Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study.

Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT).

The Impact of Fluid Balance on Acute Kidney Injury in Nontraumatic Subarachnoid Hemorrhage.

Nontraumatic subarachnoid hemorrhage (SAH) can lead to poor neurologic outcomes, particularly when delayed cerebral ischemia (DCI) occurs. Maintenance of euvolemia following SAH is thought to reduce the risk of DCI. However, attempts at maintaining euvolemia often err on the side of hypervolemia.

ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse.

Background & Aims: Patients with ulcerative colitis (UC) may experience nonresponse to biologics, possibly as a result of low drug exposure. This trial assessed the efficacy of dose optimization in patients with UC who have early nonresponse to vedolizumab and high drug clearance.

Methods: ENTERPRET was a phase 4, open-label, randomized, controlled trial that included patients with moderate to severe UC who had high drug clearance at week 5 (serum concentration, <50 μg/mL) and nonresponse to standard vedolizumab treatment at week 6.

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system.

DOCK4 Regulation of Rho GTPases Mediates Pulmonary Vascular Barrier Function.

Background: The vascular endothelium maintains tissue-fluid homeostasis by controlling the passage of large molecules and fluid between the blood and interstitial space. The interaction of catenins and the actin cytoskeleton with VE-cadherin (vascular endothelial cadherin) is the primary mechanism for stabilizing AJs (adherens junctions), thereby preventing lung vascular barrier disruption. Members of the Rho (Ras homology) family of GTPases and conventional GEFs (guanine exchange factors) of these GTPases have been demonstrated to play important roles in regulating endothelial permeability.

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.

Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn's disease.

Background: An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn's Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD.

Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients.

Background: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known.

Purpose: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging.

Study Type: Retrospective.

High-Dose Intravenous Ascorbic Acid: Ready for Prime Time in Traumatic Brain Injury?

Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise.

Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis.

Aim: The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC).

Methods: An open-label pilot study of orally delivered anti-CD3 was performed in patients with moderate-to-severe UC. The primary end points were changes in immunologic parameters and evaluation for safety.

Hormone Therapy for Cancer Is a Risk Factor for Relapse of Inflammatory Bowel Diseases.

Background & Aims: Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBDs). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD.

Methods: We conducted a retrospective cohort study, collecting data from 5 medical centers, on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018.

Challenges in IBD Research: Novel Technologies.

Novel technologies is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, environmental triggers, 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.

Cefepime challenge after piperacillin/tazobactam-induced thrombocytopenia.

Drug-induced thrombocytopenia (DITP) has been described as a sudden and severe hematologic complication of piperacillin/tazobactam. The proposed mechanism by which piperacillin/tazobactam causes DITP involves the formation of a covalent bond to platelet membrane protein thereby inducing a humoral immune response. Given the immunogenic nature of this adverse event and the structural similarities across beta-lactam antibiotics, the potential for cross-reactivity between agents within the class should be considered.

Survey on practice patterns in imaging utilization in patients with Crohn's disease.

Purpose: To perform a survey-based assessment of imaging practice preferences in Crohn's disease (CD).

Methods: An internet-based questionnaire was sent to physicians involved in CD care. The questionnaire addressed the experience, practice patterns, choice of modality, and recent trends in imaging utilization.

Acute Respiratory Distress in the Operating Room and Prone Ventilation: A Case Report.

There have been many advances in the management of acute respiratory distress syndrome, a condition which Bellani et al, in the LUNG SAFE trial (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure), found represents up to 10.4% of intensive care unit admissions and 23.4% of patients requiring mechanical ventilation, with an unadjusted intensive care unit and hospital mortality of 35.

Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis.

Background & Aims: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC after induction therapy with methotrexate and steroids.

Methods: We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score of 6-12 with endoscopy subscore ≥ 2) despite previous conventional or biological therapy.

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.

The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile.

Inflammatory bowel disease (IBD) is a chronic condition driven by loss of homeostasis between the mucosal immune system, the commensal gut microbiota, and the intestinal epithelium. Our goal is to understand how these components of the intestinal ecosystem cooperate to control homeostasis. By combining quantitative measures of epithelial hyperplasia and immune infiltration with multivariate analysis of inter- and intracellular signaling, we identified epithelial mammalian target of rapamycin (mTOR) signaling as a potential driver of inflammation in a mouse model of colitis.

Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis.

Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo.

Integrin αM activation and upregulation on esophageal eosinophils and periostin-mediated eosinophil survival in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an increasingly recognized allergic disease associated with dysphagia and esophageal fibrosis. We aimed to determine expression patterns of specific eosinophil integrins that promote eosinophilic infiltration of the esophageal epithelium, and to determine how key EoE-related cytokines influence eosinophil activation and survival. Esophageal and peripheral eosinophils were isolated from 20 adult subjects with EoE for immunophenotyping and integrin profiling using multicolor flow cytometry and immunohistochemistry.

Differences in Clinical Course, Genetics, and the Microbiome Between Familial and Sporadic Inflammatory Bowel Diseases.

Background And Aim: Family history is the strongest risk factor for developing Crohn's disease [CD] or ulcerative colitis [UC]. We investigated whether the proximity of relationship with the affected relative and concordance for type of inflammatory bowel disease [IBD] modifies the effect of family history on phenotype and disease severity.

Method: This cross-sectional study included patients with a confirmed diagnosis of IBD in a clinical registry.

Comparison of Stromal Vascular Fraction with or Without a Novel Bioscaffold to Fibrin Glue in a Porcine Model of Mechanically Induced Anorectal Fistula.

Background: Anorectal fistulas (ARFs) are a common, devastating, event in the life of a patient with Crohn's disease. ARFs occur in up to 50% of patients with Crohn's disease. Treatment begins with surgical drainage of the initial abscess, followed by antibiotic therapy, then anti-inflammatory medications.