Gut最新文献

{"title":"Rate of suitable cases for primary EUS-guided biliary drainage in distal malignant biliary obstruction","authors":"Ji Young Bang, Maryam Faraj Agha, Robert Hawes, Shyam Varadarajulu","doi":"10.1136/gutjnl-2025-334979","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334979","url":null,"abstract":"Endoscopic ultrasound (EUS) has been suggested as the primary modality in lieu of endoscopic retrograde cholangiopancreatography (ERCP) for drainage of malignant distal biliary obstruction. However, the presence of a dilated bile duct (≥12 mm) is a prerequisite for the success of the EUS approach. In a retrospective study, we found that 44.9% of 439 ERCP patients over a 3-year period had insufficiently dilated bile duct that was not conducive for an EUS-based intervention. 29 patients were treated by a salvage EUS approach, with median bile duct diameter of 16 mm (IQR 13–18 mm). Although indispensable as a rescue technique, adopting current techniques and technology, this study does not suggest a universal primary role for EUS in this setting. Although ERCP is the preferred therapeutic strategy for malignant distal biliary obstruction, duodenal invasion by tumour can limit technical success. Also, stent dysfunction from tumour ingrowth and post-ERCP pancreatitis are well recognised limitations. Since the early 2000s, EUS-guided biliary drainage (EUS-BD) has emerged as a promising treatment alternative for ERCP. The ability to bypass tumour invasion and avoid instrumentation of the pancreatic duct increases the likelihood of technical success and minimises risk for pancreatitis. A recent meta-analysis of six randomised controlled trials (RCT) comparing EUS and ERCP involving 570 subjects found that patients undergoing EUS-BD required fewer reinterventions and had reduced risk of postprocedure pancreatitis.1 Given these promising observations, it has been suggested that EUS could potentially replace ERCP as the primary treatment modality. However, technical manoeuvres such as accessing the bile duct using a 19-gauge fine needle aspiration (FNA) device to enable guidewire passage or cauterised delivery tip to facilitate lumen-apposing metal stent (LAMS) placement require the presence of a dilated common bile duct (CBD). In two of six RCTs, CBD diameter of ≥12 mm was specified as eligibility criteria …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"36 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506862","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":"Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium","authors":"Ching-Hung Tseng, Sunny Wong, Jun Yu, Yeong Yeh Lee, Jun Terauchi, Hsin-Chih Lai, Jiing-Chyuan Luo, Cheng Yen Kao, Sung-Liang Yu, Jyh-Ming Liou, Deng-Chyang Wu, Ming-Chih Hou, Ming-Shiang Wu, Jiunn-Jong Wu, Joseph J Y Sung, Emad M El-Omar, Chun-Ying Wu","doi":"10.1136/gutjnl-2024-334501","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334501","url":null,"abstract":"Objective Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta , as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development. Design Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP. Results The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place. Conclusions The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"26 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506864","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":"Serological screening for coeliac disease in an adult general population: the HUNT study","authors":"Ina Lervåg Andersen, Polina Lukina, Ole T Dyrli, Rolf Anton Klaasen, David John Warren, Nils Bolstad, Patricia Mjønes, Elin Rønne, Rasmus Iversen, Ludvig M Sollid, Knut E A Lundin, Eivind Ness-Jensen","doi":"10.1136/gutjnl-2024-333886","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333886","url":null,"abstract":"Background A large proportion of individuals with coeliac disease (CeD) remain undiagnosed. Objective The aim of this study was to assess serological screening for CeD in the adult general population. Design The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found. Results Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals. Conclusion The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD. Data are available upon reasonable request. Researchers with a PhD associated with Norwegian research institutes can apply for the use of HUNT material: data and samples - given approval by a Regional Committee for Medical and Health Research Ethics. Researchers from other countries are welcome to apply in cooperation with a Norwegian Principle Investigator. Access to the requested HUNT material is given after the application is approved of by HUNTs Data Access Committee (DAC) and an agreement is signed. The agreement gives the researcher(s) the right to research a specific topic for a limited time period and to publish a decided upon number of articles. For data information contact: HUNT Research Centre Forskningsveien 27600 Levanger, Norway. Phone +47 74 07 51 80 | +47 74 01 92 40 | +47 407 90 010. Mail: kontakt@hunt.ntnu.no","PeriodicalId":12825,"journal":{"name":"Gut","volume":"187 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506817","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":"Underwater endoscopic submucosal dissection for large non-pedunculated colorectal polyps","authors":"Roberto de Sire, Antonio Capogreco, Davide Massimi, Ludovico Alfarone, Luca Brandaleone, Vincenzo Vadalà, Francesco Minini, Spadaccini Marco, Antonio Facciorusso, Asma Alkandari, Pradeep Bhandari, Cesare Hassan, Roberta Maselli, Alessandro Repici","doi":"10.1136/gutjnl-2025-334995","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334995","url":null,"abstract":"Underwater endoscopic resections have emerged as promising alternatives to the conventional techniques for the treatment of large (≥2 cm) non-pedunculated colorectal polyps; this may also apply to colorectal endoscopic submucosal dissection (ESD) using saline. This retrospective study uses a propensity score-matched analysis of 82/208 such lesions treated during a 3-year period. Underwater ESD using saline improved R0 resection rates (97.6% vs 82.9%), enhanced dissection speed (31.8 mm2/min vs 22.9 mm2/min) and reduced the use of haemostatic forceps for intraprocedural bleeding (0% vs 14.6%). We recommend this technique to be adopted to facilitate ESD for large non-pedunculated colorectal lesions. ESD is a preferred technique for en bloc resection of large (≥2 cm) non-pedunculated colorectal polyps or adenomas, offering high R0 resection and low recurrence rates.1 2 However, its adoption in Western countries remains limited due to technical complexity, long procedure times and associated adverse events.3 Underwater ESD, which replaces CO2 insufflation with a saline-filled environment, has been proposed to enhance visualisation, traction and submucosal dissection, improving procedural outcomes.4–6 Additionally, saline impedance allows prophylactic underwater vessel coagulation when swift coagulation (effect: 4.0; electrosurgical generator: VIO3, Erbe Elektromedizin GmbH) is applied, improving submucosal vessel sealing to reduce intraprocedural bleeding.7–10 This retrospective study included all consecutive large non-pedunculated colorectal adenomas treated by ESD from January 2021 to December 2023. Underwater ESD using saline was gradually and systematically implemented after January 2023. Eligible participants were adults aged 18 years or older with large lesions (≥2 cm). Exclusion criteria were treatment by endoscopic mucosal resection, need for deeper resection (endoscopic intermuscular dissection or endoscopic full-thickness resection), or surgery, suspected sessile serrated lesions, inability to suspend anticoagulant therapy or to provide informed consent. Relevant clinical and endoscopic data were systematically collected in an electronic database. The procedures were conducted …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"35 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506820","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":"From microbiota to menu: predicting individual responses to dietary components","authors":"Hadar Romano-Zadaka, Nissan Yissachar","doi":"10.1136/gutjnl-2025-334712","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334712","url":null,"abstract":"Over the past few decades, the prevalence of chronic inflammatory and metabolic diseases has risen sharply, coinciding with significant environmental and lifestyle changes. While genetics play a role, the rapid increase suggests that non-genetic factors are key contributors. Among these, the gut microbiota—a vast community of microorganisms residing in the intestines—has emerged as a central regulator of health. A growing body of evidence links microbial imbalances, or dysbiosis, to various diseases, with reduced microbial richness and diversity observed in industrialised populations compared with those in non-industrialised settings. Many beneficial microbial species, once prevalent in the human gut, are now disappearing, likely due to changes in diet, hygiene and antibiotic use. One of the most influential factors shaping the gut microbiota is diet. The Westernised diet, characterised by high consumption of processed foods and food additives, has been associated with microbiota alterations and linked to conditions such as inflammatory bowel disease, obesity and metabolic disorders. Emerging research suggests that some food additives, including emulsifiers1 and artificial sweeteners,2 may exert their harmful effects through microbiota-mediated mechanisms. However, responses to dietary components are highly heterogeneous across individuals, raising an important question: Can we predict individual responses to diet based on microbiota composition and function? Such predictive capabilities could pave the way for personalised nutrition and medicine, tailoring dietary interventions to an individual’s unique microbial makeup. Despite its promise, this approach faces several challenges. Microbiota composition is highly variable across individuals and influenced by numerous factors, including diet, lifestyle, genetics and prior medical treatments. This variability complicates predicting how specific perturbations will affect an individual’s microbiota, as …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"66 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506863","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":"Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis","authors":"Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas, Patricia Momoyo Zitelli, Maria Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Angelo Z Mattos, Wenyi Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana S C Mendes, Victor Vargas, Mario R Alvares-da-Silva, Raj Mookerjee, Paolo L Bittencourt, Carlos Benitez, Agustín Albillos, Cláudia Couto, Manuel Mendizabal, Rafael Bañares, Claudio L Toledo, Daniel F Mazo, Martin Janicko, Mauricio Castillo-Barradas, Pedro Martin Padilla Machaca, Pietro Gatti, Adelina Zarela-Lozano Miranda, René Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair Jose Carrilho, Joan Claria, Richard Moreau, Vicente Arroyo","doi":"10.1136/gutjnl-2024-333876","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333876","url":null,"abstract":"Background and aims Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC. Methods Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients. Results The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission. Conclusions In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506927","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":"Endoscope reprocessing—resource consumption and emissions","authors":"Carlotta Crisciotti, Alessandro Fugazza, Maddalena Menini, Spadaccini Marco, Elena Vanni, Alberto Fumagalli, Paolo Oliva, Tommy Rizkala, Cesare Hassan, Serena Giordano, Rosaria Iacovino, Alessandro Repici","doi":"10.1136/gutjnl-2024-334457","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334457","url":null,"abstract":"Effective reprocessing of reusable GI endoscopes is crucial to minimising patient risks associated with contamination. However, this process poses a considerable environmental challenge. This study aimed to examine the emissions associated with endoscope disinfection, a largely unexplored area. On average, a reprocessing cycle required 57 L water, 65 L air, 1080 watts of electricity and produced 3.30 kgCO2e. These findings highlight the pressing need for sustainable solutions to reduce the environmental impact of endoscope reprocessing while ensuring patient safety remains uncompromised. GI endoscopy represents a significant contributor to greenhouse gas (GHG) emissions and hazardous waste in healthcare.1–3 Several gastroenterology associations have issued guidelines and standards for proper endoscope reprocessing to ensure patient safety and prevent health risks.4 5 Digestive endoscopes are included in the ‘semicritical’ category of items as they contact mucous membranes, thus, the need for high-level disinfection, which, according to the Center for Disease Control (CDC), is defined as the ‘complete elimination of all microorganisms in or on an instrument, except for small numbers of bacterial spores’. This is achieved using high-level disinfectants, peracetic acid being the one used by the unit. However, the impact of this essential process remains largely unknown. Recently, Pioche et al 6 highlighted that—in the life cycle assessment (LCA) of gastroscopes—the decontamination stage of reusable gastroscopes was the greatest contributor to GHG emissions accounting for more than 90% of water consumption and 45% of carbon footprint. The goal of this study is to quantify the environmental burden of reusable endoscope reprocessing, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"51 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506865","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":"Characterisation of MRGPRX2+ mast cells in irritable bowel syndrome","authors":"Lisse Decraecker, María Cuende Estévez, Samuel Van Remoortel, Runze Quan, Nathalie Stakenborg, Zheng Wang, Elisabetta De Marco, Alexandre Denadai-Souza, Maria Francesca Viola, Sonia Garcia Caraballo, Stuart Brierley, Yasuhiro Tsukimi, Gareth Hicks, Wendy Winchester, Jill Wykosky, Andrea Fanjul, Tony Gibson, Mira Wouters, Pieter Vanden Berghe, Hind Hussein, Guy Boeckxstaens","doi":"10.1136/gutjnl-2024-334037","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334037","url":null,"abstract":"Background Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown. Objective We investigated whether MRGPRX2-mediated mast cell activation plays a role in abdominal pain development in patients with IBS. Design MRGPRX2 expression in mast cells and other immune cells was characterised across colon layers using flow cytometry. We evaluated whether MRGPRX2 agonists trigger mast cell degranulation and transient receptor potential vanilloid 1 (TRPV1) sensitisation in healthy human colonic submucosal plexus samples using live imaging. Rectal biopsies were then collected from patients with IBS and healthy volunteers (HV) and MRGPRX2+ mast cell frequency, MRGPRX2 expression per cell, mast cell degranulation kinetics in response to MRGPRX2 agonists, MRGPRX2 agonistic activity and presence of MRGPRX2 agonists in biopsy supernatants were assessed. Results MRGPRX2+ mast cells are enriched in the submucosa and muscularis of the healthy human colon. MRGPRX2 agonists induce mast cell degranulation and TRPV1 sensitisation in the healthy colon submucosa. While the frequency of rectal MRGPRX2+ mast cells was unaltered in IBS, submucosal mast cells showed increased degranulation in response to MRGPRX2 agonists in IBS compared with HV. MRGPRX2 agonistic activity was increased in IBS rectal biopsy supernatant compared with HV, which was associated with increased levels of substance P. Conclusion The MRGPRX2 pathway is functionally upregulated in the colon of patients with IBS, supporting its role in abdominal pain in IBS. Data are available upon reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"4 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477599","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":"RNA-based therapies in liver metabolic diseases","authors":"Antonio Fontanellas, Pedro Berraondo, Francesco Urigo, Daniel Jericó, Paolo G V Martini, Fernando Pastor, Matias A Avila","doi":"10.1136/gutjnl-2023-331742","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-331742","url":null,"abstract":"RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA therapies have made significant progress in the treatment of genetic liver diseases, exemplified by small interfering RNA treatments for hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation to improve efficacy and safety. RNA-based gene-editing technologies, such as base editor and prime editor clustered regularly interspaced short palindromic repeats systems, also show promise with their ability to minimise genomic rearrangements and cancer risk. While RNA therapies offer high precision, challenges remain in optimising delivery methods and ensuring long-term safety and efficacy. Lipid nanoparticle-mRNA therapeutics, particularly for protein replacement in rare diseases, have gained support from preclinical successes. Compared with viral gene therapies, mRNA therapies present a safer profile with reduced risks of genomic integration and oncogene activation. However, clinical trials, especially for rare diseases, face limitations such as small sample sizes and short observation periods. Further preclinical studies, including non-human primates, will be essential for refining trial designs. Despite their potential, the high costs of RNA therapies pose a challenge that will require cost–utility models to guide pricing and accessibility. Here, we discuss the fundamental aspects of RNA-based therapeutics and showcase the most relevant preclinical and clinical developments in genetic liver metabolic diseases.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477472","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":"Multicentre randomised controlled trial of a self-assembling haemostatic gel to prevent delayed bleeding following endoscopic mucosal resection (PURPLE Trial)","authors":"Jan Drews, Markus Zachäus, Tobias Kleemann, Jörg Schirra, Oscar Cahyadi, Oliver Möschler, Christian Schulze, Ingo Steinbrück, Edris Wedi, Oliver Pech, Tobias J Weismüller, Armin Küllmer, Mohamed Abdelhafez, Jochen Wedemeyer, Torsten Beyna, Julian Riedel, Ulrich Paul Halm, Carola Güther, Riccardo Vasapolli, Christian Torres Reyes, Daniel R Quast, Oliver Bachmann, Erini Dedonaki, Jörg Ulrich, Inna Marchuk, Christina Frahm, Tanja Steffen, Peter Wohlmuth, Torsten Bunde, Nele Geßler, Thomas von Hahn","doi":"10.1136/gutjnl-2024-334229","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334229","url":null,"abstract":"Background Prophylactic application of a haemostatic gel to the resection field may be an easy way to prevent delayed bleeding, a frequent complication after endoscopic mucosal resection (EMR). Objective We aimed to evaluate if the prophylactic application of a haemostatic gel to the resection field directly after EMR can reduce the rate of clinically significant delayed bleeding events. Design We conducted a prospective randomised trial of patients undergoing hot-snare EMR of flat lesions in the duodenum (≥10 mm) and colorectum (≥20 mm) at 15 German centres. Prophylactic clip closure was not allowed, but selective clipping or coagulation could be used prior to randomisation to treat intraprocedural bleeding or for prophylactic closure of visible vessels. Patients were randomised to haemostatic gel application or no prophylaxis. The primary endpoint was delayed bleeding within 30 days. Results The trial was stopped early due to futility after an interim analysis. The primary endpoint was analysed in 232 patients (208 colorectal, 26 duodenal). Both groups were comparable in age, sex, comorbidities and lesion characteristics. Preventive measures, such as selective clipping or coagulation, were applied prior to randomisation in 51.9% of cases, with no difference between groups. Delayed bleeding occurred in 14 cases (11.7%; 95% CI 7.1% to 18.6%) after Purastat and in 7 cases (6.3%; 95% CI 3.1% to 12.3%) in the control group (p=0.227), with no difference between colorectal and duodenal subgroups. Conclusion The application of a haemostatic gel following EMR of large flat lesions in the duodenum and colorectum does not reduce the rate of delayed bleeding. Data are available on reasonable request. Data and full trial protocol are available on reasonable request. All data relevant to the study are included in the article of uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"49 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477471","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}