Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.
BackgroundEosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.MethodsThe Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance.ResultsFifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research.ConclusionsThese comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
PEG feeding is safe and well tolerated in patients with dysphagic stroke. Early PEG placement (within 2 weeks) is worthwhile with many going on to have long-term feeding. Although overall mortality is high, some patients have a long-term survival and a few attain a reasonable level of function in daily living activities. Late recovery of swallow occurs and patients should have follow-up swallowing assessment.
Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.
Background-The incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing rapidly. Barrett's oesophagus is the major risk factor. Intestinal metaplasia at the squamocolumnar junction in the absence of Barrett's oesophagus is common but its relation to adenocarcinoma and gastro-oesophageal reflux disease is unclear. Aims-To study the prevalence and clinical, endoscopic, and histological associations of intestinal metaplasia at the squamocolumnar junction. Methods-Biopsy specimens were taken from 120 randomly selected patients undergoing routine diagnostic endoscopy. Eight biopsy specimens, taken from above and below the squamocolumnar junction, gastric fundus, and gastric antrum, were stained with haematoxylin/eosin, alcian blue/periodic acid-SchiV, and Gimenez, and graded independently by one pathologist. Results-Intestinal metaplasia at the squamocolumnar junction was found in 21 patients (18%). Metaplasia was associated with increasing age (p<0.01) and antral intestinal metaplasia (p=0.04). Logistic regression analysis revealed that age was the only independent predictor (p<0.01). There was no association with symptomatic, endoscopic, or histological markers of gastro-oesophageal reflux disease. Conclusions-Intestinal metaplasia at the squamocolumnar junction is a common finding. It is associated with increasing age but not gastro-oesophageal reflux disease. (Gut 1997; 41: 585-589)
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