Pub Date : 2024-10-09DOI: 10.1053/j.gastro.2024.10.003
Tanja M. Müller, Li-Juan Liu, Manuel Wiesinger, Markus F. Neurath, Caroline J. Voskens, Sebastian Zundler
No Abstract
无摘要
{"title":"Engineering therapeutic Tregs to overexpress GPR15 improves functional fitness for in vivo gut homing","authors":"Tanja M. Müller, Li-Juan Liu, Manuel Wiesinger, Markus F. Neurath, Caroline J. Voskens, Sebastian Zundler","doi":"10.1053/j.gastro.2024.10.003","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.003","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"207 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398372","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}
Pub Date : 2024-10-03DOI: 10.1053/j.gastro.2024.09.028
Ryan Flanagan, Calley Levine, Kenneth Hung, Michelle Hughes, Cassandra D.L. Fritz, David Wan, Daniel J. Stein
No Abstract
无摘要
{"title":"The Educational Impact of the GI Hospitalist Model on Gastroenterology Fellowship Training","authors":"Ryan Flanagan, Calley Levine, Kenneth Hung, Michelle Hughes, Cassandra D.L. Fritz, David Wan, Daniel J. Stein","doi":"10.1053/j.gastro.2024.09.028","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.09.028","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"23 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369981","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}
Pub Date : 2024-10-02DOI: 10.1053/j.gastro.2024.09.030
Jessica R. Allegretti, Colleen R. Kelly, Thomas Louie, Monika Fischer, Susy Hota, Bharat Misra, Nick W. Van Hise, Eugene Yen, Jeffrey S. Bullock, Michael Silverman, Ian Davis, Sarah K. McGill, Darrell S. Pardi, Robert Orenstein, Ari Grinspan, Najwa El-Nachef, Paul Feuerstadt, Thomas J. Borody, Sahil Khanna S, Shrish Budree, Zain Kassam
Background and Aims
Recurrent Clostridioides difficile infections (CDI) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full spectrum, oral microbiome therapeutics is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.
Methods
We conducted a multi-center, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by PCR or toxin EIA for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼ 6 x 1011 CFU of lyophilized microbial cells) or placebo after standard-of-care (SOC) antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through Week 8. Safety, efficacy and microbiome endpoints were evaluated through Week 8 and 24.
Results
198 participants were analyzed; CP101 (n=102) and placebo (n=96). Overall, 27.5% with a first recurrence and 62.7% diagnosed by PCR-based testing. The proportion without CDI recurrence through Week 8 was significantly higher in the CP101 group compared to placebo (74.5% [76/102] vs 61.5% [59/96], p=0.0488) with durable efficacy observed through Week 24 (73.5% [75/102] vs 59.4% [57/96], p=0.0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to placebo. The incidence of adverse events was similar between the two groups.
Conclusions
CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. https://clinicaltrials.gov/study/NCT03110133
{"title":"Safety and Tolerability of CP101, a full spectrum, oral microbiome therapeutic for the prevention of recurrent C. difficile infection: A Phase 2 Randomized Controlled Trial.","authors":"Jessica R. Allegretti, Colleen R. Kelly, Thomas Louie, Monika Fischer, Susy Hota, Bharat Misra, Nick W. Van Hise, Eugene Yen, Jeffrey S. Bullock, Michael Silverman, Ian Davis, Sarah K. McGill, Darrell S. Pardi, Robert Orenstein, Ari Grinspan, Najwa El-Nachef, Paul Feuerstadt, Thomas J. Borody, Sahil Khanna S, Shrish Budree, Zain Kassam","doi":"10.1053/j.gastro.2024.09.030","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.09.030","url":null,"abstract":"<h3>Background and Aims</h3>Recurrent Clostridioides difficile infections (CDI) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full spectrum, oral microbiome therapeutics is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.<h3>Methods</h3>We conducted a multi-center, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by PCR or toxin EIA for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼ 6 x 10<sup>11</sup> CFU of lyophilized microbial cells) or placebo after standard-of-care (SOC) antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through Week 8. Safety, efficacy and microbiome endpoints were evaluated through Week 8 and 24.<h3>Results</h3>198 participants were analyzed; CP101 (n=102) and placebo (n=96). Overall, 27.5% with a first recurrence and 62.7% diagnosed by PCR-based testing. The proportion without CDI recurrence through Week 8 was significantly higher in the CP101 group compared to placebo (74.5% [76/102] vs 61.5% [59/96], p=0.0488) with durable efficacy observed through Week 24 (73.5% [75/102] vs 59.4% [57/96], p=0.0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to placebo. The incidence of adverse events was similar between the two groups.<h3>Conclusions</h3>CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. <strong>https://clinicaltrials.gov/study/NCT03110133</strong>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"22 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369445","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}
Pub Date : 2024-10-02DOI: 10.1053/j.gastro.2024.09.032
Vedant Acharya, Vignesh Kumaresan, Jonathan England, Shivan Mehta, Daniel Sussman, Amar Deshpande
No Abstract
无摘要
{"title":"Use of Large Language Models to Identify Surveillance Colonoscopy Intervals – A Feasibility Study","authors":"Vedant Acharya, Vignesh Kumaresan, Jonathan England, Shivan Mehta, Daniel Sussman, Amar Deshpande","doi":"10.1053/j.gastro.2024.09.032","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.09.032","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"23 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369446","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}
Pub Date : 2024-10-01DOI: 10.1053/j.gastro.2024.09.029
Yoichi Nakatsu, Makoto Furihata, Taro Osada
No Abstract
无摘要
{"title":"Hidden Footprints in Ascites: Lessons from a Mystery Enduring for 200 Years","authors":"Yoichi Nakatsu, Makoto Furihata, Taro Osada","doi":"10.1053/j.gastro.2024.09.029","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.09.029","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"57 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369447","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}
Pub Date : 2024-09-28DOI: 10.1053/j.gastro.2024.09.021
Veronika Horn, Camila A Cancino, Lisa Maria Steinheuer, Benedikt Obermayer, Konstantin Fritz, Anke L Nguyen, Kim Susan Juhran, Christina Plattner, Diana Bösel, Lotte Oldenburg, Marie Burns, Axel Ronald Schulz, Mariia Saliutina, Eleni Mantzivi, Donata Lissner, Thomas Conrad, Mir-Farzin Mashreghi, Sebastian Zundler, Elena Sonnenberg, Michael Schumann, Lea-Maxie Haag, Dieter Beule, Lukas Flatz, Zlatko Trjanoski, Geert D'Haens, Carl Weidinger, Henrik E Mei, Britta Siegmund, Kevin Thurley, Ahmed N Hegazy
Background & aims: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.
Methods: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell variable, diversity, and joining sequencing; serum proteomics; and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.
Results: Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4+ memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4β1, potentially making these cells less susceptible to direct targeting by vedolizumab.
Conclusions: These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.
背景与目的尽管生物疗法在治疗炎症性肠病（IBD）方面取得了成功，但由于缺乏可靠的治疗反应预测指标，患者管理仍面临挑战：在这项研究中，我们对接受抗整合素α4β7抗体维多珠单抗治疗的两组IBD患者进行了前瞻性采样。对样本进行了质谱、单细胞RNA测序、单细胞V(D)J测序、血清蛋白质组学和多维流式细胞仪检测，以全面评估维多珠单抗诱导的外周血免疫学变化及其与治疗反应的潜在关联：结果：维多利珠单抗治疗导致循环免疫细胞系的丰度发生重大变化，并改变了肠道归巢CD4+记忆T细胞的T细胞受体多样性。通过整合多模态参数和机器学习，我们发现与应答者相比，治疗前非应答者增殖的 CD4+ 记忆 T 细胞显著增加。这种预测性T细胞特征显示出活化的Th1/Th17表型，并表现出整合素α4β1水平的升高，这可能使这些细胞不易被韦多珠单抗直接靶向：这些发现提供了一个可靠的预测分类器，对个性化 IBD 管理具有重要意义。
{"title":"Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4<sup>+</sup> T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.","authors":"Veronika Horn, Camila A Cancino, Lisa Maria Steinheuer, Benedikt Obermayer, Konstantin Fritz, Anke L Nguyen, Kim Susan Juhran, Christina Plattner, Diana Bösel, Lotte Oldenburg, Marie Burns, Axel Ronald Schulz, Mariia Saliutina, Eleni Mantzivi, Donata Lissner, Thomas Conrad, Mir-Farzin Mashreghi, Sebastian Zundler, Elena Sonnenberg, Michael Schumann, Lea-Maxie Haag, Dieter Beule, Lukas Flatz, Zlatko Trjanoski, Geert D'Haens, Carl Weidinger, Henrik E Mei, Britta Siegmund, Kevin Thurley, Ahmed N Hegazy","doi":"10.1053/j.gastro.2024.09.021","DOIUrl":"10.1053/j.gastro.2024.09.021","url":null,"abstract":"<p><strong>Background & aims: </strong>Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.</p><p><strong>Methods: </strong>In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell variable, diversity, and joining sequencing; serum proteomics; and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.</p><p><strong>Results: </strong>Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4<sup>+</sup> memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4<sup>+</sup> memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4β1, potentially making these cells less susceptible to direct targeting by vedolizumab.</p><p><strong>Conclusions: </strong>These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344898","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}
Pub Date : 2024-09-28DOI: 10.1053/j.gastro.2024.09.025
Sarah A Najjar, Kara Gross Margolis
{"title":"A Brain-Gut Pathway for Stress-Induced Microbiome Change.","authors":"Sarah A Najjar, Kara Gross Margolis","doi":"10.1053/j.gastro.2024.09.025","DOIUrl":"10.1053/j.gastro.2024.09.025","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344895","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}
Pub Date : 2024-09-28DOI: 10.1053/j.gastro.2024.09.027
Lung-Yi Mak, Man-Fung Yuen
{"title":"Surveillance for Hepatocellular Carcinoma in Cirrhosis: End of Monopoly for Serum Alpha Fetoprotein.","authors":"Lung-Yi Mak, Man-Fung Yuen","doi":"10.1053/j.gastro.2024.09.027","DOIUrl":"10.1053/j.gastro.2024.09.027","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344899","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}
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