A Novel Biomarker-Based Nomogram for the Differential Diagnosis of Advanced and Early Appendicitis in Pediatric Patients

Abstract

Objective: Appendicitis is highly prevalent in the pediatric population worldwide. However, atypical clinical manifestations of pediatric appendicitis (PA) and the uncooperativeness during physical and imaging examinations have posed challenges for the disease diagnosis. This study was to identity the risk factors differing between early and advanced PA, and to develop a novel nomogram for differential diagnosis of advanced and early PA. Study design: We retrospectively analyzed data from 669 PA patients with 411 subjects in modeling group and 258 in validation group. The characteristics, and 24 serum biomarker results were subjected to univariate and multivariate logistic regression analysis. A nomogram for the differential diagnosis of advanced and early PA was constructed and validated. Results: Fibrin degradation product (FDP), C-reactive protein (CRP), and Na differed significantly between the advanced and early PA (P < 0.05). The nomogram was generated based on these differences. The area under the receiver operating characteristic (ROC) curve (AUC) value for the nomogram was 0.8602, which was greater than that of a single serum marker. In addition, the nomogram showed better discriminative ability with higher sensitivity, specificity, and positive predictive value (PPV) at the optimal cut-off points compared to the ability of the serum marker alone. Notably, validation of the nomogram indicated high stability and reproducibility, suggesting good clinical applicability of the nomogram. Conclusions: This study established a novel biomarker-based model to differentiate advanced from early PA. The performance of the nomogram is superior to the serum marker alone, and thus may hold promise in clinical application. Funding Statement: This study received financial support from Shanghai Hospital Development Center (SHDC12014106), Shanghai Key Disciplines (no.2017ZZ02022), the National Natural Science Foundation of China (no. 81370472, no. 81770519, no. 81771633, no. 81401243and no. 81500394), Shanghai Rising-Star Program (A type) (no. 15QA1400800), the Science Foundation of Shanghai Excellent Youth Scholars (no. 2017YQ042), and the Science Foundation of Shanghai (no. 16411952200, no. 16140902300 and no. 17411960600). Declaration of Interests: Yijie Zheng is an employee of WuxiDiagnosis. The other authors declare that they have no conflict of interest. Ethics Approval Statement: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Children’s Hospital of Fudan University (Shanghai, China). The need for informed consent was waived due to the retrospective nature of this study. The study was conducted in compliance with the Declaration of Helsinki.