Evidence map›Paper›PMID 42048067›Full record

ArticleAcademic emergency medicine : official journal of the Society for Academic Emergency Medicine2026

Age-Specific Clinical Biomarker Ranges in Acute Head Injury, Non-TBI Trauma, and Healthy Control Subjects in the Emergency Department.

Katherine D Mayes, Timothy E Van Meter, Nazanin Mirshahi, Sally Boyd, Danielle Sandsmark, Katya Rascovsky, Ramon Diaz-Arrastia, Justin Weppner, W Frank Peacock, Damon R Kuehl and 1 more

Abstract read
In one paragraph

Article in Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Age-Specific Clinical Biomarker Ranges in Acute Head Injury, Non-TBI Trauma, and Healthy Control Subjects in the Emergency Department.Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Katherine D MayesDepartment of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.ORCID 0000-0002-9069-2439
Timothy E Van MeterBRAINBox Solutions, Inc, Richmond, Virginia, USA.
Nazanin MirshahiBRAINBox Solutions, Inc, Richmond, Virginia, USA.
Sally BoydBRAINBox Solutions, Inc, Richmond, Virginia, USA.
Danielle SandsmarkDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Katya RascovskyDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Ramon Diaz-ArrastiaDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Justin WeppnerDepartment of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.
W Frank PeacockDepartment of Emergency Medicine, Baylor College of Medicine, Houston, Texas, USA.
Damon R KuehlDepartment of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.
HeadSMART II Investigators

Funding

NINDS NIH HHS 1R44NS172072-A1
6 · The paper itself

Abstract

objectivesBlood-based biomarkers for traumatic brain injury (TBI) are increasingly integrated into diagnostic algorithms, but their interpretation may be confounded by age-related neurological changes. This study quantified the relative effects of age and TBI on biomarker concentrations to determine whether age-related variation approaches or exceeds that associated with injury.

methodsSerum biomarkers were analyzed from 762 adults enrolled in the HeadSMART II and HeadSMART Geriatric studies, including healthy controls (n = 88), non-head trauma controls (n = 99), and mild TBI patients (GCS 13-15, n = 575). Participants were categorized by age (18-40, 41-64, 65-74, ≥ 75 years). Six TBI-relevant biomarkers (glial fibrillary acidic protein [GFAP], brain-derived neurotrophic factor [BDNF], neurogranin [NRGN], α-synuclein [SNCA], suppression of tumorigenicity 2 [ST2], and von Willebrand factor [vWF]) were quantified using validated immunoassays (BRAINBox Solutions). Biomarker levels were compared using two-way ANOVA, and the relative effects of age and injury were estimated using Cohen's f.

resultsAge significantly influenced several biomarkers. GFAP showed strong age-related increases, with significant elevations across age strata (p < 0.001), exceeding the effect of head injury alone. vWF also increased significantly with age (p < 0.001), while ST2 did not show a main effect of age (p = 0.404), although age interacted with group (p < 0.001). SNCA demonstrated modest age effects (p = 0.001), particularly in older trauma and TBI participants. NRGN showed no significant age-related changes (p = 0.454), and BDNF exhibited age effects within interaction terms (p < 0.001). Overall, age-associated effect sizes for GFAP and vWF were comparable to, or greater than, those of head injury.

conclusionsAge exerts substantial influence on circulating biomarker concentrations, particularly GFAP and vWF, often rivaling or exceeding TBI-related changes. Diagnostic algorithms that fail to adjust for age may risk misclassification, especially among older adults, underscoring the need for age-normalized biomarker interpretation.

Indexed as

BiomarkersBrain Injuries, TraumaticCraniocerebral TraumaAdolescentAdultAgedAge FactorsBrain-Derived Neurotrophic FactorCase-Control StudiesEmergency Service, HospitalFemaleGlial Fibrillary Acidic ProteinHumansMaleMiddle AgedReference ValuesBiomarkersBrain-Derived Neurotrophic FactorGlial Fibrillary Acidic Proteinvon Willebrand Factor

Identifiers

PMID42048067
PMCPMC13123748

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Registered trials

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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 OpenQuestion graph.