Diagnostic Accuracy of GFAP and UCH-L1 for Acute Intracranial Trauma in a Predominantly Blast-Exposed Cohort of Combat Casualties
- 1Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat Gan, Israel
Abstract
ImportanceThere is an urgent need for objective blood tests to guide triage of suspected traumatic brain injury (TBI) in far-forward combat environments, where blast exposure is common and neuroimaging is frequently unavailable. Blood-based glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) are transforming triage of suspected TBI due to their 99% negative predictive value for ruling out acute intracranial trauma in civilian impact TBI. However, accuracy in military blast-dominant TBI is unclear.
ObjectiveTo determine accuracy of day-of-injury serum or plasma GFAP and UCH-L1 levels for ruling-out acute intracranial trauma in a sequential real-world cohort of combat casualties.
DesignRetrospective cohort study leveraging existing data from a clinical laboratory validation protocol that processed and stored leftover day-of-injury clinical samples from evacuated combat casualties between January 1, 2024, and February 6, 2025 for subsequent analysis for GFAP and UCH-L1 using FDA-cleared assay thresholds.
SettingSingle-center, tertiary referral trauma center.
ParticipantsDay-of-injury plasma or serum GFAP and UCH-L1 levels were available for 137 combat casualties. The cohort was 99.3% male with a median age of 21.8 years; 75.2% sustained blast-related injuries. Most (92.7%) had blood collected within 6 hours of injury.
ExposureSerum or plasma GFAP and UCH-L1 measured with Abbott Alinity-i or i-STAT TBI assays. Elevation was defined as GFAP [≥]35 pg/mL or UCH-L1 [≥]400 pg/mL on Alinity-i, and GFAP [≥]30 pg/mL or UCH-L1 [≥]360 pg/mL on i-STAT.
Main Outcomes and MeasuresAccuracy of biomarker elevation for ruling-out intracranial trauma on head CT, including sensitivity, specificity, and negative predictive value (NPV).
ResultsAmong 137 casualties, 83 (60.6%) were biomarker-elevated. Sixteen participants (11.7%) had CT-confirmed intracranial trauma, of whom 15 were biomarker-elevated, yielding 93.8% sensitivity and 98.2% NPV, and 43.8% specificity. Twenty-three participants (16.8%) had intracranial trauma and/or head/face/c-spine fracture; 21 were biomarker-elevated, corresponding to 91.3% sensitivity, 96.3% NPV, and 45.6% specificity.
Conclusions and RelevanceIn this real-world cohort of blast-dominant combat casualties, day-of-injury GFAP and UCH-L1 demonstrated high NPV and sensitivity for intracranial trauma, with modest specificity. These findings support the utility of GFAP and UCH-L1 to aid early triage and decision-making in blast-dominant military TBI.
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BibTeX
@misc{sheldon2026diagnostic,
title = {{Diagnostic Accuracy of GFAP and UCH-L1 for Acute Intracranial Trauma in a Predominantly Blast-Exposed Cohort of Combat Casualties}},
author = {A. Sheldon and Y. Rosen Lang and A. Perry and A. Peled and R. Hershkovitch and G. Rosenthal and K. Asraf and C. Moskovitz and R. Doolman and D. Dominissini and Y. Klein and A. Ironi and A. Epstein and G. Manley and S. Shapira and R. C. Gardner},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.26364753},
url = {https://www.medrxiv.org/content/10.64898/2026.10.06.26364753v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Diagnostic Accuracy of GFAP and UCH-L1 for Acute Intracranial Trauma in a Predominantly Blast-Exposed Cohort of Combat Casualties
AU - A. Sheldon
AU - Y. Rosen Lang
AU - A. Perry
AU - A. Peled
AU - R. Hershkovitch
AU - G. Rosenthal
AU - K. Asraf
AU - C. Moskovitz
AU - R. Doolman
AU - D. Dominissini
AU - Y. Klein
AU - A. Ironi
AU - A. Epstein
AU - G. Manley
AU - S. Shapira
AU - R. C. Gardner
PY - 2026
DA - 2026/10/06
PB - medRxiv
DO - 10.64898/2026.10.06.26364753
UR - https://www.medrxiv.org/content/10.64898/2026.10.06.26364753v1
AB - ImportanceThere is an urgent need for objective blood tests to guide triage of suspected traumatic brain injury (TBI) in far-forward combat environments, where blast exposure is common and neuroimaging is frequently unavailable. Blood-based glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) are transforming triage of suspected TBI due to their 99% negative predictive value for ruling out acute intracranial trauma in civilian impact TBI. However, accuracy in military blast-dominant TBI is unclear. ObjectiveTo determine accuracy of day-of-injury serum or plasma GFAP and UCH-L1 levels for ruling-out acute intracranial trauma in a sequential real-world cohort of combat casualties. DesignRetrospective cohort study leveraging existing data from a clinical laboratory validation protocol that processed and stored leftover day-of-injury clinical samples from evacuated combat casualties between January 1, 2024, and February 6, 2025 for subsequent analysis for GFAP and UCH-L1 using FDA-cleared assay thresholds. SettingSingle-center, tertiary referral trauma center. ParticipantsDay-of-injury plasma or serum GFAP and UCH-L1 levels were available for 137 combat casualties. The cohort was 99.3% male with a median age of 21.8 years; 75.2% sustained blast-related injuries. Most (92.7%) had blood collected within 6 hours of injury. ExposureSerum or plasma GFAP and UCH-L1 measured with Abbott Alinity-i or i-STAT TBI assays. Elevation was defined as GFAP [≥]35 pg/mL or UCH-L1 [≥]400 pg/mL on Alinity-i, and GFAP [≥]30 pg/mL or UCH-L1 [≥]360 pg/mL on i-STAT. Main Outcomes and MeasuresAccuracy of biomarker elevation for ruling-out intracranial trauma on head CT, including sensitivity, specificity, and negative predictive value (NPV). ResultsAmong 137 casualties, 83 (60.6%) were biomarker-elevated. Sixteen participants (11.7%) had CT-confirmed intracranial trauma, of whom 15 were biomarker-elevated, yielding 93.8% sensitivity and 98.2% NPV, and 43.8% specificity. Twenty-three participants (16.8%) had intracranial trauma and/or head/face/c-spine fracture; 21 were biomarker-elevated, corresponding to 91.3% sensitivity, 96.3% NPV, and 45.6% specificity. Conclusions and RelevanceIn this real-world cohort of blast-dominant combat casualties, day-of-injury GFAP and UCH-L1 demonstrated high NPV and sensitivity for intracranial trauma, with modest specificity. These findings support the utility of GFAP and UCH-L1 to aid early triage and decision-making in blast-dominant military TBI.
ER -