Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases.

Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD.

Impaired motility in Barrett's esophagus: A study using high-resolution manometry with physiologic challenge.

Background: Esophageal dysmotility may predispose to Barrett's esophagus (BE). We hypothesized that high-resolution manometry (HRM) performed with additional physiologic challenge would better delineate dysmotility in BE.

Methods: Included patients had typical reflux symptoms and underwent endoscopy, HRM with single water swallows and adjunctive testing with solids and rapid drink challenge (RDC) before ambulatory pH-impedance monitoring.

Multiple nights of partial sleep deprivation do not affect prospective remembering at long delays.

Prospective memory is defined as remembering to do something at a particular moment in the future and may be modulated by sleep. Here, we investigated whether multiple nights of partial sleep deprivation would affect the successful retrieval of intentions. Fifty-nine adolescents (mean age ± SD: 16.

Crohn's disease associated strictures.

Crohn's disease (CD) is a chronic relapsing and remitting disease that can affect any segments of the gastrointestinal tract. More than 50% of patients with CD develop stricturing or penetrating complications within the first 10 years after diagnosis. Strictures can lead to intestinal obstruction, which is a common indication for surgery.

Role of hemostatic powders in the management of lower gastrointestinal bleeding: A review.

Despite the recent advances in endoscopic hemostatic techniques, the management of lower gastrointestinal bleeding could be sometimes challenging. Hemostatic powders such as Hemospray, EndoClot, and Ankaferd Blood Stopper have found their way into digestive endoscopy and are licenced in many countries especially for use in upper gastrointestinal bleeding. We reviewed the literature on the use of these hemostatic powders in different situations in lower gastrointestinal bleeding and looked at the success rate and rebleeding rate.

A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library.

Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen.

Expert-led didactic versus self-directed audiovisual training of confocal laser endomicroscopy in evaluation of mucosal barrier defects.

Background And Study Aims:  Confocal laser endomicroscopy (CLE) allows mucosal barrier defects along the intestinal epithelium to be visualized during endoscopy. Training in CLE interpretation can be achieved didactically or through self-directed learning. This study aimed to compare the effectiveness of expert-led didactic with self-directed audiovisual teaching for training inexperienced analysts on how to recognize mucosal barrier defects on endoscope-based CLE (eCLE).

Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II).

Objective: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.

Design: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods.

Pediatric Development of Molecularly Targeted Oncology Drugs.

Oncology products developed for adult cancers often receive full waivers of pediatric studies. This analysis retrospectively identified products with potential pediatric development opportunities despite a full waiver. Initial pediatric study plans submitted to the US Food and Drug Administration from 2012 to 2016 for oncology products with plans to request full waivers of pediatric studies were reviewed to determine if a scientific rationale existed for pediatric evaluation based on the molecular mechanism of action (MOA), clinical experience, nonclinical evidence, or published genome sequencing data.

Major Abdominal and Perianal Surgery in Crohn's Disease: Long-term Follow-up of Australian Patients With Crohn's Disease.

Background: Most patients with Crohn's disease still require surgery despite significant advances in medical therapy, surveillance, and management strategies.

Objective: The purpose of this study was to assess surgical strategies and outcomes in Crohn's disease, including surgical recurrence and emergency surgery.

Design: This was a multicenter, retrospective review of a prospectively collected database.

Medication adherence in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition with intestinal and extraintestinal manifestations. Medications are the cornerstone of treatment of IBD. However, patients often adhere to medication poorly.

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

Background: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines.

Aim: To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD.

Systematic review and meta-analysis: assessment of factors affecting disability in inflammatory bowel disease and the reliability of the inflammatory bowel disease disability index.

Background: The Inflammatory Bowel Disease Disability Index (IBD-DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC).

Aim: To assess the severity of disability and associated factors using the IBD-DI, and review the validity of the IBD-DI as a tool.

Method: Systematic review of cross-sectional studies.

Bridging Adult Experience to Pediatrics in Oncology Drug Development.

Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population.

Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis.

Background: Breastfeeding is a modifiable factor that may influence development of inflammatory bowel diseases. However, literature on this has been inconsistent and not accounted for heterogeneity in populations and exposure.

Aim: To conduct a meta-analysis to examine the association between breastfeeding in infancy and risk of Crohn's disease (CD) and ulcerative colitis (UC).

Symptoms of anxiety and depression are independently associated with inflammatory bowel disease-related disability.

Background: Inflammatory bowel disease (IBD) frequently results in disability. The relevance of psychological effects in causing disability, and whether disability occurs similarly in non-Western cohorts is as yet unknown.

Aim: We assessed the relationship between symptoms of anxiety and depression, quality of life and disability in a Singaporean IBD cohort and their predictors.

Rare, high-affinity mouse anti-PD-1 antibodies that function in checkpoint blockade, discovered using microfluidics and molecular genomics.

Conventionally, mouse hybridomas or well-plate screening are used to identify therapeutic monoclonal antibody candidates. In this study, we present an alternative to hybridoma-based discovery that combines microfluidics, yeast single-chain variable fragment (scFv) display, and deep sequencing to rapidly interrogate and screen mouse antibody repertoires. We used our approach on six wild-type mice to identify 269 molecules that bind to programmed cell death protein 1 (PD-1), which were present at an average of 1 in 2,000 in the pre-sort scFv libraries.

Rare, high-affinity anti-pathogen antibodies from human repertoires, discovered using microfluidics and molecular genomics.

Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These antibodies are often excellent candidates for therapeutic monoclonal antibodies. However, mining natural human antibody repertoires is a challenge.

Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial.

Objectives: To determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema.

Methods: We conducted a randomized, double-blind controlled trial of GG (LGG) supplementation on the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants ( = 92) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin (Amerifit Brands, Cromwell, CT), and control infants ( = 92) received 325 mg of inulin alone.

Inflammatory Bowel Disease Pharmacist Adherence Counseling Improves Medication Adherence in Crohn's Disease and Ulcerative Colitis.

Background: While inflammatory bowel diseases (IBD) require long-term medication usage to maintain remission, nonadherence is common and adversely associated with poorer clinical outcomes. Personalized IBD Pharmacist Adherence Counselling, based on the Health Beliefs Model of medication perception, may increase medication adherence.

Methods: This prospective multi-center longitudinal parallel study recruited consecutive IBD subjects that were classified as baseline medication non-adherers and adherers.

Proteomics in Inflammatory Bowel Disease: Approach Using Animal Models.

Recently, proteomics studies have provided important information on the role of proteins in health and disease. In the domain of inflammatory bowel disease, proteomics has shed important light on the pathogenesis and pathophysiology of inflammation and has contributed to the discovery of some putative clinical biomarkers of disease activity. By being able to obtain a large number of specimens from multiple sites and control for confounding environmental, genetic, and metabolic factors, proteomics studies using animal models of colitis offered an alternative approach to human studies.

Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting.

Impaired Intestinal Permeability Contributes to Ongoing Bowel Symptoms in Patients With Inflammatory Bowel Disease and Mucosal Healing.

Background & Aims: Many patients with inflammatory bowel diseases (IBD) have ongoing bowel symptoms of diarrhea or abdominal pain despite mucosal healing. We investigated whether impaired intestinal permeability contributes to these symptoms.

Methods: We performed a prospective study of intestinal permeability, measured by endoscopic confocal laser endomicroscopy in 110 consecutive subjects (31 with ulcerative colitis [UC], 57 with Crohn's disease [CD], and 22 healthy individuals [controls]) in Sydney, Australia from May 2009 and September 2015.

Pediatric-to-adult Transition and Medication Adherence in Patients with Inflammatory Bowel Disease.

Background: Medication nonadherence is common in inflammatory bowel disease and is associated with poor outcomes. There has been no study on pediatric-to-adult transition as a risk factor for nonadherence in inflammatory bowel disease, which has been demonstrated in other diseases. We aimed to assess whether transitioned (TR) patients have higher nonadherence rates than young adults (YAs) diagnosed in adulthood.