Gut最新文献

{"title":"Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study","authors":"Jinsei Miyoshi, Alessandro Mannucci, Marco Scarpa, Feng Gao, Shusuke Toden, Timothy Whitsett, Landon J Inge, Ross M Bremner, Tetsuji Takayama, Yulan Cheng, Teodoro Bottiglieri, Iris D Nagetaal, Martha J Shrubsole, Ali H Zaidi, Xin Wang, Helen G Coleman, Lesley A Anderson, Stephen J Meltzer, Ajay Goel","doi":"10.1136/gutjnl-2024-333364","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333364","url":null,"abstract":"Background There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s oesophagus (BE). Objective To develop and test a blood-based assay for EAC and BE. Design Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia ( EMERALD ) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries ([NCT06381583][1]) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295). Results After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%). Conclusion Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC. Trial registration number [NCT06381583][1]. Data sharing not applicable as no datasets generated and/or analysed for this study. Data collected for the study, including deidentified participant data and the code, will be made available to others at publication via a signed data access agreement and at the discretion of the investigators’ approval of the proposed use of such data. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06381583&atom=%2Fgutjnl%2Fearly%2F2024%2F11%2F18%2Fgutjnl-2024-333364.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"230 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673284","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":"Devices substitution can reduce environmental burden: what about strategies substitution?","authors":"Raphaëlle Grau, Jérémie Jacques, Jérôme Rivory, Mathieu Pioche","doi":"10.1136/gutjnl-2024-334092","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334092","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638666","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":"Recent advances in clinical practice: mastering the challenge—managing IBS symptoms in IBD","authors":"Judith Wellens, João Sabino, Tim Vanuytsel, Jan Tack, Séverine Vermeire","doi":"10.1136/gutjnl-2024-333565","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333565","url":null,"abstract":"Many patients with IBD report persisting symptoms, despite resolution of the inflammatory process. Although by definition, a diagnosis of IBS cannot be made, the prevalence of ‘IBS in IBD’ surpasses the rate of IBS in the global population by fivefold. Because IBS-like symptoms are associated with a decreased quality of life and increased healthcare utilisation in IBD, diagnosis and treatment are necessary. In this review, we summarise the current knowledge on IBS-like symptoms in IBD. A pathophysiological common ground is present, which includes genetic susceptibility, environmental triggers, gut microbial dysbiosis, increased intestinal permeability, visceral hypersensitivity and involvement of brain–gut interaction. When symptoms persist after resolution of inflammation, other GI diseases should be excluded based on the chief complaint, considering any possible psychological co-morbidity early in the diagnostic work-up. Subsequent treatment should be initiated that is evidence-based and often multimodal, including classical and non-classical pharmacological agents as well as lifestyle and microbiota-based approaches, spanning the breadth of the gut, brain and its interaction. Treatment goals in this substantial part of the IBD population should be adapted to not only focus on treating the inflammation but taking care of the patient.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601016","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":"Large proximal gastric GIST tumours: downsizing by imatinib and subsequent endoresection","authors":"Ayimukedisi Yalikong, Baohui Song, Dongli He, Enpan Xu, Zhipeng Qi, Yunshi Zhong","doi":"10.1136/gutjnl-2024-332993","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332993","url":null,"abstract":"Surgical removal is recommended for gastrointestinal stromal tumours (GISTs) larger than 3 cm due to their potential for malignancy but limited wedge resection is not possible in the proximal stomach. Endoscopic removal of larger lesions has been technically limited in complex anatomical regions such as cardia. We report two cases of large proximal (cardia/fundus) GIST tumours (51 and 60 mm) which were downsized (to 26 and 36 mm) by 3–7 months of imatinib therapy followed by transmural endoscopic resection. Follow-up of 23 and 16 months including endoscopy and CT was unremarkable. GISTs commonly occur in the stomach.1 2 Due to their malignant potential, surgery is generally recommended.3–5 Recently, endoscopic resection of submucosal tumours (SMTs) has made significant progress.6 The European Society of Gastrointestinal Endoscopy recommended endoscopic resection for gastric GISTs<35 mm projecting into the lumen.3 Endoscopic full-thickness resection (EFTR), an extension of submucosal dissection, has shown promising results for SMTs arising from the deep muscularis propria (MP), particularly in the gastric fundus.7 However, achieving R0 resection in GISTs>35 mm remains challenging.8 Large GISTs in anatomically complex areas such as the cardia and fundus may still necessitate surgical resection.2 Radical surgery, however, poses risks to cardia function and patient quality of life.9 Preoperative imatinib can shrink tumours, reduce mitotic activity and lower recurrence risk.9 10 The American College of Gastroenterology guidelines suggested neoadjuvant imatinib to facilitate tumour reduction in large GISTs, enhancing the feasibility of minimally invasive endoscopic resection. Hence, in this context, we explored the combination of preoperative imatinib with EFTR as a novel, minimally invasive strategy for treating large gastric GISTs. Our primary outcomes suggested this approach may be a viable alternative for GISTs in gastric anatomical complex regions. Case 1 was a 65-year-old woman with abdominal distension and belching for several months. Gastroscopy revealed …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"159 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601017","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":"CAF-macrophage crosstalk in tumour microenvironments governs the response to immune checkpoint blockade in gastric cancer peritoneal metastases","authors":"Yuanfang Li, Yongqiang Zheng, Jiaqian Huang, Run-Cong Nie, Qi-Nian Wu, Zhijun Zuo, Shuqiang Yuan, Kai Yu, Cheng-Cai Liang, Yi-Qian Pan, Bai-Wei Zhao, Yuhong Xu, Qihua Zhang, Yashang Zheng, Junquan Chen, Zhao-Lei Zeng, Wei Wei, Ze-Xian Liu, Rui-Hua Xu, Hui-Yan Luo","doi":"10.1136/gutjnl-2024-333617","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333617","url":null,"abstract":"Background Peritoneal metastasis is the most common metastasis pattern of gastric cancer. Patients with gastric cancer peritoneal metastasis (GCPM) have a poor prognosis and respond poorly to conventional treatments. Recently, immune checkpoint blockade (ICB) has demonstrated favourable efficacy in the treatment of GCPM. Stratification of best responders and elucidation of resistance mechanisms of ICB therapies are highly important and remain major clinical challenges. Design We performed a phase II trial involving patients with GCPM treated with ICB (sintilimab) combined with chemotherapy. The samples of primary tumours, GCPMs and peripheral blood from patients were collected for single-cell sequencing to comprehensively interpret the tumour microenvironment of GCPM and its impacts on immunotherapy efficacy. Results The GCPM ecosystem coordinates a unique immunosuppressive pattern distinct from that of primary GC, which is dominated by a stroma-myeloid niche composed of SPP1+tumour-associated macrophages (TAMs) and Thrombospondin 2 (THBS2)+matrix cancer-associated fibroblasts (mCAFs). Consequently, this stroma-myeloid crosstalk is the major mediator of ICB resistance in patients with GCPM. Mechanistically, the accumulated THBS2+mCAFs facilitate the recruitment of peritoneum-specific tissue-resident macrophages and their transformation into SPP1+TAMs via the complement C3 and its receptor C3a receptor 1 (C3AR1), thereby forming a protumoral stroma-myeloid niche. Blocking the C3-C3AR1 axis disrupts the stroma-myeloid crosstalk and thereby significantly improves the benefits of ICB in in vivo models. Conclusion Our findings provide a new molecular portrait of cell compositions associated with ICB resistance in patients with GCPM and aid in the prioritisation of therapeutic candidates to potentiate immunotherapy. Data are available in a public, open access repository. Data are available on reasonable request. The sample information is listed in online supplemental table S1. The 10X genomics raw data of this study are deposited in the Genome Sequence Archive for Human database (ID: HRA009064; link: [https://ngdc.cncb.ac.cn/gsa-human/browse/HRA009064][1]). Additionally, the GEXSCOPE single-cell matrix data are deposited in the Mendeley repository (ID: jwkc5t6r55). Previously published scRNA-seq data that were reanalysed and integrated into this study are available in the Gene Expression Omnibus database under accession code GSE183904. All the data that support the findings of this study are available from the corresponding author on reasonable request. [1]: https://ngdc.cncb.ac.cn/gsa-human/browse/HRA009064)","PeriodicalId":12825,"journal":{"name":"Gut","volume":"196 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601015","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":"Puerarin alleviates atherosclerosis via the inhibition of <i>Prevotella copri</i> and its trimethylamine production.","authors":"","doi":"10.1136/gutjnl-2024-331880","DOIUrl":"10.1136/gutjnl-2024-331880","url":null,"abstract":"<p><strong>Objective: </strong>Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans.</p><p><strong>Design: </strong>The impact of PU on AS was examined in <i>ApoE</i> ^-/- mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with <i>Prevotella copri</i> (<i>P. copri</i>) were employed.</p><p><strong>Results: </strong>PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into <i>ApoE^-/-</i> mice fed HFD. Specifically, PU reduced the abundance of <i>P. copri</i>, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of <i>P. copri</i> undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of <i>P. copri</i> and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased <i>P. copri</i> levels and reduced TMAO concentrations in patients with carotid artery plaque.</p><p><strong>Conclusion: </strong>PU may provide therapeutic benefits in combating AS by targeting <i>P. copri</i> and its production of TMA.</p><p><strong>Trial registration number: </strong>ChiCTR1900022488.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1934-1943"},"PeriodicalIF":23.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081157","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":"Short-chain fatty acids in patients with severe acute pancreatitis: friend or foe?","authors":"Fons F van den Berg, Marc G Besselink, Hjalmar van Santvoort","doi":"10.1136/gutjnl-2024-332129","DOIUrl":"10.1136/gutjnl-2024-332129","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e34"},"PeriodicalIF":23.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740863","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":"Recurrent intestinal ulcers and perforations complicated with pigmentation.","authors":"Junfeng Guo, Linxi Su, Guangsheng Du, Yuyang Chen, Cheng Liu, Bing Wang, Yangfan Lv, Shiming Yang, Xia Xie","doi":"10.1136/gutjnl-2024-332057","DOIUrl":"10.1136/gutjnl-2024-332057","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1964-1983"},"PeriodicalIF":23.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989852","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":"External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.","authors":"Nicolas Pierre, Vân Anh Huynh-Thu, Dominique Baiwir, Gabriel Mazzucchelli, Maximilien Fléron, Lisette Trzpiot, Gauthier Eppe, Edwin De Pauw, David Laharie, Jack Satsangi, Peter Bossuyt, Lucine Vuitton, Sophie Vieujean, Jean-Frédéric Colombel, Marie-Alice Meuwis, Edouard Louis","doi":"10.1136/gutjnl-2024-332648","DOIUrl":"10.1136/gutjnl-2024-332648","url":null,"abstract":"<p><strong>Objective: </strong>In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).</p><p><strong>Design: </strong>In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).</p><p><strong>Results: </strong>In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively).</p><p><strong>Conclusion: </strong>In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.</p><p><strong>Trial registration number: </strong>NCT00571337 and NCT02177071.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1965-1973"},"PeriodicalIF":23.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970961","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":"Cholecystectomy following EUS-guided gallbladder drainage in patients with acute cholecystitis at high surgical risk: friend or foe?","authors":"Alberto Larghi, Roy L J van Wanrooij, Michiel Bronswijk, Giuseppe Vanella, Rastislav Kunda, Manuel Pérez-Miranda, Jeanin E Van-Hooft, Marc A Barthet, Paolo Giorgio Arcidiacono, Schalk Willem Van der Merwe","doi":"10.1136/gutjnl-2024-332273","DOIUrl":"10.1136/gutjnl-2024-332273","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e40"},"PeriodicalIF":23.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189644","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}