Comprehensive genetic study of the insulin resistance marker TG:HDL-C in the UK Biobank.

Insulin resistance (IR) is a well-established risk factor for metabolic disease. The ratio of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) is a surrogate marker of IR. We conducted a genome-wide association study of the TG:HDL-C ratio in 402,398 Europeans within the UK Biobank.

Genetic Defects in Early-Onset Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) represents a spectrum of disease, which is characterized by chronic gastrointestinal inflammation. Monogenic mutations driving IBD pathogenesis are more highly represented in early-onset compared to adult-onset disease. The pathogenic genes which dysregulate host immune responses in monogenic IBD affect both the innate (ie, intestinal barrier, phagocytes) and adaptive immune systems (ie, T cells, B cells).

PNPLA3 Genotype and Diabetes Identify Patients With Nonalcoholic Fatty Liver Disease at High Risk of Incident Cirrhosis.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) can progress to cirrhosis and hepatic decompensation, but whether genetic variants influence the rate of progression to cirrhosis or are useful in risk stratification among patients with NAFLD is uncertain.

Methods: We included participants from 2 independent cohorts, they Michigan Genomics Initiative (MGI) and UK Biobank (UKBB), who had NAFLD defined by elevated alanine aminotransferase (ALT) levels in the absence of alternative chronic liver disease. The primary predictors were genetic variants and metabolic comorbidities associated with cirrhosis.

Risk Variants in or Near ZBTB40 AND NFATC1 Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases.

Background: Inflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.

Methods: The study cohort included patients from the Michigan Genomics Initiative.

Hepatic decompensation is accelerated in patients with cirrhosis and alpha-1 antitrypsin Pi∗MZ genotype.

Background & Aims: Alpha-1 antitrypsin deficiency is caused by mutations in , most commonly homozygosity for the Pi∗Z variant, and can present as liver disease. While heterozygosity for Pi∗Z (Pi∗MZ) is linked to increased risk of cirrhosis, whether the Pi∗MZ genotype is associated with an increased rate of decompensation among patients who already have compensated cirrhosis is not known.

Methods: This was a retrospective study of Michigan Genomics Initiative participants with baseline compensated cirrhosis.

Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer.

Background: Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether IBD susceptibility variants are also associated with skin cancer susceptibility and if such risk is augmented by use of immune-suppressive therapy.

Methods: The discovery cohort included participants in the UK Biobank.

Corrigendum to: Assessment of Benefit of Advanced Inflammatory Bowel Disease Training: Challenges and Solutions.

[This corrects the article DOI: 10.1093/crocol/otaa019.].

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.

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS.

Mapping the relationships between inflammatory bowel disease and comorbid diagnoses to identify disease associations.

Background: Massive amounts of patient data are captured daily in electronic medical records (EMR). Utilizing the power of such large data may help identify disease associations and generate hypotheses that can lead to a better understanding of disease associations and mechanisms. We aimed to comprehensively identify and validate associations between inflammatory bowel disease (IBD) and concurrent comorbid diagnoses.

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.

Safety and Efficacy of Tumor Necrosis Factor Antagonists in Older Patients With Ulcerative Colitis: Patient-Level Pooled Analysis of Data From Randomized Trials.

Background & Aims: Treatment of older patients (more than 60 years) with ulcerative colitis (UC) can be a challenge, because they might be more vulnerable to adverse events (AEs). We determined the effects of age on the safety and efficacy of anti-tumor necrosis factor (TNF) therapy in a pooled analysis of data from randomized trials.

Methods: We obtained individual patient-level data from 4 trials of anti-TNF therapy for patients with UC from the Yale Open Data Access Project.

Assessment of Benefit of Advanced Inflammatory Bowel Disease Training: Challenges and Solutions.

Background: Advanced inflammatory bowel disease (IBD) fellowships are available for gastroenterologists who wish to increase their expertise in complex IBD. However, little is known about the outcomes of such training. The aims of this study were to assess clinical and academic outcomes following advanced training in IBD.

Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission.

Background: Clinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established.

Aim: To quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission.

Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience.

Introduction: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC) is a rare phenotype. We aimed to assess patients with UC-PSC or UC alone and describe differences in clinical and phenotypic characteristics, antitumor necrosis factor (TNF) therapy, and long-term clinical outcomes.

Methods: This retrospective multicenter cohort study included patients who received a diagnosis of UC from 1962 through 2015.

CT-Visualized Colonic Mural Stratification Independently Predicts the Need for Medical or Surgical Rescue Therapy in Hospitalized Ulcerative Colitis Patients.

Background: Severe ulcerative colitis is associated with significant morbidity. Multidetector computed tomography (MDCT) scans are frequently obtained upon hospital admission, but the ability of radiographic findings to predict steroid failure is unknown.

Aim: To identify MDCT features predictive of inpatient rescue in hospitalized UC.

Novel Genetic Risk Variants Can Predict Anti-TNF Agent Response in Patients With Inflammatory Bowel Disease.

Background: It is important to identify patients with inflammatory bowel disease [IBD] refractory to anti-tumour necrosis factor [TNF] therapy, to avoid potential adverse effects and to adopt different treatment strategies. We aimed to identify and validate clinical and genetic factors to predict anti-TNF response in patients with IBD.

Materials And Methods: Mayo Clinic and Washington University IBD genetic association study cohorts were used as discovery and replicate datasets, respectively.

Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.

Background: Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity.

Methods: Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards.

Sarcopenia is a Novel Predictor of the Need for Rescue Therapy in Hospitalized Ulcerative Colitis Patients.

Background And Aims: Acute severe ulcerative colitis [ASUC] affects one in four patients with UC. Clinical parameters perform modestly in predicting the need for rescue therapy. Sarcopenia and visceral adiposity predict natural history in Crohn's disease, but the role of such metabolic factors on ASUC outcomes is unknown.

Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery.

Background: Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype. This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence.

Methods: Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968.