This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e18. Learning Objective: Upon completion of this CME activity, successful learners will be able to identify the safety profile of Janus Kinases (JAK) inhibitors in patients with Inflammatory Bowel Disease and other Immune-mediated Diseases.BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 personyears, 2.67 per 100 person-years, 0.89 per 100 personyears, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active Gastroenterology 2020;158:1554-1573 CLINICAL AT comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.

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Background:The most common adverse event of endoscopic retrograde cholangiopancreatography is pancreatitis. Precut sphincterotomy has been regarded as a risk factor. Some authors have stated that early precut may actually reduce post-ERCP pancreatitis risk. However, early precut as a preventive measure has not been compared to other preventive measures, such as pancreatic duct stent placement.Aim: To compare the efficacy of early precut sphincterotomy versus pancreatic duct stent placement in high-risk subjects undergoing endoscopic retrograde cholangiopancreatography for the prevention of post-endoscopic cholangiopancreatography. Materials and methods:This was a single-blinded, randomized trial that took place in two tertiary referral centers in Buenos Aires, from November 2011 to December 2013. ERCP subjects presented at least one of the following risk factors: female sex, age less than 40 years, clinical suspicion of sphincter of Oddi dysfunction, previous pancreatitis, and/or common bile duct diameter of less than 8 mm. Only those who presented a difficult biliary cannulation were randomized into two groups: those who received early precut sphincterotomy and those in whom persistency of biliary cannulation was intended, with subsequent pancreatic duct stent placement after cholangiography was achieved. The incidence of post-ERCP pancreatitis, as well as other adverse events incidence, was compared.Results: Overall, 101 patients were enrolled, 51 in the pancreatic duct stent group and 50 in the early precut group. Pancreatitis rate was similar in both groups (3.92% vs. 4%, p NS). In all cases, pancreatitis was classified as mild. There were no deaths registered.Conclusion: Early precut was associated with an incidence of adverse events similar to pancreatic duct stent placement.

Helicobacter pylori infection seems to be less frequent in celiac patients; among those celiac subjects with concomitant Helicobacter pylori infection, histological damage degree and presence of endoscopic markers suggesting villous atrophy seem to be similar to those without Helicobacter pylori infection.

Celiac disease was not associated with an increased risk of colorectal neoplasia. Nonadherence to a strict gluten free diet was associated with the presence of adenomas. Further studies addressing celiac disease characteristics are needed to confirm this observation.

ContextCeliac disease is an autoimmune disorder of the small intestine associated with several extra-intestinal features, such as reproductive disorders. The relationship between celiac disease and infertility has been previously assessed, with conflicting results.ObjectivesWe seek to determine the relationship between celiac disease and infertility.MethodsData was extracted from case-control or cohort design studies from 1966 to December 2013 using the MEDLINE-Pubmed, EMBASE, LILACS and Cochrane Library databases. We analyzed two kinds of trials: those assessing the risk of infertility in subjects with already diagnosed celiac disease, and those evaluating the prevalence of undiagnosed celiac disease in subjects with a diagnosis of infertility.ResultsThe search yielded 413 potentially relevant studies for revision, 12 of which were finally included for analysis. A significant association was found between women with a diagnosis of infertility and undiagnosed celiac disease [OR 3.09 (95% CI 1.74-5.49)]. When considering those studies assessing the occurrence of infertility in subjects with already-diagnosed celiac disease, no difference was found between celiac disease patients and control subjects [OR 0.99 (0.86-1.13)].ConclusionsUndiagnosed celiac disease is a risk factor for infertility. Women seeking medical advice for this particular condition should be screened for celiac disease. Adoption of a gluten-free diet could have a positive impact on fertility in this group of patients.

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