Abstract
Multiplexed profiling approaches including various ‘omics’ platforms are becoming a new standard of biomarker development for disease diagnosis and prognosis. The present study applied an integrated metabolomics and cytokine profiling approach as a potential aid to the identification of pediatric appendicitis. Metabolic analysis using serum (n = 121) and urine (n = 102) samples, and cytokine analysis using plasma (n = 121) samples from children presenting to the Emergency Department with abdominal pain were performed. Comparisons between children with appendicitis vs. non-appendicitis abdominal pain, and with perforated vs. non-perforated appendicitis were made using multivariate statistics. Serum and urine biomarker patterns were statistically significantly different between groups. The combined serum metabolomics and inflammatory mediator model revealed clear separation between appendicitis and non-appendicitis abdominal pain (AUROC: 0.92 ± 0.03) as well as for perforated and non-perforated appendicitis (AUROC: 0.88 ± 0.05). Urine metabolic analysis also demonstrated distinction between the groups appendicitis and non-appendicitis abdominal pain (AUROC: 0.85 ± 0.04), and perforated and non-perforated appendicitis (AUROC: 0.98 ± 0.02). In children presenting to the Emergency Department with abdominal pain, metabolomics and inflammatory mediator profiling are capable of distinguishing children with appendicitis from those without. The approach also differentiates between severities of disease. These results provide an important first step towards a potential aid for improving appendicitis identification.
Highlights
In the present study we aim to evaluate the potential of a novel integrated metabolomics- and inflammatory mediators- based biomarker development approach to aid the diagnosis of acute appendicitis in children
In a previous pilot study we demonstrated the feasibility of this innovative approach for differentiating pediatric appendicitis patients from pediatric control patients with no abdominal pain
The serum and urine biomarker models identified in this study exhibited excellent specificity and AUROC values when distinguishing those with and without appendicitis as well as those with and without perforation, suggesting that the use of biomarker patterns from both biofluids may have some diagnostic potential in ruling in appendicitis
Summary
In the present study we aim to evaluate the potential of a novel integrated metabolomics- and inflammatory mediators- based biomarker development approach to aid the diagnosis of acute appendicitis in children. Metabolites represent the intermediary and final products of the metabolic pathways within an organism; it is possible to achieve unique insight by studying these compounds under any given physiological condition[11]. In a previous pilot study we demonstrated the feasibility of this innovative approach for differentiating pediatric appendicitis patients from pediatric control patients with no abdominal pain (manuscript submitted). The aim of the present study is to apply this approach to accurately distinguish children presenting to the PED with abdominal pain as (a) pathology proven appendicitis from negative pathology and (b) non-perforated appendicitis from perforated appendicitis
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