Biomarkers for acute mild brain injury (BAMBI): optimising GFAP/UCH-L1 thresholds to support CT stewardship in a NICE-guided mild-traumatic-brain-injury cohort.

BACKGROUND: NICE head injury guidance prioritises sensitivity but results in high CT utilisation and low diagnostic yield, contributing to Emergency Department (ED) crowding, particularly among older adults after falls. GFAP/UCH-L1 blood biomarkers may support safer CT stewardship, although limited specificity in older adults may reduce clinical impact. OBJECTIVE: To evaluate plasma GFAP/UCH-L1 against CT findings in a Major Trauma Centre ED cohort and assess whether age-stratified interpretation improves clinical utility while preserving rule-out performance. METHODS: Adults with suspected mild traumatic brain injury (mTBI:GCS 13-15) who underwent non-contrast head CT and had plasma GFAP/UCH-L1 measured within 12 hours of injury were included (n=215). Manufacturer thresholds (GFAP 35 pg/mL; UCH-L1 400 pg/mL; OR rule) were compared with an age-stratified algorithm (GFAP 115 pg/mL;UCH-L1 335 pg/mL;OR rule) applying higher published thresholds in participants ≥65 years. RESULTS: Nineteen participants were CT-positive (8.8%). Manufacturer thresholds achieved 100% sensitivity and 29.6% specificity, with 27.0% biomarker-negative. Age-stratified interpretation preserved 100% sensitivity while improving specificity to 55.1% and increasing biomarker-negative results to 50.2%. In participants ≥65 years, specificity improved from 11.2% to 62.2%. CONCLUSION: In this NICE-imaged ED cohort, GFAP/UCH-L1 showed strong CT rule-out performance. Age-stratified interpretation substantially improved specificity, supporting larger prospective validation and pathway evaluation.