Relationship of admission blood proteomic biomarkers levels to lesion type and lesion burden in traumatic brain injury: A CENTER-TBI study.
Ontology highlight
ABSTRACT: Background
We aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI.Methods
Concentrations 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.Findings
2869 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.Interpretation
Interpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury.Funding
CENTER-TBI is funded by the European Union 7th Framework programme (EC grant 602150).
SUBMITTER: Whitehouse DP
PROVIDER: S-EPMC8718895 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.
| S-EPMC7307675 | biostudies-literature
Project description:BackgroundSerum 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.MethodsWe 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.FindingsAll 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.InterpretationCurrently 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.FundingCENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
| S-EPMC7251365 | biostudies-literature
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.
| S-EPMC9705485 | biostudies-literature
Project description:Biomarkers can be broadly defined as qualitative or quantitative measurements that convey information on the physiopathological state of a subject at a certain time point or disease state. Biomarkers can indicate health, pathology, or response to treatment, including unwanted side effects. When used as outcomes in clinical trials, biomarkers act as surrogates or substitutes for clinically meaningful endpoints. Biomarkers of disease can be diagnostic (the identification of the nature and cause of a condition) or prognostic (predicting the likelihood of a person's survival or outcome of a disease). In addition, genetic biomarkers can be used to quantify the risk of developing a certain disease. In the specific case of traumatic brain injury, surrogate blood biomarkers of imaging can improve the standard of care and reduce the costs of diagnosis. In addition, a prognostic role for biomarkers has been suggested in the case of post-traumatic epilepsy. Given the extensive literature on clinical biomarkers, we will focus herein on biomarkers which are present in peripheral body fluids such as saliva and blood. In particular, blood biomarkers, such as glial fibrillary acidic protein and salivary/blood S100B, will be discussed together with the use of nucleic acids (eg, DNA) collected from peripheral cells.
| S-EPMC6231511 | biostudies-literature
Project description:Neuropsychiatric symptoms are common, comorbid, and often disabling for patients with traumatic brain injury (TBI). Identifying transdiagnostic symptom dimensions post-TBI may help overcome limitations of traditional psychiatric diagnoses and advance treatment development. We characterized the dimensional structure of neuropsychiatric symptoms at 2-weeks postinjury in n = 1,732 TBI patients and n = 238 orthopedic-injured trauma controls (OTC) from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Symptoms were reported on the Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, PTSD Checklist for DSM-5, PROMIS Pain Intensity scale, and Insomnia Severity Index. We established a novel factor model of neuropsychiatric symptoms and evaluated how 3 TBI severity strata and OTC patients differed in symptom severity. The final factor model had 6 first-order factors subsumed by 2 second-order factors: Internalizing (encompassing Depression, Anxiety, and Fear) and Somatic symptoms (Sleep, Physical, Pain). Somatic symptoms fit better as a correlated factor of (vs. a lower-order factor within) Internalizing. All symptom dimensions except for Pain were more severe in 1 or more TBI subgroups, as compared to the OTC group. Milder brain injury was generally associated with more severe symptoms, whereas more general injury severity (higher level of care, e.g., emergency department, intensive care unit) was associated with more pain. The findings indicate a broad factor resembling the internalizing factor of general psychopathology in traumatically injured patients, alongside a distinct somatic symptom factor. Brain injury, especially milder brain injury, may exacerbate liabilities toward these symptoms. These neuropsychiatric dimensions may help advance more precision medicine research for TBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
| S-EPMC8552293 | biostudies-literature
Project description:Cerebral autoregulation, as measured using the pressure reactivity index (PRx), has been related to global patient outcome in adult patients with traumatic brain injury (TBI). To date, this has been documented without accounting for standard baseline admission characteristics and intracranial pressure (ICP). We evaluated this association, adjusting for baseline admission characteristics and ICP, in a multi-center, prospective cohort. We derived PRx as the correlation between ICP and mean arterial pressure in prospectively collected multi-center data from the High-Resolution Intensive Care Unit (ICU) cohort of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Multi-variable logistic regression models were analyzed to assess the association between global outcome (measured as either mortality or dichotomized Glasgow Outcome Score-Extended [GOSE]) and a range of covariates (IMPACT [International Mission for Prognosis and Analysis of Clinical Trials] Core and computed tomography [CT] variables, ICP, and PRx). Performance of these models in outcome association was compared using area under the receiver operating curve (AUC) and Nagelkerke's pseudo-R2. One hundred ninety-three patients had a complete data set for analysis. The addition of percent time above threshold for PRx improved AUC and displayed statistically significant increases in Nagelkerke's pseudo-R2 over the IMPACT Core and IMPACT Core + CT models for mortality. The addition of PRx monitoring to IMPACT Core ± CT + ICP models accounted for additional variance in mortality, when compared to models with IMPACT Core ± CT + ICP alone. The addition of cerebrovascular reactivity monitoring, through PRx, provides a statistically significant increase in association with mortality at 6 months. Our data suggest that cerebrovascular reactivity monitoring may provide complementary information regarding outcomes in TBI.
| S-EPMC7232651 | biostudies-literature
Project description:PURPOSE:Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes. METHODS:We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay???72 h. Tracheostomy was defined as early (??7 days from admission) or late (>?7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score. RESULTS:Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR?=?1.04, 95% CI?=?1.01-1.07, p?=?0.003), Glasgow coma scale???8 (HR?=?1.70, 95% CI?=?1.22-2.36 at 7; p?<?0.001), thoracic trauma (HR?=?1.24, 95% CI?=?1.01-1.52, p?=?0.020), hypoxemia (HR?=?1.37, 95% CI?=?1.05-1.79, p?=?0.048), unreactive pupil (HR?=?1.76, 95% CI?=?1.27-2.45 at 7; p?<?0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR?=?1.69, 95% CI?=?1.07-2.67, p?=?0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p?=?0.003). CONCLUSIONS:Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.
| S-EPMC7223805 | biostudies-literature
Project description:BackgroundTraumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma.Methods and findingsWe conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer-in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations.ConclusionsWe observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.
| S-EPMC8509890 | biostudies-literature
Project description:This study aims to assess rehabilitation needs and provision of rehabilitation services for individuals with moderate-to-severe disability and investigate factors influencing the probability of receiving rehabilitation within six months after traumatic brain injury (TBI). Overall, the analyses included 1206 individuals enrolled in the CENTER-TBI study with severe-to-moderate disability. Impairments in five outcome domains (daily life activities, physical, cognition, speech/language, and psychological) and the use of respective rehabilitation services (occupational therapy, physiotherapy, cognitive and speech therapies, and psychological counselling) were recorded. Sociodemographic and injury-related factors were used to investigate the probability of receiving rehabilitation. Physiotherapy was the most frequently provided rehabilitation service, followed by speech and occupational therapy. Psychological counselling was the least frequently accessed service. The probability of receiving a rehabilitative intervention increased for individuals with greater brain injury severity (odds ratio (OR) 1.75, CI 95%: 1.27-2.42), physical (OR 1.92, CI 95%: 1.21-3.05) and cognitive problems (OR 4.00, CI 95%: 2.34-6.83) but decreased for individuals reporting psychological problems (OR 0.57, CI 95%: 1.21-3.05). The study results emphasize the need for more extensive prescription of rehabilitation services for individuals with disability. Moreover, targeted rehabilitation programs, which aim to improve outcomes, should specifically involve psychological services to meet the needs of individuals recovering from TBI.
| S-EPMC7959119 | biostudies-literature
Project description:ImportanceA head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.ObjectiveTo identify pathological CT features associated with adverse outcomes after mTBI.Design, setting, and participantsThe longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.ExposuresAcute nonpenetrating head trauma.Main outcomes and measuresFrequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.ResultsIn 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.Conclusions and relevanceIn this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
| S-EPMC8290344 | biostudies-literature