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Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.

Background: The ratio of Helicobacter pylori/NSAID-negative gastric ulcers is increasing. Idiopathic gastric ulcers have unique clinical and endoscopic features, and are associated with more bleeding complications and a higher mortality. Alterations in gastric mucin expression and sialylation pattern may be important in ulcer pathogenesis.Aims: The purpose of this study was to determine the expression pattern of membrane-bound mucins and side chain sugars in H. pylori associated-, NSAID-, and idiopathic-gastric ulcers.Methods: We randomly selected 92 patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for T-cell CD4/CD8, MUC1, MUC4, MUC17, and ECA and SNA lectins staining was performed on sections from the ulcer margins. Inflammation score was assessed according to the Sydney system.Results: Bleeding and mortality rates were significantly higher in group 4. CD4 positive T cell count was higher in H. pylori positive patients (P = 0.009). Staining intensity of MUC17 was higher in group 1 than in group 4, foveola and glands alike, with 11.50 ± 3.47 versus 6.80 ± 4.02, and 9.61 ± 4.26 versus 7.59 ± 3.26, respectively (P < 0.0001). This was a mirror image with MUC1. SNA lectin staining was increased in group 4, in parallel to MUC1 expression, indicating more abundant α2-6 sialylation in that group.Conclusions: Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was demonstrated for MUC1. This observation might be important, since different mucins with altered sialylation patterns likely differ in their protection efficiency against acid and pepsin. [ABSTRACT FROM AUTHOR]

Frameworks are increasingly employed as a useful way to enable object-oriented reuse. However, understanding frameworks is not easy due to their size and complexity. Previous work concentrated on different ways to document frameworks, but it was unclear which ones were actually better. This paper presents a novel way of investigating the different philosophies for framework documentation. The philosophies include minimalist, patterns-style and extended javadoc (Jdoc) documentation. Using a survey of 140 novices engaged in Swing intensive coding work, this empirical study discovered some guidelines for effective framework documentation for the Swing framework. The results suggest that different documentation is better for different goals. [ABSTRACT FROM AUTHOR]

Background: Teaching medical students in the clinical setting is frequently perceived as a demanding commitment by attending physicians. There is a paucity of data measuring the duration and efficacy of teaching during clinical rounds., Aim: The aim of this study was to assess both the quantity and quality of clinical teaching time dedicated to medical students on hospital ward rounds., Methods: A cross-sectional direct structured observational study was conducted during the morning rounds of attending physicians involved in teaching undergraduate medical students at three different clinical facilities in three different specialties. A validated observational tool was used by four observers to record teaching time and quality indicators., Results: In terms of teaching duration, it was observed that 25% of the total morning round time was allocated to teaching. However, this measure varied widely between different physicians and specialties. As for teaching quality, actions categorized as active teaching by the teachers were observed in 19% of the interactions observed per round, while active learning by the students was observed in 17% of the interactions per round. Teacher high-cognition interactions were similarly observed in 23% of actions per round, while student high-cognition interactions occurred in 16% of actions per round. Internal Medicine tended to score higher than both Pediatrics and Surgery in terms of percentage teaching time as well as percentage of active teaching observed per round. Using liberal criteria, rounds characterized overall as predominantly active or high-cognition by both teachers and students were observed in only 21% of the total number of rounds observed., Conclusion: These results indicate that the percentage of teaching time during ward rounds is highly variable, and that round teaching generally consists of passive and low-cognition interactions. Future work is needed to train clinical faculty to achieve a desired level of teaching quality, and to determine if there are any changes in teaching time commitments and student outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kilian, Alshehabi, Othman, Mahmoud, du Preez, Zary and Ho.)

Background: Despite the established need to prioritize professionalism-training in developing future physicians, very few medical programs in the Gulf Region embed in their curricula discrete contextualized courses aimed at developing the corresponding competencies, while fostering self-directed learning. This study aims at exploring the perception of undergraduate medical students in a multi-cultural, multi-ethnic setting regarding their understanding of, and personal experience with professionalism through their engagement with the content of an innovative curriculum-based professionalism course, offered at a Medical School in Dubai, United Arab Emirates., Methods: The study used a qualitative phenomenological research design. Out of 33 students, 29 students had submitted reflective essays. The content of these essays was inductively analyzed following a six-step framework for conducting thematic analysis. The framework's steps include familiarizing oneself with the data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report., Findings: The inductive qualitative analysis generated the Professionalism Learning Journey model. This conceptual model includes four interconnected themes: Awareness, Acknowledgement, Realization, and Application. The generated model depicts the trajectory that the learners appear to experience while they are engaging with the content of the course., Conclusion: Integrating a professionalism-training course into an undergraduate medical curriculum is likely to be positively appraised by the learners. It raises their awareness, enables them to value the subject matter and the sophistication of its application, and empowers them to put into practice the taught principles, on an individual basis and collectively. This is especially true when the course is entrenched in constructivism experiential learning theory and designed to foster self-directed learning. The introduced conceptual model, in conjunction with the innovative professionalism-training course curriculum, can serve as a template for other competencies and other schools., (© 2024. The Author(s).)

Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in a medical ward involving patients and hospital staff from May to June 2020. Aim The aim of this study is to determine risk factors related to the outbreak of SARS-CoV-2 in six healthcare workers (HCWs) in a medical ward with initially unrecognized coronavirus disease 2019 (COVID-19) positive patients. Methods A retrospective cross-sectional study was conducted using a comprehensive questionnaire and personal interviews to determine the risk factors for COVID-19 infection in HCWs. Findings A total of 6/34 HCWs were diagnosed with COVID-19 in a medical ward. There were no differences between COVID-19 negative HCWs and COVID-19 positive HCWs in terms of mean duration of hours worked in the unit during the cluster event (180.2 vs 177.5 hours) (p>0.05), mean total time spent in contact with COVID-19 positive patients (12.8 vs 10.5 hours) (p>0.05), mean total time spent on aerosol-generating procedures (1.9 vs 0.9 hours) (p>0.05), and mean total time spent on non-aerosol generating procedures (10.9 vs 9.6 hours ) (p>0.05). There was no difference in exposure to COVID-19 positive family members among the HCWs (33% vs 3.7%, p=0.08). In contrast, exposure to COVID-19 positive contacts in the community was significantly greater in infected vs non-infected HCWs (16.7% vs 0%, p=0.03). Conclusion There was no significant difference in risk factors for contracting SARs-CoV2 among HCWs due to hospital exposures. COVID-19 positive HCWs were more likely to be exposed to positive individuals in their households and community, indicating that the source of SARS-CoV-2 infection came from outside the hospital., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nair et al.)

Background: The COVID-19 pandemic presented significant challenges to both clinical practice and the delivery of medical education. Educators and learners implemented novel techniques, including distance learning and web-based rounds, while trying to stay updated with the surge of information regarding COVID-19 epidemiology, pathogenesis, and treatment. Hence, we designed and implemented a technologically enhanced course called "COVID-19 Rounds" to educate students about the rapidly evolving pandemic., Objective: The objectives of this study are to describe a technologically enhanced course called "COVID-19 Rounds" and evaluate the following: (1) student satisfaction and program usefulness in achieving preset objectives, (2) perceived improvement in literacy regarding the pandemic, and (3) the impact of student engagement by designing infographics and initiating COVID-19-related research projects., Methods: This is a cross-sectional study measuring the impact of the implementation of the web-based "COVID-19 Rounds" course. This program included web-based clinical experiences with physicians on actual rounds in COVID-19 wards in the hospital, weekly updates on evolving data and new research, and engagement in student-led projects. The study population included 47 fourth-year medical students at the Mohamed Bin Rashid University of Medicine and Health Sciences in Dubai, the United Arab Emirates, who attended the course. We designed and administered a 47-item survey to assess student satisfaction, program usefulness, impact on knowledge, and student engagement. Data were collected at the end of program delivery via Microsoft Forms., Results: In total, 38 (81%) out of 47 fourth-year medical students participated in this study. The final course evaluation revealed an overall high satisfaction rate, with a mean rating of 3.9 (SD 0.94) on the 5-point Likert scale. Most students were satisfied with the course format (27/38, 71%), organization (31/38, 82%), and the learning experience (28/38, 74%) that the course offered. The course was particularly appreciated for offering evidence-based talks about aspects of the pandemic (34/38, 90%), providing weekly updates regarding emerging evidence (32/38, 84%), and enhancing understanding of the challenges of the pandemic (34/38, 90%). Satisfaction with distance learning was moderate (23/37, 62%), and a minority of students would have preferred an in-person version of the course (10/37, 27%). Student engagement in the course was high. All students participated in small group presentations of infographics of pandemic-related topics. Perceived advantages included conciseness and visual appeal, and disadvantages included the lack of detail and the time-consuming nature of infographic design, especially for students with no prior design experience. After the course ended, 27 (57%) students began research projects. This resulted in 6 abstracts presented at local meetings and 8 scientific papers published or submitted for publication., Conclusions: This inquiry-based adaptive approach to educating medical students about updates on COVID-19 via web-based learning was successful in achieving objectives and encouraging engagement in research. However, shortcomings of the course related to the lack of in-person teaching and clinical activities were also highlighted., (©Aya Akhras, Mariam ElSaban, Varshini Tamil Selvan, Shaika Zain Alzaabi, Abiola  Senok, Nabil Zary, Samuel B Ho. Originally published in JMIR Medical Education (https://mededu.jmir.org), 06.11.2023.)

Background: Multisystem inflammatory syndrome in children (MISC) is a phenomenon that appeared in children infected with or exposed to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response., Methods: Our study retrospectively analyzed data from a tertiary center in United Arab Emirates of MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post-PICU admission) from May 2020 to August 2021., Results: The total sample size was 50 patients, and the study included a comparison of MISC-PICU admissions with MISC-non-PICU admissions. The MISC-PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. MISC-PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. MISC-PICU patients presented with relatively higher inflammatory markers: C-reactive protein, procalcitonin, ferritin, and d-dimer. Immunological studies were significantly higher for interleukin-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in MISC-PICU patients. Likewise, MISC-PICU patients were provided with more extensive therapy. As part of our study course, we reevaluated our MISC-PICU patients twice, once at 48 h post-PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort., Conclusion: This study evaluated risk factors of MISC and potential severity features. Follow-up of patients on discharge showed improvement across all domains., (© 2023 Wiley Periodicals LLC.)

Background: The clinical placements of our medical students are almost equally distributed across private and public sectors. This study aims to assess medical students' perceptions of their Clinical learning Environment (CLE) across these two different healthcare settings, using the Undergraduate Clinical Education Environment Measure (UCEEM)., Methods: 76 undergraduate medical students (Year 5 and 6), were invited to participate. Data were collected using an online UCEEM with additional questions related to demographics and case load exposure. The UCEEM consists of two overarching domains of experiential learning and social participation, with four subdomains of learning opportunities, preparedness, workplace interaction, and inclusion., Results: 38 questionnaires were received. Of 225 responses to the individual UCEEM items, 51 (22.6%) scored a mean of ≥ 4 (range 4-4.5, representing strong areas), 31 (13.7%) scored a mean of ≤ 3 (range 2.1-3, needing attention) and 143 (63.6%) scored a mean of 3.1-3.9 (areas that could be improved). The majority (63%) of the case load exposure responses scored a mean of ≥ 4 (range 4-4.5). Compared to the private sittings, there is a significant reduction in total UCEEM (p = 0.008), preparedness for student entry (p = 0.003), and overarching dimension of social participation (p = 0.000) scores for the public sector. Similarly, both workplace interaction patterns and student inclusion and equal treatment scored significantly lower for the public sector (p = 0.000 and p = 0.011 respectively). Two out of three case load exposure items scored significantly higher for the public sector (p = 0.000)., Discussion: The students' CLE perceptions were generally positive. The lower UCEEM ratings in the public sector items were related to student entry preparedness, workplace interactions, student inclusiveness and workforce equity of treatment. In contrast the students were exposed to more variety and larger number of patients in the public sector. These differences indicated some significantly different learning environments between the two sectors., (© 2023. The Author(s).)

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy., Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors., Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022., Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals., Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year., Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25)., Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Background: Medicine is one of the most demanding academic fields with an extensive curriculum that entails plenty of potential stressors. There is sufficient evidence that medical students are more prone to psychological distress when compared to their peer group of other disciplines. Despite the established need to prioritize resilience skills building within the medical curriculum, very few medical programmes in the Middle East and North Africa region (MENA) proactively empower the students to help themselves in sustaining their mental health. The purpose of the current study is to explore the perception of medical students in Dubai, United Arab Emirates (UAE) regarding their understanding of, and personal experience with building resilience, and their engagement with the content of an innovative curriculum-based resilience skills building course, designed in alignment with the constructivism theory of education., Method: The current study utilized a qualitative phenomenological research design. The curriculum-based resilience skills building course, that was investigated as part of this study, is offered at a medical school in Dubai, UAE. A total of 37 students submitted reflective essays about resilience building, in general, and the respective course, in specific. The collected data was inductively analysed following a six-step framework., Findings: The qualitative analysis generated three interlinked themes, namely: Awareness, Application, and Appraisal., Conclusion: This study showed that integrating a resilience skills building course into medical curricula is likely to be positively appraised by the students, where it raises their level of awareness and likelihood of proactively applying the learned concepts in their daily lives. This is especially true when the course is anchored in constructivism experiential learning theory and designed to foster self-directed learning., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nair et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The COVID-19 pandemic has greatly impacted health and care workers (HCW) globally, whom are considered at greater risk of infection and death. This study aims to document emerging evidence on disease prevalence, clinical outcomes, and vaccination rates of HCWs. Methods: Three databases were surveyed resulting on 108 final articles between July-December 2020 (period 1) and January-June 2021 (period 2). Results: Amongst the overall 980,000 HCWs identified, in period 1, the estimates were 6.1% (95% CI, 4.1-8.8) for the PCR positivity rate. Regarding outcomes, the hospitalization prevalence was 1.6% (95% CI, 0.7-3.9), and mortality rate of 0.3% (95% CI, 0.1-0.8). In period 2, the PCR positivity rate was 8.1% (95% CI, 4.6-13.8). Analysis of outcomes revealed a hospitalization rate of 0.7% (95% CI 0.3-1.8), and average mortality rate of 0.3% (95% CI 0.1-0.9). Our analysis indicated a HCW vaccination rate of 59.0% (95% CI, 39.4-76.1). Conclusion: Studies from the latter half of 2020 to the first half of 2021 showed a slight increasing trend in PCR positivity among HCW, along with improved clinical outcomes in the 1-year period of exposure. These results correlate well with the improving uptake of COVID-19 vaccination globally., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Gholami, Fawad, Shadan, Rowaiee, Ghanem, Khamis and Ho.)

Among 1866 Asian women (901 Filipina women, 654 Chinese women, and 311 Japanese women) who had vitamin D assessment prior to initiation of osteoporosis therapy, Filipina women had a lower prevalence of vitamin D deficiency compared to Chinese women, despite higher body mass index. In multivariable analyses that adjusted for age, body mass index, and smoking status, the relative risk of low vitamin D was significantly higher for Chinese women (relative risk 1.4, 95% confidence interval 1.1-1.7) but not Japanese women (relative risk 1.2, 95% confidence interval 0.9-1.6). The 40% higher risk of low Vitamin D in Chinese compared to Filipina women emphasizes the importance of disaggregating Asian race when examining nutritional health attributes., Competing Interests: CONFLICT OF INTEREST: Samantha Ho, Christina Li, Malini Chandra, and Joan Lo have no conflicts of interest to disclose.

Sentiment analysis, one of the research hotspots in the natural language processing field, has attracted the attention of researchers, and research papers on the field are increasingly published. Many literature reviews on sentiment analysis involving techniques, methods, and applications have been produced using different survey methodologies and tools, but there has not been a survey dedicated to the evolution of research methods and topics of sentiment analysis. There have also been few survey works leveraging keyword co-occurrence on sentiment analysis. Therefore, this study presents a survey of sentiment analysis focusing on the evolution of research methods and topics. It incorporates keyword co-occurrence analysis with a community detection algorithm. This survey not only compares and analyzes the connections between research methods and topics over the past two decades but also uncovers the hotspots and trends over time, thus providing guidance for researchers. Furthermore, this paper presents broad practical insights into the methods and topics of sentiment analysis, while also identifying technical directions, limitations, and future work., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest or competing interest in this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a debilitating condition with a rising incidence globally over recent years. Frondanol, a widely available nutraceutical extract of the edible sea cucumber Cucumaria frondosa has been reported to possess potent anti-inflammatory effects, likely mediated by the inhibition of 5-lipoxygenase and 12-lipoxygenase pathways, whilst showing no signs of toxicity. The potent anti-inflammatory effects of Frondanol in a mouse model of IBD provide encouragement for investigating its effects in human IBD patients. Here we describe the study protocol of a pilot randomized, double-blinded, placebo-controlled trial of Frondanol in patients with mild to moderate IBD who are on standard therapy., Material and Methods: One hundred patients will be randomized (1:1) to receive Frondanol or placebo as an adjunct to their standard therapy for the period of six months. Blood and stool samples will be obtained during routine visits at baseline, and after three months and six months of treatment, and tissue samples from colon biopsies will be obtained during clinically indicated colonoscopies at baseline and after six months of treatment. The levels of inflammatory markers will be compared in serum and tissue samples between patients treated with Frondanol and those treated with placebo, and findings will be correlated with clinical and histological parameters., Discussion: If proven beneficial, treatment with Frondanol may increase the likelihood of patients remaining in remission and potentially provide an effective, natural and safe addition/alternative for treatment-naive patients in the future.(Clinical trial registration number: NCT05194007)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent., Competing Interests: Declaration of interests A.Z. and S.D.B. are co-founders and equity-holders in Endure Biotherapeutics. They have filed a provisional patent based on the work described here (US Provisional Patent No. 16/604,138)., (Published by Elsevier Inc.)

Background: Unregulated use of a variety of drugs and supplements by bodybuilders and athletes is common and can lead to severe adverse complications. Only a small proportion of acute pancreatitis cases are drug induced, and case reports are essential for identifying potential drug-related risks for pancreatitis. Here we present the first case report published of acute pancreatitis linked to recreational use of anabolic-androgenic steroids, subcutaneous growth hormone, and clenbuterol in a previously healthy male after excluding all other causes of pancreatitis., Case Presentation: A 31-year-old Arab male bodybuilder presented with acute abdominal pain associated with nausea and sharp pain radiating to the back. The patient was not using tobacco or alcohol but was using multiple drugs related to bodybuilding, including anabolic-androgenic steroids, subcutaneous growth hormone, clenbuterol, and multiple vitamin supplements. Laboratory studies revealed a normal white blood cell count, elevated C-reactive protein, minimally elevated aspartate aminotransferase and total bilirubin with normal remaining liver tests, and elevated amylase and lipase. The patient had no hypertriglyceridemia or hypercalcemia, and had had no recent infections, abdominal procedures, trauma, or scorpion exposure. Imaging and laboratory investigations were negative for biliary disease and IgG4 disease. Abdominal computed tomography revealed hepatomegaly and diffuse thickening and edema of the body and tail of the pancreas with peripancreatic fat stranding. An abdominal ultrasound showed slight hepatomegaly with no evidence of cholelithiasis. Genetic testing for hereditary pancreatitis-related mutations was negative. A diagnosis of drug-induced acute pancreatitis was made, and he was treated with aggressive intravenous hydration and pain management. The patient has avoided further use of these drugs and supplements and had no further episodes of pancreatitis during 1 year of follow-up., Conclusions: This case describes a patient with drug-induced acute pancreatitis after the intake of anabolic-androgenic steroids, subcutaneous growth hormone, and clenbuterol, where all other common causes of acute pancreatitis were excluded. Clinicians should be alert to the possibility of drug-induced acute pancreatitis occurring in bodybuilders and athletes using similar drug combinations., (© 2022. The Author(s).)

Background: The onset of the pandemic necessitated abrupt transition to telehealth consultations. Although there is a few tools that gauge the patients' perception about their experiences, none of them are contextualized to an emergency in the Middle East and North Africa region. Accordingly, this study aims at developing and validating a tool to address this gap, and deploying it to assess the patients' perception of telehealth services during COVID-19 in Dubai, United Arab Emirates (UAE). Methods: A convergent mixed methods design was adapted. A random selection of 100 patients from Dubai, UAE were invited to participate. Qualitative and quantitative datasets were collected using a tailor-made survey. The qualitative data, collected through open-ended questions, was analyzed using multi-staged thematic analysis. As for the quantitative data, it captured the patients' extent of satisfaction, and was assessed using SPSS (with a series of descriptive and inferential analyses). The qualitative and quantitative findings were then merged via joint display analysis. Results: Out of the 100 patients that were randomly selected, 94 patients participated in this study. The reliability score of Cronbach's Alpha for the instrument was 98.9%. The percentage of the total average of satisfaction was 80.67%. The Principal Component Analysis showed that 88.1% of the variance can be explained by the instrument ( p < 0.001). The qualitative data analysis expanded upon the quantitative findings enabling a better understanding of the patients' perception. Three themes, revolving around the quality of the patient telehealth experiences, surfaced: "Factors that worked to the benefit of the patients," "Factors that the patients were not in favor of," and "Opportunities for improvements as perceived by the patients." Discussion: This study introduced a novel patient satisfaction with telehealth consultation survey contextualized to the COVID-19 times in Dubai, UAE. The participants were quite satisfied with the quality of their experience, however they suggested areas for improvement. Regional healthcare decision-makers can leverage the identified advantages and opportunities for improvement of telehealth. This will enable making informed decisions regarding the continuity of telehealth irrespective of how matters unfold in relation to the pandemic. It will also better prepare the healthcare sector for potential resurgence(s) of COVID-19 and/or the occurrence of other similar emergencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Al-Sharif, Almulla, AlMerashi, Alqutami, Almoosa, Hegazi, Otaki and Ho.)

The recent increases in cancer incidences have been linked to lifestyle changes that result in obesity and metabolic syndrome. It is now evident that these trends are associated with the profound changes that occur in the intestinal microbiome, producing altered microbial population signatures that interact, directly or indirectly, with potentially pro-carcinogenic molecular pathways of transcription, proliferation, and inflammation. The effects of the entire gut microbial population on overall health are complex, but individual bacteria are known to play important and definable roles. Recent detailed examinations of a large number of subjects show a tight correlation between habitual diets, fecal microbiome signatures, and markers of metabolic health. Diets that score higher in healthfulness or diversity such as plant-based diets, have altered ratios of specific bacteria, including an increase in short-chain fatty acid producers, which in turn have been linked to improved metabolic markers and lowered cancer risk. Contrarily, numerous studies have implicated less healthy, lower-scoring diets such as the Western diet with reduced intestinal epithelial defenses and promotion of specific bacteria that affect carcinogenic pathways. In this review, we will describe how different dietary patterns affect microbial populations in the gut and illustrate the subsequent impact of bacterial products and metabolites on molecular pathways of cancer development, both locally in the gut and systemically in distant organs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ibragimova, Ramachandran, Ali, Lipovich and Ho.)

Background: COVID-19 has infected over 123 million people globally. The first confirmed case in the United Arab Emirates (UAE) was reported on January 29, 2020. According to studies conducted in the early epicenters of the pandemic, COVID-19 has fared mildly in the pediatric population. To date, there is a lack of published data about COVID-19 infection among children in the Arabian region., Objective: This study aims to investigate the clinical characteristics, laboratory findings, treatment, and outcomes of children with COVID-19., Methods: This cross-sectional, multicenter study included children with confirmed COVID-19 infection admitted to 3 large hospitals in Dubai, UAE, between March 1 and June 15, 2020. Serial COVID-19 polymerase chain reaction (PCR) testing data were collected, and patients' demographics, premorbid clinical characteristics, and inpatient hospital courses were examined., Results: In all, 111 children were included in our study and represented 22 nationalities. Of these, 59 (53.2%) were boys. The mean age of the participants was 7 (SD 5.3) years. About 15.3% of children were younger than 1 year. Only 4 (3.6%) of them had pre-existing asthma, all of whom had uneventful courses. At presentation, of the 111 children, 43 (38.7%) were asymptomatic, 68 (61.2%) had mild or moderate symptoms, and none (0%) had severe illness requiring intensive care. Fever (23/111, 20.7%), cough (22/111, 19.8%), and rhinorrhea (17/111, 15.3%) were the most common presenting symptoms, and most reported symptoms resolved by day 5 of hospitalization. Most patients had no abnormality on chest x-ray. The most common laboratory abnormalities on admission included variations in neutrophil count (22/111, 24.7%), aspartate transaminase (18/111, 22.5%), alkaline phosphatase (29/111, 36.7%), and lactate dehydrogenase (31/111, 42.5%). Children were infrequently prescribed targeted medications, with only 4 (3.6%) receiving antibiotics. None of the 52 patients tested for viral coinfections were positive. COVID-19 PCR testing turned negative at a median of 10 days (IQR: 6-14) after the first positive test. Overall, there was no significant difference of time to negative PCR results between symptomatic and asymptomatic children., Conclusions: This study of COVID-19 presentations and characteristics presents a first look into the burden of COVID-19 infection in the pediatric population in the UAE. We conclude that a large percentage of children experienced no symptoms and that severe COVID-19 disease is uncommon in the UAE. Various laboratory abnormalities were observed despite clinical stability. Ongoing surveillance, contact tracing, and public health measures will be important to contain future outbreaks., (©Farah Ennab, Mariam ElSaban, Eman Khalaf, Hanieh Tabatabaei, Amar Hassan Khamis, Bindu Radha Devi, Kashif Hanif, Hiba Elhassan, Ketharanathan Saravanan, David Cremonesini, Rizwana Popatia, Zainab Malik, Samuel B Ho, Rania Abusamra. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 05.11.2021.)

Background - Recently, there have been attempts to develop mHealth applications for asthma self-management. However, there is a lack of applications that can offer accurate predictions of asthma exacerbation using the weather triggers and demographic characteristics to give tailored response to users. This paper proposes an optimised Deep Neural Network Regression (DNNR) model to predict asthma exacerbation based on personalised weather triggers. Methods - With the aim of integrating weather, demography, and asthma tracking, an mHealth application was developed where users conduct the Asthma Control Test (ACT) to identify the chances of their asthma exacerbation. The asthma dataset consists of panel data from 10 users that includes 1010 ACT scores as the target output. Moreover, the dataset contains 10 input features which include five weather features (temperature, humidity, air-pressure, UV-index, wind-speed) and five demography features (age, gender, outdoor-job, outdoor-activities, location). Results - Using the DNNR model on the asthma dataset, a score of 0.83 was achieved with Mean Absolute Error (MAE)=1.44 and Mean Squared Error (MSE)=3.62. It was recognised that, for effective asthma self-management, the prediction errors must be in the acceptable loss range (error<0.5). Therefore, an optimisation process was proposed to reduce the error rates and increase the accuracy by applying standardisation and fragmented-grid-search. Consequently, the optimised-DNNR model (with 2 hidden-layers and 50 hidden-nodes) using the Adam optimiser achieved a 94% accuracy with MAE=0.20 and MSE=0.09. Conclusions - This study is the first of its kind that recognises the potentials of DNNR to identify the correlation patterns among asthma, weather, and demographic variables. The optimised-DNNR model provides predictions with a significantly higher accuracy rate than the existing predictive models and using less computing time. Thus, the optimisation process is useful to build an enhanced model that can be integrated into the asthma self-management for mHealth application., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Haque R et al.)

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to cause global havoc posing uncertainty to educational institutions worldwide. Understanding the clinical characteristics of COVID-19 in children is important because of the potential impact on clinical management and public health decisions., Methods: A meta-analysis was conducted for pediatric COVID-19 studies using PubMed and Scopus. It reviewed demographics, co-morbidities, clinical manifestations, laboratory investigations, radiological investigations, treatment, and outcomes. The 95% confidence interval (CI) was utilized., Results: Out of 3927 articles, 31 articles comprising of 1816 patients were selected from December 2019 to early October 2020 and were defined by 77 variables. Of these studies 58% originated from China and the remainder from North America, Europe and the Middle East. This meta-analysis revealed that 19.2% (CI 13.6%-26.4%) of patients were asymptomatic. Fever (57%, CI 49.7%-64%) and cough (44.1%, CI 38.3%-50.2%) were the most common symptoms. The most frequently encountered white blood count abnormalities were lymphopenia 13.5% (CI 8.2%-21.4%) and leukopenia 12.6% (CI 8.5%-18.3%). Ground glass opacities were the most common radiological finding of children with COVID-19 (35.5%, CI 28.9%-42.7%). Hospitalization rate was 96.3% (CI 92.4%-98.2%) of which 10.8% (CI 4.2%-25.3%) were ICU admissions, and 2.4% (CI 1.7%-3.4%) died., Conclusion: The majority of pediatric patients with COVID-19 were asymptomatic or had mild manifestations. Among hospitalized patients there remains a significant number that require intensive care unit care. Overall across the literature, a considerable level of understanding of COVID-19 in children was reached, yet emerging data related to multisystemic inflammatory syndrome in children should be explored., (© 2021 Wiley Periodicals LLC.)

Background: The COVID-19 pandemic has focused attention on the challenges and risks faced by frontline healthcare workers (HCW). This study aimed to describe the clinical outcomes and risk factors for SARS-CoV-2 infection in HCW., Methods: Three databases were surveyed and 328 articles were identified. Of these, 225 articles did not meet inclusion criteria; therefore, 97 full-text article were reviewed. Finally, after further revision, 30 articles were included in the systematic review and 28 were used for meta-analysis., Results: Twenty-eight studies were identified involving 119,883 patients. The mean age of the patients was 38.37 years (95% CI 36.72-40.03) and males comprised 21.4% (95% CI 12.4-34.2) of the population of HCW. The percentage of HCW who tested positive for COVID-19 was 51.7% (95% CI 34.7-68.2). The total prevalence of comorbidities in seven studies was 18.4% (95% CI 15.5-21.7). The most prevalent symptoms were fever 27.5% (95% CI 17.6-40.3) and cough 26.1% (95% CI 18.1-36). The prevalence of hospitalisation was 15.1% (95% CI 5.6-35) in 13 studies and of death was 1.5% (95% CI 0.5-3.9) in 12 studies. Comparisons of HCW with and without infection showed an increased relative risk for COVID-19 related to personal protective equipment, workplace setting, profession, exposure, contacts, and testing., Conclusion: A significant number of HCW were reported to be infected with COVID-19 during the first 6 months of the COVID-19 pandemic, with a prevalence of hospitalisation of 15.1% and mortality of 1.5%. Further data are needed to track the continued risks in HCW as the pandemic evolves and health systems adapt., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD., Approach and Results: We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality., Conclusions: In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH., (© 2020 by the American Association for the Study of Liver Diseases.)

Background: Early hospital readmission for patients with cirrhosis continues to challenge the healthcare system. Risk stratification may help tailor resources, but existing models were designed using small, single-institution cohorts or had modest performance., Aims: We leveraged a large clinical database from the Department of Veterans Affairs (VA) to design a readmission risk model for patients hospitalized with cirrhosis. Additionally, we analyzed potentially modifiable or unexplored readmission risk factors., Methods: A national VA retrospective cohort of patients with a history of cirrhosis hospitalized for any reason from January 1, 2006, to November 30, 2013, was developed from 123 centers. Using 174 candidate variables within demographics, laboratory results, vital signs, medications, diagnoses and procedures, and healthcare utilization, we built a 47-variable penalized logistic regression model with the outcome of all-cause 30-day readmission. We excluded patients who left against medical advice, transferred to a non-VA facility, or if the hospital length of stay was greater than 30 days. We evaluated calibration and discrimination across variable volume and compared the performance to recalibrated preexisting risk models for readmission., Results: We analyzed 67,749 patients and 179,298 index hospitalizations. The 30-day readmission rate was 23%. Ascites was the most common cirrhosis-related cause of index hospitalization and readmission. The AUC of the model was 0.670 compared to existing models (0.649, 0.566, 0.577). The Brier score of 0.165 showed good calibration., Conclusion: Our model achieved better discrimination and calibration compared to existing models, even after local recalibration. Assessment of calibration by variable parsimony revealed performance improvements for increasing variable inclusion well beyond those detectable for discrimination.

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis., (© 2019 by the American Association for the Study of Liver Diseases.)

Background and Aims: Tumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- κB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice., Methods: Human IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKβ in IEC (Ikkβ(EE) IEC ), Ripk1 D138N/D138N knockin mice, and Ripk3 -/- mice were injected with TNF or lipopolysaccharide. Enteroids were also isolated from these mice and challenged with TNF with or without RIPK1 and RIPK3 inhibitors or butylated hydroxyanisole. Ripoptosome-mediated caspase-8 activation was assessed by immunoprecipitation., Results: NF-κB activation in human IBD correlated with appearance of cleaved caspase-3. Congruently, unlike normal mouse IECs that are TNF-resistant, IECs in Ikkβ(EE) IEC mice and enteroids were susceptible to TNF-dependent apoptosis, which depended on the protein kinase function of RIPK1. Constitutively active IKKβ facilitated ripoptosome formation, a RIPK1 signaling complex that mediates caspase-8 activation by TNF. Butylated hydroxyanisole treatment and RIPK1 inhibitors attenuated TNF-induced and ripoptosome-mediated caspase-8 activation and IEC death in vitro and in vivo., Conclusions: Contrary to common expectations, chronic NF-κB activation induced intestinal crypt apoptosis after TNF stimulation, resulting in severe mucosal erosion. RIPK1 kinase inhibitors selectively inhibited TNF destructive properties while preserving its survival and proliferative properties, which do not require RIPK1 kinase activity. RIPK1 kinase inhibition could be a potential treatment for IBD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality 1-3 . Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice 4 , but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis 5,6 -as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis and early detection of evolving HRS may provide opportunities for early intervention. We developed a HRS risk model to assist early recognition of inpatient HRS., Methods: We analysed a retrospective cohort of patients hospitalised from among 122 medical centres in the US Department of Veterans Affairs between 1 January 2005 and 31 December 2013. We included cirrhotic patients who had Kidney Disease Improving Global Outcomes criteria based acute kidney injury on admission. We developed a logistic regression risk prediction model to detect HRS on admission using 10 variables. We calculated 95% confidence intervals on the model building dataset and, subsequently, calculated performance on a 1000 sample holdout test set. We report model performance with area under the curve (AUC) for discrimination and several calibration measures., Results: The cohort included 19 368 patients comprising 32 047 inpatient admissions. The event rate for hospitalised HRS was 2810/31 047 (9.1%) and 79/1000 (7.9%) in the model building and validation datasets, respectively. The variable selection procedure designed a parsimonious model involving ten predictor variables. Final model performance in the validation dataset had an AUC of 0.87, Brier score of 0.05, slope of 1.10 and intercept of 0.04., Conclusions: We developed a probabilistic risk model to diagnose HRS within 24 hours of hospital admission using routine clinical variables in the largest ever published HRS cohort. The performance was excellent and this model may help identify high-risk patients for HRS and promote early intervention., (© 2019 John Wiley & Sons Ltd.)

Objective: Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease., Design: Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model)., Results: In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered Lactobacillus reuteri to produce IL-22 ( L. reuteri /IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, L. reuteri /IL-22 did not reduce ethanol-induced liver disease in Reg3g -/- mice., Conclusion: Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are gaps in delivering evidence-based care for patients with chronic liver disease and cirrhosis., Objective: Our objective was to use interactive user-centered design methods to develop the Cirrhosis Order Set and Clinical Decision Support (CirrODS) tool in order to improve clinical decision-making and workflow., Methods: Two work groups were convened with clinicians, user experience designers, human factors and health services researchers, and information technologists to create user interface designs. CirrODS prototypes underwent several rounds of formative design. Physicians (n=20) at three hospitals were provided with clinical scenarios of patients with cirrhosis, and the admission orders made with and without the CirrODS tool were compared. The physicians rated their experience using CirrODS and provided comments, which we coded into categories and themes. We assessed the safety, usability, and quality of CirrODS using qualitative and quantitative methods., Results: We created an interactive CirrODS prototype that displays an alert when existing electronic data indicate a patient is at risk for cirrhosis. The tool consists of two primary frames, presenting relevant patient data and allowing recommended evidence-based tests and treatments to be ordered and categorized. Physicians viewed the tool positively and suggested that it would be most useful at the time of admission. When using the tool, the clinicians placed fewer orders than they placed when not using the tool, but more of the orders placed were considered to be high priority when the tool was used than when it was not used. The physicians' ratings of CirrODS indicated above average usability., Conclusions: We developed a novel Web-based combined clinical decision-making and workflow support tool to alert and assist clinicians caring for patients with cirrhosis. Further studies are underway to assess the impact on quality of care for patients with cirrhosis in actual practice., (©Jennifer Hornung Garvin, Julie Ducom, Michael Matheny, Anne Miller, Dax Westerman, Carrie Reale, Jason Slagle, Natalie Kelly, Russ Beebe, Jejo Koola, Erik J Groessl, Emily S Patterson, Matthew Weinger, Amy M Perkins, Samuel B Ho. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 03.07.2019.)

Background: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease., Aims: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease., Methods: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease., Results: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality., Conclusions: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.

Background: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed bariatric procedures and has proven effective in providing weight loss. However, considerable variance has been noted in the degree of weight loss. Physician prescription practices may be negatively affecting weight loss post-LSG and, thus, contributing to the broad range of weight loss outcomes. The aim of our study was to determine whether commonly prescribed obesogenic medications negatively affect weight loss outcomes post-LSG., Subjects/methods: This single center retrospective cohort study performed at a University hospital included 323 patients (≥18 years) within the University California, San Diego Healthcare System who underwent LSG between 2007 and 2016. We identified a list of 32 commonly prescribed medications that have weight gain as a side effect. We compared the percent excess weight loss (%EWL) of patients divided into two groups based on post-LSG exposure to obesogenic medications. A linear regression model was used to analyze %EWL at 12 months post-LSG while controlling for age, initial body mass index (BMI), and use of leptogenic medications., Results: A total of 150 patients (Meds group) were prescribed obesogenic medications within the one-year post-LSG follow up period, whereas 173 patients (Control group) were not prescribed obesogenic medications. The Meds group lost significantly less weight compared to the Control group (%EWL ± SEM at 12 months 53.8 ± 2.4 n = 78, 65.0 ± 2.6, n = 84 respectively, P = 0.002). This difference could not be attributed to differences in age, gender, initial BMI, co-morbidities, or prescription of leptogenic medications between the two groups., Conclusions: The use of provider-prescribed obesogenic medications was associated with worse weight loss outcomes post-LSG. Closer scrutiny of patient medications may be necessary to help improve outcomes of weight loss treatments.

Objective: This study aimed to evaluate a possible association between the use of obesogenic medications and inadequate weight loss in a behavioral weight-management program., Methods: This is a case-control, single-center study of 666 adult patients within a Veterans Health Administration health system who participated in the MOVE! behavioral weight-loss program. The cohort was divided into responders (n = 150), patients who achieved ≥ 5% total weight loss by the end of the MOVE! program, and nonresponders (n = 516), those who achieved < 5% total weight loss. We reviewed each patient's medical records for exposure to obesogenic medication during the time of treatment., Results: Approximately 62% (n = 411) of patients entering MOVE! had a prescription for obesogenic medications. Obesogenic medication use was associated with worse weight-loss outcomes, and participants were 37% less likely to achieve a clinically meaningful (≥ 5% total weight loss) outcome at the end of the MOVE! program (odds ratio, 0.633; 95% CI: 0.427-0.937; adjusted P = 0.022). Patients who received three or more medications (n = 72) had the greatest difficulty achieving 5% weight loss compared with the control group (odds ratio, 0.265; 95% CI: 0.108-0.646; adjusted P = 0.003)., Conclusions: The use of provider-prescribed obesogenic medications was associated with worse weight-loss outcomes in a behavioral weight-loss program. Closer scrutiny of patient medications is necessary to help improve outcomes of weight-loss treatments., (© 2019 The Obesity Society.)

Background: Novel therapeutics for inflammatory bowel disease (IBD) are under development, yet mechanistic readouts at the tissue level are lacking. Techniques to assess intestinal immune composition could represent a valuable tool for mechanism of action (MOA) studies of novel drugs. Mass cytometry enables analysis of intestinal inflammatory cell infiltrate and corresponding molecular fingerprints with unprecedented resolution. Here, we aimed to optimize the methodology for isolation and cryopreservation of cells from intestinal tissue to allow for the potential implementation of mass cytometry in MOA studies., Methods: We investigated key technical issues, including minimal tissue requirements, cell isolation protocols, and cell storage, using intestinal biopsies and peripheral blood from healthy individuals. High-dimensional mass cytometry was employed for the analyses of biopsy-derived intestinal cellular subsets., Results: Dithiothreitol and mechanical dissociation decreased epithelial cell contamination and allowed for isolation of adequate cell numbers from 2 to 4 colonic or ileal biopsies (6 × 104±2 × 104) after a 20-minute collagenase digestion, allowing for reliable detection of most major immune cell subsets. Biopsies and antibody-labeled mononuclear cells could be cryopreserved for later processing and acquisition (viability > 70%; P < 0.05)., Conclusions: Mass cytometry represents a unique tool for deep immunophenotyping intestinal cell composition. This technique has the potential to facilitate analysis of drug actions at the target tissue by identifying specific cellular subsets and their molecular signatures. Its widespread implementation may impact not only IBD research but also other gastrointestinal conditions where inflammatory cells play a role in pathogenesis.

Background & Aims: Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis., Methods: We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening., Results: There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date., Conclusions: In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests., (Copyright © 2018. Published by Elsevier Inc.)

Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity., Competing Interests: Conflict of interest statement: P.A.H., J.B., and P.J.G. are employees and shareholders of GlaxoSmithKline. The remaining authors declare no competing financial interests.

Background & Objectives: In healthcare, the routine use of evidence-based specialty care management plans is mixed. Targeted computerized clinical decision support (CCDS) interventions can improve physician adherence, but adoption depends on CCDS' 'fit' within clinical work. We analyzed clinical work in outpatient and inpatient settings as a basis for developing guidelines for optimizing CCDS design., Methods: The contextual design approach guided data collection, collation and analysis. Forty (40) consenting physicians were observed and interviewed in general internal medicine inpatient units and gastroenterology (GI) outpatient clinics at two academic medical centers. Data were collated using interpretive debriefing, and consolidated using thematic analysis and three work modeling approaches (communication flow, sequence and artifact models)., Results: Twenty-six consenting physicians were observed at Site A and 14 at Site B. Observations included attending (33%) and resident physicians. During research team debriefings, 220 of 341 unique topics were categorized into 5 CCDS-relevant themes. Resident physicians relied on patient assessment & planning processes to support their roles as communication and coordination hubs within the medical team. Artifact analysis further elucidated the evolution of assessment and planning over work shifts., Conclusions: The usefulness of CCDS tools may be enhanced in clinical care if the design: 1) accounts for clinical work that is distributed across people, space, and time; 2) targets communication and coordination hubs (specific roles) that can amplify the usefulness of CCDS interventions; 3) integrates CCDS with early clinical assessment & planning processes; and 4) provides CCDS in both electronic & hardcopy formats. These requirements provide a research agenda for future research in clinician-CCDS integration., (Published by Elsevier B.V.)

Background & Aims: The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis., Methods: Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis., Results: We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis., Conclusion: Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans., Lay Summary: Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis., (Published by Elsevier B.V.)