Gut

Barrett’s oesophagus (BE) is a known precursor to oesophageal adenocarcinoma (OAC) but current clinical data have not been consolidated to address whether BE is the origin of all incident OAC, which would reinforce evidence for BE screening efforts. We aimed to answer whether all expected prevalent BE, diagnosed and undiagnosed, could account for all incident OACs in the US cancer registry data.

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Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world

Daniel Sifrim, Sabine Roman, Edoardo Savarino, Serhat Bor, Albert J Bredenoord, Donald Castell, Michele Cicala, Nicola de Bortoli, Marzio Frazzoni, Sutep Gonlachanvit, Katsuhiko Iwakiri, Osamu Kawamura, Anne Krarup, Yeong Yeh Lee, Chai Soon Ngiu, Eugene Ndebia, Tanisa Patcharatraku, Ans Pauwels, Julio Pérez de la Serna, Rosa Ramos, Jose Maria Remes-Troche, Mentore Ribolsi, Alastair Sammon, Magnus Simren, Jan Tack, Radu Tutuian, Miguel Valdovinos, Yinglian Xiao, Frank Zerbib, C Prakash Gyawali

doi : 10.1136/gutjnl-2020-322627

Gut 2021;70:1441-1449

Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects.

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Discovery of biomarker candidates associated with the risk of short-term and mid/long-term relapse after infliximab withdrawal in Crohn’s patients: a proteomics-based study

Nicolas Pierre, Dominique Baiwir, Vân Anh Huynh-Thu, Gabriel Mazzucchelli, Nicolas Smargiasso, Edwin De Pauw, Yoram Bouhnik, David Laharie, Jean-Frédéric Colombel, Marie-Alice Meuwis, Edouard Louis

doi : 10.1136/gutjnl-2020-322100

Gut 2021;70:1450-1457

A subset of Crohn’s disease (CD) patients experiences mid/long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.

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Standalone performance of artificial intelligence for upper GI neoplasia: a meta-analysis

Julia Arribas, Giulio Antonelli, Leonardo Frazzoni, Lorenzo Fuccio, Alanna Ebigbo, Fons van der Sommen, Noha Ghatwary, Christoph Palm, Miguel Coimbra, Francesco Renna, J J G H M Bergman, Prateek Sharma, Helmut Messmann, Cesare Hassan, Mario J Dinis-Ribeiro

doi : 10.1136/gutjnl-2020-321922

Gut 2021;70:1458-1468

Artificial intelligence (AI) may reduce underdiagnosed or overlooked upper GI (UGI) neoplastic and preneoplastic conditions, due to subtle appearance and low disease prevalence. Only disease-specific AI performances have been reported, generating uncertainty on its clinical value.

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Randomised comparison of postpolypectomy surveillance intervals following a two-round baseline colonoscopy: the Japan Polyp Study Workgroup

Takahisa Matsuda, Takahiro Fujii, Yasushi Sano, Shin-ei Kudo, Yasushi Oda, Kinichi Hotta, Tadakazu Shimoda, Yutaka Saito, Nozomu Kobayashi, Masau Sekiguchi, Kazuo Konishi, Hiroaki Ikematsu, Hiroyasu Iishi, Yoji Takeuchi, Masahiro Igarashi, Kiyonori Kobayashi, Miwa Sada, Yuichiro Yamaguchi, Kiwamu Hasuda, Tomoaki Shinohara, Hideki Ishikawa, Yoshitaka Murakami, Hirokazu Taniguchi, Takahiro Fujimori, Yoichi Ajioka, Shigeaki Yoshida

doi : 10.1136/gutjnl-2020-321996

Gut 2021;70:1469-1478

To assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs).

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Endoscopic sutured gastroplasty in addition to lifestyle modification: short-term efficacy in a controlled randomised trial

Vincent Huberty, Ivo Boskoski, Vincenzo Bove, Pauline Van Ouytsel, Guido Costamagna, Marc A Barthet, Jacques Devière

doi : 10.1136/gutjnl-2020-322026

Gut 2021;70:1479-1485

Endoscopic suture gastroplasty (ESG) has been developed as an alternative treatment for moderately obese patients. We present our results of a short-term randomised controlled trial on a new suturing technique, the Endomina system (E-ESG, Endo Tools therapeutics, Belgium).

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Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn

Kaiyu Xu, Xuxuan Gao, Genghong Xia, Muxuan Chen, Nianyi Zeng, Shan Wang, Chao You, Xiaolin Tian, Huiling Di, Wenli Tang, Pan Li, Huidi Wang, Xiuli Zeng, Chuhong Tan, Fanguo Meng, Hailong Li, Yan He, Hongwei Zhou, Jia Yin

doi : 10.1136/gutjnl-2020-323263

Gut 2021;70:1486-1494

Stroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown.

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Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis

Yunben Yang, Lili Li, Chunjing Xu, Yunke Wang, Zhen Wang, Mengyao Chen, Zhou Jiang, Jun Pan, Chenghui Yang, Xiaoqian Li, Kai Song, Junfeng Yan, Wanglan Xie, Xianguo Wu, Zhigang Chen, Ying Yuan, Shu Zheng, Jun Yan, Jian Huang, Fuming Qiu

doi : 10.1136/gutjnl-2020-320777

Gut 2021;70:1495-1506

Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer.

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Exosomes derived from Fusobacterium nucleatum -infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16

Songhe Guo, Jun Chen, Fangfang Chen, Qiuyao Zeng, Wan-Li Liu, Ge Zhang

doi : 10.1136/gutjnl-2020-321187

Gut 2021;70:1507-1519

Exosomes released from tumour cells are packed with unique RNA and protein cargo, and they are emerging as an important mediator in the communication network that promotes tumour progression. The facultative intracellular bacterium Fusobacterium nucleatum (Fn) is an important colorectal cancer (CRC)-associated bacterium. To date, the function of exosomes from Fn-infected CRC cells has not been explored.

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Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study

Raoul C Reulen, Kwok F Wong, Chloe J Bright, David L Winter, Daniela Alessi, Rodrigue M Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Julianne Byrne, Elizabeth AM Feijen, Miranda M Fidler-Benaoudia, Ibrahim Diallo, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Stine Høgsholt, Moncilo Jankovic, Peter Kaatsch, Melanie Kaiser, Rahel Kuonen, Helena Linge, Hilde Øfstaas, Cecile M Ronckers, Eva-Maria Hau, Roderick Skinner, Flora E van Leeuwen, Jop C Teepen, Cristina Veres, Wael Zrafi, Ghazi Debiche, Damien Llanas, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi M Lähteenmäki, Lorna Zadravec Zaletel, Claudia E Kuehni, Jeanette F Winther, Florent de Vathaire, Leontien C Kremer, Lars Hjorth, Michael M Hawkins

doi : 10.1136/gutjnl-2020-322237

Gut 2021;70:1520-1528

Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.

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Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia

Joshua Demb, Lin Liu, Caitlin C. Murphy, Chyke A. Doubeni, María Elena Martínez, Samir Gupta

doi : 10.1136/gutjnl-2020-321849

Gut 2021;70:1529-1537

Young-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC.

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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease

Tenghao Zheng, David Ellinghaus, Simonas Juzenas, François Cossais, Greta Burmeister, Gabriele Mayr, Isabella Friis Jørgensen, Maris Teder-Laving, Anne Heidi Skogholt, Sisi Chen, Peter R Strege, Go Ito, Karina Banasik, Thomas Becker, Frank Bokelmann, Søren Brunak, Stephan Buch, Hartmut Clausnitzer, Christian Datz, DBDS Consortium, Frauke Degenhardt, Marek Doniec, Christian Erikstrup, Tõnu Esko, Michael Forster, Norbert Frey, Lars G Fritsche, Maiken Elvestad Gabrielsen, Tobias Gräßle, Andrea Gsur, Justus Gross, Jochen Hampe, Alexander Hendricks, Sebastian Hinz, Kristian Hveem, Johannes Jongen, Ralf Junker, Tom Hemming Karlsen, Georg Hemmrich-Stanisak, Wolfgang Kruis, Juozas Kupcinskas, Tilman Laubert, Philip C Rosenstiel, Christoph Röcken, Matthias Laudes, Fabian H Leendertz, Wolfgang Lieb, Verena Limperger, Nikolaos Margetis, Kerstin Mätz-Rensing, Christopher Georg Németh, Eivind Ness-Jensen, Ulrike Nowak-Göttl, Anita Pandit, Ole Birger Pedersen, Hans Günter Peleikis, Kenneth Peuker, Cristina Leal Rodriguez, Malte Christoph Rühlemann, Bodo Schniewind, Martin Schulzky, Jurgita Skieceviciene, Jürgen Tepel, Laurent Thomas, Florian Uellendahl-Werth, Henrik Ullum, Ilka Vogel, Henry Volzke, Lorenzo von Fersen, Witigo von Schönfels, Brett Vanderwerff, Julia Wilking, Michael Wittig, Sebastian Zeissig, Myrko Zobel, Matthew Zawistowski, Vladimir Vacic, Olga Sazonova, Elizabeth S Noblin, The 23andMe Research Team, Gianrico Farrugia, Arthur Beyder, Thilo Wedel, Volker Kahlke, Clemens Schafmayer, Mauro D'Amato, Andre Franke

doi : 10.1136/gutjnl-2020-323868

Gut 2021;70:1538-1549

Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.

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TOX defines the degree of CD8+ T cell dysfunction in distinct phases of chronic HBV infection

Kathrin Heim, Benedikt Binder, Sagar, Dominik Wieland, Nina Hensel, Sian Llewellyn-Lacey, Emma Gostick, David A. Price, Florian Emmerich, Hildegard Vingerhoet, Anke R M Kraft, Markus Cornberg, Tobias Boettler, Christoph Neumann-Haefelin, Dietmar Zehn, Bertram Bengsch, Maike Hofmann, Robert Thimme

doi : 10.1136/gutjnl-2020-322404

Gut 2021;70:1550-1560

Chronic hepatitis B virus (HBV) infection is characterised by HBV-specific CD8+ T cell dysfunction that has been linked to Tcell exhaustion, a distinct differentiation programme associated with persisting antigen recognition. Recently, Thymocyte Selection-Associated High Mobility Group Box (TOX) was identified as master regulator of CD8+ T cell exhaustion. Here, we addressed the role of TOX in HBV-specific CD8+ T cell dysfunction associated with different clinical phases of infection.

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Impact of test-and-treat and risk reduction strategies on HCV transmission among MSM living with HIV in France: a modelling approach

Mathieu Castry, Anthony Cousien, Virginie Supervie, Annie Velter, Jade Ghosn, A David Paltiel, Yazdan Yazdanpanah, Sylvie Deuffic-Burban

doi : 10.1136/gutjnl-2020-321744

Gut 2021;70:1561-1569

Since the early 2000s, there has been an epidemic of HCV occurring among men who have sex with men (MSM) living with HIV, mainly associated with high-risk sexual and drug-related behaviours. Early HCV diagnosis and treatment, and behavioural risk-reduction, may be effective to eliminate HCV among MSM living with HIV.

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From the origin of NASH to the future of metabolic fatty liver disease

Andreas Geier, Dina Tiniakos, Helmut Denk, Michael Trauner

doi : 10.1136/gutjnl-2020-323202

Gut 2021;70:1570-1579

Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Understanding the pathological and molecular hallmarks from its first description to definitions of disease entities, classifications and molecular phenotypes is crucial for both appropriate clinical management and research in this complex disease. We provide an overview through almost two hundred years of clinical research from the beginnings as a nebulous disease entity of unknown origin in the 19th century to the most frequent and vigorously investigated liver disease today. The clinical discrimination between alcohol-related liver disease and NAFLD was uncommon until the 1950s and likely contributed to the late acceptance of NAFLD as a metabolic disease entity for long time. Although the term ‘fatty liver hepatitis’ first appeared in 1962, it was in 1980 that the term ‘non-alcoholic steatohepatitis’ (NASH) was coined and the histopathological hallmarks that are still valid today were defined. The 2005 NASH Clinical Research Network scoring was the first globally accepted grading and staging system for the full spectrum of NAFLD and is still used to semiquantify main histological features. In 2021, liver biopsy remains the only diagnostic procedure that can reliably assess the presence of NASH and early fibrosis but increasing efforts are made towards non-invasive testing and molecular classification of NAFLD subtypes.

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Understanding the role of the gut in undernutrition: what can technology tell us?

Alex J Thompson, Claire D Bourke, Ruairi C Robertson, Nirupama Shivakumar, Christine A Edwards, Tom Preston, Elaine Holmes, Paul Kelly, Gary Frost, Douglas J Morrison

doi : 10.1136/gutjnl-2020-323609

Gut 2021;70:1580-1594

Gut function remains largely underinvestigated in undernutrition, despite its critical role in essential nutrient digestion, absorption and assimilation. In areas of high enteropathogen burden, alterations in gut barrier function and subsequent inflammatory effects are observable but remain poorly characterised. Environmental enteropathy (EE)—a condition that affects both gut morphology and function and is characterised by blunted villi, inflammation and increased permeability—is thought to play a role in impaired linear growth (stunting) and severe acute malnutrition. However, the lack of tools to quantitatively characterise gut functional capacity has hampered both our understanding of gut pathogenesis in undernutrition and evaluation of gut-targeted therapies to accelerate nutritional recovery. Here we survey the technology landscape for potential solutions to improve assessment of gut function, focussing on devices that could be deployed at point-of-care in low-income and middle-income countries (LMICs). We assess the potential for technological innovation to assess gut morphology, function, barrier integrity and immune response in undernutrition, and highlight the approaches that are currently most suitable for deployment and development. This article focuses on EE and undernutrition in LMICs, but many of these technologies may also become useful in monitoring of other gut pathologies.

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GI highlights from the literature

Philip J Smith

doi : 10.1136/gutjnl-2021-325411

Gut 2021;70:1595-1596

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Association between proton pump inhibitor use and mortality in patients with hepatocellular carcinoma receiving tyrosine kinase inhibitor

Chun-Ying Wu, Hsiu J Ho, Chen-Yi Wu, Yi-Ju Chen, Teng-Yu Lee, Yao-Chun Hsu, Jaw-Town Lin

doi : 10.1136/gutjnl-2020-321932

Gut 2021;70:1598-1599

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Comparison of the long-term efficacy between tenofovir and entecavir in chronic hepatitis B patients

Kecheng Liu, Peng Peng, Fuqing Cai, Jiean Huang

doi : 10.1136/gutjnl-2020-322642

Gut 2021;70:1599-1600

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Emerging role of endoscopic ultrasound-guided liver biopsy

John David Chetwood, Sanjivan Mudaliar, Dominic Staudenmann, Joo-Shik Shin, Ken Liu, Avik Majumdar, Arthur Kaffes, Simone Strasser, Geoffrey W McCaughan, Payal Saxena

doi : 10.1136/gutjnl-2020-322704

Gut 2021;70:1600-1601

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