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Mashup Score: 4Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2 - 11 hour(s) ago
Background Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils and hepatocytes and its role in AH pathogenesis remain unclear. Objective We investigate the regulatory role of leucocyte cell-derived chemotaxin 2 (LECT2) in hepatocyte–neutrophil interaction and its impact on AH progression. Design We used bulk and single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. We analysed serum and liver samples from AH patients and employed genetically modified mice alongside in vitro studies. Results RNA-sequencing analysis identified several neutrophil chemokines that are elevated in hepatocytes from AH patients, including LECT2 whose role in AH remains largely unknown. AH patients exhibited increased levels of LECT2 in hepatocytes, positively correlating with the severity of AH. Ethanol-fed mice also exhibited elevated liver LECT2, which was abolished
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 3Low-coverage whole genome sequencing of low-grade dysplasia strongly predicts advanced neoplasia risk in ulcerative colitis - 11 hour(s) ago
Background The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management. Objective We aimed to provide accurate AN risk stratification in UC patients with LGD. We hypothesised that the pattern and burden of somatic genomic copy number alterations (CNAs) in LGD lesions could predict future AN risk. Design We performed a retrospective multicentre validated case–control study using n=270 LGD samples from n=122 patients with UC. Patients were designated progressors (n=40) if they had a diagnosis of AN in the ~5 years following LGD diagnosis or non-progressors (n=82) if they remained AN-free during follow-up. DNA was extracted from the baseline LGD lesion, low-coverage whole genome sequencing performed and data processed to detect CNAs. Survival analysis was used to evaluate CNAs as pred
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 4In vitro microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier - 11 hour(s) ago
Background Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals. Objectives This study aimed to establish an approach for predicting an individual’s sensitivity to dietary emulsifiers via their baseline microbiota. Design We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor’s sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity. Results Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had m
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 4Colorectal cancer incidence after the first surveillance colonoscopy and the need for ongoing surveillance: a retrospective, cohort analysis - 11 hour(s) ago
Background Recommendations for the first postpolypectomy surveillance colonoscopy (SC1), based on stratifying postpolypectomy colorectal cancer (CRC) risk, are well established. Limited data inform recommendations for surveillance beyond SC1. Objective We investigated which patient groups need surveillance beyond SC1. Design Retrospective analysis of patients who underwent colonoscopy with polypectomy at 17 UK hospitals, mostly from 2000 to 2010, and had ≥1 surveillance colonoscopies. Cancer and death data were collected through 2017. We examined patients in groups defined by risk at baseline and SC1, applying risk definitions from the 2020 UK postpolypectomy surveillance guidelines: ‘low risk, low risk’ (LR-LR), ‘high risk, low risk’ (HR-LR), ‘low risk, high risk’ (LR-HR) and ‘high risk, high risk’ (HR-HR). We examined CRC incidence after SC1, censoring at any second surveillance colonoscopy (SC2), and after SC2 through end of follow-up. We compared incidence with general population i
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTOnline paper by Robbins et al entitled "Colorectal cancer incidence after the first surveillance colonoscopy and the need for ongoing surveillance: a retrospective, cohort analysis" via https://t.co/o3BnKJuvFp @DrAmandaJCross @CSPRG_Imperial @andymveitch #ColorectalCancer https://t.co/ZItDJ68Suu
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Mashup Score: 18Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression - 11 hour(s) ago
Background Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models. Objective We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum. Design A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterisation were performed. Results Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM from STMN1 cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fate
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 16
Professor El-Omar has selected Professor Jeremy Adler from the Department of Paediatric Gastroenterology and Susan B. Meister Child Health Evaluation and Research Centre, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA to do the next #GUTBlog. “Crohn’s disease can be damaging to the gut, causing strictures and fistulas if the inflammation is not adequately controlled. Children with Crohn’s disease tend to have greater inflammatory burden than adults, and suffer more frequently from
Source: blogs.bmj.comCategories: General Medicine News, GastroenterologyTweet-
Excellent #GUTBlog by @JeremyAdlerMD on the important paper in @Gut_BMJ entitled "Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn’s disease: post hoc analysis of the RISK study" via https://t.co/NWxdXMitFX Paper via https://t.co/SrkIeZeD2r
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Mashup Score: 5Lipidomics in colon cancer - 2 day(s) ago
To cite: Soundararajan R, Maurin MM, Rodriguez-Silva J, et al. Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an u…
Source: www.youtube.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 5
Background A rise in paediatric cases of acute hepatitis of unknown origin (AHUO) was observed in 2022, some requiring liver transplantation. A link to adeno-associated virus 2 infection and CD4+T-cell mediated disease was reported in cohorts in the UK and USA but does not explain all cases. Objective To determine the intrahepatic immune cell interactions in the inflamed liver and a possible contribution of SARS-CoV-2 infection. Design Patients with acute non-A non-E hepatitis (10/12 AHUO, 2/12 subacute) during February 2022–December 2022 undergoing liver biopsy were recruited in a European patient cohort. Hepatological, virological, histopathological and highly multiplexed spatial and single-cell analyses of liver biopsies were performed. Results Patients were negative for adenoviral and SARS-CoV-2 PCR. Three patients had a positive adenoviral serology and 10/12 patients had a history or serological evidence of SARS-CoV-2 infection. Imaging mass cytometry identified significant intrah
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTOnline paper by Röttele et al on "Characteristic immune cell interactions in livers of children with acute hepatitis revealed by spatial single-cell analysis identify a possible postacute sequel of COVID-19" via https://t.co/QMmFZWKLHm @teximmed2 @therealbbengsch #COVID19 https://t.co/wEs8dYcEom
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Mashup Score: 1Endoscopic resection after downstaging of oesophageal carcinoma by neoadjuvant chemoimmunotherapy: – a new multimodal concept? - 2 day(s) ago
Oesophageal surgery is the current standard for advanced oesophageal cancer within multimodal protocols involving perioperative chemoimmunotherapy and/or radiotherapy. However, oesophagectomy is afflicted with significant morbidity and mortality so that organ-preserving strategies would be worthwhile to develop. We report a case of advanced oesophageal squamous cell cancer (cT2) treated by neoadjuvant therapy and presumably downstaged to a superficial lesion. Semicircumferential endoscopic full-thickness resection (EFTR) was performed, followed by implantation of a metallic stent. Histology showed residual intramucosal high-grade dysplasia. Three months postoperation, the wound healed well, with no occurrence of oesophageal stenosis. The patient received immunotherapy until 24 months post-EFTR and has been followed for 26 months without the recurrence of the disease. Further studies have to show the oncological success, but also oncological risks associated with such an innovative appr
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 9
Background Lesion size is an independent risk factor for recurrence following endoscopic mucosal resection of large (≥20 mm) non-pedunculated colorectal polyps. Post-resection margin thermal ablation (MTA) reduces the risk of recurrence. Its impact on the uncommon larger (≥40 mm) lesions is unknown. Objective We sought to analyse the impact of MTA on ≥40 mm lesions in a large, prospective cohort. Design A prospective cohort of patients with colorectal polyps ≥20 mm treated with piecemeal endoscopic mucosal resection in an expert tissue resection centre was divided into three phases: ‘pre-MTA’, July 2009–June 2012; ‘MTA-adoption’, July 2012–June 2017 and ‘standardised-MTA’, July 2017–July 2023. Recurrence was defined as adenomatous tissue endoscopically and/or histologically detected at the first surveillance colonoscopy. The primary outcome was the recurrence rate over the three time periods in three size groups: 20–39 mm, 40–59 mm and ≥60 mm. Results Over 14 years until July 2023, 187
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
Read the #GUTOnline paper by Xu et al entitled "Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2" via https://t.co/1Dm0YzCkPI @wanghualiver #Hepatitis #Alcohol https://t.co/8M0j7GP0iI