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定义英夫利昔单抗及英夫利昔单抗 - 硫唑嘌呤联合疗法治疗新诊断的小儿小肠克罗恩病的超声纵向自然病程。

Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy.

作者信息

Dillman Jonathan R, Dehkordy Soudabeh Fazeli, Smith Ethan A, DiPietro Michael A, Sanchez Ramon, DeMatos-Maillard Vera, Adler Jeremy, Zhang Bin, Trout Andrew T

机构信息

Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., ML5031, Cincinnati, OH, 45229-3039, USA.

Department of Radiology, Section of Pediatric Radiology, C. S. Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI, USA.

出版信息

Pediatr Radiol. 2017 Jul;47(8):924-934. doi: 10.1007/s00247-017-3848-3. Epub 2017 Apr 18.

Abstract

BACKGROUND

Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-α) therapy.

OBJECTIVE

To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab.

MATERIALS AND METHODS

We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month, 3 months and 6 months after treatment initiation; these patients also had laboratory testing at baseline, 1 month and 6 months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships.

RESULTS

Mean subject age was 15.3±2.2 years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0±5.4 vs. 9.1±5.3 cm, P=0.02), maximum bowel wall thickness (5.6±1.8 vs. 4.7±1.7 mm, P=0.02), bowel wall color Doppler signal (1.7±0.9 vs. 1.2±0.8, P=0.002) and mesenteric color Doppler signal (1.1±0.9 vs. 0.6±0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1 month (P-values<0.0001). There was strong correlation between bowel wall color Doppler signal and fecal calprotectin (ρ=0.710; P<0.0001). Linear mixed models confirmed that maximum bowel wall thickness (P=0.04), length of disease involvement (P=0.0002) and bowel wall color Doppler signal (P<0.0001) change over time in response to infliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score.

CONCLUSION

The ultrasound appearance of the bowel changes as early as 2 weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.

摘要

背景

对于新诊断的小肠克罗恩病的儿科或成年患者,接受抗肿瘤坏死因子-α(抗TNF-α)治疗时,肠道和肠系膜成像表现随时间的变化了解甚少。

目的

明确新诊断的小儿小肠克罗恩病并接受英夫利昔单抗治疗的儿童,其肠道超声检查结果随时间如何变化以及与实验室炎症标志物的相关性。

材料与方法

我们纳入了28例因新诊断的回肠克罗恩病接受英夫利昔单抗治疗的儿科患者,这些患者在药物治疗前以及治疗开始后约2周、1个月、3个月和6个月接受了肠道超声检查;这些患者在基线、1个月和6个月时也进行了实验室检测。我们使用线性混合模型比较各次检查的平均结果,并评估超声测量值是否随时间变化。我们使用Spearman等级相关性评估双变量关系。

结果

受试者平均年龄为15.3±2.2岁;11名受试者为女孩(39%)。与基线相比,在英夫利昔单抗治疗开始后约2周时,我们观察到疾病累及的平均长度(12.0±5.4 vs. 9.1±5.3 cm,P = 0.02)、最大肠壁厚度(5.6±1.8 vs. 4.7±1.7 mm,P = 0.02)、肠壁彩色多普勒信号(1.7±0.9 vs. 1.2±0.8,P = 0.002)和肠系膜彩色多普勒信号(1.1±0.9 vs. 0.6±0.6,P = 0.005)均下降。所有实验室炎症标志物在1个月时均下降(P值<0.0001)。肠壁彩色多普勒信号与粪便钙卫蛋白之间存在强相关性(ρ = 0.710;P < 0.0001)。线性混合模型证实,在调整年龄、性别、硫唑嘌呤治疗、扫描放射科医生和基线小儿克罗恩病活动指数短评分数后,最大肠壁厚度(P = 0.04)、疾病累及长度(P = 0.0002)和肠壁彩色多普勒信号(P < 0.0001)随时间因英夫利昔单抗治疗而发生变化。

结论

英夫利昔单抗治疗开始后仅2周,肠道超声表现就发生变化。肠壁彩色多普勒信号与粪便钙卫蛋白之间存在强相关性。

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