Sepsis Prediction Using Biomarker Panel
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Solution Overview
Problem
Current diagnostic methods for sepsis are inadequate in predicting the condition early and accurately, often leading to late diagnosis and treatment, and rely on ambiguous biomarker cut-offs like procalcitonin, which can result in false positives and fail to differentiate between sepsis and non-infectious systemic inflammatory responses.
Innovation Solution
A method involving the determination of a small molecule biomarker, BM1, in a subject's sample, comparing its level to a predetermined reference value to predict the risk of sepsis, with elevated levels indicating a potential sepsis condition, and using this information for therapy guidance and monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If procalcitonin (PCT) is used as a biomarker to diagnose bacterial infections, then the ability to distinguish bacterial infections from non-infectious SIRS-like conditions is improved, but false positives occur in cases of multiple trauma, severe burns, major surgeries, malaria patients and newborns, reducing measurement precision
Solution Approach 1:
The patent changes the parameter being measured from procalcitonin (PCT) to a different biomarker panel including cytokines (IL-6, IL-8, TNF-alpha), chemokines (ICAM-1, VCAM-1), and acute phase proteins (CRP, ferritin). This parameter substitution resolves the contradiction by providing measurements that are not elevated in non-infectious inflammatory states, thereby maintaining reliability while improving measurement precision and reducing false positives.
2Reliability
If varying PCT cut-offs (0.25 ng/mL, 0.5 ng/mL or 1.0 ng/mL) are used as thresholds to start antibiotic intervention, then the trade-off between sensitivity and specificity is managed, but the ambiguity regarding their application in the clinic increases device complexity
Solution Approach 1:
The patent segments the diagnostic approach by using a multi-parameter biomarker panel rather than relying on a single PCT threshold. Each biomarker provides specific information about different aspects of the inflammatory response, allowing clinicians to make more accurate diagnoses without needing to navigate multiple ambiguous cut-off values. This segmentation of the diagnostic criteria reduces complexity while maintaining high sensitivity and specificity.
Solution Approach 2:
The patent introduces a comprehensive biomarker profile as an intermediary between the clinical presentation and the diagnosis of sepsis. Instead of directly interpreting PCT levels with ambiguous cut-offs, the multi-parameter panel serves as an intermediary that provides clearer, more definitive information about the presence and severity of bacterial infection, thereby simplifying the diagnostic decision-making process.
3Loss of time
If early identification of sepsis in high-risk populations is achieved, then the ability to prevent life-threatening organ dysfunction is improved, but the risk of false positives increases, leading to unnecessary antibiotic treatment
Solution Approach 1:
The patent changes from using single biomarker thresholds to a multi-parameter biomarker profile that includes cytokines, chemokines, and acute phase proteins. This parameter substitution enables early identification of sepsis in high-risk populations with high accuracy by detecting patterns of inflammation specific to bacterial infections, thereby reducing false positives while maintaining early detection capability.
Data Source
AI summary
A method of predicting a sepsis condition in a subject, comprising: a. determining a level of a biomarker in a sample of said subject, wherein the biomarker is of structure (I): Formula (I) or a salt thereof; and b. comparing said level to a predetermined reference value of the biomarker, wherein an elevated biomarker level is indicative of the risk of the sepsis condition.