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- Czeiter, Endre, et al.
(författare)
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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
- 2020
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 56
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Tidskriftsartikel (refereegranskat)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).
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- Helmrich, Isabel R. A. Retel, et al.
(författare)
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Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI) : an observational cohort study
- 2022
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Ingår i: Lancet Neurology. - : The Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 21:9, s. 792-802
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.METHODS: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.FINDINGS: Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models.INTERPRETATION: Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.
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- Mondello, Stefania, et al.
(författare)
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Blood-based protein biomarkers for the management of traumatic brain injuries in adults presenting to emergency departments with mild brain injury : A living systematic review and meta-analysis
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:8, s. 1086-1106
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Forskningsöversikt (refereegranskat)abstract
- Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE®, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.
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| 8. |
- Whitehouse, Daniel P., et al.
(författare)
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Relationship of admission blood proteomic biomarkers levels to lesion type and lesion burden in traumatic brain injury : A CENTER-TBI study
- 2022
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 75
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Tidskriftsartikel (refereegranskat)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.
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- Dimai, HP, et al.
(författare)
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Epidemiology of distal forearm fractures in Austria between 1989 and 2010
- 2014
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 25:9, s. 2297-2306
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Dimai, HP, et al.
(författare)
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Epidemiology of proximal humeral fractures in Austria between 1989 and 2008
- 2013
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 24:9, s. 2413-2421
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Richter, Sophie, et al.
(författare)
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Prognostic Value of Serum Biomarkers in Patients With Moderate-Severe Traumatic Brain Injury, Differentiated by Marshall Computer Tomography Classification
- 2023
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:21-22, s. 2297-2310
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Tidskriftsartikel (refereegranskat)abstract
- Prognostication is challenging in patients with traumatic brain injury (TBI) in whom computed tomography (CT) fails to fully explain a low level of consciousness. Serum biomarkers reflect the extent of structural damage in a different way than CT does, but it is unclear whether biomarkers provide additional prognostic value across the range of CT abnormalities. This study aimed to determine the added predictive value of biomarkers, differentiated by imaging severity. This prognostic study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (2014-2017). The analysis included patients aged & GE;16 years with a moderate-severe TBI (Glasgow Coma Scale [GCS] <13) who had an acute CT and serum biomarkers obtained & LE;24h of injury. Of six protein biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1), the most prognostic panel was selected using lasso regression. The performance of established prognostic models (CRASH and IMPACT) was assessed before and after the addition of the biomarker panel and compared between patients with different CT Marshall scores (Marshall score <3 vs. Marshall score & GE;3). Outcome was assessed at six months post-injury using the extended Glasgow Outcome Scale (GOSE), and dichotomized into favorable and unfavorable (GOSE <5). We included 872 patients with moderate-severe TBI. The mean age was 47 years (range 16-95); 647 (74%) were male and 438 (50%) had a Marshall CT score <3. The serum biomarkers GFAP, NFL, S100B and UCH-L1 provided complementary prognostic information; NSE and Tau showed no added value. The addition of the biomarker panel to established prognostic models increased the area under the curve (AUC) by 0.08 and 0.03, and the explained variation in outcome by 13-14% and 7-8%, for patients with a Marshall score of <3 and & GE;3, respectively. The incremental AUC of biomarkers for individual models was significantly greater when the Marshall score was <3 compared with & GE;3 (p < 0.001). Serum biomarkers improve outcome prediction after moderate-severe TBI across the range of imaging severities and especially in patients with a Marshall score <3.
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| 14. |
- Richter, Sophie, et al.
(författare)
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Serum biomarkers identify critically ill traumatic brain injury patients for MRI
- 2022
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings.METHODS: Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) < 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score < 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) sampled ≤ 24 h of injury, MRI < 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost-benefit analysis for the USA and UK health care settings was also performed. RESULTS: Among 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS.CONCLUSIONS: Serum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost.
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- Trivedi, Dhanisha, 1993-, et al.
(författare)
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Screening Performance of S100 Calcium-Binding Protein B, Glial Fibrillary Acidic Protein, and Ubiquitin C-Terminal Hydrolase L1 for Intracranial Injury Within Six Hours of Injury and Beyond
- 2024
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 41:3-4, s. 349-358
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The Scandinavian NeuroTrauma Committee (SNC) guidelines recommend S100B as a screening tool for early detection of Traumatic brain injury (TBI) in patients presenting with an initial Glasgow coma scale (GCS) of 14-15. The objective of the current study was to compare S100B's diagnostic performance within the recommended 6-hour window after injury, compared to GFAP and UCH-L1. The secondary outcome of interest was the ability of these biomarkers in detecting traumatic intracranial pathology beyond the 6-hour mark.METHODS: The Center-TBI core database (2014-2017) was queried for data pertaining to all TBI patients with an initial GCS of 14-15 who had a blood sample taken within 6 hours of injury in which the levels of S100B, GFAP, and UCH-L1 were measured. As a subgroup analysis, data involving patients with blood samples taken within 6-9 hours, and 9-12 hours were analyzed separately for diagnostic ability. The diagnostic ability of these biomarkers for detecting any intracranial injury was evaluated based on the area under the receiver operating characteristic curve (AUC). Each biomarker's sensitivity, specificity, and accuracy were also reported at the cutoff that maximized Youden's index.RESULTS: A total of 531 TBI patients with GCS 14-15 on admission had a blood sample taken within 6 hours, of whom 24.9% (N = 132) had radiologically confirmed intracranial injury. The AUCs of GFAP (0.86, 95% confidence interval (CI): 0.82-0.90) and UCH-L1 (0.81, 95% CI: 0.76-0.85) were statistically significantly higher than that of S100B (0.74, 95% CI: 0.69-0.79) during this time. There was no statistically significant difference in the predictive ability of S100B when sampled within 6 hours, 6-9 hours, and 9-12 hours of injury, as the p-values were >0.05 when comparing the AUCs. Overlapping AUC 95% CI suggests no benefit of a combined GFAP and UCH-L1 screening tool over GFAP during the time periods studied [ 0.87 (0.83-0.90) vs 0.86 (0.82-0.90) when sampled within 6 hours of injury, 0.83 (0.78-0.88) vs 0.83 (0.78-0.89) within 6-to-9 hours and 0.81 (0.73-0.88) vs 0.79 (0.72-0.87) within 9-12 hours].CONCLUSIONS: Targeted analysis of the CENTER-TBI core database, with focus on the patient category for which biomarker testing is recommended by the SNC guidelines, revealed that GFAP and UCH-L1 perform superior to S100B in predicting CT-positive intracranial lesions within 6 hours of injury. GFAP continued to exhibit superior predictive ability to S100B during the time periods studied. S100B displayed relatively unaltered screening performance beyond the diagnostic timeline provided by SNC guidelines. These findings suggest the need for a re-evaluation of the current SNC TBI guidelines.
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- Whitehouse, Daniel P., et al.
(författare)
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Blood biomarkers and structural imaging correlations post-traumatic brain injury : A systematic review
- 2021
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Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 90:2, s. 170-179
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Forskningsöversikt (refereegranskat)abstract
- Background: Blood biomarkers are of increasing importance in the diagnosis and assessment of traumatic brain injury (TBI). However, the relationship between them and lesions seen on imaging remains unclear.Objective: To perform a systematic review of the relationship between blood biomarkers and intracranial lesion types, intracranial lesion injury patterns, volume/number of intracranial lesions, and imaging classification systems.Methods: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, and Cumulative Index to Nursing and Allied Health Literature from inception to May 2021, and the references of included studies were also screened. Heterogeneity in study design, biomarker types, imaging modalities, and analyses inhibited quantitative analysis, with a qualitative synthesis presented.Results: Fifty-nine papers were included assessing one or more biomarker to imaging comparisons per paper: 30 assessed imaging classifications or injury patterns, 28 assessed lesion type, and 11 assessed lesion volume or number. Biomarker concentrations were associated with the burden of brain injury, as assessed by increasing intracranial lesion volume, increasing numbers of traumatic intracranial lesions, and positive correlations with imaging classification scores. There were inconsistent findings associating different biomarkers with specific imaging phenotypes including diffuse axonal injury, cerebral edema, and intracranial hemorrhage.Conclusion: Blood-based biomarker concentrations after TBI are consistently demonstrated to correlate burden of intracranial disease. The relation with specific injury types is unclear suggesting a lack of diagnostic specificity and/or is the result of the complex and heterogeneous nature of TBI.
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