SynthesisFrontiers in molecular neuroscience2026
Mechanism-informed diagnostic accuracy of blood biomarkers for sepsis-associated encephalopathy: a systematic review and Bayesian diagnostic network meta-analysis.
Synthesis in Frontiers in molecular neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Sepsis-associated encephalopathy (SAE) is a common and devastating manifestation of acute brain dysfunction in sepsis, yet mechanism-informed blood biomarkers with clinically interpretable diagnostic accuracy remain uncertain. A growing range of candidates spanning innate immune activation, blood-brain barrier dysfunction, glial response, and neuronal injury has been reported, but their comparative diagnostic performance and biological hierarchy are unclear, partly due to heterogeneity in phenotyping and sampling timing. Main body: We performed a PRISMA/PRISMA-DTA-compliant systematic review and comparative diagnostic evidence synthesis, including a Bayesian diagnostic network meta-analysis, to prioritize blood-based biomarkers for SAE. PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, and WFSD were searched from inception to October 2025. Studies were eligible if SAE case definitions and extractable (or reconstructable) 2 × 2 diagnostic data were available. To characterize heterogeneity, SAE reference standards were tiered (delirium-focused tools vs. broader encephalopathy definitions vs. unclear/mixed), and biomarker sampling was captured using an anchor-based context (anchor event and time-from-anchor). Comparative ranking in the Bayesian diagnostic network meta-analysis was based on the Advantage Index (S-value) derived from posterior distributions. Sixteen studies ( Short conclusion: Blood biomarkers for SAE exhibit a biologically coherent immune-to-neuronal cascade, and their diagnostic performance appears sensitive to phenotyping and anchor-based sampling context. These findings are hypothesis-generating and support prospective head-to-head validation to determine whether mechanism-staged biomarker panels add incremental diagnostic value beyond established clinical predictors under standardized phenotyping and anchor-based sampling protocols. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024531398, CRD42024531398.
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