Faculty Bibliography

INTRODUCTION/BACKGROUND:: Epstein-Barr virus (EBV) infection frequently involves the liver, presenting as elevations in transaminases. EBV infection associated hepatitis, presenting with hyperbilirubinemia is rare. We describe a case of infectious mononucleosis that presented with cholestatasis, and summarize 23 cases from the literature to categorize this increasingly recognized clinical spectrum of EBV infection induced cholestatic hepatitis. METHODS:: We conducted an extensive literature review of all cases of EBV in pediatric and adult literature with cholestatasis using MEDLINE and EMBASE. We also included information on one case from our institution. RESULTS:: We identified 24 cases. Median age was 20 years (range 1-72 years), with 14 (58%) females. On presentation, fever (72%), jaundice (67%) and splenomegaly (62%) were the most common signs. Laboratory data revealed the median asparate aminotransferase (AST), or alanine aminotransferase (ALT) level was 179IU/L (range 56-2518IU/L), median serum bilirubin level 12.6mg/dL (range 2.2-47.5mg/dL) and median alkaline phosphatase level 749IU/L (range 31-3105IU/L). Diagnosis was confirmed using EBV viral capsid antigen IgM in 20 (83%) patients. HIV testing was done in 7 (29%) of the cases, and was negative. One patient died from the illness, while full recovery was reported in all other cases, with median follow-up of 30 days (range 5-180 days). CONCLUSIONS:: Cholestatasis is associated with EBV infection, and should be part of the differential diagnosis in all age groups, presenting with hyperbilirubinemia.

The use of computed tomography scan (CT) of the abdomen and pelvis for surveillance of colorectal cancer (CRC) after primary curative therapy (PCT) remains controversial. Surveillance guidelines at Roswell Park Cancer Institute have included annual CT for the first 2 years after PCT. Isolated metastases from CRC may be amenable to surgical resection, potentially leading to a survival advantage. To assess this, a retrospective chart review of all 203 patients diagnosed with stage II or III CRC between January 1, 1990, and December 31, 1995, was conducted. First-year surveillance CT (CT-1) was performed for 146 of 203 patients and 81 of 146 patients had second-year surveillance CT (CT-2). CT was considered "directed" when at least 1 of the following prompted evaluation: suspicious symptoms or signs, rising carcinoembryonic antigen, findings from colonoscopies, chest x-rays, or laboratory tests. Otherwise, CT was considered "nondirected." Of 121 of 146 CT-1 and 63 of 81 CT-2 with nondirected CT, 7 of 121(5.8%) and 4 of 63 (6.4%) had proven recurrence, respectively. During 2 years of follow up, the estimated lower bound for detection of recurrence by nondirected CT was 11 of 121(9.1%). There were no apparent differences between the 2 groups in demographics, clinical presentation, surgical margins, treatment, tumor site, grade, or TNM stage. Surgical resectability of the metastases for directed and nondirected groups was 10 of 28 (36%) and 6 of 11 (54%), respectively. The median survival for the patients with recurrence in the directed and nondirected groups was 35 and 50 months, respectively. In conclusion, this retrospective study generates the hypothesis that CT surveillance may be of value. A prospective study, properly sized for power, is needed to answer this question.

Invasive filamentous fungal infection (IFFI) is an important cause of mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We reviewed 22 consecutive cases of IFFI in allogeneic HSCT recipients at Roswell Park Cancer Institute. IFFI was diagnosed after neutrophil recovery in 21 patients (95%). All had received corticosteroids within 1 month prior to IFFI diagnosis. Fourteen (64%) presented with dyspnea, and only 7 (32%) were febrile. Aspergillus species were isolated in 18 (82%) cases. Thirty day mortality after IFFI diagnosis was associated with a higher mean daily dose of corticosteroids (P=0.02) and receiving OKT3 (P=0.01) within 1 month prior to IFFI diagnosis and serum creatinine>2 mg/dl at the time of diagnosis (P=0.004). Histopathologic material from biopsy or autopsy was available in 15 patients (68%). In 8 (53%), the predominant lung histopathology was an acellular coagulative necrosis and hyphal angioinvasion was observed in some of these cases. These findings have generally been observed in neutropenic patients but not in non-neutropenic HSCT recipients. The predominance of coagulative necrosis in our series may reflect the high doses of corticosteroids used to treat graft-versus-host disease (GVHD), which may have disabled leukocyte trafficking and hyphal killing.

BACKGROUND:Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. METHODS:We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. RESULTS:We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). CONCLUSIONS:This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

BACKGROUND:Patent foramen ovale (PFO) with or without atrial septal aneurysm (ASA) is highly associated with cerebral ischemic events in young patients. The prevalence of PFO and ASA in elderly patients with cerebral ischemic events is not well described. OBJECTIVE:Our study is to evaluate the frequencies of PFO with right-to-left shunt (RLS) and ASA in elderly patients and to determine whether age is a predictor of flow-reversed PFO with RLS in cerebral ischemic events. METHODS:A prospective registry for all consecutive patients with cerebral ischemic events who were evaluated by transesophageal echocardiography (TEE) for the detection of possible cardiac source of embolization was established and maintained in a university hospital. Patients' demographics including age, gender, ethnic origin, cerebrovascular risk factors, and all positive TEE data were collected from July 2000 to August 2001 for statistical analysis. A univariate and multivariate stepwise logistic regression analysis was performed. RESULTS:In older patients the prevalence of PFO with RLS, PFO, and ASA was 25/118 (20%), 28/118 (24%), and 38/118 (32%), respectively, as opposed to younger patients, in whom it was 35/119 (30%), 39/119 (33%), and 38/119 (32%), respectively. Older patients had higher frequencies of hypertension (59; 69%), CAD (25; 21%), and prior history of stroke (23; 20%) as opposed to younger patients. Younger age (<60 years), gender, smoking history, hypertension, hyperlipidemia, CAD, and prior history of stroke were not associated with higher prevalence of PFO with RLS. Patent foramen ovale was associated with ASA (P < 0.001) and LVH (P < 0.019) in patients with TIA and stroke. In multivariate analysis only ASA (P < 0.001) remained significant with PFO, with RLS controlling for age, gender, and LVH. CONCLUSIONS:PFO with RLS and ASA are frequently present in elderly stroke and/or TIA patients and age is not a predictor for PFO. Transesophageal echocardiography should be considered for all stroke and/or TIA patients irrespective of their age.

OBJECTIVE:To identify the prevalence and characteristics of aortic atherosclerotic plaque disease and its association with cerebrovascular risk factors in patients with cerebral ischemic events. BACKGROUND:Aortic atheroma is associated with ischemic stroke. Its characteristics, including morphology and distribution among different stroke subtypes, are not well described. METHOD/METHODS:From July 2000 to August 2001, all patients evaluated by transesophageal echocardiography (TEE) with diagnoses of transient ischemic attacks (TIAs) and strokes were prospectively studied. Demographics, including age, gender, ethnicity, cerebrovascular risk factors, and stroke subtypes, were collected. RESULTS:Thoracic aortic atheromas (TAAs) were present in 141 of 237 patients (59%) (mean age = 59 +/- 14, 119 [50%] male). Mild plaque (< 2 mm) was present in 13 of 237 (5%), moderate plaque (2-4 mm) in 49 (21%), severe plaque (> or = 4 mm) in 79 (33%), and complex plaque in 64 (27%). Patients' ages (odds ratio [OR] = 1.05, confidence interval [CI] 1.03-1.08, P < .001), coronary artery disease (OR = 2.2, CI 1.02-4.8, P < .042), and patent foramen ovale (PFO) (OR = 0.39, CI 0.22-0.70, P < .002) were associated with the severity and complexity of aortic plaque. In multivariate analysis, age (OR = 1.06, CI 1.03-1.08, P < .001) and the presence of PFO (OR = 0.35, CI 0.18-0.65, P < .001) continued to be significant to the severity and complexity of aortic atheroma. Gender, history of stroke, hypertension, diabetes mellitus, hyperlipidemia, and history of smoking were not associated with TAA. CONCLUSION/CONCLUSIONS:One third of TAA plaques are severe and complex in nature and more frequently present in the descending aorta and the arch of the aorta than in the ascending aorta. TEE should be considered for the early detection and treatment of TAA in patients without identified causes of stroke.

BACKGROUND:The Injury Severity Score (ISS) is a widely accepted method of measuring severity of traumatic injury. A modification has been proposed--the New Injury Severity Score (NISS). This has been shown to predict mortality better in adult trauma patients, but it had no predictive benefit in pediatric patients. The aim of this study was to determine whether the NISS outperforms the ISS in a large pediatric trauma population. METHODS:Admissions in the National Pediatric Trauma Registry between April 1996 and September 1999 were included. The ISS and NISS were calculated for each patient. The study endpoints were mortality at hospital discharge, functional outcome in three domains (expression, locomotion, and feeding), and discharge disposition for the survivors. Predictive ability of each score was assessed by area under the receiver operating characteristic curve. RESULTS:The NISS and ISS performed equally well at predicting mortality in patients with lower injury severity (ISS < 25), but the NISS was significantly better at predicting mortality in the more severely injured patients. Both scores performed equally well at predicting expression and feeding ability. The NISS was superior to the ISS in predicting locomotion ability at discharge. Thirty-seven percent of patients had an NISS that was higher than their ISS. These patients had a significantly higher mortality and suffered worse functional outcomes. CONCLUSION/CONCLUSIONS:The NISS performs as well as the ISS in pediatric patients with lower injury severity and outperforms the ISS in those with higher injury severity.

OBJECTIVE:To report a case of rhabdomyolysis after concomitant use of simvastatin, a commonly used hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and fluconazole, an azole antifungal agent. CASE SUMMARY/METHODS:An 83-year-old white man with a history of congestive heart failure and hyperlipidemia presented to the hospital 1 week following the addition of fluconazole to a medication regimen that included simvastatin 40 mg once daily. The patient had severe muscle weakness and a markedly elevated serum creatine kinase activity, which resolved following discontinuation of simvastatin and fluconazole. DISCUSSION/CONCLUSIONS:Rhabdomyolysis is a recognized adverse effect of HMG-CoA reductase inhibitors (statins), commonly caused by their interaction with other drugs, such as azole antifungals, that inhibit the cytochrome P450 isoenzyme family. An objective causality assessment revealed that the adverse drug event was probable. Although drug interactions have been described for combinations of other HMG-CoA reductase inhibitors and azole antifungals, rhabdomyolysis likely caused by the interaction between simvastatin and fluconazole has not yet been reported. This case reinforces the importance of being vigilant for drug interactions, particularly in connection with commonly prescribed medications such as statins. CONCLUSIONS:Patients receiving statins who have cancer may receive azole antifungals and other drugs that inhibit CYP3A4 during treatment, predisposing them to toxicity. These patients should therefore be monitored closely for drug interactions.