Outcome of lifestyle intervention in relation to duration of pre-diabetes: the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study.

INTRODUCTION: In studies that enrolled people with prevalent pre-diabetes of unknown duration, lifestyle intervention (LI) delayed progression to type 2 diabetes (T2D) but did not reverse pre-diabetes in most participants. Here, we assessed the effects of LI among individuals with pre-diabetes of known duration to determine whether outcomes are related to duration of pre-diabetes. RESEARCH DESIGN AND METHODS: The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort study initiated LI in subjects with incident pre-diabetes during follow-up of initially normoglycemic African Americans and European Americans with parental T2D. Participants were stratified into those initiating LI after <3, 3-5, or >5 years of pre-diabetes diagnosis. Assessments included anthropometry, body fat, fasting and 2-hour plasma glucose (FPG, 2hPG), and insulin sensitivity and secretion. The outcomes were normal glucose regulation (NGR; ie, normal FPG and 2hPG), persistent pre-diabetes, or T2D. Participants who maintained normal FPG and normal 2hPG levels during follow-up served as the control. The control subjects did not receive lifestyle or other intervention to alter the course of glycemia or body weight. RESULTS: Of 223 participants (age 53.3±9.28 years, body mass index 30.6±6.70 kg/m2), 72 (control) maintained normoglycemia during follow-up and 138 subjects with incident pre-diabetes initiated LI after 4.08±2.02 years (range 3 months-8.3 years) of diagnosis. Compared with control, LI participants showed decrease in glucose, weight, and body fat; 42.8% reverted to NGR, 50% had persistent pre-diabetes, and 7.2% developed T2D after 5 years. These outcomes were similar across race and pre-diabetes duration strata, but greater glycemic decrease occurred when LI was initiated within 5 years of pre-diabetes diagnosis. CONCLUSIONS: Ninety-three per cent of adults with parental T2D who initiated LI within 3 months to 8.3 years of developing pre-diabetes did not progress to T2D; nearly half reverted to NGR.Trial registration number NCT02027571.

Aortic stenosis and Heyde's syndrome: A comprehensive review.

Heyde's syndrome is an under reported systemic disease of gastrointestinal and cardiac manifestation in older adults. It is characterized by a triad of aortic stenosis, angiodysplasia with bleeding and acquired von Willebrand syndrome. It is characterized by proteolysis of high molecular weight multimers of von Willebrand Factor and loss of platelet mediated homeostasis. Heyde's syndrome is a treatable condition in most cases, especially in the current era of evolution in interventional cardiology and gastroenterology. There are currently no established guidelines in the management of this condition due to paucity of high quality studies, which warrant future trials. High index of suspicion and increasing the awareness of the syndrome among the general practitioners and sub-specialists will improve the diagnostic potential of Heyde's syndrome. Future studies may change the management aspect of Heyde's syndrome and pave a path for drawing specific guidelines and algorithms. The aim of our review article is to summarize the basic pathophysiology, diagnostics and management of Heyde's syndrome with a special attention to Transcatheter aortic valve replacement.

A Patient with Eosinophilic Esophagitis and Herpes Simplex Esophagitis: A Case Report and Literature Review.

Acute herpes simplex esophagitis (HSE) is common in immunocompromised patients. Eosinophilic esophagitis (EoE) is characterized by immune-mediated eosinophil-predominant esophageal inflammation. We report a patient with human immunodeficiency virus infection who presented with dysphagia and odynophagia and was found to have HSE and EoE. The combination of these two relatively rare conditions suggests possible predisposition.

Impact of left ventricular diastolic dysfunction on liver transplantation outcomes based on the latest American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations.

Aim of the study: Cirrhotic cardiomyopathy encompasses systolic dysfunction, left ventricular diastolic dysfunction (LVDD), and conduction abnormalities. This study aims to investigate the impact of LVDD on mortality in patients undergoing liver transplantation (LT). Material and methods: A retrospective review of 400 consecutive patients who underwent LT at our institution was performed. Patient demographics, clinical data, and transthoracic echocardiogram (TTE) were reviewed to identify LVDD. The total cohort consisted of 266 patients after excluding patients with insufficient TTE data (n = 56), patients with indeterminate LVDD (n = 71), and patients with ejection fraction (EF) < 55% (n = 7). Statistical analysis was performed using descriptive statistics. Cox regressions with hazard ratios (HRs) and 95% confidence intervals (CI) were applied to predict 5-year all-cause mortality. Kaplan-Meier survival analysis was conducted to understand the impact of LVDD on 5-year all-cause mortality. Results: Patients with LVDD have higher incidence of hyperlipidemia (36% vs. 17%, p = 0.003), hypertension (50% vs. 27%, p = 0.001) and diabetes (52% vs. 30%, p = 0.003). In addition, patients with non-alcoholic steatohepatitis (NASH) were more likely to have LVDD (48% vs. 24%, p = 0.001). A multivariate logistic regression analysis was performed with age, body mass index (BMI), NASH, alcoholic cirrhosis, hepatitis C, history of diabetes, history of hyperlipidemia, and history of hypertension. In this multivariate logistic regression analysis, NASH (odds ratio [OR] = 4.43 [1.10-17.8], p = 0.04), and history of hypertension (OR = 2.33 [1.16-4.66], p = 0.01) were independent predictors of LVDD. The Kaplan-Meier survival analysis and multivariate Cox regression demonstrated that the presence of LVDD had no impact on 5-year all-cause mortality (log-rank test nonsignificant). Conclusions: This study indicates that LVDD in end-stage liver disease (ESLD) patients does not affect immediate post-transplant outcomes or 5-year all-cause mortality.

Clinical and Genetic Risk Factors of Recurrent Nonalcoholic Fatty Liver Disease After Liver Transplantation.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been increasingly reported among recipients of liver transplantation (LT). We aimed to identify clinical and genetic risk factors responsible for the development of early recurrent NAFLD in nonalcoholic steatohepatitis transplant recipients. METHODS: Forty-six total single nucleotide polymorphisms with known association with NAFLD were tested among both recipient and donor liver samples in 66 LT recipients with nonalcoholic steatohepatitis to characterize influences on NAFLD recurrence at ∼1 year post-LT (median interval from LT to biopsy: 377 days). RESULTS: Recurrent NAFLD was identified in 43 (65.2%) patients, 20 (30.3%) with mild recurrence, and 23 (34.8%) with moderate to severe NAFLD. On adjusted analysis, change in the body mass index (BMI) (ΔBMI) was significantly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. ADIPOR1 rs10920533 in the recipient was associated with increased risk of moderate to severe NAFLD recurrence, whereas the minor allele of SOD2 rs4880 in the recipient was associated with reduced risk. Similar reduced risk was noted in the presence of donor SOD2 rs4880 and HSD17B13 rs6834314 polymorphism. DISCUSSION: Increased BMI post-LT is strongly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. Both donor and recipient SOD2 rs4880 and donor HSD17B13 rs6834314 single nucleotide polymorphisms may be associated with reduced risk of early NAFLD recurrence, whereas presence of the minor allele form of ADIPOR1 rs10920533 in the recipient is associated with increased severity NAFLD recurrence.

Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT. METHODS: Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018-December 2018). Genomic DNA extraction, next-generation sequencing, and quantitative PCR analysis were performed on stool samples collected within 1.1 ± 1.6 y from time of liver biopsy. RESULTS: Recurrent NAFLD was noted in 15 of the 21 included patients. Stool microbiome analysis at the genus level showed significant loss of Akkermansia and increasing Fusobacterium associated with NAFLD recurrence. Quantitative PCR analysis revealed significantly decreased relative abundance of Firmicutes in patients with NAFLD activity scores (NASs) ≥5 as compared with patients with lower NAS scores, whereas Bacteroidetes were significantly increased with higher NAS (P < 0.05). Firmicutes (P = 0.007) and Bifidobacterium group (P = 0.037) were inversely correlated, whereas Bacteroidetes (P = 0.001) showed a positive correlation with higher hepatic steatosis content. The Firmicutes/Bacteroidetes ratios were higher in patients without NAFLD or NASH as compared with patients diagnosed with NAFLD or NASH at the time of sample collection. CONCLUSIONS: Akkermansia, Firmicutes, and Bifidobacterium may play protective roles in the development of recurrent NAFLD in LT recipients, whereas Fusobacteria and Bacteroidetes may play pathogenic roles. These findings highlight the potential role of the "gut-liver" axis in the pathogenesis of NAFLD recurrence after LT.