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Plant-based Diets for Inflammatory Bowel Disease: What Is the Evidence? 植物性饮食治疗炎症性肠病:证据是什么?
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izad213
Gordon X H Liu, Andrew S Day

Background: Inflammatory bowel disease is a chronic incurable condition that carries a high morbidity burden for patients. Plant-based diets have emerged as a potentially safe and effective treatment strategy for this condition. However, no attempt has been made to summarize the literature in this field. In this review, we aim to define variants of plant-based diets that have been studied, evaluate their findings, and identify knowledge gaps that warrant further investigation.

Methods: A literature search was conducted on MEDLINE and Embase.

Results: Twenty-three studies with 2304 participants were included in this review. Eleven studies (48%) were case reports and 8 (35%) were single-arm trials. Semivegetarian diets were the most commonly studied plant-based diet (n = 14, 61%). Most studies reported that plant-based diets were safe and effective in managing inflammatory bowel disease. However, significant limitations restrict the quality and interpretability of these findings, including a paucity of controlled data, small sample sizes, and inconsistent reporting of dietary adherence.

Conclusions: Although initial findings appear promising, it remains unclear whether plant-based diets are an effective adjunct or sole therapy for managing inflammatory bowel disease. Future investigators should aim to conduct methodologically rigorous interventional trials with appropriate control data and consistent and meaningful outcome reporting.

背景:炎症性肠病是一种慢性不可治愈的疾病,给患者带来了很高的发病负担。植物性饮食已成为一种潜在的安全有效的治疗策略。然而,目前尚未对这一领域的文献进行总结。在这篇综述中,我们旨在定义已研究的植物性饮食的变体,评估其发现,并确定需要进一步调查的知识差距。方法:在MEDLINE和Embase上进行文献检索。结果:本综述包括23项研究,2304名参与者。11项研究(48%)为病例报告,8项研究(35%)为单臂试验。半素食是最常被研究的植物性饮食(n = 14%、61%)。大多数研究报告称,植物性饮食在治疗炎症性肠病方面是安全有效的。然而,这些发现的质量和可解释性受到了重大限制,包括缺乏受控数据、样本量小以及饮食依从性报告不一致。结论:尽管最初的发现似乎很有希望,但目前尚不清楚植物性饮食是治疗炎症性肠病的有效辅助疗法还是唯一疗法。未来的研究人员应致力于通过适当的对照数据和一致且有意义的结果报告进行方法上严格的介入试验。
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引用次数: 0
Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study. 继发性反应丧失时阿达木单抗药物水平不能预测克罗恩病对剂量强化的反应:一项回顾性的国际多中心研究
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izad248
Robert D Little, Adrian Swaine, Rebecca Reynolds, David J Gibson, Mathilde Barrau, Francesca D'Errico, Rumneek Hampal, Miles P Sparrow, Xavier Roblin, Peter M Irving, Mark G Ward

Background: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification.

Methods: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated.

Results: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively.

Conclusions: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

背景:与英夫利昔单抗相比,阿达木单抗(ADA)在炎症性肠病(IBD)中的暴露-反应关系尚不明确。支持ADA剂量强化后治疗药物监测的证据有限。我们的目的是探讨ADA药物水平与克罗恩病(CD)活性在反应丧失时以及剂量强化后6个月和12个月之间的关系。方法:我们进行了一项回顾性研究,对5年内3个三级中心继发性反应丧失后接受剂量强化每周ADA治疗的成年CD患者进行了研究。使用药物敏感酶联免疫吸附法分析ADA谷水平,在反应丧失和剂量增强后6个月和12个月。临床缓解率、客观缓解率(c反应蛋白)结果:共纳入131例CD患者,中位病程为9年(四分位数范围4-17年)。51%的人在ADA之前有生物暴露,50%的人同时接受了免疫调节剂。在继发性反应丧失时测量的基线药物水平在剂量强化后6个月或12个月对随后的反应者和无反应者没有区别。然而,在6个月和12个月时较高的药物水平和较基线的较高增量与改善的结果相关。在受体工作特征分析中,升级后ADA药物水平>为10.7µg/mL(受体工作特征曲线下面积[AUROC], 0.66;P = 0.013)和>10.9µg/mL (AUROC, 0.67;P = 0.032)分别与6个月和12个月的客观缓解相关。结论:剂量强化后的药物水平与随后的CD缓解相关,而不是继发性反应丧失时的药物水平。
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引用次数: 0
Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics. 英夫利西单抗与联合疗法治疗小儿克罗恩病的药代动力学相似。
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izad307
Ruben J Colman, Stephanie A Vuijk, Ron A A Mathôt, Johan Van Limbergen, Maria M E Jongsma, Marco W J Schreurs, Phillip Minar, Lissy de Ridder, Geert R A M D'Haens

Background: The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).

Methods: This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.

Results: This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.

Conclusions: This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.

背景:同时使用硫唑嘌呤可提高英夫利西单抗(IFX)的疗效和药代动力学(PK)特性,但也会增加不良反应的风险。IFX单药治疗的主动治疗药物监测(pTDM)是改善PK的另一种策略。本研究旨在评估在小儿克罗恩病(CD)中,IFX联合免疫调节剂(combo)是否比IFX-pTDM(单药)具有PK优势:该PK分析包括开始使用IFX组合(TISKids研究)或IFX单药与pTDM(REFINE队列)的小儿克罗恩病患者。在输注第 3、4 和 5 次时评估了 IFX 复方和单方的谷值 (TL) 和英夫利昔单抗抗体。建立了一个群体 PK 模型,以比较联合组和单药组在输注第 4 次和第 5 次时的 IFX PK 结果(清除率 [CL]、TLs 和累积暴露量)。在输注第4次和第5次时评估临床反应和无类固醇临床缓解(SFCR):这项研究包括 128 名儿童 CD 患者(66 名单药组和 62 名复合药组)。输注第 5 次时,单药和复方中位 TL 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) 或中位 CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81) 之间无显著差异。单药患者在输注第 5 次时的 SFCR 率较低(53% [59 例中的 31 例] vs 80% [40 例中的 32 例];P = .01)。在第 4 次和第 5 次输注时,组合患者的临床应答率均明显高于单一患者:本研究表明,在开始接受 IFX 治疗的儿童 CD 患者中,联合疗法和单一疗法之间不存在 PK 差异(TL 和 CL)。
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引用次数: 0
Short-Term Use of Upadacitinib in Combination With Biologic Therapy for Inducing Clinical Remission in Patients With Active Inflammatory Bowel Disease. 短期使用乌达帕替尼联合生物疗法诱导活动性炎症性肠病患者实现临床缓解
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izae105
Jianyi Yin, Yassin El-Najjar, Noelle Cordova, Mary-Joe Touma, Noelle Nguyen, Moheb Boktor, Ezra Burstein, David I Fudman
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引用次数: 0
The Pouch Corner: A Review of Functional Pouch Disorders. Pouch Corner:功能性眼袋疾病综述。
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izae118
Maia Kayal, Edward L Barnes, David M Schwartzberg
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引用次数: 0
Reply: Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer? 回复:预测硫嘌呤类药物在 IBD 中的不良反应:我们是否更近了一步?
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izae130
Tracy Coelho, Guo Cheng, Fernando Vazquez Lopez, James J Ashton, Robert M Beattie, Sarah Ennis
{"title":"Reply: Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer?","authors":"Tracy Coelho, Guo Cheng, Fernando Vazquez Lopez, James J Ashton, Robert M Beattie, Sarah Ennis","doi":"10.1093/ibd/izae130","DOIUrl":"10.1093/ibd/izae130","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Severe Inflammatory Bowel Disease, the Onset of Effectiveness of Biologics and Small Molecules Depends More on the Medication Than on the Diagnosis. 在严重炎症性肠病中,生物制剂和小分子药物的起效更多取决于药物而非诊断。
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izae183
Mohamed Attauabi, Johan Burisch, Ole Haagen Nielsen, Jakob Benedict Seidelin
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引用次数: 0
Lack of ATP2B1 in CD4+ T Cells Causes Colitis. CD4+ T 细胞缺乏 ATP2B1 会导致结肠炎
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izae045
Amarsanaa Javkhlant, Kensuke Toyama, Yasunori Abe, Joshua M Spin, Masaki Mogi

Background: The ATP2B1 gene encodes for a calcium pump, which plays a role in removing Ca2+ from cells and maintaining intracellular Ca2+ homeostasis. Reduction of the intracellular Ca2+ concentration in CD4+ T cells is thought to reduce the severity of colitis, while elevation of Ca2+ in CD4+ T cells induces T cell hyperactivity. Our aim was to clarify the role of ATP2B1 in CD4+ T cells and in inflammatory bowel disease development.

Methods: A murine CD4+ T cell-specific knockout (KO) of ATP2B1 was created using a Cre-loxP system. CD4+ T cells were isolated from thymus, spleen, and blood using fluorescence-activated cell sorting. To quantify messenger RNA levels, quantitative real-time polymerase chain reaction was performed.

Results: Although the percentages of CD4+ T cells in both KO mouse spleen and blood decreased compared with those of the control samples, both T-bet (a T helper 1 [Th1] activity marker) and GATA3 (a Th2 activity marker) expression levels were further increased in KO mouse blood CD4+ T cells (vs control blood). Diarrhea and colonic wall thickening (with mucosal changes, including crypt distortion) were seen in KO mice but not in control mice. Prior to diarrhea onset, the KO mouse colon length was already noted to be shorter, and the KO mouse stool water and lipid content were higher than that of the control mice. Tumor necrosis factor α and gp91 expressions were increased in KO mouse colon.

Conclusions: Lack of ATP2B1 in CD4+ T cells leads to Th1 and Th2 activation, which contributes to colitis via elevation of tumor necrosis factor α and oxidative stress.

背景:ATP2B1 基因编码一种钙泵,它在清除细胞内 Ca2+ 和维持细胞内 Ca2+ 平衡方面发挥作用。降低 CD4+ T 细胞内 Ca2+ 的浓度被认为可减轻结肠炎的严重程度,而 CD4+ T 细胞内 Ca2+ 的升高则会诱发 T 细胞过度活跃。我们的目的是阐明 ATP2B1 在 CD4+ T 细胞和炎症性肠病发展中的作用:方法:利用 Cre-loxP 系统创建了小鼠 CD4+ T 细胞特异性 ATP2B1 基因敲除 (KO)。利用荧光激活细胞分拣技术从胸腺、脾脏和血液中分离出 CD4+ T 细胞。为了量化信使 RNA 水平,进行了定量实时聚合酶链反应:结果:尽管与对照样本相比,KO小鼠脾脏和血液中CD4+ T细胞的百分比都有所下降,但在KO小鼠血液CD4+ T细胞中,T-bet(T辅助细胞1 [Th1]活性标记)和GATA3(Th2活性标记)的表达水平都进一步升高(与对照血液相比)。KO 小鼠出现腹泻和结肠壁增厚(伴有粘膜变化,包括隐窝变形),而对照组小鼠则没有。在腹泻发生之前,KO 小鼠的结肠长度已经缩短,KO 小鼠粪便中的水分和脂质含量也高于对照组小鼠。KO小鼠结肠中肿瘤坏死因子α和gp91的表达增加:结论:CD4+ T细胞中缺乏ATP2B1会导致Th1和Th2活化,从而通过肿瘤坏死因子α和氧化应激的升高导致结肠炎。
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引用次数: 0
All-or-Nothing Behavior and Catastrophic Thinking Predict Fatigue in Inflammatory Bowel Disease: A Prospective Cohort Study. 全有或全无行为和灾难性思维可预测炎症性肠病患者的疲劳:前瞻性队列研究
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izad193
Calum D Moulton, Cheryl Jordan, Bu'Hussain Hayee, Trudie Chalder
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引用次数: 0
Childhood Socioeconomic Characteristics and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study. 儿童社会经济特征与炎症性肠病风险:斯堪的纳维亚出生队列研究。
IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-03 DOI: 10.1093/ibd/izad220
Ida Sigvardsson, Ketil Størdal, Malin Östensson, Annie Guo, Johnny Ludvigsson, Karl Mårild

Background: Ecological observations suggest a negative relationship between childhood socioeconomic status (SES) and inflammatory bowel disease (IBD) risk. Individual-level analyses have been inconsistent and mostly lacked refined assessments of SES. We aimed to comprehensively study the association between early-life SES and later IBD.

Methods: This study included 117 493 participants from the Norwegian Mother, Father and Child cohort and Swedish All Babies in Southeast Sweden cohorts. Participants were followed from birth (1997-2009) through 2021. IBD was identified through national patient registers. Questionnaire and register data were used to define parental educational level, employment, and household income level. Cox regression estimated adjusted hazard ratios (aHRs), accounting for other SES exposures and covariates (eg, parental IBD). Cohort-specific estimates were pooled using a random-effects model.

Results: During 2 024 299 person-years of follow-up, 451 participants were diagnosed with IBD (All Babies in Southeast Sweden cohort, n = 113 and Norwegian Mother, Father and Child cohort, n = 338). Early-life maternal, but not paternal, educational level was associated with later IBD (low vs high educational level; pooled aHR, 1.81; 95% confidence interval [CI], 1.16-2.82; and pooled aHR, 1.20; 95% CI, 0.80-1.80; respectively). Having a nonworking mother or father was not significantly associated with IBD (pooled aHR, 0.69; 95% CI, 0.47-1.02; pooled aHR, 0.79; 95% CI, 0.45-1.37). High vs low household income level yielded a pooled aHR of 1.33 (95% CI, 0.94-1.89). Overall, results were largely consistent across cohorts.

Conclusions: In this prospective Scandinavian cohort study, low maternal educational level was, independent of other SES and covariates, significantly associated with later IBD in her child. Further research is needed to elucidate factors that may mediate this relationship.

背景:生态学观察表明,儿童社会经济地位(SES)与炎症性肠病(IBD)风险之间存在负相关关系。个人层面的分析不一致,大多缺乏对SES的精细评估。我们旨在全面研究早期社会经济地位与晚期IBD之间的关系。方法:本研究包括117493名来自挪威母亲、父亲和儿童队列和瑞典东南部所有婴儿队列的参与者。参与者从出生(1997-2009)到2021年进行了随访。IBD是通过国家患者登记确定的。问卷和登记数据用于确定父母的教育水平、就业和家庭收入水平。Cox回归估计了调整后的风险比(aHR),考虑了其他SES暴露和协变量(如父母IBD)。使用随机效应模型对特定队列的估计进行汇总。结果:在2 024 299人年的随访中,451名参与者被诊断为IBD(瑞典东南部的所有婴儿队列 = 113和挪威母亲、父亲和儿童队列,n = 338)。早期母亲而非父亲的教育水平与后期IBD相关(教育水平低与高;合并aHR,1.81;95%置信区间[CI],1.16-2.82;合并aHR1.20;95%CI0.80-1.80;分别)。母亲或父亲不工作与IBD没有显著相关性(合并aHR,0.69;95%置信区间,0.47-1.02;合并aHR为0.79;95%可信区间,0.45-1.37)。高家庭收入水平与低家庭收入水平的合并aHR分别为1.33(95%置信区间为0.94-1.89)。总体而言,各队列的结果基本一致。结论:在这项斯堪的纳维亚前瞻性队列研究中,母亲受教育水平低,独立于其他社会经济地位和协变量,与她孩子的后期IBD显著相关。需要进一步的研究来阐明可能介导这种关系的因素。
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引用次数: 0
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Inflammatory Bowel Diseases
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