Gut最新文献

{"title":"Sex-based differences in prescribed medications, surgical procedures and disease-related complications in IBD","authors":"Celine Cumming, Emad Mansoor, Jaime Abraham Perez, Davide Pietropaoli, Rita Del Pinto, Theresa T Pizarro","doi":"10.1136/gutjnl-2024-332318","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332318","url":null,"abstract":"Danese et al 1 emphasise the urgency to implement advanced combination treatments (ACTs) for inflammatory bowel disease (IBD), suggesting that ACTs may be particularly effective in certain patient populations. In this context, sex as a biological variable is paramount to consider, but remains understudied in all aspects of research reporting and analyses (referred to as ‘sex-aware’ analyses2), and represents an essential element when evaluating disease prevention, intervention(s) and precision medicine. This is especially applicable to IBD since increasing evidence supports sex-based differences, including response to treatment(s), between male and female patients living with Crohn’s disease (CD) or ulcerative colitis (UC),3 4 yet specific studies to date are sparse. To this end, we sought to determine the current state of sex disparities in prescribed medications, surgical interventions and disease-related complications in IBD. Using the TriNetX platform, which allows real-time access to deidentified electronic health records of over 116 million patients, we performed a retrospective, sex-aware cohort study on 2 July 2024, implementing a previously described approach5 (validated with a positive predictive value of ≥92%).6 We identified over 359 426 patients having an index event of at least two instances of the same CD/UC diagnosis, with an added ≥2 instances of drug/therapy when considering outcomes. These patient groups were divided by sex and the resulting …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100877","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":"CD64⁺ fibroblast-targeted vilanterol and a STING agonist augment CLDN18.2 BiTEs efficacy against pancreatic cancer by reducing desmoplasia and enriching stem-like CD8⁺ T cells.","authors":"Tianxing Zhou, Xupeng Hou, Jingrui Yan, Lin Li, Yongjie Xie, Weiwei Bai, Wenna Jiang, Yiping Zou, Xueyang Li, Ziyun Liu, Zhaoyu Zhang, Bohang Xu, Guohua Mao, Yifei Wang, Song Gao, Xiuchao Wang, Tiansuo Zhao, Hongwei Wang, Hongxia Sun, Xiufeng Zhang, Jun Yu, Chongbiao Huang, Jing Liu, Jihui Hao","doi":"10.1136/gutjnl-2024-332371","DOIUrl":"10.1136/gutjnl-2024-332371","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to improve the efficacy of CLDN18.2/CD3 bispecific T-cell engagers (BiTEs) as a promising immunotherapy against pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Design: </strong>Humanised hCD34⁺/hCD3e⁺, Trp53^R172HKras^G12DPdx1-Cre (KPC), pancreas-specific Cldn18.2 knockout (KO), fibroblast-specific Fcgr1 KO and patient-derived xenograft/organoid mouse models were constructed. Flow cytometry, Masson staining, Cell Titer Glo assay, virtual drug screening, molecular docking and chromatin immunoprecipitation were conducted.</p><p><strong>Results: </strong>CLDN18.2 BiTEs effectively inhibited early tumour growth, but late-stage efficacy was significantly diminished. Mechanically, the Fc fragment of BiTEs interacted with CD64⁺ cancer-associated fibroblasts (CAFs) via activation of the SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A-α-SMA/collagen-I pathway, which enhanced desmoplasia and limited late-stage infiltration of T cells. Molecular docking analysis found that vilanterol suppressed BiTEs-induced phosphorylation of VAV2 (Y172) in CD64⁺ CAFs and weakened desmoplasia. Additionally, decreased cyclic guanosine-adenosine monophosphate synthase/stimulator of interferon genes (STING) activity reduced proliferation of TCF-1⁺PD-1⁺ stem-like CD8⁺ T cells, which limited late-stage effects of BiTEs. Finally, vilanterol and the STING agonist synergistically boosted the efficacy of BiTEs by inhibiting the activation of CD64⁺ CAFs and enriching proliferation of stem-like CD8⁺ T cells, resulting in sustained anti-tumour activity.</p><p><strong>Conclusion: </strong>Vilanterol plus the STING agonist sensitised PDAC to CLDN18.2 BiTEs and augmented efficacy as a potential novel strategy.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072602","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":"Hepatomegaly and ascites in a patient with UC","authors":"Jintong Chen, Ye Xu, Yanjun Lin, Chengdang Wang","doi":"10.1136/gutjnl-2024-333587","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333587","url":null,"abstract":"A 29-year-old Chinese man with a 6-year history of UC (Montreal classification E3) had achieved symptom remission 4 years ago after 1 year of treatment with infliximab (5 mg/kg at 0, 2 and 6 weeks, followed by every 8 weeks) combined with azathioprine (50 mg/day). He then self-switched to mesalazine (4 g/day). He returned to our hospital with severe bloody diarrhoea (over 20 bowel movements/day) for 1 week. On admission, he had a mild fever (37.8°C), tachycardia (120 bpm), pallor and pitting oedema in both lower extremities. Laboratory analysis revealed anaemia (7.5 g/dL), hypoalbuminaemia (2.8 g/dL), thrombocytosis (638 k/mm3), leucocytosis (23.71 k/mm3), elevated C reactive protein (112.3 mg/L), elevated erythrocyte sedimentation rate (55 mm/h) and mildly elevated GGT (80 U/L). Viral markers for HIV, HBV and HCV were negative. A colonoscopy revealed severe pancolitis with deep ulcers (figure 1A). Given the consideration of acute …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101947","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":"Colectomy in microscopic colitis: a rare indication","authors":"David Bergman, Anders Forss, Jiangwei Sun, Fahim Ebrahimi, Jonas F Ludvigsson","doi":"10.1136/gutjnl-2024-333505","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333505","url":null,"abstract":"We read with great interest the systematic review by Honap et al 1 and commend the authors for highlighting the elevated risk of colectomy in patients with acute severe UC. While there is ample knowledge about colectomy as a last resort treatment in UC,2 little is known about the colectomy risk in microscopic colitis (MC).3–6 As the incidence of MC has been on the rise over the past decades,7 with current incidence rates (IRs) rivalling those of UC and Crohn’s disease,8 knowledge on the risk of colectomy in patients with MC is warranted. Leveraging the nationwide Swedish ESPRESSO histopathology cohort,9 we estimated the risk of colectomy in patients with biopsy-verified MC (diagnosed 1990–2017) compared with matched reference individuals from the general population (matched by age, sex, county of residence and calendar year). Colectomy was defined as having a corresponding surgical procedure code indicating total colectomy recorded in the National Patient Register (online supplemental table S1).### Supplementary data [gutjnl-2024-333505supp001.pdf] Follow-up began on the date of MC diagnosis (any of the subtypes of collagenous colitis or lymphocytic colitis) and on the matching date for the reference individuals. Study participants were followed until 31 December 2021 for colectomy, death, emigration or a medical …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100876","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":"The Q for immune evasion in HCC: ER stress in myeloid cells","authors":"Charlotte Rennert, Maike Hofmann","doi":"10.1136/gutjnl-2024-333249","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333249","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. In most cases, HCC develops in an already perturbed liver microenvironment with pre-existing liver cirrhosis and tissue remodelling. Once a tumour nodule evolves, a complex ecosystem comprising tumour, immune, structural cells and extracellular matrix develops and forms the so-called tumour microenvironment (TME).1 This TME is shaped by distinct metabolic networks particularly driven by metabolic reprogramming of tumour cells, which supports their function, as one of the hallmarks of cancer.2 For example, in many cancer types, tumour cells mostly depend on glucose consumption for their energy supply, leading to lactate production and acidic conditions in the TME even with enough oxygen (Warburg effect).3 In addition, tumour cells also heavily rely on the amino acid glutamine (single letter code: Q) for their nucleotide biosynthesis and thus proliferation as well as for lipid biosynthesis and energy supply.4 On the other hand, similar metabolic demands also apply for highly active and proliferative immune cells such as T cells and macrophages, cell populations depending on glucose and glutamine for cell function and proliferation.5 Consequently, harsh conditions with low nutrient availability, metabolic competition and an acidic milieu in the TME emerge and impair immunosurveillance thus fuelling immune evasion.6 Yet, the exact mechanisms of how metabolic reprogramming of tumour cells results in immune evasion remain only partly understood. In Gut, Yang et al addressed this question in a preclinical setting using mouse models and employing human samples.7 The study was based on the observation, that in …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100882","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":"Letter to the editor: Autoimmune gastritis may be less susceptible to cancer development than Helicobacter pylori-related gastritis based on histological analysis","authors":"Zijin Liu, Jiayi Hong, Fang He","doi":"10.1136/gutjnl-2024-333604","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333604","url":null,"abstract":"We read with great interest the postscript by Arai et al in response to the article by Rugge et al .1 2 The authors did a great job in comparing immunohistochemical staining results of gastric cancer (GC) due to autoimmune gastritis (AIG) and H. pylori infection. They claimed that AIG may be less susceptible to cancer development than H. pylori -related gastritis; however, a few concerns need to be addressed. Firstly, the authors found that the dysplastic transition (TROP2) score of AIG non-cancerous lesions …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100880","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":"Is mailed outreach and patient navigation a perfect solution to improve HCC screening?","authors":"Iuliana Pompilia Radu","doi":"10.1136/gutjnl-2024-332920","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332920","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a significant global health problem, and its incidence is expected to exceed 1 million new HCC annually by 2025.1 The reported 3-year survival rate for advanced-stage HCC is less than 17%, while 70% of patients diagnosed with early-stage HCC can achieve 5-year survival.2 Despite well-established guidelines and the clear benefits of early detection, the meta-analysis results (29 papers, 1 18 799 patients) showed that only 24% of individuals at risk for developing HCC were screened.3 Efforts to surmount barriers at patient, provider and healthcare levels have shown a minimal screening rate increase over time.3 4 One of the reasons for the disappointing results might be the fact that authors focused on individual barriers, rather than considering the screening failure the result of the interplay of different factors. Additionally, the published studies have the following limitations, detailed reasons for screening failure are missing, the majority of the studies are done in single centre and the results generalisability is not possible, the definition of HCC screening differs per study, short follow-up periods.2 3 Singal et al have to be commended for their work published recently in Gut .5 The authors conducted a multicentre (three centres) randomised clinical trial between April …","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045459","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":"Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms","authors":"Maria Manuela Estevinho, Vishal Midya, Shirley Cohen-Mekelburg, Kristine Højgaard Allin, Mathurin Fumery, Salome Pinho, Jean-Frederic Colombel, Manasi Agrawal","doi":"10.1136/gutjnl-2024-332523","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332523","url":null,"abstract":"Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn’s disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":24.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045460","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":"Artificial intelligence applied to 'omics data in liver disease: towards a personalised approach for diagnosis, prognosis and treatment.","authors":"Soumita Ghosh, Xun Zhao, Mouaid Alim, Michael Brudno, Mamatha Bhat","doi":"10.1136/gutjnl-2023-331740","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-331740","url":null,"abstract":"<p><p>Advancements in omics technologies and artificial intelligence (AI) methodologies are fuelling our progress towards personalised diagnosis, prognosis and treatment strategies in hepatology. This review provides a comprehensive overview of the current landscape of AI methods used for analysis of omics data in liver diseases. We present an overview of the prevalence of different omics levels across various liver diseases, as well as categorise the AI methodology used across the studies. Specifically, we highlight the predominance of transcriptomic and genomic profiling and the relatively sparse exploration of other levels such as the proteome and methylome, which represent untapped potential for novel insights. Publicly available database initiatives such as The Cancer Genome Atlas and The International Cancer Genome Consortium have paved the way for advancements in the diagnosis and treatment of hepatocellular carcinoma. However, the same availability of large omics datasets remains limited for other liver diseases. Furthermore, the application of sophisticated AI methods to handle the complexities of multiomics datasets requires substantial data to train and validate the models and faces challenges in achieving bias-free results with clinical utility. Strategies to address the paucity of data and capitalise on opportunities are discussed. Given the substantial global burden of chronic liver diseases, it is imperative that multicentre collaborations be established to generate large-scale omics data for early disease recognition and intervention. Exploring advanced AI methods is also necessary to maximise the potential of these datasets and improve early detection and personalised treatment strategies.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035653","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":"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":"https://doi.org/10.1136/gutjnl-2024-332971","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":null,"pages":null},"PeriodicalIF":23.0,"publicationDate":"2024-08-22","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}