Evaluation of a Novel Smart Capsule Bacterial Detection System Device for Diagnosis of Small Intestinal Bacterial Overgrowth.

Background: There is a large unmet need for alternative, non-invasive, and accurate diagnosis of small intestinal bacterial overgrowth (SIBO). The smart capsule bacterial detection system (SCBDS) device contains a targeted sampling technology and an onboard SCBDS assay to detect metabolically active bacteria in the small intestine. Here, we evaluated the agreement of SCBDS assay with duodenal aspiration/culture ex vivo in a multicenter clinical study.

Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.

Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease.

Development of a Novel Drug Delivery System to Deliver Drugs Directly to the Colonic Mucosa, Resulting in Improved Efficacy and Reduced Systemic Exposure for the Treatment of Ulcerative Colitis.

Despite recent drug approvals for the treatment of inflammatory bowel diseases (IBDs), there remains a high unmet need for new technologies that can increase drug efficacy by improving site-specific drug delivery while reducing systemic exposure. These technologies must address challenges with formulation; in particular, drugs that are liquid, peptides, or proteins are difficult to formulate using existing delayed and extended oral release technologies. They also have the potential to improve efficacy and reduce systemic exposure for certain drugs by delivering higher doses directly to the site of inflammation.

Randomised clinical trial: safety, pharmacokinetics and pharmacodynamics of trazpiroben (TAK-906), a dopamine D /D receptor antagonist, in patients with gastroparesis.

Background: Gastroparesis is a chronic gastric motility disorder. Dopamine D /D receptor antagonists metoclopramide and domperidone are current treatment options but are associated with central nervous system and cardiovascular safety concerns, respectively, precluding chronic use. Trazpiroben (TAK-906), a dopamine D /D receptor antagonist, is under development for chronic treatment of moderate-to-severe gastroparesis.

Challenges in IBD Research: Environmental Triggers.

Environmental triggers is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization.

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use, health-related quality of life, safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome.

Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP.

Alosetron use in clinical practice: significant improvement in irritable bowel syndrome symptoms evaluated using the US Food and Drug Administration composite endpoint.

Background: Alosetron is approved to treat women with severe IBS and diarrhea (IBS-D) who have failed standard therapy. In our study, we aimed to evaluate alosetron efficacy using new US Food and Drug Administration (FDA) endpoints and utilization in clinical practice.

Methods: This prospective, open-label, multicenter, observational 12-week study evaluated women with severe IBS-D enrolled in the alosetron prescribing program.

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.

Food regulations: low FODMAP labeling and communication goals.

There is growing clinical evidence in support of a diet for irritable bowel syndrome (IBS) that is low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). This low FODMAP diet is gaining acceptance globally among clinicians and IBS sufferers alike. However, there is disparity concerning the success rates of the FODMAP diet between patients, which can be attributed to differences in the recommended diet itself and to adherence issues.

Serum Infliximab, Antidrug Antibodies, and Tumor Necrosis Factor Predict Sustained Response in Pediatric Crohn's Disease.

Background: Serum infliximab (s-IFX) levels, antibodies to IFX (ATI), and inflammatory markers are important in predicting clinical outcomes in adults, but their roles in pediatric Crohn's disease (CD) require further study. The primary aim of this study was to determine the association between serologic parameters during induction and ongoing IFX therapy at 12 months in pediatric CD.

Methods: S-IFX, ATI, serum tumor necrosis factor alpha (s-TNF-α), and C-reactive protein were measured at IFX initiation, 10 weeks, 6 months, and 12 months in a prospective cohort study of children with CD at a single tertiary care center.

Antibodies to infliximab are associated with lower infliximab levels and increased likelihood of surgery in pediatric IBD.

Background: Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited.

Methods: We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded.

Systems biology approaches for inflammatory bowel disease: emphasis on gut microbial metabolism.

Although the prevalence of main idiopathic forms of inflammatory bowel disease (IBD) has risen considerably over the last decades, their clinical features do not allow accurate prediction of prognosis, likelihood of disease progression, or response to specific therapy. Through a better understanding of the molecular pathways involved in IBD and the promise of more targeted therapies, the personalized approach to the management of IBD shows potential. To achieve this, there remains a significant need to better understand the disease process at cellular and molecular levels for any given individual with IBD.

A 9-year evaluation of temporal trends in alosetron postmarketing safety under the risk management program.

Objectives: Adverse events (AEs) of ischemic colitis (IC) and complications of constipation (CoC) associated with alosetron are rare and have been adjudicated during the first 5.5 years of the risk management program (RMP); however, changes in incidence rates relative to reductions in AE reports and increases in alosetron prescriptions over the 9-year RMP have not been evaluated. The authors aim to evaluate temporal trends in alosetron postmarketing safety over the 9-year RMP.

Combined serological, genetic, and inflammatory markers differentiate non-IBD, Crohn's disease, and ulcerative colitis patients.

Background: Previous studies have demonstrated that serological markers can assist in diagnosing inflammatory bowel disease (IBD). In this study, we aim to build a diagnostic tool incorporating serological markers, genetic variants, and markers of inflammation into a computational algorithm to examine patterns of combinations of markers to (1) identify patients with IBD and (2) differentiate patients with Crohn's disease (CD) from ulcerative colitis (UC).

Methods: In this cross-sectional study, patient blood samples from 572 CD, 328 UC, 437 non-IBD controls, and 183 healthy controls from academic and community centers were analyzed for 17 markers: 8 serological markers (ASCA-IgA, ASCA-IgG, ANCA, pANCA, OmpC, CBir1, A4-Fla2, and FlaX), 4 genetic markers (ATG16L1, NKX2-3, ECM1, and STAT3), and 5 inflammatory markers (CRP, SAA, ICAM-1, VCAM-1, and VEGF).

Monitoring of adalimumab and antibodies-to-adalimumab levels in patient serum by the homogeneous mobility shift assay.

This report describes the analytical validation and application of the homogeneous mobility shift assay (HMSA) method for the measurement of adalimumab and human antibodies-to-adalimumab (ATA) in serum samples from patients who have lost response to adalimumab treatment. Validation of the ATA- and the adalimumab-HMSA revealed a lower limit of detection to be 0.026 U/mL for ATA and 0.

Evaluation of treatment continuation with alosetron by IBS-D severity criteria.

Objectives: This article evaluates the characteristics and treatment patterns of female patients with severe diarrhea-predominant irritable bowel syndrome (IBS-D) who were treated with alosetron under a risk management program.

Methods: Patients prescribed alosetron (2002-2009) and who voluntarily enrolled in the follow-up study were evaluated. Questionnaires were administered at baseline, Wk 5, Wk 10, and quarterly thereafter for ≤1 year.

Combination of genetic and quantitative serological immune markers are associated with complicated Crohn's disease behavior.

Background: Treatment of Crohn's disease (CD) with biologics may alter disease progression, leading to fewer disease-related complications, but cost and adverse event profiles often limit their effective use. Tools identifying patients at high risk of complications, who would benefit the most from biologics, would be valuable. Previous studies suggest that biomarkers may aid in determining the course of CD.

Multicenter, placebo-controlled trial of lorcaserin for weight management.

Background: Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight.

Methods: In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks.

Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia.

5-Hydroxytryptamine (5-HT)(2A) receptor inverse agonists are promising therapeutic agents for the treatment of sleep maintenance insomnias. Among these agents is nelotanserin, a potent, selective 5-HT(2A) inverse agonist. Both radioligand binding and functional inositol phosphate accumulation assays suggest that nelotanserin has low nanomolar potency on the 5-HT(2A) receptor with at least 30- and 5000-fold selectivity compared with 5-HT(2C) and 5-HT(2B) receptors, respectively.

APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia.

Introduction: Insomnia is a condition affecting 10% to 15% of the adult population and is characterized by difficulty falling asleep, difficulty staying asleep, or nonrestorative sleep, accompanied by daytime impairment or distress. This study evaluates APD125, a selective inverse agonist of the 5-HT(2A) receptor, for treatment of chronic insomnia, with particular emphasis on sleep maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well tolerated.

A randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn's disease.

Background & Aims: The aim of this study was to compare the safety and efficacy of alicaforsen, a first-generation antisense inhibitor of intercellular adhesion molecule 1, with placebo in subjects with active Crohn's disease, a disorder in which intercellular adhesion molecule 1 is overexpressed.

Methods: In 2 identical double-masked, placebo-controlled studies, 331 subjects with active Crohn's disease were treated with either alicaforsen (221 subjects) or placebo (110 subjects) administered via 2-hour intravenous infusion 3 times a week for 4 weeks. Patients then returned for follow-up every 2 weeks.

Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B.

Background: Apolipoprotein B (apoB) is an important structural component of low-density lipoprotein cholesterol (LDL-C) and plays a key role in LDL-C transport and removal. Reduction in apoB synthesis is expected to reduce circulating LDL-C, a proven risk factor of cardiovascular disease. In the present study, we describe the outcome of the first-in-humans study on the safety and efficacy of an antisense oligonucleotide inhibitor of apoB.

Primary sclerosing cholangitis in children: a histologic follow-up study.

Primary sclerosing cholangitis (PSC) is rare in the pediatric population. Little information exists on the progression of the disease in children. This study evaluated the experience with PSC at the Children's Hospital of Philadelphia over the past 20 years, with an emphasis on the histologic features at presentation, during disease progression, and after liver transplantation.

Biomedicines to reduce inflammation but not viral load in chronic HCV--what's the sense?

Although cytokines and cytotoxic T lymphocytes (CTL) are among the predominant mechanisms of host defense against viral pathogens, they can induce an inflammatory response that often leads to tissue injury. Hepatitis C virus (HCV) infection, a major cause of liver-related disease, results in the induction of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and CTL activity, followed by liver injury. Although inflammation facilitates the wound healing process, chronic persistence over several decades results in scar accumulation, fibrosis and often cirrhosis.