Gut最新文献

{"title":"Histology of subepithelial lesions (SELs) in the gastrointestinal tract-resected endoscopic: a database study of 4901 patients.","authors":"Zhipeng Qi, Enpan Xu, Shuchang Xu, Leiming Xu, XiaoBo Li, Liang Zhong, Dongli He, Pinghong Zhou, Zhendong Jin, Yunshi Zhong","doi":"10.1136/gutjnl-2024-333150","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333150","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma.","authors":"Henrike Salié, Lara Wischer, Antonio D'Alessio, Ira Godbole, Yuan Suo, Patricia Otto-Mora, Juergen Beck, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher, Claudia A M Fulgenzi, Andreas Blaumeiser, Melanie Boerries, Natascha Roehlen, Michael Schultheiß, Maike Hofmann, Robert Thimme, David J Pinato, Thomas Longerich, Bertram Bengsch","doi":"10.1136/gutjnl-2024-332837","DOIUrl":"10.1136/gutjnl-2024-332837","url":null,"abstract":"<p><strong>Background: </strong>The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.</p><p><strong>Objective: </strong>We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.</p><p><strong>Design: </strong>We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.</p><p><strong>Results: </strong>Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"451-466"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quest for HBV functional cure: what have we learnt from silencing RNAs?","authors":"Norah Terrault, Anna S Lok","doi":"10.1136/gutjnl-2024-333763","DOIUrl":"10.1136/gutjnl-2024-333763","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"340-342"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Definite benefits of GLP-1 receptor agonists: what is the risk of gastroparesis and lung aspiration?","authors":"Michael Camilleri","doi":"10.1136/gutjnl-2024-333036","DOIUrl":"10.1136/gutjnl-2024-333036","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"342-345"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing gastroscopy practices: the need for improved methodology and interpretation - author's reply.","authors":"David Robert Beaton, Linda Sharp, Matthew D Rutter","doi":"10.1136/gutjnl-2024-333437","DOIUrl":"10.1136/gutjnl-2024-333437","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"503-504"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidelines Development Group for the British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma.","authors":"Shahid A Khan, Simon M Rushbrook, Timothy James Kendall, Yoh Zen, Raneem Albazaz, Prakash Manoharan, Stephen P Pereira, Richard Sturgess, Brian R Davidson, Hassan Z Malik, Derek Manas, Nigel Heaton, K Raj Prasad, Juan W Valle, Rebecca Goody, Maria Hawkins, Wendy Prentice, Helen Morement, Martine Walmsley, John Bridgewater","doi":"10.1136/gutjnl-2024-333359","DOIUrl":"10.1136/gutjnl-2024-333359","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"504-505"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TPX2 serves as a novel target for expanding the utility of PARPi in pancreatic cancer through conferring synthetic lethality.","authors":"Mingming Xiao, Rong Tang, Haoqi Pan, Jing Yang, Xuhui Tong, He Xu, Yanmei Guo, Yalan Lei, Di Wu, Yubin Lei, Yamei Han, Zhilong Ma, Wei Wang, Jin Xu, Xianjun Yu, Si Shi","doi":"10.1136/gutjnl-2024-332782","DOIUrl":"10.1136/gutjnl-2024-332782","url":null,"abstract":"<p><strong>Background: </strong>PARP inhibitors (PARPi) have been licensed for the maintenance therapy of patients with metastatic pancreatic cancer carrying pathogenic germline BRCA1/2 mutations. However, mutations in BRCA1/2 are notably rare in pancreatic cancer.</p><p><strong>Objective: </strong>There is a significant unmet clinical need to broaden the utility of PARPi.</p><p><strong>Design: </strong>RNA sequencing was performed to screen potential targets for PARPi sensitivity. The synthetic lethal effects were verified in patient-derived xenograft (PDX), xenograft and patient-derived organoid models. Mechanisms were explored via LC‒MS/MS, coimmunoprecipitation, laser microirradiation, immunofluorescence, the homologous recombination (HR) or non-homologous end joining (NHEJ) reporter system, in situ proximity ligation assay and live-cell time-lapse imaging analyses.</p><p><strong>Results: </strong>Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is an exploitable vulnerability. TPX2 was downregulated in PDX models sensitive to PARPi, and TPX2 inhibition conferred synthetic lethality to PARPi both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, TPX2 functions in a cell cycle-dependent manner. In the S/G2 phase, ATM-mediated TPX2 S634 phosphorylation promotes BRCA1 recruitment to double-strand breaks (DSBs) for HR repair, whereas non-phosphorylated TPX2 interacts with 53BP1 to recruit it for NHEJ. The balance between phosphorylated and non-phosphorylated TPX2 determines the DSB repair pathway choice. During mitosis, TPX2 phosphorylation enhances Aurora A activity, promoting mitotic progression and chromosomal stability. Targeting TPX2 S634 phosphorylation with a cell-penetrating peptide causes genomic instability and mitotic catastrophe and enhances PARPi sensitivity. Additionally, the inhibition of TPX2 or S634 phosphorylation combined with gemcitabine further sensitised pancreatic cancer to PARPi.</p><p><strong>Conclusions: </strong>Our findings revealed the dual-functional significance of TPX2 in controlling DNA DSB repair pathway choice and mitotic progression, suggesting a potential therapeutic strategy involving PARPi for patients with pancreatic cancer.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"410-423"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological consistency between EUS and ERCP in diagnosing biliary sludge and microlithiasis.","authors":"Chen Shi, Jianglong Hong, Bingqing Bai, Suwen Li, Lihong Chen, Hao Ding, Zhangwei Xu, Junjun Bao, Qiao Mei","doi":"10.1136/gutjnl-2024-332971","DOIUrl":"10.1136/gutjnl-2024-332971","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"505-506"},"PeriodicalIF":23.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications.","authors":"Victoria Gudiño, Raquel Bartolomé-Casado, Azucena Salas","doi":"10.1136/gutjnl-2024-334165","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334165","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all intestinal cell types, including immune, epithelial and stromal cells, have been described in these diseases. The study of IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse cell types, limiting insights. Single-cell omic technologies overcome the intrinsic limitations of bulk analysis and reveal the complexity of multicellular tissues at a cell-by-cell resolution. Within healthy and inflamed intestinal tissues, single-cell omics, particularly single-cell RNA sequencing, have contributed to uncovering novel cell types and cell functions linked to disease activity or the development of complications. Collectively, these results help identify therapeutic targets in difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae or inflammation of the pouch. More recently, single-cell omics have gradually been adopted in studies to understand therapeutic responses, identify mechanisms of drug failure and potentially develop predictors with clinical utility. Although these are early days, such studies lay the groundwork for the implementation in clinical practice of new technologies in diagnostics, monitoring and prediction of disease prognosis. With this review, we aim to provide a comprehensive survey of the studies that have applied single-cell omics to the study of UC or CD, and offer our perspective on the main findings these studies contribute. Finally, we discuss the limitations and potential benefits that the integration of single-cell omics into clinical practice and drug development could offer.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon footprinting and environmental impact of gastrointestinal endoscopy procedures at a tertiary care institution: a prospective multi-dimensional assessment.","authors":"Hardik Rughwani, Rakesh Kalapala, Anudeep Katrevula, Nitin Jagtap, Madhav Desai, Sara Teles de Campos, Mohan Ramchandani, Sundeep Lakhtakia, Rupjyoti Talukdar, Santosh Darisetty, Sana Fatima Memon, Guduru Venkat Rao, Marco Bruno, Prateek Sharma, D Nageshwar Reddy","doi":"10.1136/gutjnl-2024-332471","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332471","url":null,"abstract":"<p><strong>Background: </strong>Given the imperative to combat climate change, reducing the healthcare sector's implications on the environment is crucial.</p><p><strong>Objective: </strong>This study aims to offer a comprehensive assessment of the environmental impact of gastrointestinal endoscopy (GIE) procedures, specifically focusing on greenhouse gas (GHG) emissions and waste generation.</p><p><strong>Design: </strong>A prospective study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from 29 May to 10 June 2023, including all consecutive GIE procedures. Carbon emissions for various variables involved were calculated with specific emission factors using 'The GHG Protocol'.</p><p><strong>Results: </strong>Based on data from 3244 consecutive patients undergoing 3873 procedures, the study revealed a total carbon footprint of 148 947.32 kg CO₂e or 38.45 kg CO₂e per procedure. Excluding patient travel, the emissions were 6.50 kg CO₂e per procedure. The total waste generated was 1952.50 kg, averaging 0.504 kg per procedure, far less than 2-3 kg per procedure in the West. The waste disposal breakdown was 9.5% direct landfilling, 64.8% incineration, then landfilling and 25.7% recycling, which saved 380 kg CO₂e. India effectively recycles 25.7% of hospital-related waste, which undergoes landfilling in the West. The primary contributors to GHG emissions were patient travel (83.09%), electricity consumption (10.42%), medical gas transport and usage (3.63%) and water consumption (1.86%). Diagnostic procedures generate less waste and lower carbon footprint than therapeutic procedures.</p><p><strong>Conclusion: </strong>This study highlights the significant environmental footprint of GIE procedures, emphasising the importance of optimising practices to reduce patient travel and repeat procedures, alongside improving electricity and water management for sustainable healthcare.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}