The genetic regulation of the gastric transcriptome is associated with metabolic and obesity-related traits and diseases.

Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. Gastric corpus and antrum mucosa biopsies were collected during routine gastroscopies from up to 431 healthy individuals. We obtained genotype and transcriptome data and performed transcriptome profiling and expression quantitative trait locus (eQTL) studies. We further used data from genome-wide association studies (GWAS) of various diseases and traits to partition their heritability and to perform transcriptome-wide association studies (TWAS). The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. Particularly, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition. Our findings show that gastric corpus and antrum vary in their transcriptome and genetic regulatory profiles indicating physiological differences which are mostly related to digestion and epithelial protection. Moreover, our findings demonstrate that the genetic regulation of the gastric transcriptome is linked to biological mechanisms associated with metabolic, obesity-related, and cardiovascular traits and diseases. NEW & NOTEWORTHY We analyzed the transcriptomes and genetic regulatory profiles of gastric corpus and for the first time also of antrum mucosa in 431 healthy individuals. Through tissue-specific gene expression and eQTL analyses, we uncovered unique and common physiological processes across both primary gastric sites. Notably, our findings reveal that stomach-specific eQTLs are enriched in loci associated with metabolic traits and diseases, highlighting the pivotal role of gene expression regulation in gastric physiology and potential pathophysiology.

The effect of isolation precautions on care processes and medical outcomes in patients colonized with MRSA.

Background: Isolation precautions used in methicillin-resistant Staph ylo coc cus aureus (MRSA) infection control are effective in inhibiting pathogen transmission, but may cause unintended consequences in medical care. In addition, while costs attributed to MRSA are known to be substantial, little is known about their reimbursement in the German Diagnosis Related Groups (G-DRG) payment system. The aim of our study was to examine the effect of isolation precautions used in MRSA infection control on care processes, patient outcomes and deliver reliable data on MRSA-attributed reimbursement. Methods: A retrospective, matched cohort study of inpatients admitted to a general care teaching hospital in Bad Neuenahr, Germany, between January 1st, 2016, and December 31st, 2017 was performed. Patients isolated for MRSA colonization were matched to non-isolated controls based on age, gender, MRSA-adjusted Patient Clinical Complexity Level (Ma-PCCL) and Major Diagnostic Category (MDC). Main outcome measures on care processes and patient outcomes included adverse events, patient complaints, 30-day readmission rates, length of stay, type of discharge, and performance of instrument-based diagnostics. MRSA-attributed reimbursement was measured by conducting two separate G-DRG groupings, one with inclusion of MRSA-related codes and one without. Results: A total of 26,059 patients were admitted to Maria Hilf Hospital in Bad Neuenahr, Germany, during the study period. We identified 304 patients isolated for MRSA colonization. Compared to non-isolated matched controls, those on isolation precautions for MRSA colonization acquired about 45% more pressure ulcers and experienced significant delays in the performance of radiological diagnostics and echocardiographs. Patients isolated for MRSA colonization received about 49% fewer echocardiographs and had about 38% fewer abdominal ultrasound exams performed compared to non-isolated matched controls. A non-significant tendency towards fewer discharges to rehabilitation clinics and higher mortality rates were observed in patients isolated for MRSA colonization. Reimbursements were negligibly affected when MRSA-related codes were integrated by the grouper. Conclusion: Isolation precautions are associated with adverse consequences for care processes. These consequences need to be mitigated in order to justify placing patients at risk.

Coexisting gastric varices should not preclude prophylactic ligation of large esophageal varices in cirrhosis.

BACKGROUND/AIMS: Coexisting gastric varices at baseline or the risk of their formation during treatment could alter the approach for primary bleeding prophylaxis in patients with large esophageal varices. METHODS: Data analysis of 152 patients with cirrhosis and large esophageal varices included in the German multicenter trial on primary prevention of variceal bleeding. RESULTS: 20 patients (13.6%) had coexisting gastric varices at baseline (GOV+). 10 of those each received either band ligation or propranolol, respectively. During follow-up (34.4 +/- 18.9 months) new gastric varices occurred in 2/75 (2.7%, ligation) and 4/77 (5.2%, propranolol) patients, respectively. One patient with newly developed gastric varices bled (propranolol group). GOV+ patients had a better baseline liver function and overall survival. Bleeding incidence did not differ significantly between GOV+ and GOV- patients (3-year actuarial risk: 20.0 +/- 10.6% (GOV+), 38.1 +/- 4.4% (GOV-), p = 0.195). Among GOV+ patients, bleeding occurred in 3/10 patients of the propranolol group and in 0/10 in the ligation group (p = 0.038). CONCLUSION: Prophylactic band ligation of large esophageal varices is safe and effective also in patients with coexisting gastric varices. Band ligation did not increase the risk of secondary gastric varices compared to propranolol.

Etiology, management, and outcome of the Budd-Chiari syndrome.

BACKGROUND: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. OBJECTIVE: To characterize the causes and treatment of incident BCS. DESIGN: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. SETTING: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. PATIENTS: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. MEASUREMENTS: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. RESULTS: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. LIMITATION: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. CONCLUSION: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. PRIMARY FUNDING SOURCE: Fifth Framework Programme of the European Commission.