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Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study.

ABSTRACT: BACKGROUND:Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities. METHODS:We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals. FINDINGS:All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone. INTERPRETATION:Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required. FUNDING:CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).

SUBMITTER: Czeiter E

PROVIDER: S-EPMC7251365 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study.

Czeiter Endre E Amrein Krisztina K Gravesteijn Benjamin Y BY Lecky Fiona F Menon David K DK Mondello Stefania S Newcombe Virginia F J VFJ Richter Sophie S Steyerberg Ewout W EW Vyvere Thijs Vande TV Verheyden Jan J Xu Haiyan H Yang Zhihui Z Maas Andrew I R AIR Wang Kevin K W KKW Büki András A

EBioMedicine 20200525

<h4>Background</h4>Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.<h4>Methods</h4>We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collabo ...[more]

PMID: 32464528

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Project description:Backgroundvon Willebrand factor (VWF) has been widely recognized as a biomarker for endothelial cell activation in trauma and inflammation. Traumatic brain injury (TBI) is characterized by cerebral vascular injury and subsequent inflammation. The objective of this study was to investigate the correlation between VWF levels and clinical severity, as well as imaging abnormalities, in TBI patients. Additionally, the predictive value of VWF for patient outcomes was assessed.MethodsWe conducted a prospective study to recruit acute TBI patients who were admitted to the emergency department within 24 h. Healthy individuals from the medical examination center were recruited as the control group. This study aimed to compare the accuracy of VWF in discriminating TBI severity and imaging abnormalities with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) scores. We also analyzed the predictive value of these outcomes using the Glasgow Outcome Scale (GOS) and 6-month mortality.ResultsThe plasma concentration of VWF in TBI patients (84.7 ± 29.7 ng/ml) was significantly higher than in healthy individuals (40 ± 8.8 ng/ml). There was a negative correlation between VWF levels and GCS scores, as well as a positive correlation between VWF levels and Rotterdam CT scores. The area under the curve (AUC) for VWF in discriminating mild TBI was 0.76 (95% CI: 0.64, 0.88), and for predicting negative CT findings, it was 0.82 (95% CI: 0.72, 0.92). Meanwhile, the AUC of VWF in predicting mortality within 6 months was 0.70 (95% CI: 0.56, 0.84), and for a GOS score lower 4, it was 0.78 (95% CI: 0.67, 0.88). Combining VWF with either the GCS or Rotterdam CT score improved the prediction ability compared to using VWF alone.ConclusionVWF levels were significantly elevated in patients with TBI compared with healthy individuals. Furthermore, VWF levels demonstrated a negative correlation with GCS scores and a positive correlation with Rotterdam CT scores. In terms of predicting mortality, VWF alone was not sufficient, but its predictive power was enhanced when combined with either the Rotterdam CT score or GCS. These findings suggest that VWF may serve as a potential biomarker for assessing the severity and prognosis of TBI patients.

Project description:BackgroundWe aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI.MethodsConcentrations of six serum biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1) were measured in samples obtained <24 hours post-injury from 2869 patients with all severities of TBI, enrolled in the CENTER-TBI prospective cohort study (NCT02210221). Imaging phenotypes were defined as intraparenchymal haemorrhage (IPH), oedema, subdural haematoma (SDH), extradural haematoma (EDH), traumatic subarachnoid haemorrhage (tSAH), diffuse axonal injury (DAI), and intraventricular haemorrhage (IVH). Multivariable polynomial regression was performed to examine the association between biomarker levels and both distinct lesion types and lesion volumes. Hierarchical clustering was used to explore imaging phenotypes; and principal component analysis and k-means clustering of acute biomarker concentrations to explore patterns of biomarker clustering.Findings2869 patient were included, 68% (n=1946) male with a median age of 49 years (range 2-96). All severities of TBI (mild, moderate and severe) were included for analysis with majority (n=1946, 68%) having a mild injury (GCS 13-15). Patients with severe diffuse injury (Marshall III/IV) showed significantly higher levels of all measured biomarkers, with the exception of NFL, than patients with focal mass lesions (Marshall grades V/VI). Patients with either DAI+IVH or SDH+IPH+tSAH, had significantly higher biomarker concentrations than patients with EDH. Higher biomarker concentrations were associated with greater volume of IPH (GFAP, S100B, t-tau;adj r2 range:0·48-0·49; p<0·05), oedema (GFAP, NFL, NSE, t-tau, UCH-L1;adj r2 range:0·44-0·44; p<0·01), IVH (S100B;adj r2 range:0.48-0.49; p<0.05), Unsupervised k-means biomarker clustering revealed two clusters explaining 83·9% of variance, with phenotyping characteristics related to clinical injury severity.InterpretationInterpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury.FundingCENTER-TBI is funded by the European Union 7th Framework programme (EC grant 602150).

Project description:IntroductionSevere traumatic brain injury (TBI) is a catastrophic neurological condition with significant economic burden. Early in-hospital mortality (<48 hours) with severe TBI is estimated at 50%. Several clinical examinations exist to determine brain death; however, most are difficult to elicit in the acute setting in patients with severe TBI. Having a definitive assessment tool would help predict early in-hospital mortality in this population. CT perfusion (CTP) has shown promise diagnosing early in-hospital mortality in patients with severe TBI and other populations. The purpose of this study is to validate admission CTP features of brain death relative to the clinical examination outcome for characterizing early in-hospital mortality in patients with severe TBI.Methods and analysisThe Early Diagnosis of Mortality using Admission CT Perfusion in Severe Traumatic Brain Injury Patients study, is a prospective cohort study in patients with severe TBI funded by a grant from the Canadian Institute of Health Research. Adults aged 18 or older, with evidence of a severe TBI (Glasgow Coma Scale score ≤8 before initial resuscitation) and, on mechanical ventilation at the time of imaging are eligible. Patients will undergo CTP at the time of first imaging on their hospital admission. Admission CTP compares with the reference standard of an accepted bedside clinical assessment for brainstem function. Deferred consent will be used. The primary outcome is a binary outcome of mortality (dead) or survival (not dead) in the first 48 hours of admission. The planned sample size for achieving a sensitivity of 75% and a specificity of 95% with a CI of ±5% is 200 patients.Ethics and disseminationThis study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed through forums at the end of the study.Trial registration numberNCT04318665.

Project description:PurposeThe effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation.MethodsThis is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO2) and the oxygen inspired fraction (FiO2). We explored the association between high PaO2 and FiO2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO2 and FiO2 levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).ResultsThe analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO2 ranged from 93 to 166 mmHg. Exposure to higher PaO2 and FiO2 in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO2 levels, which remained independently associated with 6-month mortality.ConclusionsIn two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO2 and FiO2 varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO2 were due to use of higher FiO2 in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO2 and PaO2 are titrated to brain tissue oxygen monitoring (PbtO2) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.

Project description:Background: Traumatic brain injury (TBI) is the leading cause of death and disability in children. It includes a range of different pathologies that differ considerably from adult TBI. Analyzing and understanding injury patterns of pediatric TBI is essential to establishing new preventive efforts as well as to improve clinical management. Methods: The multi-center, prospectively collected CENTER-TBI core and registry databases were screened and patients were included when younger than 18 years at enrollment and admitted to the regular ward (admission stratum) or intensive care unit (ICU stratum) following TBI. Patient demographics, injury causes, clinical findings, brain CT imaging details, and outcome (GOSE at 6 months follow-up) were retrieved and analyzed. Injury characteristics were compared between patients admitted to the regular ward and ICU and multivariate analysis of factors predicting an unfavorable outcome (GOSE 1-4) was performed. Results from the core study were compared to the registry dataset which includes larger patient numbers but no follow-up data. Results: Two hundred and twenty seven patients in the core dataset and 687 patients in the registry dataset were included in this study. In the core dataset, road-traffic incidents were the most common cause of injury overall and in the ICU stratum, while incidental falls were most common in the admission stratum. Brain injury was considered serious to severe in the majority of patients and concurrent injuries in other body parts were very common. Intracranial abnormalities were detected in 60% of initial brain CTs. Intra- and extracranial surgical interventions were performed in one-fifth of patients. The overall mortality rate was 3% and the rate of unfavorable outcome 10%, with those numbers being considerably higher among ICU patients. GCS and the occurrence of secondary insults could be identified as independent predictors for an unfavorable outcome. Injury characteristics from the core study could be confirmed in the registry dataset. Conclusion: Our study displays the most common injury causes and characteristics of pediatric TBI patients that are treated in the regular ward or ICU in Europe. Road-traffic incidents were especially common in ICU patients, indicating that preventive efforts could be effective in decreasing the incidence of severe TBI in children.

Dataset Information

Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study.

Publications

Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study.

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