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Disease Recurrence and Long-term Outcomes Following the Development of Intestinal Failure in Crohn's Disease: Over 20 Years of Experience from a National Reference Centre. 克罗恩病肠衰竭发展后的疾病复发和长期结局:来自国家参考中心的20多年经验
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad105
Maja Kopczynska, Benjamin Crooks, Liat Deutsch, Thomas Conley, Catherine Stansfield, Ashley Bond, Mattias Soop, Gordon Carlson, Simon Lal

Background and aims: Intestinal failure [IF] is a recognised complication of Crohn's disease [CD]. The aim of this study was to identify factors predicting the development and recurrence of CD in patients with IF [CD-IF], and their long-term outcomes.

Methods: This was a cohort study of adults with CD-IF admitted to a national UK IF reference centre between 2000 and 2021. Patients were followed from discharge with home parenteral nutrition [HPN] until death or February 28, 2021.

Results: In all, 124 patients were included; 47 [37.9%] changed disease location and 55 [44.4%] changed disease behaviour between CD and CD-IF diagnosis, with increased upper gastrointestinal involvement [4.0% vs 22.6% patients], p <0.001. Following IF diagnosis, 29/124 [23.4%] patients commenced CD prophylactic medical therapy; 18 [62.1%] had a history of stricturing or penetrating small bowel disease; and nine [31.0%] had ileocolonic phenotype brought back into continuity. The cumulative incidence of disease recurrence was 2.4% at 1 year, 16.3% at 5 years and 27.2% at 10 years; colon-in-continuity and prophylactic treatment were associated with an increased likelihood of disease recurrence. Catheter-related bloodstream infection [CRBSI] rate was 0.32 episodes/1000 catheter days, with no association between medical therapy and CRBSI rate.

Conclusions: This is the largest series reporting disease behaviour and long-term outcomes in CD-IF and the first describing prophylactic therapy use. The incidence of disease recurrence was low. Immunosuppressive therapy appears to be safe in HPN-dependent patients with no increased risk of CRBSI. The management of CD-IF needs to be tailored to the patient's surgical disease history alongside disease phenotype.

背景和目的:肠衰竭(IF)是克罗恩病(CD)公认的并发症。本研究的目的是确定预测IF (CD-IF)患者CD发生和复发的因素,以及他们的长期预后。方法:这是一项队列研究,纳入了2000-2021年期间进入英国国家IF参考中心的成年CD-IF患者。患者出院后接受家庭肠外营养(HPN)随访至2021年2月28日死亡。结果:纳入124例患者;在CD和CD- if诊断之间,47例(37.9%)改变了疾病部位,55例(44.4%)改变了疾病行为,增加了上胃肠道受损伤(4.0%对22.6%)。结论:这是报道CD- if患者疾病行为和长期结果的最大系列研究,也是首次描述预防性治疗使用的研究。疾病复发率低。免疫抑制治疗在hpn依赖患者中似乎是安全的,没有增加CRBSI的风险。CD-IF的管理需要根据患者的手术病史和疾病表型进行调整。
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引用次数: 0
Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy-a Nationwide Population-based Study in Sweden. 炎症性肠病与较高的结肠镜检查不良事件发生率无关--基于瑞典全国人口的研究。
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad114
Bjarki T Alexandersson, Anna Andreasson, Charlotte Hedin, Gabriella Broms, Peter T Schmidt, Anna Forsberg

Background and aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.

Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.

Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.

Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.

背景和目的:炎症性肠病可能导致长期炎症和纤维化,并可能增加结肠镜检查中发生不良事件的风险。我们在一项全国性、基于人群的瑞典研究中评估了炎症性肠病和其他潜在风险因素是否与出血或穿孔相关:从全国患者登记册中检索了 2003 年至 2019 年期间 969 532 例结肠镜检查的数据,其中包括 164 012 例[17%]炎症性肠病患者。记录了结肠镜检查后 30 天内出血 [T810] 和穿孔 [T812] 的 ICD-10 编码。采用多变量逻辑回归来检验炎症性肠病状态、住院环境、时间段、全身麻醉、年龄、性别、内镜手术和抗血栓治疗是否与出血和穿孔的高几率有关:所有结肠镜检查中分别有 0.19% 和 0.11% 出现出血和穿孔。出血[几率比 0.66,P与没有炎症性肠病的人相比,患有炎症性肠病的人发生的不良事件并不多。然而,住院环境与更多不良事件有关,尤其是炎症性肠病患者。全身麻醉与更高的穿孔风险有关。
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引用次数: 0
Visceral Fat Indices: Do They Help Differentiate Crohn's Disease and Intestinal Tuberculosis in Children? 内脏脂肪指数:它们有助于区分儿童克罗恩病和肠结核吗?
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad109
Jayendra Seetharaman, Anshu Srivastava, Rajanikant R Yadav, Sumit K Singh, Prabhakar Mishra, Moinak Sen Sarma, Ujjal Poddar

Background and aims: Crohn's disease [CD] and intestinal tuberculosis [ITB] are often difficult to differentiate. Mesenteric fat hypertrophy is a feature of CD. We evaluated the utility of fat indices (visceral fat [VF] and subcutaneous fat [SF]) in differentiating CD and ITB in children.

Methods: Symptomatic children diagnosed to have CD or ITB based on recommended criteria were enrolled. Clinical, anthropometric, and laboratory details were noted. Abdominal fat was measured on computed tomography in supine position at the level of L4 vertebrae. VF and SF area was measured separately by a radiologist, blinded to the diagnosis. The sum of VF and SF was taken as total fat [TF]. VF/SF and VF/TF ratios were calculated.

Results: Thirty-four (age 14 years [10.8-17.0], 14 boys) children were recruited: 12 had CD [seven boys, age 13.0 years] and 22 had ITB [seven boys, age 14.5 years]. VF area was higher in CD compared to ITB (18.34 cm2 [15.62-40.01] vs 6.48 cm2 [2.65-21.96]; p = 0.012). The SF and TF area was similar in ITB and CD. The ratios of VF/SF (0.82 [0.57-1.5] vs 0.33 [0.16-0.48]; p = 0.004) and VF/TF (0.45 [0.36-0.60] vs 0.25 [0.13-0.32]; p = 0.004) were significantly higher in CD. On comparing CD and ITB in boys and girls separately, the difference was significant for boys but not for girls. A VF/SF ratio of 0.609 predicted CD with a good sensitivity [75%] and specificity [86.4%] [area under the curve 0.795, 95% confidence interval 0.636-0.955; p = 0.005].

Conclusion: The VF/SF ratio is a simple, non-invasive, objective parameter to differentiate CD and ITB in children, particularly boys. Larger studies are needed to validate this in girls.

背景和目的:克罗恩病 [CD] 和肠结核 [ITB] 通常很难区分。肠系膜脂肪肥厚是 CD 的一个特征。我们评估了脂肪指数(内脏脂肪[VF]和皮下脂肪[SF])在区分儿童克罗恩病和肠结核方面的效用:方法:根据推荐标准诊断为 CD 或 ITB 的无症状儿童入组。注意临床、人体测量和实验室细节。仰卧位时,在L4椎体水平通过计算机断层扫描测量腹部脂肪。VF和SF面积由一名放射科医生分别测量,该医生对诊断结果保密。VF和SF的总和为总脂肪[TF]。计算VF/SF和VF/TF比率:共招募了 34 名儿童(14 岁 [10.8-17.0],14 名男孩):其中 12 名儿童患有 CD(7 名男孩,13.0 岁),22 名儿童患有 ITB(7 名男孩,14.5 岁)。与 ITB 相比,CD 儿童的 VF 面积更大(18.34 平方厘米 [15.62-40.01] vs 6.48 平方厘米 [2.65-21.96];P = 0.012)。ITB 和 CD 的 SF 和 TF 面积相似。CD患儿的VF/SF(0.82 [0.57-1.5] vs 0.33 [0.16-0.48];p = 0.004)和VF/TF(0.45 [0.36-0.60] vs 0.25 [0.13-0.32];p = 0.004)之比明显高于ITB患儿。在分别比较男孩和女孩的 CD 和 ITB 时,男孩的差异显著,女孩则不显著。VF/SF比值为0.609可预测CD,具有良好的敏感性[75%]和特异性[86.4%][曲线下面积为0.795,95%置信区间为0.636-0.955;P = 0.005]:VF/SF比值是区分儿童(尤其是男孩)CD和ITB的一个简单、无创、客观的参数。需要进行更大规模的研究,以便在女孩中验证这一结果。
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引用次数: 0
Neutrophil-only Histological Assessment of Ulcerative Colitis Correlates with Endoscopic Activity and Predicts Long-term Outcomes in a Multicentre Study. 在一项多中心研究中,溃疡性结肠炎的纯中性粒细胞组织学评估与内镜活动相关,并可预测长期疗效。
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad110
Tommaso L Parigi, Rosanna Cannatelli, Olga M Nardone, Irene Zammarchi, Uday Shivaji, Federica Furfaro, Davide Zardo, Paola Spaggiari, Rachele Del Sordo, Orsola Setti, Snehali Majumder, Samuel C L Smith, Silvio Danese, Alessandro Armuzzi, Vincenzo Villanacci, Subrata Ghosh, Marietta Iacucci

Backgrounds and aims: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices.

Methods: Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves.

Results: A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively].

Conclusion: PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

背景和目的:无中性粒细胞是溃疡性结肠炎(UC)组织学缓解的最低标准。PICaSSO组织学缓解指数[PHRI]是一种新的溃疡性结肠炎简易指数,仅基于中性粒细胞的检测。我们评估了 PHRI 与内镜检查的相关性,以及与其他已有指标相比的预后价值:方法:在两个转诊中心(英国伯明翰和意大利米兰)对连续的 UC 患者进行结肠镜检查,并随访 2 年。组织学(PHRI、南希[NHI]和罗巴茨[RHI]指数)与内镜检查(梅奥内镜评分[MES]、溃疡性结肠炎内镜严重程度指数[UCEIS]和 PICaSSO 指数)之间的相关性以 Spearman 系数计算。用接收器操作特征曲线(ROC)评估内镜检查的诊断性能,用卡普兰-梅耶曲线评估结果分层:结果:共192名UC患者接受了内镜检查,代表了内镜检查的所有严重程度。当使用 PHRI 代替 NHI 或 RHI 时,组织学与内镜检查之间的相关性没有明显差异。其中,PHRI 与 MES、UCEIS 和 PICaSSO 的相关性分别为 0.745、0.718 和 0.694。内镜评估的缓解反映了没有中性粒细胞[PHRI = 0],MES、UCEIS 和 PICaSSO 的 ROC 曲线下面积分别为 0.905、0.906 和 0.877。组织学活动期/缓解期患者之间疾病复发的危险比在不同指标上具有统计学相似性[P >0.05][RHI、NHI 和 PHRI 分别为 2.752、2.706 和 2.871]:结论:PHRI 与内镜检查相关,其复发风险分层与 RHI 和 NHI 相似。仅中性粒细胞的 UC 评估是一种简单而可行的方法,可替代已有的组织学评分。
{"title":"Neutrophil-only Histological Assessment of Ulcerative Colitis Correlates with Endoscopic Activity and Predicts Long-term Outcomes in a Multicentre Study.","authors":"Tommaso L Parigi, Rosanna Cannatelli, Olga M Nardone, Irene Zammarchi, Uday Shivaji, Federica Furfaro, Davide Zardo, Paola Spaggiari, Rachele Del Sordo, Orsola Setti, Snehali Majumder, Samuel C L Smith, Silvio Danese, Alessandro Armuzzi, Vincenzo Villanacci, Subrata Ghosh, Marietta Iacucci","doi":"10.1093/ecco-jcc/jjad110","DOIUrl":"10.1093/ecco-jcc/jjad110","url":null,"abstract":"<p><strong>Backgrounds and aims: </strong>Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices.</p><p><strong>Methods: </strong>Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves.</p><p><strong>Results: </strong>A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively].</p><p><strong>Conclusion: </strong>PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence. 溃疡性结肠炎早期升级为高级疗法缺乏益处:对现有证据的批判性评估。
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad106
Johan Burisch, Ekaterina Safroneeva, Raphael Laoun, Christopher Ma

Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.

尽管溃疡性结肠炎(UC)与克罗恩病(CD)有许多共同的发病途径和治疗方案,但在生物时代,CD 患者在患病 10 年后接受手术的几率是 UC 患者的四倍,而且更有可能出现肠外表现。事实证明,CD 的早期治疗可改变疾病的自然史,并有可能推迟手术时间。以往有关这一主题的综述借鉴了 CD 的证据,提出了针对 UC 的建议。本综述强调了来自大型队列研究的 UC 特异性数据以及全面的单个患者数据系统综述和荟萃分析,以批判性地评估早期升级为先进疗法在短期、中期和长期预后方面的效用。在 UC 中,现有数据并不支持早期升级概念对改变自然病史(包括减少结肠切除术和住院治疗)的效用。我们需要针对临床、生化、内镜和组织学结果的数据,以证明这些数据对于减少住院和手术、改善生活质量和减少残疾具有重要意义。迫切需要对 UC 患者的不同人群进行分析,如 "复发与缓解 "患者、重症患者或病程复杂的患者。应仔细考虑一些较新的先进疗法的成本和风险/收益情况。在这种临床情况下,主张在 UC 病程早期不加区分地 "一刀切 "升级到先进疗法似乎为时尚早。
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引用次数: 0
Clinician's Guide to Using Ozanimod for the Treatment of Ulcerative Colitis. 使用奥扎莫德治疗溃疡性结肠炎的临床医师指南》。
IF 8.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad112
Bruce E Sands, Stefan Schreiber, Irina Blumenstein, Michael V Chiorean, Ryan C Ungaro, David T Rubin

The emergence of advanced therapies [eg, biologics, Janus kinase inhibitors] over the past few decades has revolutionised the treatment of ulcerative colitis. However, the limitations of these therapies leave an unmet need for safer and more effective or convenient treatment options. There is growing interest in the development of novel oral small molecule therapies for the treatment of ulcerative colitis. Ozanimod is an oral small molecule therapy that is approved in the USA, the European Union, and other countries as the first sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active ulcerative colitis in adults. This review provides guidance for ozanimod use for the treatment of ulcerative colitis, based on the prescribing information, clinical trial and real-world data, and the authors' clinical experiences. This guidance outlines patient characteristics to consider when deciding if ozanimod treatment is suitable and describes how to educate patients on risks and best practices. It also details the nature and frequency of monitoring during treatment, which should be adapted to the individual patient based on pre-existing risk factors and events that possibly occur during treatment. This review also provides insights into the patient characteristics and clinical scenarios best suited for ozanimod treatment, based on its efficacy, safety profile, and risks compared with other therapies.

过去几十年来,先进疗法(如生物制剂、Janus 激酶抑制剂)的出现彻底改变了溃疡性结肠炎的治疗方法。然而,由于这些疗法的局限性,人们对更安全、更有效或更方便的治疗方案的需求仍未得到满足。人们对开发治疗溃疡性结肠炎的新型口服小分子疗法越来越感兴趣。奥扎尼莫是一种口服小分子疗法,在美国、欧盟和其他国家已获批准,是首个用于治疗成人中度至重度活动性溃疡性结肠炎的鞘磷脂受体调节剂。本综述根据处方信息、临床试验和实际数据以及作者的临床经验,为使用奥扎尼莫治疗溃疡性结肠炎提供指导。本指南概述了在决定是否适合使用奥扎莫德治疗时应考虑的患者特征,并介绍了如何向患者进行风险教育和最佳实践。它还详细介绍了治疗过程中监测的性质和频率,应根据患者原有的风险因素和治疗过程中可能发生的事件对监测进行调整。本综述还根据奥扎莫德的疗效、安全性以及与其他疗法相比的风险,深入分析了最适合接受奥扎莫德治疗的患者特征和临床情况。
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引用次数: 0
An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli. 肠道 Th17 亚群与克罗恩病的炎症有关,并被粘附性侵袭性大肠埃希氏菌激活
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad119
Moira Paroni, Gabriella Leccese, Valeria Ranzani, Giorgia Moschetti, Matteo Chiara, Federica Perillo, Sara Ferri, Francesca Clemente, Daniele Noviello, Francesco Simone Conforti, Stefano Ferrero, Bhavna Karnani, Roberto Bosotti, Chiara Vasco, Serena Curti, Maria Cristina Crosti, Paola Gruarin, Grazisa Rossetti, Maria Pia Conte, Maurizio Vecchi, Massimiliano Pagani, Paolo Landini, Federica Facciotti, Sergio Abrignani, Flavio Caprioli, Jens Geginat

IFNγ-producing ex-Th17 cells ['Th1/17'] were shown to play a key pathogenic role in experimental colitis and are abundant in the intestine. Here, we identified and characterised a novel, potentially colitogenic subset of Th17 cells in the intestine of patients with Crohn's disease [CD]. Human Th17 cells expressing CCR5 ['pTh17'] co-expressed T-bet and RORC/γt and produced very high levels of IL-17, together with IFN-γ. They had a gene signature of Th17 effector cells and were distinct from established Th1/17 cells. pTh17 cells, but not Th1/17 cells, were associated with intestinal inflammation in CD, and decreased upon successful anti-TNF therapy with infliximab. Conventional CCR5[-]Th17 cells differentiated to pTh17 cells with IL-23 in vitro. Moreover, anti-IL-23 therapy with risankizumab strongly reduced pTh17 cells in the intestine. Importantly, intestinal pTh17 cells were selectively activated by adherent-invasive Escherichia coli [AIEC], but not by a commensal/probiotic E. coli strain. AIEC induced high levels of IL-23 and RANTES from dendritic cells [DC]. Intestinal CCR5+Th1/17 cells responded instead to cytomegalovirus and were reduced in ulcerative colitis [UC], suggesting an unexpected protective role. In conclusion, we identified an IL-23-inducible subset of human intestinal Th17 cells. pTh17 cells produced high levels of pro-inflammatory cytokines, were selectively associated with intestinal inflammation in CD, and responded to CD-associated AIEC, suggesting a key colitogenic role.

研究表明,产生 IFNγ 的外 Th17 细胞("Th1/17")在实验性结肠炎中起着关键的致病作用,并且在肠道中含量丰富。在这里,我们发现并描述了克罗恩病患者肠道中一种新的、可能导致结肠炎的 Th17 细胞亚群。表达 CCR5 的人类 Th17 细胞("pTh17")共同表达 T-bet 和 RORC/γt,并产生高水平的 IL-17 和 IFN-γ。它们具有 Th17 效应细胞的基因特征,与已建立的 Th1/17 细胞截然不同。pTh17 细胞(而非 Th1/17 细胞)与 CD 的肠道炎症有关,在使用英夫利昔单抗成功进行抗肿瘤坏死因子治疗后会减少。传统的CCR5[-]Th17细胞在体外IL-23的作用下分化为pTh17细胞。此外,利桑珠单抗抗IL-23疗法可显著减少肠道中的pTh17细胞。重要的是,肠道 pTh17 细胞会被粘附侵袭性大肠杆菌 [AIEC] 选择性激活,但不会被共生/益生性大肠杆菌菌株激活。AIEC诱导树突状细胞(DC)产生高水平的IL-23和RANTES。肠道 CCR5+Th1/17 细胞反而对巨细胞病毒有反应,并在溃疡性结肠炎(UC)中减少,这表明它具有意想不到的保护作用。总之,我们发现了一个 IL-23 诱导的人类肠 Th17 细胞亚群。pTh17 细胞产生大量促炎细胞因子,选择性地与 CD 中的肠道炎症相关,并对 CD 相关的 AIEC 有反应,这表明它具有关键的结肠生成作用。
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引用次数: 0
Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study. 生物时代克罗恩病患者术后吻合口区域的内镜病变:日本多中心全国队列研究》。
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad116
Takeshi Ueda, Fumikazu Koyama, Akira Sugita, Hiroki Ikeuchi, Kitaro Futami, Kouhei Fukushima, Riichiro Nezu, Hideki Iijima, Tsunekazu Mizushima, Michio Itabashi, Kazuhiro Watanabe, Keisuke Hata, Takahide Shinagawa, Katsuyoshi Matsuoka, Kento Takenaka, Makoto Sasaki, Manabu Nagayama, Hironori Yamamoto, Masaru Shinozaki, Mikihiro Fujiya, Jun Kato, Yoshitaka Ueno, Shinji Tanaka, Yoshiki Okita, Yoshinari Hashimoto, Taku Kobayashi, Kazutaka Koganei, Motoi Uchino, Hisao Fujii, Yasuo Suzuki, Tadakazu Hisamatsu

Background and aims: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients.

Methods: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis.

Results: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions.

Conclusions: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

背景和目的:许多患者在肠道切除术后 1 年,内镜检查发现克罗恩病 [CD] 复发。这些病变可预测未来的临床复发。我们对一大批术后 CD 患者的术后吻合口病变进行了内镜评估:我们回顾性地纳入了 2008 年至 2013 年期间在 19 家炎症性肠病 [IBD] 专家机构接受手术切除的 CD 患者。初步分析包括肠切除术后约 1 年接受回肠结肠镜检查的患者。随访分析评估了内镜检查结果随时间推移发生的任何变化。我们评估了术后内镜检查结果,并将吻合口线和吻合口周围部位的内镜检查结果分为四类[无病变、轻度、中度、重度]:共有267名CD患者接受了术后回肠结肠镜检查。术后吻合口病变在索引回肠结肠镜检查中被广泛发现[61.0%],在随访回肠结肠镜检查中被更频繁地发现[74.9%]。内镜检查的严重程度也有所增加。与病变轻微或无病变的患者相比,在索引回肠结肠镜检查中发现中度或重度吻合口周围病变或吻合口线病变的患者需要更多的干预措施,包括内镜扩张或手术:结论:术后首次回肠结肠镜检查发现吻合口经常出现病变。这些病变在随后的回肠结肠镜检查中逐渐增加,即使在生物时代也是如此。关于吻合口线上的病变,吻合口线上的中度病变(如不规则或深度溃疡)可视为复发性疾病,而轻度病变(如线状浅表溃疡)可视为非复发性疾病。要解决这个问题,需要进行前瞻性研究,包括加强治疗。
{"title":"Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.","authors":"Takeshi Ueda, Fumikazu Koyama, Akira Sugita, Hiroki Ikeuchi, Kitaro Futami, Kouhei Fukushima, Riichiro Nezu, Hideki Iijima, Tsunekazu Mizushima, Michio Itabashi, Kazuhiro Watanabe, Keisuke Hata, Takahide Shinagawa, Katsuyoshi Matsuoka, Kento Takenaka, Makoto Sasaki, Manabu Nagayama, Hironori Yamamoto, Masaru Shinozaki, Mikihiro Fujiya, Jun Kato, Yoshitaka Ueno, Shinji Tanaka, Yoshiki Okita, Yoshinari Hashimoto, Taku Kobayashi, Kazutaka Koganei, Motoi Uchino, Hisao Fujii, Yasuo Suzuki, Tadakazu Hisamatsu","doi":"10.1093/ecco-jcc/jjad116","DOIUrl":"10.1093/ecco-jcc/jjad116","url":null,"abstract":"<p><strong>Background and aims: </strong>Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients.</p><p><strong>Methods: </strong>We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis.</p><p><strong>Results: </strong>In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions.</p><p><strong>Conclusions: </strong>Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis. 为有英夫利西单抗经验的急性重度溃疡性结肠炎患者提供乌达替尼挽救疗法
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad115
Robert Gilmore, Wei Lian Tan, Richard Fernandes, Yoon-Kyo An, Jakob Begun

Background and aims: Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.

Methods: Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.

Results: All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.

Conclusions: Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.

背景和目的:急性重症溃疡性结肠炎(ASUC)是一种医疗急症,静脉注射类固醇后,在类固醇无效的情况下使用英夫利昔单抗或环孢素,难治性或重症病例需要进行紧急结肠切除术。已有系列病例报道了托法替尼治疗难治性疾病的疗效,但有关达帕替尼在这种情况下的疗效的数据此前尚未见报道。我们描述了使用达帕替尼治疗类固醇难治性ASUC的情况,这些患者曾对英夫利西单抗失去反应:我们在澳大利亚的两家三级炎症性肠病中心找到了六名接受达帕替尼治疗类固醇难治性ASUC的患者。出院后,对患者进行了长达16周的随访,以了解临床、生化和肠道超声[IUS]结果:结果:所有六名患者在住院期间都对达达替尼诱导治疗产生了临床反应。4名患者在第8周时实现了无皮质类固醇临床缓解,包括IUS评估的直肠出血完全止住和经壁愈合,并在第16周时实现了持续临床缓解。一名患者因难治性疾病在第 15 周时进行了结肠切除术。未发现可直接归因于乌达替尼的不良事件:结论:奥达帕替尼可作为一种安全有效的挽救疗法,用于既往对英夫利西单抗治疗无效的类固醇难治性ASUC患者。在推荐常规使用前,需要进行前瞻性研究以确定在这种情况下使用奥达替尼的安全性和有效性。
{"title":"Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis.","authors":"Robert Gilmore, Wei Lian Tan, Richard Fernandes, Yoon-Kyo An, Jakob Begun","doi":"10.1093/ecco-jcc/jjad115","DOIUrl":"10.1093/ecco-jcc/jjad115","url":null,"abstract":"<p><strong>Background and aims: </strong>Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.</p><p><strong>Methods: </strong>Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.</p><p><strong>Results: </strong>All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.</p><p><strong>Conclusions: </strong>Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10120620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. 炎症性肠病中 NUDT15 基因变异的流行与硫嘌呤诱发的白细胞减少症的发生率:系统回顾与元分析》。
IF 8 2区 医学 Q1 Medicine Pub Date : 2023-12-30 DOI: 10.1093/ecco-jcc/jjad107
Natalie Yu, Danujan Sriranganathan, Gareth J Walker, Aleksejs Sazonovs, Helen Wilding, Christopher Roberts, Nicholas A Kennedy, Tariq Ahmad, Ray K Boyapati, Nik S Ding, Jonathan P Segal

Background and aims: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.

Methods: Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia.

Results: Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients.

Conclusions: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.

背景和目的:Nudix hydrolase 15 [NUDT15]基因变异会增加硫嘌呤诱导的白细胞减少症[TIL]的风险;然而,这些变异在炎症性肠病[IBD]患者中的总体患病率尚不清楚。我们的目的是评估 NUDT15 变体在 IBD 患者中的总体流行率以及这些患者中 TIL 的发病率:方法:检索了从开始到 2022 年 7 月的六个数据库。方法:检索了从开始到 2022 年 7 月的六个数据库,纳入了报告任何 NUDT15 变体频率和/或具有这些变体的成年 IBD 患者白细胞减少症频率的研究。采用随机效应模型估算变异体的汇总患病率、早期[≤8周]和晚期[>8周]白细胞减少症的发病率以及患白细胞减少症的相对风险:共纳入 20 项研究,5232 名患者。*1/*3 c.415C > T C/T 二联型的汇总患病率为 13%(95% 置信区间 [CI]:10-18%),*3/*3 c.415C > T T/T 二联型为 2% [95% CI:1-2%],*1/*5 c.52G > A G/A 二联型为 2% [95% CI:1-3%],*1/*6 c.36_37insGGAGTC ins/- 二联型为 7% [95% CI:4-12%]。*1/*3 在日本人[20%,95% CI:16-24%]和中国人[18%,95% CI:12-27%]中的合计发病率较高。*1/*3患者早期白细胞减少的发生率为20% [95% CI:16-26%],*3/*3患者为99% [95% CI:7-100%],*1/*6患者为49% [95% CI:29-69%]。在*1/*3患者中,晚期白细胞减少症的发生率为36% [95% CI:26-49%]:结论:NUDT15变异很常见,可强烈预测IBD患者的TIL。应考虑在治疗前进行 NUDT15 基因分型,尤其是在亚洲人群中,以指导硫嘌呤剂量并预防骨髓毒性。
{"title":"Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.","authors":"Natalie Yu, Danujan Sriranganathan, Gareth J Walker, Aleksejs Sazonovs, Helen Wilding, Christopher Roberts, Nicholas A Kennedy, Tariq Ahmad, Ray K Boyapati, Nik S Ding, Jonathan P Segal","doi":"10.1093/ecco-jcc/jjad107","DOIUrl":"10.1093/ecco-jcc/jjad107","url":null,"abstract":"<p><strong>Background and aims: </strong>Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.</p><p><strong>Methods: </strong>Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia.</p><p><strong>Results: </strong>Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients.</p><p><strong>Conclusions: </strong>NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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Journal of Crohns & Colitis
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