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Mashup Score: 0Gut: 73 (5) - 16 hour(s) ago
(21 November, 2023) Emily L Black, Emma Ococks, Ginny Devonshire, Alvin Wei Tian Ng, Maria O’Donovan, Shalini Malhotra, Monika Tripathi, Ahmad Miremadi, Adam Freeman, Hannah Coles, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Rebecca C Fitzgerald (8 February, 2024) Free Kurtis F Budden, Shakti D Shukla, Kate L Bowerman, Annalicia Vaughan, Shaan L Gellatly, David L A Wood, Nancy Lachner, Sobia Idrees, Saima Firdous Rehman, Alen Faiz, Vyoma K Patel, Chantal Donovan, Charlotte
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 33Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease - 16 hour(s) ago
Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell’s C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of li
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImages from the paper by @AngeloArmandi et al on "Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease" via https://t.co/oap3sTWjmt @DinaTiniakos @lucavalenti75 @lmiele74 @hanneshagstrom @mromerogomez https://t.co/6KG8WdxzSU
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Mashup Score: 14TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism - 16 hour(s) ago
Objective Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment. Design We identified TLR8 -expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN’s indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN’s effect were validated using tran
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 6British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults - 1 day(s) ago
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Servi
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 9
Objective Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett’s oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance. Design We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC). Results We found that 58 of 77 short-segment ( < 3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImages from the paper by @RC_Fitzgerald @RFitzgerald_lab on "Understanding the malignant potential of gastric metaplasia of the oesophagus & its relevance to Barrett’s oesophagus surveillance: individual-level data analysis" via https://t.co/vv4B6YNRfk #BarrettsOesophagus https://t.co/fkW5571DDJ
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Mashup Score: 10
Objective This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. Design A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett’s oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. Results 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50). Highest cancer aPPVs were reached in the over 5
Source: gut.bmj.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 7Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss - 2 day(s) ago
Objective Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. In this study, we aimed to explore whether transcriptionally active HBV integration events spread throughout the liver tissue in different phases of chronic HBV infection, especially in patients with HBsAg loss. Design We constructed high-resolution spatial transcriptomes of liver biopsies containing 13 059 tissue spots from 18 patients with chronic HBV infection to analyse the occurrence and relative distribution of transcriptionally active viral integration events. Immunohistochemistry was performed to evaluate the expression of HBsAg and HBV core antigen. Intrahepatic covalently closed circular DNA (cccDNA) levels were quantified by real-time qPCR. Results Spatial transcriptome sequencing identified the presence of 13 154 virus-host chimeric reads in 7.86% (1026 of 13 059) of liver tissue spot
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 14
Objective Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment. Design We identified TLR8 -expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN’s indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN’s effect were validated using tran
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 14
Objective Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. Design Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. Results FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastro
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 6Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease - 5 day(s) ago
Objective Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI). Design Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab. Results FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
The glorious Sydney Opera House during the Vivid light festival in May. Read in this @Gut_BMJ issue the great paper by Budden et al reporting how Faecal microbial transfer and complex carbohydrates mediate protection against COPD via https://t.co/CuKXqDLRPN https://t.co/rHEVVQcvan