Journal of Crohn's & colitis最新文献

{"title":"Machine learning and metabolomics identify biomarkers associated with the disease extent of ulcerative colitis.","authors":"Changchang Ge, Yi Lu, Zhaofeng Shen, Yizhou Lu, Xiaojuan Liu, Mengyuan Zhang, Yijing Liu, Hong Shen, Lei Zhu","doi":"10.1093/ecco-jcc/jjaf020","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf020","url":null,"abstract":"<p><strong>Background and aims: </strong>Ulcerative colitis (UC) is a metabolism-related chronic intestinal inflammatory disease. Disease extent is a key parameter of UC. Using serum metabolic profiling to identify non-invasive biomarkers of disease extent may inform therapeutic decisions and risk stratification.</p><p><strong>Methods: </strong>The orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to identify the metabolites. Least absolute shrinkage and selection operator (LASSO) regression, random forest-recursive feature elimination (RF-RFE), and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to screen metabolites. Five machine learning algorithms (XGboost, KNN, NB, RF, and SVM) were used to construct prediction model.</p><p><strong>Results: </strong>A total of 220 differential metabolites between the patients with UC and healthy controls (HCs) were confirmed by the OPLS-DA model. Machine learning screened eight essential metabolites for distinguishing patients with UC from HCs. A total of 23, 6, and 6 differential metabolites were obtained through machine learning between group E1 and E2, E1 and E3, and E2 and E3. The RF model had a prediction accuracy of up to 100% in all three training sets. The serum levels of tridecanoic acid were significantly lower and pelargonic acid were significantly higher in patients with extensive colitis than in the other groups. The serum level of asparaginyl valine in patients with rectal UC was significantly lower than that in E2 and E3 groups.</p><p><strong>Conclusions: </strong>Our findings revealed the metabolic landscape of UC and identified biomarkers for different disease extents, confirming the value of metabolites in predicting the occurrence and progression of UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191560","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":"Childhood-onset inflammatory bowel disease and chronic non-bacterial osteomyelitis: a Swedish nationwide cohort study 2002-2022.","authors":"Marianne Malmquist, Siri Voghera, Stefan Berg, Robert Saalman, Ola Olén","doi":"10.1093/ecco-jcc/jjaf007","DOIUrl":"10.1093/ecco-jcc/jjaf007","url":null,"abstract":"<p><strong>Background and aims: </strong>Nationwide, population-based studies of chronic non-bacterial osteomyelitis (CNO) in patients with childhood-onset inflammatory bowel disease (IBD) are lacking.</p><p><strong>Methods: </strong>We used nationwide registers to identify all children in Sweden diagnosed with IBD during 2002-2022 and the occurrence of CNO in this IBD cohort and general population non-IBD comparators. To estimate the temporal associations between IBD and CNO we used Cox regression. We compared clinical data for IBD patients with CNO (IBD+CNO) and the IBD patients without CNO.</p><p><strong>Results: </strong>We identified 8244 children with IBD and 82 400 non-IBD comparators. At IBD diagnosis, CNO had been diagnosed in 0.13% (11/8244) of the IBD cohort and 0.03% (26/82 400) of the non-IBD comparators. During follow-up, 13 additional CNO cases occurred in the IBD cohort and 22 in the non-IBD comparators (adjusted hazard ratio = 5.87 [95% CI 2.95-11.66]). The prevalence of CNO among all prevalent children with IBD and prevalent matched non-IBD comparators December 31, 2022 was 0.48% (9/1885) and 0.02% (4/18 567), respectively. Median age at IBD diagnosis was lower in IBD + CNO compared to IBD without CNO (11 vs 14 years [-3 years, 95% CI -5 to -1]). Extraintestinal manifestations (except CNO) were more frequent in IBD + CNO (62% vs 21%, P < .0001). Treatment with biologics was more common in the IBD + CNO group (78% vs 44%, P = .004), prescribed for IBD and/or CNO.</p><p><strong>Conclusions: </strong>We found a 6-fold increased risk of CNO in childhood-onset IBD compared to non-IBD comparators. Patients with IBD + CNO are characterized by younger age at IBD onset, more frequent extraintestinal manifestations, and higher usage of biologics.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981085","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":"Non-Conventional Dysplasia in Patients with Inflammatory Bowel Disease and Colorectal Adenocarcinoma: A Case-Cohort Study.","authors":"Siri A Urquhart, Namratha Pallipamu, Hima Varsha Voruganti, Bhavana Baraskar, Pratyusha Muddaloor, Arshia K Sethi, Renisha Redij, Keirthana Aedma, Keerthy Gopalakrishnan, Shivaram Poigai Arunachalam, Kelli N Burger, Douglas W Mahoney, Blake A Kassmeyer, Ryan J Lennon, John B Kisiel, Nayantara Coelho-Prabhu","doi":"10.1093/ecco-jcc/jjaf022","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf022","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with inflammatory bowel disease (IBD) face increased risk of colorectal cancer (CRC). While the natural history of conventional dysplastic precursor lesions has been well-studied, the neoplastic potential of recently described non-conventional (NC) IBD-associated colonic mucosal lesions is unclear. We aimed to assess the incidence of antecedent NC lesions in patients with IBD who developed CRC.</p><p><strong>Methods: </strong>A case-cohort study was performed to include patients with a diagnosis of IBD with or without CRC who underwent at least two surveillance endoscopic procedures at our institution between 1/1/2007 and 5/31/2023. NC lesions included serrated change and indefinite for dysplasia. Detection rates pre- and post-introduction of high definition (HD) surveillance colonoscopy were compared.</p><p><strong>Results: </strong>In total, 87 patients with IBD and CRC and 200 patients with IBD without CRC were identified. Of the cases, a majority had ulcerative colitis (n=52, 60%), most commonly with extensive involvement (n=46, 89%). Conventional (HR 2.18, 95% CI 1.34-3.52) and NC (HR 2.28, 95% CI 1.59-3.26) lesions were associated with increased risk of CRC. Conventional lesions in the post-HD era appeared to have a stronger association with CRC (HR 2.79, 95% CI 1.62-4.77) than NC lesions (HR 1.62, 95% CI 0.86-3.06).</p><p><strong>Conclusions: </strong>Both conventional and NC lesions seem to be associated with increased risk of CRC. Conventional lesions are more strongly associated with CRC than NC lesions in the post-HD era, but misclassifications in the pre-HD era may have resulted in a biased increased risk estimate for NC lesions.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124307","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":"Assessment of activity and severity of inflammatory bowel disease in cross-sectional imaging techniques: a systematic review.","authors":"Arianna Dal Buono, Francesco Faita, Alessandro Armuzzi, Vipul Jairath, Laurent Peyrin-Biroulet, Silvio Danese, Mariangela Allocca","doi":"10.1093/ecco-jcc/jjaf023","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf023","url":null,"abstract":"<p><strong>Background and aims: </strong>Cross-sectional imaging techniques, including intestinal ultrasonography (IUS), computed tomography enterography (CTE), magnetic resonance enterography (MRE), are increasingly used for evaluation of inflammatory bowel diseases (IBD). We aimed to systematically review literature evidence on the assessment of disease activity, and/or severity through cross-sectional imaging in IBD patients, and to offer guidance on their most effective utilization.</p><p><strong>Methods: </strong>We performed a systematic review of PubMed, EMBASE, and Scopus to identify citations pertaining the assessment of disease activity, and/or severity at cross-sectional imaging techniques compared to a reference standard (i.e., other radiological techniques, endoscopy, histopathology, and surgery) in IBD patients published until December 2023.</p><p><strong>Results: </strong>Overall, 179 papers published between 1990 and 2023 were included, with a total of 10988 IBD patients (9304 CD [84.7%], 1206 UC [11.0%], 38 IBD-U [0.3%], 440 unspecified [4.0%]). 39/179 studies investigated IUS, 22/179 CTE, 101/179 MRE, in the remaining papers two techniques were addressed together. In 81.6% of the papers, endoscopy (with or without histopathology) was used as a reference standard. All studies included evaluated disease activity, while just over half (100/179, 55.8%) also evaluated disease severity of the addressed cross-sectional methodology. Pooled sensitivity, specificity, and overall accuracy of IUS, MRE, and CTE compared to the reference standard were 60-99%, 60-100%, and 70-99%, respectively.</p><p><strong>Conclusion: </strong>All cross-sectional imaging techniques demonstrated moderate-to-good accuracy in assessing disease activity, and severity of IBD. This finding highlights the potential, especially for MRE and IUS to be widely utilized in managing IBD in both clinical practice and clinical trials.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124305","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":"A pro-inflammatory diet is associated with growth and virulence of Escherichia coli in pediatric Crohn's disease.","authors":"Jessica Breton, Vincent Tu, Ceylan Tanes, Naomi Wilson, Ryan Quinn, Kelly Kachelries, Elliot S Friedman, Kyle Bittinger, Robert N Baldassano, Charlene Compher, Lindsey Albenberg","doi":"10.1093/ecco-jcc/jjaf018","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf018","url":null,"abstract":"<p><strong>Background & aims: </strong>Epidemiological studies have suggested an association between the inflammatory potential of dietary patterns and Crohn's disease (CD). However, relationships of these inflammatory dietary determinants with the microbiome remain largely unknown. In this cross-sectional study, we evaluate the association between the inflammatory potential of habitual diet, as assessed by the modified Children-Dietary Inflammatory Index (mC-DII), and the fecal microbiome and metabolome of children with CD in comparison to healthy children.</p><p><strong>Methods: </strong>A cross-sectional study including 51 children with CD between 6 and 18 years of age and 50 healthy controls was conducted. Dietary inflammatory potential was measured using the modified Children-Dietary Inflammatory Index (mC-DII) and diet quality assessed by the Healthy Eating Index (HEI)-2015 and alternate Mediterranean eating index (aMed). Microbiome was analysed using shotgun metagenomic sequencing and untargeted metabolomic analysis.</p><p><strong>Results: </strong>A poor-quality, pro-inflammatory diet with similar mC-DII, HEI-2015 and aMed scores was found across healthy children and children with CD. In children with active disease, a pro-inflammatory diet was associated with decreased diversity, increased virulence potential and expansion of the Proteobacteria phylum dominated by Escherichia coli (E. coli) spp. Positive correlation between E. coli relative abundance and mC-DII was associated with a low intake of a cluster composed of fibers, vitamins and minerals with anti-inflammatory potential. A negative association between metabolites of fatty acid metabolism and HEI was found.</p><p><strong>Conclusions: </strong>In total, our results suggest that a pro-inflammatory diet may potentiate hallmarks of the inflammation-associated dysbiosis in CD and highlight the need for microbiome-targeted dietary interventions optimizing the anti-inflammatory potential of habitual diet in the management of pediatric CD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070525","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":"Lysophosphatidylcholine-Induced Aberrant Adipogenesis in Mesenchymal Stem Cells and Impaired Antibacterial Function in Adipocytes of Creeping Fat.","authors":"Fangting Wu, Wenting Xie, Anqi Yu, Xiaoxia Lin, Ting Ouyang, Jieying Fei, Xi Liu, Hui Yang, Da Zhang, Jintao Shi, Weidong Wang, Miaoxing Huang, Guiquan Chen, Fang Xie, Fengfei Wu, Lan Bai","doi":"10.1093/ecco-jcc/jjaf019","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf019","url":null,"abstract":"<p><strong>Background and aim: </strong>Creeping fat (CF) in Crohn's disease (CD) is characterized by hyperplastic mesenteric adipose tissue (MAT) encasing fibrotic intestinal segments. CF exhibits disruptions in microbiota and lipid metabolism, particularly in lysophospholipids (LPC). This study aims to elucidate the impact of LPC on adipogenic differentiation of mesenchymal stem cells in CF and its effects on immune defense functions in the differentiated adipocytes.</p><p><strong>Methods: </strong>Isolated adipocytes of MAT from CD and Non-CD patients were analyzed for bacterial counts and composition using AQ-PCR and 16S rRNA. RNA sequencing was performed on isolated adipocytes to assess functionality. LPC levels in CD patients and their effects on adipocyte immune defense were measured using lipidomics, ELISA, and bacterial killing assays. A TNBS-induced colitis model was used to measure LPC levels in plasma and gene expression in MAT.</p><p><strong>Results: </strong>Significant shifts in microbial diversity and bacterial load were observed in CF-derived adipocytes, characterized by increased colonization by pathogenic bacteria and diminished antibacterial capabilities. Sequencing analysis revealed downregulation of antimicrobial genes, including SAA1/2, and upregulation of lipid metabolism-related genes. Lipidomic analysis of CF showed elevated LPC levels, a pro-inflammatory lipid also found in plasma of CD patients. In vitro experiments demonstrated LPC promotes adipogenesis through EGR2, while impairing adipocytes' antibacterial immunity. These findings were consistent in the TNBS-treated mouse model, where increased LPC levels in the blood, and a significant reduction in SAA1/2-positive adipocytes were noted.</p><p><strong>Conclusions: </strong>LPC-induced aberrant adipogenesis in CF is a newly identified pathological feature in CD patients and a potential therapeutic target.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070531","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":"Janus kinase inhibitors in the management of acute severe ulcerative colitis: a comprehensive review.","authors":"Javier P Gisbert, María Chaparro","doi":"10.1093/ecco-jcc/jjaf021","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf021","url":null,"abstract":"<p><strong>Background: </strong>One third of patients with acute severe ulcerative colitis (ASUC) are steroid-refractory. Cyclosporine and infliximab are currently the mainstays of salvage therapy. Janus kinase inhibitors (JAKi) could play a role in the treatment of ASUC.</p><p><strong>Aim: </strong>To review the evidence on JAKi in the management of ASUC.</p><p><strong>Methods: </strong>We performed a bibliographic search to identify studies focusing on the treatment of ASUC with JAKi.</p><p><strong>Results: </strong>Potential advantages of JAKi for the management of ASUC include their oral administration, rapid onset of action, short half-life, lack of immunogenicity, and effectiveness in patients with prior biologic exposure. Thirty studies (including 373 patients) have evaluated the efficacy of tofacitinib in ASUC, with a response rate (avoidance of colectomy) ranging between 43% and 100%, with a weighted mean of 82%. Experience with upadacitinib is more limited (only 10 studies and 74 patients are available), but also encouraging: mean colectomy-free rate ranging between 67% and 100%, with a weighted mean of 79%. However, experience with filgotinib in ASUC is currently nonexistent. Regarding safety, the available data does not reveal any new safety concerns when JAKi are used in ASUC, although follow-up periods are still short.</p><p><strong>Conclusion: </strong>JAKi seem to be a promising treatment option for ASUC, with both tofacitinib and upadacitinib achieving colectomy-free rates of approximately 80%. Further studies are essential to define whether JAKi can replace cyclosporine/infliximab as second line therapy for the medical management of ASUC, or whether they can even be used as initial treatment in place of intravenous corticosteroids.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070528","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":"Intestinal Epithelial Ptpn23 Is Essential For Gut Barrier Integrity And Prevention Of Fatal Bacterial Translocation.","authors":"Rocio Sanchez Alvarez, Ana Montalban-Arques, Yasser Morsy, Claudia Gottier, Janine Häfliger, Kirstin Atrott, Anna Bircher, Egle Katkeviciute, Doris Pöhlmann, Luise Linzmeier, Madita Determann, Céline Mamie, Anna Niechcial, Marlene Schwarzfischer, Sebastian Zeissig, Silvia Lang, Michael Scharl, Marianne Spalinger","doi":"10.1093/ecco-jcc/jjaf016","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf016","url":null,"abstract":"<p><strong>Background and aims: </strong>Protein tyrosine phosphatase non-receptor type 23 (PTPN23) regulates the internalization of growth factor receptors such as the epithelial growth factor receptor (EGFR). Given the crucial function of such receptors in intestinal epithelial cells (IECs), we assessed the involvement of PTPN23 in intestinal homeostasis and epithelial proliferation.</p><p><strong>Methods: </strong>We generated mouse models with constitutive (PTPN23fl/flVilCre+/-) or inducible (PTPN23fl/flVilCreERT+/-) deletion of PTPN23 in IEC. To elucidate the functional consequences of PTPN23 deletion in IEC, we performed barrier function studies, flow cytometry, RNAseq and in vivo experiments applying EGFR inhibition, antibiotic treatment, or co-housing approaches to further delineate the observed phenotype.</p><p><strong>Results: </strong>Deletion of PTPN23 in IECs resulted in a severe early-onset phenotype in both models. Mice were characterized by elongated colon, epithelial hyperproliferation, splenomegaly and diarrhea leading to the death of the mice within 3 weeks of PTNP23 deletion. Compromised gut barrier integrity resulted in enhanced bacterial translocation accompanied by reduced IgA transcytosis in PTPN23fl/flVilCreERT+/- compared to wild-type mice. Although EGFR surface expression was increased upon PTPN23-deletion, inhibition of EGFR signaling did not prevent disease. In contrast, and in accordance with defective bacterial handling, antibiotic treatment, but not co-housing, fully rescued the phenotype.</p><p><strong>Conclusion: </strong>The absence of PTPN23 in IECs leads to lethal dysregulation of intestinal homeostasis, triggered by bacterial infiltration due to defects in the intestinal epithelial barrier and impaired IgA transcytosis. Thus, we identify PTPN23 as a novel key player in preserving intestinal epithelial homeostasis, ultimately preventing bacterial overgrowth and excessive immune activation in the intestine.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054687","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":"The Impact of Advanced Medical Therapies on Time to Resection and Colorectal Cancer Outcomes in Ulcerative Colitis Patients Undergoing Colectomy.","authors":"Eva Visser, Antonio Luberto, Lianne Heuthorst, Roel Hompes, Séverine Vermeire, Geert R D'Haens, Willem A Bemelman, Andre D'Hoore, Gabriele Bislenghi, Christianne J Buskens","doi":"10.1093/ecco-jcc/jjaf015","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf015","url":null,"abstract":"<p><strong>Background: </strong>We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in UC.</p><p><strong>Methods: </strong>This cohort study included UC patients who underwent colectomy between 2003 and 2022 at two referral centres in Belgium and the Netherlands. Exposure was use of advanced medical therapies. Primary outcomes were time to colectomy and colorectal cancer (CRC) rate, compared between four periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017), P4 (2018-2022). Secondary outcomes were oncological outcomes, including incidental cancers found unexpectedly in resection specimens or during endoscopic follow-up for medication switch.</p><p><strong>Results: </strong>Among 716 patients, the usage of advanced therapies increased from 36.8% in P1 to 89.7% in P4 (p<0.0001). Median time to colectomy remained comparable (P1: 7.1 years [IQR, 2.8-12.9] vs P4: 7.2 years [IQR, 2.7-14.6]; p=not significant). CRC was diagnosed in 72 (10.1%) patients, with no significant change over time (p=0.44). Proportion of CRC was lower in patients treated with advanced therapies (4.7% vs 23.6%, p<0.0001), related to a shorter follow-up (median 6.1 vs 10.3 years, p<0.0001). Advanced therapy patients had higher incidental cancer rates (37.5% vs 8.3%, p=0.002), which was associated with reduced CRC-related survival (HR for CRC-related death: 3.3, 95% CI 1.17-9.4; p=0.02).</p><p><strong>Conclusion: </strong>Despite increased usage of advanced medical therapies, time to resection and CRC rates have remained unchanged in UC patients undergoing colectomy over the past two decades. Advanced therapy patients had higher incidental cancers rates, associated with decreased CRC-survival. Awareness of timely colectomy is crucial for this group.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030528","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":"GSDMB modulates intestinal epithelial homeostasis via regulating hyperactive unfolded protein response in Crohn's disease.","authors":"Wenbin Gong, Peizhao Liu, Juanhan Liu, Yangguang Li, Haiyang Jiang, Weizhen Li, Jiaqi Kang, Fan Jiao, Xiuwen Wu, Yun Zhao, Jianan Ren","doi":"10.1093/ecco-jcc/jjaf012","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf012","url":null,"abstract":"<p><strong>Background: </strong>Impaired intestinal epithelial barrier has been considered to be associated with an increasing variety of gastrointestinal diseases, especially inflammatory bowel disease (IBD) encompassing Crohn's disease (CD) and ulcerative colitis (UC). We aimed to investigate the role of Gasdermin B (GSDMB) in modulating intestinal epithelial barrier integrity and proposed a promising therapeutic strategy.</p><p><strong>Methods: </strong>GSDMB expression was evaluated in adult CD samples by molecular biology means and single-cell transcriptomes. We generated GSDMB (Rosa26-lsl/lsl-GSDMB;Villin-Cre) and one of its functional missense variant rs2305480 (Rosa26-lsl/lsl-GSDMB-MU;Villin-Cre) intestinal epithelial-specific knock in mice to observe the functions of GSDMB in intestinal epithelial barrier. RNA-seq analysis as well as human and murine intestine-derived organoids were used to determine the pathogenic mechanism of GSDMB.</p><p><strong>Results: </strong>The expression of GSDMB was increased during active intestinal inflammation and principally localized in intestinal epithelial cells (IECs). Rosa26-lsl/lsl-GSDMB;Villin-Cre mice developed enterocolitis and exhibited aberrant intestinal barrier integrity. Mechanistically, epithelial GSDMB modulated hyperactive unfolded protein response of IECs by up-regulating BHLHA15 to mediate intestinal barrier injury. Rosa26-lsl/lsl-GSDMB-MU;Villin-Cre mice with the mutant rs2305480 of GSDMB aggravated such inflammatory effects.</p><p><strong>Conclusion: </strong>We have uncovered an important and a previously unrecognized role of GSDMB in intestinal homeostasis, which represents a potential therapeutic target for intestinal inflammation.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019027","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}