title: Urinary biomarkers in pediatric appendicitis.
abstract: OBJECTIVE
  The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis.
  
  
  METHODS
  A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis.
  
  
  RESULTS
  Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p < 0.001), and was higher in children with gangrenous and perforated appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79-0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value.
  
  
  CONCLUSIONS
  LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance.
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden. martin.salo@med.lu.se.|Department of Pediatric Surgery, Skåne University Hospital, Lasarettsgatan 48, 221 85, Lund, Sweden. martin.salo@med.lu.se.
authors.forename: Martin
authors.identifier: http://orcid.org/0000-0002-6617-6784
authors.initials: M
authors.lastname: Salö
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, 205 02, Lund, Sweden.
authors.forename: Bodil
authors.initials: B
authors.lastname: Roth
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.|Department of Pediatric Surgery, Skåne University Hospital, Lasarettsgatan 48, 221 85, Lund, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Stenström
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.|Department of Pediatric Surgery, Skåne University Hospital, Lasarettsgatan 48, 221 85, Lund, Sweden.
authors.forename: Einar
authors.initials: E
authors.lastname: Arnbjörnsson
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, 205 02, Lund, Sweden.
authors.forename: Bodil
authors.initials: B
authors.lastname: Ohlsson
mesh_terms: D000293:Adolescent; D001064:Appendicitis / Q000175:diagnosis*; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000652:urine; D006801:Humans; D015850:Interleukin-6 / Q000652:urine; D039841:Leukocyte L1 Antigen Complex / Q000652:urine; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013373:Substance P / Q000652:urine
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D015850:Interleukin-6; D039841:Leukocyte L1 Antigen Complex; D013373:Substance P
keywords: Abdominal pain; Appendicitis; Biomarkers; Children