Early Life and Childhood Environmental Exposures, More Than Genetic Predisposition, Influence Age of Diagnosis in a Diverse Cohort of 2952 Patients With IBD.

Background And Aims: Inflammatory bowel disease (IBD) develops from a combination of genetic and environmental factors. The aim of this study was to determine the contribution of established environmental risk factors and genetic risk on age of IBD diagnosis in a diverse cohort.

Methods: IBD patients in clinic completed detailed questionnaires.

Food as Medicine: How to Influence the Microbiome and Improve Symptoms in Patients with Irritable Bowel Syndrome.

Purpose Of Review: This review highlights effects of dietary interventions on the gut microbiome and gastrointestinal symptoms in those with irritable bowel syndrome (IBS).

Recent Findings: It is hypothesized that gut dysbiosis factors into the pathophysiology of IBS. Various diets that influence the microbiome and intestinal physiology may have therapeutic properties.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

Background & Aims: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer.

Methods: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis.

Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis.

Background: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy.

Methods: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.

Social barriers influence inflammatory bowel disease (IBD) outcomes and disproportionally affect Hispanics and non-Hispanic Blacks with IBD.

Background: The impact of social determinants of health in inflammatory bowel disease (IBD) remains understudied. We evaluated the impact of social barriers on IBD outcomes within a diverse cohort of patients.

Methods: We performed a cross-sectional study on adult IBD patients and assessed known social determinants of health.

Impact of Obesity on Inflammatory Bowel Disease.

Purpose Of Review: This review highlights recent work that evaluates the impact of obesity on inflammatory bowel disease (IBD) pathogenesis and management.

Recent Findings: The impact of obesity on IBD prevalence, clinical course, and management, has been studied and described more so in recent years. Studies have shown that obesity increases IBD disease activity, leads to longer hospitalization courses, and increases the likelihood of the development of extraintestinal manifestations.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH).

Patients And Methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication.

Rates of decompensation, hepatocellular carcinoma and mortality in AMA-negative primary biliary cholangitis cirrhosis.

Background: The natural history of patients with anti-mitochondrial antibody (AMA)-negative Primary Biliary Cholangitis (PBC) cirrhosis has not been well defined, with prior studies showing discordant results. Furthermore, most studies of AMA-negative PBC have limited numbers of patients with cirrhosis and liver-related outcomes.

Methods: We investigated the association of AMA-negative PBC and the development of death, liver-related death, decompensation and hepatocellular carcinoma (HCC), in a large cohort of predominantly male patients with PBC cirrhosis assembled from the Veterans Health Administration.

Ursodeoxycholic Acid Response Is Associated With Reduced Mortality in Primary Biliary Cholangitis With Compensated Cirrhosis.

Introduction: Patients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis.

Methods: We conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

Background And Aims: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking.

Approach And Results: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death.

Male Sex Is Associated With Higher Rates of Liver-Related Mortality in Primary Biliary Cholangitis and Cirrhosis.

Background And Aims: The impact of sex on the postcirrhosis progression of primary biliary cholangitis (PBC) has not been well defined. Prior studies have suggested that men have worse outcomes but present at more advanced stages of fibrosis than women. This observation, however, has been limited by small numbers of men and even fewer patients with cirrhosis.

Negative regulators of TGF-β1 signaling in renal fibrosis; pathological mechanisms and novel therapeutic opportunities.

Elevated expression of the multifunctional cytokine transforming growth factor β1 (TGF-β1) is causatively linked to kidney fibrosis progression initiated by diabetic, hypertensive, obstructive, ischemic and toxin-induced injury. Therapeutically relevant approaches to directly target the TGF-β1 pathway (e.g.

Case of anti-Zic4 antibody-mediated cerebellar toxicity induced by dual checkpoint inhibition in head and neck squamous cell carcinoma.

Combined checkpoint inhibition therapy targeting the programmed cell death 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 pathways has been a successful approach in the treatment of metastatic melanoma, leading to its investigation in the treatment of head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression. Despite the potential for excellent responses, an increased rate of autoimmune neurological toxicity and paraneoplastic conditions has been observed when using these treatment modalities. We present the case of a patient with metastatic HNSCC treated with combination ipilimumab/nivolumab who experienced severe cerebellar ataxia with a positive screen for the anti-Zic4 antibody.

Reclassifying Pseudopolyps in Inflammatory Bowel Disease: Histologic and Endoscopic Description in the New Era of Mucosal Healing.

Introduction: In this study, we identify the frequency of pseudopolyps (PPs) with normal histology and their association to surrounding tissue.

Methods: Patients were enrolled in a study identifying endoscopic characteristics of PPs (n = 29) or were collected as part of our IBD biobank (n = 16). Statistical analysis included Stata v.

Predicting Postoperative Complications after Acute Care Surgery: How Accurate Is the ACS NSQIP Surgical Risk Calculator?

The ACS NSQIP Surgical Risk Calculator (SRC) is an evidence-based clinical tool commonly used for evaluating postoperative risk. The goal of this study was to validate SRC-predicted complications by comparing them with observed outcomes in the acute care surgical setting. In this study, pre- and postoperative data from 1693 acute care surgeries (hernia repair, enterolysis, intestinal incision/excision and enterectomy, gastrectomy, debridement, colectomy, appendectomy, cholecystectomy, gastrorrhaphy, and incision and drainage of soft tissue, breast abscesses, and removal of foreign bodies) performed at a Level I trauma center over a five-year time period were abstracted.

Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-β signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown. PPM1A expression was dramatically decreased in the tubulointerstitium in obstructive and aristolochic acid nephropathy, which correlates with progression of fibrotic disease. Stable silencing of PPM1A in human kidney-2 human renal epithelial cells increased SMAD3 phosphorylation, stimulated expression of fibrotic genes, induced dedifferentiation, and orchestrated epithelial cell-cycle arrest via SMAD3-mediated connective tissue growth factor and plasminogen activator inhibitor-1 up-regulation.

Loss of tumour suppressor PTEN expression in renal injury initiates SMAD3- and p53-dependent fibrotic responses.

Deregulation of the tumour suppressor PTEN occurs in lung and skin fibrosis and diabetic and ischaemic renal injury. However, the potential role of PTEN and associated mechanisms in the progression of kidney fibrosis is unknown. Tubular and interstitial PTEN expression was dramatically decreased in several models of renal injury, including aristolochic acid nephropathy (AAN), streptozotocin (STZ)-mediated injury and ureteral unilateral obstruction (UUO), correlating with Akt, p53 and SMAD3 activation and fibrosis.