ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Relevance of ineffective esophageal motility with erosive and nonerosive gastroesophageal reflux disease.

INTRODUCTION: Ineffective esophageal motility (IEM) is a frequent finding in patients with gastroesophageal reflux disease (GERD). It is responsible for delayed acid clearance as it affects esophageal emptying and saliva transport. Since erosive GERD is a more severe disease than nonerosive GERD, it may be associated with IEM, which delays esophageal clearance. Objective : We investigated the role of IEM in patients with erosive and nonerosive GERD. METHODS: We enrolled 100 patients with heartburn and a primary diagnosis of GERD referred to the GI motility department of RCGLD of Shahid Beheshti University between January 2002 and January 2005. Based on endoscopic findings, the patients were classified into two groups of erosive GERD and nonerosive GERD. Manometry and 24-hour ambulatory pH-metry was performed in all patients. RESULTS: Seventy-seven patients completed the study: 31 (40.3%) with erosive GERD and 46 (59.7%) with nonerosive GERD. IEM was present in 38.7% of patients with erosive GERD and in 28.3% of those with nonerosive GERD (p=0.18). A low lower esophageal sphincter pressure was present in 45.2% of patients with erosive GERD, and in 45.7% of those with nonerosive GERD (p=0.97). Abnormal acid reflux was present in 32.3% and 41.3% of patients with erosive and nonerosive GERD, respectively (p=0.42). CONCLUSION: There was no difference in the prevalence of IEM between patients with erosive and nonerosive GERD. IEM could be an integral part of GERD and may not always be associated with mucosal injury.

The trend of national and sub-national burden of gastrointestinal and liver diseases in Iran 1990 to 2013; study protocol.

BACKGROUND: It is expected that gastrointestinal (GI) and liver diseases inflict considerable burden on health systems in Iran; therefore, highlighting the significance of GI disorders across the other most burdensome diseases requires comprehensive assessment and regular updates of the statistics of such diseases in Iran. OBJECTIVE: To assess in-depth sub-national estimates and trends for the incidence and prevalence of selected GI and liver diseases by age, gender and province over the period 1990 - 2013 in Iran. METHODS: This is a national and sub-national burden of disease study on 21 GI diseases using all available data sources, including cancer registry, death registration system data, hospital data, and all available published data. Analyses will be performed separately by gender, age groups, year, and province. We will conduct 21 separated systematic reviews of the literature for 21 diseases categories through searching online international electronic databases (i.e. the Medline database of the National Library of Medicine, Web of Science, and Scopus), Iranian search engines (i.e., IranMedex, Scientific Information Database (SID), and IRANDOC), and gray literature. We will search the medical literature published between January 1985 and December 2013. We generated two models, Spatio-temporal and Multilevel Autoregressive models, to estimate mean and uncertainty interval for the parameters of interest by gender, age, year, and province. The models will be informed by data of gender, age, year, and province. Markov Chain Monte Carlo (MCMC) methods will be used to perform Bayesian inference in both modeling framework. All programs will be written in R statistical packages (version 3.0.1). RESULTS: We will calculate and present 1990 to 2013 trends in terms of prevalence, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs), and disability-adjusted life years DALYs for the 21 selected GI diseases by gender, and province. We will also quantify the uncertainty interval for the estimates of interest. CONCLUSION: Results of the present study will have implications for policy making; as they allow for understanding geographic distributions of the selected GI diseases, and identifying health disparities across provinces.