{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:01:12Z","timestamp":1773723672397,"version":"3.50.1"},"reference-count":64,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Pediatr"],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:sec id=\"ab-poi230099-4\"><jats:title>Importance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-5\"><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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\u2019s Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-7\"><jats:title>Exposure<\/jats:title><jats:p>SA, PA, or nonappendicitis abdominal pain.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-9\"><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-poi230099-10\"><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapediatrics.2023.6721","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T16:32:14Z","timestamp":1708360334000},"page":"391","source":"Crossref","is-referenced-by-count":9,"title":["Gene Expression Profiling in Pediatric Appendicitis"],"prefix":"10.1001","volume":"178","author":[{"given":"Bhavjinder K.","family":"Dhillon","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Kortbeek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun","family":"Baghela","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Brindle","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dori-Ann","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig N.","family":"Jenne","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans J.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy H. 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