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Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study). 在中重度克罗恩病成年患者中使用维多珠单抗配合纯肠内营养治疗(CEEN 研究)。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-21 DOI: 10.14309/ctg.0000000000000759
Jing Wang, Zhishun Tang, Jiao Li, Anning Yin, Yaqing Xu, Liping Zou, Haixia Ren, Jian Kang, Juan Su, Qian Zhou, Yang Wang, Wei Wang, Jing Zhang, Huipeng Wan, Ping An

Introduction: Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD.

Methods: From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52.

Results: There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events.

Discussion: VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.

背景:尽管越来越多的研究证实了维多珠单抗对克罗恩病(CD)的疗效,但在临床实践中,改善对这种生物制剂的反应仍具有挑战性。在此,我们研究了维多珠单抗和16周纯肠内营养(EEN)联合治疗中度至重度活动性克罗恩病的疗效:回顾性选取了2020年10月至2023年10月期间,来自三个IBD中心的81例接受维多珠单抗治疗的中重度活动性CD患者。41名患者接受了韦多珠单抗治疗,并同时接受了为期16周的EEN治疗(韦多珠单抗,VDZ+EEN队列),40名患者单独接受了韦多珠单抗治疗(VDZ队列)。对临床和生物学结果进行了评估。在第16周和第52周通过结肠镜检查评估内镜反应和粘膜愈合情况:结果:两组患者在人口统计学和临床特征方面的基线差异无统计学意义。与单独接受维多珠单抗治疗的患者相比,VDZ+EEN组患者在第16周时的临床应答率(84.2% vs. 40.0%)、临床缓解率(81.6% vs. 30.0%)、内镜应答率(91.4% vs. 34.6%)和粘膜愈合率(85.7% vs. 26.9%)均较高。VDZ+EEN治疗的优越性在维持治疗中得以保持,第52周时,临床应答率为76.7%(vs 33.3%),临床缓解率为70.0%(vs 26.7%),内镜应答率为76.9%(vs 33.3%),粘膜愈合率为61.5%(vs 26.7%)。没有患者出现严重不良反应:韦多珠单抗联合16周EEN可能是诱导和维持治疗活动性CD的一种有效且疗效确切的优化方法。
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引用次数: 0
A brief model evaluated outcomes after liver transplantation based on the matching of donor graft and recipient. 一个简短的模型根据供体移植物和受体的匹配情况对肝移植后的结果进行了评估。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-21 DOI: 10.14309/ctg.0000000000000761
Yuancheng Li, Xingchao Liu, Chengcheng Zhang, Ran Tao, Bi Pan, Wei Liu, Di Jiang, Feng Hu, Zeliang Xu, Dehong Tan, Yanjiao Ou, Xun Li, Yuemei You, Leida Zhang

Background: A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes.

Methods: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications.

Results: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications.

Conclusions: Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.

背景:指导围手术期管理需要一个精确的预后模型。随着肝移植(LT)学科的发展,以前的模型可能变得不合适或不全面。因此,我们旨在开发一种整合供体和受体变量的新型模型,以快速评估移植结果:方法:该风险模型基于随机选择的衍生队列中的 Cox 回归,并在验证队列中得到验证。比较了按X-分层分组的围手术期数据和总生存率。采用接收者操作特征曲线和决策曲线分析来比较模型。生成的小提琴图和雨云图显示了不同分层中LT术后并发症的分布情况:共有来自两个中心的528名接受LT的患者,其中2/3属于推导队列,1/3属于验证队列。Cox回归分析显示,冷缺血时间(CIT)(P=0.012)和终末期肝病模型(MELD)(P=0.007)评分是预测生存率的因素。与对数模型比较后,CIT 和 MELD 的原始算法被定义为 CIT-MELD 指数(CMI)。CMI按X分层(1级≤1.06,1.06< 2级≤1.87,3级>1.87)进行分层。在两个队列中,CMI在计算移植结果(包括围手术期事件和并发症发生率)方面的表现均优于风险平衡评分:结论:整合移植物和受体变量的模型使预测更准确、更可用。CMI为LT的结果评估和风险因素管理提供了新的视角。
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引用次数: 0
Hepatic Insulin Resistance Increases Risk of Gallstone Disease in Indigenous Americans in the Southwestern United States. 肝脏胰岛素抵抗会增加美国西南部土著美国人患胆石症的风险。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-21 DOI: 10.14309/ctg.0000000000000763
Beyza N Aydin, Emma J Stinson, Robert L Hanson, Helen C Looker, Tomás Cabeza De Baca, Jonathan Krakoff, Douglas C Chang

Introduction: Animal models indicate that hepatic insulin resistance (IR) promotes cholesterol gallstone disease (GSD). We sought to determine whether hepatic and whole-body IR is associated with incident GSD.

Methods: At baseline, 450 Southwestern Indigenous American adults without GSD were included. Participants had a 2-step hyperinsulinemic-euglycemic clamp with glucose tracer at submaximal and maximal insulin stimulation (240 and 2,400 pmol/m 2 /min) for whole-body IR (M-low and M-high) and hepatic glucose production (HGP) before and during submaximal insulin infusion (HGP-basal and HGP-insulin). Incident GSD was identified during follow-up visits conducted at ∼2-year intervals. The associations of HGP (basal, insulin, and % suppression), M-low, and M-high with risk of GSD were assessed by Cox regression models adjusted for age, sex, body fat (%), glucose, and insulin.

Results: Sixty participants (13%) developed GSD (median follow-up: 11.6 years). Participants who developed GSD were of similar age and whole-body IR as those who did not ( P 's > 0.07) but were more likely to be female; have higher body fat, higher HGP-basal, and HGP-insulin; and lower % suppression of HGP ( P 's < 0.02). In separate adjusted models, higher HGP-insulin and lower % suppression of HGP were associated with increased risk for GSD (hazard ratio [HR] per SD: HR 1.38, 95% CI 1.12-1.69, P = 0.002; HR 1.41, 95% CI 1.16-1.72, P = 0.0007). HGP-basal, M-low, and M-high were not associated with GSD in adjusted models ( P 's > 0.22).

Discussion: Resistance to insulin suppression of HGP increases risk for GSD. Hepatic IR is a link between GSD and other conditions of the metabolic syndrome.

目的:动物模型表明,肝脏胰岛素抵抗(IR)会促进胆固醇性胆石症(GSD)。我们试图确定肝脏和全身 IR 是否与 GSD 发病有关:方法:我们纳入了 450 名无 GSD 的美国西南部土著成年人。参与者在胰岛素刺激亚极限和极限(240 和 2400 pmol/m2/min)时使用葡萄糖示踪剂进行两步高胰岛素血糖钳夹,以测定全身 IR(M-低和 M-高)和肝脏葡萄糖生成量(HGP),然后再输注亚极限胰岛素(HGP-基本和 HGP-胰岛素)。每隔 2 年进行一次随访,以确定是否发生 GSD。通过Cox回归模型评估了HGP(基础、胰岛素和抑制百分比)、M-低和M-高与GSD风险的关系,并对年龄、性别、体脂(百分比)、血糖和胰岛素进行了调整:结果:60 名参与者(13%)出现了 GSD(中位随访时间:11.6 年)。出现 GSD 的参与者与未出现 GSD 的参与者的年龄和全身 IR 值相似(P's> 0.07),但更有可能是女性、体脂较高、HGP-基础值和 HGP-胰岛素值较高以及 HGP 抑制率较低(P's0.22):结论:胰岛素抑制 HGP 的阻力会增加 GSD 的风险。结论:胰岛素抑制 HGP 的抵抗会增加 GSD 的风险,肝 IR 是 GSD 与代谢综合征其他病症之间的联系。
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引用次数: 0
Intravenous lidocaine for refractory pain in patients with pancreatic ductal adenocarcinoma and chronic pancreatitis (LIDOPAN): a multicenter prospective non-randomized pilot study. 静脉注射利多卡因治疗胰腺导管腺癌和慢性胰腺炎患者的难治性疼痛(LIDOPAN):一项多中心前瞻性非随机试验研究。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-19 DOI: 10.14309/ctg.0000000000000760
Simone Augustinus, Matthanja Bieze, Charlotte L Van Veldhuisen, Marja A Boermeester, Bert A Bonsing, Stefan A W Bouwense, Marco J Bruno, Olivier R Busch, Werner Ten Hoope, Jan-Willem Kallewaard, Henk J van Kranen, Marieke Niesters, Niels C J Schellekens, Monique A H Steegers, Rogier P Voermans, Judith de Vos-Geelen, Johanna W Wilmink, Jan H M Van Zundert, Casper H van Eijck, Marc G Besselink, Markus W Hollmann

Introduction: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.

Methods: Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant.

Results: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life.

Conclusion: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

导言:难治性疼痛是胰腺导管腺癌(PDAC)和慢性胰腺炎(CP)患者的主要临床问题。目前迫切需要新的、有效的止痛疗法。静脉注射利多卡因被用于 PDAC 和 CP 患者的临床实践,但尚未对其疗效进行前瞻性研究:多中心前瞻性非随机试验研究,包括荷兰 5 个中心的中度或重度疼痛(NRS ≥ 4)的 PDAC 或 CP 患者。静脉注射利多卡因 1.5 毫克/千克,然后以 1.5 毫克/千克/小时的剂量持续输注。剂量每15分钟增加一次,直至治疗反应(最高剂量为2毫克/千克/小时),连续输注两小时。主要结果是输液前和输液后第一天疼痛严重程度的平均差异(简明疼痛量表[BPI]评分 1-10)。BPI下降≥1.3分被认为具有临床意义:共纳入 30 名患者,其中 PDAC 患者 19 名(占 63%),CP 患者 11 名(占 37%)。第一天,PDAC 患者的 BPI 平均差异为 1.1(SD±1.3)分,CP 患者的 BPI 平均差异为 0.5(SD±1.7)分。有 9/29 例患者(31%)报告第一天的 BPI 出现临床相关性下降,这种反应持续了一个月。无严重并发症报告,仅有 3 例轻微并发症(眩晕、恶心、口腔刺痛)。利多卡因治疗不会影响生活质量:结论:静脉注射利多卡因治疗疼痛的 PDAC 和 CP 患者并未显示出临床相关的总体减痛效果。然而,这项试验性研究表明,这种治疗方法在这一患者群体中是可行的,并对三分之一的患者产生了积极的影响,这种影响可持续一个月之久,且只有轻微的副作用。为了证明或排除静脉注射利多卡因的疗效,这项研究应该在样本量更大、异质性更小的患者群体中进行。
{"title":"Intravenous lidocaine for refractory pain in patients with pancreatic ductal adenocarcinoma and chronic pancreatitis (LIDOPAN): a multicenter prospective non-randomized pilot study.","authors":"Simone Augustinus, Matthanja Bieze, Charlotte L Van Veldhuisen, Marja A Boermeester, Bert A Bonsing, Stefan A W Bouwense, Marco J Bruno, Olivier R Busch, Werner Ten Hoope, Jan-Willem Kallewaard, Henk J van Kranen, Marieke Niesters, Niels C J Schellekens, Monique A H Steegers, Rogier P Voermans, Judith de Vos-Geelen, Johanna W Wilmink, Jan H M Van Zundert, Casper H van Eijck, Marc G Besselink, Markus W Hollmann","doi":"10.14309/ctg.0000000000000760","DOIUrl":"10.14309/ctg.0000000000000760","url":null,"abstract":"<p><strong>Introduction: </strong>Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.</p><p><strong>Methods: </strong>Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant.</p><p><strong>Results: </strong>Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life.</p><p><strong>Conclusion: </strong>Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort. 评估美国队列中的慢性胰腺炎预后评分。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-13 DOI: 10.14309/ctg.0000000000000758
Soo Kyung Park, Darwin L Conwell, Phil A Hart, Shuang Li, Kimberly Stello, Evan L Fogel, William E Fisher, Christopher E Forsmark, Stephen J Pandol, Walter G Park, Mark Topazian, Jose Serrano, Santhi Swaroop Vege, Stephen K Van Den Eeden, Liang Li, Dhiraj Yadav, Jami L Saloman

Introduction: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.

Methods: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up.

Results: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups.

Discussion: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

简介慢性胰腺炎预后评分(COPPS)旨在区分疾病严重程度并预测未来住院风险。在这项队列研究中,我们评估了 COPPS 是否能预测美国队列中住院的可能性:CPDPC联盟提供了慢性胰腺炎受试者的数据和血清(N=279)。根据基线数据计算 COPPS,并按严重程度(低、中、高)进行分层。主要终点包括12个月随访期间的住院次数和住院时间:结果:COPPS的平均值(含)为8.4±1.6。COPPS与所有主要结局相关:任何原因住院(次数:r=0.15,p=0.01;持续时间:r=0.16,p=0.01)和胰腺相关住院(次数:r=0.15,p=0.02;持续时间:r=0.13,p=0.04)。严重程度分布为低度 13.3%、中度 66.0%、高度 20.8%。37.6%的受试者因任何原因住院≥1次;32.2%的受试者因胰腺相关原因住院≥1次。所有主要结果在严重程度组之间均有明显差异:任何原因住院(次数,P=0.004;持续时间,P=0.007)和胰腺相关住院(次数,P=0.02;持续时间,P=0.04)。低度组和中度组在随访时继续饮酒的比例更高(p=0.04)。入组时(p=0.02)和随访时(p=0.04)的焦虑发生率较高:从统计学角度看,COPPS与住院结果有明显的相关性,但相关性比以往的研究要弱,这可能与PROCEED队列的门诊性质和高严重程度疾病的发病率较低有关。要了解 COPPS 作为临床风险评估和干预潜在工具的全部效用,还需要对其他前瞻性队列进行研究。
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引用次数: 0
Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis. 血清色氨酸减少和结肠粘膜严重溃疡性损伤可确定炎症性肠病患者是 CMV 结肠炎的高危人群。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-01 DOI: 10.14309/ctg.0000000000000731
Sophia Rüsing, Lina Welz, Constanze Pfitzer, Danielle Monica Harris, Christoph Röcken, Philip Rosenstiel, Susanna Nikolaus, Florian Tran, Stefan Schreiber, Konrad Aden, Laura Katharina Sievers

Introduction: Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination of disease flares and colonic CMV reactivation is difficult in patients with established diagnosis of IBD, and there are no reliable noninvasive diagnostic tools yet. Furthermore, the influence of novel therapeutics including biologicals and Janus kinase inhibitors on the risk of CMV colitis is unclear. The goal of this study was to identify risk factors and clinical determinants of CMV colitis that could serve as minimally invasive markers both for active CMV colitis and relapse.

Methods: To this end, a retrospective analysis of 376 patients with suspected or confirmed CMV colitis 2016-2023 was performed.

Results: Previous administration of systemic steroids increased the odds of CMV colitis to OR 4.6. Biologicals did not change the incidence of CMV colitis but decreased the OR of a relapse to 0.13. Clinical parameters such as severely bloody diarrhea, intense microscopic ulcerative damage, and decreased serum tryptophan correlated with detection of CMV. Importantly, persistent decrease of tryptophan was observed in patients with CMV relapse. Furthermore, tryptophan degradation through the kynurenine pathway was increased in CMV-positive patients.

Discussion: Taken together, we identify decreased serum tryptophan as a novel potential minimally invasive marker to aid identification of IBD patients with active CMV colitis and at high risk for relapse.

导言:炎症性肠病(IBD)患者易重新激活病毒感染,如巨细胞病毒(CMV)。对于已确诊为 IBD 的患者,临床上很难分辨疾病复发和结肠 CMV 再激活,而且目前还没有可靠的非侵入性诊断工具。此外,包括生物制剂和 Janus 激酶 (JAK) 抑制剂在内的新型疗法对 CMV 结肠炎风险的影响尚不明确。本研究的目的是确定CMV结肠炎的风险因素和临床决定因素,这些因素可作为活动性CMV结肠炎和复发的微创标记物:为此,对2016-2023年376例疑似或确诊CMV结肠炎患者进行了回顾性分析:结果:既往使用过全身性类固醇会使CMV结肠炎的几率增加到OR 4.6。生物制剂并未改变CMV结肠炎的发病率,但将复发的OR值降至0.13。临床参数,如严重的血性腹泻、严重的显微溃疡性损伤和血清色氨酸的减少与 CMV 的检测相关。重要的是,在 CMV 复发患者中观察到色氨酸持续减少。此外,在 CMV 阳性患者中,色氨酸通过犬尿氨酸途径的降解增加:综上所述,我们发现血清色氨酸的减少是一种潜在的新型微创标记物,有助于识别患有活动性 CMV 结肠炎和复发高风险的 IBD 患者。
{"title":"Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis.","authors":"Sophia Rüsing, Lina Welz, Constanze Pfitzer, Danielle Monica Harris, Christoph Röcken, Philip Rosenstiel, Susanna Nikolaus, Florian Tran, Stefan Schreiber, Konrad Aden, Laura Katharina Sievers","doi":"10.14309/ctg.0000000000000731","DOIUrl":"10.14309/ctg.0000000000000731","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination of disease flares and colonic CMV reactivation is difficult in patients with established diagnosis of IBD, and there are no reliable noninvasive diagnostic tools yet. Furthermore, the influence of novel therapeutics including biologicals and Janus kinase inhibitors on the risk of CMV colitis is unclear. The goal of this study was to identify risk factors and clinical determinants of CMV colitis that could serve as minimally invasive markers both for active CMV colitis and relapse.</p><p><strong>Methods: </strong>To this end, a retrospective analysis of 376 patients with suspected or confirmed CMV colitis 2016-2023 was performed.</p><p><strong>Results: </strong>Previous administration of systemic steroids increased the odds of CMV colitis to OR 4.6. Biologicals did not change the incidence of CMV colitis but decreased the OR of a relapse to 0.13. Clinical parameters such as severely bloody diarrhea, intense microscopic ulcerative damage, and decreased serum tryptophan correlated with detection of CMV. Importantly, persistent decrease of tryptophan was observed in patients with CMV relapse. Furthermore, tryptophan degradation through the kynurenine pathway was increased in CMV-positive patients.</p><p><strong>Discussion: </strong>Taken together, we identify decreased serum tryptophan as a novel potential minimally invasive marker to aid identification of IBD patients with active CMV colitis and at high risk for relapse.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mucosal Healing Among Black and White Patients With Inflammatory Bowel Disease. 黑人和白人炎症性肠病患者的黏膜愈合情况。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-01 DOI: 10.14309/ctg.0000000000000737
Devika Dixit, Nicole C Ruiz, Steve Shen, Arvin Daneshmand, Vanessa I Rodriguez, Steve Qian, Dan Neal, S Devi Rampertab, Ellen M Zimmermann, Amir Y Kamel

Introduction: Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD. This study assessed MH between Black and White patients with IBD.

Methods: Retrospective analysis was performed on Black and White adults with IBD who were hospitalized for an active flare. The presence of MH was assessed at 6-18 months after hospitalization. IBD treatments received before and during hospitalization, within 6 months, and 6-18 months after discharge were recorded. C-reactive protein (CRP) levels were collected at hospitalization and 6-18 months after discharge; the difference was reported as delta CRP.

Results: One hundred nine patients were followed up after hospitalization. Of those 88 (80.7%) were White patients, and 21 (19.3%) were Black patients. White and Black patients received similar proportions of IBD treatment before ( P = 0.2) and during ( P = 0.6) hospitalization, within 6 months ( P = 0.1), and 6-18 months ( P = 0.1) after discharge. Black patients achieved numerically higher rates of MH (15/21 = 71.4% vs 53/88 = 60.2%, P = 0.3) and delta CRP ( P = 0.2) than White patients, however, not statistically significant.

Discussion: In patients admitted to the hospital with an IBD flare with similar treatment and care, there was a trend toward higher rates of MH in Black patients compared with White patients. These data suggest that MH is likely not the only factor that is associated with Black patients experiencing worse clinical outcomes when compared with White patients.

简介克罗恩病(CD)和溃疡性结肠炎(UC)以胃肠道慢性炎症为特征。黏膜愈合(MH)是 IBD 患者的治疗目标。目前的数据表明,黑人 IBD 患者的临床疗效可能不如白人患者。本研究对黑人和白人 IBD 患者的黏膜愈合情况进行了评估:方法:对因病情发作住院的黑人和白人成年 IBD 患者进行回顾性分析。入院后 6-18 个月时对是否存在 MH 进行了评估。记录了住院前、住院期间、住院6个月内和出院后6-18个月内接受的IBD治疗。收集住院时和出院后 6-18 个月的 C 反应蛋白(CRP)水平;差异以 delta CRP 报告:结果:109 名患者在住院后接受了随访。其中 88 人(80.7%)为白人患者,21 人(19.3%)为黑人患者。白人和黑人患者在住院前(p=0.2)、住院期间(p=0.6)、出院后 6 个月内(p=0.1)和 6-18 个月内(p=0.1)接受 IBD 治疗的比例相似。黑人患者的 MH(15/21=71.4% vs. 53/88=60.2%,p=0.3)和 delta CRP(p=0.2)率均高于白人患者,但无统计学意义:结论:在接受类似治疗和护理的 IBD 复发入院患者中,黑人患者的 MH 发生率有高于白人患者的趋势。这些数据表明,与白人患者相比,MH 可能不是导致黑人患者临床治疗效果较差的唯一因素。
{"title":"Mucosal Healing Among Black and White Patients With Inflammatory Bowel Disease.","authors":"Devika Dixit, Nicole C Ruiz, Steve Shen, Arvin Daneshmand, Vanessa I Rodriguez, Steve Qian, Dan Neal, S Devi Rampertab, Ellen M Zimmermann, Amir Y Kamel","doi":"10.14309/ctg.0000000000000737","DOIUrl":"10.14309/ctg.0000000000000737","url":null,"abstract":"<p><strong>Introduction: </strong>Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD. This study assessed MH between Black and White patients with IBD.</p><p><strong>Methods: </strong>Retrospective analysis was performed on Black and White adults with IBD who were hospitalized for an active flare. The presence of MH was assessed at 6-18 months after hospitalization. IBD treatments received before and during hospitalization, within 6 months, and 6-18 months after discharge were recorded. C-reactive protein (CRP) levels were collected at hospitalization and 6-18 months after discharge; the difference was reported as delta CRP.</p><p><strong>Results: </strong>One hundred nine patients were followed up after hospitalization. Of those 88 (80.7%) were White patients, and 21 (19.3%) were Black patients. White and Black patients received similar proportions of IBD treatment before ( P = 0.2) and during ( P = 0.6) hospitalization, within 6 months ( P = 0.1), and 6-18 months ( P = 0.1) after discharge. Black patients achieved numerically higher rates of MH (15/21 = 71.4% vs 53/88 = 60.2%, P = 0.3) and delta CRP ( P = 0.2) than White patients, however, not statistically significant.</p><p><strong>Discussion: </strong>In patients admitted to the hospital with an IBD flare with similar treatment and care, there was a trend toward higher rates of MH in Black patients compared with White patients. These data suggest that MH is likely not the only factor that is associated with Black patients experiencing worse clinical outcomes when compared with White patients.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study. 原发性硬化性胆管炎所致代偿性肝硬化患者的西洛非索:开放标签 1B 期研究
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-01 DOI: 10.14309/ctg.0000000000000744
Cynthia Levy, Stephen Caldwell, Parvez Mantry, Velimir Luketic, Charles S Landis, Jonathan Huang, Edward Mena, Rahul Maheshwari, Kevin Rank, Jun Xu, Vladislav A Malkov, Andrew N Billin, Xiangyu Liu, Xiaomin Lu, William T Barchuk, Timothy R Watkins, Chuhan Chung, Robert P Myers, Kris V Kowdley

Introduction: This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis.

Methods: Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers and pharmacodynamic biomarkers of bile acid homeostasis.

Results: Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug-related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7 to -7.4) for alanine transaminase, -13.0% (-21.9 to -8.6) for alkaline phosphatase, -43.5% (-52.1 to -30.8) for γ-glutamyl transferase, -12.7% (-25.0 to 0.0) for total bilirubin, and -21.2% (-40.0 to 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8 to -31.6) for C4 and -60.5% (-81.8 to -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration.

Discussion: Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to primary sclerosing cholangitis (NCT04060147).

研究目的这项概念验证、开放标签的 1b 期研究评估了强效选择性法尼类固醇 X 受体激动剂 cilofexor 在原发性硬化性胆管炎(PSC)引起的代偿性肝硬化患者中的安全性和有效性:递增剂量的cilofexor(30毫克[第1-4周]、60毫克[第5-8周]、100毫克[第9-12周])每天口服一次,持续12周。主要终点是安全性。探索性指标包括胆汁淤积和纤维化标志物以及胆汁酸平衡的药效生物标志物:共招募了 11 名患者(中位年龄:48 岁;55% 为男性)。最常见的治疗突发不良事件(TEAEs)为瘙痒(8/11 [72.7%])、疲劳、头痛、恶心和上呼吸道感染(各为 2/11 [18.2%])。有 7 名患者出现了瘙痒 TEAE(1 例 3 级),被认为与药物有关。一名患者因外周水肿暂时停用了西洛非索。没有出现死亡、严重 TEAE 或导致永久停药的 TEAE。从基线到第 12 周(用药前,空腹),丙氨酸转氨酶的中位变化(四分位数间距)为 -24.8% (-35.7, -7.4),碱性磷酸酶的中位变化(四分位数间距)为 -13.0% (-21.9, -8.6)。碱性磷酸酶为-13.0%(-21.9,-8.6),γ-谷氨酰转移酶为-43.5%(-52.1,-30.8),总胆红素为-12.7%(-25.0,0.0),直接胆红素为-21.2%(-40.0,0.0)。从基线到第12周谷底的最小二乘平均百分比变化(95%置信区间)为:C4-55.3%(-70.8,-31.6),胆酸-60.5%(-81.8,-14.2)。服用西洛非索后,空腹成纤维细胞生长因子19水平短暂升高:12周的递增剂量西洛非索耐受性良好,并能改善PSC引起的代偿性肝硬化患者的胆汁淤积指标(NCT04060147)。
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引用次数: 0
Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers. 基于发病率的上消化道癌症综合死亡率的种族、民族和性别差异。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-01 DOI: 10.14309/ctg.0000000000000745
Alyyah Malick, Jennifer S Ferris, Chin Hur, Julian A Abrams, Ali Soroush

Introduction: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities.

Methods: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines.

Results: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95).

Discussion: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.

导言:目前的上消化道癌症(UGI)筛查策略主要针对癌症特异性风险,重点关注食管腺癌(EAC)。然而,所有上消化道癌症都可以通过上内窥镜检查进行筛查和早期检测。本研究评估并探讨了累积性上消化道癌症基于发病率的死亡率(IBM),旨在确定基于种族或性别的差异:我们利用监测、流行病学和最终结果研究数据分析了 2000 年至 2019 年期间确诊为 EAC、食管鳞状细胞癌 (ESCC)、贲门胃癌 (CGC)、非贲门胃癌 (NCGC) 或结直肠腺癌的患者。年龄调整后的 IBM 以每 10 万人的比率计算,并按性别和种族/人种进行分层。我们还将上消化道癌的IBM与结直肠癌的IBM进行了比较,结直肠癌已制定了全民内窥镜筛查指南:结果:上消化道癌的累积IBM为8.40(95% CI为8.34-8.46)。癌症特异性IBM率最高的是EAC(2.26,95% CI 2.23-2.29),其次是NCGC(2.07,95% CI 2.04-2.10)、CGC(1.60,95% CI 1.57-1.62)、ESCC(1.21,95% CI 1.19-1.23)和其他UGI癌症(1.27,95% CI 1.13-1.40)。UGI 癌症 IBM 在黑人男性(16.43,95% CI 15.97-16.89)、美国印第安人/阿拉斯加原住民男性(15.23,95% CI 13.75-16.82)和西班牙裔男性(13.76,95% CI 13.42-14.11)中发病率最高。这些比率明显高于白人男性(12.81,95% CI 12.68-12.95):结论:UGI 癌症给非白人人口亚群带来了更高的死亡率负担,而这些亚群目前并不是任何系统筛查方法的目标人群。
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引用次数: 0
Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy. 对内镜治疗中顽固性和复发性巴雷特食管的分子分析。
IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-08-01 DOI: 10.14309/ctg.0000000000000751
Aarti Kumar, Marianne Rara, Ming Yu, Kwun Wah Wen, William M Grady, Amitabh Chak, Prasad G Iyer, Anil K Rustgi, Timothy C Wang, Joel H Rubenstein, Yue Liu, Laura Kresty, Maria Westerhoff, Richard S Kwon, Erik Wamsteker, Tom Wang, Lynne Berry, Marcia I Canto, Nicholas J Shaheen, Kenneth K Wang, Julian A Abrams, Matthew D Stachler

Introduction: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.

Methods: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.

Results: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations.

Discussion: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

导言:巴雷特食管(Barrett's esophagus,BE)的早期肿瘤性进展通常采用内窥镜治疗。虽然疗效显著,但有些患者会出现难治性或在明显根除 BE 后复发。本研究的目的是确定接受治疗的 BE 的基因组改变是否与疾病的持续或复发有关:我们对 45 名经内镜治疗成功且未复发的患者的治疗前食管样本、40 名肿瘤持续存在的患者和 21 名肿瘤复发患者的治疗前和治疗后样本进行了 DNA 测序。对各组间的基因组变化进行了比较:结果:各组间的基因组结构相似。久治不愈的患者更有可能在治疗前发生涉及受体酪氨酸激酶通路(p=0.01)、癌基因扩增(p=0.01)和抑癌基因缺失(p=0.02)的改变。在对患者年龄和BE长度进行调整后,这些关联不再显著。超过一半的顽固性疾病(52.5%)或复发性疾病(57.2%)患者在治疗前和治疗后样本中至少有50%的驱动基因突变是相同的:结论:对内镜治疗有反应的患者与疾病持续或复发的患者在治疗前样本的基因组学上相似,这表明治疗反应的基因组因素并不强。虽然预计在顽固性疾病患者的治疗前和治疗后样本中会发现共同的驱动基因突变,但发现同样数量的复发性疾病患者也显示出这种关系,这表明许多复发性疾病是未被发现的最小残留疾病。
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引用次数: 0
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Clinical and Translational Gastroenterology
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