ORCID Profile
0000-0002-5925-5193
Current Organisations
Turku University Hospital
,
University of Helsinki
,
University of Turku
,
Hospital district of Southwest Finland
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Publisher: Mary Ann Liebert Inc
Date: 10-2020
Publisher: Elsevier BV
Date: 03-2022
Publisher: Mary Ann Liebert Inc
Date: 06-2020
Abstract: The aim of this study is to investigate the prognostic value of using the National Institute of Neurological Disorders and Stroke (NINDS) standardized imaging-based pathoanatomic descriptors for the evaluation and reporting of acute traumatic brain injury (TBI) lesions. For a total of 3392 patients (2244 males and 1148 females, median age = 51 years) enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we extracted 96 Common Data Elements (CDEs) from the structured reports, spanning all three levels of pathoanatomic information (i.e., 20 "basic," 60 "descriptive," and 16 "advanced" CDE variables per patient). Six-month clinical outcome scores were dichotomized into favorable (Glasgow Outcome Scale Extended [GOS-E] = 5-8) versus unfavorable (GOS-E = 1-4). Regularized logistic regression models were constructed and compared using the optimism-corrected area under the curve (AUC). An abnormality was reported for the majority of patients (64.51%). In 79.11% of those patients, there was at least one coexisting pathoanatomic lesion or associated finding. An increase in lesion severity, laterality, and volume was associated with more unfavorable outcomes. Compared with the full set of pathoanatomic descriptors (i.e., all three categories of information), reporting "basic" CDE information provides at least equal discrimination between patients with favorable versus unfavorable outcome (AUC = 0.8121 vs. 0.8155, respectively). Addition of a selected subset of "descriptive" detail to the basic CDEs could improve outcome prediction (AUC = 0.8248). Addition of "advanced" or "emerging/exploratory" information had minimal prognostic value. Our results show that the NINDS standardized-imaging based pathoanatomic descriptors can be used in large-scale studies and provide important insights into acute TBI lesion patterns. When used in clinical predictive models, they can provide excellent discrimination between patients with favorable and unfavorable 6-month outcomes. If further validated, our findings could support the development of structured and itemized templates in routine clinical radiology.
Publisher: BMJ
Date: 10-05-2022
Abstract: Following traumatic brain injury (TBI), the clinical focus is often on disability. However, patients’ perceptions of well-being can be discordant with their disability level, referred to as the ‘disability paradox’. We aimed to examine the relationship between disability and health-related quality of life (HRQoL) following TBI, while taking variation in personal, injury-related and environment factors into account. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. Disability was assessed 6 months post-injury by the Glasgow Outcome Scale-Extended (GOSE). HRQoL was assessed by the SF-12v2 physical and mental component summary scores and the Quality of Life after Traumatic Brain Injury overall scale. We examined mean total and domain HRQoL scores by GOSE. We quantified variance in HRQoL explained by GOSE, personal, injury-related and environment factors with multivariable regression. Six-month outcome assessments were completed in 2075 patients, of whom 78% had mild TBI (Glasgow Coma Scale 13–15). Patients with severe disability had higher HRQoL than expected on the basis of GOSE alone, particularly after mild TBI. Up to 50% of patients with severe disability reported HRQoL scores within the normative range. GOSE, personal, injury-related and environment factors explained a limited amount of variance in HRQoL (up to 29%). Contrary to the idea that discrepancies are unusual, many patients with poor functional outcomes reported well-being that was at or above the boundary considered satisfactory for the normative s le. These findings challenge the idea that satisfactory HRQoL in patients with disability should be described as ‘paradoxical’ and question common views of what constitutes ‘unfavourable’ outcome.
Publisher: Springer Science and Business Media LLC
Date: 20-10-2022
Publisher: Elsevier BV
Date: 10-2021
Publisher: Frontiers Media SA
Date: 02-06-2020
Publisher: Mary Ann Liebert Inc
Date: 24-02-2023
Publisher: Mary Ann Liebert Inc
Date: 03-2022
Abstract: We investigated the topology of structural brain connectivity networks and its association with outcome after mild traumatic brain injury, a major cause of permanent disability. Eighty-five patients with mild traumatic brain injury underwent magnetic resonance imaging (MRI) twice, about three weeks and eight months after injury, and 30 age-matched orthopedic trauma control subjects were scanned. Outcome was assessed with Extended Glasgow Outcome Scale on average eight months after injury. We performed constrained spherical deconvolution-based probabilistic streamlines tractography on diffusion MRI data and parcellated cortical and subcortical gray matter into 84 regions based on T1-weighted data to reconstruct structural brain connectivity networks weighted by the number of streamlines. Graph theoretical methods were employed to measure network properties in both patients and controls, and correlations between these properties and outcome were calculated. We found no global differences in the network properties between patients with mild traumatic brain injury and orthopedic control subjects at either stage. We found significantly increased betweenness centrality of the right pars opercularis in the chronic stage compared with control subjects, however. Further, both global and local network properties correlated significantly with outcome. Higher normalized global efficiency, degree, and strength as well as lower small-worldness were associated with better outcome. Correlations between the outcome and the local network properties were the most prominent in the left putamen and the left postcentral gyrus. Our results indicate that both global and local network properties provide valuable information about the outcome already in the acute/subacute stage and, therefore, are promising biomarkers for prognostic purposes in mild traumatic brain injury.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2021
DOI: 10.1007/S12028-021-01400-3
Abstract: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury. Results from blood s les (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) ( n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR 1.2 and (2) INR ≥ 1.2. An INR 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers. Patients with iTBI with INR ≥ 1.2 ( n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR 1.2 ( n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR 1.2 to 1,301 mg/L in patients with INR ≥ 1.2. This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
Publisher: Mary Ann Liebert Inc
Date: 15-12-2020
Publisher: Elsevier BV
Date: 08-2021
Publisher: Frontiers Media SA
Date: 30-10-2020
Publisher: Springer Science and Business Media LLC
Date: 27-07-2022
DOI: 10.1186/S13054-022-04079-W
Abstract: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights. We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation ( 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset ( N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation. Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p 0.001). Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
Publisher: Elsevier BV
Date: 12-2022
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
DOI: 10.1186/S13054-020-2791-0
Abstract: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant ( p 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high five out of seven had less than 10 events per centre. Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
Publisher: Elsevier BV
Date: 06-2020
Publisher: Mary Ann Liebert Inc
Date: 15-08-2020
Publisher: Mary Ann Liebert Inc
Date: 04-2017
Abstract: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) have been studied as potential biomarkers of mild traumatic brain injury (mTBI). We report the levels of GFAP and UCH-L1 in patients with acute orthopedic injuries without central nervous system involvement, and relate them to the type of extracranial injury, head magnetic resonance imaging (MRI) findings, and levels of GFAP and UCH-L1 in patients with CT-negative mTBI. Serum UCH-L1 and GFAP were longitudinally measured from 73 patients with acute orthopedic injury on arrival and on days 1, 2, 3, 7 after admission, and on the follow-up visit 3-10 months after the injury. The injury types were recorded, and 71% patients underwent also head MRI. The results were compared with those found in patients with CT-negative mTBI (n = 93). The levels of GFAP were higher in patients with acute orthopedic trauma than in patients with CT-negative mTBI (p = 0.026) on arrival however, no differences were found on the following days. The levels of UCH-L1 were not significantly different between these two groups at any measured point of time. Levels of GFAP and UCH-L1 were not able to distinguish patients with CT-negative mTBI from patients with orthopedic trauma. Patients with orthopedic trauma and high levels of UCH-L1 or GFAP values may be falsely diagnosed as having a concomitant mTBI, predisposing them to unwarranted diagnostics and unnecessary brain imaging. This casts a significant doubt on the diagnostic value of GFAP and UCH-L1 in cases with mTBI.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.WNEU.2015.10.066
Abstract: Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale-Extended (GOSE). Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score ≤ 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities.
Publisher: Frontiers Media SA
Date: 31-05-2022
DOI: 10.3389/FNEUR.2022.888815
Abstract: Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI.
Publisher: American Medical Association (AMA)
Date: 09-2021
Publisher: American Medical Association (AMA)
Date: 11-11-2021
Publisher: Mary Ann Liebert Inc
Date: 07-2023
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1186/S12910-020-00480-8
Abstract: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally ( N = 11, 61%) or locally ( N = 7, 39%) and primary IRB approval was obtained after one ( N = 8, 44%), two ( N = 6, 33%) or three ( N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.
Publisher: Informa UK Limited
Date: 17-10-2020
DOI: 10.1080/09638288.2020.1832589
Abstract: There is conflicting literature on the effect of post- utation pain on quality of life (QOL) and no available literature on the relationship of pain medications to QOL of utees in pain. The aims of the study were to compare QOL in lower limb utees with significant pain to those with minimal pain and compare QOL in utees on multiple pain medications (≥3 and/or ≥ 40 mg morphine equivalent/day) to those on minimal. Cross-sectional study of utees ( Post- utation pain was common (69%), but only 13% of the participants were using more pain medications. High-pain interference and poor self-efficacy were associated with poorer QOL after adjusting for age, gender and cause of utation. High medication use was associated with high-pain interference and poor self-efficacy, but there was minimal correlation between pain scores and medication usage ( Post- utation pain continues to be a major determinant of QOL in lower limb utees, but the role of pain medications on an utee's QOL remains unclear.IMPLICATIONS FOR REHABILITATIONAn utee's QOL is affected by the severity of their post- utation pain even beyond six months post their utation.An utee with more pain may not necessarily take more pain medications to manage their pain. The amount of pain medications taken may not influence their self-reported QOL.Pain and QOL assessment should be integrated into routine clinical evaluation of adult utees. Standardized screening tools and/or formative assessment can be utilized for assessing QOL.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2022
DOI: 10.1186/S12913-022-08908-0
Abstract: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Patients ( n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. ClinicalTrials.gov NCT02210221.
Publisher: American Medical Association (AMA)
Date: 18-03-2021
Publisher: Elsevier BV
Date: 02-2022
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
Publisher: Springer Science and Business Media LLC
Date: 24-07-2021
Publisher: Mary Ann Liebert Inc
Date: 12-2021
Abstract: Men and women differ in outcomes following mild traumatic brain injury (TBI). In the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we previously found that women had worse 6-month functional outcome (Glasgow Outcome Score Extended [GOSE]), health-related quality of life (HRQoL), and mental health following mild TBI. The aim of this study was to investigate whether those differences were mediated by psychiatric history, gender-related sociodemographic variables, or by care pathways. We analyzed sex/gender differences in 6-month GOSE, generic and TBI-specific HRQoL, and post-concussion and mental health symptoms using three sets of mediators: psychiatric history, sociodemographic variables (living alone, living with children, education and employment status/job category), and care-pathways (referral to study hospital and discharge destination after emergency department) while controlling for a substantial number of potential confounders (pre-injury health and injury-related characteristics). We included 1842 men and 1022 women (16+) with a Glasgow Coma Score 13-15, among whom 83% had GOSE available and about 60% other 6-month outcomes. We used natural effects models to decompose the total effect of sex/gender on the outcomes into indirect effects that passed through the specified mediators and the remaining direct effects. In our study population, women had worse outcomes and these were only partly explained by psychiatric history, and not considerably explained by sociodemographic variables nor by care pathways. Factors other than differences in specified variables seem to underlie observed differences between men and women in outcomes after mild TBI. Future studies should explore more aspects of gender roles and identity and biological factors underpinning sex and gender differences in TBI outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
Publisher: Elsevier BV
Date: 2022
Publisher: BMJ
Date: 16-12-2021
DOI: 10.1136/EMERMED-2020-209471
Abstract: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI) GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum s les were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.
Publisher: Springer Science and Business Media LLC
Date: 11-12-2020
DOI: 10.1007/S12028-020-01151-7
Abstract: Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood. This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) ( n = 598) were selected for this analysis. Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly. Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 05-2021
Abstract: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13–15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p 0.001). Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.
Publisher: Mary Ann Liebert Inc
Date: 15-05-2019
Abstract: The purpose of this study was to correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). A total of 107 patients with mTBI (Glasgow Coma Scale ≥13) who had blood s les for GFAP and NF-L available within 24 h of arrival were included. Patients with mTBI were ided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale-Extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) versus incomplete (GOSE <8), and favorable (GOSE 5-8) versus unfavorable (GOSE 1-4). GFAP and NF-L concentrations in blood were measured using ultrasensitive single molecule array technology. Patients with incomplete recovery had significantly higher levels of NF-L compared with those with complete recovery (
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Abstract: In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns 2) choose a method of imputation 3) perform imputation 4) assess diagnostics of the imputation and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.
Publisher: Springer Science and Business Media LLC
Date: 19-12-2018
Publisher: Mary Ann Liebert Inc
Date: 15-11-2018
Abstract: There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish among different types of injuries observed. Logistical regression models using metabolite data from the discovery cohort (n = 144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and those with negative findings on head CT. The resultant models were then tested in the validation cohort (n = 66, Cambridge, United Kingdom). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (area under the curve [AUC] = 0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives, and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC = 0.77 in Turku patients and AUC = 0.73 in Cambridge patients). Further, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC = 0.87 in Turku patients and AUC = 0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
Publisher: Frontiers Media SA
Date: 04-04-2023
DOI: 10.3389/FNEUR.2023.1133764
Abstract: Interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have gained interest as diagnostic biomarkers of traumatic brain injury (TBI), but factors affecting their blood levels in patients with moderate-to-severe TBI are largely unknown. To investigate the trajectories of IL-10 and H-FABP between TBI patients with and without extracranial injuries (ECI) to investigate if there is a correlation between the levels of IL-10 and H-FABP with the levels of inflammation/infection markers C-reactive protein (CRP) and leukocytes and to investigate if there is a correlation between the admission level of H-FABP with admission levels of cardiac injury markers, troponin (TnT), creatine kinase (CK), and creatine kinase MB isoenzyme mass (CK-MBm). The admission levels of IL-10, H-FABP, CRP, and leukocytes were measured within 24 h post-TBI and on days 1, 2, 3, and 7 after TBI. The admission levels of TnT, CK, and CK-MBm were measured within 24 h post-TBI. There was a significant difference in the concentration of H-FABP between TBI patients with and without ECI on day 0 (48.2 ± 20.5 and 12.4 ± 14.7 ng/ml, p = 0.02, respectively). There was no significant difference in the levels of IL-10 between these groups at any timepoints. There was a statistically significant positive correlation between IL-10 and CRP on days 2 (R = 0.43, p & 0.01) and 7 (R = 0.46, p = 0.03) after injury, and a negative correlation between H-FABP and CRP on day 0 (R = -0.45, p = 0.01). The levels of IL-10 or H-FABP did not correlate with leukocyte counts at any timepoint. The admission levels of H-FABP correlated with CK (R = 0.70, p & 0.001) and CK-MBm (R = 0.61, p & 0.001), but not with TnT. Inflammatory reactions during the early days after a TBI do not significantly confound the use of IL-10 and H-FABP as TBI biomarkers. Extracranial injuries and cardiac sources may influence the levels of H-FABP in patients with moderate-to-severe TBI.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-05-2020
Publisher: Frontiers Media SA
Date: 18-08-2022
DOI: 10.3389/FNEUR.2022.861688
Abstract: Spine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI). Data from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended GOSe & 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up. A total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI. Rates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2022
DOI: 10.1038/S41598-022-20170-2
Abstract: Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in in iduals after TBI with differential severity. Data for six language groups ( n ≥ 200 Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in in iduals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of in iduals suffering from PTSD symptoms after TBI.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
Publisher: Springer Science and Business Media LLC
Date: 15-07-2020
DOI: 10.1007/S11136-020-02583-6
Abstract: The Quality of Life after Brain Injury overall scale (QOLIBRI-OS) measures health-related quality of life (HRQoL) after traumatic brain injury (TBI). The aim of this study was to derive value sets for the QOLIBRI-OS in three European countries, which will allow calculation of utility scores for TBI health states. A QOLIBRI-OS value set was derived by using discrete choice experiments (DCEs) and visual analogue scales (VAS) in general population s les from the Netherlands, United Kingdom and Italy. A three-stage procedure was used: (1) A selection of health states, covering the entire spectrum of severity, was defined (2) General population s les performed the health state valuation task using a web-based survey with three VAS questions and an at random selection of sixteen DCEs (3) DCEs were analysed using a conditional logistic regression and were then anchored on the VAS data. Utility scores for QOLIBRI-OS health states were generated resulting in estimates for all potential health states. The questionnaire was completed by 13,623 respondents. The biggest weight increase for all attributes is seen from “slightly” to “not at all satisfied”, resulting in the largest impact on HRQoL. “Not at all satisfied with how brain is working” should receive the greatest weight in utility calculations in all three countries. By transforming the QOLIBRI-OS into utility scores, we enabled the application in economic evaluations and in summary measures of population health, which may be used to inform decision-makers on the best interventions and strategies for TBI patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1998
DOI: 10.1097/00003246-199801000-00031
Abstract: To determine the degree of regional and systemic coagulation activation soon after isolated severe head injury. Prospective, controlled clinical study. The emergency room and intensive care unit (ICU) of a trauma center in a university hospital serving a population of 5 million people. Twenty-four trauma victims: 20 patients with isolated severe head injury (head trauma group, Glasgow Coma Score of < or =8) and four patients with isolated bone fracture (control group). Insertion of central venous, i.e. superior caval vein, jugular bulb, and arterial catheters for blood s ling. Central venous (i.e., superior caval vein) global coagulation variables (i.e., prothrombin time, activated partial thromboplastin time, fibrinogen concentration, antithrombin III activity, and platelet count) and central venous and jugular bulb activation coagulation and fibrinolysis variables (i.e., prothrombin fragment F1+2, thrombin-antithrombin III complex, soluble fibrin, and D-dimer concentration) were measured soon after trauma (<6 hrs) and 3 hrs later. When compared with the control group patients, upon ICU admission, fibrinogen concentration (p < .005) and platelet count (p < .025) were significantly decreased in the head trauma group. Thrombin-antithrombin III complex (p < .025), prothrombin fragment F1+2 (p < .025), and D-dimer (p < .005) concentrations measured at the time of ICU admission were significantly higher in the head trauma group than in the control group. Only in the head trauma group were soluble fibrin concentrations increased above the normal range thrombin-antithrombin III complex and the prothrombin fragment F1+2 were found to be significantly higher in cerebrovenous blood than in central venous blood (p < .025). There was no cerebrocentral venous difference in the concentrations of soluble fibrin or D-dimer in either group. Within 6 hrs after severe isolated head trauma, systemic procoagulant overflow from the traumatized cerebral microvasculature proceeds to the thrombin level and is then inhibited by antithrombin III. Regional and systemic hypercoagulability and increased D-dimer concentrations appear to be common among head trauma patients. Increased procoagulant and consecutive fibrinolytic turnover may, therefore, spark disseminated intravascular coagulation in this patient group.
Publisher: Mary Ann Liebert Inc
Date: 15-07-2019
Publisher: Oxford University Press (OUP)
Date: 22-02-2023
Abstract: Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13–15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of in idual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.
Publisher: Oxford University Press (OUP)
Date: 06-2022
Abstract: There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts 6 months post-injury (n = 165) and >5 years post-injury (n = 38 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker s ling (n = 199) and MRI (n = 172 including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2021
DOI: 10.1007/S12028-021-01386-Y
Abstract: In traumatic brain injury (TBI), large between-center differences in treatment and outcome for patients managed in the intensive care unit (ICU) have been shown. The aim of this study is to explore if European neurotrauma centers can be clustered, based on their treatment preference in different domains of TBI care in the ICU. Provider profiles of centers participating in the Collaborative European Neurotrauma Effectiveness Research in TBI study were used to assess correlations within and between the predefined domains: intracranial pressure monitoring, coagulation and transfusion, surgery, prophylactic antibiotics, and more general ICU treatment policies. Hierarchical clustering using Ward’s minimum variance method was applied to group data with the highest similarity. Heat maps were used to visualize whether hospitals could be grouped to uncover types of hospitals adhering to certain treatment strategies. Provider profiles were available from 66 centers in 20 different countries in Europe and Israel. Correlations within most of the predefined domains varied from low to high correlations (mean correlation coefficients 0.2–0.7). Correlations between domains were lower, with mean correlation coefficients of 0.2. Cluster analysis showed that policies could be grouped, but hospitals could not be grouped based on their preference. Although correlations between treatment policies within domains were found, the failure to cluster hospitals indicates that a specific treatment choice within a domain is not a proxy for other treatment choices within or outside the domain. These results imply that studying the effects of specific TBI interventions on outcome can be based on between-center variation without being substantially confounded by other treatments. We do not report the results of a health care intervention.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2023
Publisher: Springer Science and Business Media LLC
Date: 29-11-2022
DOI: 10.1186/S13054-022-04250-3
Abstract: 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. 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) s led ≤ 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. 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. 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.
Publisher: Wiley
Date: 13-09-2019
DOI: 10.1111/ANAE.14838
Publisher: Springer Science and Business Media LLC
Date: 13-06-2020
DOI: 10.1007/S00415-020-09979-X
Abstract: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand in idual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3–6 months. Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting in iduals with persisting impairment.
Publisher: Mary Ann Liebert Inc
Date: 15-05-2021
Abstract: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (
Publisher: Springer Science and Business Media LLC
Date: 10-05-2022
DOI: 10.1038/S41467-022-30227-5
Abstract: Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2018
Publisher: Springer Science and Business Media LLC
Date: 10-09-2020
DOI: 10.1007/S00415-020-10174-1
Abstract: The original version of this article unfortunately contained a mistake.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2014
DOI: 10.1186/S13049-021-00930-1
Abstract: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients. Patients with moderate and severe TBI (Glasgow Coma Scale 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively. A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78–1.69), nor with survival at discharge (1.05, 0.58–1.90). Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.
Publisher: Cold Spring Harbor Laboratory
Date: 20-03-2023
DOI: 10.1101/2023.03.14.23287262
Abstract: Acute traumatic brain injury (TBI) is associated with substantial metabolic abnormalities, both centrally and in the periphery. We have previously reported extensive changes in the circulating metabolome resulting from TBI, including changes proportional to disease severity and associated with patient outcomes. The observed metabolome changes in TBI likely reflect several pathophysiological mechanisms supporting the concept that TBI is a systemic disease after the primary injury. However, one of the main metabolic changes we have observed following a TBI are changes in lipids, including the structural lipids that are known to be present in the myelin in the brain. Here, we conducted a study to investigate the relationship between traumatic microstructural changes in white matter seen on magnetic resonance imaging (MRI) and quantitative lipidomic changes in the blood in a subset of patients with TBI recruited to the MRI sub-study of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. In total, there were 103 patients who had both a magnetic resonance imaging (MRI) scan and serum s les available for analysis. From serum, 201 known lipids were quantified. Diffusion tensor fitting generated fractional anisotropy (FA) and mean diffusivity (MD) maps for the MRI scans, in addition to volumetric data. Association matrices and partial correlation networks were built to elucidate the connections between the lipid groups and the maps. We found that there are distinct directions of associations between the neuroimage data (FA and MD sets) and the concentrations of circulating lipids after injury. The FA and MD values were in inverse relationship with the severity of TBI (higher MD values, lower FA). We also observed that the lipid associations to FA and MD show different metabolic signatures. Lysophosphatidylcholines (LPC) associate mostly with FA while sphingomyelins (SM) associate with MD. Only phosphatidylcholines(PC) have strong associations with both as well as with the volumetric data. Finally, we found that the lipid changes are not associated with the number of regions with abnormalities. In conclusion, we have identified groups of lipids which assocate with specific MRI imaging metrics following TBI. There appears to be consistent patterns of lipid changes associating with the specific microstructure changes in the CNS white matter. There is also a pattern of lipids with regional specficity, suggesting that blood-based lipidomics may provide an insight into the underlying disease mechanisms in TBI.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Mary Ann Liebert Inc
Date: 19-10-2020
Publisher: Elsevier BV
Date: 07-2022
Publisher: Mary Ann Liebert Inc
Date: 04-2019
Abstract: Observer variability in local radiological reading is a major concern in large-scale multi-center traumatic brain injury (TBI) studies. A central review process has been advocated to minimize this variability. The aim of this study is to compare central with local reading of TBI imaging datasets and to investigate the added value of central review. A total of 2050 admission computed tomography (CT) scans from subjects enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were analyzed for seven main CT characteristics. Kappa statistics were used to calculate agreement between central and local evaluations and a center-specific analysis was performed. The McNemar test was used to detect whether discordances were significant. Central interobserver and intra-observer agreement was calculated in a subset of patients. Good agreement was found between central and local assessment for the presence or absence of structural pathology (CT+, CT-, κ = 0.73) and most CT characteristics (κ = 0.62 to 0.71), except for traumatic axonal injury lesions (κ = 0.37). Despite good kappa values, discordances were significant in four of seven CT characteristics (i.e., midline shift, contusion, traumatic subarachnoid hemorrhage, and cisternal compression p = 0.0005). Central reviewers showed substantial to excellent interobserver and intra-observer agreement (κ = 0.73 to κ = 0.96), contrasted by considerable variability in local radiological reading. Compared with local evaluation, a central review process offers a more consistent radiological reading of acute CT characteristics in TBI. It generates reliable, reproducible data and should be recommended for use in multi-center TBI studies.
Publisher: Springer Science and Business Media LLC
Date: 23-02-2021
DOI: 10.1186/S13054-020-03370-Y
Abstract: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). We studied high TIL treatments (metabolic suppression, hypothermia ( 35 °C), intensive hyperventilation (PaCO 2 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0–2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome. Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies. Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments. The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, t2/show/NCT02210221?id=NCT02210221& draw=1& rank=1 and with Resource Identification Portal (RRID: SCR_015582).
Publisher: Elsevier BV
Date: 10-2020
Publisher: Mary Ann Liebert Inc
Date: 04-2020
Abstract: Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (
Publisher: Frontiers Media SA
Date: 13-05-2020
Publisher: Mary Ann Liebert Inc
Date: 15-09-2021
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 25-02-2020
Publisher: BMJ
Date: 02-12-2020
Abstract: Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability. 1554 patients with mild-to-severe TBI were assessed at 6 months post injury on the Glasgow Outcome Scale—Extended (GOSE), the Short Form-12v2 and a battery of cognitive tests. Outcomes across GOSE categories were compared using analysis of covariance adjusting for age, sex and education. Overall effect sizes were small to medium, and greatest for tests involving processing speed ( η p 2 0.057–0.067) and learning and memory ( η p 2 0.048–0.052). Deficits in cognitive performance were particularly evident in patients who were dependent (GOSE 3 or 4) or who were unable to participate in one or more major life activities (GOSE 5). At higher levels of function (GOSE 6–8), cognitive performance was surprisingly similar across categories. There were decreases in performance even in patients reporting complete recovery without significant symptoms. Medium to large effect sizes were present for summary measures of cognition ( η p 2 0.111), mental health ( η p 2 0.131) and physical health ( η p 2 0.252). This large-scale study provides novel insights into cognitive performance at different levels of disability and highlights the importance of processing speed in function in daily life. At upper levels of outcome, any influence of cognition on overall function is markedly attenuated and differences in mental health are salient.
Publisher: Springer Science and Business Media LLC
Date: 02-2023
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1007/S00701-022-05257-Z
Abstract: To compare outcomes between patients with primary external ventricular device (EVD)–driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)–driven treatment. The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with “center” as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36–1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34–2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor–guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-10-2020
DOI: 10.1097/CCM.0000000000004673
Abstract: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. Sixty-five ICUs across Europe. For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5–1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours acute kidney injury stage 2 equals to serum creatinine × 2–2.9 times baseline acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% ( n = 100), acute kidney injury stage 2 equals to 1% ( n = 14), and acute kidney injury stage 3 equals to 3% ( n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1–4 d). Renal history (hazard ratio = 2.48 95% CI, 1.39–4.43 p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52 95% CI, 1.22–5.197 p = 0.012), hypernatremia (hazard ratio = 1.88 95% CI, 1.31–2.71 p = 0.001), and osmotic therapy administration (hazard ratio = 2.08 95% CI, 1.45–2.99 p 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
DOI: 10.1007/S00415-020-10022-2
Abstract: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported. Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and in iduals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue. A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.
Publisher: Mary Ann Liebert Inc
Date: 19-10-2020
Publisher: SAGE Publications
Date: 07-08-2020
Abstract: Although rehabilitation is beneficial for in iduals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care. Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI. Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge. In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62 reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47 reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24). Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 09-2023
No related grants have been discovered for Jussi Posti.