A 45 Year Old with Sudden Stroke: A Rare and Silent Culprit

A 45 Year Old with Sudden Stroke: A Rare and Silent Culprit
Ahmed A. Behery, MD1, Sai Devarapalli, MD FACC2
¹Indiana University Health Ball Memorial Hospital Department of Internal Medicine, Muncie, IN, ²Indiana University Health Ball Memorial Hospital Department of Cardiology, Muncie, IN
Differential Diagnoses
Introduction
Acute ischemic stroke in young
individuals can be a sign of serious underlying
pathology in which prompt recognition is
essential for effective treatment and better
physical outcomes. In most cases, on initial
presentation of these patients, cardiac
embolism from either intramural thrombi or
vegetations or even arterial dissection are
most commonly considered where as much
rare causes are often overlooked. This case
demonstrates an unexpected disease entity
that caused acute ischemic stroke in a young
patient.
Paroxysmal
Atrial
Fibrillation
Acute
Thrombotic
Occlusion
Paradoxical
Embolism
via PFO
Infective
Endocarditis
Thrombophilia
 Additional work up was negative for
infective endocarditis, clinically significant
carotid artery stenosis, or thrombophilia.
 The patient underwent a left cardiac
catheterization which found a chronic total
occlusion of right coronary artery requiring no
stent placement.
 The patient had a favorable outcome
regaining most of her functional capacity with
conservative management and physical
therapy.
 She eventually underwent successful
planned surgical resection of the
fibroelastoma to reduce risk of future
recurrence.
2nd day
Case
 Pt is a 45 y/o F who presented with
sudden syncope while taking a shower and
was found to have left hemiparesis with left
facial droop and dysarthria after she woke
up.
 No chest pain, SOB, aura, convulsions,
or post-ictal state.
 History of Hodgkin’s lymphoma treated
with radiation 20< years ago.
 History of severe menorrhagia with
chronic anemia.
 LMP 2-3 weeks ago
 No significant surgical, family or
medication history.
 No history of illicit drug use
 20 pack year smoking history
 Except for leukocytosis of 16.8
k/cumm, there are no major laboratory
abnormalities on admission.
 Head CT w/o contrast on admission was
unremarkable.
 The decision to use TPA was deferred
in light of recent severe menstrual
bleeding.
 MRI of brain on the second day
confirmed bilateral cerebellar and right
posterior frontal cortex consistent with
cardio-embolic source.
 The patient also developed an acute
inferior wall NSTEMI on the same day with
a 3rd degree AV block requiring temporary
transvenous pacing.
 Anticoagulation was not pursued given
risk of hemorrhagic conversion.
Discussion
 Cardiac Papillary Fibroelastoma is a rare
primary cardiac tumor with prevalence of less
than 0.002%. It mostly originates on the
valves with the greatest predilection to aortic
followed by mitral valve.
Right
Sided
4%
Left
Atrium
2%
Mitral
Valve
42%
 The list of differential diagnosis was
rearranged rearranged with intramural
thrombi vs. infective endocarditis being at
the top.
 A transthoracic ECHO with bubble study
was then performed and was negative for
intramural thrombi or PFO.
 Subsequently the diagnosis of Mitral
valve papillary fibroelastoma was
confirmed on transesophageal ECHO as a 1
cm mobile mass on the posterior leaflet
of the mitral valve as shown below.
 Transesophageal echocardiography is the
best modality to establish the diagnosis.
(76.6% sensitivity compared with transthoracic
echocardiogram 61.9%). Sensitivity improves
with sizes 0.2 cm <
 Characterisics on TEE:
- Pedunculated and mobile
- Homogenous
- Peripheral speckled appearance
 Risk of stroke is directly proportional to
size and mobility.
Aortic
Valve
52%
 Mitral Valve Papillary Fibroelastoma
(MVPF) is comprised of a homogenous
fibroelastic and collagenous core encased
with endocardium.
Figure 3. (A) Left Atrial myxoma . (B) A papillary
fibroelastoma of the mitral valve. (C) Lambl excrescence of
the aortic valve. (D) On apical four-chamber view, a right
ventricular mass is attached to the interventricular septum.
Indications for surgical resection:
- Presence of MVPF with complications
due to embolic phenomenon
- Very large greater than or equal to 1
cm even if asymptomatic
 No data to suggest any benefit with
anticoagulation or antiplatelets.
 Resection is completely curative with no
recurrence rate.
References
1. Sun J, Asher C, et al. Clinical and Echocardiographic
Characteristics of Papillary Fibroelastomas: A
Retrospective and Prospective Study in 162 Patients.
Circulation. 2001;103:2687-2693
2. Kuwashiro T, Toyoda K, et al.Cardiac Papillary
Fibroelastoma as a cause of Embolic Stroke:
Ultrasound and Histopathologic Characteristics. Inter
Med 2009; 48: 77-80
Acknowledgements
 Figure 1. Buttan A K et al. Circulation. 2012;125.
Figure 1. Histology of papillary
fibroelastoma with endothelial cells
(red arrows) and hyalinized stroma
(red asterisks).
Figure 2. Gross specimen of CPF
revealing the characteristic frond-like
appearance.
 Figure 2. Sun J P et al. Circulation. 2001;103:26872693
 Figure 3. Lippincott Williams & Wilkins from
Feigenbaum et al. Feigenbaum’s Echocardiography. 6th
ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2005. Panel D from American College of Chest
Physicians from Krasuski et al. Cardiac rhabdomyoma
in an adult patient presenting with ventricular
arrhythmia. Chest 2000;118:1217–1221 .
Searching for Sarcoid: Utility of PET/CT Scan
Emily Cochard, MD, PGY3; Ishan Gohil, MS4; Robert J. Fick, MD
St. Vincent Hospital, Indianapolis, Indiana
Introduction
Discussion
Sarcoidosis is an inflammatory, granulomatous disease of
unknown etiology. The disease most often presents with
pulmonary involvement and symptoms such as cough and/or
shortness of breath. Chest radiography demonstrates
characteristic findings of hilar lymphadenopathy.
Extrapulmonary sarcoidosis presents a diagnostic challenge.
Sarcoidosis primarily involves the lungs and while
extrapulmonary sarcoidosis is common (30-50%), it is usually
concomitant with pulmonary involvement. In a study with 736
sarcoidosis patients, 95% had thoracic involvement, 50% had
concomitant extrathoracic disease and only 2% had isolated
extrathoracic sarcoidosis.
Figure 1. PA/lateral CXR demonstrating cardiomegaly
Case
Extrapulmonary disease can be severe and life threatening
and its presence affects the therapeutic approach. Diagnostic
dilemmas arise when trying to search for affected organs,
particularly when patients are asymptomatic. The use of
PET/CT relies on glucose hypermetabolism by granuloma cells
and can be used for mapping of inflammatory sites and
identification of occult disease. In one study PET/CT revealed
an occult site, not detected by exam or standard imaging
(CXR/ CT), in 15% of patients.
A 61 year-old Caucasian gentleman presented with malaise,
anorexia, weight loss, mild cognitive changes and
hypercalcemia.
Past medical history includes paroxysmal atrial fibrillation,
coronary artery disease, congestive heart failure, obstructive
sleep apnea, and diabetes mellitus. None of his medications
were known to cause hypercalcemia.
No lymphadenopathy, pulmonary findings,
hepatosplenomegaly or skin changes were found on exam.
Figure 3. Bone marrow biopsy
demonstrating increased
macrophages.
Laboratory Data
•Calcium: 14.1 mg/dL (8.4 mg/dL-10.5 mg/dL)
•Albumin 3.1 gm/dL (3.5-5.0 gm/dL)
•PTH: 5 pg/mL (10-65 pg/mL)
•PTHrp: normal
The sensitivity of PET/CT in detecting active sarcoidosis is 8090%. Tissue biopsy is then required for diagnosis as specificity
is low. The wide range of involvement of sarcoidosis does
affect disease detection with PET/CT. In one study, PET/CT
detected 100% of intrapulmonary lesions and 90% of
extrapulmonary lesions in patients with biopsy-proven
disease.
Our case illustrates the role PET/CT can play in the diagnosis
of extrathoracic sarcoidosis. It is especially useful in those
with unusual presentations and normal chest imaging.
•Serum and urine protein electrophoresis: normal
•Urine Ca:Cr ratio: normal
•Kappa/lambda light chain ratio: normal
•Alkaline phosphatase: 212 U/L (38-126 U/L)
References
•1-25 hydroxy-vitamin D: 99 pg/mL (18-72 pg/mL)
•Angiotensin converting enzyme level: 99 U/L (9-67 U/L)
Imaging
Figure 4. Bone marrow biopsy
demonstrating typical granuloma.
•PA/lateral CXR: cardiomegaly (Figure 1)
•Skeletal survey: negative for osteolytic lesions
•CT: multiple <5mm calcified nodules throughout the lungs
and mild splenomegaly
•Whole-body PET/CT: heterogeneous uptake throughout the
bone marrow, one hypermetabolic, non-enlarged lymph node
in the left neck, and mildly prominent splenic uptake (Figure 2)
•Bone marrow biopsy: normocellular bone marrow with noncaseating granulomas (Figure 3 and Figure 4)
Figure 2. PET/CT demonstrating
heterogeneous uptake throughout the bone
marrow.
Diagnosis
The presence of non-caseating granulomas in the bone marrow along with the patient’s
clinical presentation confirmed the diagnosis of isolated extrathoracic sarcoidosis as a rare
etiology of refractory hypercalcemia.
•Baughman RP, Lower EE. Chapter 329. Sarcoidosis. Harrison's Principles of Internal
Medicine, 18e. New York, NY: McGraw-Hill; 2012.
•Brackers de Hugo L, et al. Granulomatous lesions in bone marrow: clinicopathologic
findings and significance in a study of 48 cases. Eur J Intern Med. 2013; 24:468-473.
•Donovan PJ, et al. Calcitriol-mediated hypercalcemia: causes and course in 101
patients. J Clin Endocrinol Metab 2013; 98(10): 4023-4029.
•Nishiyama Y, et al. Comparative evaluation of F-FDG PET and Ga scintigraphy in
patients with sarcoidosis. J Nucl Med 2006; 47: 1571-76.
•Rao DA, et al. Extrapulmonary manifestations of sarcoidosis. Rheum Dis Clin North
Am 2013; 39(2): 277-297.
•Sharma OP. Hypercalcemia in granulomatous disorders: a clinical review. Curr Opin
Pulm Med 2000; 6(5): 442-447
•Soussan M, et al. Functional imaging in extrapulmonary sarcoidosis: FDG-PET/CT and
MR features. Clin Nucl Med 2014; 39(2): 146-159.
•Teirstein AS, et al. Results of 188 whole-body F-fluorodeoxyglucose positron emission
tomography scans in 137 patients with sarcoidosis. Chest 2007;132:1949-1953.
•Treglia G, et al. Emerging role of whole-body F-fluorodeoxyglucose positron emission
tomography as a marker of disease activity in patients with sarcoidosis: a systematic
review. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28:87-94.
Warfarin as the Culprit of Calciphylaxis
Nicholas W. Creasap, MD St. Vincent Hospital, Indianapolis, Indiana
Overview
Well-known to occur in end-stage renal disease,
calciphylaxis can occur in other settings as well,
such as treatment with warfarin.
Considering warfarin-induced skin disorders in a
patient on warfarin with skin lesions.
Excisional biopsy and bone scan are appropriate
for accurate diagnosis.
Prognosis is poor, especially in those with
ulcers.
Sodium thiosulfate is the treatment of choice.
Clinical Presentation
A debilitated, 46-year-old, Caucasian woman
presented from a nursing facility due to concern
of superimposed infection on chronic nonhealing ulcers.
She developed wounds on her hips
approximately 5 months earlier, after
hospitalization for acute lower extremity deep
venous thrombosis. At that time, anticoagulation
with warfarin was started.
Approximately 3 weeks following initiation of
warfarin, she developed painful ulcerations that
did not respond to standard outpatient wound
treatment.
Past Medical History
Deep Venous Thrombosis
Obesity
Gastric Bypass
Iron Deficiency Anemia
Physical Exam
Obesity (BMI 36.9 kg/m2)
Multiple ulcers with little surrounding erythema.
The 4 cm x 5 cm lateral left thigh ulcer extended
into necrotic subcutaneous tissue with no
purulent discharge or erythema. Ulcers overlying
the left medial thigh, right hip, left anterior tibia,
and right heel had clean bases with granulation
tissue.
No abnormal black or blue skin discoloration.
Labs/Imaging
WBC 5.5 k/cumm with normal differential
Hgb 10 g/dL with MCV 78.1 fL
BUN 6 mg/dL
Creatinine 0.44 mg/dL
Calcium 9.0 mg/dL (highest)
Phosphorus 3.5 mg/dL
Total protein 5.7 g/dL
Albumin 1.9 g/dL with prealbumin 6 mg/dL
ESR 105 mm/hour
CRP 8.8 mg/dL
ANA negative
HIV non-reactive
Hypercoagulation workup normal
Nuclear Bone Scan:
Biopsy
Several biopsies had previously obtained, which
demonstrated epidermal ulceration, fat necrosis,
acute inflammation, granulation, and intramural
calcification. No fibrin thrombi were present to
suggest typical warfarin-induced necrosis.
Outcome
Warfarin replaced by rivaroxaban. She was
discharged back to the skilled nursing facility with
wound therapy. The wounds completely healed 3
months later. Her severe pain resolved. She is
now ambulating with a walker and is hopeful to
walk independently soon.
Final diagnosis
Patient was diagnosed with warfarin-induced
calciphylaxis based on the timing of ulcers,
biopsy & bone scan results, and improvement of
ulcers with cessation of warfarin.
Discussion
Risk factors include female sex; obesity;
hyperphosphatemia; hypoalbuminemia;
hypercoagulable states; white race; elevated
ESR; and exposure to medications such as
warfarin, calcium-based binders, vitamin D
supplementation, and glucocorticoids.
Skin biopsy with subcutaneous fat is the standard.
Punch biopsy may not be sufficient, so more
extensive excisional biopsy is required. Bone
scan shows extensive calcification in 97% of
patients.
Pathophysiology
The exact mechanism is still unknown. It is
postulated that vascular smooth muscle cells
transdifferentiate into osteoblast-like cells through
several cell-signaling pathways that converge on
a common transcription factor, nuclear factor k-B,
eventually expressing other factors such as bone
morphogenic protein and endothelin-1. Warfarin
may inhibit matrix G1a protein, an inhibitor of
bone morphogenic protein.
Therapy
The most imperative intervention is to address
the underlying pathology promoting
calciphylaxis. Examples include removing the
offending agent; avoiding trauma; correcting
calcium and phosphate abnormalities with noncalcium-phosphate binders; and cinacalcet for
elevated PTH.
Sodium thiosulfate, dose adjusted for renal
function, may be used in treating cases related,
and unrelated, to ESRD; however, it does not
appear that there are any randomized controlled
trials establishing its efficacy. Retrospective
studies have shown some benefit. The
mechanism of action is unknown.
Oxygen therapy may be an adjunctive therapy
as well.
Prognosis
In the presence of ESRD, calciphylaxis may
have a 6-month mortality rate as high as 33% in
non-ulcerating cases and 80% in those with
ulcers. Rates in non-ESRD related cases are
unknown.
References
1. Kalajian AH et al. Calciphylaxis With Normal Renal
and Parathyroid Function: Not as Rare as
Previously Believed. Arch Dermatol.
2009;145(4):451-458.
2. Weenig RH et al. Calciphylaxis: natural history, risk
factor analysis, and outcome. J Am Acad Dermatol.
2007;56(4):569-579.
3. Basile C et al. Hyperbaric oxygen therapy for
calcific uremic arteriolopathy: a case series. J
Nephrol. 2002;15(6):676.
4. Nigwekar AU et al. Sodium thiosulfate therapy for
calcific uremic arteriolopathy. Clin J Am Soc
Nephrol. 2013;8(7):1162.
Chronic diarrhea in pregnancy: Don't blame it all on the baby
A peripartum presentation of ulcerative colitis
Kyle Glienke MD, Ishan Gohil MSIV, and Anthony Martin MD
St. Vincent Internal/Family Medicine Residency Program, Indianapolis, IN
Further Evaluation
Learning Objectives
 Identify inflammatory bowel disease (IBD) as a chronic disease of young
patients in their reproductive years
 Review the general principles of management of IBD in pregnancy and the
postpartum period
 Identify common complications of pregnancy associated with IBD
General Principles
 Spontaneous improvement in platelets and renal function, persistence of anemia and metabolic acidosis
 Stools found to be grossly bloody
 Hematology consultation and evaluation negative for consumptive coagulopathy
 Obstetric consultation and evaluation consistent with normal post-partum changes
 Colonoscopy with random biopsies: Moderate to severely erythematous and ulcerated mucosa noted from the
anus to the cecum
nonpregnant patients
 Cesarean section recommended with active perianal
 IBD commonly affects women during reproductive years, therefore pregnancy
disease seen in Crohn’s disease
may complicate the diagnosis and significantly alter treatment options
 IBD patients are at increased risk of complications
 Pregnant women with IBD are at a higher risk for complications, including
- Early and late preterm birth
- Small for gestational age birth
- Hypertensive disorders of pregnancy
- Prolonged or premature rupture of membranes
- Neonatal death
- Maternal—thromboembolism, malnutrition
- Likely higher risk with increased disease severity
preterm birth, small for gestational age birth, hypertensive disorders of
pregnancy, and prolonged or premature rupture of membranes.
Patient Presentation
der. No other notable abdominal tenderness, rebound, or guarding
 Extremities: 1+ pretibial edema
 Neurological: 1+ Achilles, patellar, and brachioradialis reflexes without clonus
 GU: Foley catheter in place, with grossly bloody urine
 Initial Laboratory Evaluation:
 WBC: 16.0 with toxic granulation, Hgb 9.2, platelets 42
 Na: 129, K: 5.3, Cl: 107, CO2: 12, Cr: 0.97
 Uric acid: 7.6, LDH: 556, fibrinogen 223, INR 1.08
 AST/ALT: 23/8
 Urinalysis: RBCs, otherwise unremarkable
 Fecal occult blood: Positive
 Chest X-ray, renal ultrasound: Unremarkable
 Stool culture, c. diff antigen and toxin: Negative
flare
 Management of flares in pregnancy similar to that in
teenagers and younger adults
 Physical Exam:
 Vitals: Temp: 98.1°F, HR: 112; BP: 89/80; RR: 12; O2 Sat: 97% on room air
 General: No acute distress, notable pallor of the skin and conjunctiva
 CV: Tachycardia, grade II/VI systolic murmur
 Abdomen: Soft, uterine fundus palpable below the umbilicus and mildly ten-
 Pregnancy not proven to increase likelihood of disease
disease activity prior to pregnancy, but may vary
 IBD is a common cause of subacute or chronic, often bloody, diarrhea in
acidosis, acute kidney injury, and ongoing diarrhea
treatment
- Exceptions of surgical intervention
 Risk of flare during pregnancy most likely to reflect
Background
 22 year old G1P1 Caucasian female, postpartum day one
 Four month history of watery, non-formed stools , 3-5 episodes per day
 Crampy abdominal pain and tenesmus
 Initially characterized as non-bloody on history
 Denied recent antibiotic use, sick contacts, or travel
 Review of systems positive for dyspnea on exertion and lightheadedness
 Daily prenatal vitamin
 Pregnancy became complicated by pre-eclampsia
 Induction of labor at 37 weeks gestation at an outside hospital
 Status post vaginal delivery of a viable 7 pound, 4 ounce infant female
 No immediate anatomic obstetric complications
 Seen on transfer due to anemia, thrombocytopenia, non-anion gap metabolic
 Counseling regarding heritability
 Fertility preserved or mildly reduced with adequate
 Achieving and maintaining disease remission key to
reducing fetal and maternal complications
 Breastfeeding may reduce disease severity postpartum
Diagnosis and Treatment
 Pathology evaluation of biopsies: Diffuse moderate colitis with cryptitis and crypt abcesses, most consistent
with ulcerative colitis
 Treatment started with prednisone orally and mesalamine after confirmation of safety with breastfeeding
 Marked improvement in diarrhea, with subsequent improvement in non-anion gap metabolic acidosis
 Formed stools returned after two days of therapy
 Patient discharged home with outpatient gastroenterology follow-up
Take Home Points
 Complete history and physical important for
accurate diagnosis in setting of chronic diarrhea
 Poorly-controlled IBD in pregnancy is associated with
pre-eclampsia, as well as other disorders
 Pregnancy has a variable effect on the severity of
disease and frequency of flares
Treatment Safety in Pregnancy and Breastfeeding
 Most medications used in the management of IBD are
compatible with pregnancy, other than methotrexate
Class
Mesalamine
Aminosalicylate
Prednisone
Corticosteriod
Azathioprine
Purine
antimetabolite
Methotrexate
Folate antagonist
Cyclosporine
Calcineurin
inhibitor
Infliximab
Anti-TNF
antibody
Pregnancy
Category
Adverse
Effects
Comments
Breastfeeding
B/C
Folate
deficiency
Preparationdependent risk
Compatible
C
Orofacial clefts
premature ROM
Flare treatment
Compatible
D
VSD, ASD,
preterm delivery
X
Multiple
congenital
anomalies
C
Preterm delivery
SGA
B
Not
recommended
Discontinue 6
months prior to
conception
Contraindicated
Contraindicated
Limited human
data
Not
recommended
References
1. Vermeire S, et al. Management of inflammatory bowel disease in
pregnancy. Journal of Crohn’s and Colitis. 2012; 6(8): 811-823.
2. Ng SW and Mahadevan U. Management of inflammatory bowel disease
in pregnancy. Expert Rev.Clin. Immunol. 2013; 9(2): 161-174.
3. Ferrero S, Ragni N. Inflammatory bowel disease: management issues
during pregnancy. Arch Gynecol Obstet 2004; 270: 79-85.
4. Friedman S, Blumberg RS. Friedman S, Blumberg R.S. Chapter 295.
Inflammatory Bowel Disease. In: Longo DL, Fauci AS, Kasper DL,
Hauser SL, Jameson J, Loscalzo J. Longo D.L., Fauci A.S., Kasper
D.L., Hauser S.L., Jameson J, Loscalzo J eds. Harrison's Principles of
Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
5. Cunningham F, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY.
Cunningham F, Leveno K.J., Bloom S.L., Hauth J.C., Rouse D.J.,
Spong C.Y. Chapter 49. Gastrointestinal Disorders. In: Cunningham F,
Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Cunningham F,
Leveno K.J., Bloom S.L., Hauth J.C., Rouse D.J., Spong C.Y. eds.
Williams Obstetrics, 23e. New York, NY: McGraw-Hill; 2010.
A Rare Myopathic Complication of Statin Use
Daniel Hugenberg, Neil Keshvani, Tobin Greensweig, Steven Hugenberg
Indiana University School of Medicine,
Medicine Indianapolis,
Indianapolis Indiana
INTRODUCTION
Statin-associated necrotizing
g autoimmune myopathy
y p y is a rare
condition with an incidence of approximately two in one million
people per year.5 The etiology of this condition is thought to be
due to an auto-antibody directed at 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Patients with this condition
present with proximal muscle weakness, myalgia, and
elevated creatine kinase (CK) levels. As opposed to other
statin-induced myopathies, patients continue to be
symptomatic even after discontinuation of the offending
medication. Diagnosis is based on clinical presentation and
muscle biopsy, which shows a necrotizing myopathy with little
inflammatory component. The condition typically improves
with systemic steroids.2-5
PATIENT PRESENTATION
• 66 year old white male with a history of hypertension and
hypercholesterolemia.
• Medications are lisinopril and atorvastatin, both of
which are had been prescribed for years.
DISCUSSION
HOSPITAL COURSE
Our patient presented with a subacute myopathic process
consistent with an inflammatory myopathy. Within the
category of inflammatory myopathies is a recently recognized
subgroup entitled necrotizing autoimmune myopathy (NAM).2
This subgroup shares common histopathologic features which
differentiate it from the broader category: myocyte necrosis
without significant inflammation. Although sometimes
idiopathic, recent case series have shown an association with
25
thi condition
this
diti and
d statin
t ti use.2-5
• The patient was treated for presumed rhabdomyolysis with
aggressive intravenous hydration.
• Despite this, the patient’s CK rose as high as 25,824.
• The patient developed symmetric proximal weakness,
most pronounced in the upper extremities.
• Renal function remained normal.
• EMG was consistent with either a necrotizing or early
inflammatory process
process.
• Muscle biopsy revealed significant myofiber necrosis with
prominent infiltration of macrophages within necrotic fibers and
the endomysium.
• No evidence of polymyositis or dermatomyositis.
• Necrotizing autoimmune myopathy, most likely related to
statin use, is diagnosed.
• Upon initiation of prednisone at a dose of 1 mg/kg/day, the
patient’s symptoms and CK levels improved rapidly.
CONCLUSION
CPK Level Through Hospital Course
30000
CPK (IU/L
L)
25000
• Presented to his primary care physician with complaints of
malaise and generalized weakness for approximately two
weeks.
• His symptoms began after working outside on his car
during a hot day.
20000
15000
10000
Prednisone started
5000
0
• One month prior to presentation the patient was noted to
have an asymptomatic transaminitis.
• AST 144, ALT 266 IU/L.
• Atorvastatin was discontinued at this time.
1
2
3
4
5
6
7
8
9
10
11
Hospital Day
Knowledge of this diagnosis is important for clinicians as the
number of prescriptions of statins is increasing in the United
S
States.
Statin-associated
S i
i d NAM may persist
i ffor weeks
k to
months, and even progress, despite discontinuation of the
medication.2-5 This is in contrast to the toxic myopathy
associated with statins, which usually improves after the
medicine is discontinued.1,5 Furthermore, treatment with
steroids or other forms of immunosuppression is required to
control this condition.2-5
REFERENCES
• On physical exam the patient had 4/5 hip flexor strength
bilaterally, but otherwise his vitals and exam were normal.
• Initial laboratory data:
• AST 570,
570 ALT 553 IU/L
IU/L.
• CK 16,295 IU/L.
• Serum aldolase 149 U/L.
• Urine myoglobin was elevated beyond our laboratory’s
upper limit.
• ESR 85 mm/hr.
The pathophysiology of this condition is likely related to upregulation of HMGCR and subsequent antibody formation to
this enzyme.2-5 This antibody is 94% sensitive and 99%
specific for statin-associated NAM.5 We did not test for this
antibody in our patient as it not yet standard of care and it
would not have changed our clinical management
management.
a) Normal muscle biopsy. b) Muscle biopsy of a patient with autoimmune
necrotizing myopathy. Note the necrotic muscle fibers infiltrated by macrophages.
Reproduced with permission, courtesy of Mammen, AL.4
1. Dalakas, MC. Toxic and drug-induced myopathies. J Neurol Neurosurg
Psychiatry. 2009; 80: 832–838.
2. Grable-Esposito, P. et al. Immune-mediated necrotizing myopathy
associated with statins.
statins Muscle Nerve
Nerve. 2010; 41: 185–190.
185 190
3. Liang C, Needham M. Necrotizing autoimmune myopathy. Curr Opin
Rheumatol. 2011; 23: 612–619.
4. Mammen, AL. Autoimmune myopathies: autoantibodies, phenotypes and
pathogenesis. Nat. Rev. Neurol. 2011; 7: 343–354.
5. Mohassel, P. Mammen, AL. The spectrum of statin myopathy. Curr Opin
Rheumatol. 2013; 25: 747–752.
Spinal Cord Ischemia After Methamphetamine Abuse: A Case Report
Maitri Kalra, MBBS ; Andrew Walker
Methamphetamine is a stimulant type of recreational drug, very
commonly abused in the United States. It enhances transmission
at the catecholaminergic and dopaminergic synapses and produce
elation and increased alertness, with increased motor activity.
Stroke is the most common lasting adverse neurological event
associated with methamphetamine use. Spinal cord effects are
rarely reported. Here is a case of spinal cord ischemia after
recreational use of methamphetamine.
MRI Images of Thoracic and Lumbar
Spine
MRI of spine revealed abnormal T2 signal in the
central cord at the level of the T11-T12 vertebral
bodies. The lesion was in the watershed area with
sparing of posterior column suggestive of infarct.
A lumbar puncture was planned but patient
refused. After 24 hours, his lower extremity
weakness started improving along with return of
sensations gradually over the following days.
Muscle strength was 5/5 in left lower extremity and
4/5 in right lower extremity muscles. At the time of
discharge he was able to walk 2 feet with rolling
walker.
35 year old Caucasian male was brought to the emergency room
after being found down by his roommate.
On examination, his vital signs were stable except for oxygen
saturation of 81% on room air. He was unresponsive; pupils were
equal, round and reactive to light. Muscle tone was normal and deep
tendon reflexes (DTR) were 2+ in all four extremities. Rest of his
examination was unremakable.
Laboratory investigations revealed serum creatinine 2.65, troponin
1.39 and lactate 5.1. Urine tested positive for amphetamines. CT
scan of head showed no acute changes.
Clinical Course: He was intubated for airway protection in ER.
He received aggressive fluid resuscitation and became responsive
after eight hours.
He was subsequently extubated but, the following day, patient
developed weakness in bilateral lower extremities acutely along with
urinary retention. On examination, he had decreased muscle tone in
bilateral lower extremities. Muscle strength was 3/5 for left hip
flexion and knee extension, 1/5 for right hip flexion and knee
extension, 4/5 for ankle plantar/dorsiflexion bilaterally. DTR were 2+
symmetrically in upper and lower extremities. Babinski’s sign was
absent bilaterally. Sensations in lower extremities were decreased to
light and sharp touch distal to the right knee, but normal on left leg.
Rest of the neurological examination including cerebellar
examination was normal.
D
Patient had multi-organ injury with Type II NSTEMI, acute
kidney injury and spinal cord ischemia. Though lumbar
puncture could not be done, the transient, rapidly
improving symptoms make spinal ischemia the likely
diagnosis. The mechanism may be related to elevated
catecholamine concentration, which causes vasospasm,
platelet aggregation, and thrombus formation. Long-term
use of amphetamines can cause repetitive episodes of
vasospasm and paroxysms of hypertension, which may
result in endothelial damage, and acceleration of
atherosclerosis.
Methamphetamine use can cause spinal cord ischemia
by vessel thrombosis or vasospasm.
Impact of Evidence-Based Guidelines for Management of Clostridium Difficile Infection
Emily Cochard, MD, PGY3; Carol Rupprecht, MD PGY2; Stephen Knaus, MD; Lindsay Saum, PharmD
Introduction
Discussion
Clostridium difficile infection (CDI) is a prevalent and potentially fatal
cause of infectious diarrhea in hospitals, thus responsible for a
significant cost to the healthcare system and adverse patient
outcomes.
•500,000 cases per year in the United States
•15,000-20,000 deaths attributed to CDI
•Primary CDI
•$2,870-$4,846 attributed to CDI per case
•$9,822-$13,854 total costs of treatment per case
•Recurrent CDI
•$13,655-$18,067 attributed to CDI per case
•Total cost of treatment 3X higher than primary CDI
While none of our outcomes reached statistical significance, we did
discover trends towards improvement in some of the outcomes
measured.
•mLOS, though shorter in patients treated with guideline-based
therapy, could have been confounded by other co-morbidities. We
subtracted the days prior to diagnosis of CDI to attempts to obtain a
better measurement of the LOS attributable to CDI.
•Mortality was lower in the group treated with guideline-based
therapy but a larger sample size may be needed to reach significance.
•Readmissions were lower in the group treated with guideline-based
therapy but a larger sample size may be needed to reach significance.
All-cause readmissions were assessed, which may not reflect initial
CDI therapy.
Background
In order to follow best evidence for treatment of CDI and improve
quality care and patient outcomes, a group of internal medicine
faculty, residents and pharmacists reviewed relevant literature to
devise a set of evidence-based diagnosis and treatment guidelines for
the teaching hospitalist service. These guidelines were publicized via a
noon conference, an email, an internal website and a resident
handbook. The guidelines emphasized severity-based treatment and
provided institution-specific guidance for infection control and
diagnosis of CDI.
•Cost may have been higher due to multiple confounding variables.
mLOS
Readmission
8
40
7.9
38
7.8
36
7.7
Methods
We retrospectively analyzed data on all patients (79) treated for CDI at
our hospital in a three-month period after publication of the updated
guidelines in 2013. Outcomes examined included length of stay after
diagnosis (mLOS), mortality, cost and readmission rate in the group of
patients treated with guideline-based (GB) therapy and those not
treated with guideline-based therapy. IRB approval was obtained.
We also surveyed residents after the most recent conference on the
updated CDI guidelines to assess our influence.
34
7.6
7.4
30
7.3
28
7.2
26
7.1
24
7
22
GB
Non-GB
Figure 1. mLOS was shorter for those
patients treated with GB therapy, 7.45
days vs. 7.9 days (not statistically
significant)
20
GB
Non-GB
Figure 2. 30-day readmission rate was
lower for those treated with GB
therapy, 29% vs. 38% (not statistically
significant)
Cost
Mortality
$17,000
8
This study analyzed the effect of a best-practice guideline for
treatment of CDI on patient outcomes and educational benefit within
a hospitalist service in a teaching hospital. We discovered trends
toward improved outcomes, but they did not reach statistical
significance. Our study was underpowered and confounding factors
(co-morbid conditions) may have affected results. We propose that
development of best practice guidelines for quality care within an
internal medicine residency program can improve education of
residents and management of patients with CDI.
$16,000
$15,000
6
•On a 5-point Likert scale, residents (11 respondents) reported that the
conference was educationally beneficial (4.18) and that attending the
conference would change their management (4.36).
Conclusion
32
7.5
7
Results
•Interestingly, despite the educational resources provided, resident
and hospitalist physicians followed guideline-based therapy only
45.2% of the time. Increasing awareness of the guidelines’ existence
might improve utilization.
5
$14,000
4
$13,000
3
References
$12,000
2
$11,000
1
$10,000
0
GB
Non-GB
Figure 3. Mortality rate was lower for
those patients treated with GB therapy,
3.2% vs. 6.3% (not statistically
significant)
GB
Non-GB
Figure 4. Cost was higher for those
patients treated with GB therapy,
$16,657.10 vs. $12,787.08.29 (not
statistically significant)
•Bartlett JG and DN Gerding. Clinical recognition and diagnosis of Clostridium difficile infection. CID 2008;46:S12-18.
Bartlett JG. Antibiotic-associated diarrhea. NEJM 2002;346:334-339.
•Alcala L et al. Comparison of three commercial methods for rapid detection of Clostridium difficile toxins A and B from fecal
specimens. Journal of Clinical Microbiology 2008;46:3833-3835.
•Zar FA et. al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified
by disease severity. CID. 2007;45:302-7.
•Wenisch C et. al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficileassociated diarrhea. CID. 1996;22:813-8.
•Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. The American Journal
of Gastroenterology. 1997;92:739-750.
•Ghantoji SS et al. Economic healthcare costs of Clostridium difficile infection: a systematic review. Journal of Hospital Infection
2010;74:309-318.
Intentional Isoniazid Overdose: An Uncommon Toxicity
Chris Kniese, MD • Grant Gilroy, MD • Praveen Mathur, MD
Indiana University School of Medicine, Indianapolis Indiana
Learning Objectives
Introduction
Newly diagnosed cases of tuberculosis in the United States
have continued to decline over the past two decades due to
increased diagnosis and management of latent tuberculosis
infections1. Despite documented adverse events, isoniazid
combined with pyridoxine remains first-line therapy. We present
a case of status epilepticus and metabolic acidosis precipitated
by intentional overdose of isoniazid and pyridoxine.
1. Isoniazid (INH) toxicity can present with elevated anion gap
metabolic acidosis with or without seizure activity
2. Single-dose pyridoxine is safe and effective therapy for INH
toxicity
3. Transient abnormalities in liver function tests may be seen within
72 hours and can improve with supportive care
Lab Results
Case Presentation
Our patient is a 30 year old Hispanic female who was brought to
the emergency department due to seizures. Empty bottles of
pyridoxine and isoniazid were found next to her. She required
multiple doses of benzodiazepines for recurrent seizures and
eventually required intubation for profound post-ictal state.
Toxicology was consulted for suspected isoniazid toxicity and
she was given 5 grams of intravenous pyridoxine based on an
estimated ingestion dose of 4.6 grams.
The patient had little past medical history other than a positive
PPD dating back to 2011 with normal chest radiography. She
was not treated at that time, but had been initiated on therapy for
latent TB with isoniazid 300 mg daily and pyridoxine 50 daily
three days prior to admission. She had also recently given birth
to her third child and documentation from her PCP was
suggestive of post-partum depression.
Her initial work-up showed a serum bicarbonate level of 9
mmol/L with an anion gap of 24 mmol/L. Her initial transaminase
levels were normal. Neurology was consulted and further
imaging was recommended. Ultimately, head CT, as well as
brain MRI and EEG studies were unremarkable. She was
managed supportively with mechanical ventilation and sedation
as needed, and eventually extubated within 72 hours. Her
transaminase levels increased to a maximum AST of 204 IU/L
and ALT of 109 IU/L at 96 hours post-ingestion but trended
down 48 hours later. Psychiatry was consulted; she was given a
diagnosis of major depressive disorder, and ultimately
discharged on oral sertraline with outpatient Psychiatry followup.
Initial Labs
WBC
19.3 k/cumm
Hemoglobin
13.1
g/dL
Hematocrit
39
%
Troponin
<0.05 ng/mL
Sodium
136 mmol/L
Potassium
3.3 mmol/L
Chloride
103 mmol/L
Bicarbonate
9
mmol/L
Anion gap,
24 mmol/L
calculated
Blood urea nitrogen 16
mg/dL
Creatinine
0.62 mg/dL
Glucose
240 mg/dL
Calcium
6.8 mg/dL
Albumin
4
g/dL
Bilirubin, total
0.3 mg/dL
Alkaline
101
IU/L
phosphatase
AST
47
IU/L
ALT
52
IU/L
Protein, total
8.5
g/dL
Acetaminophen,
mcg/m
< 2.0
serum
L
Ethanol, serum
< 3 mg/dL
Salicylate
2
mg/dL
Discussion
Status epilepticus with anion-gap metabolic acidosis has
previously been described in patients who have taken an
intentional isoniazid overdose, and treatment with single-dose
pyridoxine has shown to be effective2. Although studies in
animal models have demonstrated the potential neurotoxicity of
significant doses of pyridoxine3, particularly sensory neuropathy,
studies in humans suggest that this is likely to be seen with high
doses given over days to weeks, or in lower doses given
chronically4.
The mechanism of neurotoxicity due to isoniazid is poorly
elucidated in the literature but it is thought to be related to
interruption of pyridoxine-dependent metabolic pathways. While
this more commonly manifests as peripheral neuropathy, there
are several documented cases of seizure activity as well. This is
likely due to interruption of gamma-amino butyric acid (GABA)
production in the central nervous system5, thus inducing a state
of relative GABA deficiency.
Our patient initially experienced repeated seizures despite
multiple rounds of treatment with benzodiazepines. However,
after receiving a single-dose of intravenous pyridoxine, she
experienced no further seizure activity.
Isoniazid toxicity should be considered in patients presenting
with seizures and metabolic acidosis of unknown etiology,
particularly in the setting of possible ingestion or history of latent
tuberculosis infection.
REFERENCES
1. Alami NN, Yuen CM, Miramontes R, et al. Trends in tuberculosis – United States, 2013. Morbidity
and Mortality Weekly Report 2014; 63: 229-233
2. Wason S, Lacouture PG, Lovejoy FH. Single high-dose pyridoxine treatment for isoniazid
overdose. JAMA 1981; 246: 1102-1104.
3. Perry TA, Weerasuriya A, Mouton PR, et al. Pyridoxine-induced toxicity in rats: a stereological
quantification of the sensory neuropathy. Exp Neurol 2004 Nov; 190(1): 133-44.
4. Berger AR, Schaumburg HH, Schroeder C, et al. Dose response, coasting, and differential fiber
vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity. Neurology
1992 Jul; 42(7): 1367-70.
5. Carta M, Murru L, Barabino E, et al. Isoniazid-induced reduction in GABAergic neurotransmission
alters the function of the cerebellar cortical circuit. Neuroscience 2008 June; 154(2): 710-719.
It Takes a Village To Cure Recurrent Pneumothorax
Learning Objectives
‣To recognize that catamenial pneumothorax (CP)
represents a spectrum entity.
‣To emphasize an early multi-disciplinary approach to
diagnosis and management of CP.
Case Description
Kimberly Ku, MD
Department of Medicine, Indiana University School of
Medicine
Indianapolis, IN
CT chest with IV contrast – ED visit
Discussion
‣Flexible definition: recurrent pneumothoraces,
reproductive age, temporal relationship with menses,
with or without histologic evidence of endometriosis.
‣Etiology still not well understood.
‣Incidence of CP ranges from 25-30% among all
women with recurrent, spontaneous pneumothoraces
referred for surgical treatment.
History
‣39 year old West African female with multiple prior
right-sided pneumothoraces while on her period
status post video-assisted thoracic surgery (VATS)
pleurodesis presents to the ED with acute onset rightsided chest pain. She was on her menstrual cycle.
‣Diagnosis based on clinical history is adequate in CP.
Definitive diagnosis of thoracic endometriosis requires
histological evidence.
‣Combined surgical and hormonal treatment approach
most optimally decreases recurrence rates.
‣Vitals and exam were normal.
‣CXR showed interval development of right-sided
septated pneumothorax (compared to a normalized
CXR after pleurodesis three months ago). Chest CT
confirms findings, also shows small pleural effusion.
‣Instructions were to establish a primary care
physician; and to follow up in pulmonary, thoracic
surgery, and gynecology clinics.
Evaluation
‣Symptoms began in 2009. Five total recurrent
spontaneous pneumothoraces (recurred despite
VATS talc pleurodesis done both 2011 and 2013).
‣Vitals normal. Decreased breath sounds over right
upper and lower lobes; decreased right-sided
diaphragmatic excursion. Otherwise unremarkable
exam.
‣Pleural fluid cytology in 2011 noted “suspicious for
endometrial cells”. Pleural biopsy in 2013 showed
benign fibrous tissue; no malignancy in 2011.
Clinical Course
‣Leuprolide acetate injection for three months; depot
medroxyprogesterone acetate indefinitely.
Thoracic endometriosis
References
1.
2.
3.
‣No further incidents of pneumothorax or chest pain.
4.
‣Pulmonary and thoracic surgery clinics following on
symptom basis with no further planned surgeries.
5.
6.
Aljehani, Y. Catamenial pneumothora. Is it time to approach differently? Saudi
Medical Journal, 2014. 35(2): p.115-22.
Korom, S., et al., Catamenial pneumothorax revisited: clinical approach and
systematic review of the literature. J Thorac Cardiovasc Surg, 2004. 128(4): p.
502-8.
Papafragaki, D. and L. Concannon, Catamenial pneumothorax: a case report
and review of the literature. J Womens Health (Larchmt), 2008. 17(3): p. 367-72
Peikert, T., D.J. Gillespie, and S.D. Cassivi, Catamenial pneumothorax. Mayo
Clin Proc, 2005. 80(5): p. 677-80.
Trehan, A. (2014, Oct. 12). Mr. Ashwini Trehan Endometriosis Specialist.
Retreived from http://www.endometriosis-consultant.co.uk/endometriosisdiagnosis/
Visouli, A.N., et al., Catamenial pneumothorax: a rare entity? Report of 5 cases
and review of the literature. J Thorac Dis, 2012. 4(Suppl 1): p. 17-31.
Evaluation of differences in statin recommendations
between ATP3 and ACC/AHA guidelines in a primary care population
Stephanie N Martin, MD, Amanda J Place, PharmD, BCACP, Karie A Morrical-Kline, PharmD, BCACP, Victor Collier, MD, FACP
St. Vincent Hospital, Indianapolis, IN
Background
 In 2010, over 700,000 people died
of heart attack or stroke
 Cholesterol reduction, specifically
with statins, plays an important role
in primary and secondary prevention
of atherosclerotic cardiovascular
disease (ASCVD)
 ATP III lipid guidelines published in
2001 have been widely implemented
and were the standard of care until
new AHA/ACC guidelines published
in 2013
 The new guidelines have
significantly change our approach to
cholesterol treatment
 Retrospective chart review: of 3,194 patients in our residency clinic of which 299
were randomly selected for analysis
 Active clinic patients aged 40-75
 Lipid panels performed between November 2011 and November 2013
 Demographic and cardiovascular information collected included the necessary
variables to input into Framingham and ASCVD Risk Calculators.
 Need for statin determined using ATP III and ACC/AHA guidelines and calculators
Results
Is statin therapy
recommended?
.
Hypothesis
We theorized that more patients
would qualify for statin therapy with
implementation of the ACC/AHA
guidelines
Objectives
Primary: To demonstrate the
difference in recommendations for
statin use, in statin naïve patients,
between the 2001 and 2013
guidelines
Secondary: To demonstrate that
patients already receiving statin
therapy would require more potent
formulations as a result of the new
guidelines
IRB # R2013-155
Conclusion
Methods
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
ACC/AHA recommends
increased statin potency
Yes
No
p<0.001
49%
ATP3 ACC/AHA
% of patients who should receive statins
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
African
American
patients
Diabetics
Female
patients
Male Patients
Patients with
CAD
Discussion
 Many editorials published since
the release of the ACC/AHA 2013
guidelines have hypothesized large
increases in patients requiring
statins; our data appears to support
this hypothesis
 The limitations of this study
include:
 Relatively small sample size
 Some patients already on statins
at the time of the study
 Twice as many females in
random sampling of patients
No
statin
Statin
51%
 Statin therapy was recommended in
more patients overall with ACC/AHA
than ATPIII
 ACC/AHA guidelines recommended
increased statin intensity in almost
50% of patients who were already
receiving statin therapy
 Statin therapy was recommended
for more patients in all special
populations analyzed in this study
ATPIII
ACC/AHA
Patients with
HTN
References
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM,
Blum CB, McBride P, Eckel RH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith Jr SC, Levy D,
Watson K, Wilson PWF, 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013).
2013 Prevention Guidelines Tools: CV Risk Calculator (November 12, 2013). In American Heart
Association. Retrieved November 19, 2013, from my.americanheart.org/cvriskcalculator.
Goff Jr DC, Lloyd-Jones DM, Bennett G, O’Donnell CJ, Coady S, Robinson J,
D’Agostino Sr RB, Schwartz JS, Gibbons R, Shero ST, Greenland P, Smith Jr SC, Lackland DT, Sorlie P,
Levy D, Stone NJ, Wilson PWF, 2013 ACC/AHA Guideline on the Assessment of Cardiovascular
Risk, Journal of the American College of Cardiology (2013).
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National
Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106:3143.
Wilson PWF, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary
heart disease using risk factor categories. Circulation 1998;97:1837-47.
D'Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary
care: the Framingham Heart Study. Circulation 2008; 117:743.
Leading Causes of Death (January 27, 2012). In Centers for Disease Control and Prevention. Retrieved
November 23, 2013, from http://www.cdc.gov/nchs/fastats/lcod.htm.
Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease.
Lancet 1999; 353:89.
ACC/AHA Publish New Guideline for Management of Blood Cholesterol (November 12, 2013). In
American Heart Association. Retrieved November 23, 2013, from
http://newsroom.heart.org/news/acc-aha-publish-new-guideline-for-management-of-bloodcholesterol.
O'Riordan, M. (November 14, 2013). New Cholesterol Guidelines Abandon LDL Targets. In Medscape
Cardiology. Retrieved November 23, 2013, from http://www.medscape.com/viewarticle/814152#1.
Authors have no conflicts of interest to disclose
Salmonella isolation from perinephric abscess
Rohan Mehta MD, Victor Collier MD
St. Vincent Internal Medicine
Introduction
A perinephric abscess is a collection of suppurative material in the
perinephric space between the renal capsule and Gerota's fascia, if
the abscess is able to extend beyond the said fascia; it is termed a
paranephric abscess. The perinephric space also contains some
blood vessels and lymphatics, which facilitate the spread of
infection. Most of perirenal abscesses result from either the
rupture of an intrarenal abscess into the perinephric space, or
chronic recurrent pyelonephritis. Approximately 30% of cases are
attributed to hematogenous or lymphatic dissemination of
organisms from focal sources of infection such as wound infection
and furuncles. Occasionally, a perinephric abscess results from the
spread of infection from extraperitoneal sites, such as in
retroperitoneal appendicitis, diverticulitis, pancreatitis, pelvic
inflammatory conditions and osteomyelitis of adjacent ribs or
vertebrae.1
The case discussed here demonstrates the difficulty in diagnosing
perinephric abscess due to the slow onset of presentation,
radiographic limitations and the limited penetration of certain
antibiotics. It also illustrates that unusual pathogens can
complicate the clinical picture. The common etiologic agents of
perinephric abscesses are E. coli, Proteus species, and S. aureus.
The following is a very rare case in terms of the organism isolate
Salmonella sp. from a perinephric abscess.
.
Case Description
A 44-year-old man with past medical history significant for End
stage renal disease (ESRD) from autosomal dominant polycystic
kidney disease (ADPKD) presented to emergency department with a
fever of 102.9°F and left lower quadrant abdominal pain. Other
pertinent medical history includes the patient being a hemodialysis
recipient three times a week, and is also a type II diabetic. Two
weeks prior to this particular visit, the patient had intermittent
fevers, vomiting, and non-bloody diarrhea for 5 days which resolved
with supportive treatment. Physical exam was positive for mild LLQ
and flank pain without any urinary symptoms. CT scan of the
abdomen without contrast revealed bilateral renal enlargement and
innumerable cysts consistent with his condition without any
evidence of an infectious process in the abdomen or pelvis. IV
contrast was not used due to his chronic kidney disease. He was
empirically treated with Vancomcyin and Piperacillin-Tazobactam.
However over the next few days, he continued to have intermittent
high grade fevers with severe leukocytosis and was thus switched
to intravenous ciprofloxacin concerning for possible cyst infection.
A repeat CT scan showed some left sided perinephric stranding
confirming the suspicion of a cyst super infection but no definitive
abscess or fluid collection was visualized. Patient’s blood cultures
also continued to yield negative growth. He was transferred to our
institution for further evaluation and treatment, given his refractory
fevers and leukocytosis. At this point, antibiotics were switched to
cefotaxime due to improved cyst penetration and prior failure of
ciprofloxacin. He remained febrile with significant LLQ abdominal
pain but repeat CT imaging with contrast this time, showed a large
interval enlargement of 11 x 10 x 7.5 cm abscess appearing to arise
from the peripelvic region of the left kidney and extending into the
left psoas musculature. (shown in Figure 1)
Presentation
Etiology
The symptoms of a perinephric abscess develop insidiously
making early recognition at times difficult. Fever is the most
common presenting symptom and occurs in virtually all patients.
Our patient as described earlier, presented with fever and
unilateral flank pain. Table 1 below provides a breakdown of the
most common signs and symptoms depicting a clinical picture of
perinephric abscess.
The common etiologic agents of perinephric abscesses are E.
coli, Proteus species, and S. aureus. Perinephric abscesses are
polymicrobial in cause in 25% of cases. Figure 3 details a
breakdown of perinephric abscess etiology4
Fungi (1%)
Anerobes (9%)
Table 1. Clinical signs and symptoms of perinephric absces1
Symptoms
Figure1. Left perinephric fluid collection is identified consistent
with an abscess infecting left renal pelvis.
He was sent to interventional radiology for abscess drainage.
Culture studies of this serous fluid subsequently grew
Salmonella sp. Following drainage, he had resolution of fever
and leukocytosis. He was discharged in stable condition to
complete two weeks of outpatient antibiotic therapy. Further
review of outside records revealed that he had grown a
Salmonella species from stool culture collected on admission.
Discussion
Elevated
temperature
Pain-Flank
-Abdominal
-Unspecified
Chills
(%)
Signs
(%) patients
patients
affected
affected
89
Flank tenderness
73
80
60
72
42
Dysuria
39
Nausea, vomiting
Weight loss
Weakness
23
25
14
Abdominal
tenderness
63
Temp >100F
Temp >102F
Flank mass
Abdominal mass
59
11
47
35
Diagnosis
CT scan is considered the diagnostic technique of choice as it
identifies the abscess and defines its extent beyond the renal
capsule and the surrounding anatomy. Although US is
noninvasive, CT has been documented to be superior to US for
diagnosing renal or peri-renal abscesses, with an accuracy rate
of 90~100%4
Gram
Positive (23%)
Gram
Negative
(73%)
Proteus
Other Gram
negative
Figure 3. Organisms isolated from perinephric abscess in 78 patients4
Management
The mainstay of treatment for perinephric abscess is drainage.
Antibiotics are mainly used as an adjunct to percutaneous
drainage because they help to control sepsis. Empirical
antimicrobial therapy should be directed at the most likely
pathogen but tailored to the antimicrobial susceptibilities
obtained with culture data. When kidneys become severely
infected, and refractory to antibiotics, nephrectomy (open or
laparoscopic) is the last resort treatment for perinephric
abscesses.5
Conclusion
There have been previously reported cases of salmonella spread
leading to hepatic abscess, tubo-ovarian abscess and even a
reported case of renal abscess. These extremely rare instances
support the observation of a hematogenous spread of
salmonella. It appears that our patient likely had salmonella
enteritis followed by bacteremia, and possible hematogenous
seeding to his left kidney resulting in abscess formation.
Recognition of this infection is essential to instituting surgical
drainage in concordance with appropriate penetrative
antimicrobial therapy.
Pathophysiology
Perinephric abscess can be a life-threatening entity. Nonspecific
findings in patient’s history and physical exam make this a
difficult diagnosis even for an astute physician. Perinephric
abscesses carry mortality rate of 8-22% and significant morbidity
occurs in 35% of patients. This rate partly is due to long delays in
diagnosis and the comorbid conditions. The mortality rate is
higher in sepsis, urinary tract obstruction, the presence of more
underlying diseases such as diabetic ketoacidosis, WBC count
greater than 25,000 cells/μL, and positive blood cultures.2
Diagnosis of a perinephric abscess should be considered in any
patient with fever and abdominal or flank pain. Predisposing
factors include renal or ureteral calculi/stricture, vesicoureteral
reflux, neoplasm, polycystic kidney disease, renal
transplantation, and trauma.3 Patients with diabetes account for
one third of all perinephric abscess cases. Patients with
polycystic renal disease undergoing hemodialysis may be
particularly susceptible to developing perinephric abscess (62%
of cases). The case in discussion fulfilled each of these latter
criteria, and thus unfortunately our patient was at a high risk of
developing the infection.
Eschreichia coli
References
Figure 2.Thickwalled and peripherally irregular low-density lesion
appearing from the left kidney measuring 10 x 7.5 cm, extending
into the left psoas musculature.
1. Saiki J, Vaziri ND, Perinephric and intranephric abscesses: A
review of the literature. West J Med 136:95-102, Feb 1982
2. Shukla, Prem C., and Edward David Kim. "Perinephric
Abscess." eMedicine. et al. 7 Nov. 2004.. 13 Jan. 2005
3. Wickre CG, Major JL, Wolfson M. Perinephric abscess: an
unusual late infectious complication of renal biopsy. Ann Clin
Lab Sci. Nov-Dec 1982;12(6):453-4.
4. Bong Eun Lee, Hee Yun Seol et al. Korean J Intern Med. 2008
September; 23(3): 140–148. 2008, September 20.
5. Schlossberg, David. "Renal Abscess." Clinical Infectious
Disease. Cambridge: Cambridge UP, 2008.
Quality Improvement: Safe Prescribing Habits of
Citalopram in the Elderly
Staci Hollar MD, Amanda Place PharmD, Grace Greist MD
St. Vincent Joshua Max Simon Primary Care Center, Indianapolis, IN
Introduction
Citalopram is a commonly prescribed SSRI used in the
treatment of depression and anxiety. In 2011 the FDA
issued a drug safety communication regarding citalopram
dosing.1 It was recommended that doses greater than
20mg daily be avoided in patients 60 years and older due
to increased risk of QTc prolongation and potentially fatal
arrhythmias.4,5,6 Additional risk factors for prolonged QTc
include female sex, electrolyte abnormalities, renal or
hepatic dysfunction, and use of other QTc prolonging
medications.2,3
The St Vincent Joshua Max Simon Primary Care Center
(PCC) is a medical residency training facility. Residents in
the Internal Medicine (IM) and Family Medicine (FM)
programs routinely see patients 60 years and older, and in
many cases may be responsible for prescribing
antidepressant therapy.
Hypothesis
 It is hypothesized that PCC prescriber adherence to FDA
recommendations for citalopram prescribing in patients 60
years and older will be low.
Objectives
Methods
 Institutional Review Board exempt quality improvement
project using retrospective chart reviews pre- and posteducational intervention.
 Inclusion criteria for baseline analysis: active PCC IM
or FM patients 60 years and older who received a
citalopram prescription between January 2013 and
August 2014.
 If adherence to prescribing recommendations is low,
will perform an educational intervention to improve
awareness and change prescribing patterns.
Any Dose
Citalopram
40mg Dose
Citalopram
QTc
Prolonging
Med
Other
Interacting
Medication*
Loop Diuretic
28.98%
84.06%
10.14%
31.03%
82.76%
10.34%
*Includes medications acting on 2CYP19 and CYP3A4. Most
common interacting medications statins, PPIs, benzos
 Data collected included patient demographics,
prescription data, and presence of concurrent risk factors
for QTc prolongation.
 Of all patients on citalopram only 17.4% have had a
baseline EKG within a year of their citalopram
prescription.
 Educational intervention will be conducted in
November 2014.
 Of patients on 40mg dose, only 34.5% have had an
EKG performed while on the 40mg dose.
 Post-intervention data will be collected May 2015.
 No patients on the 40mg dose were found to have a
prolonged QTc.
Results
 69 patients over the age of 60 years identified as
taking some dose of citalopram
 98% of patients were female
 42% of these patients on higher than recommended
dose.
 QTc prolongation risk factor distribution:
 Primary: Identify the percentage of patients over age
60 at the PCC prescribed higher than recommended
doses of citalopram.
 Secondary: Compare frequency of concurrent risk
factors for QTc prolongation in patients taking
recommended doses and those prescribed greater than
recommended doses.
 Concurrent use of interacting medications:
GFR <30
ml/min
Patients
on any
dose
citalopram
Patients
on 40mg
dose
4.35%
3.45%
Hypokalemia or Pre-existing
Hepatic
HypoQtc
disease
magnesemia prolongation
4.35%
0%
5.80%
3.45%
Conclusion
 Initial data analysis revealed a substantial number of
prescriptions written for a higher than recommended dose
of citalopram.
 Of those patients on higher than recommended dosage,
very few had appropriate EKG monitoring.
 An educational intervention has been designed in the
form of a presentation at resident conference.
 Data will be re-queried several months after educational
intervention to determine whether prescribing habits have
changed.
References
1.45%
3.45%
1.
“FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal
heart rhythms with high doses.” US Food and Drug Association. March 28,2012 <http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm>.
2.
Spina, Edoardo et al. “Clinically Relevant Pharmacokinetic Drug Interactions with Second Generation Antidepressants: An Update.” Clinical
Therapeutics 30 (2008): 1206-1227.
3.
“Combined List of Medications That Prolong QT and/or Cause Torsades de Pointes.” CredibleMeds. September 26, 2014
<https://www.crediblemeds.org/pdftemp/pdf/CombinedList.pdf>.
4.
Castro, Victor et al. “QT interval and antidepressant use: A Cross sectional study of electronic health records.” BMJ 346 (2013): f288.
5.
Vande Griende, JP et al. “FDA Drug Safety Communications: A Narrative Review and Clinical Considerations for Older Adults” Am J Geriatr
Pharmacother. 10 (2012): 264-271.
6.
Wenzel-Seifert, K et al. “QTc Prolongation by Psychotropic Drugs and the Risk of Torsades de Pointes.” Dtsch Arztebl Int, 108 (2011):687-693).
Hemoptysis: A red flag for pseudoaneurysm after pulmonary artery
catheterization
Min Qi DO¹, Keriann VanNostrand MD², Mary Baker
2
MD ,
William Carlos MD², Farzad Loghmani MD²
¹Indiana University Internal Medicine Department and
²Indiana University Pulmonary and Critical Care Department, Indianapolis, Indiana
• Pulmonary artery catheters (PAC) are
routinely used in the diagnosis and
management of pulmonary hypertension with
minimal risks.
• Pulmonary artery pseudoaneurysm rupture is
a rare but potentially fatal complication.
DISCUSSION
Table 1
INTRODUCTION
Risk factors for pulmonary artery pseudoaneurysm formation:
•
•Chronic steroid use
•Systemic anticoagulation
•Age >60 years
Hemoptysis is the initial presenting symptom
suggestive of PA injury in more than 80% of
cases.
•
For those who survive the initial hemoptysis from
a PA rupture, pseudoaneurysm has been reported
to occur between minutes to 7 months later.
•
The right PA is involved in 93% of cases. A high
index of suspicion is required when postcatheterization patients develop hemoptysis.
•
Left untreated, risk of re-bleeding from the
pseudoaneurysm is 30-40% with mortality rate of
40-70%.
•Female gender (69% preponderance)
•Cardiac decompression
•Cardiac manipulation during surgery
CASE DESCRIPTION
• A 69 year old female with history of diabetes
and hypertension was evaluated for 3 months
of lower extremity edema, abdominal
distension and orthopnea.
• Transthoracic echocardiogram showed
diastolic dysfunction and RVSP of
~55mmHg.
CONCLUSION
• Left heart catheterization was notable for
single vessel disease and LVEDP of
27mmHg.
• Right heart catheterization performed under
fluoroscopic guidance: pulmonary artery
pressure of 56/33 mmHg and wedge
pressure of 21mmHg.
Fig 1. Confluent infiltrate in the mid lobe with 1.3 cm center
containing dense contrast media suggestive of the
aneurysm.
Fig 2. Right middle lobe dense consolidation with 1.3 cm
pseudoaneurysm.
• Massive hemoptysis (~300 mL) occurred
unexpectedly with removal of PAC.
• Chest CT revealed a right middle lobe
pulmonary artery pseudoaneurysm (Fig 1-2).
Hemoptysis in patients who have undergone
PAC should raise suspicion for
pseudoaneurysm formation. The R. PA is
involved in 93% of cases.
•
Prompt evaluation with imaging is crucial and
can be accomplished through contrast-enhanced
CT or, time permitting, a CT angiogram.
•
Timely recognition and treatment with surgery
or coil embolization are necessary to prevent
morbidity and mortality.
REFERENCES
• Pulmonary angiography confirmed this as
the source of hemoptysis (Fig 3).
1. Pulmonary artery pseudoaneurysm after Swan-Ganz
catherization: a case presentation and review of literature.
Nellaiyappan M, et al. European Heart Journal: Acute
Cardiovascular Care 2014; Published online January 27,
2014.
• Two coils were successfully deployed: one in
the pseudoaneurysm and a second coil in the
feeding branch (Fig 4).
• Patient subsequently required a transfusion
for a 4 gram drop in her hemoglobin.
• She didn’t have any further hemoptysis
during her hospitalization and was discharged
home.
•
2. Catheter-induced pulmonary artery pseudoaneurysm
formation: Three case reports and a review of the literature.
Poplausky M, et al. Chest 2001; 120:2105-2111.
Fig 3. R. Pulmonary artery pseudoaneurysm visualized as
an enhancing mass with adjacent vessel.
Fig 4. Successful coil embolization for a right middle lobe
branch artery pseudoaneurysm.
3. Pulmonary artery rupture associated with the Swan-Ganz
catheter. Kearney TJ, Shabot MM. Chest 1995; 108:1349–
1352.
It’s Not Iodoform Packing:
An Uncommon Presentation of Pneumonia
Stephen J. Schutzman, MD and Scott Oosting, MD
Saint Vincent Hospital, Indianapolis, Indiana
Objectives
Initial Presentation
• Discussion of typical
characteristics of Ascaris
Lumbricodies infection
•
75 y/o male Burmese refugee presented
with acute respiratory failure and possible
pneumonia
•
In consultation with the Infectious Disease
physicians, it was felt that this was an
Ascaris Lumbricodies.
•
Long history of heavy smoking and COPD
•
• Review of a case presentation
•
Admitted to the MICU, intubated, and
treated with empirically for COPD and
possible Community Acquired Pneumonia
Infection with possible exacerbation by the
recent steroid therapy causing mobilization.
•
The patient was placed on Albendazole and
received a full course of therapy.
•
Developed acute hyper-carbic respiratory
failure when therapy was initiated
necessitating a return to the MICU and
ventilator.
• Discussion of Loffler
Syndrome
•
•
Ascaris Lumbricodies
•
Most common parasitic infection in the
world with 1/6 of population infected
•
Uncommon in the developed world
•
Spread by fecal oral route
•
Complicated life cycle
•
Adult worms can reach 35 cm in length
•
Pulmonary stage: intense inflammatory
response may occur producing Loffler’s
Syndrome, an eosinophilic pneumonia
secondary to a parasitic infection.
•
Patient developed diffuse pulmonary
infiltrates but all cultures remained
negative including thoracentesis
Patients condition improved and he was
transferred to the floor after weaning off
the vent.
The medical staff received a call from the
floor nurse that she had “removed
several feet of iodoform packing
from the patient’s rectum while
cleaning him after a bowel
movement”
Clinical Course
•
Bronchoscopy did not show any larval
forms.
•
Pulmonary and Infectious Disease services
believe that this is the likely explanation of
his initial presentation.
•
The patient was able to return to his home
after an intensive ventilator wean at an
LTAC facility.
Loffler Syndrome
• Essentially is eosinophilic pulmonary
disease secondary to the transit of helmith
larval forms through the lung.
• Can be caused by Ascaris lumbricoides,
hookworms, and Strongyloides stercoralis.
• Sputum may contain eosinophil-derived
Charcot-Leyden crystals.
• Peripheral eosinophilia is usually present
but not always (not seen in this case).
• No specific therapy required
Image 4: Charcot-Leyden crystals
Conclusion
Another graphic or chart
can go here
• Ascaris Lumbricodies is a common
disease outside of the United States
• Loffler’s Syndrome is a well documented
pulmonary complication of these parasitic
worms
• Some foreign bodies are living!
Reference
Available upon request.
Image 1: Ascaris life cycle
(http://www.metapathogen.com/roundworm)
Image 2: “Packing foam” found by medical staff
upon arrival to bedside.
Image 3: CT chest from this patient showing
diffuse pulmonary infiltrates.
Disclosure
None.
Unlucky 13: Bleeding Mystery of an 88-year-old Female
2
MD ,
Harsh Shah DO¹, Greg Durm
Samantha Armstrong MS IV², Annette Moore MD², Naveen
Manchanda MBBS², Indiana University Internal Medicine Department and ²Indiana
University Hematology and Oncology Department, Indianapolis, Indiana
INTRODUCTION
Acquired Factor XIII deficiency due to anti-FXIII antibodies is a
rare but life-threatening bleeding disorder. Factor XIII is a fibrin
stabilizing enzyme which crosslinks fibrin monomers. Deficiency
of Factor XIII results in destabilization of formed clots within 2448 hours, resulting in delayed hemorrhage. Because the standard
coagulation tests are normal, the diagnosis of this disease requires
a high degree of suspicion and specialized testing. Here, we report
a case of an 88-year-old female presenting with severe hemorrhage
of unknown origin.
DISCUSSION
CLINICAL COURSE
AIHA Flare
Bilateral UE
Hematoma
Right Knee,
Thigh and
Buttock
Ecchymosis
CASE DESCRIPTION
An 88-year-old female with a recent diagnosis of autoimmune
hemolytic anemia on oral Prednisone developed left arm swelling,
pain, and ecchymosis. CT scan of the arm showed a biceps muscle
hematoma measuring 17cm in length. On the 4th day, she developed a
rapidly evolving hematoma on the contralateral forearm, which
prompted bilateral fasciotomies and evacuation. Patient continued to
have bleeding from her right forearm hematoma, requiring further
exploration and evacuation of multiple clots. Her Hg dropped from
9.2 g/dl to 6.6 g/dl and she needed packed RBC transfusions. Patient
had a normal coagulation profile including PT, PTT, Fibrinogen and
Thrombin Time. Peripheral blood smear revealed features of chronic
hemolysis.
Patient’s Factor VIII, IX and X levels were normal. Platelet function
checked by Platelet Function Analyzer, VWD antigen and assay were
also unremarkable Subsequently, patient’s Factor XIII levels came
back low at 8%. We suspected this to be a case of acquired factor XIII
deficiency as patient lacked any history of excessive bleeding. Testing
for inhibitor with serial dilutions showed an antibody titer of 1:40.
Patient was started on 100mg of Cyclophosphamide and continued on
20mg of Prednisone for inhibitor eradication. On day 66, patient had
AIHA flare up (Hg: 6.6g/dL) and was started on Rituximab
375mg/m^2 for 4 infusions and her prednisone was increased to 40mg
daily. Her Factor XIII inhibitor level on day 68 came up to 12% and
inhibitor titer went down to 1:10. On day 98, patient developed
several areas of large ecchymosis on the right knee, thigh and buttock
believed to be related to persistent Factor XIII antibodies. Her Factor
XIII activity dropped to < 10% again and inhibitor titer went up to
1:20 on serial dilution. She was transfused and was started on IVIG at
1000mg/kg X 5 for inhibitor eradication. Cyclophosphamide was
stopped and Prednisone was decreased to 10mg daily. Currently,
patient is recovering in a rehab institution and is not actively bleeding.
Cyclophosphamide
100mg daily
Rituximab 375mg/m^2
Infusions started
IVIG 1000mg/kg X 5 started
and Cyclophosphamide
stopped
Patient presented on day 1 with bilateral UE hematomas. Cyclophosphamide was started on
Day 20. Rituximab was started on day 66 and Prednisone increased to 40mg due to AIHA
flare up. On day 98, IVIG was started due to increasing inhibitor levels and ecchymosis.
PROPOSED MANAGEMENT
There are less than 60 reported cases of acquired factor XIII
deficiency in the literature, with most of them being in
Japan. In a recent systematic review that looked at 28
cases, median age of presentation was 65.5 years [1]. 79%
of the patients presented with spontaneous hematomas as
in our case and 18% presented with ICH. 10 of the cases
were associated with medications (6 with Isoniazid) and 7
with autoimmune disorders. However, this is the first
reported case presenting with warm antibody hemolytic
anemia. Prompt characterization of factor XIII activity and
measurement of antibody level using dilution method is
required if there is a high degree of suspicion in an elderly
presenting with hemorrhage of unknown origin.
Transfusions with PRBC and Factor XIII replacement have
been successfully employed to promote hemostasis in
10/11 cases. For inhibitor eradication, immunosuppression
with Cyclophosphamide or Rituximab in combination with
steroids has been successful in 10/16 (62%) of cases.
Second-line therapy with IVIG was successful in 1/2 cases.
Mortality rate was 29% in general and 60% in patients
presenting with ICH. Complete Remission with eradication
of the inhibitor was seen in 46% of the cases and partial
remission in 18% of cases [1].
In our case, we suspect that patient presented with higher
than expected factor XIII activity (8%) at the onset
because she was already on Prednisone for her AIHA. She
has been refractory to first-line therapy with Rituximab
and Cyclophosphamide for complete inhibitor eradication.
Second line therapy with IVIG was recently given and we
wait to see her response.
CONCLUSION
Acquired FXIII deficiency due to anti-FXIII antibodies is a
rare bleeding disorder that can cause moderate to severe
bleeding and carries a significant mortality rate. This
case illustrates the clinical paradigm that if a patient
presents with bleeding symptoms in the setting of
normal routine coagulation tests, the diagnosis of
acquired FXIII deficiency should be considered. Prompt
characterization of Factor XIII activity and inhibitor
level is essential in order to provide the most appropriate
therapy for inhibitor eradication and control of
hemorrhagic complications.
REFERENCES
[1] Massimo et al. Acquired FXIII inhibitors: a systematic
review. J Thromb Thrombolysis (2013) 36:109-114.
The Cost of A Cardiac M arker:
I t’s Enough to Give You Chest P ain
Stephen J. Schutzman, MD and Victor Collier, MD
Saint Vincent Hospital, Indianapolis, Indiana
The Question
The Analysis
The practice of ordering “serial cardiac
markers” is ingrained in our practice
culture. Inpatient and ER physicians
frequently order cardiac markers for
symptoms in and around the chest without
considering the pre-test probability of acute
coronary syndrome. This often leads to
confusion in interpreting results, additional
testing and cost. This leads us to question the
cost and clinical value of the standard “cardiac
marker” panel.
Saint Vincent Hospital, Indianapolis is a 700
bed inpatient facility located in Central Indiana.
The facility is the tertiary hub for a 16 hospital
system covering central Indiana. Laboratory
and billing information were reviewed for a 6
month period. The laboratory processed 11,
901 Troponins and 11,349 CKMBs during this
period. Inpatient billing charges for both of
these labs were: $323.00 Troponin and $194.00
CKMB. Thus for a 6 month period
$6,045,729.00 in charges were created for
cardiac markers. Of this total $2,201,706.00 of
charges would have been from CKMB in only a
6 month time frame.
The Background
Cardiac markers have been conventionally
defined as a Troponin along with CKMB or
CK Panel (Total CK and CKMB). A cardiac
marker series is held as three separate
testing points usually at six to eight hour
intervals. This is done as the laboratory
values are known to peak hours after injury
has occurred. Historically CK and CKMB
were the first identified possible markers of
cardiac tissue injury. These markers however
were not specific enough to the cardiac tissue
and have since been replaced by Troponin as
the primary marker of cardiac tissue injury.
This replacement with Troponin as the
standard is evident in our clinical
conversations. Discussion amongst
physicians concerns “what was the troponin”
and does not include the other laboratory
values. Despite the shift in how clinical
decisions are made CKMB Panels have
remained as part of the “serial marker” set.
Test
Patient
Cost
Conclusion
Total
Ordered
Total
Cost
Troponin
$323.00
CPT Code:
84484
11,901
$3,844,023
CKMB
$194.00
CPT Code:
82550,
82552
11,349
$2,201,706
In the era of increasing cost conscience medicine
and possible capitated care models providing high
value care is going to be the gold standard of the
future. One of the easiest places to improve care
towards this goal is to examine practices that
occur as part of a culture but do not actually
influence clinical care or decision. Elimination of
the CKMB from the standard cardiac marker series
could eliminate as much as 4.5 million dollars of
charges to patients in a year’s time at one facility
alone. The examination of the use of this one lab,
on a national scale, could represent significant
savings.
CKMB’s may provide insight into the timing of the
injury that can provide clinical guidance in certain
circumstances. The lab should be available as an
opt-in as opposed to the current opt-out.
Call To Action
• It is important for providers to be aware of
testing costs.
• Pre-populated order sets while efficient can
perpetuate charge heavy medicine.
• ASK THE QUESTION: Will this change my
management?
Limitations
. We looked at total billable charges and not those that
Table 1: 6 month totals for cardiac markers at St. Vincent
Indianapolis and associated total charges
were reimbursed and we also did not look at the
charge to the hospital.
References available upon request