Biomarker-enhanced Artificial Intelligence-Based Pediatric Sepsis Screening Tool Towards Early Recognition and Personalized Therapeutics

PROJECT SUMMARY The overall objective of this proposed STTR effort is focused on the derivation and validation of a commercialized biomarker-enhanced artificial intelligence (AI)-based pediatric sepsis screening tool (PSCT) that can be incorporated into emergency department (ED) workflows to enhance early recognition and the initiation of timely, aggressive personalized sepsis therapy. The early recognition and timely personalized management of sepsis remain among the greatest challenges in pediatric emergency medicine. The early ED recognition of established or impending critical sepsis is hampered by high prevalence of common febrile infections, poor specificity of discriminating features, capacity of children to compensate until advanced stages of shock, and delays/limited sensitivity of infection confirming microbiological tests. In a recent study, 47% of 7 million cases of sepsis admitted to ICUs had negative cultures. Improved diagnostics are needed to distinguish between sterile inflammation, viral infection, and bacterial infection in patients with suspected sepsis. While useful, commonly used laboratory-based diagnostics such as WBC, CRP, PCT and lactate of limited utility in the management of pediatric sepsis. Novel panels of biomarkers for the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) have shown to be effective in prediction of deterioration and mortality in immunocompromised patients. The performance of PERSEVERE biomarkers in a more undifferentiated population of children with possible sepsis, where the aim is to identify those that are about to deteriorate remains unknown. Septic patients, especially when critically ill, represent a highly heterogenous population. The role of the host- specific dysregulated immune response in the pathophysiology of sepsis, coupled with the diversity of phenotypes, highlights the need for a precision medicine PSCT approach that identifies patients who are most likely to benefit from targeted interventions such as restrictive fluid resuscitation where early vasoactive therapy is initiated rather than repeated fluid boluses. Automated sepsis screening tools in the market today are generally brittle, embedded modules in a large EHR system that exhibit poor specificity and positive predictive value, ignore important evidence available in free text notes, and do not reflect decision-making criteria used by expert ED physicians in initiating sepsis care. We believe there is a significant need for a continuously learning commercial PSCT that leverages widely available EHR interface standards to deliver the combined analytic power of expert knowledge, biomarkers, NLP and machine learning to enhance early pediatric sepsis recognition and detect phenotypes that can predict treatment responses/outcomes towards personalized medicine. .