Histone and proADM Biomarker Mortality Prediction
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Solution Overview
Problem
Current methods for predicting mortality in critically ill patients are time-consuming, subjective, and reliant on multiple parameters, making them inefficient for rapid risk assessment and prognosis in intensive care units.
Innovation Solution
Determining the levels of at least one histone (H2B, H4, H2A, H3) and proadrenomedullin (proADM) in blood or plasma samples, comparing these levels to reference values, and using them to predict mortality within 7 days.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If severity scores (APACHE, SAPS, SOFA) are used for mortality prediction, then comprehensive assessment is achieved, but determination is time-consuming (≥1 day)
Solution Approach 1:
The patent extracts the essential predictive information from complex severity scores by identifying specific biomarkers (histones and proADM) that can independently predict mortality. Instead of calculating multiple physiological parameters and organ function scores, the method measures only these key biomarkers in blood samples, reducing determination time from ≥1 day to significantly shorter periods while maintaining prediction accuracy.
Solution Approach 2:
The patent changes the measurement parameters from multiple physiological parameters (17 for APACHE, 14 for SAPS, 6 for SOFA) to a focused set of biomarker concentrations (histones H2B, H4, H2A, H3 and proADM). This parameter transformation enables rapid quantification using standard laboratory techniques while preserving the ability to predict mortality outcomes.
2Reliability
If multiple parameters are assessed for severity scoring, then comprehensive prognosis is obtained, but the process requires subjective clinician evaluation and frequent recalibration
Solution Approach 1:
The patent implements a self-service system where biomarker levels (histones and proADM) automatically provide mortality risk information without requiring clinician interpretation. The biomarkers themselves serve as the assessment tool, eliminating subjective evaluation and the need for frequent recalibration of scoring systems. The method simply measures and compares biomarker concentrations to established thresholds.
Solution Approach 2:
The patent creates a universal assessment tool that can be applied to all critically ill patients regardless of their specific condition. The same biomarkers (histones and proADM) serve multiple functions: indicating mortality risk, assessing disease severity, and monitoring patient progression, replacing the need for multiple different scoring systems.
3Measurement precision
If traditional severity scores are used, then multiple physiological parameters must be individually determined, but this increases device complexity and resource requirements
Solution Approach 1:
The patent extracts the critical predictive signal from complex physiological data by focusing on specific biomarkers released during cellular stress and death. Instead of measuring and integrating 17+ physiological parameters, the method isolates and measures only histone and proADM concentrations, which directly reflect cellular injury and predict mortality with high accuracy.
Solution Approach 2:
The patent merges multiple sources of mortality risk information into a single integrated biomarker assessment. Histones and proADM collectively capture information about cellular injury, inflammation, and organ dysfunction that would otherwise require multiple separate physiological measurements, simplifying the assessment system while maintaining comprehensive evaluation.
Data Source
AI summary
The present invention relates to diagnosis, prognosis, risk assessment, and/or risk stratification of an adverse event, particularly mortality, of a subject. The invention relates to a method that comprises determining a level of at least one histone, particularly histone H2B, H4, H2A and/or H3, in a sample of said subject, and wherein said level of at least one histone is indicative of said adverse event of said subject; and/or determining a level of proadrenomedullin (proADM) in a sample of said subject, and wherein said level of proADM is indicative of said adverse event of said subject. The invention further relates to kits for carrying out the methods of the invention.