A 45 Year Old with Sudden Stroke: A Rare and Silent Culprit...A 45 Year Old with Sudden Stroke: A...
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A 45 Year Old with Sudden Stroke: A Rare and Silent Culprit Ahmed A. Behery, MD 1 , Sai Devarapalli, MD FACC 2 ¹Indiana University Health Ball Memorial Hospital Department of Internal Medicine, Muncie, IN, ²Indiana University Health Ball Memorial Hospital Department of Cardiology, Muncie, IN Introduction Case References 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. 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 Discussion Acknowledgements Figure 1. Buttan A K et al. Circulation. 2012;125. Figure 2. Sun J P et al. Circulation. 2001;103:2687- 2693 Figure 3. Lippincott Williams & Wilkins from Feigenbaum et al. Feigenbaum’s Echocardiography. 6 th 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 . Paroxysmal Atrial Fibrillation Infective Endocarditis Paradoxical Embolism via PFO Thrombophilia Acute Thrombotic Occlusion 2 nd day 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 3 rd degree AV block requiring temporary transvenous pacing. Anticoagulation was not pursued given risk of hemorrhagic conversion. 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. 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. Differential Diagnoses 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. 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. Mitral Valve Papillary Fibroelastoma (MVPF) is comprised of a homogenous fibroelastic and collagenous core encased with endocardium. 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. 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. Aortic Valve 52% Mitral Valve 42% Right Sided 4% Left Atrium 2% 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 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.
Transcript of A 45 Year Old with Sudden Stroke: A Rare and Silent Culprit...A 45 Year Old with Sudden Stroke: A...
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
Introduction
Case
References
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.
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
Discussion
Acknowledgements Figure 1. Buttan A K et al. Circulation. 2012;125.
Figure 2. Sun J P et al. Circulation. 2001;103:2687-
2693
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 .
Paroxysmal
Atrial
Fibrillation
Infective
Endocarditis
Paradoxical
Embolism
via PFO Thrombophilia
Acute
Thrombotic
Occlusion
2nd day
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.
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.
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.
Differential Diagnoses
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.
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.
Mitral Valve Papillary Fibroelastoma
(MVPF) is comprised of a homogenous
fibroelastic and collagenous core encased
with endocardium.
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.
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.
Aortic Valve 52%
Mitral Valve 42%
Right Sided 4%
Left Atrium
2%
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 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.
Searching for Sarcoid: Utility of PET/CT Scan Emily Cochard, MD, PGY3; Ishan Gohil, MS4; Robert J. Fick, MD
St. Vincent Hospital, Indianapolis, Indiana
Discussion 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. 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. The sensitivity of PET/CT in detecting active sarcoidosis is 80-90%. 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.
References •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.
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.
Diagnosis
Introduction 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.
Case 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.
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 •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) •1-25 hydroxy-vitamin D: 99 pg/mL (18-72 pg/mL) •Angiotensin converting enzyme level: 99 U/L (9-67 U/L)
Imaging •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 non-caseating granulomas (Figure 3 and Figure 4)
Figure 2. PET/CT demonstrating heterogeneous uptake throughout the bone marrow.
Figure 3. Bone marrow biopsy demonstrating increased macrophages.
Figure 4. Bone marrow biopsy demonstrating typical granuloma.
Figure 1. PA/lateral CXR demonstrating cardiomegaly
Warfarin as the Culprit of Calciphylaxis
Overview
Physical Exam
References
Clinical Presentation
Labs/Imaging
Prognosis
A debilitated, 46-year-old, Caucasian woman presented from a nursing facility due to concern of superimposed infection on chronic non-healing 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.
Outcome
Biopsy
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.
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.
Deep Venous Thrombosis Obesity Gastric Bypass Iron Deficiency Anemia
Past Medical History
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.
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:
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.
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.
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 non-calcium-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.
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.
Nicholas W. Creasap, MD St. Vincent Hospital, Indianapolis, Indiana
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.
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.
Therapy
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.
Background IBD is a common cause of subacute or chronic, often bloody, diarrhea in
teenagers and younger adults
IBD commonly affects women during reproductive years, therefore pregnancy may complicate the diagnosis and significantly alter treatment options
Pregnant women with IBD are at a higher risk for complications, including preterm birth, small for gestational age birth, hypertensive disorders of pregnancy, and prolonged or premature rupture of membranes.
Further Evaluation 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
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.
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
Patient Presentation 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 acidosis, acute kidney injury, and ongoing diarrhea
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-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
General Principles Counseling regarding heritability
Fertility preserved or mildly reduced with adequate
treatment
- Exceptions of surgical intervention
Pregnancy not proven to increase likelihood of disease
flare
Risk of flare during pregnancy most likely to reflect
disease activity prior to pregnancy, but may vary
Management of flares in pregnancy similar to that in
nonpregnant patients
Cesarean section recommended with active perianal
disease seen in Crohn’s disease
IBD patients are at increased risk of complications
- 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
Achieving and maintaining disease remission key to
reducing fetal and maternal complications
Breastfeeding may reduce disease severity postpartum
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
Most medications used in the management of IBD are
compatible with pregnancy, other than methotrexate
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
Treatment Safety in Pregnancy and Breastfeeding
Class Pregnancy Category
Adverse Effects
Comments Breastfeeding
Mesalamine Aminosalicylate B/C Folate
deficiency Preparation-
dependent risk Compatible
Prednisone Corticosteriod C Orofacial clefts premature ROM
Flare treatment Compatible
Azathioprine Purine
antimetabolite D
VSD, ASD, preterm delivery
Not
recommended
Methotrexate Folate antagonist X Multiple
congenital anomalies
Discontinue 6 months prior to
conception Contraindicated
Cyclosporine Calcineurin
inhibitor C
Preterm delivery SGA
Contraindicated
Infliximab Anti-TNF antibody
B Limited human
data Not
recommended
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
Daniel Hugenberg, Neil Keshvani, Tobin Greensweig, Steven HugenbergIndiana University School of Medicine Indianapolis Indiana
A Rare Myopathic Complication of Statin Use
Indiana University School of Medicine, Indianapolis, Indiana
INTRODUCTION
Statin-associated necrotizing autoimmune myopathy is a rare
DISCUSSIONHOSPITAL COURSE
Our patient presented with a subacute myopathic process• The patient was treated for presumed rhabdomyolysis withg y p ycondition 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-methyl-glutaryl-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
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).2This 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 thi diti d t ti 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
PATIENT PRESENTATION
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
this condition and statin use.2-5
The pathophysiology of this condition is likely related to up-regulation 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
inflammatory 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.
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.
• Presented to his primary care physician with complaints of
would not have changed our clinical management.
Knowledge of this diagnosis is important for clinicians as the number of prescriptions of statins is increasing in the United S S i i d NAM i f k
• Upon initiation of prednisone at a dose of 1 mg/kg/day, the patient’s symptoms and CK levels improved rapidly.
20000
25000
30000
L)
CPK Level Through Hospital Course CONCLUSION
• 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.
• One month prior to presentation the patient was noted to have an asymptomatic transaminitis.
States. Statin-associated NAM may persist for weeks 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
0
5000
10000
15000
20000
1 2 3 4 5 6 7 8 9 10 11
CPK
(IU
/L
Hospital Day
Prednisone started
• AST 144, ALT 266 IU/L.• Atorvastatin was discontinued at this time.
• 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 ALT 553 IU/L
REFERENCES1. Dalakas, MC. Toxic and drug-induced myopathies. J Neurol NeurosurgPsychiatry. 2009; 80: 832–838. 2. Grable-Esposito, P. et al. Immune-mediated necrotizing myopathyassociated with statins Muscle Nerve 2010; 41: 185 190• AST 570, ALT 553 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.
associated with statins. Muscle Nerve. 2010; 41: 185–190.3. Liang C, Needham M. Necrotizing autoimmune myopathy. Curr OpinRheumatol. 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 OpinRheumatol. 2013; 25: 747–752.
a) Normal muscle biopsy. b) Muscle biopsy of a patient with autoimmunenecrotizing myopathy. Note the necrotic muscle fibers infiltrated by macrophages. Reproduced with permission, courtesy of Mammen, AL.4
Maitri Kalra, MBBS ; Andrew Walker
Spinal Cord Ischemia After Methamphetamine Abuse: A Case Report
D
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.
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.
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.
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.
MRI Images of Thoracic and Lumbar Spine
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
References •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 difficile-associated 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.
Conclusion 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.
Discussion 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. •Cost may have been higher due to multiple confounding variables. •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.
•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).
Introduction 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
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.
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.
Results
7
7.1
7.2
7.3
7.4
7.5
7.6
7.7
7.8
7.9
8
GB Non-GB
mLOS
Figure 1. mLOS was shorter for those patients treated with GB therapy, 7.45 days vs. 7.9 days (not statistically significant)
20
22
24
26
28
30
32
34
36
38
40
GB Non-GB
Readmission
Figure 2. 30-day readmission rate was lower for those treated with GB therapy, 29% vs. 38% (not statistically significant)
0
1
2
3
4
5
6
7
8
GB Non-GB
Mortality
Figure 3. Mortality rate was lower for those patients treated with GB therapy, 3.2% vs. 6.3% (not statistically significant)
$10,000
$11,000
$12,000
$13,000
$14,000
$15,000
$16,000
$17,000
GB Non-GB
Cost
Figure 4. Cost was higher for those patients treated with GB therapy, $16,657.10 vs. $12,787.08.29 (not statistically significant)
Chris Kniese, MD • Grant Gilroy, MD • Praveen Mathur, MD Indiana University School of Medicine, Indianapolis Indiana
Intentional Isoniazid Overdose: An Uncommon Toxicity
Introduction
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 follow-up.
Learning Objectives Discussion
REFERENCES
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.
Lab Results
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.
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, calculated 24 mmol/L
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 phosphatase 101 IU/L
AST 47 IU/L ALT 52 IU/L Protein, total 8.5 g/dL Acetaminophen, serum < 2.0 mcg/m
L Ethanol, serum < 3 mg/dL Salicylate 2 mg/dL
Initial Labs
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
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.
Discussion Kimberly Ku, MD
Department of Medicine, Indiana University School of Medicine
Indianapolis, IN
It Takes a Village To Cure Recurrent Pneumothorax
‣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.
‣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.
Case Description
References 1. Aljehani, Y. Catamenial pneumothora. Is it time to approach differently? Saudi
Medical Journal, 2014. 35(2): p.115-22. 2. 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.
3. 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
4. Peikert, T., D.J. Gillespie, and S.D. Cassivi, Catamenial pneumothorax. Mayo Clin Proc, 2005. 80(5): p. 677-80.
5. Trehan, A. (2014, Oct. 12). Mr. Ashwini Trehan Endometriosis Specialist. Retreived from http://www.endometriosis-consultant.co.uk/endometriosis-diagnosis/
6. 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.
CT chest with IV contrast – ED visit
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.
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 right-sided chest pain. She was on her menstrual cycle.
‣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.
‣No further incidents of pneumothorax or chest pain.
‣Pulmonary and thoracic surgery clinics following on symptom basis with no further planned surgeries.
Thoracic endometriosis
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
Objectives
Methods
Discussion
Conclusion
References
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
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
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
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-blood-cholesterol.
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.
.
0%10%20%30%40%50%60%70%80%90%
100%
ATP3 ACC/AHA
Is statin therapy recommended?
NostatinStatin
p<0.001
Hypothesis
We theorized that more patients would qualify for statin therapy with implementation of the ACC/AHA guidelines
Results
0%10%20%30%40%50%60%70%80%90%
100%
AfricanAmericanpatients
Diabetics Femalepatients
Male Patients Patients withCAD
Patients withHTN
% of patients who should receive statins ATPIIIACC/AHA
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
49% 51%
ACC/AHA recommends increased statin potency
Yes No
Authors have no conflicts of interest to disclose
IRB # R2013-155
Salmonella isolation from perinephric abscess Rohan Mehta MD, Victor Collier MD
St. Vincent Internal Medicine
Discussion
References
Introduction
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)
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. .
Presentation 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.
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.
Figure1. Left perinephric fluid collection is identified consistent with an abscess infecting left renal pelvis.
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.
Symptoms (%) patients affected
Signs (%) patients affected
Elevated temperature
89 Flank tenderness 73
Pain-Flank -Abdominal -Unspecified
80 60 72
Abdominal tenderness
63
Chills 42 Temp >100F Temp >102F
59 11
Dysuria 39 Flank mass Abdominal mass
47 35
Nausea, vomiting 23 Weight loss 25 Weakness 14
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.
Etiology 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
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
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.
Table 1. Clinical signs and symptoms of perinephric absces1
Eschreichia coli
Proteus Other Gram
negative
Anerobes (9%)
Fungi (1%)
Gram Positive (23%) Gram
Negative (73%)
Figure 3. Organisms isolated from perinephric abscess in 78 patients4
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 Methods
Conclusion
Objectives
References
Results
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.
If adherence to prescribing recommendations is low, will perform an educational intervention to improve awareness and change prescribing patterns.
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).
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.
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.
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:
GFR <30 ml/min
Hepatic disease
Hypokalemia or Hypo-
magnesemia
Pre-existing Qtc
prolongation
Patients on any dose
citalopram
4.35% 4.35% 5.80% 1.45%
Patients on 40mg
dose 3.45% 0% 3.45% 3.45%
Concurrent use of interacting medications:
*Includes medications acting on 2CYP19 and CYP3A4. Most common interacting medications statins, PPIs, benzos
Of all patients on citalopram only 17.4% have had a baseline EKG within a year of their citalopram prescription.
Of patients on 40mg dose, only 34.5% have had an EKG performed while on the 40mg dose.
No patients on the 40mg dose were found to have a prolonged QTc.
QTc Prolonging
Med
Other Interacting Medication*
Loop Diuretic
Any Dose Citalopram 28.98% 84.06% 10.14%
40mg Dose Citalopram 31.03% 82.76% 10.34%
Hypothesis
It is hypothesized that PCC prescriber adherence to FDA recommendations for citalopram prescribing in patients 60 years and older will be low.
Institutional Review Board exempt quality improvement project using retrospective chart reviews pre- and post-educational 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.
Data collected included patient demographics, prescription data, and presence of concurrent risk factors for QTc prolongation.
Educational intervention will be conducted in November 2014.
Post-intervention data will be collected May 2015.
Min Qi DO¹, Keriann VanNostrand MD², Mary Baker MD2, William Carlos MD², Farzad Loghmani MD² ¹Indiana University Internal Medicine Department and
²Indiana University Pulmonary and Critical Care Department, Indianapolis, Indiana
Hemoptysis: A red flag for pseudoaneurysm after pulmonary artery catheterization
INTRODUCTION
CASE DESCRIPTION
• 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.
• 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.
• 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.
• Massive hemoptysis (~300 mL) occurred unexpectedly with removal of PAC.
• Chest CT revealed a right middle lobe
pulmonary artery pseudoaneurysm (Fig 1-2).
• Pulmonary angiography confirmed this as the source of hemoptysis (Fig 3).
• 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.
DISCUSSION
REFERENCES 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.
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.
3. Pulmonary artery rupture associated with the Swan-Ganz catheter. Kearney TJ, Shabot MM. Chest 1995; 108:1349–1352.
• 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 post-catheterization patients develop hemoptysis.
• Left untreated, risk of re-bleeding from the
pseudoaneurysm is 30-40% with mortality rate of 40-70%.
• 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.
CONCLUSION
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.
Fig 4. Successful coil embolization for a right middle lobe branch artery pseudoaneurysm.
Fig 3. R. Pulmonary artery pseudoaneurysm visualized as an enhancing mass with adjacent vessel.
•Chronic steroid use •Systemic anticoagulation •Age >60 years
•Female gender (69% preponderance) •Cardiac decompression •Cardiac manipulation during surgery
Risk factors for pulmonary artery pseudoaneurysm formation:
Table 1
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.
Objectives
• Discussion of typical characteristics of Ascaris Lumbricodies infection
• Review of a case presentation
• Discussion of Loffler Syndrome
It’s Not Iodoform Packing: An Uncommon Presentation of Pneumonia Stephen J. Schutzman, MD and Scott Oosting, MD Saint Vincent Hospital, Indianapolis, Indiana
Disclosure None.
Conclusion • 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!
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
Initial Presentation • 75 y/o male Burmese refugee presented
with acute respiratory failure and possible pneumonia
• Long history of heavy smoking and COPD
• Admitted to the MICU, intubated, and treated with empirically for COPD and possible Community Acquired Pneumonia
• 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”
Another graphic or chart can go here
Clinical Course • In consultation with the Infectious Disease
physicians, it was felt that this was an Ascaris Lumbricodies.
• 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.
• 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.
Image 2: “Packing foam” found by medical staff upon arrival to bedside. Image 1: Ascaris life cycle
(http://www.metapathogen.com/roundworm)
Reference Available upon request.
Image 3: CT chest from this patient showing diffuse pulmonary infiltrates.
Image 4: Charcot-Leyden crystals
Harsh Shah DO¹, Greg Durm MD2, Samantha Armstrong MS IV², Annette Moore MD², Naveen Manchanda MBBS², Indiana University Internal Medicine Department and ²Indiana
University Hematology and Oncology Department, Indianapolis, Indiana
Unlucky 13: Bleeding Mystery of an 88-year-old Female
INTRODUCTION
CASE DESCRIPTION
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 24-48 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.
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.
DISCUSSION
REFERENCES
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.
CONCLUSION
Bilateral UE Hematoma
AIHA Flare
Right Knee, Thigh and Buttock Ecchymosis
Cyclophosphamide 100mg daily
Rituximab 375mg/m^2 Infusions started
IVIG 1000mg/kg X 5 started and Cyclophosphamide stopped
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.
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.
[1] Massimo et al. Acquired FXIII inhibitors: a systematic review. J Thromb Thrombolysis (2013) 36:109-114.
CLINICAL COURSE
PROPOSED MANAGEMENT
The Cost of A Cardiac Marker: I t’s Enough to Give You Chest Pain
The Background
The Question
Limitations .
Conclusion
Call To Action
Stephen J. Schutzman, MD and Victor Collier, MD Saint Vincent Hospital, Indianapolis, Indiana
The Analysis 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.
Table 1: 6 month totals for cardiac markers at St. Vincent Indianapolis and associated total charges
We looked at total billable charges and not those that were reimbursed and we also did not look at the charge to the hospital.
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.
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.
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
Total Ordered
Total Cost
Troponin CPT Code: 84484
$323.00 11,901 $3,844,023
CKMB CPT Code: 82550, 82552
$194.00 11,349 $2,201,706
• 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?
References available upon request
![The Culprit [2]](https://static.fdocuments.net/doc/165x107/56816247550346895dd28534/the-culprit-2.jpg)
