title: Can new inflammatory markers improve the diagnosis of acute appendicitis?
abstract: BACKGROUND
  The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new inflammatory markers for improving the diagnosis of appendicitis.
  
  
  METHODS
  The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients with suspected appendicitis by uni- and multivariable regression models.
  
  
  RESULTS
  Of the new inflammatory variables, SAA, MPO, and MMP9 were the strongest discriminators for all appendicitis (receiver operating characteristics [ROC] 0.71) and SAA was the strongest discriminator for advanced appendicitis (ROC 0.80) compared with defence or rebound tenderness, which were the strongest traditional discriminators for all appendicitis (ROC 0.84) and the WBC count for advanced appendicitis (ROC 0.89). CCL2 was the strongest independent discriminator beside the AIR score variables in a multivariable model. The AIR score had an ROC area of 0.91 and could correctly classify 58.3 % of the patients, with an accuracy of 92.9 %. This was not improved by inclusion of the new inflammatory markers.
  
  
  CONCLUSIONS
  The conventional diagnostic variables for appendicitis, as combined in the AIR score, is an efficient screening instrument for classifying patients as low-, indeterminate-, or high-risk for appendicitis. The addition of the new inflammatory variables did not improve diagnostic performance further.
authors.affiliation: Department of Clinical and Experimental Medicine, Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden, manne.andersson@lj.se.
authors.forename: Manne
authors.initials: M
authors.lastname: Andersson
authors.forename: Marie
authors.initials: M
authors.lastname: Rubér
authors.forename: Christina
authors.initials: C
authors.lastname: Ekerfelt
authors.forename: Hanna Björnsson
authors.initials: HB
authors.lastname: Hallgren
authors.forename: Gunnar
authors.initials: G
authors.lastname: Olaison
authors.forename: Roland E
authors.initials: RE
authors.lastname: Andersson
mesh_terms: D000208:Acute Disease; D000368:Aged; D001064:Appendicitis / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood; D012372:ROC Curve; D000685:Serum Amyloid A Protein / Q000032:analysis
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9
references.citation: Am J Emerg Med. 2012 Sep;30(7):1245-7
references.pmid: 21908136
references.citation: Clin Chem Lab Med. 2005;43(1):49-53
references.pmid: 15653442
references.citation: Ann Surg. 2001 Apr;233(4):455-60
references.pmid: 11303128
references.citation: J Surg Res. 2011 Jun 1;168(1):70-5
references.pmid: 20097375
references.citation: J Invest Surg. 2006 Nov-Dec;19(6):345-52
references.pmid: 17101603
references.citation: Ann Intern Med. 2004 Oct 5;141(7):537-46
references.pmid: 15466771
references.citation: BMC Surg. 2006 Nov 28;6:15
references.pmid: 17132173
references.citation: Am Surg. 2001 Nov;67(11):1017-21
references.pmid: 11730216
references.citation: Br J Surg. 2004 Jan;91(1):28-37
references.pmid: 14716790
references.citation: Surgery. 2010 Mar;147(3):366-72
references.pmid: 19892382
references.citation: Ann Surg. 2008 Mar;247(3):553; author reply 553
references.pmid: 18376205
references.citation: World J Surg. 2008 Aug;32(8):1843-9
references.pmid: 18553045
references.citation: Crit Care Med. 2000 Mar;28(3):736-42
references.pmid: 10752823
references.citation: Ann Surg. 2003 Mar;237(3):408-16
references.pmid: 12616126
references.citation: Surgery. 2011 Jan;149(1):87-93
references.pmid: 20466403
references.citation: J Am Coll Surg. 2005 Dec;201(6):933-9
references.pmid: 16310698
references.citation: J Interferon Cytokine Res. 2009 Jun;29(6):313-26
references.pmid: 19441883
references.citation: Scand J Clin Lab Invest. 2002;62(8):579-84
references.pmid: 12564616
references.citation: Langenbecks Arch Surg. 2000 Nov;385(7):470-81
references.pmid: 11131250
references.citation: Acad Emerg Med. 2011 Jun;18(6):567-74
references.pmid: 21676053
references.citation: Langenbecks Arch Surg. 2010 Nov;395(8):1061-8
references.pmid: 19924436
references.citation: Ann Surg. 2011 Jul;254(1):103-7
references.pmid: 21577090
references.citation: Am Surg. 2002 Dec;68(12):1033-7
references.pmid: 12516803
references.citation: World J Surg. 2008 Feb;32(2):305-9; discussion 310-1
references.pmid: 18043966
references.citation: JAMA. 2001 Oct 10;286(14):1748-53
references.pmid: 11594900
references.citation: Ann Surg. 2007 Jun;245(6):886-92
references.pmid: 17522514
references.citation: Am J Surg. 2011 Apr;201(4):433-7
references.pmid: 21421095