Overexpression of TNFα in TNF∆ARE+/- mice increases hepatic periportal inflammation and alters bile acid signaling in mice.

Background: Intestinal inflammation is a common factor in ~70% of patients diagnosed with primary sclerosing cholangitis. The TNF∆ARE+/- mouse overexpresses TNFα and spontaneously develops ileitis after weaning. The aim of this study was to examine the influence of ileitis and TNFα overexpression on hepatic injury, fibrosis, inflammation, and bile acid homeostasis.

AXL: A novel therapeutic target in IBD.

Inflammatory bowel diseases (IBD) and their sequela (colitis-associate carcinoma and fibrostenotic complications) remain a significant clinical challenge and novel therapeutic targets are desperately needed. AXL, a receptor tyrosine kinase, has been implicated in myriad cellular functions central to the pathogenesis of IBD. These include facilitating epithelial-to-mesenchymal transition, dampening of Toll-like receptor and natural killer cell mediated immune responses, driving proliferation, and propagating fibrogenic signaling.

Chlorination of epithelial tight junction proteins by neutrophil myeloperoxidase promotes barrier dysfunction and mucosal inflammation.

Neutrophils (polymorphonuclear leukocytes, PMNs) comprise a major component of the immune cell infiltrate during acute mucosal inflammation and have an important role in molding the inflammatory tissue environment. While PMNs are essential to clearance of invading microbes, the major PMN antimicrobial enzyme myeloperoxidase (MPO) can also promote bystander tissue damage. We hypothesized that blocking MPO would attenuate acute colitis and prevent the development of chronic colitis by limiting bystander tissue damage.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

Introduction: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy.

Methods: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate.

The TNF Mouse as a Model of Intestinal Fibrosis.

Crohn disease (CD) is a highly morbid chronic inflammatory disease. Although many patients with CD also develop fibrostenosing complications, there are no medical therapies for intestinal fibrosis. This is due, in part, to a lack of high-fidelity biomimetic models to enhance understanding and drug development, which highlights the need for developing in vivo models of inflammatory bowel disease-related intestinal fibrosis.

A Predictive Model to Identify Complicated Infection.

Background: infection (CDI) is a leading cause of health care-associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

Background: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD.

Methods: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021.

The TNF mouse as a model of intestinal fibrosis.

Background & Aims: Crohn's disease (CD) is a highly morbid chronic inflammatory disease. The majority of CD patients also develop fibrostenosing complications. Despite this, there are no medical therapies for intestinal fibrosis.

Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis.

The healthy mammalian intestine is lined by a single layer of epithelial cells. These cells provide a selectively permeable barrier to luminal contents and normally do so in an efficient and effective manner. Barrier function in the healthy mucosa is provided via several mechanisms including epithelial junctional complexes, mucus production, as well as mucosal-derived antimicrobial proteins.

Contact-dependent, polarized acidification response during neutrophil-epithelial interactions.

Neutrophil (PMN) infiltration during active inflammation imprints changes in the local tissue environment. Such responses are often accompanied by significant extracellular acidosis that result in predictable transcriptional responses. In this study, we explore the mechanisms involved in inflammatory acidification as a result of PMN-intestinal epithelial cell (IEC) interactions.

The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited.

Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model.

Background: Intestinal fibrosis and subsequent intestinal obstruction are common complications of Crohn's disease (CD). Current therapeutics combat inflammation, but no pharmacological therapy exists for fibrostenotic disease. Pathological persistence of activated intestinal myofibroblasts is a key driver of fibrosis in CD.

Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review.

Background And Aims: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures.

Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study.

Background & Aims: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC.

Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19.

Background: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations.

AXL Is a Potential Target for the Treatment of Intestinal Fibrosis.

Background: Fibrosis is the final common pathway to intestinal failure in Crohn's disease, but no medical therapies exist to treat intestinal fibrosis. Activated myofibroblasts are key effector cells of fibrosis in multiple organ systems, including the intestine. AXL is a receptor tyrosine kinase that has been implicated in fibrogenic pathways involving myofibroblast activation.

Variations in Health Care Utilization Patterns Among Inflammatory Bowel Disease Patients at Risk for High Medical Service Utilization Enrolled in High Deductible Health Plans.

Background: High-deductible health plans (HDHPs) are increasing in prevalence as a cost control device for slowing health care cost growth by reducing nonessential medical service utilization. High cost-sharing associated with HDHPs can lead to significant financial distress and worse disease outcomes. We hypothesize that chronic disease patients are delaying or foregoing necessary medical care due to health care costs.

Association of Household Pets, Common Dietary Factors, and Lifestyle Factors with Clostridium difficile Infection.

Background: Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI.

Aims: We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI.

Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Objectives: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS.

Efficacy of Induction Therapy With High-Intensity Tofacitinib in 4 Patients With Acute Severe Ulcerative Colitis.

As many as 25% of patients diagnosed with ulcerative colitis are hospitalized with an episode of acute severe ulcerative colitis (ASUC). The standard of care for patients hospitalized with ASUC relies on rapid induction with intravenous (IV) corticosteroids. Up to 30% of patients do not respond to corticosteroids alone.