Graft-versus-Host Disease-Like Pattern in Mycophenolate Mofetil Related Colon Mucosal Injury: Role of FISH in Establishing the Diagnosis

Mycophenolate mofetil (CellCept®), a commonly used immunosuppressive drug in solid organ transplantation, has recently been shown to cause graft-versus-host disease (GVHD)-like changes in the gastrointestinal tract. On rare occasions, true GVHD has also been documented in the gastrointestinal tract of solid organ transplant patients. Because the treatment for these two entities is different, i.e. removal of the offending agent versus the administration of steroids, proper identification of the cause is imperative. We present a case of mycophenolate mofetil colitis mimicking grade I GVHD of the gut. In our study, we used fluorescence in situ hybridization for the Y chromosome to document the lack of male donor lymphocytes in the female recipient colon biopsy. We suggest that molecular techniques including fluorescence in situ hybridization could be used to discriminate between MMF-related colitis and true GVHD in order to help guide therapy

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Background & aimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed

Colorectal cancer

© Springer International Publishing Switzerland 2016. All rights reserved. Molecular testing of colorectal cancer (CRC) has become the standard practice in the management of patients who are candidates for chemotherapy and geneor pathway-targeted therapies, providing critical information for precision therapy. Current and emerging testing approaches and guidelines used to select EGFR pathway-targeted therapies for CRC are reviewed, as well as the use of DNA mismatch repair deficiency testing in CRC for identification of patients who might not benefit from conventional therapies containing 5-fluorouracil (5FU). Recent recommendations for extended RAS mutation testing encompassing exons 2, 3, and 4 of KRAS and NRAS in CRC are highlighted. An overview of laboratory considerations includes the critical role of tumor tissue evaluation by pathologists, in order to select the best areas of tumor for testing. In addition to a number of conventional testing platforms, given the increasing number of gene mutations that may be critical to achieve targeted therapy efficacy in CRC, advances in the use of gene panels for mutation analysis with platforms that permit detection of hundreds of mutations in a single sample, such as next-generation sequencing (NGS) gene panels, are described

Fatal Gastrointestinal Hemorrhage in a Patient with Brunner’s Gland Hyperplasia

Brunner’s gland hyperplasia is a rare cause of duodenal mass and gastrointestinal hemorrhage. Imaging and esophagoduodenoscopic evaluation of this condition are frequently consistent with a duodenal malignancy often resulting in surgical resection. However, the malignant potential of these lesions is still unknown, and most are benign. We report the case of a 74-year-old man who presented with fatal gastrointestinal bleeding and esophagoduodenoscopy findings consistent with a duodenal mass and mucosal ulceration. At autopsy, histologic examination of the mass revealed Brunner’s gland hyperplasia with associated ulcer formation. In this report, we review the findings associated with this case as well the literature regarding presentation, clinical associations, and treatment of Brunner’s gland hyperplasia

Team-Based Learning in a Pipeline Course in Medical Microbiology for Under-Represented Student Populations in Medicine Improves Learning of Microbiology Concepts

As part of an undergraduate pipeline program at our institution for students from underrepresented minorities in medicine backgrounds, we created an intensive four-week medical microbiology course. Team-based learning (TBL) was implemented in this course to enhance student learning of course content. Three different student cohorts participated in the study, and there were no significant differences in their prior academic achievement based on their undergraduate grade point average (GPA) and pre-course examination scores. Teaching techniques included engaged lectures using an audience response system, TBL, and guided self-directed learning. We hypothesized that more active learning exercises, irrespective of the amount of lecture time, would help students master course content. In year 2 as compared with year 1, TBL exercises were decreased from six to three with a concomitant increase in lecture time, while in year 3, TBL exercises were increased from three to six while maintaining the same amount of lecture time as in year 2. As we hypothesized, there was significant (p < 0.01) improvement in performance on the post-course examination in years 1 and 3 compared with year 2, when only three TBL exercises were used. In contrast to the students’ perceptions that more lecture time enhances learning of course content, our findings suggest that active learning strategies, such as TBL, are more effective than engaged lectures in improving student understanding of course content, as measured by post-course examination performance. Introduction of TBL in pipeline program courses may help achieve better student learning outcomes

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease.

BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P &lt; 0.0001) and at 3T (r = 0.586, P &lt; 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength.Data conclusionHepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only.Level of evidence4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456-1466