Histone and proADM Biomarkers for Objective Organ Dysfunction Assessment
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Solution Overview
Problem
Current ICU scoring systems for assessing organ dysfunction in critically ill patients are subjective, time-consuming, and prone to misinterpretation, leading to inaccurate prognosis and delayed treatment decisions.
Innovation Solution
A method involving the determination of histone levels (H2B, H4, H2A, and H3) and proadrenomedullin (proADM) in blood samples to objectively predict organ failure, using specific detection reagents and reference data for comparison.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If ICU scoring systems (APACHE II, SAPS II, SOFA) are used to assess organ dysfunction, then comprehensive physiological assessment is achieved, but the assessment becomes subjective and time-consuming
Solution Approach 1:
The patent extracts the essential diagnostic information from complex multi-parameter scoring systems by identifying and measuring specific biomarkers (histones H2B, H4, H2A, H3 and proADM) that directly indicate organ failure. This extraction converts a time-consuming comprehensive assessment into a focused measurement of key indicators, reducing assessment time while maintaining diagnostic accuracy.
Solution Approach 2:
The patent replaces the manual, subjective mechanical process of clinical scoring with an automated biochemical measurement system. By using immunoassays or mass spectrometry to quantify histone and proADM levels, the system eliminates human subjectivity and significantly reduces the time required for assessment compared to manual scoring procedures.
2Reliability
If multiple parameters are assessed in ICU scoring systems, then comprehensive organ dysfunction evaluation is achieved, but the complexity of assessment increases
Solution Approach 1:
The patent extracts the prognostic value from multiple physiological parameters by consolidating them into measurements of two key biomarker groups (histones and proADM). This extraction maintains the reliability of prognosis by focusing on the most informative indicators while eliminating the complexity of evaluating numerous separate parameters.
Solution Approach 2:
The patent merges the information from multiple organ system assessments into a unified biomarker panel. By combining histone measurements (indicating cellular damage) with proADM measurements (indicating cardiovascular and renal stress), the system achieves comprehensive organ dysfunction evaluation through a integrated approach that is simpler than assessing multiple separate parameters.
3Loss of information
If cumulative data from multiple parameters are aggregated for scoring, then overall patient status is assessed, but misinterpretation and lead time bias occur
Solution Approach 1:
The patent performs preliminary action by measuring biomarker levels immediately upon patient admission or at critical decision points, before cumulative data aggregation can introduce bias. By obtaining histone and proADM measurements early and independently, the system provides timely information for treatment decisions without waiting for multiple subsequent assessments to accumulate.
Solution Approach 2:
The patent replaces the cumulative data aggregation process with direct biomarker measurement that provides immediate information about organ failure status. This substitution eliminates lead time bias by measuring the actual physiological state rather than aggregating historical data that may be influenced by prior treatments or spontaneous variability.
Data Source
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AI summary
The present invention relates to the diagnosis, prognosis, risk assessment, risk stratification, monitoring, therapy guidance and/or therapy control of organ dysfunction in a subject. The invention relates to a method that comprises determining a level of at least one histone, particularly 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 organ dysfunction. Further, the invention relates to a method that comprises determining a level of proadrenomedullin (proADM), particularly midregional proadrenomedullin (MR-proADM), in a sample of said subject and wherein said level of proADM is indicative of said organ dysfunction. The invention further relates to kits for carrying out the methods of the invention.