ImportanceAppendicitis 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.ObjectiveTo 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 ParticipantsThe 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.ExposureSA, PA, or nonappendicitis abdominal pain.Main Outcomes and MeasuresBlood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics.ResultsSeventy-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.ConclusionsThis 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.

中文翻译：

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小儿阑尾炎的基因表达谱

重要性阑尾炎是儿科人群中最常见的紧急手术适应症，其严重程度各异，并发症也各不相同。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适当的治疗选择，包括抗生素的选择和手术时机。 目的提供对阑尾炎疾病严重程度差异的机制理解，目的是开发改进的诊断和治疗方法，特别是针对儿科人群。 设计、设置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，对从一组 10 岁以下儿童收集的外周血进行转录组分析2016 年 11 月至 2017 年 4 月期间，在加拿大阿尔伯塔省卡尔加里的阿尔伯塔儿童医院，患有腹痛和疑似阑尾炎的 5 至 17 岁患者，数据分析于 2023 年 8 月报告。本研究中没有患者随访。ExposureSA, PA或非阑尾炎腹痛。主要结果和措施血液转录组学用于建立 SA 和 PA 之间潜在机制差异的假设，以建立机制假设和基于血液的诊断。结果 71 名儿童（平均 [SD] 年龄，11.8 [3.0]年; 使用全血转录组学对 48 名因腹痛和疑似阑尾炎到急诊科就诊的男性（67.6%）进行了调查。PA 中揭示了免疫系统途径的核心作用，包括抑制主要的先天干扰素反应。PA 患者的基因表达变化与免疫反应和炎症途径的下调一致，并且与脓毒症患者（包括最严重的脓毒症内型）的基因表达特征具有相似性。尽管在识别严重阑尾炎的早期生物标志物方面存在挑战，但与 SA 相比，4 个基因特征可以预测 PA，准确度为 85.7%（95% CI，72.8-94.1）。结论这项研究发现 PA 很复杂由免疫反应失调引起。这一发现将为改进严重程度的诊断、早期治疗策略和预防进一步的术后并发症提供信息。