Inflammatory Bowel Diseases最新文献

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Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis. 解决结肠炎期间驻留结肠肌层巨噬细胞的多样性和可塑性问题
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-05 DOI: 10.1093/ibd/izae155
Kensuke Ohishi, David Dora, Christopher Y Han, Richard A Guyer, Takahiro Ohkura, Simon Kazimierczyk, Nicole Picard, Abigail R Leavitt, Leah C Ott, Ahmed A Rahman, Jessica L Mueller, Nahum Y Shpigel, Nitya Jain, Nandor Nagy, Ryo Hotta, Allan M Goldstein, Rhian Stavely
{"title":"Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis.","authors":"Kensuke Ohishi, David Dora, Christopher Y Han, Richard A Guyer, Takahiro Ohkura, Simon Kazimierczyk, Nicole Picard, Abigail R Leavitt, Leah C Ott, Ahmed A Rahman, Jessica L Mueller, Nahum Y Shpigel, Nitya Jain, Nandor Nagy, Ryo Hotta, Allan M Goldstein, Rhian Stavely","doi":"10.1093/ibd/izae155","DOIUrl":"https://doi.org/10.1093/ibd/izae155","url":null,"abstract":"<p><strong>Background: </strong>Immune cell populations in the intestinal muscularis propria during colitis are poorly resolved. Maintaining homeostasis in this niche is critical, highlighted by the poorer prognosis of inflammatory bowel disease associated with muscularis propria inflammation.</p><p><strong>Methods: </strong>This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and dextran sodium sulfate-induced colitis. Findings are validated by immunohistochemistry, flow cytometry and cell-lineage tracing in vivo, and in vitro assays with muscularis macrophages (MMφ).</p><p><strong>Results: </strong>In naïve conditions, transcriptional duality is observed in MMφs with 2 major subpopulations: conventional resident Cx3cr1+ MMφs and Lyve1+ MMφs. The Lyve1+ population is phagocytic and expresses several known MMφ markers in mouse and human, confirming their identity as a bona fide MMφ subset. Single-cell transcriptomics indicate that resident MMφs are retained during colitis and exhibit plasticity toward an inflammatory profile. Lyve1+ MMφs, which express anti-inflammatory marker CD163, are absent during colitis, as confirmed by flow cytometry. In contrast, lineage tracing finds that resident Cx3cr1+ MMφs remain during colitis and are not completely replaced by the inflammatory infiltrating monocytes. In vitro studies provide biological evidence of the plasticity of resident Cx3cr1+ MMφs in response to lipopolysaccharide (LPS), mirroring transcriptional observations in vivo of their inflammatory plasticity. Potential markers for colitic MMφs, validated in animal models and in individuals with ulcerative colitis, are identified.</p><p><strong>Conclusions: </strong>Our findings contribute to the understanding of the immune system in the muscularis propria niche during colitis by resolving the heterogeneity and origins of colitic MMφs.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lifestyle Intervention Modulates the CD4+ T Cell Profile in the Blood of Crohn's Disease Patients. 生活方式干预可调节克罗恩病患者血液中的 CD4+ T 细胞谱。
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-05 DOI: 10.1093/ibd/izae154
Alexandra Mekes-Adamczyk, Nadine Gausmann, Özlem Öznur, Katrin Pfuhlmann, Jan Dziobaka, Jan Buer, Jost Langhorst, Astrid M Westendorf
{"title":"Lifestyle Intervention Modulates the CD4+ T Cell Profile in the Blood of Crohn's Disease Patients.","authors":"Alexandra Mekes-Adamczyk, Nadine Gausmann, Özlem Öznur, Katrin Pfuhlmann, Jan Dziobaka, Jan Buer, Jost Langhorst, Astrid M Westendorf","doi":"10.1093/ibd/izae154","DOIUrl":"https://doi.org/10.1093/ibd/izae154","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease (CD) significantly affects patients' well-being and is influenced by stress and lifestyle factors, highlighting the importance of improving quality of life in CD management. An imbalance between pro- and anti-inflammatory CD4+ T cell responses is a key factor in CD, and stress has been shown to alter the function of CD4+ T cells. Therefore, this study aimed to evaluate the effect of a mind-body medicine stress management and lifestyle modification (MBM) program on the CD4+ T cell profile in CD patients.</p><p><strong>Methods: </strong>Circulating CD4+ T cells from CD patients were analyzed by flow cytometry following the MBM program. Patients were randomly assigned to either a guided intervention group (IG) or a self-guided waitlist control group (CG) over a 9-month trial and compared with healthy blood donors.</p><p><strong>Results: </strong>Lifestyle intervention reduced regulatory T cell (Treg) frequencies in the blood of CD patients. Notably, we observed a significant correlation between the quality of life improvement and Treg frequencies in the IG but not in the CG. Furthermore, differential activation and expression of the gut-homing molecules G protein-coupled receptor 15 and CCR9 on circulating Tregs and CD4+ effector T cells were detected in both the IG and CG.</p><p><strong>Conclusions: </strong>The MBM program, whether guided or self-directed, has the potential to restore the CD4+ T cell profile of CD patients to levels comparable to healthy blood donors. Lifestyle interventions may benefit CD progression, symptoms, and immunological status, but further analysis is needed to substantiate these findings and to fully understand their clinical implications. (ClinicalTrials.gov: NCT05182645).</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of Vaccination and Revaccination Against Hepatitis B Virus Using 2 Different Strategies in Patients With Inflammatory Bowel Disease. 炎症性肠病患者使用两种不同策略接种和再接种乙型肝炎病毒疫苗的效果
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-05 DOI: 10.1093/ibd/izae173
Panagiotis Markopoulos, Konstantinos Karmiris, Ioannis Dimas, Evangelos Voudoukis, Spyridon Siakavellas, Georgios Axiaris, Eirini Zacharopoulou, Evanthia Zampeli, Eftychia Tsironi, Maria Tzouvala, Georgios Papatheodoridis, Georgios Bamias
{"title":"Efficacy of Vaccination and Revaccination Against Hepatitis B Virus Using 2 Different Strategies in Patients With Inflammatory Bowel Disease.","authors":"Panagiotis Markopoulos, Konstantinos Karmiris, Ioannis Dimas, Evangelos Voudoukis, Spyridon Siakavellas, Georgios Axiaris, Eirini Zacharopoulou, Evanthia Zampeli, Eftychia Tsironi, Maria Tzouvala, Georgios Papatheodoridis, Georgios Bamias","doi":"10.1093/ibd/izae173","DOIUrl":"https://doi.org/10.1093/ibd/izae173","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel disease (IBD) exhibit an increased risk for acquiring hepatitis B virus (HBV), thus they should be vaccinated preferably, if not already infected or immunized. We assessed the efficacy of HBV vaccination in IBD patients and impact of different factors on the immune response. We also evaluated the success rate of 2 different revaccination strategies in the nonresponders.</p><p><strong>Methods: </strong>This was a retrospective observational cohort study carried out in 5 tertiary centers. All patients were tested for hepatitis B surface antigen, antibodies against hepatitis B surface antigen (anti-HBs), and antibodies against hepatitis B core antigen. Patients tested negative and underwent the standard schedule with 20 µg at 0, 1, and 6 months. Nonresponders (anti-HBs <10 IU/L) were offered a revaccination scheme with either 3 doses of 40 µg at 0, 1, and 6 months or an accelerated scheme with 20 µg at 0, 1, and 2 months.</p><p><strong>Results: </strong>A total of 409 patients were included, and 273 (66.7%) of those (females: 49.5%; Crohn's disease [CD]: 56.7%) responded to baseline vaccination. A total of 189 (69.2%) of 273 (females: 48.1%; CD: 60.3%) developed anti-HBs >100 IU/L. Body mass index <30 kg/m2 (P = .017) was positively associated, while diagnosis of CD (P = .013), extensive UC (P <.0001), extraintestinal manifestations (P = .001), and treatment with immunomodulators/anti-tumor necrosis factor (P < .00) negatively affected the response. Revaccination was offered to 103 patients, and 58.3% of them achieved anti-HBs >10 IU/L. Both revaccination strategies were equally effective.</p><p><strong>Conclusions: </strong>IBD patients demonstrate lower response to HBV vaccination compared with the general population. Age, body mass index, type, disease activity, and immunosuppression negatively affect the response. Half of nonresponders may benefit from an enhanced revaccination attempt.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study. Ustekinumab 用于克罗恩病患者的一年安全性和有效性:K-STAR研究
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-03 DOI: 10.1093/ibd/izae171
Chang Kyun Lee, Won Moon, Jaeyoung Chun, Eun Soo Kim, Hyung Wook Kim, Hyuk Yoon, Hyun Soo Kim, Yoo Jin Lee, Chang Hwan Choi, Yunho Jung, Sung Chul Park, Geun Am Song, Jong Hun Lee, Eun Suk Jung, Youngdoe Kim, Su Young Jung, Jong Min Choi, Byong Duk Ye
{"title":"One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.","authors":"Chang Kyun Lee, Won Moon, Jaeyoung Chun, Eun Soo Kim, Hyung Wook Kim, Hyuk Yoon, Hyun Soo Kim, Yoo Jin Lee, Chang Hwan Choi, Yunho Jung, Sung Chul Park, Geun Am Song, Jong Hun Lee, Eun Suk Jung, Youngdoe Kim, Su Young Jung, Jong Min Choi, Byong Duk Ye","doi":"10.1093/ibd/izae171","DOIUrl":"https://doi.org/10.1093/ibd/izae171","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD).</p><p><strong>Methods: </strong>Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120).</p><p><strong>Results: </strong>Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment.</p><p><strong>Conclusions: </strong>Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients. 乌司替库单抗和抗肿瘤坏死因子在老年克罗恩病患者中的安全性和有效性比较
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-03 DOI: 10.1093/ibd/izae174
Gerum Gashaw Gebeyehu, Giacomo Broglio, Eleanor Liu, Jimmy K Limdi, Christian Selinger, Joseph Fiske, Violeta Razanskaite, Philip J Smith, Paul K Flanagan, Sreedhar Subramanian
{"title":"Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.","authors":"Gerum Gashaw Gebeyehu, Giacomo Broglio, Eleanor Liu, Jimmy K Limdi, Christian Selinger, Joseph Fiske, Violeta Razanskaite, Philip J Smith, Paul K Flanagan, Sreedhar Subramanian","doi":"10.1093/ibd/izae174","DOIUrl":"https://doi.org/10.1093/ibd/izae174","url":null,"abstract":"<p><strong>Background: </strong>Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly.</p><p><strong>Methods: </strong>The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence.</p><p><strong>Results: </strong>Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months.</p><p><strong>Conclusions: </strong>We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling Twisted Pouch Syndrome: A Narrative Review of Classification, Diagnosis, Treatment, and Prevention. 揭开扭曲袋综合征的神秘面纱:关于分类、诊断、治疗和预防的叙述性综述。
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-03 DOI: 10.1093/ibd/izae161
Stefan D Holubar
{"title":"Unraveling Twisted Pouch Syndrome: A Narrative Review of Classification, Diagnosis, Treatment, and Prevention.","authors":"Stefan D Holubar","doi":"10.1093/ibd/izae161","DOIUrl":"https://doi.org/10.1093/ibd/izae161","url":null,"abstract":"<p><strong>Background: </strong>We recently described a cluster of symptoms known as twisted pouch syndrome that rarely affects patients with ileoanal pouches. Herein, we present a narrative review in which we describe the diagnosis, treatment, and prevention of twisted pouch syndrome, with a focus on a simple classification schema.</p><p><strong>Methods: </strong>Diagnostic signs from endoscopic and radiological examinations, treatment, and prevention strategies are presented.</p><p><strong>Results: </strong>Patients with twisted pouch syndrome suffer from a triad of obstructive symptoms, erratic bowel habits, and pain which may be severe, debilitating visceral pain, all in the setting of a mechanical pouch abnormality. Diagnostic modalities include imaging, careful pouchoscopy, functional testing, diagnostic laparoscopy or laparotomy, and recently 3-dimensional pouchography. Classification of twisted pouch syndrome is based on the location and degree of rotation of the pouch and its mesentery. Outlet twists may result when the distal pouch rotates >90° to 360° clockwise inadvertently during anastomosis; when only the distal most pouch is twisted, it results in an iris-like deformity of the pouch outlet, or when the distal half of the pouch is twisted, a mid-pouch stenosis and an hourglass-shaped pouch may result. Inlet twists are either a full 360° (mesentery posterior), unintentional 180° (mesentery anterior), or 90° counterclockwise twists. Both inlet and outlet twists are fixed deformities and may only be reduced by disconnecting the entire pouch from the anus. If they result in twisted pouch syndrome, a redo pouch procedure or pouch excision is required to reduce the twist; 90° counterclockwise twists may undergo pouch inlet transposition. Adhesive twists result when the pouch becomes fixed in the pelvis in an abnormal configuration, such as when the efferent limb becomes twisted underneath the afferent limb secondary to an occult tip of the J leak, and may be reduced by pelvic adhesiolysis with or without pouch revision.</p><p><strong>Conclusions: </strong>Pouches may rarely be inadvertently twisted during construction or twisted owing to adhesive disease or leaks. A high index of suspicion is needed to establish the diagnosis. We present a simple classification of twisted pouch syndrome that may aid in the prevention and recognition of these often difficult to diagnose postoperative complications.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MYO5B and the Polygenic Landscape of Very Early-Onset Inflammatory Bowel Disease in an Ethnically Diverse Population. MYO5B与不同种族人群中极早发炎性肠病的多基因景观
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-03 DOI: 10.1093/ibd/izae169
Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer
{"title":"MYO5B and the Polygenic Landscape of Very Early-Onset Inflammatory Bowel Disease in an Ethnically Diverse Population.","authors":"Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer","doi":"10.1093/ibd/izae169","DOIUrl":"https://doi.org/10.1093/ibd/izae169","url":null,"abstract":"<p><strong>Background: </strong>Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.</p><p><strong>Methods: </strong>Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD \"susceptibility\" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored by Combined Annotation Dependent Depletion for deleteriousness. Gene networks carrying susceptibility SNVs were created. Myosin 5b immunofluorescence was also studied.</p><p><strong>Results: </strong>Fifty-six patients met inclusion criteria, and 32.1% identified as Hispanic. Monogenic disease was infrequent (8.9%). Significant enrichment of GOI susceptibility SNVs was observed, notably in MYO5B, especially in Hispanics. MEFV, TNFAIP3, SH3TC2, and NCF2 were also central participants in the GOI networks. Myosin 5b immunofluorescence in colonic mucosa was significantly reduced in those with MYO5B susceptibility SNVs compared with control subjects. Seven genes (ESRRA, HLA-DQ1, RETSAT, PABPC1, PARP4, CCDC102A, and SUSD2) were central participants in the non-GOI networks.</p><p><strong>Conclusions: </strong>Our results support the polygenic nature of VEO-IBD, in which key participants, like MYO5B, were identified through network analytics. Rare variant load within susceptibility genes may be relevant not only for the genetic origins of inflammatory bowel disease, but also for the age of disease onset. Our findings could guide future work in precision medicine.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mirikizumab Sustained Impact on Fatigue in Patients with Moderately to Severely Active Crohn's Disease in the Phase 2 AMAG Study. 在 AMAG 2 期研究中,米利珠单抗对中度至重度活动性克罗恩病患者的疲劳产生了持续影响。
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-02 DOI: 10.1093/ibd/izae166
Miguel Regueiro, Monika Fischer, Peter Bossuyt, Kim McGinnis, Marijana Protic, Theresa Hunter Gibble, Tommaso Panni, Lai Shan Chan, Toshifumi Hibi, David T Rubin
{"title":"Mirikizumab Sustained Impact on Fatigue in Patients with Moderately to Severely Active Crohn's Disease in the Phase 2 AMAG Study.","authors":"Miguel Regueiro, Monika Fischer, Peter Bossuyt, Kim McGinnis, Marijana Protic, Theresa Hunter Gibble, Tommaso Panni, Lai Shan Chan, Toshifumi Hibi, David T Rubin","doi":"10.1093/ibd/izae166","DOIUrl":"https://doi.org/10.1093/ibd/izae166","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is a burdensome, under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104).</p><p><strong>Methods: </strong>Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200 mg, 600 mg, or 1000 mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300 mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300 mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient.</p><p><strong>Results: </strong>At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers.</p><p><strong>Conclusions: </strong>Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Treat-to-Target Strategy Guided by Pan-Enteric Evaluation in Children With Crohn's Disease Improves Outcomes at 2 Years. 以泛肠道评估为指导的克罗恩病患儿 "靶向治疗 "策略改善了 2 年后的疗效。
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-01 DOI: 10.1093/ibd/izad173
Giulia D'Arcangelo, Giusy Russo, Marina Aloi, Cosimo Ruggiero, Francesca Maccioni, Cesare Hassan, Paola Papoff, Stanley Allen Cohen, Salvatore Oliva
{"title":"A Treat-to-Target Strategy Guided by Pan-Enteric Evaluation in Children With Crohn's Disease Improves Outcomes at 2 Years.","authors":"Giulia D'Arcangelo, Giusy Russo, Marina Aloi, Cosimo Ruggiero, Francesca Maccioni, Cesare Hassan, Paola Papoff, Stanley Allen Cohen, Salvatore Oliva","doi":"10.1093/ibd/izad173","DOIUrl":"10.1093/ibd/izad173","url":null,"abstract":"<p><strong>Background and aims: </strong>It is uncertain whether a treat-to-target approach could be an effective strategy for improving outcomes in children with Crohn's disease (CD). Previously, we reported mucosal healing (MH) and deep remission rates throughout the intestinal tract by performing 3 pan-enteric capsule assessments and using a treat-to-target strategy over 52 weeks in children with CD. This report describes the outcomes of this approach at 104 weeks.</p><p><strong>Methods: </strong>Children with known CD who completed the 52-week protocol repeated pan-enteric capsule endoscopy (PCE) at 104 weeks. Results at weeks 52 and 104 were compared, and long-term outcomes between patients, with and without MH, were calculated using an intention-to-treat analysis of clinical relapse, need for steroids, treatment escalation, hospitalization, and surgery.</p><p><strong>Results: </strong>Of the previous study cohort of 48 patients, 46 (96%) were available for this extension study (28 [61%] of 46 with MH and 18 [39%] of 46 without MH at 52 weeks). When evaluated at 104 weeks, MH was maintained in 93% of patients with MH at 52 weeks. In the intention-to-treat analysis, complete MH at 52 weeks was associated with reduced risk of steroid use (log-rank P < .0001), treatment escalation (log-rank P < .0001), hospitalization (log-rank P < .0001), and clinical relapse (log-rank P < .0001).</p><p><strong>Conclusions: </strong>When a PCE-based, treat-to-target strategy is employed, MH is sustainable (93%) over a 1-year period and is correlated with improved patient outcomes, including reduced need for steroids, treatment escalation, hospitalization, and clinical relapses at 104 weeks.ClinicalTrials.gov number: NCT03161886.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10413932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Postvaccination Symptoms After a Fourth Dose of mRNA SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease. 炎症性肠病患者接种第四剂信使核糖核酸严重急性呼吸系统综合征冠状病毒2疫苗后的疫苗接种后症状。
IF 4.5 3区 医学
Inflammatory Bowel Diseases Pub Date : 2024-08-01 DOI: 10.1093/ibd/izad198
Yoo Jin Lee, Dalin Li, Angela Mujukian, Philip Debbas, Melissa Hampton, Emebet Mengesha, Susan Cheng, Joseph E Ebinger, Michael Chiorean, Donald Lum, Oriana M Damas, Jonathan Braun, Dermot P B McGovern, Gil Y Melmed
{"title":"Postvaccination Symptoms After a Fourth Dose of mRNA SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease.","authors":"Yoo Jin Lee, Dalin Li, Angela Mujukian, Philip Debbas, Melissa Hampton, Emebet Mengesha, Susan Cheng, Joseph E Ebinger, Michael Chiorean, Donald Lum, Oriana M Damas, Jonathan Braun, Dermot P B McGovern, Gil Y Melmed","doi":"10.1093/ibd/izad198","DOIUrl":"10.1093/ibd/izad198","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41126956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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