title: A novel biomarker panel to rule out acute appendicitis in pediatric patients with abdominal pain.
abstract: OBJECTIVE
  To identify a biomarker panel with sufficient sensitivity and negative predictive value to identify children with abdominal pain at low risk for acute appendicitis in order to avoid unnecessary imaging.
  
  
  METHODS
  We prospectively enrolled 503 subjects aged two to 20 years with <72 hours of abdominal pain consistent with appendicitis. Blood samples from each patient were analyzed for CBC, differential, and 5 candidate proteins. Biomarker values were evaluated using principal component, recursive partitioning and logistic regression to select the combination that best discriminated between those subjects with and without disease.
  
  
  RESULTS
  The prevalence of acute appendicitis was 28.6%. A mathematical combination of three inflammation-related markers in a panel comprised of white blood cell count (WBC), C-reactive protein (CRP), and myeloid-related protein 8/14 complex (MRP 8/14) provided the best discrimination. This panel exhibited a sensitivity of 96.5% (95% CI, 92-99%), a negative predictive value of 96.9% (95% CI, 93-99%), a negative likelihood ratio of 0.08 (95% CI, 0.03- 0.19), and a specificity of 43.2% (95% CI, 38-48%) for acute appendicitis. Sixty of 185 CT scans (32.4%) were done for patients with negative biomarker panel results which, if deferred, would have reduced CT utilization at initial presentation by one third at the cost of missing five of 144 (3.5%) patients with appendicitis.
  
  
  CONCLUSIONS
  This panel may be useful in identifying pediatric patients with signs and symptoms suggestive of acute appendicitis who are at low risk and can be followed clinically, potentially sparing them exposure to the ionizing radiation of CT.
authors.affiliation: Division of Emergency Medicine, Newton-Wellesley Hospital, Newton, MA, USA. Electronic address: dhuckins@partners.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Huckins
authors.forename: Harold K
authors.initials: HK
authors.lastname: Simon
authors.forename: Karen
authors.initials: K
authors.lastname: Copeland
authors.forename: David M
authors.initials: DM
authors.lastname: Spiro
authors.forename: Joseph
authors.initials: J
authors.lastname: Gogain
authors.forename: Michael
authors.initials: M
authors.lastname: Wandell
mesh_terms: D015746:Abdominal Pain / Q000097:blood / Q000175:diagnosis*; D000293:Adolescent; D001064:Appendicitis / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000032:analysis; D040501:Calgranulin A / Q000097:blood; D040502:Calgranulin B / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D002097:C-Reactive Protein