Diagnostic Characteristics of S100A8/A9 in a Multicenter Study of Patients With Acute Right Lower Quadrant Abdominal Pain

• Published in: Academic emergency medicine 2012-01, Vol.19 (1), p.48-55
• Main Authors: Mills, Angela M., Huckins, David S., Kwok, Heemun, Baumann, Brigitte M., Ruddy, Richard M., Rothman, Richard E., Schrock, Jon W., Lovecchio, Frank, Krief, William I., Hexdall, Aaron, Caspari, Robert, Cohen, Beth, Lewis, Roger J.
• Format: Article
• Language: English
• Subjects: Abdomen; Abdominal Pain - diagnosis; Abdominal Pain - surgery; Adolescent; Adult; Appendectomy; Appendicitis - diagnosis; Appendicitis - surgery; Biomarkers; Biomarkers - blood; Diagnosis, Differential; Double-Blind Method; Emergency medical care; Emergency Service, Hospital; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoassay; Leukocyte L1 Antigen Complex - blood; Linear Models; Male; Mass Screening - methods; Pain; Prospective Studies; ROC Curve; Sensitivity and Specificity
• ISSN: 1069-6563; 1553-2712
• DOI: 10.1111/j.1553-2712.2011.01259.x

ACADEMIC EMERGENCY MEDICINE 2012; 19:48–55 © 2012 by the Society for Academic Emergency Medicine Objectives:  Over the past decade, clinicians have become increasingly reliant on computed tomography (CT) for the evaluation of patients with suspected acute appendicitis. To limit the radiation risks and costs of CT, investigators have searched for biomarkers to aid in diagnostic decision‐making. We evaluated one such biomarker, calprotectin or S100A8/A9, and determined the diagnostic performance characteristics of a developmental biomarker assay in a multicenter investigation of patients presenting with acute right lower quadrant abdominal pain. Methods:  This was a prospective, double‐blinded, single‐arm, multicenter investigation performed in 13 emergency departments (EDs) from August 2009 to April 2010 of patients presenting with acute right lower quadrant abdominal pain. Plasma samples were tested using the investigational S100A8/A9 assay. The primary outcome of acute appendicitis was determined by histopathology for patients undergoing appendectomy or 2‐week telephone follow‐up for patients discharged without surgery. The sensitivity, specificity, negative likelihood ratio (LR–), and positive likelihood ratio (LR+) of the biomarker assay were calculated using the prespecified cutoff value of 14 units. A post hoc stability study was performed to investigate the potential effect of time and courier transport on the measured value of the S100A8/A9 assay test results. Results:  Of 1,052 enrolled patients, 848 met criteria for analysis. The median age was 24.5 years (interquartile range [IQR] = 16–38 years), 57% were female, and 50% were white. There was a 27.5% prevalence of acute appendicitis. The sensitivity and specificity for the investigational S100A8/A9 assay in diagnosing acute appendicitis were estimated to be 96% (95% confidence interval [CI] = 93% to 98%) and 16% (95% CI = 13% to 19%), respectively. The LR− ratio was 0.24 (95% CI = 0.12 to 0.47), and the LR+ was 1.14 (95% CI = 1.10 to 1.19). The post hoc stability study demonstrated that in the samples that were shipped, the estimated time coefficient was 7.6 × 10−3 ± 2.0 × 10−3 log units/hour, representing an average increase of 43% in the measured value over 48 hours; in the samples that were not shipped, the estimated time coefficient was 2.5 × 10−3 ± 0.4 × 10−3 log units/hour, representing a 13% increase on average in the measured value over 48 hours, which was the maximum delay allowed by the