Korley, Frederick K.

Abstract Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers—plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase—among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17–39 years, middle-aged: 40–64 years, older: 65–90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84–0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13–15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3–15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3–15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472–3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26–397) or orthopedic trauma controls ( n = 122; median = 13 pg/mL, IQR: 7–20), p < 0.001. Serum S100B levels were likewise higher in CT+ TBI subjects (median = 0.17 μg/L, IQR: 0.09–0.38) than in CT- TBI subjects (median = 0.10 μg/L, IQR: 0.06–0.18), p < 0.001. Receiver operating characteristic curves were generated for prediction of intracranial injury on admission CT scan; area under the curve (AUC) for GFAP was significantly higher than for S100B in the same cohort (GFAP AUC – 0.85, 95% confidence interval [CI] 0.83–0.87; S100B AUC – 0.67, 95% CI 0.64-0.70; p < 0.001). GFAP, measured on a point-of-care platform prototype assay, has high discriminative ability to predict intracranial abnormalities on CT scan in patients with TBI across the full injury spectrum of GCS 3–15 through 24 h post-injury. GFAP substantially outperforms S100B.

AbstractObjectivesWith clinical use of high‐sensitivity troponin I (hsTnI), more frequent troponin elevations will occur. However, the burden and implications of these elevations are not well understood. The authors quantified the prevalence of elevated hsTnI in patients presenting with possible acute coronary syndrome (ACS) who do not have elevated troponin with a current generation assay (cardiac troponin I [cTnI]) and determined the association of these newly detected elevations with a composite of all‐cause mortality and subsequent cardiac hospitalization.MethodsThis was a prospective observational study of 808 subjects evaluated for possible ACS and followed for up to 1 year. Troponin values were measured with hsTnI (Abbott Laboratories) and cTnI (Abbott and Beckman Coulter). Cardiac hospitalization was defined as hospitalization for ACS, revascularization, acute heart failure (AHF), or tachy/brady arrhythmia that occurred after the index emergency department (ED) visit or hospital discharge.ResultsForty subjects (5%) were diagnosed with ACS (26 myocardial infarction and 14 unstable angina). On the initial sample, the prevalence of elevated hsTnI among subjects with nonelevated cTnI was 9.2% using a gender‐neutral cutoff (95% confidence interval [CI] = 7.1% to 11.4%) and 11.1% using a gender‐specific cutoff (95% CI = 8.8% to 13.4%). Adjudicated diagnoses for subjects whose initial samples had elevated hsTnI but nonelevated cTnI (gender‐neutral cutoff) were as follows: three (4.6%) ACS, 15 (23.1%) AHF, three (4.6%) volume overload etiology unclear/noncardiac, three (4.6%) cardiac (non‐ACS), and 41 (63.1%) other. Of the 65 patients whose initial samples had hsTnI but nonelevated cTnI, eight developed cTnI elevation on subsequent serial sampling. After traditional cardiovascular risk factors and renal function were adjusted for, subjects with elevated initial hsTnI but nonelevated cTnI (initial and serial sampling) had a higher risk of all‐cause mortality and subsequent cardiac hospitalization than subjects with both nonelevated hsTnI and nonelevated cTnI (hazard ratio [HR] = 1.91, 95% CI = 1.14 to 3.19).ConclusionsOn the initial sample, 9% to 11% of subjects without cTnI elevation had hsTnI elevation. Although the majority of the patients with these newly detected hsTnI elevations did not have ACS, they had a higher risk for all‐cause mortality and subsequent cardiac hospitalization.