Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Obstructive Sleep Apnea Increases the Risk of Cardiopulmonary Adverse Events Associated with Ambulatory Colonoscopy Independent of Body Mass Index.

BACKGROUND: The relationship between body mass index (BMI) and cardiopulmonary adverse events (CAEs) for ambulatory colonoscopy is unclear. AIM: To assess the association of BMI and CAEs associated with ambulatory colonoscopy. METHODS: This is a retrospective cohort analysis of 418 patients who underwent outpatient colonoscopy at the Durham Veterans Affairs Medical Center categorized as normal/overweight (BMI < 30), obese (BMI 30-34), or morbidly obese (BMI ≥ 35). Adjusted logistic regression analyses were performed. RESULTS: At least one CAE occurred in 46.4% of patients (220 events, 72.7% were hypoxia). The rate of CAEs (BMI < 30: 43.8%, BMI 30-34: 48.0%, BMI ≥ 35: 50.6%, p = 0.53) and rate of hypoxia (BMI < 30: 34.8%, BMI 30-34: 40.9%, BMI ≥ 35: 43.2%, p = 0.32) were numerically higher for obese and morbidly obese patients, but not statistically significant. Obese (OR 1.10, 95% CI 0.70-1.73) and morbidly obese (OR 1.07, 95% CI 0.61-1.85) patients did not have an increased risk of CAEs after adjusting for age, ASA class, obstructive sleep apnea (OSA), and type of sedation. OSA was independently associated with an increased risk of CAEs (OR 1.71, 95% CI 1.09-2.74, p = 0.02) after adjusting for BMI, age, ASA class, and type of sedation. CONCLUSION: OSA confers a higher risk of CAEs independent of BMI and sedation type. Consideration of undiagnosed OSA is recommended for appropriate pre-procedure risk stratification. While not statistically significant in this study, there may be clinically significant increased risks of CAEs and hypoxia for patient with BMI > 30 that require further evaluation with larger studies.

Performance Characteristics of Magnetic Resonance Imaging in Patients With Pancreas Divisum.

OBJECTIVE: This study was designed to assess the diagnostic accuracy of standard nonsecretin-enhanced preprocedural magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) in patients with and without pancreas divisum. METHODS: Patients undergoing MRI/MRCP followed by endoscopic retrograde cholangiopancreatography with between 2009 and 2016 were reviewed. The diagnostic accuracy of the MRI/MRCP was evaluated against the pancreatography. A subsequent independent blinded re-review performed by an expert abdominal radiologist was also evaluated. Multivariate binary logistic regression was performed to assess the impact of clinicopathologic factors on the diagnostic accuracy. RESULTS: A total of 189 patients were included in analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI/MRCP for pancreas divisum were 63%, 97%, 94%, and 82% initially and 81%, 91%, 91%, and 82% on the expert review. Motion artifact, the presence of pancreatic tumor, and pancreatic necrosis were not found to significantly impact the accuracy. A normal diameter pancreatic duct (P = 0.04) and complete divisum anatomy were correlated with improved accuracy (P = 0.001). CONCLUSIONS: Although expert review, normal duct diameter, and complete divisum are associated with increased sensitivity, pancreas divisum may be uncharacterized by preprocedural MRI in 19% to 37% of patients before the index endoscopic retrograde cholangiopancreatography.

Characterization of a novel CRAC inhibitor that potently blocks human T cell activation and effector functions.

Store operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly through the Calcium Release Activated Calcium (CRAC) channel. Here, we compared the effects of a novel, potent and selective CRAC current inhibitor, 2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide (RO2959), on T cell effector functions with that of a previously reported CRAC channel inhibitor, YM-58483, and a calcineurin inhibitor Cyclosporin A (CsA). Using both electrophysiological and calcium-based fluorescence measurements, we showed that RO2959 is a potent SOCE inhibitor that blocked an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4(+) T cells triggered by either TCR stimulation or thapsigargin treatment. Furthermore, we demonstrated that RO2959 completely inhibited cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (mixed lymphocyte reaction). Lastly, we showed by gene expression array analysis that RO2959 potently blocked TCR triggered gene expression and T cell functional pathways similar to CsA and another calcineurin inhibitor FK506. Thus, both from a functional and transcriptional level, our data provide evidence that RO2959 is a novel and selective CRAC current inhibitor that potently inhibits human T cell functions.