
bij MS patiënten behandeld met Natalizumab. Neurologie Actueel, 2011;14(5):1-4.
Sanders EACM. Fingolimod het eerste orale middels als behandeling voor multiple sclerose.
Neurologie Actueel 2011;14(6):1-4.
Boogerd W, Sanders EACM. Neuro-oncologie in beeld. Houten: Bohn Stafleu van Loghum /
Springer, 2011. ISBN: 9789031386642.
Neurologie
150
Sanders MWCB, Debels VEC, Sanders EACM, Hansens PEJ, Verheul JB. Pain relief in
trigeminal neurologica related to multiple sclerosis. A comparison of different
treatment strategies. [Poster P565]. Multiple Sclerosis J.. 2011;17(10 suppl):S245.
Sanders EACM, van Munster ETL, de Graaf J, Verhagen W. Progressive multifocal
encephalopathy in the Netherlands 4 cases. [poster P519] Multiple Sclerosis J..
2011;17(10 suppl):S223.
Sanders EACM, Cakmak A. Causes of death amongst multiple sclerosis patients.
[Poster P1059] Multiple Sclerosis J.. 2011;17(10 suppl):S483.
Edgar C, Jongen PJ, Sanders E, Sindic C, Goffette S, Dupuis M, Jacquerye P, Guillaume D,
Reznik R, Wesnes K. Cognitive performance in relapsing remitting multiple sclerosis:
a longitudinal study in daily practice using a brief computerized cognitive battery.
BMC Neurol. 2011 Jun 7;11:68.
Elfferich P, Verleun-Mooijman MC, Maat-Kievit JA, van de Warrenburg BP, Abdo WF, Eshuis
SA, Leenders KL, Hovestadt A, Zijlmans JC, Stroy JP, van Swieten JC, Boon AJ, van
Engelen K, Verschuuren-Bemelmans CC, Lesnik-Oberstein SA, Tassorelli C, Lopiano
L, Bonifati V, Dooijes D, van Minkelen R. Breakpoint mapping of 13 large parkin
deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder
mutations. Neurogenetics. 2011 Nov;12(4):263-71. Epub 2011 Oct 13.
Zijlmans JC. Vascular Chorea in Adults and Children. Handb Clin Neurol. 2011;100:26170. Elfferich P, Verleun-Mooijman MC, Maat-Kievit JA, van de Warrenburg BP, Abdo WF,
Eshuis SA, Leenders KL, Hovestadt A, Zijlmans JC, Stroy JP, van Swieten JC, Boon AJ,
van Engelen K, Verschuuren-Bemelmans CC, Lesnik-Oberstein SA, Tassorelli C, Lopiano
Nucleaire geneeskunde
Kerngegevens zorgkern Nucleaire geneeskunde
• 2 nucleair geneeskundigen: J. (Jim) Baas, voorzitter maatschap, P.J. (Peter)
van Noorden
151
Nucleaire geneeskunde
Publicatielijst
152
Oogheelkunde
Kerngegevens zorgkern Oogheelkunde
• 11 oogartsen: G.A. (Bert) Bakker, dr. T.P. (Thomas) Colen, F.J. (Fijs) van Dobben de
Bruijn, dr. B.T.H. (Bart) van Dooren, mw. G. (Trudy) de Grip, mw. L.J.C. (Lidy) Hartman,
mw. O. (Olivera) Jovanovic, mw. I.L.A. (Irene) van Liempt, dr. G.L. (Giorgio) Porro,
mw. O.A.M. (Odette) Tigchelaar-Besling, mw. dr. J.J.M. (Jacqueline) Willemse-Assink
• subspecialismen: traanwegafwijkingen, refractiechirurgie, glaucoom,
hoornvliesafwijkingen, laserbehandelingen voor refractieafwijkingen, ooglidchirurgie,
behandeling maculadegeneratie, kinderoogheelkunde, medische retina,
neurophthalmologie, scheelzien en erfelijke aandoeningen
Dooren BT, Saelens IE, Bleyen I, Mulder PG, Bartels MC, Rij GV. Endothelial cell decay
after descemet’s stripping automated endothelial keratoplasty and top hat penetrating
keratoplasty. Invest Ophthalmol Vis Sci. 2011 Nov 29;52(12):9226-31.
PURPOSE: To analyze endothelial cell density (ECD) decay after Descemet’s stripping automated
endothelial keratoplasty (DSAEK) and top hat keratoplasty (THPK) in patients with Fuchs’
endothelial dystrophy (FED) and/or pseudophakic bullous keratopathy (PPBK). METHODS:
Patients underwent either THPK (n = 33) or DSAEK (n = 39) at the Erasmus Medical Center,
Rotterdam. For each nonrandomized cohort, a biexponential regression model for ECD decay
was fitted. Factors associated with higher ECD decay were evaluated. RESULTS: Median followup was 31.2 months (range, 11-91) in the THPK cohort, and 23.4 months (range, 6-61) in the
DSAEK group. The early ECD decay was much higher after DSAEK (half time, 2.2 months) than
after THPK (half time, 12.8 months). The late ECD decay after DSAEK was less steep (half time,
75.5 months) than after THPK (half time, 62 months). The 1-, 3- and 5-year endothelial cell
Oogheelkunde
153
losses derived from the models after DSAEK were 56%, 66%, and 73%, respectively, and after
THPK were 24%, 50%, and 64%, respectively. For the DSAEK cohort, PPBK as an indication for
surgery was associated with significantly higher late-phase decay rates. For the top-hat cohort,
a significantly lower late-phase decay rate was found in PPBK. FED and same-session cataract
surgery were confounding variables in the DSAEK cohort. Regarding DSAEK, postoperative rebubbling was not found to have significant effects on early or late ECD decay rates. However,
the small sample size and other limitations related to the method of evaluation may have
influenced these findings. CONCLUSIONS: After DSAEK, early ECD decay was stronger than after
THPK, as opposed to late decay. Late decay was faster for PPBK than for FED after DSAEK.
Publicatielijst
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Orthopedie
Drie vrouwelijke orthopedisch chirurgen in het Amphia Ziekenhuis
In het Amphia Ziekenhuis werken fulltime drie vrouwelijke orthopedisch chirurgen:
dr. D. (Denise) Eygendaal, dr. A. (Annechien) Beumer en M.P.J. (Maaike) van den
Borne, die niet bij het gesprek aanwezig is. “Drie vrouwen is best bijzonder”, zegt
dr. Denise Eygendaal. “Zeker als je nagaat dat er tijdens mijn opleiding maar drie
vrouwelijke orthopeden in Nederland waren.” Fleurige gordijnen, grote planten en
houten meubels geven het kantoor een warme uitstraling die opvalt in een verder
klinische omgeving.
mw. dr. A. (Annechien) Beumer, mw. dr. D. (Denise) Eygendaal
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155
Beide orthopeden hebben zich gespecialiseerd in de orthopedie van de bovenste
extremiteiten: Eygendaal in de elleboog en de pols, Beumer in de hand en de pols. En
Van den Borne in schouders. “Maar vandaag gaat het niet over ons, maar over de groep.
We willen duidelijk maken wat een mooie groep we hebben hier in het Amphia”, zegt
Eygendaal. “Zo hebben we bijvoorbeeld zelf de website orthopedie-amphia.nl opgezet en
daar zijn onze patiënten erg enthousiast over. We hebben veel moeite gedaan om zo een
eigen identiteit te creëren.”
Kwaliteit
156
Zeker in zo’n grote organisatie als het Amphia Ziekenhuis is het een uitdaging om een
vakgroep Orthopedie gestalte te geven – zowel naar binnen als naar buiten toe. “Vooral
nu”, licht Eygendaal toe. “Nu je als je het even niet goed doet patiënten kwijt bent aan
een privécentrum om de hoek, of aan België.” Beumer vult aan dat de orthopeden een
bijzondere database met gegevens opbouwden van alle geopereerde patiënten. “Voor
kwaliteitscontrole en wetenschappelijk onderzoek hebben we patiënten verzocht om
vragenlijsten in te vullen en hebben we hun functies gecontroleerd. Die gegevens voeren
we – geanonimiseerd – in, zodat we onze kwaliteit kunnen controleren en artikelen
kunnen schrijven. Zo controleer je heel systematisch je eigen chirurgisch handelen aan de
hand van wetenschappelijke parameters. Er is exact vastgelegd hoeveel ingrepen je doet,
hoe en op welk niveau, en wat de resultaten hiervan zijn.”
Differentiatie
Een belangrijk sleutelwoord bij de zorgkern Orthopedie is differentiatie. Voor alle
orthopedische onderdelen is een specialist aanwezig. “We hebben allemaal een eigen aandachtsgebied. Dat maakt onze groep zo divers. Dat maakt het zo leuk om hier te werken”,
glimlacht Eygendaal. “Dat blijkt ook uit het feit dat tussen 2006 en 2011 elf van de
veertien nieuwe collega’s zijn aangesteld. Dat zijn niet allemaal starters, maar juist ervaren
orthopeden uit andere medische centra. Bijzonder voor een beroepsgroep die niet graag
verkast. De combinatie differentiatie, onderwijs en wetenschap heeft aantrekkingskracht.”
Proefschrift in samenwerking
Na een lange aanloop is in juli 2011 eindelijk ‘de opleiding’ binnengehaald, in
samenwerking met het Academisch Medisch Centrum. “En nu zit de vaart erin”, zegt
Beumer. “De eisen zijn streng, maar het ging vooral moeizaam omdat het aantal op te
leiden orthopeden was gehalveerd. Dus dan zijn er geen mensen over om op te leiden als
nieuwe groep. Op papier voldeden we toen allang aan de eisen.” In april werd het eerste
Amphia-AMC-proefschrift verdedigd, over de studie ‘Proximale radiusfractuur’. Een studie
over radiuskopfracturen dus, letsel dat vaak voorkomt en volgens Eygendaal nogal eens
wordt onderschat. De aanbevelingen uit het proefschrift zullen leiden tot een verbetering
van de behandeling van dit type elleboogletsel. “Bijzonder is dat het een proefschrift is
van de vakgroep orthopedie, waarbij chirurgie en radiologie participeerden. Mooi voorbeeld
van verbroedering tussen vakgroepen toch?” In totaal zijn drie van de vijf assistenten
bezig met promoveren.
Innovatie
Bij kniechirurgie worden knieprotheses geplaatst die zijn gestoeld op de individuele
anatomie van de patiënt. “Bovendien zijn we referencecenter voor de schouderprothesiologie”, voegt Beumer toe. “Veel buitenregionale patiënten worden naar ons
verwezen met klachten aan de bovenste ledematen, ook door academische centra. We
hebben veel expertise op dat gebied opgebouwd en zijn een verwijzingscentrum geworden.
Ook qua beste zorg voor de patiënt gaat het goed. In de Elsevier-enquête zijn we hoog
geëindigd met ingrepen aan heupen en knieën. En voor de herniazorg hebben we drie
sterren toegekend gekregen.”
Ambities
Ook spine-chirugie is een speerpunt, maar Beumer legt uit dat dit een beetje dreigt vast
te lopen door onvoldoende middelen. “Kinderen met scoliose hebben heel bijzondere
operaties nodig om de zenuwbanen te monitoren en dwarslaesies te voorkomen. Terwijl
we de expertise en de wens hebben voor zulke operaties, krijgen we het organisatorisch
nog niet rond. Hier zullen we zeker energie in blijven steken, om ook de monitoring en
anesthesie georganiseerd te krijgen. We willen graag meer vakgroepoverstijgend werken.”
De droom van de vakgroep is om op termijn een eigen orthopedisch centrum te beginnen.
Nu al werken ze gespecialiseerd in straten en pleinen per soort ingreep, waardoor een
patiënt meteen doorkan. De bedoeling is om daar ook gespecialiseerd aanvullend personeel
bij te betrekken. Nu al hebben ze een maatschapsmanager benoemd, de wens is om ook
een fulltime orthopediewetenschapper aan te trekken. “Dan kunnen wij blijven opereren
en – een deel van – de onderzoeksactiviteiten delegeren”, zegt Eygendaal.
Kerngegevens zorgkern Orthopedie
• 13 orthopedisch chirurgen: A.F.A. (Ad) van Beurden, R. (Ronald) Boer,
dr. S.B.T. (Stefan) Bolder, mw. M.P.J. (Maaike) van den Borne, L.H.G.J. (Leon) Elmans,
mw. dr. D. (Denise) Eygendaal, dr. R.C.I. (Rutger) van Geenen , W.H.J.C. (Wim) van
Heeswijk, E.A. (Eric) Hoebink, J.A.A.M. (Joost) van den Hout, A.J.P. (Peter) Joosten,
dr. A.F.C.M. (Sjors) Moonen, dr. R. (Robert) Wagenmakers.
• 1 assistent in opleiding
• subspecialismen: wervelkolom, kinderorthopedie, bovenste extremiteit, onderste
extremiteit, traumatologie, sportorthopedie
Orthopedie
157
• 14 orthopeden: mw. dr. A. (Annechien) Beumer, A.F.A. (Ad) van Beurden, R. (Ronald)
Boer, dr. S.B.T. (Stefan) Bolder, mw. M.P.J. (Maaike) van den Borne, L.H.G.J. (Leon)
Elmans, mw. dr. D. (Denise) Eygendaal, dr. R.C.I. (Rutger) van Geenen, W.H.J.C. (Wim)
van Heeswijk, E.A. (Eric) Hoebink, J.A.A.M. (Joost) van den Hout, A.J.P. (Peter)
Joosten, dr. A. (Arthur) Lim, dr. A.F.C.M. (Sjors) Moonen, dr. R. (Robert) Wagenmakers
• 2 fellows
• 2 gespecialiseerd verpleegkundigen
Lopende onderzoeken (een selectie)
158
• MRI after resurfacing arthroplasty of the shoulder. A feasibility study. Door gebruik te
maken van het nieuwste type kop bij schouderprotheses is beoordelen van de spieren
rondom de schouder na de ingreep mogelijk middels MRI.
• Een aantal studies rond de heupprothese. Bijvoorbeeld wel of geen cementgebruik bij
kop-halsprotheses; deelname aan een multicenterstudie naar kop-halsprotheses en het
beoordelen van de botkwaliteit bij een speciale heupcup.
• Tissue sparing approach and rapid recovery after total knee arthroplasty. Studielijn naar
knieprothese: versneld herstel van de patiënt door minimaal invasieve techniek.
• Transcranial electro stimulation in spinal deformities. Studielijn naar de controle van
zenuwbanen tijdens chirurgie en het vergelijken van verschillende technieken bij
wervelkolomchirurgie.
• Spondylolisthesis study: observational study of three different techniques.
Hermans JJ, Beumer A, Hop WC, Moonen AF, Ginai AZ. Tibiofibular syndesmosis in acute
ankle fractures: additional value of an oblique MR image plane. Skeletal Radiol.
2012 Feb;41(2):193-202. Epub 2011 Apr 30.
OBJECTIVE: To evaluate the additional value of a 45° oblique MRI scan plane for assessing
the anterior and posterior distal tibiofibular syndesmotic ligaments in patients with an acute
ankle fracture. MATERIALS AND METHODS: Prospectively, data were collected for 44 consecutive
patients with an acute ankle fracture who underwent a radiograph (AP, lateral, and mortise
view) as well as an MRI in both the standard three orthogonal planes and in an additional 45°
oblique plane. The fractures on the radiographs were classified according to Lauge-Hansen (LH).
The anterior (ATIFL) and posterior (PTIFL) distal tibiofibular ligaments, as well as the presence
of a bony avulsion in both the axial and oblique planes was evaluated on MRI. MRI findings
regarding syndesmotic injury in the axial and oblique planes were compared to syndesmotic
injury predicted by LH. Kappa and the agreement score were calculated to determine the
interobserver agreement. The Wilcoxon signed rank test and McNemar’s test were used to
compare the two scan planes. RESULTS: The interobserver agreement (k) and agreement score
[AS (%)] regarding injury of the ATIFL and PTIFL and the presence of a fibular or tibial avulsion
fracture were good to excellent in both the axial and oblique image planes (k 0.61-0.92, AS
84-95%). For both ligaments the oblique image plane indicated significantly less injury than the
axial plane (p < 0.001). There was no significant difference in detection of an avulsion fracture
in the axial or oblique plane, neither anteriorly (p = 0.50) nor posteriorly (p = 1.00). With
syndesmotic injury as predicted by LH as comparison, the specificity in the oblique MR plane
increased for both anterior (to 86% from 7%) and posterior (to 86% from 48%) syndesmotic
injury when compared to the axial plane. CONCLUSION: Our results show the additional value
of an 45° oblique MR image plane for detection of injury of the anterior and posterior distal
tibiofibular syndesmoses in acute ankle fractures. Findings of syndesmotic injury in the oblique
MRI plane were closer to the diagnosis as assumed by the Lauge-Hansen classification than
in the axial plane. With more accurate information, the surgeon can better decide when to
stabilize syndesmotic injury in acute ankle fractures.
159
PMCID:PMC3244606
Hermans JJ, Wentink N, Beumer A, Hop WC, Heijboer MP, Moonen AF, Ginai AZ.
Correlation between radiological assessment of acute ankle fractures and syndesmotic
injury on MRI. Skeletal Radiol. 2011 Oct 20. [Epub ahead of print]
OBJECTIVE: Owing to the shortcomings of clinical examination and radiographs, injury to the
syndesmotic ligaments is often misdiagnosed. When there is no indication requiring that the
fractured ankle be operated on, the syndesmosis is not tested intra-operatively, and rupture
of this ligamentous complex may be missed. Subsequently the patient is not treated properly
leading to chronic complaints such as instability, pain, and swelling. We evaluated three fracture
classification methods and radiographic measurements with respect to syndesmotic injury.
MATERIALS AND METHODS: Prospectively the radiographs of 51 consecutive ankle fractures were
classified according to Weber, AO-Müller, and Lauge-Hansen. Both the fracture type and additional
measurements of the tibiofibular clear space (TFCS), tibiofibular overlap (TFO), medial clear space
(MCS), and superior clear space (SCS) were used to assess syndesmotic injury. MRI, as standard
of reference, was performed to evaluate the integrity of the distal tibiofibular syndesmosis. The
sensitivity and specificity for detection of syndesmotic injury with radiography were compared
to MRI. RESULTS: The Weber and AO-Müller fracture classification system, in combination with
additional measurements, detected syndesmotic injury with a sensitivity of 47% and a specificity
of 100%, and Lauge-Hansen with both a sensitivity and a specificity of 92%. TFCS and TFO did
not correlate with syndesmotic injury, and a widened MCS did not correlate with deltoid ligament
injury. CONCLUSION: Syndesmotic injury as predicted by the Lauge-Hansen fracture classification
Orthopedie
correlated well with MRI findings. With MRI the extent of syndesmotic injury and therefore
fracture stage can be assessed more accurately compared to radiographs.
Hermans JJ, Ginai AZ, Wentink N, Hop WC, Beumer A. The additional value of an oblique
image plane for MRI of the anterior and posterior distal tibiofibular syndesmosis. Skeletal
Radiol. 2011 Jan;40(1):75-83. Epub 2010 Jun 13.
OBJECTIVE: The optimal MRI scan planes of collateral ligaments of the ankle have been
described extensively, with the exception of the syndesmotic ligaments. We assessed the optimal
scan plane for depicting the distal tibiofibular syndesmosis. MATERIALS AND METHODS: In order
to determine the optimal oblique caudal-cranial and lateral-medial MRI scan plane, two fresh
frozen cadaveric ankles were used. The angle of the scan plane that demonstrated the anterior
and posterior distal tibiofibular ligament uninterrupted in their full length was determined. In
a prospective study this oblique scan plane was then used in addition to the axial and coronal
planes, for MRI scans of both ankles in 21 healthy volunteers. Two observers independently
160
evaluated the anterior tibiofibular ligament (ATIFL) and posterior tibiofibular ligament
(PTIFL) regarding the continuity of the individual fascicles, thickness and wavy contour of
the ligaments in both the axial and the oblique plane. Kappa was calculated to determine the
interobserver agreement. McNemar’s test was used to statistically quantify the significance
of the two scan planes. RESULTS: In the axial plane the ATIFL was in 31% (13/42) partly and
in 69% (29/42) completely discontinuous; in the oblique plane the ATIFL was continuous in
88% (37/42) and partly discontinuous in 12% (5/42). Compared with the axial plane, the
oblique plane demonstrated significantly less discontinuity (p<0.001), but not significantly
less thickening (p=1.00) or less wavy contour (p=0.06) of the ATIFL. In the axial scan plane the
PTIFL was continuous in 76% (32/42), partially discontinuous in 19% (8/42) and completely
discontinuous in 5% (2/42); in the oblique plane the PTIFL was continuous in 100% (42/42).
Compared with the axial plane, the oblique plane demonstrated significantly less discontinuity
(p=0.002), but not significantly less thickening (p=1.00) or less wavy contour (p=0.50) of
the PTIFL. The interobserver agreement score and kappa (k) regArding the continuity for the
ATIFL in the axial and oblique planes was 91% (k =0.79) and 91% (k =0.55) respectively; for
the PTIFL it was 86% (k=0.65) and 100% (k = noT defined). CONCLUSION: The ATIFL and PTIFL
are routinuely scanned in the orthogonal planes. The advantage of MRI scanning in an oblique
image plane of about 45 degrees permits a better evaluation of the ligaments compared with
the axial plane, particularly a better interpretation of ligament continuity, thickening and wavy
contour. This may lead to a reduction in false-positive results, especially regarding partial or
complete ligament ruptures. This can be of considerable aid in therapeutic management.
PMCID:PMC2989003
Wagener ML, Beumer A, Swierstra BA. Chronic instability of the anterior tibiofibular
syndesmosis of the ankle. Arthroscopic findings and results of anatomical reconstruction.
BMC Musculoskelet Disord. 2011 Sep 27;12:212.
BACKGROUND: The arthroscopic findings in patients with chronic anterior syndesmotic
instability that need reconstructive surgery have never been described extensively. METHODS:
In 12 patients the clinical suspicion of chronic instability of the syndesmosis was confirmed
during arthroscopy of the ankle. All findings during the arthroscopy were scored. Anatomical
reconstruction of the anterior tibiofibular syndesmosis was performed in all patients. The AOFAS
score was assessed to evaluate the result of the reconstruction. At an average of 43 months after
the reconstruction all patients were seen for follow-up. RESULTS: The syndesmosis being easily
accessible for the 3 mm transverse end of probe which could be rotated around its longitudinal
axis in all cases during arthroscopy of the ankle joint, confirmed the diagnosis. Cartilage damage
was seen in 8 ankles, of which in 7 patients the damage was situated at the medial side of the
ankle joint. The intraarticular part of anterior tibiofibular ligament was visibly damaged in 5
patients. Synovitis was seen in all but one ankle joint. After surgical reconstruction the AOFAS
score improved from an average of 72 pre-operatively to 92 post-operatively. CONCLUSIONS:
To confirm the clinical suspicion, the final diagnosis of chronic instability of the anterior
syndesmosis can be made during arthroscopy of the ankle. Cartilage damage to the medial side
of the tibiotalar joint is often seen and might be the result of syndesmotic instability. Good
results are achieved by anatomic reconstruction of the anterior syndesmosis, and all patients in
this study would undergo the surgery again if necessary.
PMCID:PMC3191511
Guitton TG, Ring D; Science of Variation Group* [Elmans LH et al...]. Interobserver
reliability of radial head fracture classification: two-dimensional compared with threedimensional CT. J Bone Joint Surg Am. 2011 Nov 2;93(21):2015-21.
BACKGROUND: The Broberg and Morrey modification of the Mason classification of radial
head fractures has substantial interobserver variation. This study used a large web-based
collaborative of experienced orthopaedic surgeons to test the hypothesis that three-dimensional
reconstructions of computed tomography (CT) scans improve the interobserver reliability of the
classification of radial head fractures according to the Broberg and Morrey modification of the
Mason classification. METHODS: Eighty-five orthopaedic surgeons evaluated twelve radial head
fractures. They were randomly assigned to review either radiographs and two-dimensional CT
scans or radiographs and three-dimensional CT images to determine the fracture classification,
fracture characteristics, and treatment recommendations. The kappa multirater measure ( )
was calculated to estimate agreement between observers. RESULTS: Three-dimensional CT had
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161
moderate agreement and two-dimensional CT had fair agreement among observers for the
Broberg and Morrey modification of the Mason classification, a difference that was significant.
Observers assessed seven fracture characteristics, including fracture line, comminution, articular
surface involvement, articular step or gap of =2 mm, central impaction, recognition of more
than three fracture fragments, and fracture fragments too small to repair. There was a significant
difference in kappa values between three-dimensional CT and two-dimensional CT for fracture
fragments too small to repair, recognition of three fracture fragments, and central impaction.
The difference between the other four fracture characteristics was not significant. Among
treatment recommendations, there was fair agreement for both three-dimensional CT and twodimensional CT. CONCLUSIONS: Although three-dimensional CT led to some small but significant
decreases in interobserver variation, there is still considerable disagreement regarding
classification and characterization of radial head fractures. Three-dimensional CT may be
insufficient to optimize interobserver agreement. *Collaborators (88): Earp BE, Ladd AL, Evans
PJ, Kuo CE, Biert J, van Dijk CN, Dantuluri PK, Ruchelsman DE, Ponsen KJ, Soong M, Davis T,
Shyam AK, Phieffer LS, LeCroy CM, Richardson M, Schmidt AH, Jebson PL, Levin PE, Della Rocca
GJ, Goldfarb CA, Jeray KJ, Kalainov DM, Dyer GS, Chen NT, Osterman AL, Athwal GS, Leenen LP,
162
Wright TW, Swiontkowski MF, Slutsky DJ, Frihagen F, Duncan SF, Papandrea RF, Chung KC, Blazar
P, Feibel RJ, Zura RD, van der Heide HJ, Tashjian RZ, Elmans L, Jiuliano JA, Rizzo M, Sodha S,
McAuliffe JA, Culp RW, Orbay J, Cassidy C, Albers RG, Katolik LI, Abrams RA, Baratz ME, Egol
KA, Conflitti JM, Hanel DP, Nolla JM, Hausman M, Caputo AE, Poolman RW, Axelrod TS, McKee
MD, Goslings JC, Sancheti PK, Brink PR, Swigart CR, Hughes TB, Segalman KA, van Eerten PV,
Crist BD, Diao E, Page RS, Lattanza LL, Thomas G, Fanuele JC, Kloen P, Gosens T, Zalavras C,
Taras JS, Greenberg JA, Hammerberg EM, Catalano LW 3rd, Pesantez RF, van Vugt AB, Kronlage
SC, Baskies MA, Boyer MI, Giannoudis PV, Prayson MJ, Grosso E.
Lackner M, De Man FH, Eygendaal D, Wintermans RG, Kluytmans JA, Klaassen CH, Meis JF.
Severe prosthetic joint infection in an immunocompetent male patient due to a therapy
refractory Pseudallescheria apiosperma. Mycoses. 2011 Oct;54 Suppl 3:22-7.
Prosthetic joint infections (PJI) are rarely due to fungal agents and if so they are mainly caused
by Candida strains. This case represents a PJI caused by a multi-drug resistant Pseudallescheria
apiosperma, with poor in vivo response to itraconazole and voriconazole. This case differs
also by the way of infection, since the joint infection did not follow a penetrating trauma. In
the majority of cases, Scedosporium extremity infections remain local in immunocompetent
individuals. We report a persistent joint infection with multiple therapeutic failures, and
subsequent amputation of the left leg. Detailed clinical data, patient history, treatment regime
and outcome of a very long-lasting (>4 years) P. apiosperma prosthetic knee infection in an
immunocompetent, 61-year-old male patient are presented with this case. The patient was
finally cured by the combination of multiple and extensive surgical interventions and prolonged
antifungal combination therapy with voriconazole and terbinafine. © 2011 Blackwell Verlag
GmbH.
Cefo I, Eygendaal D. Arthroscopic arthrolysis for posttraumatic elbow stiffness. J Shoulder
Elbow Surg. 2011 Apr;20(3):434-9.
BACKGROUND: Loss of motion of the elbow joint is a common finding after elbow trauma.
Restoration of motion of the posttraumatic stiff elbow can be a difficult, time-consuming, and
costly challenge. Arthroscopic capsular release of stiff elbows has recently been introduced as a
safe but technically demanding technique. The outcome in 27 patients treated by arthroscopic
capsular release was assessed. MATERIALS AND METHODS: We evaluated 27 patients (17 women)
who were an average age of 42 years (range, 14-65) at 3, 12, and 24 months after arthroscopic
capsular release of a posttraumatic stiff elbow. Range of motion (ROM) and Elbow Function
Assessment (EFA) were measured. RESULTS: Before the arthroscopic procedure, the mean flexion
was 123° (SD 8°), extension was 24° (SD 9°), and total ROM was 99° (SD 11°), and after
surgery, flexion improved significantly to 133° (SD 5°), extension to 7° (SD 6°), and total ROM
to 125° (SD 10°). The mean (SD) EFA showed improvement from 69 (SD 4) preoperatively to
91 (SD 4) postoperatively. The postoperative outcomes at 3, 12 and 24 months were similar.
One postoperative superficial infection of the lateral portal occurred and was successfully
treated with oral antibiotics. No vascular or neurologic complications were noted. DISCUSSION:
Historical data underscore the fact that arthroscopic release of posttraumatic elbow contracture
is technically demanding but can effective improve the elbow arc of motion. CONCLUSION:
Arthroscopic capsular release of the elbow is a safe and reliable treatment for patients with a
posttraumatic elbow contracture. Copyright © 2011 Journal of Shoulder and Elbow Surgery Board
of Trustees. Published by Mosby, Inc. All rights reserved.
with 42 radial head fractures underwent a MRI scan after a mean of 7.0 days after trauma and
were reviewed after a mean of 13.3 months. RESULTS: MRI showed 24 of 42 elbows had a lateral
collateral ligament (LCL) lesion, 1 had a medial collateral ligament (MCL) and LCL lesion, 16
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163
had an injury of the capitellum, 1 had a coronoid fracture, and 2 had loose osteochondral
with no significant difference between patients with and without associated injuries (P = .8).
CONCLUSION: Most injuries found with MRI in patients with radial head fractures are not
Van Rijn J, Dorleijn DM, Boetes B, Wiersma-Tuinstra S, Moonen S. Missing the lisfranc
fracture: a case report and review of the literature. J Foot Ankle Surg.
2012 Mar;51(2):270-4. Epub 2011 Dec 9.
Injuries to the tarsometatarsal joint are infrequent and the presentation varies. The radiologic
164
evaluation can be difficult, and injuries are missed initially in up to one third of cases. A
60-year-old female sports instructor presented to the emergency department with a Lisfranc
fracture dislocation of the foot as result of an indirect trauma. The patient attended to a
hospital the day she sustained the injury, where the Lisfranc fracture was missed. At our
hospital, the patient underwent immediate restoration of the dislocation. Because of swelling,
internal fixation was applied 2 weeks later. Postoperatively, the patient was mobilized in a nonweight-bearing plaster cast for 6 weeks, continued by progressive weight-bearing in a walker.
The fixation screws were removed 3 months after surgery. Lisfranc fractures are rare injuries and
can be missed at first sight. Careful clinical examination and radiographs in 3 different planes
are required to identify the injury. Computed tomography might be helpful when the findings
from the above-mentioned examinations are inconclusive. Operative treatment, including
anatomic reduction and fixation, is required in almost all cases to achieve the best satisfactory
result. Long-term complications include secondary arthritis and foot deformities, which can be
treated by foot ortheses or arthrodesis. Copyright © 2012 American College of Foot and Ankle
Surgeons. Published by Elsevier Inc. All rights reserved.
Wagenmakers R, Stevens M, Groothoff JW, Zijlstra W, Bulstra SK, van Beveren J, van Raaij
JJ, van den Akker-Scheek I. Physical activity behavior of patients 1 year after primary
total hip arthroplasty: a prospective multicenter cohort study. Phys Ther.
2011 Mar;91(3):373-80. Epub 2011 Jan 13.
BACKGROUND: Besides the important beneficial effects of regular physical activity on general
health, some of the musculoskeletal effects of physical activity are of particular interest for
older adults after total hip arthroplasty (THA). However, research on physical activity behavior
of patients after THA is scarce. OBJECTIVE: The purpose of this study was to gain insight into
the physical activity behavior and fulfillment of guidelines for health-enhancing physical
activity of patients 1 year after THA. Design This was a prospective multicenter cohort study.
METHODS: To determine level of physical activity, 653 participants (response rate=77%)
completed the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH).
Comparisons were made between participants in 2 age groups (=75 and >75 years). Determinants
of physical activity behavior were assessed. RESULTS: The participants were physically active
a mean of 1,468 minutes per week. Most time was spent in household and leisure activities.
Younger participants were physically more active than older participants. A lower body mass
index was predictive of a higher level of physical activity. Participants adhered to the guidelines
of health-enhancing physical activity in 67% of cases. The guidelines were met more often by
younger participants, male participants, and those without problems in the lower extremities.
Limitations A nonresponse analysis was not conducted; thus, there might have been a selection
bias. Use of a self-administered recall questionnaire to assess physical activity behavior may
have been subject to memory and recall skill limitations of the participants, and patients tend
to overestimate their physical activity level. CONCLUSIONS: This study gives detailed insight into
the physical activity of patients 1 year after primary THA. As among the general population,
a considerable number of patients were found to be insufficiently physically active.
Reininga IH, Stevens M, Wagenmakers R, Boerboom AL, Groothoff JW, Bulstra SK, Zijlstra
W. Compensatory trunk movements in patients with hip osteoarthritis: accuracy and
reproducibility of a body-fixed sensor-based assessment. Am J Phys Med Rehabil. 2011
Aug;90(8):681-7.
This study examined the accuracy and reproducibility of a body-fixed sensor-based assessment
for quantifying frontal plane angular movements of the (upper) thorax and pelvis of patients
with hip osteoarthritis at different walking speeds. To evaluate accuracy, the angular movements
of sensors attached to the thorax and pelvis of three patients were compared with results based
on an optical motion analysis system. Accuracy was high, with small and consistent mean
differences (<1.0 degree) and corresponding standard deviations (<1.3 degrees) between optical
motion analysis system and body-fixed sensor data. To evaluate reproducibility, angular trunk
movements were assessed twice in 15 patients. Reproducibility was high (intraclass correlation
coefficients ranged from 0.86 to 0.97), and the values of the mean differences between the
test and retest were small, with the 95% confidence interval containing zero. This body-fixed
sensor-based assessment is an accurate and reproducible method for quantifying frontal plane
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165
compensatory trunk movements during gait of patients with hip osteoarthritis at different
walking speeds.
Stevens M, Paans N, Wagenmakers R, van Beveren J, van Raay JJ, van der Meer K,
Stewart R, Bulstra SK, Reininga IH, van den Akker-Scheek I The influence of overweight/
obesity on patient-perceived physical functioning and health-related quality of life after
primary total hip arthroplasty. Obes Surg. 2011 Jul 29. [Epub ahead of print]
BACKGROUND: Overweight/obesity in patients after total hip arthroplasty (THA) is a growing
problem and is associated with postoperative complications and a negative effect on functional
outcome. The objective of this study is to determine to what extent overweight/obesity is
associated with physical functioning and health-related quality of life 1 year after primary
THA. METHODS: A retrospective analysis of prospectively collected data from 653 patients who
had undergone a primary THA was conducted. Physical functioning, health-related quality of
life, body mass index (BMI), comorbidity, and postoperative complications were assessed by
166
means of a questionnaire and from medical records. To determine to what extent overweight/
obesity is associated with physical functioning and health-related quality of life after THA,
a structural equation model (SEM) analysis was conducted. RESULTS: The association of BMI
corrected for age, gender, complications, and comorbidity with physical functioning is -0.63.
This means that an increase in 1 kg/m(2) BMI leads to a reduction of 0.63 points in the
physical functioning score as measured with the Western Ontario and McMaster Universities
Osteoarthritis Index (100-point scale). The prevalence of complications or comorbidity leads to
a reduction of, respectively, 5.63 and 7.25 (one or two comorbidities) and 14.50 points in the
case of more than two comorbidities on the physical functioning score. The same pattern is
observed for health-related quality of life. CONCLUSIONS: The influence of overweight/obesity
on physical functioning and health-related quality of life is low. The impact of complications
and comorbidity is considerable. Refusing a patient a THA solely on the basis of overweight or
obesity does not seem justified.
PMID: 21800224[PubMed - as supplied by publisher]
ankle fractures: additional value of an oblique MR image plane. Skeletal Radiol.
2012 Feb;41(2):193-202. Epub 2011 Apr 30.
image plane for MRI of the anterior and posterior distal tibiofibular syndesmosis.
Skeletal Radiol. 2011 Jan;40(1):75-83. Epub 2010 Jun 13.
syndesmosis of the ankle. Arthroscopic findings and results of anatomical
reconstruction. BMC Musculoskelet Disord. 2011 Sep 27;12:212.
Guitton TG, Ring D; Science of Variation Group* [ Elmans LH et al...]. Interobserver
Elbow Surg. 2011 Apr;20(3):434-9.
Rahusen F, Eygendaal D. Arthroscopic surgery of the elbow; Indications, contraIndications, Complications and operative technique. Surg. Science
2011;2(5):219-223.
167
Kaas L, Jupiter JB, van Dijk CN, Eygendaal D. Management of radial head fractures:
current concepts. Shoulder and Elbow 2011;3:34–40.
ankle fractures: additional value of an oblique MR image plane. Skeletal Radiol. 2012
Feb;41(2):193-202. Epub 2011 Apr 30.
fracture: a case report and review of the literature. J Foot Ankle Surg. 2012
Mar;51(2):270-4. Epub 2011 Dec 9.
2011 Mar;91(3):373-80. Epub 2011 Jan 13.
Wagenmakers R, Degener JE. Infecties van botten en gewrichten. In: Microbiologie en
Infectieziekten / Hoepelman [red.] [et al...]. Houten : Bohn Stafleu van Loghum,
2011. ISBN 9789031379439.
Orthopedie
Stevens M, van den Akker - Scheek I, Hamelink J, Reininga I, den Uyl - Verlinden K,
Wagenmakers R, Bulstra S. Een Nieuwe Heup of Knie: Hoe Wordt U Weer Lichamelijk
en Sportief Actief. Houten: Bohn, Stafleu van Loghum, 2011. ISBN 9789031387991.
Reininga IH, Stevens M, Wagenmakers R, Boerboom AL, Groothoff JW, Bulstra SK,
Zijlstra W.
Compensatory trunk movements in patients with hip osteoarthritis: accuracy and
reproducibility of a
body-fixed sensor-based assessment. Am J Phys Med Rehabil. 2011 Aug;90(8):681-7.
Stevens M, Paans N, Wagenmakers R, van Beveren J, van Raay JJ, van der Meer K,
Stewart R,
Bulstra SK, Reininga IH, van den Akker-Scheek I The influence of overweight/obesity on
patient-perceived physical functioning and health-related quality of life after primary
total hip arthroplasty. Obes Surg. 2011 Jul 29. [Epub ahead of print]
168
Pathologie
Kerngegevens zorgkern Pathologie
• 5 Pathologen: mw. L.S.M. (Luthy) Alcalá, mw. dr. D.E. (Dorothee) Arnold,
K.E.S. (Kristoff) Duthoi, J. (Jan) Los, dr. P.E.J. (Peter) de Wit
169
2011;2011:785425. Epub 2011 Apr 10.
inherent in cytology obtained by routine FNA.
PMID: 21559244 [PubMed]
PMCID: PMC3087462
Pathologie
Publicatielijst
2011;2011:785425. Epub 2011 Apr 10.
170
Radiologie
Kerngegevens zorgkern Radiologie
• 16 radiologen: K. (Koen) Borsje, H.F.C.M. (Hein) Brands, H.A.J. (Homme) Dijkstra,
G.P.J. (Gé) Geenen, H.A.W. (Dirk) Haans, Th.E.A.M. (Thijs) de Jong, P.A.M. (Peter) Kint,
M.M. (Mark) Krouwels, mw. I. (Ilse) Niers-Stobbe, P.A.M. (Peter) Raaijmakers,
M.G. (Mark) Romijn, E. (Evert) Sanders, M.F.A.M. (Maarten) Sturm, dr. E. (Eric)
Tetteroo, J.L. (Jeroen) Turkenburg, R.J. (Rob) Versteylen, L.D. (Douwe) Vos.
• subspecialismen: interventieradiologie, mammaradiologie
Van Schaik DE, Dolmans DE, Ho G, Geenen GP, Vos L, Van Der Waal JC, De Groot HG,
Van der Laan L. Ruptured abdominal aortic aneurysm: endovascular or open approach in a
AIM: We compared the outcomes of 56 patients with a ruptured abdominal aortic aneurysm
(RAAA) who underwent either open repair or emergency endovascular aneurysm repair (eEVAR)
in a general hospital. It seems feasible that the availability of eEVAR for treatment of RAAA
could lead to a decrease in hospital mortality. METHODS: We analyzed all admitted patients with
a RAAA, between January 2006 and April 2008, eEVAR is compared to open repair. We studied
30 days mortality, intensive care unit stay, hospital stay, total blood loss and complications.
RESULTS: Fifteen eEVAR procedures (26.8%) were performed. Mortality in the eEVAR-group
was 26%, in the open repair-group 46%. Mean intensive care unit stay was 3.9 days and 4.8
days in the eEVAR-group and open repair-group, respectively. Mean hospital stay was 13 days
and 10.5 days. The average blood loss was 210cc and 2760cc. The amount of blood products
for transfusion was significantly higher in the open repair. Overall complication rate was not
significantly different in both treatment groups. CONCLUSION: Treatment in a Dutch general
Radiologie
171
hospital of a RAAA with an eEVAR procedure has a lower mortality in comparison to the open
repair. Therefore, whenever possible the eEVAR is the preferred treatment method.
resonance imaging reveals edema-like changes not only subcutaneously, but also in muscle
tissue after femoropopliteal bypass surgery. Ann Vasc Surg. 2012 Feb;26(2):233-41. Epub
2011 Nov 1.
BACKGROUND: The pathophysiological mechanisms that induce postrevascularization edema
after femoropopliteal bypass surgery are not completely understood. Reperfusion-associated
injury to revascularized tissue and damage to lymphatic structures are both likely to play a role.
Aim of this study was to study edema formation after peripheral bypass surgery with magnetic
resonance imaging. MATERIALS AND METHODS: Nine patients suffering from severe peripheral
arterial occlusive disease were subjected to magnetic resonance imaging scans before and 1 week
after autologous femoropopliteal or femorocrural bypass surgery. RESULTS: A 12% increase
172
in volume of the upper legs and an 11% increase in volume of the lower legs were measured
in patients postoperatively. The increase of volume was largely due to expansion of the
subcutaneous compartments: a 35% increase in the upper legs and a 41% increase in the lower
legs. Edema in the upper legs was predominantly located medially at the site of the surgical
wound. In contrast, edema in the lower legs was homogenously distributed around the entire
leg circumference. The muscle compartment showed no significant change of volume. However,
in the majority of patients, edema-like changes were seen in selected muscles as well after a
peripheral bypass reconstruction. CONCLUSION: Swelling of the subcutaneous compartments
is mainly responsible for the volume increases in upper and lower legs similar to lymphatic
edema. In addition, in a majority of patients, edema-like changes in selected muscles were seen
especially in the upper legs. Reperfusion-associated injury as a cause of these changes cannot
be ruled out. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All
rights reserved.
with 42 radial head fractures underwent a MRI scan after a mean of 7.0 days after trauma
and were reviewed after a mean of 13.3 months. RESULTS: MRI showed 24 of 42 elbows had a
lateral collateral ligament (LCL) lesion, 1 had a medial collateral ligament (MCL) and LCL lesion,
16 had an injury of the capitellum, 1 had a coronoid fracture, and 2 had loose osteochondral
with no significant difference between patients with and without associated injuries (P = .8).
CONCLUSION: Most injuries found with MRI in patients with radial head fractures are not
173
Van Schaik DE, Dolmans DE, Ho G, Geenen GP, Vos L, Van dr Waal JC, De Groot HG, Van
Radiologie
174
Ned Tijdschr Traumatol. 2011;2:38-41.
2012 Feb;26(2):233-41. Epub 2011 Nov 1.
Van Schaik DE, Dolmans DE, Ho G, Geenen GP, Vos L, Van Der Waal JC, De Groot HG, Van
2012 Feb;26(2):233-41. Epub 2011 Nov 1.
Reumatologie
Kerngegevens zorgkern Reumatologie
• 5 reumatologen: mw. C.W.Y. (Cathelijne) Appels, mw. N.H.A.M. (Natasja) Denissen,
mw. B. (Bouchra) Lechkar, F.M.A. (Frank) Slaats, mw. P.A.J.M. (Petra) Vos
175
Vos PA, Mastbergen SC, Huisman AM, de Boer TN, Degroot J, Polak AA, Lafeber FP. In end
stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters
of cartilage damage. Osteoarthritis Cartilage. 2012 Mar;20(3):233-40. Epub 2011 Dec 21.
OBJECTIVES: Age is the most prominent predisposition for development of osteoarthritis
(OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation
endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the
biomechanical properties of the cartilage matrix and influence chondrocyte activity. In clinical
studies AGEing of cartilage and its relation to actual cartilage damage can only be measured
by surrogate markers (e.g., serum, skin or urine AGE levels and imaging or biochemical
markers of cartilage damage). In this study actual cartilage AGE levels were directly related to
actual cartilage damage by use of cartilage obtained at joint replacement surgery. METHODS:
Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement.
Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated
macroscopically, histologically, and biochemically. RESULTS: Cartilage and urine pentosidine
both increased with increasing age. The higher the macroscopic, histological, and biochemical
cartilage damage the lower the cartilage pentosidine levels were. In multiple regression analysis
age is not found to be a confounder. CONCLUSION: There is an inverse relation between cartilage
AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective)
Reumatologie
increased turnover of cartilage matrix proteins even in end stage disease. Copyright © 2011
Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Publicatielijst
Vos PA, Mastbergen SC, Huisman AM, de Boer TN, Degroot J, Polak AA, Lafeber FP. In end
stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters
of cartilage damage. Osteoarthritis Cartilage. 2012 Mar;20(3):233-40. Epub 2011 Dec 21.
176
Seksuologie
Kerngegevens zorgkern Seksuologie
• 2 seksuologen: mw. J. (Coby) van Essen, mw. H. (Hester) Pastoor
Pastoor H. Polycysteusovariumsyndroom en seksualiteit. In: Reproductieve geneeskunde,
gynaecologie en obstetrie anno 2011. Slager E.[ed.]. Haarlem : DCHC, 2011:662-66.
Polycysteus ovariumsyndroom (PCOS) is een veel voorkomende (5-10%) endrocriene aandoening
bij vrouwen. De kenmerken zijn: 1. polycysteuze ovaria, 2. klinische of biochemische
aanwijzingen voor hyperandrogenisme, 3. oligomenorroe of amenorroe.Voor de diagnose volgens
de wereldwijd geldende Rotterdamse consensus moet een vrouw aan minstens twee van de drie
kenmerken voldoen.
Daarnaast is PCOS vaak geassocieerd met obesitas en insulineresistentie. Ook blijkt het metabool
syndroom vaker bij patiënten met PCOS voor te komen. Ten slotte kan PCOS naast deze risico’s
en onvruchtbaarheid ook aanleiding geven tot invaliderende overbeharing en acne.
Diverse studies tonen aan dat de kwaliteit van leven bij vrouwen met PCOS verlaagd is. Er
is sprake van verschillende psychosociale gevolgen als angst, depressie en onzekerheid door
bijvoorbeeld de uiterlijke kenmerken (obesitas, acne, hirsutisme) of fertiliteitsproblemen
als gevolg van PCOS. Vrouwen zelf rapporteren angsten met betrekking tot verlies van
vrouwelijkheid en seksualiteit.
Tot op heden is relatief weinig bekend over de gevolgen van PCOS op seksueel functioneren.
Ondanks verhoogde androgenenniveau’s wordt regelmatig verminderd seksueel verlangen
gemeld. Er zijn aanwijzingen dat gebruik van anti-androgenen het seksueel verlangen verder
kan verlagen. Seksueel functioneren in zijn geheel en seksuele satisfactie zijn verminderd ten
Seksuologie
177
opzichte van controlegroepen. Psychosociale factoren zijn tevens verantwoordelijk voor deze
bevindingen.
Bespreekbaar maken van psychosociale en seksuele factoren bij vrouwen met PCOS is raadzaam.
Evenals rekening houden met de samenstelling van voor te schrijven orale anticonceptie.
178
Urologie
Kerngegevens zorgkern Urologie
• 6 urologen: P.J. (Pieter) van den Broeke, H. (Harald) Jansen, mw. I E.W. (Ilze) van
Onna, E.H.G.M. (Eric) Oomens, P.J. (Péjé) Posthumus, D.K.E. (Deric) van der Schoot
• 1 assistent in opleiding
• subspecialismen: oncologie (kwaadaardige aandoeningen), stenen (in nieren,
urineleiders of blaas), functionele urologie (incontinentie, plasklachten en
neurologische blaasproblemen), andrologie (erectiestoornissen, fertiliteit en ouder
wordende man), kinderen (aangeboren afwijkingen), algemeen (vergrote prostaat en
plasbuisafwijkingen)
Meijer RP, van Onna IE, Kok ET, Bosch R. The risk profiles of three clinical types of
carcinoma in situ of the bladder. BJU Int. 2011 Sep;108(6):839-43. Epub 2010 Dec 16.
OBJECTIVE: • To further clarify the risk profiles of three clinical types of carcinoma in situ (CIS)
of the bladder. MATERIALS AND METHODS: • Population-based data from the Comprehensive
Cancer Centre Middle Netherlands, as part of the nationwide Netherlands Cancer Registry,
were used for patients presenting with CIS in the period from 1987 to 2009. • Patients with
muscle-invasive bladder cancer on primary diagnosis were excluded. The patients were divided
into three groups according to their ‘clinical type’, being primary, concomitant or secondary
CIS. RESULTS: • Overall, 90 patients with CIS were identified with a mean age of 63.4 years,
predominantly men (91.1%). Primary CIS (P-CIS) was found in 43 patients (47.8%), concomitant
CIS (C-CIS) in 21 patients (23.3%) and secondary CIS (S-CIS) in 26 patients (28.9%). Mean
follow up was 81.3 months (range 8-222 months). Recurrence of disease was observed in 68.9%
of patients, with significantly more recurrences in the S-CIS group (88.5%). • Progression to
Urologie
179
muscle-invasive disease was seen in 17 patients (18.9%): eight patients (18.7%) with P-CIS, four
(19.0%) with C-CIS and five (19.2%) with S-CIS. Overall, 29 patients underwent a cystectomy,
equally distributed over the three groups. The duration of bladder preservation was worse in the
C-CIS group but did not differ significantly between the groups. • Overall survival at 5 years was
79.6% for the total group, with poorer results for the C-CIS group, although the difference was
not significant. CONCLUSIONS: • Carcinoma in situ is clearly an entity that requires meticulous
treatment and thorough follow up because of its high recurrence rate (68.9%) and high rate
of progression to muscle-invasive bladder cancer (18.9%). • The C-CIS group appears to have a
poorer prognosis with a shorter duration of bladder preservation and a worse overall survival. ©
2010 The authors. BJU International © 2011 BJU International.
Van Vugt HA, Roobol MJ, van der Poel HG, van Muilekom EH, Busstra M, Kil P, Oomens EH,
Leliveld A, Bangma CH, Korfage I, Steyerberg EW. Selecting men diagnosed with prostate
cancer for active surveillance using a risk calculator: a prospective impact study. BJU Int.
2011 Nov 23. Epub ahead of print].
180
STUDY TYPE: Prognosis (cohort series) Level of Evidence 2a What’s known on the subject?
and What does the study add? The present study is one of the first to investigate urologists’
and patients’ compliance with recommendations based on a risk calculator that calculates
the probability of indolent prostate cancer. A threshold was set for a recommendation of
active surveillance vs active treatment. Active surveillance recommendations based on a
prostate cancer risk calculator were followed by most patients, but 30% with active treatment
recommendations chose active surveillance instead. This indicates that the threshold may be
too high for urologists and patients. OBJECTIVES: To assess urologists’ and patients’ compliance
with treatment recommendations based on a prostate cancer risk calculator (RC) and the reasons
for non-compliance. • To assess the difference between patients who were compliant and noncompliant with recommendations based on this RC. PATIENTS AND METHODS: Eight urologists
from five Dutch hospitals included 240 patients with prostate cancer (PCa), aged 55-75 years,
from December 2008 to February 2011. • The urologists used the European Randomized Study
of Screening for Prostate Cancer RC which predicts the probability of potentially indolent PCa
(P[indolent]), using serum prostate-specific antigen (PSA), prostate volume and pathological
findings on biopsy. • Inclusion criteria were PSA <20 ng/mL, clinical stage T1 or T2a-c disease,
<50% positive sextant biopsy cores, =20 mm cancer tissue, =40 mm benign tissue and Gleason
=3 + 3. If the P(indolent) was >70%, active surveillance (AS) was recommended, and active
treatment (AT) otherwise. • After the treatment decision, patients completed a questionnaire
about their treatment choice, related (dis)advantages, and validated measurements of other
factors, e.g. anxiety. RESULTS: Most patients (45/55, 82%) were compliant with an AS
recommendation. Another 54 chose AS despite an AT recommendation (54/185, 29%).
• The most common reason for non-compliance with AT recommendations by urologists was the
patient’s preference for AS (n= 30). These patients most often reported the delay of physical side
effects of AT as the main advantage (n= 19). • Those who complied with AT recommendations
had higher mean PSA levels (8 vs 7 ng/mL, P= 0.02), higher mean amount of cancer tissue
(7 vs 3 mm, P < 0.001), lower mean P(indolent) (36% vs 55%, P < 0.001), and higher mean
generic anxiety scores (42 vs 38, P= 0.03) than those who did not comply. CONCLUSIONS: AS
recommendations were followed by most patients, while 29% with AT recommendations chose AS
instead. • Although further research is needed to validate the RC threshold, the current version
is already useful in treatment decision-making in men with localized PCa. © The authors.
BJU International © 2011 BJU International.
Van Vugt HA, Roobol MJ, Busstra M, Kil P, Oomens EH, de Jong IJ, Bangma CH, Steyerberg
EW, Korfage I. Compliance with biopsy recommendations of a prostate cancer risk
calculator. BJU Int. 2011 Sep 20. [Epub ahead of print].
STUDY TYPE: Diagnostic (cohort) Level of Evidence 2b What’s known on the subject? and What
does the study add? So far, few publications have shown that a prediction model influences
the behaviour of both physicians and patients. To our knowledge, it was unknown whether
urologists and patients are compliant with the recommendations of a prostate cancer risk
calculator and their reasons for non-compliance. Recommendations of the European Randomized
study of Screening for Prostate Cancer risk calculator (ERSPC RC) about the need of a prostate
biopsy were followed in most patients. In most cases of non-compliance with ‘no biopsy’
recommendations, a PSA level =3 ng/mL was decisive to opt for biopsy. Before implementation
of the ERSPC RC in urological practices at a large scale, it is important to obtain insight into
the use of guidelines that might counteract the adoption of the use of the RC as a result of
opposing recommendations. OBJECTIVES: To assess both urologist and patient compliance with
a ‘no biopsy’ or ‘biopsy’ recommendation of the European Randomized study of Screening for
Prostate Cancer (ERSPC) Risk Calculator (RC), as well as their reasons for non-compliance. • To
assess determinants of patient compliance. PATIENTS AND METHODS: The ERSPC RC calculates
the probability on a positive sextant prostate biopsy (P(posb)) using serum prostate-specific
antigen (PSA) level, outcomes of digital rectal examination and transrectal ultrasonography,
and ultrasonographically assessed prostate volume. A biopsy was recommended if P(posb) =20%.
• Between 2008 and 2011, eight urologists from five Dutch hospitals included 443 patients (aged
55-75 years) after a PSA test with no previous biopsy. • Urologists calculated the P(posb) using
the RC in the presence of patients and completed a questionnaire about compliance. • Patients
completed a questionnaire about prostate cancer knowledge, attitude towards prostate biopsy,
self-rated health (12-Item Short Form Health Survey), anxiety (State Trait Anxiety Inventory-6,
Memorial Anxiety Scale for Prostate Cancer) and decision-making measures (Decisional Conflict
Urologie
181
Scale). RESULTS: Both urologists and patients complied with the RC recommendation in 368 of
443 (83%) cases. • If a biopsy was recommended, almost all patients (96%; 257/269) complied,
although 63 of the 174 (36%) patients were biopsied against the recommendation of the RC.
• Compliers with a ‘no biopsy’ recommendation had a lower mean P(posb) than non-compliers
(9% vs 14%; P < 0.001). • Urologists opted for biopsies against the recommendations of the RC
because of an elevated PSA level (=3 ng/mL) (78%; 49/63) and patients because they wanted
certainty (60%; 38/63). CONCLUSIONS: Recommendations of the ERSPC RC on prostate biopsy
were followed in most patients. • The RC hence may be a promising tool for supporting clinical
decision-making. © The authors. BJU International © 2011 BJU International.
182
Van Vugt HA, Roobol MJ, van der Poel HG, van Muilekom EH, Busstra M, Kil P, Oomens
EH, Leliveld A, Bangma CH, Korfage I, Steyerberg EW. Selecting men diagnosed with
prostate cancer for active surveillance using a risk calculator: a prospective impact
study. BJU Int. 2011 Nov 23. [Epub ahead of print].
Publicaties Medisch
Specialisten 2011
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Verdam FJ, Dolmans DE, Loos MJ, Raber MH, de Wit RJ, Charbon JA, Vroemen JP.
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WC, Vaessen-Verberne AA. Comparing Global Initiative for Asthma (GINA) criteria with
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J. 2011 Sep;38(3):561-6. Epub 2011 Mar 15.
WC, Vaessen-Verberne AA. Validation of a web-based version of the asthma control test
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Overdevest I, Willemsen I, Rijnsburger M, Eustace A, Xu L, Hawkey P, Heck M,
Savelkoul P, Vandenbroucke-Grauls C, van der Zwaluw K, Huijsdens X, Kluytmans J.
Extendedspectrum
Willemsen I, Overdevest I, Al Naiemi N, Rijnsburger M, Savelkoul P, VandenbrouckeGrauls C, Kluytmans J; TRIANGLe Study Group. New diagnostic microarray (Check-KPC
ESBL) for detection and identifi cation of extended-spectrum beta-lactamases in highly
Azizi F, Reichman BL, de Groot HG, van der Laan L. Primary aortoduodenal fi stula in
fracture: a case report and review of the literature. J Foot Ankle Surg.
2012 Mar;51(2):270-4. Epub 2011 Dec 9.
Te Slaa A, Dolmans DE, Ho GH, Mulder PG, van der Waal JC, de Groot HG, van der Laan L.
Prospective randomized controlled trial to analyze the effects of intermittent
World J Surg. 2011 Feb;35(2):446-54.
Epub 2011 Jul 14.
207
208
2012 Feb;26(2):233-41. Epub 2011 Nov 1.
Verdam FJ, Dolmans DE, Loos MJ, Raber MH, de Wit RJ, Charbon JA, Vroemen JP.
Delayed primary closure of the septic open abdomen with a dynamic closure system.
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Rep. 2011;1(2): 119-122.
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ISBN 978-953-307-466-5.
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209
210
Overdevest I, Willemsen I, Rijnsburger M, Eustace A, Xu L, Hawkey P, Heck M,
Savelkoul P, Vandenbroucke-Grauls C, van der Zwaluw K, Huijsdens X, Kluytmans J.
Extendedspectrum
Willemsen I, Overdevest I, Al Naiemi N, Rijnsburger M, Savelkoul P, VandenbrouckeGrauls C, Kluytmans J; TRIANGLe Study Group. New diagnostic microarray (Check-KPC
ESBL) for detection and identifi cation of extended-spectrum beta-lactamases in highly
Oct;49(10):3551-4. Epub 2011 Aug 24.
Colofon
Uitgave: Prelum Uitgevers, Houten
Ontwerp omslag en binnenwerk: CO2 Premedia bv, Amersfoort
Vormgeving: CO2 Premedia bv, Amersfoort
Druk- en bindwerk: Drukkerij Wilco b.v., Amersfoort
Oplage:
900 exemplaren
Interviews:
Leonore Pulleman Tekstpartners, Breda
212
Fotografie:
Esther Hereijgers, Breda
Overzicht publicaties:
Jan van Trier
Eindredactie:
Joachim Aerts, Janine de Jongh-Koolen, Michel Ju, Leonore Pulleman,
Bart Pieter van Putte, Eric Verheijden
Verspreiding:
Kenniskern Amphia Academie
De Kenniskern Amphia Academie maakt deel uit van het Amphia Ziekenhuis Breda/
Oosterhout

2011 - Amphia Ziekenhuis

Transcription

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