Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) are increasingly used to rule out intracranial injury in patients with mild traumatic brain injury (mTBI); however, their circulating levels may be influenced by demographic factors. This study evaluated the effects of age and sex on GFAP and UCH-L1 concentrations and assessed whether adjusted cut-off values improve the diagnostic performance of head computed tomography (CT). In this retrospective observational study, 820 consecutive patients with mTBI presenting within 12 h of injury underwent CT imaging and biomarker measurements using a chemiluminescent immunoassay. CT-positive findings were identified in 11.8% of patients (n = 97). Biomarker levels were analyzed according to age and sex, and optimized cut-off values were derived and evaluated. GFAP concentrations varied significantly according to both age and sex, whereas UCH-L1 demonstrated mainly sex-related differences. The use of manufacturer-recommended fixed cut-offs resulted in markedly reduced specificity in older patients, particularly for GFAP. Age-adjusted cut-offs improved specificity while maintaining high negative predictive values across all age groups, although this was accompanied by a reduction in sensitivity and an increase in false-negative results. For the combined GFAP/UCH-L1 assay, sensitivity ranged from 90.9% to 100%, specificity from 42.6% to 57.0%, and negative predictive values from 97.7% to 100%. Age-adjusted cut-off values for GFAP ranged from 82.1 to 112.2 pg/mL across adult age groups, whereas age-adjusted UCH-L1 cut-off values ranged from 469.6 to 1072.5 pg/mL. In conclusion, age and sex significantly influence GFAP and UCH-L1 concentrations in mTBI patients. Demographic-adjusted cut-offs improve diagnostic calibration and reduce false-positive classifications while maintaining high negative predictive values despite a moderate reduction in sensitivity.
Espinar-Barranco et al. (Fri,) studied this question.