Journal of Crohn's & colitis最新文献

{"title":"Magnetic Resonance Enterography and Intestinal Ultrasound for the Assessment and Monitoring of Crohn's Disease.","authors":"Shankar Kumar, Isabelle De Kock, William Blad, Richard Hare, Richard Pollok, Stuart A Taylor","doi":"10.1093/ecco-jcc/jjae042","DOIUrl":"10.1093/ecco-jcc/jjae042","url":null,"abstract":"<p><p>Magnetic resonance enterography [MRE] and intestinal ultrasound [IUS] have developed rapidly in the past few decades, emerging as the primary non-invasive options for both diagnosing and monitoring Crohn's disease [CD]. In this review, we evaluate the pertinent data relating to the use of MRE and IUS in CD. We summarise the key imaging features of CD activity, highlight their increasing role in both the clinical and the research settings, and discuss how these modalities fit within the diagnostic pathway. We discuss how they can be used to assess disease activity and treatment responsiveness, including the emergence of activity scores for standardised reporting. Additionally, we address areas of controversy such as the use of contrast agents, the role of diffusion-weighted imaging, and point-of-care ultrasound. We also highlight exciting new developments, including the applications of artificial intelligence. Finally, we provide suggestions for future research priorities.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally Invasive Surgery for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Robotic Versus Laparoscopic Surgical Techniques.","authors":"Shafquat Zaman, Ali Yasen Y Mohamedahmed, Nuha A Yassin","doi":"10.1093/ecco-jcc/jjae065","DOIUrl":"10.1093/ecco-jcc/jjae065","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally Invasive Surgery for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Robotic Versus Laparoscopic Surgical Techniques.","authors":"Miguel F Cunha, Joana Roseira","doi":"10.1093/ecco-jcc/jjae045","DOIUrl":"10.1093/ecco-jcc/jjae045","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VIBRATO's Symphony: Orchestrating Biomarker Harmony for Ritlecitinib in UC Therapy.","authors":"Bram Verstockt","doi":"10.1093/ecco-jcc/jjae103","DOIUrl":"10.1093/ecco-jcc/jjae103","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spondyloarthritis in First-Degree Relatives and Spouses of Patients with Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study from Sweden.","authors":"Sarita Shrestha, Judith S Brand, Mehdi Osooli, Carl Eriksson, Ida Schoultz, Johan Askling, Tine Jess, Scott Montgomery, Ola Olén, Jonas Halfvarson","doi":"10.1093/ecco-jcc/jjae041","DOIUrl":"10.1093/ecco-jcc/jjae041","url":null,"abstract":"<p><strong>Background and aims: </strong>Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We aimed to compare the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched, population-based, reference individuals.</p><p><strong>Methods: </strong>We identified 147 080 FDRs and 25 945 spouses of patients with incident IBD [N = 39 203] during 2006-2016, and 1 453 429 FDRs and 258 098 spouses of matched reference individuals [N = 390 490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA.</p><p><strong>Results: </strong>During follow-up, 2430 FDRs of IBD patients [6.5/10 000 person-years] and 17 761 FDRs of reference individuals [4.8/10 000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95% CI:1.29, 1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR = 1.44; 95% CI:1.34,1.5 6] and of IBD patients aged <18 years at diagnosis [HR = 1.46; 95% CI: 1.27, 1.68]. IBD patients' spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs 3.5/10 000 person-years; HR = 1.22; 95% CI:1.09, 1.37]. No subgroup-specific risk pattern was identified among spouses.</p><p><strong>Conclusions: </strong>The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Serum and Stool Microbiome Biomarkers Predict Clinical Efficacy and Tissue Molecular Response After Ritlecitinib Induction Therapy in Ulcerative Colitis.","authors":"Mina Hassan-Zahraee, Zhan Ye, Li Xi, Elizabeth Dushin, Julie Lee, Jacek Romatowski, Jaroslaw Leszczyszyn, Silvio Danese, William J Sandborn, Christopher Banfield, Jeremy D Gale, Elena Peeva, Randy S Longman, Craig L Hyde, Kenneth E Hung","doi":"10.1093/ecco-jcc/jjad213","DOIUrl":"10.1093/ecco-jcc/jjad213","url":null,"abstract":"<p><strong>Background and aims: </strong>Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, was well-tolerated and efficacious in the phase 2b VIBRATO study in participants with moderate-to-severe ulcerative colitis [UC]. The aim of this study was to identify baseline serum and microbiome markers that predict subsequent clinical efficacy and to develop noninvasive serum signatures as potential real-time noninvasive surrogates of clinical efficacy after ritlecitinib.</p><p><strong>Methods: </strong>Tissue and peripheral blood proteomics, transcriptomics, and faecal metagenomics were performed on samples before and after 8 weeks of oral ritlecitinib induction therapy [20 mg, 70 mg, 200 mg, or placebo once daily, N = 39, 41, 33, and 18, respectively]. Linear mixed models were used to identify baseline and longitudinal protein markers associated with efficacy. The combined predictivity of these proteins was evaluated using a logistic model with permuted efficacy data. Differential expression of faecal metagenomics was used to differentiate responders and nonresponders.</p><p><strong>Results: </strong>Peripheral blood serum proteomics identified four baseline serum markers [LTA, CCL21, HLA-E, MEGF10] predictive of modified clinical remission [MR], endoscopic improvement [EI], histological remission [HR], and integrative score of tissue molecular improvement. In responders, 37 serum proteins significantly changed at Week 8 compared with baseline [false discovery rate of <0.05]; of these, changes in four [IL4R, TNFRSF4, SPINK4, and LAIR-1] predicted concurrent EI and HR responses. Faecal metagenomics analysis revealed baseline and treatment response signatures that correlated with EI, MR, and tissue molecular improvement.</p><p><strong>Conclusions: </strong>Blood and microbiome biomarkers stratify endoscopic, histological, and tissue molecular responses to ritlecitinib, which may help guide future precision medicine approaches to UC treatment. ClinicalTrials.gov NCT02958865.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139033118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological inhibition of N-Acylethanolamine acid amidase (NAAA) mitigates intestinal fibrosis through modulation of macrophage activity.","authors":"Maria Francesca Nanì, Ester Pagano, Paola De Cicco, Giuseppe Lucariello, Fabio Cattaneo, Francesca Paola Tropeano, Donatella Cicia, Rebecca Amico, Federica Raucci, Giuseppe Ercolano, Francesco Maione, Maria Michela Rinaldi, Fabiana Esposito, Rosario Ammendola, Gaetano Luglio, Raffaele Capasso, Alexandros Makriyannis, Stefania Petrosino, Francesca Borrelli, Barbara Romano, Angelo A Izzo","doi":"10.1093/ecco-jcc/jjae132","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae132","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal fibrosis, a frequent complication of inflammatory bowel disease, is characterized by stricture formation with no pharmacological treatment to date. N-acylethanolamine acid amidase (NAAA) is responsible of acylethanolamides (AEs, e.g., palmitoylethanolamide and oleoylethanolamide) hydrolysis. Here, we investigated NAAA and AEs signalling in gut fibrosis.</p><p><strong>Methods: </strong>NAAA and AEs signalling were evaluated in human intestinal specimens from stenotic Crohn's diseases (CD) patients. Gut fibrosis was induced by TNBS, monitored by colonoscopy and unascertained by qRT-PCR, histological analyses, and confocal microscopy. Immune cells were analysed in mesenteric lymph nodes by FACS. Colonic fibroblasts were cultured in conditioned media derived from polarized or not bone marrow-derived macrophages (BMDM). IL-23 signalling was evaluated by qRT-PCR, ELISA, FACS, and western blot in BMDM and in lamina propria CX3CR1+ cells.</p><p><strong>Results: </strong>In ileocolonic human CD strictures, increased transcript expression of NAAA was observed with a decrease of its substrates OEA and PEA. NAAA inhibition reduced intestinal fibrosis in vivo, as revealed by decrease in inflammatory parameters, collagen deposition and fibrosis genes, including epithelial to mesenchymal transition. More in-depth studies revealed modulation of the immune response related to IL-23 following NAAA inhibition. The antifibrotic actions of NAAA inhibition are mediated by Mφ and M2 macrophages that indirectly affect fibroblast collagenogenesis. NAAA inhibitor AM9053 normalized IL-23 signalling in BMDM and in lamina propria CX3CR1+ cells.</p><p><strong>Conclusions: </strong>Our findings provide new insights into the pathophysiological mechanism of intestinal fibrosis and identify NAAA as a promising target for the development of therapeutic treatments to alleviate CD fibrosis.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.","authors":"Dominik Roth, Miriam M Düll, Ludwig J Horst, Aylin Lindemann, Xenia Malzer, Kristina Koop, Sebastian Zundler, Marcel Vetter, André Jefremow, Raja Atreya, Carol Geppert, Sören Weidemann, Maximilian J Waldner, Peter Dietrich, Claudia Günther, Luis E Munoz, Martin Herrmann, Alexander Scheffold, Markus F Neurath, Jürgen Siebler, Christoph Schramm, Andreas E Kremer, Moritz Leppkes","doi":"10.1093/ecco-jcc/jjae131","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae131","url":null,"abstract":"<p><strong>Objective: </strong>Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy.</p><p><strong>Design: </strong>We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections and colon of PSC patients.</p><p><strong>Results: </strong>Anti- αVβ6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC or MASLD. Integrin αVβ6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti- αVβ6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease.</p><p><strong>Conclusion: </strong>Anti- αVβ6 frequently occur in patients suffering from PSC, especially in PSC-IBD. Anti- αVß6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosatetraynoic Acid Regulates Pro-Fibrotic Pathways in an Induced Pluripotent Stem Cell Derived Macrophage:Human Intestinal Organoid Model of Crohn's Disease.","authors":"Ingrid Jurickova, Benjamin W Dreskin, Elizabeth Angerman, Erin Bonkowski, Jack Nguyen, Richard Villarreal, Kentaro Tominaga, Kentaro Iwasawa, Tzipi Braun, Takanori Takebe, Michael A Helmrath, Yael Haberman, James M Wells, Lee A Denson","doi":"10.1093/ecco-jcc/jjae139","DOIUrl":"10.1093/ecco-jcc/jjae139","url":null,"abstract":"<p><strong>Background and aims: </strong>We previously identified small molecules predicted to reverse an ileal gene signature for future Crohn's Disease (CD) strictures. Here we used a new human intestinal organoid (HIO) model system containing macrophages to test a lead candidate, eicosatetraynoic acid (ETYA).</p><p><strong>Methods: </strong>Induced pluripotent stem cell lines (iPSC) were derived from CD patients and differentiated into macrophages and HIOs. Macrophages and macrophage:HIO co-cultures were exposed to lipopolysaccharide (LPS) with and without ETYA pre-treatment. Cytospin and flow cytometry characterized macrophage morphology and activation markers, and RNA sequencing defined the global pattern of macrophage gene expression. TaqMan Low Density Array, Luminex multiplex assay, immunohistologic staining, and sirius red polarized light microscopy were performed to measure macrophage cytokine production and HIO pro-fibrotic gene expression and collagen content.</p><p><strong>Results: </strong>iPSC-derived macrophages exhibited morphology similar to primary macrophages and expressed inflammatory macrophage cell surface markers including CD64 and CD68. LPS-stimulated macrophages expressed a global pattern of gene expression enriched in CD ileal inflammatory macrophages and matrisome secreted products, and produced cytokines and chemokines including CCL2, IL1B, and OSM implicated in refractory disease. ETYA suppressed CD64 abundance and pro-fibrotic gene expression pathways in LPS stimulated macrophages. Co-culture of LPS-primed macrophages with HIO led to up-regulation of fibroblast activation genes including ACTA2 and COL1A1, and an increase in HIO collagen content. ETYA pre-treatment prevented pro-fibrotic effects of LPS-primed macrophages.</p><p><strong>Conclusions: </strong>ETYA inhibits pro-fibrotic effects of LPS-primed macrophages upon co-cultured HIO. This model may be used in future untargeted screens for small molecules to treat refractory CD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.","authors":"Remo Panaccione, Christopher Ma, Vipul Jairath, Axel Dignass, Namita Joshi, Ryan Clark, Jenny Griffith, Kristina Kligys, Monika Semwal, Zachary Smith, Dominic Mitchell, Dominic Nunag, Marc Ferrante","doi":"10.1093/ecco-jcc/jjae128","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae128","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD.</p><p><strong>Methods: </strong>Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm.</p><p><strong>Results: </strong>Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively.</p><p><strong>Conclusions: </strong>Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}