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Molecular Basis of Intestinal Fibrosis in Inflammatory Bowel Disease. 炎症性肠病肠纤维化的分子基础。
Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1159/000528312
Akira Andoh, Atsushi Nishida

Background: Intestinal fibrosis in Crohn's disease (CD) is considered to be irreversible and induces persistent luminal narrowing and strictures. In the past decades, substantial advances have been made in the understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD).

Summary: Intestinal fibrosis is typically associated with mesenchymal cell hyperplasia, tissue disorganization, and deposition of extracellular matrix (ECM). The transient appearance of mesenchymal cells is a feature of normal wound healing, but the persistence of these cells is associated with ECM deposition and fibrosis, leading to loss of normal architecture and function. When homeostatic control of the repair process becomes dysregulated, perpetual activation of profibrotic responses and sustained accumulation of ECM are induced. In the process of intestinal fibrosis, myofibroblasts are considered to be the key effector cells, being responsible for the synthesis of ECM proteins. Activation and accumulation of myofibroblasts in the stricturing lesions of CD patients are mediated by various factors such as growth factors, cytokines, epithelial-to-mesenchymal or endothelial-to-mesenchymal transitions. Despite the identification of many putative targets and target pathways applicable to antifibrotic therapies, no such treatment has yet been successful. Predictive biomarkers and non-invasive diagnostic tools for intestinal fibrosis are still insufficient in IBD.

Key message: We summarize recent advances in the understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in IBD.

背景:肠纤维化在克罗恩病(CD)被认为是不可逆的,并诱导持续的管腔狭窄和狭窄。在过去的几十年里,在理解炎症性肠病(IBD)肠道纤维化的细胞和分子机制方面取得了实质性进展。摘要:肠纤维化通常与间充质细胞增生、组织紊乱和细胞外基质(ECM)沉积有关。间充质细胞的短暂出现是正常伤口愈合的一个特征,但这些细胞的持续存在与ECM沉积和纤维化有关,导致正常结构和功能的丧失。当修复过程的稳态控制失调时,促纤维化反应的永久激活和ECM的持续积累就会被诱导。在肠纤维化过程中,肌成纤维细胞被认为是关键的效应细胞,负责ECM蛋白的合成。肌成纤维细胞在CD患者狭窄病变中的激活和积累是由多种因素介导的,如生长因子、细胞因子、上皮到间质或内皮到间质转化。尽管确定了许多适用于抗纤维化治疗的假定靶点和靶点通路,但尚未有此类治疗成功。在IBD中,预测肠纤维化的生物标志物和非侵入性诊断工具仍然不足。关键信息:我们总结了IBD肠道纤维化的细胞和分子机制的最新进展。
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引用次数: 3
Early-Phase Partial Mayo Score following Golimumab Treatment Is Associated with Endoscopic Improvement at 1 Year in Ulcerative Colitis: A post hoc Analysis of PURSUIT-J Randomized Controlled Trial. Golimumab治疗后的早期部分Mayo评分与溃疡性结肠炎1年的内镜改善相关:一项对PURSUIT-J随机对照试验的事后分析
Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1159/000526264
Katsumasa Nagano, Yuya Imai, Yoshifumi Ukyo, Taku Kobayashi, Seiji Yokoyama

Introduction: Golimumab (GLM) is an anti-tumor necrosis factor-alpha antibody therapy for moderately to severely active ulcerative colitis (UC). Endoscopic improvement is considered one of UC treatment's main goals, and earlier prediction of future endoscopic improvement has clinical implications. We retrospectively analyzed data from the PURSUIT-J, a phase III randomized controlled trial evaluating the efficacy of GLM in the maintenance phase, to find predictors for endoscopic improvement after 60 weeks of GLM treatment.

Methods: Ninety-two patients who had completed the maintenance phase of the PURSUIT-J were divided into two groups: those with mucosal healing (MH: Mayo endoscopic subscore of 0 or 1) and those without MH at week 60 (non-MHs). Multivariate logistic regression analysis was conducted using baseline data in the induction phase to determine predictive factors for MHs compared to non-MHs.

Results: Twenty-nine patients were classified as MHs and 63 as non-MHs. The multivariate logistic regression analysis showed that the odds ratio for partial Mayo (pMayo) score was highest in MHs (1.87 [95% CI: 1.18-2.98]) at baseline in the induction phase. The receiver operating characteristic analysis to determine the timing of predictions of MHs using pMayo showed that an area under the curve reached 0.8 at week 14 after the first GLM administration.

Discussion/conclusion: pMayo scores at week 14 of GLM treatment are associated with MH at week 60. These results suggest the timing when a clinical decision to continue GLM based on the patient-reported outcomes and the physician's general assessment could be considered.

Golimumab (GLM)是一种抗肿瘤坏死因子- α抗体治疗中度至重度活动性溃疡性结肠炎(UC)的药物。内镜改善被认为是UC治疗的主要目标之一,早期预测未来内镜改善具有临床意义。我们回顾性分析了一项评估GLM在维持期疗效的III期随机对照试验的数据,以寻找GLM治疗60周后内镜改善的预测因素。方法:92例完成了维持期的患者分为两组:粘膜愈合组(MH: Mayo内镜亚评分为0或1)和60周无MH组(非MH组)。采用诱导期基线数据进行多变量logistic回归分析,以确定mhhs与非mhhs的预测因素。结果:mhh 29例,非mhh 63例。多因素logistic回归分析显示,在诱导期基线时,MHs部分Mayo评分的比值比最高(1.87 [95% CI: 1.18-2.98])。使用pMayo确定mhh预测时间的受试者工作特征分析显示,在第一次GLM给药后的第14周,曲线下面积达到0.8。讨论/结论:GLM治疗第14周的pMayo评分与第60周的MH相关。这些结果表明,根据患者报告的结果和医生的一般评估,可以考虑临床决定继续GLM的时机。
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引用次数: 0
Smoking Is Not an Independent Risk Factor for Surgery in Patients with Crohn's Disease on Biologic Therapy. 吸烟不是克罗恩病患者接受生物治疗手术的独立危险因素。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1159/000530689
Saleem M Halablab, Ayman Alrazim, Christian Sadaka, Hasan Slika, Nour Adra, Wissam Ghusn, Manar Shmais, Ala I Sharara

Introduction: The development and course of inflammatory bowel disease appear to be influenced by environmental factors. Particularly, smoking has been shown to assume a harmful role in Crohn's disease (CD) and a protective role in ulcerative colitis. This study aims to examine the effect of smoking on need for surgery in patients with moderate to severe CD receiving biologic therapy.

Methods: This was a retrospective study of adult patients with CD at a University Medical Center over a 20-year period.

Results: A total of 251 patients were included (mean age 36.0 ± 15.0; 70.1% males; current, former, and nonsmokers: 44.2%, 11.6%, and 43.8%, respectively). Mean duration on biologics was 5.0 ± 3.1 years (>2/3 received anti-TNFs, followed by ustekinumab in 25.9%) and a third of patients (29.5%) received more than one biologic. Disease-related surgeries (abdominal, perianal, or both) occurred in 97 patients (38.6%): 50 patients had surgeries prior to starting biologics only, 41 had some surgeries after, and 6 had insufficient information. There was no significant difference in surgeries between ever-smokers (current or previous) versus nonsmokers in the overall study group. On logistic regression, the odds of having any CD surgery were higher in patients with longer disease duration (OR = 1.05, 95% CI = 1.01, 1.09) and in those receiving more than one biologic (OR = 2.31, 95% CI = 1.16, 4.59). However, among patients who had surgery prior to biologic therapy, smokers were more likely to have perianal surgery compared to nonsmokers (OR = 10.6, 95% CI = 2.0, 57.4; p = 0.006).

Conclusion: In biologic-naive CD patients requiring surgery, smoking is an independent predictor of perianal surgery. Smoking, however, is not an independent risk factor for surgery in this cohort after starting biologics. The risk of surgery in those patients is primarily associated with disease duration and the use of more than one biologic.

炎症性肠病的发展和病程似乎受环境因素的影响。特别是,吸烟已被证明在克罗恩病(CD)中起有害作用,在溃疡性结肠炎中起保护作用。本研究旨在探讨吸烟对接受生物治疗的中重度CD患者手术需求的影响。方法:这是一项对大学医学中心20年期间的成年乳糜泻患者的回顾性研究。结果:共纳入251例患者(平均年龄36.0±15.0;男性70.1%;目前、曾经和不吸烟者:分别为44.2%、11.6%和43.8%)。生物制剂的平均持续时间为5.0±3.1年(>2/3接受了抗tnf,其次是25.9%的ustekinumab),三分之一的患者(29.5%)接受了一种以上的生物制剂。97例患者(38.6%)进行了与疾病相关的手术(腹部、肛周或两者):50例患者仅在开始使用生物制剂前进行了手术,41例患者在开始使用生物制剂后进行了一些手术,6例患者信息不足。在整个研究组中,吸烟者(现在或以前)与不吸烟者之间的手术没有显著差异。在logistic回归中,病程较长的患者(OR = 1.05, 95% CI = 1.01, 1.09)和接受一种以上生物制剂治疗的患者(OR = 2.31, 95% CI = 1.16, 4.59)接受任何CD手术的几率更高。然而,在生物治疗前进行手术的患者中,吸烟者比不吸烟者更有可能进行肛周手术(OR = 10.6, 95% CI = 2.0, 57.4;P = 0.006)。结论:在需要手术的生物源性乳糜泻患者中,吸烟是肛周手术的独立预测因素。然而,在该队列中,吸烟并不是开始使用生物制剂后手术的独立危险因素。这些患者的手术风险主要与病程和使用一种以上生物制剂有关。
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引用次数: 0
A Systematic Review of Self-Management Interventions for Patients with Inflammatory Bowel Disease. 炎症性肠病患者自我管理干预的系统综述
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1159/000530021
Masami Iizawa, Lisa Hirose, Maya Nunotani, Mikiko Nakashoji, Ai Tairaka, Jovelle L Fernandez

Introduction: Previous studies have reported the effectiveness of inflammatory bowel disease (IBD) self-management. However, it is unclear which types of self-management interventions are effective. We conducted a systematic literature review to clarify the status and efficacy of self-management interventions for IBD.

Methods: Searches were performed in databases including Embase, Medline, and Cochrane Library. Randomized, controlled studies of interventions in adult human participants with IBD involving a self-management component published in English from 2000 to 2020 were included. Studies were stratified based on study design, baseline demographic characteristics, methodological quality, and how outcomes were measured and analyzed for statistically significant improvements in outcomes, such as psychological health, quality of life, and healthcare resource usage.

Results: Among 50 studies included, 31 considered patients with IBD and 14 and 5 focused on patients with ulcerative colitis and Crohn's disease, respectively. Improvements in an outcome were reported in 33 (66%) studies. Most of the interventions that significantly improved an outcome index were based on symptom management and many of these were also delivered in combination with provision of information. We also note that among effective interventions, many were conducted with individualized and patient-participatory activities, and multidisciplinary healthcare practitioners were responsible for delivery of the interventions.

Conclusion: Ongoing interventions that focus on symptom management with provision of information may support self-management behavior in patients with IBD. A participatory intervention targeting individuals was suggested to be an effective intervention method.

先前的研究已经报道了炎症性肠病(IBD)自我管理的有效性。然而,目前尚不清楚哪种类型的自我管理干预是有效的。我们进行了系统的文献综述,以阐明IBD自我管理干预的现状和疗效。方法:在Embase、Medline、Cochrane Library等数据库中进行检索。本研究纳入了2000年至2020年期间发表的针对成年IBD患者的随机对照研究,这些研究涉及自我管理成分。根据研究设计、基线人口统计学特征、方法学质量以及如何测量和分析结果的统计显著改善(如心理健康、生活质量和医疗资源使用)对研究进行分层。结果:纳入的50项研究中,31项针对IBD患者,14项针对溃疡性结肠炎患者,5项针对克罗恩病患者。33项(66%)研究报告了结果的改善。大多数显著改善结果指数的干预措施都是基于症状管理的,其中许多干预措施还与提供信息相结合。我们还注意到,在有效的干预措施中,许多是通过个性化和患者参与的活动进行的,多学科的医疗保健从业者负责提供干预措施。结论:关注症状管理并提供信息的持续干预可能支持IBD患者的自我管理行为。针对个体的参与式干预是一种有效的干预方法。
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引用次数: 0
Front & Back Matter 正面和背面
Q2 Medicine Pub Date : 2022-07-01 DOI: 10.1159/000525875
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引用次数: 0
Editorial. 社论。
Q2 Medicine Pub Date : 2022-05-24 eCollection Date: 2022-07-01 DOI: 10.1159/000525236
Toshifumi Hibi, Gerhard Rogler
none
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引用次数: 0
Therapy Patterns and Surveillance Measures of Inflammatory Bowel Disease Patients beyond Disease-Related Hospitalization: A Claims-Based Cohort Study. 炎症性肠病患者在疾病相关住院治疗后的治疗模式和监测措施:一项基于索赔的队列研究
Q2 Medicine Pub Date : 2022-04-27 eCollection Date: 2022-07-01 DOI: 10.1159/000524741
Caroline Bähler, Beat Brüngger, Eva Blozik, Stephan R Vavricka, Alain M Schoepfer

Introduction: Medical care and surveillance of inflammatory bowel disease (IBD) patients have been shown to be far from satisfactory. Data on therapy patterns and surveillance measures in IBD patients are scarce. We, therefore, aimed to compare the therapy patterns and surveillance management of IBD patients in the year before and after IBD-related hospitalization.

Methods: We examined medical therapy, surveillance management (influenza vaccination, dermatologist visits, Pap smear screening, creatinine measurements, iron measurements, and ophthalmologist visits) and healthcare utilization in 214 ulcerative colitis (UC) and 259 Crohn's disease (CD) patients who underwent IBD-related hospitalization from 2012 to 2014.

Results: IBD-related drug classes changed in 64.5% of IBD patients following hospitalization. During the 1-year follow-up period, biological treatment increased in UC and CD patients, while steroid use decreased. Following hospitalization, 63.1% of UC and 27.0% of CD patients received 5-ASA. Only 21.6% of all IBD patients had a flu shot, and 19.6% of immunosuppressed IBD patients were seen by a dermatologist in the follow-up; other surveillance measures were more frequent. Surveillance before hospital admission and consultations by gastroenterologists were strongly correlated with surveillance during the postoperative follow-up, while gender and diagnosis (UC vs. CD) were not. During the 1-year follow-up, 20.5% of all IBD patients had no diagnostic or disease-monitoring procedure.

Discussion/conclusion: Surveillance measures for IBD patients are underused in Switzerland. Further research is needed to examine the impact of annual screenings and surveillance on patient outcomes.

简介:炎症性肠病(IBD)患者的医疗保健和监测显示远不能令人满意。关于IBD患者的治疗模式和监测措施的数据很少。因此,我们的目的是比较IBD患者在IBD相关住院前后一年的治疗模式和监测管理。方法:我们调查了2012年至2014年期间接受ibd相关住院治疗的214例溃疡性结肠炎(UC)和259例克罗恩病(CD)患者的药物治疗、监测管理(流感疫苗接种、皮肤科就诊、巴氏涂片筛查、肌酐测量、铁测量和眼科就诊)和医疗保健利用情况。结果:64.5%的IBD患者住院后IBD相关药物类别发生变化。在1年的随访期间,UC和CD患者的生物治疗增加,而类固醇使用减少。住院后,63.1%的UC和27.0%的CD患者接受5-ASA治疗。在随访中,仅有21.6%的IBD患者接种了流感疫苗,19.6%的免疫抑制IBD患者接受了皮肤科医生的检查;其他监测措施更为频繁。入院前的监测和胃肠病学家的咨询与术后随访期间的监测密切相关,而性别和诊断(UC与CD)无关。在1年的随访中,20.5%的IBD患者没有诊断或疾病监测程序。讨论/结论:瑞士对IBD患者的监测措施未得到充分利用。需要进一步的研究来检验年度筛查和监测对患者预后的影响。
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引用次数: 0
Title Page/Table of Contents 标题页/目录
Q2 Medicine Pub Date : 2022-01-01 DOI: 10.1159/000521666
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引用次数: 0
Early Laparoscopic Ileal Resection for Localized Ileocecal Crohn's Disease: Hard Sell or a Revolutionary New Norm? 早期腹腔镜回肠切除术治疗局部回盲克罗恩病:硬推销还是革命性的新规范?
Q2 Medicine Pub Date : 2022-01-01 DOI: 10.1159/000515959
Beatriz Yuki Maruyama, Christopher Ma, Remo Panaccione, Paulo Gustavo Kotze

Background: Despite reductions in surgical rates that have been observed with earlier use of biological therapy, surgery still constitutes an important tool in the therapeutic armamentarium in Crohn's disease (CD), particularly in patients with stenotic and penetrating phenotypes. In these scenarios, early surgical intervention is recommended, as bowel damage is present and irreversible, leading to lower efficacy with biologics.

Summary: The concept of early surgery in CD supposes the possible advantages of better surgical outcomes in luminal CD after initial resection. Optimal timing of surgical intervention is associated with better postoperative outcomes, whilst delays can lead to more technically difficult and extensive procedures, which may result in an increase in postoperative complication rates and higher rates of stoma formation. Furthermore, data from the LIR!C trial have demonstrated that early surgery in luminal localized inflammatory ileocecal CD is an adequate alternative to medical therapy, with lower societal costs in the long term. In this review, we discuss the position of early resection in ileocecal CD by critically reviewing available data, describing the ideal patients to be considered for early surgery, and weighing the potential advantages and disadvantages of an early surgery paradigm.

Key messages: While early surgery may not be the right choice for every patient, the ultimate decision regarding whether surgical or medical therapy should come first in the treatment paradigm must be individualized for each patient based on the disease characteristics, phenotype, risk factors, and personal preference. This highlights the importance of the multidisciplinary team, which remains a key pillar in deciding the overall management plan for patients with CD.

背景:尽管早期使用生物疗法可以降低手术率,但手术仍然是治疗克罗恩病(CD)的重要手段,特别是在狭窄和穿透型患者中。在这些情况下,建议早期手术干预,因为肠道损伤存在且不可逆,导致生物制剂的疗效较低。摘要:早期手术治疗乳糜泄的概念假设初始切除后的腔内乳糜泄可能有更好的手术效果。手术干预的最佳时机与更好的术后结果相关,而延迟可能导致技术上更困难和更广泛的手术,这可能导致术后并发症发生率的增加和更高的造口率。此外,来自LIR!C项试验表明,早期手术治疗腔内局限性炎性回盲部CD是一种适当的替代药物治疗方法,从长远来看具有较低的社会成本。在这篇综述中,我们通过批判性地回顾现有数据,描述早期手术的理想患者,并权衡早期手术模式的潜在优点和缺点,讨论了早期切除在回盲部CD中的地位。关键信息:虽然早期手术可能不是每个患者的正确选择,但最终决定是手术还是药物治疗应该在治疗模式中优先考虑,必须根据每个患者的疾病特征、表型、风险因素和个人偏好进行个性化治疗。这突出了多学科团队的重要性,这仍然是决定乳糜泻患者整体管理计划的关键支柱。
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引用次数: 13
Author Index Vol. 7, No. 1, 2022 作者索引第7卷第1期,2022年
Q2 Medicine Pub Date : 2022-01-01 DOI: 10.1159/000521667
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引用次数: 0
期刊
Inflammatory Intestinal Diseases
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