Biomarkers to estimate the probability of complicated appendicitis.

BACKGROUND: The conventional paradigm that all children with appendicitis require an appendectomy is being challenged by the idea that some patients may be successfully managed non-operatively. The study aimed to determine if matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are candidate biomarkers for estimating the probability of complicated appendicitis in pediatric patients.

METHODS: The study was a single-institution, prospective cohort study. MMP and TIMP serum protein concentrations were measured in patients with suspected appendicitis. Three hundred and thirty-one patients were enrolled with appendicitis. Classification and Regression Tree (CART) analysis was used to determine the combination of candidate biomarkers that best predicted complicated appendicitis.

RESULTS: The CART-generated decision tree for the derivation cohort included WBC count, MMP-8, MMP-9, MMP-12, TIMP-2, and TIMP-4 and had the following test characteristics for estimating the probability of complicated appendicitis (95% CI): AUC 0.86 (0.81-0.90); sensitivity 91% (83-96); specificity 61% (53-68); positive predictive value 58% (50-66); negative predictive value 92% (84-96); positive likelihood ratio (LR) 2.3 (1.9-2.8); and negative LR 0.15 (0.08-0.3).

CONCLUSIONS: MMPs and TIMPs have the potential to serve as biomarkers to estimate the probability of complicated appendicitis in pediatric patients. The multi-biomarker-based decision tree has test characteristics suggesting clinical utility for decision making.

LEVEL OF EVIDENCE: Level II: Study of Diagnostic Test.