SynthesisJournal of neurology2026
Early-phase fluid diagnostic biomarkers in acute ischemic stroke: a hybrid umbrella review.
Synthesis in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
4 citing papers in PubMed.
- Article
- Neuroinflammation after stroke: initiation, amplification and therapeutic prospects.Journal of translational medicine · 2026Review
- An integrative clinical and bioinformatic analysis identifies MicroRNAs as biomarkers of ischemic stroke severity.Scientific reports · 2026Article
- Diagnostic performance of circulating microRNAs for the early diagnosis of different types of acute cerebrovascular disease.PloS one · 2026Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAcute ischemic stroke (AIS) is a time-critical emergency in which rapid diagnosis within established therapeutic windows is essential to optimize outcomes. Fluid biomarkers offer a promising adjunct to clinical and neuroimaging assessment but their temporal dynamics in the acute phases remain incompletely characterized.
methodsWe performed a hybrid umbrella review of systematic reviews and meta-analyses evaluating fluid biomarkers in AIS versus controls or stroke mimics. Quantitative synthesis of primary studies (random effects meta-analysis of standardized mean differences) was stratified by clinically relevant time windows. Heterogeneity, small-study effects, and excess significance bias were assessed.
resultsWe included 27 publications (18 biochemistry, 1 metabolomic, 10 transcriptomic, 5 cell-free-DNA [cfDNA]). Across all time points, the largest effect sizes were observed for neuron-specific enolase (NSE), ischemia-modified albumin (IMA), D-dimer, S100B, GFAP, and IL-6. Looking at metabolites, studies revealed early accumulation of lactate, succinate, glutamate and lysophosphatidylcholines, alongside depletion of arginine, citrulline, and citrate. A catalog of 220 micro-RNAs (132 upregulated; 108 downregulated) identified robust markers (miR-16-5p, let-7e-5p, miR-107, miR-451a, and miR-126-3p). 46 circulating RNAs and 55 long-non-coding RNAs were consistently dysregulated. Five studies reported elevated nuclear and mitochondrial cfDNA within 6 h.
conclusionsFluid biomarkers exhibit a temporally evolving signature: early coagulopathy (D-dimer), glial activation (GFAP, S100B), and inflammation (IL-6), followed by neuronal necrosis (NSE) and oxidative stress (IMA) within 24 h. Multi-omic integration, including metabolomics, transcriptomics and cfDNA, highlights convergent pathways (PI3K/Akt, NF-κB, immunometabolism) and supports the development of rapid, point-of-care panels. Standardized sampling windows and harmonized assay protocols are essential for clinical translation and prospective validation in prehospital settings.
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Identifiers
41708995What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.