Digestive System Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study.

INTRODUCTION: Although digestive system disease affects gut microbiota and their metabolites associated with dementia risk, the association between digestive system diseases and incident dementia has not yet been established. METHODS: This cohort analysis included 458,181 participants free of baseline dementia in the UK Biobank (2006-2021). The associations of 14 digestive system diseases with dementia incidence were examined in 2022 using Cox proportional hazards regression models. Analyses were performed to differentiate the associations for early-onset (age <65 years) and late-onset (age ≥65 years) dementia. Interaction and stratification analyses were performed for polygenic risk score and APOE. RESULTS: During a median follow-up of 12.4 years, 6,415 incident dementia cases were diagnosed. Eleven digestive system diseases showed significant associations with an increased risk of dementia after controlling for covariates and multiple testing. Compared with hazard ratios for individuals without digestive system diseases, the hazard ratios of dementia increased from 1.15 (95% confidence interval=1.09, 1.23) for patients with intestinal diverticular disease to 2.31 (95% confidence interval=1.98, 2.70) for patients with cirrhosis. The associations were different between certain digestive system diseases and dementia by onset age. The associations appeared to be stronger for cirrhosis (Q=0.001), irritable bowel syndrome (Q<0.001), gastritis and duodenitis (Q=0.002), gastroesophageal reflux disease (Q<0.001), ulcerative colitis (Q=0.047), gallbladder disease (Q=0.012), and peptic ulcer (Q=0.030) with early-onset dementia. There were no interactions for polygenic risk score or APOE (p>0.05). CONCLUSIONS: These findings suggest an increased need for dementia prevention among patients with digestive system diseases.

Prevalence of digestive disorders associated with imported Chagas disease (PADChI study): an observational study.

BACKGROUND: Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi, in which up to 10-20% of those affected may suffer digestive disorders. Multiple studies have been carried out on CD in non-endemic countries, mainly related to cardiological involvement. However, digestive disorders have not been analyzed in such depth. The objective of the study was to determine the prevalence of digestive disorders in imported CD at the time of first care. METHODS: An observational cross-sectional descriptive analysis of imported CD was performed. Chagasic structural damage and infectious digestive comorbidity were evaluated. The association between Chagasic structural damage and heart disease in Chagas patients was also investigated. RESULTS: After reviewing a total of 1,216 medical records, those of 464 patients were selected for analysis. Globally, the prevalence of digestive disorders in imported Chagas was 57.76%, 95% CI (53.25-62.27). The prevalence of comorbidity of infectious diseases was 40.73% CI 95% (36.25-45.22). Colonic abnormalities were found in 84 of 378 barium enema patients. CD-related esophageal abnormalities were present in 63 of 380 patients studied with esophagogram. CONCLUSIONS: The prevalence of digestive disorders associated with CD is high, so the presence of infectious diseases (mainly parasitic and H. pylori infection) should be ruled out. It is important to exclude structural involvement in all symptomatic patients, and asymptomatic patients should also be considered and offered.

Associations between Extracellular Matrix Protein 1 Gene Polymorphism and Progression of Liver Disease.

Background: Our study aimed to investigate the relationship between extracellular matrix 1 (ECM1) gene polymorphism and progression of liver fibrosis in the Chinese population. Methods: A total 656 patients with hepatitis B virus (HBV) infection and 298 healthy individuals of the Chinese Han population were recruited for a retrospective case-control study. Of the disease group, 104 cases had chronic hepatitis B (CHB), 266 had LC, and 286 had hepatocellular carcinoma (HCC). Subjects were frequency-matched according to age and gender. Polymorphisms of the ECM1 gene were examined using the MassARRAY SNP genotyping method. Results: There were no associations between genotype and allele frequencies of ECM1 rs3737240 and rs13294 loci with the risk of CHB and CHB-related HCC. After adjustment for age, sex, smoking status, and drinking habits, the GT genotype was dramatically related to a reduced risk of chronic HBV infection in both non-HCC (OR = 0.68, 95% CI: 0.49-0.94) and total chronic HBV infection patients (OR = 0.75, 95% CI: 0.56-1.00). Haplotype analyses revealed twelve protective haplotypes against total chronic HBV infection and four against non-HCC chronic HBV infection. Conclusion: ECM1 gene polymorphism in rs3834087 and rs3754217 loci is associated with a reduced risk of chronic HBV infection but not with liver fibrosis development and the occurrence of HCC.

[The gut-liver axis: how the gut promotes liver disease]. / Darm-Leber-Achse ­ wie der Darm die Leber krank macht.

Research over the last two decades has highlighted the major role played by the gut microbiota in health and disease, including chronic liver diseases. The liver and intestine communicate via the portal vein, biliary system, and mediators in the circulation (gut-liver axis). Microbes in the intestine are involved in the maintenance of liver homeostasis. Conversely, alterations in the normal composition or diversity of the gut microbiome-a condition called dysbiosis-can also serve as a source of pathogens and molecules that contribute to the onset or progression of chronic liver diseases, like non-alcoholic fatty liver disease. Through the increased production of bacteria-derived ethanol, altered bile acid metabolism, altered production of short-chain fatty acids, greater abundance of lipopolysaccharide (LPS) containing Gram-negative bacteria and an increased intestinal permeability, dysbiosis impacts metabolic pathways and inflammatory processes. However, the clinical relevance of specific gut microbial alterations associated with chronic liver diseases remains unclear. This review discusses how microbes and their products contribute to liver disease pathogenesis and how targeting the microbiota might be used for therapeutic approaches.

[Systemic pruritus: what is new in diagnosis and treatment?] / Systemischer Pruritus: Was gibt es Neues in Diagnostik und Therapie?

BACKGROUND: Chronic pruritus is a common symptom of various systemic diseases. In particular, patients with chronic renal failure, hepatobiliary diseases, and myeloproliferative neoplasms are affected. OBJECTIVES: The purpose of this review is to provide an overview of laboratory chemistry and imaging diagnostics as well as current and novel therapeutic approaches to pruritus of systemic diseases. MATERIALS AND METHODS: An extensive PubMed search was performed. RESULTS: To clarify the cause of chronic pruritus, a step-by-step diagnosis is recommended, which is based on the frequency of pruritus-associated diseases. A basic diagnosis enables a cost-effective and targeted clarification at the level of a general practitioner. Current topical and drug therapy recommendations of pruritus in chronic renal failure, hepatobiliary diseases, myeloproliferative neoplasms, and rarer causes are summarized. In addition, novel therapeutic approaches such as the κ­opioid receptor agonist difelikefalin, bezafibrate, inhibitors of the ileal bile acid transporter (IBAT), and the JAK-STAT pathway are highlighted. CONCLUSIONS: Chronic pruritus in systemic diseases can be a diagnostic challenge. A staged diagnostic approach facilitates identification of the underlying disease. Improved pathophysiological understanding has led to the first approved therapeutic options for chronic kidney disease-associated and hepatic pruritus.

Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity.

Inborn errors of immunity (IEIs) consist of numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States. As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges. A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity. A generalized approach to diagnosis and management of hepatic complications is provided, and collaboration with hepatologists, immunologists, and pathologists is emphasized as a requirement for optimizing management and outcomes.

Chronic Drug Use and Abdominal Pain.

There are a variety of gastrointestinal pathologies that may be emergently identified in the patient who chronically uses alcohol or other substances. Patients may present to an Emergency Department with abdominal complaints existing on a spectrum from vague and benign to systemically toxic and potentially life-threatening. This article highlights ethanol, opioids, and other common substances of abuse and how they may contribute to gastrointestinal complaints.

Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

BACKGROUND: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited. OBJECTIVE: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban. DESIGN: Nationwide population-based cohort study. SETTING: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland. PATIENTS: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. MEASUREMENTS: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression. RESULTS: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses. LIMITATIONS: Unmeasured confounding and small subgroup analyses. CONCLUSION: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication. PRIMARY FUNDING SOURCE: Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.

Screening and identifying hepatobiliary diseases through deep learning using ocular images: a prospective, multicentre study.

BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.

Comprehensive assessment of nutritional status and nutritional-related complications in newly diagnosed esophageal cancer patients: A cross-sectional study.

BACKGROUND & AIMS: Malnutrition is prevalent in upper gastrointestinal cancer patients. The purpose of this study was a comprehensive assessment of nutritional status in newly diagnosed patients with esophageal cancer. METHODS: Newly diagnosed esophageal cancer patients were referred to a chemo-radiation referral center in Mashhad, Iran, between February 2017 to February 2019. Anthropometric indices, a Patient-Generated Subjective Global Assessment (PG-SGA) tool, body composition, dietary intake, nutritional-related complications, and laboratory tests were assessed. RESULTS: One hundred and eighty-nine patients with a mean age of 67.1 ± 12 and a male to female ratio of 98 to 91 were included. Ninety-seven (51.3%) of patients had experienced significant weight loss and 56 (29.6%) were underweight at diagnosis. According to PG-SGA, 179 (94.7%) needed nutritional interventions. Reduced muscle mass and low handgrip strength were observed in 70 (39.4%) and 26 (14.4%) of patients, respectively. Inadequate intakes of energy (less than 24 kcal/kg/day) and protein (less than 1.2 g/kg/day) were found in 146 (77.8%) and 171 (91%) patients, respectively. The mean total daily energy and protein intakes of subjects were 943.8 ± 540 kcal/day, and 30.6 ± 21 g/day, respectively. The most common nutritional-related complications were as follows: dysphagia (84.8%), anorexia (31.6%), constipation (62.1%), esophageal pain (48.4%), and dyspepsia (41.1%). CONCLUSION: Our study demonstrated a high prevalence of malnutrition in newly diagnosed esophageal cancer patients. This fact demonstrates the importance of early screening of nutritional status via PG-SGA tool, clinical evaluation, dietary intake evaluations, and laboratory tests, based on which effective nutritional interventions and Symptoms management may be introduced in these patients.

Abdominal Surgery in Patients with Ventricular Assist Devices: a Single-Center Report.

This study was performed to evaluate the incidence and outcome of patients with ventricular assist devices (VADs) undergoing abdominal surgery at our institution. A total of 604 adult patients who underwent VAD implantation between February 2004 and February 2018 were analyzed retrospectively with a median follow-up time of 66 (6-174) months. Thirty-nine patients (6.5%) underwent abdominal surgery. Elective surgical procedures were performed in 22 patients (56.4%), mainly for abdominal wall hernia repairs, partial colectomies, and cholecystectomies. Early after elective abdominal surgery no patient died, resulting in a median survival of 23 (1-78) months. Emergency surgery was performed in 17 patients (43.6%). The most common emergency indications were intestinal ischemia and/or perforation. Eight patients undergoing emergent surgery (44.4%) died within the first 30 days after primary abdominal operation, mainly due to sepsis and consecutive multiple organ failure, resulting in a dismal median survival of one month (0-52). Patients undergoing abdominal surgery had significantly lower rates of realized heart-transplantation (p = 0.031) and a significantly higher rate of VAD exchange, before or after abdominal surgery, due to thromboses or infections (p = 0.037). Nonetheless, overall survival after primary VAD implantation in these patients (median 38 months; 0-107) was not significantly impaired when compared to all other patients undergoing VAD implantation (median 30 months; 0-171). In summary, elective abdominal surgery can be performed safely when well planned by an experienced multidisciplinary team. Abdominal complications in VAD patients requiring emergent surgery, however, lead to a significant increase in short-term morbidity and a high 30-day mortality rate.

Clinical Utility of Carnett and closed eye sign in emergency department.

BACKGROUND: Carnett's sign (CAR) and Closed Eye sign (CE) have been suggested for use in the emergency department setting in the management of abdominal pain. The present study sought to determine the sensitivity/specificity of CAR and CE for pathological CT findings as a primary outcome and for subsequent hospital admission or surgical intervention as secondary outcomes in a community emergency department setting. METHODS: A convenience sample of adults (≥18 y) presenting with acute (<48 h) nontraumatic and non-postoperative abdominal pain determined by treating provider to warrant CT imaging were eligible for enrollment. Treating providers completed a datasheet describing physical examination findings prior to CT imaging. RESULTS: 320 patients were enrolled. 245/320 (76.5%) of enrolled patients had findings on CT Imaging. CAR+ was recorded in 145 and CAR- in 175 patients. CE+ was in 187 and CAR- in 133 patients. Sensitivity and specificity of CAR- for hospital admission was 42.2% and 38.9% and for surgery-44.8% and 43.1%. Sensitivity and specificity of CE- for hospital admission was 28% and 51.6% and for surgery-25.9% and 55%. CAR+ patients were more likely to be admitted or undergo surgery as compared to CAR-. CE+ patients were more likely to be admitted or undergo surgery as compared to CAR-. There were no differences in frequency of pathological CT findings between CAR+ and CAR- or CE+ and CE- patients. CONCLUSION: CAR and CE are neither sufficiently sensitive nor specific for use in the emergency department setting. CT findings were equally likely in CAR+ and CAR- patients. CT Findings were also equally likely in CE+ and CE- patients.

Plans to Reactivate Gastroenterology Practices Following the COVID-19 Pandemic: A Survey of North American Centers.

BACKGROUND & AIMS: Practices dramatically reduced endoscopy services due to the COVID-19 pandemic. Because practices now are considering reintroduction of elective endoscopy, we conducted a survey of North American practices to identify reactivation barriers and strategies. METHODS: We designed and electronically distributed a web-based survey to North American gastroenterologists consisting of 7 domains: institutional demographics, impact of COVID-19 on endoscopy practice, elective endoscopy resumption plans, anesthesia modifications, personal protective equipment policies, fellowship training, and telemedicine use. Responses were stratified by practice type: ambulatory surgery center (ASC) or hospital-based. RESULTS: In total, 123 practices (55% ASC-based and 45% hospital-based) responded. At the pandemic's peak (as reported by the respondents), practices saw a 90% decrease in endoscopy volume, with most centers planning to resume elective endoscopy a median of 55 days after initial restrictions. Declining community prevalence of COVID-19, personal protective equipment availability, and preprocedure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing availability were ranked as the 3 primary factors influencing reactivation timing. ASC-based practices were more likely to identify preprocedure testing availability as a major factor limiting elective endoscopy resumption (P = .001). Preprocedure SARS-CoV-2 testing was planned by only 49.2% of practices overall; when testing is performed and negative, 52.9% of practices will continue to use N95 masks. CONCLUSIONS: This survey highlights barriers and variable strategies for reactivation of elective endoscopy services after the COVID-19 pandemic. Our results suggest that more widespread access to preprocedure SARS-CoV-2 tests with superior performance characteristics is needed to increase provider and patient comfort in proceeding with elective endoscopy.