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儿童炎症性肠病中甲基强的松龙精准给药的病例系列研究:可行性、临床结局及血管炎转录程序的鉴定

Case Series of Precision Delivery of Methylprednisolone in Pediatric Inflammatory Bowel Disease: Feasibility, Clinical Outcomes, and Identification of a Vasculitic Transcriptional Program.

作者信息

Levitte Steven, Yarani Reza, Ganguly Abantika, Martin Lynne, Gubatan John, Nadel Helen R, Franc Benjamin, Gugig Roberto, Syed Ali, Goyal Alka, Park K T, Thakor Avnesh S

机构信息

Interventional Radiology Innovation at Stanford (IRIS), 3155 Porter Drive, Palo Alto, CA 94304, USA.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, Palo Alto, CA 94304, USA.

出版信息

J Clin Med. 2023 Mar 20;12(6):2386. doi: 10.3390/jcm12062386.

Abstract

Systemic steroid exposure, while useful for the treatment of acute flares in inflammatory bowel disease (IBD), is associated with an array of side effects that are particularly significant in children. Technical advancements have enabled locoregional intraarterial steroid delivery directly into specific segments of the gastrointestinal tract, thereby maximizing tissue concentration while limiting systemic exposure. We investigated the feasibility of intraarterial steroid administration into the bowel in a cohort of nine pediatric patients who had IBD. This treatment approach provided symptom relief in all patients, with sustained relief (>2 weeks) in seven out of nine; no serious adverse effects occurred in any patient. In addition, we identified patterns of vascular morphologic changes indicative of a vasculopathy within the mesenteric circulation of inflamed segments of the bowel in pediatric patients with Crohn's disease, which correlated with disease activity. An analysis of publicly available transcriptomic studies identified vasculitis-associated molecular pathways activated in the endothelial cells of patients with active Crohn's disease, suggesting a possible shared transcriptional program between vasculitis and IBD. Intraarterial corticosteroid treatment is safe and has the potential to be widely accepted as a locoregional approach for therapy delivery directly into the bowel; however, this approach still warrants further consideration as a short-term "bridge" between therapy transitions for symptomatic IBD patients with refractory disease, as part of a broader steroid-minimizing treatment strategy.

摘要

全身使用类固醇虽然对治疗炎症性肠病(IBD)的急性发作有用,但会带来一系列副作用,这在儿童中尤为显著。技术进步使局部动脉内类固醇能够直接输送到胃肠道的特定节段,从而在限制全身暴露的同时使组织浓度最大化。我们在一组9名患有IBD的儿科患者中研究了动脉内给予类固醇至肠道的可行性。这种治疗方法使所有患者的症状都得到缓解,9名患者中有7名症状持续缓解(>2周);没有任何患者出现严重不良反应。此外,我们发现了血管形态学变化模式,表明患有克罗恩病的儿科患者肠道炎症节段的肠系膜循环中存在血管病变,这与疾病活动相关。对公开可用的转录组学研究的分析确定了在活动性克罗恩病患者的内皮细胞中激活的血管炎相关分子途径,提示血管炎和IBD之间可能存在共同的转录程序。动脉内皮质类固醇治疗是安全的,有可能作为一种直接输送到肠道的局部治疗方法被广泛接受;然而,作为症状性难治性IBD患者治疗过渡之间的短期“桥梁”,作为更广泛的类固醇最小化治疗策略的一部分,这种方法仍值得进一步考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/10053508/0b89c1c2e24c/jcm-12-02386-g001.jpg

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