Dhillon Bhavjinder K, Kortbeek Simone, Baghela Arjun, Brindle Mary, Martin Dori-Ann, Jenne Craig N, Vogel Hans J, Lee Amy H Y, Thompson Graham C, Hancock Robert E W
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
JAMA Pediatr. 2024 Apr 1;178(4):391-400. doi: 10.1001/jamapediatrics.2023.6721.
Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery.
To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population.
DESIGN, SETTING, AND PARTICIPANTS: The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study.
SA, PA, or nonappendicitis abdominal pain.
Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics.
Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified.
This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.
阑尾炎是儿科人群紧急手术最常见的指征，其严重程度不一，并发症也各不相同。在就诊时区分单纯性阑尾炎（SA）和穿孔性阑尾炎（PA）可能有助于指导进一步的诊断检查和选择合适的治疗方法，包括抗生素的选择和手术时机。
为深入了解阑尾炎疾病严重程度的差异，以开发改进的诊断方法和治疗手段，特别是针对儿科人群。
设计、地点和参与者：儿科阑尾炎基因表达谱（GEPPA）研究是一项单中心前瞻性探索性诊断研究，对2016年11月至2017年4月在加拿大艾伯塔省卡尔加里市艾伯塔儿童医院就诊的5至17岁腹痛且疑似阑尾炎儿童队列采集的外周血进行转录组分析，数据分析于2023年8月报告。本研究未对患者进行随访。
SA、PA或非阑尾炎性腹痛。
利用血液转录组学来阐明SA和PA潜在机制差异的假说，以建立机制假说和基于血液的诊断方法。
71名因腹痛和疑似阑尾炎就诊于急诊科的儿童（平均[标准差]年龄为11.8[3.0]岁；48名[67.6%]为男性）接受了全血转录组学研究。结果显示免疫系统通路在PA中起核心作用，包括主要先天性干扰素反应的减弱。PA患者的基因表达变化与免疫反应和炎症通路的下调一致，且与脓毒症患者的基因表达特征有相似之处，包括最严重的脓毒症内型。尽管在识别严重阑尾炎早期生物标志物方面存在挑战，但仍鉴定出一个4基因特征，与SA相比，该特征对PA具有预测性，准确率为85.7%（95%CI，72.8 - 94.1）。
本研究发现PA伴有免疫反应失调。这一发现应为改进严重程度诊断、早期管理策略及预防术后进一步并发症提供依据。
