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Background Serum interleukin-6 (IL-6) has a moderate diagnostic performance in pediatric acute appendicitis (PAA). The evidence regarding its capacity to discern between complicated and uncomplicated PAA is scarce. Methods We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated PAA. This study included 205 patients divided into three groups: (1) patients who underwent major outpatient surgery (n = 57); (2) patients with non-surgical abdominal pain (NSAP) in whom the diagnosis of PAA was excluded (n = 53), and (3) patients with a confirmed diagnosis of PAA (n = 95). The PAA patients were further classified as uncomplicated or complicated PAA. IL-6 concentration was determined in all patients at diagnosis. Comparative statistical analysis was performed using the Mann-Whitney U test, the Fisher exact test and the Kruskall Wallis test. The area under the receiver operating characteristic curves (AUC) were calculated. Results Median (interquartile range, IQR) serum IL-6 values were 2 pg/mL (2.0-3.4) in group 1, 3.9 pg/mL (2.4-11.9) in group 2, and 23.9 pg/mL (11.1-61.0) in group 3 (P < 0.001). Among the participants in group 3, those with uncomplicated PAA had median (IQR) serum IL-6 values of 17.2 pg/mL (8.5-36.8), and those with complicated PAA had 60.25 pg/mL (27.1-169) serum IL-6 (P < 0.001). At the cut-off point of 19.55 pg/mL, the AUC for the discrimination between patients in group 2 vs. 3 was 0.83 [95% confidence interval (CI) 0.76-0.90], with a sensitivity of 61.3% and a specificity of 86.8. The AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77 (95% CI 0.68-0.86) and the cut-off point was 25.90 pg/mL, with a sensitivity and specificity of 84.6% and 65.6%, respectively. Conclusions Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA. A score including clinical and radiological variables may increase the diagnostic performance of this molecule.

Introduction NGAL has recently been studied as a biomarker in the diagnostic context of pediatric acute appendicitis (PAA), although existing series are scarce and have limited sample sizes. Materials and methods A prospective observational study was designed to validate serum NGAL as a diagnostic tool in PAA. This study included 215 patients, divided into 3 groups: (1) patients undergoing major outpatient surgery (n = 63), (2) patients with non-surgical abdominal pain in whom a diagnosis of PAA was excluded (n = 53) and (3) patients with a confirmed diagnosis of PAA (n = 99). Patients in group 3 were divided into complicated or uncomplicated appendicitis. In 201 patients, a serum sample was obtained at the time of diagnosis and NGAL concentration was determined by ELISA. The Kolmogorov–Smirnov test was used to assess normality. Comparative statistical analyses were performed using the Mann–Whitney U test, the Kruskal-Wallis test and the Fisher’s exact test. To calculate the discriminative ability of the molecule, the area under the receiver-operating characteristic curves (AUC) was calculated. A p value < 0.05 established statistical significance. Results Median (interquartile range) of serum NGAL values were 38.88 (27.15–48.04) ng/mL (group 1), 51.84 (37.33–69.80) ng/mL (group 2) and 65.06 (50.50–86.60) ng/mL (group 3). The AUC (group 2 vs 3) was 0.642 (95% CI 0.542–0.741) (p < 0.001) and the best cutoff point was found to be at 40.97 ng/mL, with a sensitivity of 89% and a specificity of 34.6%. No statistically significant differences in serum NGAL values were found between patients with uncomplicated PAA and those with complicated PAA. Conclusions This prospective validation study with a large sample size confirms that the diagnostic yield of NGAL in the context of PAA is only moderate, and therefore, it should not be used as a unique diagnostic tool. Furthermore, NGAL is not a valid biomarker to discern between uncomplicated and complicated PAA.