Biomarkers to estimate the probability of complicated appendicitis

Abstract 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.