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Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma Gut (IF 24.5) Pub Date : 2024-05-13 Jun Wen, Xiang Zhang, Chi Chun Wong, Yating Zhang, Yasi Pan, Yunfei Zhou, Alvin Ho-Kwan Cheung, Yali Liu, Fenfen Ji, Xing Kang, Dabin Liu, Jun Yu
Objective Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear. Design We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce
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Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice Gut (IF 24.5) Pub Date : 2024-05-13 Paola Paone, Dimitris Latousakis, Romano Terrasi, Didier Vertommen, Ching Jian, Valentina Borlandelli, Francesco Suriano, Malin E V Johansson, Anthony Puel, Caroline Bouzin, Nathalie M Delzenne, Anne Salonen, Nathalie Juge, Bogdan I Florea, Giulio G Muccioli, Herman Overkleeft, Matthias Van Hul, Patrice D Cani
Objective To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2’FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota
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Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury Gut (IF 24.5) Pub Date : 2024-05-09 Yang Yang, Long Xu, Constance Atkins, Lily Kuhlman, Jie Zhao, Jong-Min Jeong, Yankai Wen, Nicolas Moreno, Kang Ho Kim, Yu A An, Fenfen Wang, Steve Bynon, Vincenzo Villani, Bin Gao, Frank Brombacher, Raymond Harris, Holger K Eltzschig, Elizabeth Jacobsen, Cynthia Ju
Objective Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. Design Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed
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Landscape of the gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health Gut (IF 24.5) Pub Date : 2024-05-09 Yuanqing Fu, Wanglong Gou, Ping Wu, Yuwei Lai, Xinxiu Liang, Ke Zhang, Menglei Shuai, Jun Tang, Zelei Miao, Jieteng Chen, Jiaying Yuan, Bin Zhao, Yunhaonan Yang, Xiaojuan Liu, Yayi Hu, An Pan, Xiong-Fei Pan, Ju-Sheng Zheng
Objective The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. Design Based on a prospective birth cohort in central China (2017 to
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Diagnostic dilemma: sudden onset of multiple skin lesions in a patient with intestinal disease Gut (IF 24.5) Pub Date : 2024-05-09 Cong Dai, Yu-hong Huang
The patient was a 36-year-old man, who had a 4-year history of ulcerative colitis (UC), for which he had received mesalazine, oral prednisolone and infliximab, neither of which had any long-lasting therapeutic benefit. This patient was admitted to our hospital with skin lesions, abdominal pain and diarrhoea. Two types of skin lesions were evident. First, one well-demarcated superficial ulcer, covered
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Selective decontamination of the digestive tract in critically ill children: fighting fire with fire or burning down the house? Gut (IF 24.5) Pub Date : 2024-06-01 Debby Bogaert, Willem van Schaik
The microbial ecosystem of the human gut (‘the gut microbiome’) plays an important role in human health through a variety of mechanisms, including the degradation of complex carbohydrates, the production of vitamins and other beneficial compounds and by providing a barrier to invading pathogens.1 The gut can also be the source of pathobionts, including the Gram-negatives Escherichia coli , Klebsiella
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Dietary fibre (and animal products) modulate the association between tryptophan intake, gut microbiota and type 2 diabetes: but how? Gut (IF 24.5) Pub Date : 2024-06-01 Lin Shi, Rikard Landberg
There is an increased interest in the interplay among diet, gut microbiota and health. Studies have often investigated the influence of diets, foods and dietary components on gut microbiota or whether microbiota can modify the effect of dietary interventions and the role of such modifications on health outcomes.1 This has been fueled by promising results emerging from large landmark studies pinpointing
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Antiobesity interventions: options, evidence and value Gut (IF 24.5) Pub Date : 2024-06-01 Elena B Elkin, Chin Hur
Adults with obesity have more choices than ever before of therapies that reduce body mass index (BMI) and consequently improve related chronic health conditions. Bariatric procedures are among the most well-studied options with the longest follow-up. Despite achieving the greatest reductions in BMI and rates of diabetes remission, uptake of bariatric surgery remains low. Endoscopic sleeve gastroplasty
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Enhancing the opportunities for cholangiocarcinoma precision therapy Gut (IF 24.5) Pub Date : 2024-06-01 Reka Toth, Paul J Brindley, Javier Vaquero
Cholangiocarcinoma (CCA), the second most prevalent liver cancer, encompasses a heterogenous group of bile duct malignancies. It predominantly arises from the epithelial cells lining the bile ducts termed cholangiocytes. Most CCA are highly desmoplastic adenocarcinomas, enmeshed in a tumour immune microenvironment. It exhibits a poor prognosis owing to its invasiveness and therapeutic resistance. Based
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Targeting metalloproteases is a promising strategy to enhance immunotherapy responses by overcoming immune exclusion in hepatocellular carcinoma Gut (IF 24.5) Pub Date : 2024-06-01 Marina Barcena-Varela, Pedro Berraondo
The advent of immune checkpoint inhibitors, particularly monoclonal antibodies (mAbs) that target the programmed cell death protein 1 (PD-1) or its ligand (PD-L1), has revolutionised cancer treatment across various malignancies. Despite this groundbreaking progress, a considerable cohort of patients fails to derive benefit from anti-PD(L)1 mAb therapy due to primary and secondary resistance mechanisms
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Impact of power consumption and power saving for GI endoscopy (power on study) on reducing CO2 emissions Gut (IF 24.5) Pub Date : 2024-06-01 Anna Fichtl, Veronika Tacheva, Niklas Sturm, Karim Hamesch, Doerte Wichmann, Benjamin Mayer, Martin Müller, Martin Wagner, Thomas Seufferlein, Benjamin M Walter
Endoscopy is among the top three contributors to CO2 emissions in hospitals, with power consumption being a key factor that can be directly addressed. Our multicentre study measured power consumption during endoscopic procedures, offering easily implementable approaches for energy conservation (figure 1). Comparing a 30-day period with special energy-saving measures to a baseline period, we observed
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National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett’s oesophagus and stage I oesophageal adenocarcinoma Gut (IF 24.5) Pub Date : 2024-06-01 Massimiliano di Pietro, Nigel J Trudgill, Melina Vasileiou, Gaius Longcroft-Wheaton, Alexander W Phillips, James Gossage, Philip V Kaye, Kieran G Foley, Tom Crosby, Sophie Nelson, Helen Griffiths, Muksitur Rahman, Gill Ritchie, Amy Crisp, Stephen Deed, John N Primrose
Barrett’s oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett’s oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett’s oesophagus to cancer occurs via an intermediate stage, known as dysplasia
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Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study) Gut (IF 24.5) Pub Date : 2024-06-01 Iain Robert Louis Kean, John A Clark, Zhenguang Zhang, Esther Daubney, Deborah White, Paloma Ferrando-Vivas, Gema Milla, Brian Cuthbertson, John Pappachan, Nigel Klein, Paul Mouncey, Kathy Rowan, John Myburgh, Theodore Gouliouris, Stephen Baker, Julian Parkhill, Nazima Pathan, ARCTIC research team
Objective Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced infection control compared with conventional infection control. Design We conducted shotgun
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Association of healthy lifestyle behaviours with incident irritable bowel syndrome: a large population-based prospective cohort study Gut (IF 24.5) Pub Date : 2024-06-01 Fai Fai Ho, Hui Sun, Hong Zheng, David C N Wong, Yin-Yan Gao, Chen Mao, Yin Ting Cheung, Chun Sing Lam, Maggie H Wang, Irene Xin-Yin Wu, Justin C Y Wu, Vincent C H Chung
Objectives To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS). Design Population-based prospective cohort study. Setting The UK Biobank. Participants 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022. Main exposure The five healthy lifestyle behaviours studied
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Genetic and transcriptomic landscape of colonic diverticulosis Gut (IF 24.5) Pub Date : 2024-06-01 Jungkyun Seo, Hongwei Liu, Kristin Young, Xinruo Zhang, Temitope O Keku, Corbin D Jones, Kari E North, Robert S Sandler, Anne F Peery
Objective Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case–control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders
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A mucus production programme promotes classical pancreatic ductal adenocarcinoma Gut (IF 24.5) Pub Date : 2024-06-01 Claudia Tonelli, Georgi N Yordanov, Yuan Hao, Astrid Deschênes, Juliene Hinds, Pascal Belleau, Olaf Klingbeil, Erin Brosnan, Abhishek Doshi, Youngkyu Park, Ralph H Hruban, Christopher R Vakoc, Alexander Dobin, Jonathan Preall, David A Tuveson
Objective The optimal therapeutic response in cancer patients is highly dependent upon the differentiation state of their tumours. Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer that harbours distinct phenotypic subtypes with preferential sensitivities to standard therapies. This study aimed to investigate intratumour heterogeneity and plasticity of cancer cell states in PDA in order to
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Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age Gut (IF 24.5) Pub Date : 2024-06-01 Tsuyoshi Hamada, Hiroki Oyama, Ataru Igarashi, Yoshikuni Kawaguchi, Mihye Lee, Hiroki Matsui, Nobuaki Michihata, Yousuke Nakai, Kiyohide Fushimi, Hideo Yasunaga, Mitsuhiro Fujishiro
Objective Current guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at different ages and define the optimal age to stop surveillance. Design We constructed a Markov model with a lifetime horizon to
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Integrative multiomics enhancer activity profiling identifies therapeutic vulnerabilities in cholangiocarcinoma of different etiologies Gut (IF 24.5) Pub Date : 2024-06-01 Jing Han Hong, Chern Han Yong, Hong Lee Heng, Jason Yongsheng Chan, Mai Chan Lau, Jianfeng Chen, Jing Yi Lee, Abner Herbert Lim, Zhimei Li, Peiyong Guan, Pek Lim Chu, Arnoud Boot, Sheng Rong Ng, Xiaosai Yao, Felicia Yu Ting Wee, Jeffrey Chun Tatt Lim, Wei Liu, Peili Wang, Rong Xiao, Xian Zeng, Yichen Sun, Joanna Koh, Xiu Yi Kwek, Cedric Chuan Young Ng, Poramate Klanrit, Yaojun Zhang, Jiaming Lai, David
Objectives Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA. Our aim is to identify
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Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8+ T cell-mediated antitumour immunity and improves anti-PD-1 efficacy Gut (IF 24.5) Pub Date : 2024-06-01 Ning Cai, Kun Cheng, Yue Ma, Sha Liu, Ran Tao, Yani Li, Danfeng Li, Bin Guo, Wenlong Jia, Huifang Liang, Jianping Zhao, Limin Xia, Ze-yang Ding, Jinhong Chen, Wanguang Zhang
Objective The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. Design RNA sequencing was performed to identify the key downstream genes of CTNNB1
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Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis Gut (IF 24.5) Pub Date : 2024-06-01 Hashem El-Serag, Fasiha Kanwal, Jing Ning, Hannah Powell, Saira Khaderi, Amit G Singal, Sumeet Asrani, Jorge A Marrero, Christopher I Amos, Aaron P Thrift, Michelle Luster, Abeer Alsarraj, Luis Olivares, Darlene Skapura, Jenny Deng, Emad Salem, Omar Najjar, Xian Yu, Hao Duong, Michael E Scheurer, Christie M Ballantyne, Salma Kaochar
Background Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. Methods We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the
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PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans Gut (IF 24.5) Pub Date : 2024-06-01 Andreas Geier, Jonas Trost, Ke Wang, Clemens Schmid, Marcin Krawczyk, Stephan Schiffels
Objective Fat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and how this variant evolved in humans has not been studied to date. Design Here we analyse ancient DNA to track the history of this allele throughout human history
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Recent advances in the prevention and treatment of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and the role of biomarkers Gut (IF 24.5) Pub Date : 2024-06-01 Jonel Trebicka, Ruben Hernaez, Debbie Lindsay Shawcross, Alexander L Gerbes
The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation
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Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): a systematic review Gut (IF 24.5) Pub Date : 2024-06-01 Rita WY Ng, Priyanga Dharmaratne, Sunny Wong, Peter Hawkey, Paul Chan, Margaret Ip
We read with interest the recent work by Haifer et al ,1 which highlighted the importance of donor selection in determining the clinical efficacy of treating ulcerative colitis (UC) using faecal microbiota transplantation (FMT), with one donor having 100% efficacy compared with a second donor (36% efficacy). Considering the impact of COVID-19 pandemic on FMT, updated guidance including patient selection
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Basal levels of microbiota-driven subclinical inflammation are associated with anastomotic leak in patients with colorectal cancer Gut (IF 24.5) Pub Date : 2024-06-01 Roy Hajjar, Gabriela Fragoso, Manon Oliero, Ahmed Amine Alaoui, Annie Calvé, Hervé Vennin Rendos, Thibault Cuisiniere, Nassima Taleb, Sophie Thérien, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Frank Schwenter, Ramses Wassef, Richard Ratelle, Eric Debroux, Carole Richard, Manuela M Santos
In our recent publication in Gut ,1 we showed that preoperative gut microbiota was causally linked to the development of anastomotic leak (AL) after colorectal cancer (CRC) surgery. AL results from impaired healing of the colonic wound and leads to the leakage of intestinal content into the abdomen. Using faecal microbiota transplantation (FMT) in mice with faecal samples from 18 patients with CRC
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Connecting inflammatory bowel and neurodegenerative diseases: microRNAs as a shared therapeutic intervention Gut (IF 24.5) Pub Date : 2024-06-01 Tanya M Monaghan, Aslihan Ugun-Klusek, Mattea Finelli, Pratik Gurnani, Lisa Chakrabarti, Dina Kao, Cameron Alexander, Christos Polytarchou
We read with interest the recent article by Zhang et al that reported a higher risk of developing dementia in patients with inflammatory bowel disease (IBD), with the largest increase in Alzheimer’s disease (AD).1 These findings align with a growing body of evidence which links gut inflammation or leaky gut with neurodegeneration. Lee et al discussed the known shared pathophysiological links between
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Multiple and diverse consequences of inhibiting gastric acid secretion: remembering the bicentenary of William Prout’s discovery Gut (IF 24.5) Pub Date : 2024-06-01 D Mark Pritchard, Robert Logan
We have read with interest several recent papers in Gut that have reported novel insights about the potential consequences of reduced gastric acid secretion. These include reports that proton pump inhibitor (PPI) use increases the risks of developing diverse diseases including gastric adenocarcinoma1 2 and severe COVID-19 infection.3 An intriguing recent paper has also shown that pathological suppression
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Autoimmune gastritis may be less susceptible to cancer development than Helicobacter pylori-related gastritis based on histological analysis Gut (IF 24.5) Pub Date : 2024-06-01 Junya Arai, Ryota Niikura, Yoku Hayakawa, Yoshihiro Hirata, Tetsuo Ushiku, Mitsuhiro Fujishiro
We read with great interest the recent publication by Rugge et al ,1 in which the authors conducted a cohort study to evaluate the association between autoimmune gastritis (AIG) and gastric cancer (GC). No excess risk of gastric or other malignancies was observed over a cumulative follow-up time of 10 541 person-years, except for (marginally significant) thyroid cancer (standardised incidence ratio=3
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Hypophosphataemia following ferric carboxymaltose and ferric derisomaltose: case closed, but questions remain Gut (IF 24.5) Pub Date : 2024-06-01 Ayushi Chauhan, Sarah Lucas, Mayur Garg
We read with interest the paper by Zoller et al comparing the rate of hypophosphataemia with ferric carboxymaltose (FCM) versus ferric derisomaltose (FDI) infusions in patients with inflammatory bowel disease (IBD).1 The higher rate of hypophosphataemia following FCM replicates findings of other studies in patients with and without IBD.2 3 Iron deficiency anaemia is associated with reduced quality
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Short versus long endoscopic myotomy: how short is too short and how long is too long? Gut (IF 24.5) Pub Date : 2024-06-01 Zaheer Nabi, D Nageshwar Reddy
We read with great interest the study by Familiari et al entitled ‘Long versus short peroral endoscopic myotomy (POEM) for the treatment of achalasia: results of a non-inferiority randomised controlled trial’.1 Short myotomy was non-inferior to long myotomy with regard to clinical success at 2 years with the added advantage of reduced procedure time. Gastro-oesophageal reflux was similar in both the
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Impact of acute alcohol consumption on circulating microbiome in asymptomatic alcohol-related liver disease Gut (IF 24.5) Pub Date : 2024-06-01 Mads Israelsen, Camila Alvarez-Silva, Bjørn Stæhr Madsen, Camilla Dalby Hansen, Nikolaj Christian Torp, Stine Johansen, Johanne Kragh Hansen, Katrine Prier Lindvig, Jeanlouis Insonere, Virginie Riviere, Helene Bæk Juel, Asker Brejnrod, Lars Juhl Jensen, Maja Thiele, Benjamin Lelouvier, Torben Hansen, Manimozhiyan Arumugam, Aleksander Krag, MicrobLiver consortium
We read with great interest the review by Tranah et al ,1 which highlighted that alcohol consumption, alterations in the gut microbiome and impairment of the gut barrier function were linked to the development of alcohol-related liver disease (ALD). However, the impact of acute alcohol consumption on the circulating microbiome in patients with ALD remains unclear. To address this gap, we conducted
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Rare cause of obstructive jaundice Gut (IF 24.5) Pub Date : 2024-06-01 Sota Nakagami, Toshihiro Morita, Shujiro Yazumi
An 85-year-old woman, with a high-grade fever (40°C) and abdominal pain, was referred to our hospital. Blood examination revealed an elevated white blood cell count (25.8×10⁹/L) and elevated levels of C reactive protein (8.54 mg/dL), alanine aminotransferase (95 IU/L), aspartate transaminase (138 IU/L), alkaline phosphatase (804 IU/L), gamma-glutamyl transpeptidase (703 IU/L), and total (5.0 mg/dL)
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Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer Gut (IF 24.5) Pub Date : 2024-05-06 Huisi He, Shuzhen Chen, Yong Yu, Zhecai Fan, Youwen Qian, Yaping Dong, Yuting Song, Caiming Zhong, Xiaojuan Sun, Qiqi Cao, Shiyao Li, Weihan Huang, Wenxin Li, Mingzhu Zhuang, Jinxian Yang, Xianming Wang, Jiaqian Wang, Dongfang Wu, Hongyang Wang, Wen Wen
Objective Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. Design We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings
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Perplexing case of abdominal pain with eosinophilia and fasciitis Gut (IF 24.5) Pub Date : 2024-05-06 Robert Sean O'Neill, Logan Gardner, Anthony Kelleher, Roger Pamphlett, Laila Girgis, Alina Stoita
A 34-year-old man presented to our institution for review with recurrent abdominal pain, constipation, lethargy, fevers and episodic migratory soft tissue severe cellulitis of the limbs after minimal exercise. This was on a background of a diagnosis of eosinophilic enterocolitis at the age of 10 when due to recurrent abdominal pain, endoscopy was performed with biopsies showing eosinophilic infiltration
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Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target Gut (IF 24.5) Pub Date : 2024-05-02 Alexander C Ford, Heidi M Staudacher, Nicholas J Talley
Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric
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Concerns about instrumental variable selection for biological effect versus uptake of proton pump inhibitors in Mendelian randomisation analysis Gut (IF 24.5) Pub Date : 2024-05-02 Shuai Yuan, Susanna C Larsson, Dipender Gill, Stephen Burgess
A recent population-based cohort study found an association between proton pump inhibitor (PPI) prescription and risk of inflammatory bowel disease which they attributed to protopathic bias (ie, the drug was prescribed in response to initial disease symptoms) rather than a causal effect of PPI usage.1 In a following Mendelian randomisation (MR) study, An et al selected genetic variants associated with
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TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism Gut (IF 24.5) Pub Date : 2024-05-02 Armando Andres Roca Suarez, Marie-Laure Plissonnier, Xavier Grand, Maud Michelet, Guillaume Giraud, Maria Saez-Palma, Anaëlle Dubois, Sarah Heintz, Audrey Diederichs, Nicolaas Van Renne, Thomas Vanwolleghem, Stephane Daffis, Li Li, Nikita Kolhatkar, Yao-Chun Hsu, Jeffrey J Wallin, Audrey H Lau, Simon P Fletcher, Michel Rivoire, Massimo Levrero, Barbara Testoni, Fabien Zoulim
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
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Diagnostic yield from symptomatic gastroscopy in the UK: British Society of Gastroenterology analysis using data from the National Endoscopy Database Gut (IF 24.5) Pub Date : 2024-05-02 David Robert Beaton, Linda Sharp, Liya Lu, Nigel J Trudgill, Mo Thoufeeq, Brian D Nicholson, Peter Rogers, James Docherty, Anna Jenkins, Allan John Morris, Thomas Rösch, Matthew D Rutter
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
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Alzheimer’s disease-related presenilins are key to intestinal epithelial cell function and gut immune homoeostasis Gut (IF 24.5) Pub Date : 2024-04-29 Lena Erkert, Reyes Gamez-Belmonte, Melanie Kabisch, Lena Schödel, Jay V Patankar, Miguel Gonzalez-Acera, Mousumi Mahapatro, Li-Li Bao, Christina Plattner, Anja A Kühl, Jie Shen, Lutgarde Serneels, Bart De Strooper, TRR241 IBDome Consortium, Markus F Neurath, Stefan Wirtz, Christoph Becker
Objective Mutations in presenilin genes are the major cause of Alzheimer’s disease. However, little is known about their expression and function in the gut. In this study, we identify the presenilins Psen1 and Psen2 as key molecules that maintain intestinal homoeostasis. Design Human inflammatory bowel disease (IBD) and control samples were analysed for Psen1 expression. Newly generated intestinal
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British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults Gut (IF 24.5) Pub Date : 2024-04-29 Abid Suddle, Helen Reeves, Richard Hubner, Aileen Marshall, Ian Rowe, Dina Tiniakos, Stefan Hubscher, Mark Callaway, Dinesh Sharma, Teik Choon See, Maria Hawkins, Suzanne Ford-Dunn, Sarah Selemani, Tim Meyer
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
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Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis Gut (IF 24.5) Pub Date : 2024-04-25 Jinxia Liu, Jane MacNaughtan, Annarein J C Kerbert, Theo Portlock, Javier Martínez Gonzalez, Yi Jin, Frederick Clasen, Abeba Habtesion, Huoyan Ji, Qin Jin, Alexandra Phillips, Francesco De Chiara, Ganesh Ingavle, Cesar Jimenez, Giacomo Zaccherini, Katherine Husi, Miguel Angel Rodriguez Gandia, Paul Cordero, Junpei Soeda, Lynda McConaghy, Jude Oben, Karen Church, Jia V Li, Haifeng Wu, Aarti Jalan, Pere
Objective Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. Design Performance of
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Targeting hepatic stellate cells to combat liver fibrosis: where do we stand? Gut (IF 24.5) Pub Date : 2024-04-25 Katja Breitkopf-Heinlein, Maria Luz Martinez-Chantar
Liver fibrosis is characterised by the excessive deposition of extracellular matrix (ECM) in response to chronic and sustained liver damage, triggering a prolonged wound healing response. The accumulation of ECM proteins disrupts the normal hepatic architecture, resulting in the development of fibrotic scars and nodules of regenerated hepatocytes, ultimately progressing to cirrhosis. While the acute
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Underdiagnosed cause of gastrointestinal bleeding Gut (IF 24.5) Pub Date : 2024-04-25 Xin-Yue Ma, Yun Cui, Jing-Yuan Fang, Danfeng Sun
A 16-year-old Chinese woman presented with a 7-year history of recurrent abdominal pain, haematemesis, melena and anaemia. Her previous oesophagogastroduodenoscopies (OGD) revealed nodular gastritis with discontinuous mucosal folds of the corpus. Gastric mucosa bleeding was described once and sclerosant injection together with titanium clip were performed. Biopsies were taken multiple times which indicated
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Inappropriate use of proton pump inhibitors in clinical practice globally: a systematic review and meta-analysis Gut (IF 24.5) Pub Date : 2024-04-26 Amit K Dutta, Vishal Sharma, Abhinav Jain, Anshuman Elhence, Manas K Panigrahi, Srikant Mohta, Richard Kirubakaran, Mathew Philip, Mahesh Goenka, Shobna Bhatia, Usha Dutta, D Nageshwar Reddy, Rakesh Kochhar, Govind K Makharia
We read with interest the population-based cohort studies by Abrahami et al on proton pump inhibitors (PPI) and the risk of gastric and colon cancers.1 2 PPI are used at all levels of healthcare and across different subspecialties for various indications.3 4 A recent systematic review on the global trends and practices of PPI recognised 28 million PPI users from 23 countries, suggesting that 23.4%
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Novel transcriptomic panel identifies histologically active oesinophilic oesophagitis Gut (IF 24.5) Pub Date : 2024-04-26 Emilie Gueguen, Yasser Morsy, Céline Mamie, Alain Schoepfer, Catherine Saner, Luc Biedermann, Alex Straumann, Andrea Kreienbühl, Swiss EoE Cohort Study Group, Michael Scharl, Marcin Wawrzyniak
Background and aims Oesinophilic oesophagitis (EoE) is characterised by symptoms of oesophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration
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Axon guidance cue SEMA3A promotes the aggressive phenotype of basal-like PDAC Gut (IF 24.5) Pub Date : 2024-04-26 Francesca Lupo, Francesco Pezzini, Davide Pasini, Elena Fiorini, Annalisa Adamo, Lisa Veghini, Michele Bevere, Cristina Frusteri, Pietro Delfino, Sabrina D'agosto, Silvia Andreani, Geny Piro, Antonia Malinova, Tian Wang, Francesco De Sanctis, Rita Teresa Lawlor, Chang-il Hwang, Carmine Carbone, Ivano Amelio, Peter Bailey, Vincenzo Bronte, David Tuveson, Aldo Scarpa, Stefano Ugel, Vincenzo Corbo
Objective The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression. Design We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients’
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Correction: Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers Gut (IF 24.5) Pub Date : 2024-04-23 BMJ Publishing Group Ltd and British Society of Gastroenterology
Carotenuto P, Fassan M, Pandolfo R, et al . Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut 2017;66:1268-1277. The legend of Figure …
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Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis Gut (IF 24.5) Pub Date : 2024-04-23 Stefano Crippa, Giovanni Marchegiani, Giulio Belfiori, Paola Vittoria Maria Rancoita, Tommaso Pollini, Anna Burelli, Laura Apadula, Maria Giovanna Scarale, Davide Socci, Marco Biancotto, Giuseppe Vanella, Paolo Giorgio Arcidiacono, Gabriele Capurso, Roberto Salvia, Massimo Falconi
Objective Cost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies. Design Retrospective analysis of 926 presumed BD-IPMNs lacking worrisome features (WFs)/high-risk stigmata (HRS) under surveillance. Charlson Comorbidity
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Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett’s oesophagus patients Gut (IF 24.5) Pub Date : 2024-04-19 Qiuyang Zhang, Kerry B Dunbar, Robert D Odze, Agoston T Agoston, Xuan Wang, Tianhong Su, Anh D Nguyen, Xi Zhang, Stuart Jon Spechler, Rhonda F Souza
Introduction Epithelial-mesenchymal plasticity (EMP), the process through which epithelial cells acquire mesenchymal features, is needed for wound repair but also might contribute to cancer initiation. Earlier, in vitro studies showed that Barrett’s cells exposed to acidic bile salt solutions (ABS) develop EMP. Now, we have (1) induced reflux oesophagitis in Barrett’s oesophagus (BO) patients by stopping
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Mast cells and histamine in cholangiocarcinoma: exploring overlooked avenues for enhanced patient management Gut (IF 24.5) Pub Date : 2024-04-18 Luca Fabris, Jonathan Pol
In the realm of cholangiocarcinoma (CCA), a malignancy often presenting with biliary stenosis, the clinical need to re-establish duct patency offers a unique opportunity to profile bile content, facilitating the identification of potential diagnostic and prognostic biomarkers. Various studies have explored the significance of biochemically distinct molecules in the bile of patients with CCA by comparing
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Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer Gut (IF 24.5) Pub Date : 2024-04-15 Feifei Zhang, Varun Sahu, Ke Peng, Yichen Wang, Tianxia Li, Pratyusha Bala, Daulet Aitymbayev, Pranshu Sahgal, Antje Schaefer, Channing J Der, Sandra Ryeom, Sam Yoon, Nilay Sethi, Adam J Bass, Haisheng Zhang
Objective Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of
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Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients Gut (IF 24.5) Pub Date : 2024-04-15 Christina S Thornton, Barbara J Waddell, Stephen E Congly, Julianna Svishchuk, Ranjani Somayaji, Linda Fatovich, Debra Isaac, Karen Doucette, Kevin Fonseca, Steven J Drews, Jamie Borlang, Carla Osiowy, Michael D Parkins
Objectives In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. Design All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was
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EUS-guided gallbladder drainage in acute cholecystitis: response to letter to the editor Gut (IF 24.5) Pub Date : 2024-04-12 Ji Young Bang, Juan Pablo Arnoletti, Andrew Wagner, Shyam Varadarajulu
We thank the authors for their interest in our report on endoscopic ultrasound-guided gallbladder drainage (EUS-GBD).1 Management of gallbladder disease is not within the sole domain of gastroenterologists. It includes surgeons and interventional radiologists. When guidelines are developed without multidisciplinary consensus, problems can occur as reported in our series.2 The distinction between never-surgery
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The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines Gut (IF 24.5) Pub Date : 2024-04-12 Benjamin H Mullish, Blair Merrick, Mohammed Nabil Quraishi, Aggie Bak, Christopher A Green, David J Moore, Robert J Porter, Ngozi T Elumogo, Jonathan P Segal, Naveen Sharma, Belinda Marsh, Graziella Kontkowski, Susan E Manzoor, Ailsa L Hart, Christopher Settle, Josbert J Keller, Peter Hawkey, Tariq H Iqbal, Simon D Goldenberg, Horace R T Williams
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition
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Lactococcus lactis HkyuLL 10 suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase Gut (IF 24.5) Pub Date : 2024-04-10 Anthony Chin Yang Su, Xiao Ding, Harry Cheuk Hay Lau, Xing Kang, Qing Li, Xueliang Wang, Yali Liu, Lanping Jiang, Yinghong Lu, Weixin Liu, Yanqiang Ding, Alvin Ho-Kwan Cheung, Ka Fai To, Jun Yu
Objective Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). Design L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis
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Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease Gut (IF 24.5) Pub Date : 2024-04-05 Ruben Y Gabriëls, Anne M van der Waaij, Matthijs D Linssen, Michael Dobosz, Pia Volkmer, Sumreen Jalal, Dominic Robinson, Marcela A Hermoso, Marjolijn N Lub-de Hooge, Eleonora A M Festen, Gursah Kats-Ugurlu, Gerard Dijkstra, Wouter B Nagengast
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
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Enhanced efficiency of the ‘family index-case method’: why and when? Gut (IF 24.5) Pub Date : 2024-04-03 Yifan Qiu, Wenbo Zhu, Shihan Xu, Jiayue Wang, Chanjuan Wang, Geliang Yang, Zhaoshen Li, Huiyun Zhu, Xianzhu Zhou, Yiqi Du
With great interest, we carefully read the article by Lei et al .1 The authors introduced a novel ‘family index-case method’ to efficiently screen for and eradicate Helicobacter pylori ( H. pylori ) infections by reaching out to the family members of individuals who tested positive. However, the article predominantly focused on detailing the methodology of the ‘family index-case method’, rather than
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Gut microbial metabolism of 5-aminosalicylic acid in inflammatory bowel disease Gut (IF 24.5) Pub Date : 2024-04-03 Naomi Karmi, Shiqiang Sun, Eleonora A M Festen, Arnau Vich Vila, Ranko Gacesa, Rinse K Weersma
The effect of the gut microbiome on the bioavailability and efficacy of orally administered drugs is of considerable importance for personalised medicine.1 We, therefore, read with great interest the ‘GI highlights from the literature’ focussing on gut microbial metabolism of 5-aminosalicylic acid (5-ASA) in inflammatory bowel disease (IBD), originally published in the journal Nature Medicine .2 3
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Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study Gut (IF 24.5) Pub Date : 2024-04-03 Xianhua Mao, Ka Shing Cheung, Jing-Tong Tan, Lung-Yi Mak, Chi-Ho Lee, Chi-Leung Chiang, Ho Ming Cheng, Rex Wan-Hin Hui, Man Fung Yuen, Wai Keung Leung, Wai-Kay Seto
Objective Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. Design Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity
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Refining definitions of Barrett’s oesophagus to improve clinical resource utilisation Gut (IF 24.5) Pub Date : 2024-05-01 Matthew D Stachler, Qurat Ul Ain
Oesophageal adenocarcinoma (OAC) is a devastating disease with an average 5-year survival of around 15%.1 Moreover, rates of OAC have increased substantially in recent decades, adding greatly to the clinical and economic burden of this disease.2 OAC arises out of a metaplastic precursor in which the normal squamous lining of the oesophagus is replaced with columnar, mucin-secreting cells. This is termed
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CD39 deletion in TCR-engineered T cells enhances antitumour immunity Gut (IF 24.5) Pub Date : 2024-05-01 Alexander K Tsai, Ingunn M Stromnes
Tumour-reactive T cells infiltrating solid tumours are often rendered exhausted, a cell differentiation state characterised by upregulation of inhibitory receptors and reduced effector function. The process of T-cell exhaustion permits cancer progression and interferes with immunotherapy response. Efforts to overcome T-cell exhaustion, such as immune checkpoint blockade (ICB), can lead to remarkable