首页 > 最新文献

Inflammatory Intestinal Diseases最新文献

英文 中文
Dedicated Psychiatry Clinic for Inflammatory Bowel Disease Patients Has a Positive Impact on Depression Scores. 炎性肠病患者精神病专科门诊对抑郁评分有积极影响。
Q2 Medicine Pub Date : 2021-11-10 eCollection Date: 2022-07-01 DOI: 10.1159/000520797
Kaleb Bogale, Sanjay Yadav, August Stuart, Allen R Kunselman, Shannon Dalessio, Nana Bernasko, Andrew Tinsley, Kofi Clarke, Emmanuelle Williams, Matthew D Coates

Background: Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience.

Methods: We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys.

Results: Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (p = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire.

Conclusions: This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.

背景:精神疾病,包括焦虑和抑郁,在炎症性肠病(IBD)患者中更为常见。我们在我们的三级中心IBD诊所为IBD患者建立了一个综合精神病学诊所,为患者提供关键但经常无法获得的协调精神卫生服务。我们进行这项研究是为了评估这项服务对精神结局、生活质量和症状体验的影响。方法:我们进行了一项纵向前瞻性研究,比较在我们的综合ibd精神病学诊所接受治疗的患者和没有接受治疗的患者。我们提取了人口统计和临床信息,以及对有效调查的同期反应。结果:36名在IBD精神病学诊所接受治疗的患者与35名IBD患者的对照队列进行了比较。在研究队列中,随着时间的推移,医院焦虑和抑郁量表(HADS)抑郁评分显著降低(p = 0.001),但HADS焦虑评分没有显著降低。与对照组相比,研究队列显示HADS抑郁评分显著降低。在Harvey-Bradshaw指数、简单临床结肠炎活动指数或IBD简短问卷调查中,没有观察到显著差异。结论:这是第一项评估综合精神病学诊所对IBD患者影响的研究。与对照组不同的是,在这家诊所接受治疗的个体的平均HADS抑郁评分显著降低。需要更大规模的研究来验证这些发现。然而,这项研究表明,即使在IBD活动没有显著变化的情况下,使用综合精神病学IBD临床模型也可以改善心理健康结果。
{"title":"Dedicated Psychiatry Clinic for Inflammatory Bowel Disease Patients Has a Positive Impact on Depression Scores.","authors":"Kaleb Bogale,&nbsp;Sanjay Yadav,&nbsp;August Stuart,&nbsp;Allen R Kunselman,&nbsp;Shannon Dalessio,&nbsp;Nana Bernasko,&nbsp;Andrew Tinsley,&nbsp;Kofi Clarke,&nbsp;Emmanuelle Williams,&nbsp;Matthew D Coates","doi":"10.1159/000520797","DOIUrl":"https://doi.org/10.1159/000520797","url":null,"abstract":"<p><strong>Background: </strong>Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience.</p><p><strong>Methods: </strong>We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys.</p><p><strong>Results: </strong>Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (<i>p</i> = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire.</p><p><strong>Conclusions: </strong>This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"7 2","pages":"81-86"},"PeriodicalIF":0.0,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/fc/iid-0007-0081.PMC9294925.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40706569","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}
引用次数: 2
Behcet's Disease: An In-Depth Review about Pathogenesis, Gastrointestinal Manifestations, and Management. 白塞氏病:关于发病机制、胃肠道表现和治疗的深入综述。
Q2 Medicine Pub Date : 2021-11-04 eCollection Date: 2021-12-01 DOI: 10.1159/000520696
Anthony Nguyen, Shubhra Upadhyay, Muhammad Ali Javaid, Abdul Moiz Qureshi, Shahan Haseeb, Nismat Javed, Christopher Cormier, Asif Farooq, Abu Baker Sheikh

Background: Behcet's disease (BD) is a complex inflammatory vascular disorder that follows a relapsing-remitting course with diverse clinical manifestations. The prevalence of the disease varies throughout the globe and targets different age-groups. There are many variations of BD; however, intestinal BD is not only more common but has many signs and symptoms.

Summary: BD is a relapsing-remitting inflammatory vascular disorder with multiple system involvement, affecting vessels of all types and sizes that targets young adults. The etiology of BD is unknown but many factors including genetic mechanisms, vascular changes, hypercoagulability, and dysregulation of immune function are believed to be responsible. BD usually presents with signs and symptoms of ulcerative disease of the small intestine; endoscopy being consistent with the clinical manifestations. The mainstay of treatment depends upon the severity of the disease. Corticosteroids are recommended for severe forms of the disease and aminosalicylic acids are used in maintaining remission in mild to moderate forms of the disease.

Key messages: In this review, we have tried to summarize in the present review the clinical manifestations, differential diagnoses, and management of intestinal BD. Hopefully, this review will enable health policymakers to ponder over establishing clear endpoints for treatment, surveillance investigations, and creating robust algorithms.

背景:白塞病(BD)是一种复杂的炎症性血管疾病,具有多种临床表现,复发缓解过程。该疾病在全球的流行情况各不相同,针对不同的年龄组。双相障碍有很多变体;然而,肠道BD不仅更常见,而且有许多体征和症状。摘要:BD是一种复发缓解性炎症性血管疾病,累及多系统,影响所有类型和大小的血管,主要针对年轻人。双相障碍的病因尚不清楚,但许多因素包括遗传机制,血管改变,高凝性和免疫功能失调被认为是负责任的。BD通常表现为小肠溃疡性疾病的体征和症状;内窥镜检查与临床表现相符。主要的治疗方法取决于疾病的严重程度。皮质类固醇被推荐用于治疗严重形式的疾病,氨基水杨酸被用于维持轻度至中度形式的疾病的缓解。在这篇综述中,我们试图总结肠道双相障碍的临床表现、鉴别诊断和治疗。希望这篇综述能使卫生政策制定者思考建立明确的治疗终点、监测调查和创建稳健的算法。
{"title":"Behcet's Disease: An In-Depth Review about Pathogenesis, Gastrointestinal Manifestations, and Management.","authors":"Anthony Nguyen,&nbsp;Shubhra Upadhyay,&nbsp;Muhammad Ali Javaid,&nbsp;Abdul Moiz Qureshi,&nbsp;Shahan Haseeb,&nbsp;Nismat Javed,&nbsp;Christopher Cormier,&nbsp;Asif Farooq,&nbsp;Abu Baker Sheikh","doi":"10.1159/000520696","DOIUrl":"https://doi.org/10.1159/000520696","url":null,"abstract":"<p><strong>Background: </strong>Behcet's disease (BD) is a complex inflammatory vascular disorder that follows a relapsing-remitting course with diverse clinical manifestations. The prevalence of the disease varies throughout the globe and targets different age-groups. There are many variations of BD; however, intestinal BD is not only more common but has many signs and symptoms.</p><p><strong>Summary: </strong>BD is a relapsing-remitting inflammatory vascular disorder with multiple system involvement, affecting vessels of all types and sizes that targets young adults. The etiology of BD is unknown but many factors including genetic mechanisms, vascular changes, hypercoagulability, and dysregulation of immune function are believed to be responsible. BD usually presents with signs and symptoms of ulcerative disease of the small intestine; endoscopy being consistent with the clinical manifestations. The mainstay of treatment depends upon the severity of the disease. Corticosteroids are recommended for severe forms of the disease and aminosalicylic acids are used in maintaining remission in mild to moderate forms of the disease.</p><p><strong>Key messages: </strong>In this review, we have tried to summarize in the present review the clinical manifestations, differential diagnoses, and management of intestinal BD. Hopefully, this review will enable health policymakers to ponder over establishing clear endpoints for treatment, surveillance investigations, and creating robust algorithms.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"6 4","pages":"175-185"},"PeriodicalIF":0.0,"publicationDate":"2021-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740277/pdf/iid-0006-0175.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39862415","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}
引用次数: 10
Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? “The Pro Position” 克罗恩病的粘膜愈合:靶心还是胸围?“赞成立场”
Q2 Medicine Pub Date : 2021-11-03 DOI: 10.1159/000519521
N. O’Moráin, J. Doherty, R. Stack, G. Doherty
Background: Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. Summary: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. Key Messages: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.
背景:克罗恩病(CD)是一种影响胃肠道的慢性炎症性疾病,其疾病行为基于粘膜损伤的深度和严重程度。累积性损伤可导致并发症,包括狭窄形成和穿透性并发症,通常需要手术切除患病的肠段,导致显著的发病率。准确评估疾病活动性和适当治疗对于预防并发症至关重要。摘要:随着更有效的免疫抑制疗法的出现,乳糜泻治疗的治疗目标也在不断发展。针对亚临床炎症的解决,实现粘膜愈合与预防狭窄和穿透并发症有关。确定非侵入性方式来评估粘膜愈合仍然是一个挑战。关键信息:粘膜愈合可最大限度地降低疾病并发症的发生风险,延长无类固醇生存期,减少住院治疗和手术干预的需要。
{"title":"Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? “The Pro Position”","authors":"N. O’Moráin, J. Doherty, R. Stack, G. Doherty","doi":"10.1159/000519521","DOIUrl":"https://doi.org/10.1159/000519521","url":null,"abstract":"Background: Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. Summary: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. Key Messages: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"9 1","pages":"36 - 41"},"PeriodicalIF":0.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89472086","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}
引用次数: 1
Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? The “Relative” Con Position 克罗恩病的粘膜愈合:靶心还是胸围?“相对”谬误
Q2 Medicine Pub Date : 2021-10-20 DOI: 10.1159/000519731
M. Mosli, T. AlAmeel, A. Sharara
Background: Crohn’s disease is a progressive inflammatory bowel disease. Persistent untreated inflammation can cumulatively result in bowel damage in the form of strictures, fistulas, and fibrosis, which can ultimately result in the need for major abdominal surgery. Mucosal healing has emerged as an attractive, yet ambitious goal in the hope of preventing long-term complications. Summary: Clinical remission is an inadequate measure of disease activity. Noninvasive markers such as fecal calprotectin, CRP, or small bowel ultrasound are useful adjunct tools. However, endoscopic assessment remains the cornerstone in building a treatment plan. Achieving complete mucosal healing has proved to be an elusive goal even in the ideal setting of a clinical trial. Key Messages: Aiming for complete mucosal healing in all patients may result in overuse of medications, higher costs, and potential side effects of aggressive immunosuppressive treatment. More practical goals such as relative or partial healing, for example, 50% improvement in inflammation and reduction in size of ulcers, ought to be considered, particularly in difficult-to-treat populations.
背景:克罗恩病是一种进行性炎性肠病。持续未经治疗的炎症可累积导致肠道损伤,表现为狭窄、瘘管和纤维化,最终可能导致需要进行腹部大手术。粘膜愈合已成为一个有吸引力的,但雄心勃勃的目标,希望预防长期并发症。总结:临床缓解是疾病活动的一个不充分的衡量标准。无创标志物如粪便钙保护蛋白、CRP或小肠超声是有用的辅助工具。然而,内窥镜评估仍然是制定治疗计划的基石。即使在理想的临床试验环境中,实现完全的粘膜愈合也被证明是一个难以捉摸的目标。关键信息:以所有患者的粘膜完全愈合为目标可能导致药物过度使用,成本更高,以及积极免疫抑制治疗的潜在副作用。应该考虑更实际的目标,如相对或部分愈合,例如,炎症改善50%,溃疡缩小,特别是在难以治疗的人群中。
{"title":"Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? The “Relative” Con Position","authors":"M. Mosli, T. AlAmeel, A. Sharara","doi":"10.1159/000519731","DOIUrl":"https://doi.org/10.1159/000519731","url":null,"abstract":"Background: Crohn’s disease is a progressive inflammatory bowel disease. Persistent untreated inflammation can cumulatively result in bowel damage in the form of strictures, fistulas, and fibrosis, which can ultimately result in the need for major abdominal surgery. Mucosal healing has emerged as an attractive, yet ambitious goal in the hope of preventing long-term complications. Summary: Clinical remission is an inadequate measure of disease activity. Noninvasive markers such as fecal calprotectin, CRP, or small bowel ultrasound are useful adjunct tools. However, endoscopic assessment remains the cornerstone in building a treatment plan. Achieving complete mucosal healing has proved to be an elusive goal even in the ideal setting of a clinical trial. Key Messages: Aiming for complete mucosal healing in all patients may result in overuse of medications, higher costs, and potential side effects of aggressive immunosuppressive treatment. More practical goals such as relative or partial healing, for example, 50% improvement in inflammation and reduction in size of ulcers, ought to be considered, particularly in difficult-to-treat populations.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"99 1","pages":"42 - 49"},"PeriodicalIF":0.0,"publicationDate":"2021-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85820954","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}
引用次数: 1
Transmural Inflammation, Ileitis, and Granulomas at the Time of Proctocolectomy in Patients with Ulcerative Colitis Do Not Predict Future Development of Pouchitis. 溃疡性结肠炎患者行直结肠切除术时的经壁炎症、回肠炎和肉芽肿不能预测未来的袋炎发展。
Q2 Medicine Pub Date : 2021-10-07 eCollection Date: 2021-12-01 DOI: 10.1159/000519325
Edward L Barnes, Joshua Hudson, Scott Esckilsen, Bharati Kochar, Michael D Kappelman, Millie D Long, Mark Koruda, Robert S Sandler, Hans H Herfarth

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA.

Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis.

Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08).

Discussion/conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.

背景:溃疡性结肠炎(UC)患者行回肠袋-肛门吻合术(IPAA)后最常见的并发症是袋炎。我们的研究旨在探讨临床和内镜诊断为UC的患者结肠切除术标本上的回肠炎、肉芽肿或跨壁炎症的组织病理学表现与IPAA后前2年内发生袋炎的关系。方法:我们进行了一项回顾性队列研究,评估2004年1月1日至2016年12月31日期间接受IPAA结肠切除术治疗UC的患者。采用双变量分析评价临床因素与袋炎发生的关系。我们采用多变量logistic回归来评估结肠切除术时的组织学、临床和人口统计学因素与随后发生的袋炎之间的关系。结果:626例患者中,246例(39%)发生囊炎。原发性硬化性胆管炎患者更容易发生袋炎(调整优势比[aOR] 2.81, 95%可信区间[CI] 1.02-7.72),有炎症性肠病家族史的患者也是如此(aOR为1.75,95% CI为1.11-2.77)。回肠炎、肉芽肿或跨壁炎症的组织学表现与发生袋炎的几率增加无关(aOR 0.70, 95% CI 0.45-1.08)。讨论/结论:结肠切除术时患有回肠炎、肉芽肿或跨壁炎症的患者在IPAA后2年内发展为袋炎的风险不高。这些病理结果不应排除UC的IPAA。
{"title":"Transmural Inflammation, Ileitis, and Granulomas at the Time of Proctocolectomy in Patients with Ulcerative Colitis Do Not Predict Future Development of Pouchitis.","authors":"Edward L Barnes,&nbsp;Joshua Hudson,&nbsp;Scott Esckilsen,&nbsp;Bharati Kochar,&nbsp;Michael D Kappelman,&nbsp;Millie D Long,&nbsp;Mark Koruda,&nbsp;Robert S Sandler,&nbsp;Hans H Herfarth","doi":"10.1159/000519325","DOIUrl":"https://doi.org/10.1159/000519325","url":null,"abstract":"<p><strong>Background: </strong>The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA.</p><p><strong>Methods: </strong>We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis.</p><p><strong>Results: </strong>Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08).</p><p><strong>Discussion/conclusion: </strong>Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"6 4","pages":"210-217"},"PeriodicalIF":0.0,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739936/pdf/iid-0006-0210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39863392","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}
引用次数: 0
Epithelial-Specific TLR4 Knockout Challenges Current Evidence of TLR4 Homeostatic Control of Gut Permeability. 上皮特异性TLR4敲除挑战了目前关于TLR4稳态控制肠道通透性的证据。
Q2 Medicine Pub Date : 2021-09-28 eCollection Date: 2021-12-01 DOI: 10.1159/000519200
Elise E Crame, Joanne M Bowen, Kate R Secombe, Janet K Coller, Maxime François, Wayne Leifert, Hannah R Wardill

Introduction: Toll-like receptor 4 (TLR4) is a highly conserved immunosurveillance protein of innate immunity, displaying well-established roles in homeostasis and intestinal inflammation. Current evidence shows complex relationships between TLR4 activation, maintenance of health, and disease progression; however, it commonly overlooks the importance of site-specific TLR4 expression. This omission has the potential to influence translation of results as previous evidence shows the differing and distinct roles that TLR4 exhibits are dependent on its spatiotemporal expression.

Methods: An intestinal epithelial TLR4 conditional knockout (KO) mouse line (Tlr4ΔIEC, n = 6-8) was utilized to dissect the contribution of epithelial TLR4 expression to intestinal homeostasis with comparisons to wild-type (WT) (n = 5-7) counterparts. Functions of the intestinal barrier in the ileum and colon were assessed with tissue resistance in Ussing chambers. Molecular and structural comparisons in the ileum and colon were assessed via histological staining, expression of tight junction proteins (occludin and zonular occludin 1 [ZO-1]), and presence of CD11b-positive immune cells.

Results: There was no impact of the intestinal epithelial TLR4 KO, with no differences in (1) tissue resistance-ileum (mean ± standard error of mean [SEM]): WT 22 ± 7.2 versus Tlr4ΔIEC 20 ± 5.6 (Ω × cm2) p = 0.831, colon WT 30.8 ± 3.6 versus Tlr4ΔIEC 45.1 ± 9.5 p = 0.191; (2) histological staining (overall tissue structure); and (3) tight junction protein expression (% area stain, mean ± SEM)-ZO-1: ileum-WT 1.49 ± 0.155 versus Tlr4ΔIEC 1.17 ± 0.07, p = 0.09; colon-WT 1.36 ± 0.26 versus Tlr4ΔIEC 1.12 ± 0.18 p = 0.47; occludin: ileum-WT 1.07 ± 0.12 versus Tlr4ΔIEC 0.95 ± 0.13, p = 0.53; colon-WT 1.26 ± 0.26 versus Tlr4ΔIEC 1.02 ± 0.16 p = 0.45. CD11b-positive immune cells (% area stain, mean ± SEM) in the ileum were mildly decreased in WT mice: WT 0.14 ± 0.02 versus Tlr4ΔIEC 0.09 ± 0.01 p = 0.04. However, in the colon, there was no difference in CD11b-positive immune cells between strains: WT 0.53 ± 0.08 versus Tlr4ΔIEC 0.49 ± 0.08 p = 0.73.

Conclusions: These data have 2 important implications. First, these data refute the assumption that epithelial TLR4 exerts physiological control of intestinal physiology and immunity in health. Second, and most importantly, these data support the use of the Tlr4ΔIEC line in future models interrogating health and disease, confirming no confounding effects of genetic manipulation.

toll样受体4 (TLR4)是一种高度保守的先天免疫免疫监视蛋白,在体内平衡和肠道炎症中发挥着重要作用。目前的证据表明,TLR4激活、健康维持和疾病进展之间存在复杂的关系;然而,它通常忽略了位点特异性TLR4表达的重要性。这一遗漏有可能影响结果的翻译,因为先前的证据表明,TLR4所表现出的不同和独特的作用取决于其时空表达。方法:利用肠上皮TLR4条件敲除(KO)小鼠系(Tlr4ΔIEC, n = 6-8),分析上皮TLR4表达对肠道稳态的贡献,并与野生型(WT) (n = 5-7)进行比较。回肠和结肠的肠屏障功能用Ussing腔进行组织阻力评估。通过组织学染色、紧密连接蛋白(occludin和zular occludin 1 [ZO-1])的表达以及cd11b阳性免疫细胞的存在来评估回肠和结肠的分子和结构比较。结果:肠道上皮TLR4 KO无影响,(1)组织阻力-回肠(平均±标准误差平均值[SEM]): WT 22±7.2 vs Tlr4ΔIEC 20±5.6 (Ω × cm2) p = 0.831,结肠WT 30.8±3.6 vs Tlr4ΔIEC 45.1±9.5 p = 0.191;(2)组织学染色(组织整体结构);(3)紧密连接蛋白表达(%面积染色,平均值±SEM)-ZO-1:回肠- wt 1.49±0.155 vs Tlr4ΔIEC 1.17±0.07,p = 0.09;结肠- wt 1.36±0.26 vs Tlr4ΔIEC 1.12±0.18 p = 0.47;occludin:回肠wt 1.07±0.12 vs Tlr4ΔIEC 0.95±0.13,p = 0.53;冒号- wt = 1.26±0.26 vs . Tlr4ΔIEC = 1.02±0.16 p = 0.45。WT小鼠回肠cd11b阳性免疫细胞(%面积染色,平均±SEM)轻度减少:WT 0.14±0.02 vs Tlr4ΔIEC 0.09±0.01 p = 0.04。然而,在结肠中,不同菌株之间cd11b阳性免疫细胞没有差异:WT为0.53±0.08,Tlr4ΔIEC为0.49±0.08,p = 0.73。结论:这些数据有两个重要的含义。首先,这些数据驳斥了上皮TLR4在健康状态下对肠道生理和免疫进行生理控制的假设。其次,最重要的是,这些数据支持在未来的模型中使用Tlr4ΔIEC线来询问健康和疾病,确认没有基因操作的混淆效应。
{"title":"Epithelial-Specific TLR4 Knockout Challenges Current Evidence of TLR4 Homeostatic Control of Gut Permeability.","authors":"Elise E Crame,&nbsp;Joanne M Bowen,&nbsp;Kate R Secombe,&nbsp;Janet K Coller,&nbsp;Maxime François,&nbsp;Wayne Leifert,&nbsp;Hannah R Wardill","doi":"10.1159/000519200","DOIUrl":"https://doi.org/10.1159/000519200","url":null,"abstract":"<p><strong>Introduction: </strong>Toll-like receptor 4 (TLR4) is a highly conserved immunosurveillance protein of innate immunity, displaying well-established roles in homeostasis and intestinal inflammation. Current evidence shows complex relationships between TLR4 activation, maintenance of health, and disease progression; however, it commonly overlooks the importance of site-specific TLR4 expression. This omission has the potential to influence translation of results as previous evidence shows the differing and distinct roles that TLR4 exhibits are dependent on its spatiotemporal expression.</p><p><strong>Methods: </strong>An intestinal epithelial TLR4 conditional knockout (KO) mouse line (<i>Tlr4</i><sup><i>ΔIEC</i></sup>, <i>n</i> = 6-8) was utilized to dissect the contribution of epithelial TLR4 expression to intestinal homeostasis with comparisons to wild-type (WT) (<i>n</i> = 5-7) counterparts. Functions of the intestinal barrier in the ileum and colon were assessed with tissue resistance in Ussing chambers. Molecular and structural comparisons in the ileum and colon were assessed via histological staining, expression of tight junction proteins (occludin and zonular occludin 1 [ZO-1]), and presence of CD11b-positive immune cells.</p><p><strong>Results: </strong>There was no impact of the intestinal epithelial TLR4 KO, with no differences in (1) tissue resistance-ileum (mean ± standard error of mean [SEM]): WT 22 ± 7.2 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 20 ± 5.6 (Ω × cm<sup>2</sup>) <i>p</i> = 0.831, colon WT 30.8 ± 3.6 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 45.1 ± 9.5 <i>p</i> = 0.191; (2) histological staining (overall tissue structure); and (3) tight junction protein expression (% area stain, mean ± SEM)-ZO-1: ileum-WT 1.49 ± 0.155 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 1.17 ± 0.07, <i>p</i> = 0.09; colon-WT 1.36 ± 0.26 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 1.12 ± 0.18 <i>p</i> = 0.47; occludin: ileum-WT 1.07 ± 0.12 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 0.95 ± 0.13, <i>p</i> = 0.53; colon-WT 1.26 ± 0.26 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 1.02 ± 0.16 <i>p</i> = 0.45. CD11b-positive immune cells (% area stain, mean ± SEM) in the ileum were mildly decreased in WT mice: WT 0.14 ± 0.02 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 0.09 ± 0.01 <i>p</i> = 0.04. However, in the colon, there was no difference in CD11b-positive immune cells between strains: WT 0.53 ± 0.08 versus <i>Tlr4</i><sup><i>ΔIEC</i></sup> 0.49 ± 0.08 <i>p</i> = 0.73.</p><p><strong>Conclusions: </strong>These data have 2 important implications. First, these data refute the assumption that epithelial TLR4 exerts physiological control of intestinal physiology and immunity in health. Second, and most importantly, these data support the use of the <i>Tlr4</i><sup><i>ΔIEC</i></sup> line in future models interrogating health and disease, confirming no confounding effects of genetic manipulation.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"6 4","pages":"199-209"},"PeriodicalIF":0.0,"publicationDate":"2021-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739639/pdf/iid-0006-0199.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39863391","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}
引用次数: 3
Incidence, Prevalence, and Clinical Epidemiology of Inflammatory Bowel Disease in the Arab World: A Systematic Review and Meta-Analysis. 阿拉伯世界炎症性肠病的发病率、患病率和临床流行病学:系统回顾和荟萃分析。
Q2 Medicine Pub Date : 2021-09-07 eCollection Date: 2021-09-01 DOI: 10.1159/000518003
Mahmoud Mosli, Sameer Alawadhi, Fuad Hasan, Antoine Abou Rached, Faisal Sanai, Silvio Danese

Objectives: Despite the recent findings of the rising incidence of inflammatory bowel disease (IBD) in Arab countries, there are limited data on the characteristics of IBD patients and the disease course in the Arab world. This systematic review aimed to investigate the incidence and epidemiology of IBD in the Arab world.

Material and methods: We conducted a systematic literature review that utilized a comprehensive search of PubMed, Cochrane Central, SCOPUS, Google Scholar, and Web of Science from their inception till August 2020. We included cross-sectional, prospective, and retrospective studies that examined the prevalence and/or epidemiological characteristics of IBD in Arab countries.

Results: A total of 16 studies that examined IBD in Saudi Arabia, Egypt, Kuwait, the United Arab Emirates, Bahrain, Lebanon, and Oman were included. Generally, the included studies covered the period from the early 1990s to the late 2010s. A total of 1,627 ulcerative colitis (UC) patients and 1,588 Crohn's disease (CD) patients were included in this systematic review. The mean age at diagnosis ranged from 24.13 to 43.6 years in adult cases and from 4.5 to 16 years in pediatric cases. In most of the included studies, the majority of patients were male. The quantitative analysis revealed a pooled incidence rate of 2.33 (95% confidence interval [CI] 1.2-3.4) per 100,000 persons per year for UC in the Arab world. Likewise, the pooled incidence rate for CD in the Arab world was 1.46 (95% CI 1.03-1.89) per 100,000 persons per year.

Conclusion: There is a growing incidence of IBD in the Arab world, while IBD patients from Arab countries may present with some different characteristics, compared to their counterparts in Europe.

目的:尽管最近发现阿拉伯国家炎症性肠病(IBD)发病率上升,但关于阿拉伯世界IBD患者特征和病程的数据有限。本系统综述旨在调查阿拉伯世界IBD的发病率和流行病学。材料和方法:我们进行了一项系统的文献综述,利用PubMed、Cochrane Central、SCOPUS、Google Scholar和Web of Science从成立到2020年8月的全面搜索。我们纳入了调查阿拉伯国家IBD患病率和/或流行病学特征的横断面、前瞻性和回顾性研究。结果:共纳入了沙特阿拉伯、埃及、科威特、阿拉伯联合酋长国、巴林、黎巴嫩和阿曼的16项研究。一般来说,纳入的研究涵盖了从20世纪90年代初到21世纪10年代末的时期。本系统综述共纳入1627例溃疡性结肠炎(UC)患者和1588例克罗恩病(CD)患者。成人病例的平均诊断年龄为24.13至43.6岁,儿科病例为4.5至16岁。在大多数纳入的研究中,大多数患者是男性。定量分析显示,阿拉伯世界每年UC的总发病率为每10万人2.33例(95%可信区间[CI] 1.2-3.4)。同样,阿拉伯世界CD的总发病率为每年每10万人1.46例(95% CI 1.03-1.89)。结论:IBD在阿拉伯世界的发病率越来越高,但与欧洲的IBD患者相比,阿拉伯国家的IBD患者可能表现出一些不同的特征。
{"title":"Incidence, Prevalence, and Clinical Epidemiology of Inflammatory Bowel Disease in the Arab World: A Systematic Review and Meta-Analysis.","authors":"Mahmoud Mosli,&nbsp;Sameer Alawadhi,&nbsp;Fuad Hasan,&nbsp;Antoine Abou Rached,&nbsp;Faisal Sanai,&nbsp;Silvio Danese","doi":"10.1159/000518003","DOIUrl":"https://doi.org/10.1159/000518003","url":null,"abstract":"<p><strong>Objectives: </strong>Despite the recent findings of the rising incidence of inflammatory bowel disease (IBD) in Arab countries, there are limited data on the characteristics of IBD patients and the disease course in the Arab world. This systematic review aimed to investigate the incidence and epidemiology of IBD in the Arab world.</p><p><strong>Material and methods: </strong>We conducted a systematic literature review that utilized a comprehensive search of PubMed, Cochrane Central, SCOPUS, Google Scholar, and Web of Science from their inception till August 2020. We included cross-sectional, prospective, and retrospective studies that examined the prevalence and/or epidemiological characteristics of IBD in Arab countries.</p><p><strong>Results: </strong>A total of 16 studies that examined IBD in Saudi Arabia, Egypt, Kuwait, the United Arab Emirates, Bahrain, Lebanon, and Oman were included. Generally, the included studies covered the period from the early 1990s to the late 2010s. A total of 1,627 ulcerative colitis (UC) patients and 1,588 Crohn's disease (CD) patients were included in this systematic review. The mean age at diagnosis ranged from 24.13 to 43.6 years in adult cases and from 4.5 to 16 years in pediatric cases. In most of the included studies, the majority of patients were male. The quantitative analysis revealed a pooled incidence rate of 2.33 (95% confidence interval [CI] 1.2-3.4) per 100,000 persons per year for UC in the Arab world. Likewise, the pooled incidence rate for CD in the Arab world was 1.46 (95% CI 1.03-1.89) per 100,000 persons per year.</p><p><strong>Conclusion: </strong>There is a growing incidence of IBD in the Arab world, while IBD patients from Arab countries may present with some different characteristics, compared to their counterparts in Europe.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"6 3","pages":"123-131"},"PeriodicalIF":0.0,"publicationDate":"2021-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527904/pdf/iid-0006-0123.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39833230","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}
引用次数: 21
Proactive versus Reactive Therapeutic Drug Monitoring: Why, When, and How? 主动与被动治疗药物监测:为什么,何时,如何?
Q2 Medicine Pub Date : 2021-09-06 DOI: 10.1159/000518755
Manar Shmais, M. Regueiro, Jana G Hashash
Background: Up to a third of inflammatory bowel disease) patients show primary nonresponse to antitumor necrosis factor (anti-TNF) biological therapy, and of those who respond, up to 40% develop secondary loss of response (LOR). Therapeutic drug monitoring (TDM) plays a crucial role in assessing patients with LOR to guide therapy by giving more of the drug or switching to a different biological agent. Although reactive TDM is suggested or recommended by the majority of gastroenterology associations, proactive TDM seems to be more controversial. Summary: In this article, we discuss the updated guidelines on TDM and will also discuss the available data supporting proactive and reactive TDM in patients with Crohn’s disease and those with ulcerative colitis using the different available biological agents. Key Messages: Therapeutic drug monitoring (TDM) is a valuable tool to aid in inflammatory bowel disease (IBD) therapy optimization. Reactive TDM is widely accepted in IBD patients with suspected loss of response, especially in those receiving antitumor necrosis factor (anti-TNF) agents. Proactive TDM is emerging as a reasonable approach to patients initiated on anti-TNF therapy, specifically infliximab and, to some extent, adalimumab, particularly for patients with severe ulcerative colitis and fistulizing Crohn’s disease. Similarly, TDM may play a role in patients considering de-escalation from combination therapy. To date, proactive TDM is not widely applied to ustekinumab and vedolizumab and more data are required before this becomes part of clinical practice.
背景:多达三分之一的炎症性肠病患者对抗肿瘤坏死因子(anti-TNF)生物治疗表现出原发性无反应,而在有反应的患者中,高达40%的患者出现继发性反应丧失(LOR)。治疗性药物监测(TDM)在评估LOR患者中起着至关重要的作用,以指导治疗,给予更多的药物或切换到不同的生物制剂。虽然大多数胃肠病学协会建议或推荐反应性TDM,但主动TDM似乎更具争议性。摘要:在本文中,我们讨论了TDM的最新指南,并将讨论支持克罗恩病和溃疡性结肠炎患者使用不同可用生物制剂进行主动和反应性TDM的现有数据。关键信息:治疗药物监测(TDM)是帮助炎症性肠病(IBD)治疗优化的有价值的工具。反应性TDM被广泛接受于怀疑反应丧失的IBD患者,特别是那些接受抗肿瘤坏死因子(anti-TNF)药物治疗的患者。对于开始接受抗肿瘤坏死因子治疗的患者,特别是英夫利昔单抗和阿达木单抗,尤其是患有严重溃疡性结肠炎和纤维化克罗恩病的患者,主动TDM正在成为一种合理的治疗方法。同样,TDM可能在考虑从联合治疗中降级的患者中发挥作用。迄今为止,主动TDM尚未广泛应用于ustekinumab和vedolizumab,在其成为临床实践的一部分之前需要更多的数据。
{"title":"Proactive versus Reactive Therapeutic Drug Monitoring: Why, When, and How?","authors":"Manar Shmais, M. Regueiro, Jana G Hashash","doi":"10.1159/000518755","DOIUrl":"https://doi.org/10.1159/000518755","url":null,"abstract":"Background: Up to a third of inflammatory bowel disease) patients show primary nonresponse to antitumor necrosis factor (anti-TNF) biological therapy, and of those who respond, up to 40% develop secondary loss of response (LOR). Therapeutic drug monitoring (TDM) plays a crucial role in assessing patients with LOR to guide therapy by giving more of the drug or switching to a different biological agent. Although reactive TDM is suggested or recommended by the majority of gastroenterology associations, proactive TDM seems to be more controversial. Summary: In this article, we discuss the updated guidelines on TDM and will also discuss the available data supporting proactive and reactive TDM in patients with Crohn’s disease and those with ulcerative colitis using the different available biological agents. Key Messages: Therapeutic drug monitoring (TDM) is a valuable tool to aid in inflammatory bowel disease (IBD) therapy optimization. Reactive TDM is widely accepted in IBD patients with suspected loss of response, especially in those receiving antitumor necrosis factor (anti-TNF) agents. Proactive TDM is emerging as a reasonable approach to patients initiated on anti-TNF therapy, specifically infliximab and, to some extent, adalimumab, particularly for patients with severe ulcerative colitis and fistulizing Crohn’s disease. Similarly, TDM may play a role in patients considering de-escalation from combination therapy. To date, proactive TDM is not widely applied to ustekinumab and vedolizumab and more data are required before this becomes part of clinical practice.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"53 1","pages":"50 - 58"},"PeriodicalIF":0.0,"publicationDate":"2021-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76208148","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}
引用次数: 21
5-Aminosalicylic Acid Chemoprevention in Inflammatory Bowel Diseases: Is It Necessary in the Age of Biologics and Small Molecules? 5-氨基水杨酸化学预防炎症性肠病:在生物制剂和小分子时代有必要吗?
Q2 Medicine Pub Date : 2021-09-03 DOI: 10.1159/000518865
H. Herfarth, S. Vavricka
Background: Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly debated in the past decade. This review describes available evidence and the current recommendations for chemoprevention in national and international guidelines IBD guidelines. Summary: 5-Aminosalicylic acid (5-ASA) compounds are the preferred therapeutic option for mild to moderate ulcerative colitis (UC). Aside from the known anti-inflammatory effects, their chemopreventive abilities have been described in vitro and in vivo. Pooling the increasing number of retrospective and population-based clinical studies over the last 15 years, 7 consecutive meta-analyses revealed partially conflicting results for the chemopreventive efficacy of 5-ASA, and thus, not all IBD guidelines currently recommend chemoprevention with mesalamine compounds. Accumulating evidence for decreasing the colorectal cancer (CRC) risk in support of thiopurines more recently shows a protective effect. This effect seems solely mediated by control of intestinal inflammation since, for this drug class, another mechanistic interference in IBD-associated CRC pathogenesis is not known. The results regarding chemopreventive efficacy for ursodeoxycholic acid or folic acid are equivocal, and the use of these medications to prevent CRC is not firmly established. Like UC, the risk of CRC is also significantly increased in patients with Crohn’s disease (CD), especially Crohn’s colitis. However, no published studies exclusively assess the effects of surveillance on the early detection of cancer or CRC chemoprevention in CD patients. In meta-analyses, which predominantly included UC patients, 5-ASA or thiopurines were not beneficial in small CD subgroups. The level of evidence for anti-TNFα agents, anti-integrin (e.g., vedolizumab), or anti-IL-12/IL-23 agents (e.g., ustekinumab) and Janus kinase inhibitors is currently too low or nonexistent to use them solely for chemoprevention in UC or CD patients. Key Message: Intestinal inflammation is one of the main risk factors for developing CRC in IBD, and all drugs that induce and maintain mucosal healing most likely also decrease the IBD-associated CRC risk. Thus, a therapeutic strategy of adding a 5-ASA therapy to a successfully mucosal healing-inducing therapy, for example, with a biologic or a small molecule merely to prevent CRC appears to be obsolete.
背景:由于炎症性肠病(IBDs)中结直肠癌的发病率增加,在过去的十年中,对这一患者群体进行化学预防的价值一直存在争议。这篇综述描述了现有的证据以及目前IBD国家和国际指南中关于化学预防的建议。摘要:5-氨基水杨酸(5-ASA)化合物是轻度至中度溃疡性结肠炎(UC)的首选治疗方案。除了已知的抗炎作用外,它们的化学预防能力已经在体外和体内得到了描述。汇总过去15年来越来越多的回顾性和基于人群的临床研究,7个连续的荟萃分析揭示了5-ASA化学预防效果的部分矛盾结果,因此,目前并非所有IBD指南都推荐美沙拉胺化合物进行化学预防。越来越多的证据表明,硫嘌呤具有降低结直肠癌(CRC)风险的保护作用。这种作用似乎完全是通过控制肠道炎症介导的,因为对于这类药物,ibd相关的结直肠癌发病机制的另一种机制干扰尚不清楚。关于熊去氧胆酸或叶酸的化学预防效果的结果是模棱两可的,使用这些药物预防结直肠癌的结果也不确定。与UC一样,克罗恩病(CD)尤其是克罗恩结肠炎患者发生CRC的风险也显著增加。然而,没有发表的研究专门评估监测对CD患者早期发现癌症或CRC化学预防的影响。在主要包括UC患者的荟萃分析中,5-ASA或硫嘌呤在小的CD亚组中没有益处。抗tnf α药物、抗整合素(如vedolizumab)或抗il -12/IL-23药物(如ustekinumab)和Janus激酶抑制剂的证据水平目前太低或不存在,无法仅用于UC或CD患者的化学预防。关键信息:肠道炎症是IBD患者发生结直肠癌的主要危险因素之一,所有诱导和维持粘膜愈合的药物都很可能降低IBD相关结直肠癌的风险。因此,在成功诱导粘膜愈合的治疗中添加5-ASA治疗的治疗策略,例如,仅使用生物或小分子来预防CRC似乎已经过时。
{"title":"5-Aminosalicylic Acid Chemoprevention in Inflammatory Bowel Diseases: Is It Necessary in the Age of Biologics and Small Molecules?","authors":"H. Herfarth, S. Vavricka","doi":"10.1159/000518865","DOIUrl":"https://doi.org/10.1159/000518865","url":null,"abstract":"Background: Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly debated in the past decade. This review describes available evidence and the current recommendations for chemoprevention in national and international guidelines IBD guidelines. Summary: 5-Aminosalicylic acid (5-ASA) compounds are the preferred therapeutic option for mild to moderate ulcerative colitis (UC). Aside from the known anti-inflammatory effects, their chemopreventive abilities have been described in vitro and in vivo. Pooling the increasing number of retrospective and population-based clinical studies over the last 15 years, 7 consecutive meta-analyses revealed partially conflicting results for the chemopreventive efficacy of 5-ASA, and thus, not all IBD guidelines currently recommend chemoprevention with mesalamine compounds. Accumulating evidence for decreasing the colorectal cancer (CRC) risk in support of thiopurines more recently shows a protective effect. This effect seems solely mediated by control of intestinal inflammation since, for this drug class, another mechanistic interference in IBD-associated CRC pathogenesis is not known. The results regarding chemopreventive efficacy for ursodeoxycholic acid or folic acid are equivocal, and the use of these medications to prevent CRC is not firmly established. Like UC, the risk of CRC is also significantly increased in patients with Crohn’s disease (CD), especially Crohn’s colitis. However, no published studies exclusively assess the effects of surveillance on the early detection of cancer or CRC chemoprevention in CD patients. In meta-analyses, which predominantly included UC patients, 5-ASA or thiopurines were not beneficial in small CD subgroups. The level of evidence for anti-TNFα agents, anti-integrin (e.g., vedolizumab), or anti-IL-12/IL-23 agents (e.g., ustekinumab) and Janus kinase inhibitors is currently too low or nonexistent to use them solely for chemoprevention in UC or CD patients. Key Message: Intestinal inflammation is one of the main risk factors for developing CRC in IBD, and all drugs that induce and maintain mucosal healing most likely also decrease the IBD-associated CRC risk. Thus, a therapeutic strategy of adding a 5-ASA therapy to a successfully mucosal healing-inducing therapy, for example, with a biologic or a small molecule merely to prevent CRC appears to be obsolete.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"56 1","pages":"28 - 35"},"PeriodicalIF":0.0,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90728281","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}
引用次数: 4
Analysis of the Long-Term Prognosis in Japanese Patients with Ulcerative Colitis Treated with New Therapeutic Agents and the Correlation between Prognosis and Disease Susceptibility Loci. 日本溃疡性结肠炎患者新药物治疗的远期预后分析及预后与疾病易感位点的关系
Q2 Medicine Pub Date : 2021-09-02 eCollection Date: 2021-09-01 DOI: 10.1159/000518371
Kasumi Hishinuma, Rintaro Moroi, Daisuke Okamoto, Yusuke Shimoyama, Masatake Kuroha, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Background: New therapeutic agents, including biologics and small-molecule drugs, are widely used to treat ulcerative colitis (UC). This study evaluates long-term prognosis in Japanese patients treated with these agents and the association between prognosis and genetic susceptibility to UC.

Methods: We evaluated surgery-free rates using the Kaplan-Meier method in the total cohort and in patients treated with prednisolone and new therapeutic agents. Multivariate analysis was performed to identify clinical factors affecting surgical rates using Cox's proportional hazard model. The rate of use of new therapeutic agents was compared using the Kaplan-Meier method, and multivariate analysis was conducted to investigate the correlation between the single-nucleotide polymorphism (SNP) rs117506082 and long-term prognosis.

Results: Surgery-free survival decreased over time. There was no significant difference in this parameter between patients who were administered prednisolone and those who were administered new therapeutic agents. Poor response to prednisolone and treatment without topical 5-aminosalicylic acid were poor prognostic factors. Shorter time from diagnosis to initiation of treatment with new therapeutic agents was a risk factor for colectomy. The AA genotype of SNP rs117506082 was associated with a shorter time to surgery and increased use of new therapeutic agents.

Conclusions: The use of new therapeutic agents might improve long-term prognosis in patients with more severe UC. Previously identified genetic risk factors were not significantly associated with a higher rate of colectomy.

背景:包括生物制剂和小分子药物在内的新型治疗药物被广泛用于治疗溃疡性结肠炎(UC)。本研究评估了日本接受这些药物治疗的患者的长期预后以及预后与UC遗传易感性之间的关系。方法:我们使用Kaplan-Meier方法评估总队列和接受强的松龙和新治疗药物治疗的患者的无手术率。采用Cox比例风险模型进行多因素分析,以确定影响手术率的临床因素。采用Kaplan-Meier法比较两组患者新药物使用率,并进行多因素分析,探讨rs117506082单核苷酸多态性(SNP)与远期预后的相关性。结果:无手术生存率随着时间的推移而下降。在接受强的松龙治疗的患者和接受新治疗药物治疗的患者之间,该参数无显著差异。对强的松龙反应不良和不外用5-氨基水杨酸治疗是预后不良的因素。从诊断到开始使用新药物治疗的时间较短是结肠切除术的危险因素。SNP rs117506082的AA基因型与手术时间缩短和新治疗剂使用增加相关。结论:使用新的治疗药物可以改善重症UC患者的长期预后。先前确定的遗传风险因素与较高的结肠切除术率没有显著关联。
{"title":"Analysis of the Long-Term Prognosis in Japanese Patients with Ulcerative Colitis Treated with New Therapeutic Agents and the Correlation between Prognosis and Disease Susceptibility Loci.","authors":"Kasumi Hishinuma,&nbsp;Rintaro Moroi,&nbsp;Daisuke Okamoto,&nbsp;Yusuke Shimoyama,&nbsp;Masatake Kuroha,&nbsp;Hisashi Shiga,&nbsp;Yoichi Kakuta,&nbsp;Yoshitaka Kinouchi,&nbsp;Atsushi Masamune","doi":"10.1159/000518371","DOIUrl":"https://doi.org/10.1159/000518371","url":null,"abstract":"<p><strong>Background: </strong>New therapeutic agents, including biologics and small-molecule drugs, are widely used to treat ulcerative colitis (UC). This study evaluates long-term prognosis in Japanese patients treated with these agents and the association between prognosis and genetic susceptibility to UC.</p><p><strong>Methods: </strong>We evaluated surgery-free rates using the Kaplan-Meier method in the total cohort and in patients treated with prednisolone and new therapeutic agents. Multivariate analysis was performed to identify clinical factors affecting surgical rates using Cox's proportional hazard model. The rate of use of new therapeutic agents was compared using the Kaplan-Meier method, and multivariate analysis was conducted to investigate the correlation between the single-nucleotide polymorphism (SNP) rs117506082 and long-term prognosis.</p><p><strong>Results: </strong>Surgery-free survival decreased over time. There was no significant difference in this parameter between patients who were administered prednisolone and those who were administered new therapeutic agents. Poor response to prednisolone and treatment without topical 5-aminosalicylic acid were poor prognostic factors. Shorter time from diagnosis to initiation of treatment with new therapeutic agents was a risk factor for colectomy. The AA genotype of SNP rs117506082 was associated with a shorter time to surgery and increased use of new therapeutic agents.</p><p><strong>Conclusions: </strong>The use of new therapeutic agents might improve long-term prognosis in patients with more severe UC. Previously identified genetic risk factors were not significantly associated with a higher rate of colectomy.</p>","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"6 3","pages":"154-164"},"PeriodicalIF":0.0,"publicationDate":"2021-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527903/pdf/iid-0006-0154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39847232","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}
引用次数: 0
期刊
Inflammatory Intestinal Diseases
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1