PERSEVEREnce Biomarker Model for Pediatric Septic Shock MODS Risk
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Solution Overview
Problem
Current standard care for septic shock in children is inadequate for patients with multiple organ dysfunction syndrome (MODS), and there is a lack of reliable tools to identify those who will benefit from targeted therapies, leading to challenges in patient heterogeneity and inefficient allocation of critical care resources.
Innovation Solution
A biomarker-based risk model, PERSEVEREnce, integrates endothelial dysfunction markers and the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to predict the risk of death or persistent organ dysfunctions in pediatric septic shock by analyzing serum biomarkers such as IL-8, HSP70, ICAM-1, Angpt-2/Angpt-1, and Thrombomodulin, allowing for prognostic enrichment in clinical trials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard care (antibiotics and intensive care) is provided to all pediatric septic shock patients, then most patients receive appropriate treatment, but patients with MODS do not receive timely targeted therapeutics due to inability to identify them early
Solution Approach 1:
The patent applies preliminary action by developing and validating the PERSEVEREnce biomarker model to identify MODS-risk patients before they deteriorate. The model uses baseline biomarker levels (IL-8, HSP70, ICAM-1, Thrombomodulin, Angpt-2/Angpt-1, Angpt-2/Tie-2) measured at septic shock onset to predict persistent MODS and mortality risk, enabling clinicians to proactively initiate targeted therapies in high-risk patients before organ dysfunction progresses, thereby resolving the time loss issue while maintaining appropriate standard care for all patients
2Loss of time
If biomarker analysis is performed to identify high-risk patients, then targeted therapy can be initiated timely, but the complexity of analyzing multiple biomarkers increases
Solution Approach 1:
The patent applies universality by creating a multi-functional biomarker panel where six different biomarkers (IL-8, HSP70, ICAM-1, Thrombomodulin, Angpt-2/Angpt-1, Angpt-2/Tie-2) work together to simultaneously assess multiple aspects of disease pathophysiology including inflammation, endothelial dysfunction, and coagulation activation. This unified approach allows a single comprehensive test to predict both persistent MODS and mortality risk, reducing the need for multiple separate assessments and simplifying clinical decision-making despite the multiple markers involved
Solution Approach 2:
The patent applies the intermediary principle by using the PERSEVEREnce biomarker model as a mediator between raw biomarker measurements and clinical decision-making. The model translates complex multi-biomarker data into a simplified risk classification (high-risk vs. not high-risk) that directly guides therapeutic decisions, thereby reducing the complexity burden on clinicians while maintaining the diagnostic power of multiple biomarkers
3Ease of operation
If current standard care is used for all patients, then resource allocation is simplified, but patients with MODS receive insufficient targeted treatment leading to poor outcomes
Solution Approach 1:
The patent applies local quality by differentiating care strategies based on patient-specific biomarker profiles. High-risk patients identified by the PERSEVEREnce model receive intensified targeted therapies including immunomodulation, anticoagulation, and aggressive organ support, while low-risk patients receive standard care. This localized approach to treatment intensity based on individual risk assessment improves outcomes for MODS patients without unnecessarily complicating care for low-risk patients, thereby maintaining operational simplicity while enhancing reliability for those who need it most
Data Source
AI summary
Methods and compositions disclosed herein generally relate to methods of identifying, validating, and measuring clinically relevant, quantifiable biomarkers of diagnostic and therapeutic responses for blood, vascular, cardiac, and respiratory tract dysfunction, particularly as those responses relate to septic shock in pediatric patients. Certain aspects of the disclosure relate to identifying one or more biomarkers associated with septic shock in pediatric patients in combination with one or more endothelial-derived biomarkers, receiving a sample from a pediatric patient having at least one indication of septic shock, then quantifying from the sample an amount of said biomarkers, wherein the level of said biomarker correlates with a predicted outcome.