Appendicitis is the most common non-traumatic surgical presentation in Pediatric
Emergency Departments. The diagnosis of appendicitis is quite challenging in children due to multifactorial barriers resulting in delayed or missed diagnosis, which may either lead to severe complications requiring advanced management and prolonged hospital stay or unnecessary appendectomy. The health care cost related to appendicitis exceeds $680 million per year in the United States alone; in addition, it has the second highest lawsuit rate in pediatric emergency medicine. While there are many studies related to pediatric appendicitis diagnostic strategies including clinical scoring systems, laboratory tests of infection and inflammation and imaging studies, there are gaps in our ability to accurately diagnose appendicitis, and predict disease progression. In the present study we applied multiplexed metabolomics and inflammatory mediator profiling approaches to develop biomarker patterns and explore the potential to aid the diagnosis and prognosis of pediatric appendicitis. At first we aimed to identify appendicitis in pediatric patients using the biomarker profiling approach by comparing them with pediatric control patients showing no signs of inflammation or infection. After obtaining promising results from
the initial pilot study, we applied a similar approach to aid in triaging children presenting with suspected appendicitis in the emergency department. For this purpose comparisons were made between children with appendicitis vs. those without appendicitis but presenting with similar abdominal pain, and between children with perforated vs. nonperforated appendicitis; the obtained separations were statistically significant. We next applied the profiling approach to better understand the disease prognosis by exploring the biochemical profile of the children who developed severe complications after surgical removal of the perforated appendix compared with the ones who did not. In addition to the metabolomics and inflammatory mediator based biomarker profiling, we also applied a novel metallomics approach to explore the potential of biometal profiles to detect appendicitis in children presenting with suspected appendicitis. The results obtained from different phases of the study provide an important first step towards developing a potential aid for improving appendicitis diagnosis and prognosis.