Eirik Helseth

• Galteland, Pål; Døving, Mats; Næss, Ingar; Sehic, Amer; Utheim, Tor Paaske & Eken, Torsten [Show all 9 contributors for this article] (2024). The association between head injury and facial fracture treatment: an observational study of hospitalized bicyclists from a level 1 trauma centre. Acta Neurochirurgica. ISSN 0001-6268. 166(1). doi: 10.1007/s00701-024-06019-9.
• Netteland, Dag Ferner; Aarhus, Mads; Sandset, Else Charlotte; Padayachy, Llewellyn; Helseth, Eirik & Brekken, Reidar (2024). Noninvasive Assessment of Intracranial Pressure: Deformability Index as an Adjunct to Optic Nerve Sheath Diameter to Increase Diagnostic Ability. Neurocritical Care. ISSN 1541-6933. doi: 10.1007/s12028-024-01955-x.
• Blakstad, Hanne Kristin; Mireles, Eduardo Erasmo Mendoza; Heggebø, Liv Cathrine; Magelssen, Henriette; Sprauten, Mette & Johannesen, Tom Børge [Show all 13 contributors for this article] (2023). Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study. Neuro-Oncology Practice. ISSN 2054-2577. 11(1), p. 36–45. doi: 10.1093/nop/npad063.
• Riemann, Lennart; Mikolic, Ana; Maas, Andrew; Unterberg, Andreas; Younsi, Alexander & Åkerlund, Cecilia [Show all 67 contributors for this article] (2023). Computed Tomography Lesions and Their Association With Global Outcome in Young People With Mild Traumatic Brain Injury. Journal of Neurotrauma. ISSN 0897-7151. 40(11-12), p. 1243–1254. doi: 10.1089/neu.2022.0055.
• Woodrow, Rebecca E; Winzeck, Stefan; Luppi, Andrea I; Kelleher-Unger, Isaac R; Spindler, Lennart R B & Wilson, J T Lindsay [Show all 86 contributors for this article] (2023). Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury. Brain. ISSN 0006-8950. 146(8), p. 3484–3499. doi: 10.1093/brain/awad056. Full text in Research Archive
• Åkerlund, Cecilia A. I.; Holst, Anders; Bhattacharyay, Shubhayu; Stocchetti, Nino; Steyerberg, Ewout & Smielewski, Peter [Show all 111 contributors for this article] (2023). Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study. Lancet Neurology. ISSN 1474-4422. 1, p. 71–80. doi: 10.1016/S1474-4422(23)00358-7.
• Mireles, Eduardo Erasmo Mendoza; Skaga, Erlend; Server, Andrés; Leske, Henning; Brandal, Petter & Helseth, Eirik [Show all 8 contributors for this article] (2023). The benefit of complete resection of contrast enhancing tumor in glioblastoma patients: A population-based study. Neuro-Oncology Practice. ISSN 2054-2577. 10(6), p. 555–564. doi: 10.1093/nop/npad037. Full text in Research Archive
• Schäfer, Christoph; Moksnes, Håkon Øgreid; Rasmussen, Mari Storli; Hellstrøm, Torgeir; Søberg, Helene L. & Røise, Olav [Show all 15 contributors for this article] (2023). Adherence to Guidelines for Acute Rehabilitation in the Norwegian Trauma Plan. Journal of Rehabilitation Medicine. ISSN 1650-1977. 55. doi: 10.2340/jrm.v55.6552. Full text in Research Archive
• Mikolić, Ana; Steyerberg, Ewout W.; Polinder, Suzanne; Wilson, Lindsay; Zeldovich, Marina & von Steinbueche, Nicole [Show all 258 contributors for this article] (2023). Prognostic Models for Global Functional Outcome and Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study. Journal of Neurotrauma. ISSN 0897-7151. 40(15-16), p. 1651–1670. doi: 10.1089/neu.2022.0320. Full text in Research Archive
• Moksnes, Håkon Øgreid; Schäfer, Christoph; Rasmussen, Mari Storli; Søberg, Helene L.; Røise, Olav & Anke, Audny Gabriele Wagner [Show all 15 contributors for this article] (2023). Functional Outcomes at 6 and 12 Months Post-Injury in a Trauma Centre Population with Moderate-to-Severe Traumatic Injuries. Journal of Clinical Medicine. ISSN 2077-0383. 12(16). doi: 10.3390/jcm12165300. Full text in Research Archive
• Cuevas-Østrem, Mathias; Thorsen, Kjetil; Wisborg, Torben; Røise, Olav; Helseth, Eirik & Jeppesen, Elisabeth (2023). Care pathways and factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe traumatic brain injury: a population-based study from the Norwegian trauma registry. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. ISSN 1757-7241. 31(1). doi: 10.1186/s13049-023-01097-7. Full text in Research Archive
• Moksnes, Håkon Øgreid; Schäfer, Christoph; Rasmussen, Mari Storli; Søberg, Helene L.; Røise, Olav & Anke, Audny Gabriele Wagner [Show all 15 contributors for this article] (2023). Factors associated with discharge destination from acute care after moderate-to-severe traumatic injuries in Norway: a prospective population-based study. Injury Epidemiology. ISSN 2197-1714. 10. doi: 10.1186/s40621-023-00431-y. Full text in Research Archive
• Netteland, Dag Ferner; Aarhus, Mads; Smistad, Erik; Sandset, Else Charlotte; Padayachy, Llewellyn & Helseth, Eirik [Show all 7 contributors for this article] (2023). Noninvasive intracranial pressure assessment by optic nerve sheath diameter: Automated measurements as an alternative to clinician-performed measurements. Frontiers in Neurology. ISSN 1664-2295. 14. doi: 10.3389/fneur.2023.1064492. Full text in Research Archive
• Galteland, Pål; Næss, Ingar; Døving, Mats; Sehic, Amer; Utheim, Tor Paaske & Skaga, Nils Oddvar [Show all 9 contributors for this article] (2023). Facial Fractures and Their Relation to Head and Cervical Spine Injuries in Hospitalized Bicyclists. The Journal of craniofacial surgery (Print). ISSN 1049-2275. 34(1), p. 34–39. doi: 10.1097/SCS.0000000000009032.
• Netteland, Dag Ferner; Sandset, Else Charlotte; Mejlænder-Evjensvold, Magnus; Aarhus, Mads; Jeppesen, Elisabeth & Sousa, Diana [Show all 8 contributors for this article] (2023). Cerebral venous sinus thrombosis in traumatic brain injury: A systematic review of its complications, effect on mortality, diagnostic and therapeutic management, and follow-up. Frontiers in Neurology. ISSN 1664-2295. 13(2022). doi: 10.3389/fneur.2022.1079579. Full text in Research Archive
• Van Praag, Dominique L.G.; Wouters, Kristien; Van Den Eede, Filip; Wilson, Lindsay; Maas, Andrew I.R. & Åkerlund, Cecilia [Show all 250 contributors for this article] (2022). Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury. Brain and Spine. ISSN 2772-5294. 2. doi: 10.1016/j.bas.2021.100854.
• Wilson, Lindsay; Horton, Lindsay; Polinder, Suzanne; Newcombe, Virginia F.J.; Steinbuechel, Nicole v. & Maas, Andrew I. R. [Show all 50 contributors for this article] (2022). Tailoring Multi-Dimensional Outcomes to Level of Functional Recovery after Traumatic Brain Injury. Journal of Neurotrauma. ISSN 0897-7151. 39(19-20), p. 1363–1381. doi: 10.1089/neu.2022.0013.
• Helmrich, Isabel Retel; Czeiter, Endre; Amrein, Krisztina; Büki, András; Lingsma, Hester F & Menon, David K [Show all 50 contributors for this article] (2022). Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study. Lancet Neurology. ISSN 1474-4422. 21(9), p. 792–802. doi: 10.1016/S1474-4422(22)00218-6. Show summary

  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. Funding European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences

• Åkerlund, Cecilia; Holst, Anders; Stocchetti, Nino; Steyerberg, Ewout W; Menon, David K & Ercole, Ari [Show all 50 contributors for this article] (2022). Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study. Critical Care. ISSN 1364-8535. 26. doi: 10.1186/s13054-022-04079-w. Full text in Research Archive Show summary

  Background 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. Methods 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. Results 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). Conclusions 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.

• Volovici, Victor; Pisică, Dana; Gravesteijn, Benjamin; Dirven, Clemens M. F.; Steyerberg, Ewout W. & Ercole, Ari [Show all 50 contributors for this article] (2022). Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study. Acta Neurochirurgica. ISSN 0001-6268. 164, p. 1693–1705. doi: 10.1007/s00701-022-05257-z. Full text in Research Archive
• Rivera, Diego; Greving, Sven; Arango-Lasprilla, Juan Carlos; von Steinbuechel, Nicole; Zeldovich, Marina & Åkerlund, Cecilia [Show all 85 contributors for this article] (2022). Comparability of (Post-Concussion) Symptoms across Time in Individuals after Traumatic Brain Injury: Results from the CENTER-TBI Study. Journal of Clinical Medicine. ISSN 2077-0383. 11(14), p. 1–23. doi: 10.3390/jcm11144090. Full text in Research Archive Show summary

  settingsOrder Article Reprints Open AccessArticle Comparability of (Post-Concussion) Symptoms across Time in Individuals after Traumatic Brain Injury: Results from the CENTER-TBI Study by Diego Rivera 1,2ORCID,Sven Greving 3,Juan Carlos Arango-Lasprilla 4ORCID,Nicole von Steinbuechel 3,Marina Zeldovich 3,*ORCID andCENTER-TBI Participants and Investigators † 1 Department of Health Sciences, Public University of Navarre, Arrosadia Campus, 31006 Pamplona, Spain 2 Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea Street 3, 31008 Pamplona, Spain 3 Institute of Medical Psychology and Medical Sociology, University Medical Center Göttingen, Waldweg 37A, 37073 Göttingen, Germany 4 Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284-2018, USA * Author to whom correspondence should be addressed. † The full list of the CENTER-TBI participants and investigators can be found in the Supplementary Materials. J. Clin. Med. 2022, 11(14), 4090; https://doi.org/10.3390/jcm11144090 Received: 20 May 2022 / Revised: 10 July 2022 / Accepted: 13 July 2022 / Published: 14 July 2022 (This article belongs to the Special Issue Traumatic Brain Injury: Diagnosis, Management, and Outcomes) Download Browse Figures Versions Notes Abstract Post-concussion symptoms often occur after TBI, persist and cause disabilities. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is widely used in this population, but little is known about the comparability of the symptoms over time, i.e., longitudinal measurement invariance (MI). The objectives of this study were to analyze the longitudinal MI of RPQ symptoms from three to twelve months after TBI and to find factors related to RPQ symptoms. The study involved 1023 individuals after TBI who took part in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study and completed the RPQ at three, six and twelve months post-injury. Longitudinal confirmatory factor analysis showed that the three-factor structure (somatic, emotional and cognitive) remains stable within one year after TBI. Linear mixed models revealed that sex, injury cause and prior psychiatric problems were related to the RPQ three-factor structure as well as to the RPQ total score. The study strengthens evidence for the RPQ’s factorial structure stability within one year after TBI and identifies sex, injury cause and prior psychiatric problems as important factors that may help clinicians to prevent future complications of symptomatology after TBI.

• Van Essen, Thomas; Lingsma, Hester F; Pisică, Dana; Singh, Ranjit D.; Volovici, Victor & den Boogert, Hugo F [Show all 50 contributors for this article] (2022). Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study. Lancet Neurology. ISSN 1474-4422. 21(7), p. 620–631. doi: 10.1016/s1474-4422(22)00166-1. Show summary

  Background Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. Methods We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3–35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77–1·09). Interpretation Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. Funding The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).

• Rezoagli, Emanuele; Petrosino, Matteo; Rebora, Paola; Menon, David K.; Mondello, Stefania & Cooper, D. James [Show all 50 contributors for this article] (2022). High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI. Intensive Care Medicine. ISSN 0342-4642. 48, p. 1709–1725. doi: 10.1007/s00134-022-06884-x. Full text in Research Archive Show summary

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

• Whitehouse, Daniel; Monteiro, Miguel; Czeiter, Endre; Vyvere, Thijs Vande; Valerio, Fernanda & Ye, Zheng [Show all 50 contributors for this article] (2022). Relationship of admission blood proteomic biomarkers levels to lesion type and lesion burden in traumatic brain injury: A CENTER-TBI study. EBioMedicine. ISSN 2352-3964. 75, p. 1–15. doi: 10.1016/j.ebiom.2021.103777. Full text in Research Archive Show summary

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

• Maas, Andrew I. R.; Menon, David K.; Manley, Geoffrey; Abrams, Mathew; Åkerlund, Cecilia & Andelic, Nada [Show all 50 contributors for this article] (2022). Traumatic brain injury: progress and challenges in prevention, clinical care, and research. Lancet Neurology. ISSN 1474-4422. 21(11), p. 1004–1060. doi: 10.1016/S1474-4422(22)00309-X.
• Løke, Daniel; Andelic, Nada; Helseth, Eirik; Vassend, Olav Mandt; Andersson, Stein & Ponsford, Jennie [Show all 9 contributors for this article] (2022). Stability and Change in Biopsychosocial Factors Associated With Fatigue 6 and 12 Months After Traumatic Brain Injury: An Exploratory Multilevel Study. The journal of head trauma rehabilitation. ISSN 0885-9701. 38(4). doi: 10.1097/HTR.0000000000000847.
• Tverdal, Cathrine Buaas; Brunborg, Cathrine; Helseth, Eirik; Andelic, Nada; Koch, Marte Ellersgaard & Røe, Cecilie [Show all 8 contributors for this article] (2022). Referrals to early specialized rehabilitation after traumatic brain iinjury during the Covid-19 pandemic. Journal of Rehabilitation Medicine. ISSN 1650-1977. 54:jrm00334, p. 1–9. doi: 10.2340/jrm.v54.2203. Full text in Research Archive
• Howe, Emilie; Zeldovich, Marina; Andelic, Nada; von Steinbuechel, Nicole; Fure, Silje Christine Reistad & Borgen, Ida Maria Henriksen [Show all 51 contributors for this article] (2022). Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study. BMC Health Services Research. ISSN 1472-6963. 22(1), p. 1–16. doi: 10.1186/s12913-022-08908-0. Full text in Research Archive Show summary

  Background 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. Methods 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. Results 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. Conclusions 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.

• Stray, August Vincent; SIVERTS, HENRIK; Melhuus, Knut; Enger, Martine Merete; Galteland, Pål & Næss, Ingar [Show all 8 contributors for this article] (2022). Characteristics of Electric Scooter and Bicycle Injuries After Introduction of Electric Scooter Rentals in Oslo, Norway. JAMA Network Open. ISSN 2574-3805. doi: 10.1001/jamanetworkopen.2022.26701.
• Bockhop, Fabian; Zeldovich, Marina; Cunitz, Katrin; Van Praag, Dominique; van der Vlegel, Marjolein & Beissbarth, Tim [Show all 258 contributors for this article] (2022). Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury. Scientific Reports. ISSN 2045-2322. 12(1), p. 1–15. doi: 10.1038/s41598-022-20170-2. Full text in Research Archive
• Eng, Svend Filip; Næss, Ingar; Linnerud, Hege; Rønning, Pål Andre; Brommeland, Tor & Mejlænder-Evjensvold, Magnus [Show all 12 contributors for this article] (2022). Bicycle-related cervical spine injuries. North American Spine Society Journal (NASSJ). ISSN 2666-5484. 10. doi: 10.1016/j.xnsj.2022.100119.
• Thomas, Ilias; Dickens, Alex M.; Posti, Jussi P.; Czeiter, Endre; Duberg, Daniel & Sinioja, Tim [Show all 255 contributors for this article] (2022). Serum metabolome associated with severity of acute traumatic brain injury. Nature Communications. ISSN 2041-1723. 13(1), p. 1–15. doi: 10.1038/s41467-022-30227-5. Full text in Research Archive
• van der Vlegel, Marjolein; Mikolić, Ana; Lee Hee, Quentin; Kaplan, Z.L. Rana; Retel Helmrich, Isabel R.A. & van Veen, Ernest [Show all 255 contributors for this article] (2022). Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study. Injury. ISSN 0020-1383. 53(8), p. 2774–2782. doi: 10.1016/j.injury.2022.05.009. Full text in Research Archive Show summary

  Introduction The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI. Methods We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury. Results Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms. Conclusion The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.

• Sødal, Hild Flatmark; Storvig, Gøril; Tverdal, Cathrine Buaas; Robinson, Hilde Stendal; Helseth, Eirik & Taubøll, Erik (2022). Early post-traumatic seizures in hospitalized patients with traumatic brain injury. Acta Neurologica Scandinavica. ISSN 0001-6314. 146(5), p. 485–491. doi: 10.1111/ane.13670. Full text in Research Archive
• Sørensen, Petter Toivo; Nyborg, Geir; Lorentsen, Torleif; Olasveengen, Theresa M.; Langerud, Anne Kathrine & Aarhus, Mads [Show all 9 contributors for this article] (2022). Vasospasm Surveillance by a Simplified Transcranial Doppler Protocol in Traumatic Brain Injury. World Neurosurgery. ISSN 1878-8750. 164, p. e318–e325. doi: 10.1016/j.wneu.2022.04.108. Show summary

  Objective To detect post-traumatic vasospasm in patients with traumatic brain injury (TBI), we implemented a simplified transcranial Doppler (TCD) surveillance protocol in a neurointensive care setting. In this study, we evaluate the yield of this protocol. Methods Adult patients with TBI admitted to the neurointensive care unit were examined with TCD by 2 intensive care nurses trained in TCD examinations. Flow velocities of the middle cerebral arteries were recorded. TCD suspected vasospasm was defined as the mean flow velocity >120 cm/s, and when detected, the protocol recommended a supplementary computed tomography angiography. The rate of detection of TCD suspected vasospasm and the subsequent rate of radiological diagnosis of vasospasm were recorded. In multivariate logistic regression analysis, we evaluated age, initial Glasgow Coma Scale, craniotomy, and decompressive craniectomy as potential predictors of developing increased TCD velocity. Results A total of 84 patients with TBI with a median initial Glasgow Coma Scale score of 6 were examined by TCD. TCD suspected vasospasm was found in the middle cerebral arteries of 18% of examined patients. Two-thirds of patients with TCD suspected vasospasm were investigated with a subsequent computed tomography angiography, and 80% of these patients received a radiological diagnosis of vasospasm. In logistic regression analysis, decompressive craniectomy was significantly associated with increased risk of developing TCD suspected vasospasm (odds ratio: 11.57, 95% confidence interval: 2.59–51.73, P = 0.001). Conclusions The implementation of a simplified TCD surveillance protocol in a neurointensive care setting yielded an 18% detection rate of TCD suspected vasospasm. In our cohort of patients with TBI, decompressive craniectomy was associated with increased risk of developing TCD suspected vasospasm.

• Tønne, Elin; Due-Tønnessen, Bernt Johan; Vigeland, Magnus Dehli; Amundsen, Silja Svanstrøm; Ribarska, Teodora Plamenova & Åsten, Pamela [Show all 11 contributors for this article] (2022). Whole-exome sequencing in syndromic craniosynostosis increases diagnostic yield and identifies candidate genes in osteogenic signaling pathways. American Journal of Medical Genetics. Part A. ISSN 1552-4825. 188A(5), p. 1464–1475. doi: 10.1002/ajmg.a.62663. Full text in Research Archive Show summary

  Craniosynostosis (CS) is a common congenital anomaly defined by premature fusionof one or more cranial sutures. Syndromic CS involves additional organ anomalies orneurocognitive deficits and accounts for 25%–30% of the cases. In a recentpopulation-based study by our group, 84% of the syndromic CS cases had a geneti-cally verified diagnosis after targeted analyses. A number of different genetic causeswere detected, confirming that syndromic CS is highly heterogeneous. In this study,we performed whole-exome sequencing of 10 children and parents from the samecohort where previous genetic results were negative. We detected pathogenic, orlikely pathogenic, variants in four additional genes (NFIA,EXTL3,POLR2A, andFOXP2)associated with rare conditions. In two of these (POLR2AandFOXP2), CS has notpreviously been reported. We further detected a rare predicted damaging variant inSH3BP4, which has not previously been related to human disease. All findings wereclustered in genes involved in the pathways of osteogenesis and suture patency.Weconclude that whole-exome sequencing expands the list of genes associated withsyndromic CS, and provides new candidate genes in osteogenic signaling pathways.

• Gheorghiu, Ana; Brunborg, Cathrine; Johannessen, Tom Børge; Helseth, Eirik; Zwart, John Anker Henrik & Wiedmann, Markus (2022). The impact of body mass index and height on risk for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in 1.7 million norwegian women and men: a prospective cohort study. Acta Oncologica. ISSN 0284-186X. 61(1), p. 1–6. doi: 10.1080/0284186X.2021.2009562. Show summary

  Background Primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves comprise a heterogenous group of pathology, dominantly represented by meningioma, nerve sheath tumours (NST) and glioma. Body height and body mass index (BMI) are risk factors for certain brain tumour subgroups, but no other study has specifically assessed height and BMI in relation to primary tumours of the spine and peripheral nerves in women and men. Methods In this prospective population-based cohort study height and weight were measured in 1.7 million adult Norwegian women and men at baseline. Incident cases of primary tumours arising from the spinal cord, spinal meninges, spinal and peripheral nerves during follow-up were identified by linkage to the National Cancer Registry. Tumour risk was assessed by Cox regression analyses in relation to height and BMI. Results During 49 million person-years of follow-up, 857 primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves were identified. Overweight and obesity were not associated with risk for all tumours or any tumour subgroup. Height was positively associated with risk for all tumours (HR per 10 cm increase: 1.30, 95% CI 1.16–1.46). The association between height and tumour risk varied between tumour subgroups: while height was not significantly associated with NST, height increased the risk for meningioma (HR 1.42, 95% CI 1.13–1.78) and glioma (HR 1.56, 95% CI 1.06–2.28). The strongest association between height and tumour risk was found for the glioma subgroup of ependymoma in women (HR 3.38, 95% CI 1.64–6.94). Conclusion This study could not identify overweight and obesity as risk factors for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in women or men. Increasing body height was associated with increased tumour risk overall, but not universal for all tumour subgroups. Importance of the study Primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves have received little focus in epidemiologic studies, although the incidence and histo-pathological tumour subgroups differ significantly from primary brain tumours. Risk factors for these tumours have hardly been assessed in previous studies. Height, overweight and obesity are known risk factors for several cancers, including certain brain tumour subgroups, such as meningioma. This is the first study to report the association between height, overweight and obesity and primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves. This includes tumour subgroups of meningioma, nerve sheath tumour, glioma and the most common spinal glioma subgroup of ependymoma. While overweight and obesity were not associated with either of the tumour subgroups, an association between increasing body height and risk for spinal meningioma and glioma, including ependymoma, was found. Nerve sheath tumour risk was not associated with increasing body height.

• Tverdal, Cathrine Buaas; Aarhus, Mads; Rønning, Pål Andre; Skaansar, Ola Fougner; Skogen, Karoline & Andelic, Nada [Show all 7 contributors for this article] (2022). Incidence of emergency neurosurgical TBI procedures: a population-based study. BMC Emergency Medicine. ISSN 1471-227X. 22(1), p. 1–11. doi: 10.1186/s12873-021-00561-w. Full text in Research Archive
• Døving, Mats; Næss, Ingar; Galteland, Pål; Ramm-Pettersen, Jon-Terje; Dalby, Marius & Utheim, Tor Paaske [Show all 9 contributors for this article] (2022). Anatomical distribution of mandibular fractures from severe bicycling accidents: A 12-year experience from a Norwegian level 1 trauma center. Dental Traumatology. ISSN 1600-4469. 38(5), p. 424–430. doi: 10.1111/edt.12756. Full text in Research Archive
• Rootwelt, Rebecca; Hjermstad, Marianne Jensen; Skovlund, Eva; Aass, Nina Kathrine; Helseth, Eirik & Kaasa, Stein [Show all 8 contributors for this article] (2022). Surgery for brain metastases—impact of the extent of resection. Acta Neurochirurgica. ISSN 0001-6268. 164, p. 2773–2780. doi: 10.1007/s00701-021-05104-7. Full text in Research Archive
• Utheim, Nils Christian; Helseth, Eirik; Strøm, Mona; Rydning, pål Nicolay; Mejlænder-Evjensvold, Magnus & Glott, Thomas [Show all 10 contributors for this article] (2022). Epidemiology of traumatic cervical spinal fractures in a general Norwegian population. Injury Epidemiology. ISSN 2197-1714. 9(10). doi: 10.1186/s40621-022-00374-w. Show summary

  Background: In Western countries, the typical cervical spine fracture (CS‑Fx) patient has historically been a young male injured in a road traffic accident. Recent reports and daily clinical practice clearly indicate a change in the typical patient from a young male to an elderly male or female with comorbidities. This study aimed to establish contempo‑ rary population‑based epidemiological data of traumatic CS‑Fx for use in health‑care planning and injury prevention. Methods: This is a population‑based retrospective database study (with prospectively collected data) from the Southeast Norway health region with 3.0 million inhabitants. We included all consecutive cases diagnosed with a CS‑Fx between 2015 and 2019. Information regarding demographics, preinjury comorbidities, trauma mechanisms, injury description, treatment, and level of hospital admittance is presented. Results: We registered 2153 consecutive cases with CS‑Fx during a 5‑year period, with an overall crude incidence of CS‑Fx of 14.9/100,000 person‑years. Age‑adjusted incidences using the standard population for Europe and the World was 15.6/100,000 person‑years and 10.4/100,000 person‑years, respectively. The median patient age was 62 years, 68% were males, 37% had a preinjury severe systemic disease, 16% were under the influence of ethanol, 53% had multiple trauma, and 12% had concomitant cervical spinal cord injury (incomplete in 85% and complete in 15%). The most common trauma mechanisms were falls (57%), followed by bicycle injuries (12%), and four‑wheel motorized vehicle accidents (10%). The most common upper CS‑Fx was C2 odontoid Fx, while the most common subaxial Fx was facet joint Fx involving cervical level C6/C7. Treatment was external immobilization with a stiff neck collar alone in 65%, open surgical fixation in 26% (giving a 3.7/100,000 person‑years surgery rate), and no stabilization in 9%. The overall 90‑day mortality was 153/2153 (7.1%). Conclusions: This study provides an overview of the extent of the issue and patient complexity necessary for plan‑ ning the health‑care management and injury prevention of CS‑Fx. The typical CS‑Fx patient was an elderly male or female with significant comorbidities injured in a low‑energy trauma. The overall crude incidences of CS‑Fx and surgi‑ cal fixation of CS‑Fx in Southeast Norway were 14.9/100,000 person‑years and 3.7/100,000 person‑years, respectively. Keywords: Spinal fracture, Spinal cord injury, Cervical, Traumatic, Epidemiology, Population‑based

• Løke, Daniel; Andelic, Nada; Helseth, Eirik; Vassend, Olav Mandt; Andersson, Stein & Ponsford, Jennie L. [Show all 9 contributors for this article] (2022). Impact of Somatic Vulnerability, Psychosocial Robustness and Injury-Related Factors on Fatigue following Traumatic Brain Injury—A Cross-Sectional Study. Journal of Clinical Medicine. ISSN 2077-0383. 11(6), p. 1–19. doi: 10.3390/jcm11061733. Full text in Research Archive
• Hellstrøm, Torgeir; Andelic, Nada; Holthe, Øyvor; Helseth, Eirik; Server, Andrés & Eiklid, Kristin Louise [Show all 7 contributors for this article] (2022). APOE-ε4 Is Associated With Reduced Verbal Memory Performance and Higher Emotional, Cognitive, and Everyday Executive Function Symptoms Two Months After Mild Traumatic Brain Injury. Frontiers in Neurology. ISSN 1664-2295. 13, p. 1–9. doi: 10.3389/fneur.2022.735206. Full text in Research Archive
• Netteland, Dag Ferner; Mejlænder-Evjensvold, Magnus; Skaga, Nils Oddvar; Sandset, Else Charlotte; Aarhus, Mads & Helseth, Eirik (2021). Cerebral venous thrombosis in traumatic brain injury: A cause of secondary insults and added mortality. Journal of Neurosurgery. ISSN 0022-3085. 134(6), p. 1912–1920. doi: 10.3171/2020.4.JNS20511. Show summary

  OBJECTIVE Cerebral venous thrombosis (CVT) is increasingly recognized in traumatic brain injury (TBI), but its complications and effect on outcome remain undetermined. In this study, the authors characterize the complications and outcome effect of CVT in TBI patients. METHODS In a retrospective, case-control study of patients included in the Oslo University Hospital trauma registry and radiology registry from 2008 to 2014, the authors identified TBI patients with CVT (cases) and without CVT (controls). The groups were matched regarding Abbreviated Injury Scale 1990, update 1998 (AIS’98) head region severity score 3–6. Cases were identified by AIS’98 or ICD-10 code for CVT and CT or MR venography findings confirmed to be positive for CVT, whereas controls had no AIS’98 or ICD-10 code for CVT and CT venography or MR venography findings confirmed to be negative for CVT. All images were reviewed by a neuroradiologist. Rates of complications due to CVT were recorded, and mortality was assessed both unadjusted and in a multivariable logistic regression analysis adjusting for initial Glasgow Coma Scale score, Rotterdam CT score, and Injury Severity Score. Complications and mortality were also assessed in prespecified subgroup analysis according to CVT location and degree of occlusion from CVT. Lastly, mortality was assessed in an exploratory subgroup analysis according to the presence of complications from CVT. RESULTS The CVT group (73 patients) and control group (120 patients) were well matched regarding baseline characteristics. In the CVT group, 18% developed venous infarction, 11% developed intracerebral hemorrhage, and 19% developed edema, all representing complications secondary to CVT. Unadjusted 30-day mortality was 16% in the CVT group and 4% in the no-CVT group (p = 0.004); however, the difference was no longer significant in the adjusted analysis (OR 2.24, 95% CI 0.63–8.03; p = 0.215). Subgroup analysis by CVT location showed an association between CVT location and rate of complications and an unadjusted 30-day mortality of 50% for midline or bilateral CVT and 8% for unilateral CVT compared with 4% for no CVT (p < 0.001). The adjusted analysis showed a significantly higher mortality in the midline/ bilateral CVT group than in the no-CVT group (OR 8.41, 95% CI 1.56–45.25; p = 0.032). CONCLUSIONS There is a significant rate of complications from CVT in TBI patients, leading to secondary brain insults. The rate of complications is dependent on the anatomical location of the CVT, and midline and bilateral CVT is associated with an increased 30-day mortality in TBI patients. https://thejns.org/doi/abs/10.3171/2020.4.JNS20511 KEYWORDS cerebral venous thrombosis; traumatic brain injury; complications; mortality; outcome

• Yuh, Esther; Jain, Sonia; Sun, Xiaoying; Pisică, Dana; Harris, Mark H. & Taylor, Sabrina R. [Show all 56 contributors for this article] (2021). Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI. JAMA Neurology. ISSN 2168-6149. 78(9), p. 1137–1148. doi: 10.1001/jamaneurol.2021.2120. Full text in Research Archive Show summary

  Importance A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale–Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures Acute nonpenetrating head trauma. Main Outcomes and Measures Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

• Mikolic, Ana; Groeniger, Joost Oude; Zeldovich, Marina; Wilson, Lindsay; van Lennep, Jeanine Roeters & van Klaveren, David [Show all 51 contributors for this article] (2021). Explaining Outcome Differences between Men and Women following Mild Traumatic Brain Injury. Journal of Neurotrauma. ISSN 0897-7151. 38(23). doi: 10.1089/neu.2021.0116. Full text in Research Archive Show summary

  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.

• Riemann, Lennart; Voormolen, Daphne; Rauen, Katrin; Zweckberger, Klaus; Unterberg, Andreas & Younsi, Alexander [Show all 50 contributors for this article] (2021). Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 27(5), p. 538–547. doi: 10.3171/2020.9.PEDS20421.
• Ceyisakar, Iris; Huijben, Jilske A.; Maas, Andrew I. R.; Lingsma, Hester F.; van Leeuwen, Nikki & Andelic, Nada [Show all 49 contributors for this article] (2021). Can We Cluster ICU Treatment Strategies for Traumatic Brain Injury by Hospital Treatment Preferences? Neurocritical Care. ISSN 1541-6933. doi: 10.1007/s12028-021-01386-y. Full text in Research Archive
• Huijben, Jilske A.; Dixit, Abhishek; Stocchetti, Nino; Maas, Andrew I. R.; Lingsma, Hester F. & van der Jagt, Mathieu [Show all 55 contributors for this article] (2021). Use and impact of high intensity treatments in patients with traumatic brain injury across Europe: a CENTER-TBI analysis. Critical Care. ISSN 1364-8535. 25(78). doi: 10.1186/s13054-020-03370-y. Full text in Research Archive
• Citerio, Giuseppe; Robba, Chiara; Rebora, Paola; Petrosino, Matteo; Rossi, elenora & Malgeri, L [Show all 53 contributors for this article] (2021). Management of arterial partial pressure of carbon dioxide in the frst week after traumatic brain injury: results from the CENTER-TBI study. Intensive Care Medicine. ISSN 0342-4642. 47, p. 961–973. doi: 10.1007/s00134-021-06470-7. Full text in Research Archive
• Horton, lindsay; Rhodes, Jonathan; Menon, David K.; Maas, Andrew I. R.; Wilson, Lindsay & Andelic, Nada [Show all 48 contributors for this article] (2021). Questionnaires vs Interviews for the Assessment of Global Functional Outcomes After Traumatic Brain Injury. JAMA Network Open. ISSN 2574-3805. 4(11). Full text in Research Archive
• Wiegers, E; Lingsma, Hester F.; Huijben, Jilske A.; Cooper, David James; Citerio, Giuseppe & Frisvold, Shirin [Show all 53 contributors for this article] (2021). Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study. Lancet Neurology. ISSN 1474-4422. 20(8), p. 627–638. doi: 10.1016/S1474-4422(21)00162-9.
• van Veen, Ernest; Van Der Jagt, Mathieu; Citerio, Giuseppe; Stocchetti, Nino; Gommers, Diederik & Burdorf, Alex [Show all 51 contributors for this article] (2021). Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients: a CENTER-TBI study. Intensive Care Medicine. ISSN 0342-4642. 47, p. 1115–1129. doi: 10.1007/s00134-021-06484-1. Full text in Research Archive
• Gravesteijn, Benjamin; Sewalt, Charlie; Venema, Esmee; Nieboer, Daan; Steyerberg, Ewout W. & Andelic, Nada [Show all 49 contributors for this article] (2021). Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study. Journal of Neurotrauma. ISSN 0897-7151. 13(38), p. 1842–1857. doi: 10.1089/neu.2020.7218.
• Sewalt, Charlie; Gravesteijn, Benjamin; Menon, David; Lingsma, Hester F.; Maas, Andrew I. R. & Stocchetti, Nino [Show all 51 contributors for this article] (2021). Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury: a CENTER TBI study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. ISSN 1757-7241. 29(1), p. 1–11. doi: 10.1186/s13049-021-00930-1. Full text in Research Archive
• Böhm, Julia K.; Schaeben, Victoria; Schäfer, Nadine; Güting, Helge; Lefering, Rolf & Thorn, Sophie [Show all 52 contributors for this article] (2021). Extended Coagulation Profling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis. Neurocritical Care. ISSN 1541-6933. doi: 10.1007/s12028-021-01400-3. Full text in Research Archive Show summary

  Background 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. Methods Results from blood samples (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. Results 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. Conclusions 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.

• Skaga, Erlend; Skretteberg, Marthe Andrea; Johannesen, Tom Børge; Brandal, Petter; Vik-Mo, Einar O. & Helseth, Eirik [Show all 7 contributors for this article] (2021). Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: To whom do the results of the trials apply? Neuro-Oncology Advances (NOA). 3(1). doi: 10.1093/noajnl/vdab008. Full text in Research Archive Show summary

  Background The survival rates in population-based series of glioblastoma (GBM) differ substantially from those reported in clinical trials. This discrepancy may be attributed to that patients recruited to trials tend to be younger with better performance status. However, the proportion and characteristics of the patients in a population considered either eligible or ineligible for trials is unknown. The generalizability of trial results is therefore also uncertain. Methods Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012–2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM. Results We identified 512 patients. The median survival was 11.7 months. When we selected a potential trial population at the start of concurrent chemoradiotherapy (radiotherapy [RT]/ temozolomide [TMZ]) by the parameters age (18–70 y), passed surgery for a supratentorial GBM, Eastern Cooperative Oncology Group (ECOG) ≤2, normal hematologic, hepatic and renal function, and lack of severe comorbidity, 57% of the patients were excluded. Further filtering the patients who progressed during RT/TMZ and never completed RT/TMZ resulted in exclusion of 59% and 63% of the patients, respectively. The survival of patients potentially eligible for trials was significantly higher than of the patients not fulfilling trial eligibility criteria (P < .0001). Conclusions Patients considered eligible for phase III clinical trials represent a highly selected minority of patients in a real-world GBM population.

• RØNNING, PÅL ANDRE; Helseth, Eirik; Skaansar, Ola Fougner; Tverdal, Cathrine Buaas; Andelic, Nada & Bhatnagar, Rahul [Show all 11 contributors for this article] (2021). Impact of Preinjury Antithrombotic Therapy on 30-Day Mortality in Older Patients Hospitalized With Traumatic Brain Injury (TBI). Frontiers in Neurology. ISSN 1664-2295. doi: 10.3389/fneur.2021.650695. Full text in Research Archive
• Munkvold, Bodil Karoline Ravn; Solheim, Ole; Bartek, Jiri; Corell, Alba; De Dios, Eddie & Gulati, Sasha [Show all 27 contributors for this article] (2021). Variations in the management of diffuse low-grade gliomas - A Scandinavian multicenter study. Neuro-Oncology Practice. ISSN 2054-2577. 8(6), p. 706–717. doi: 10.1093/nop/npab054. Full text in Research Archive Show summary

  Background Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected “high-risk” patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems. Methods Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored. Results A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy. Conclusions Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.

• Wang, Biyao; Zeldovich, Marina; Rauen, Katrin; Wu, Yi-Jhen; Covic, Amra & Muller, Isabelle [Show all 50 contributors for this article] (2021). Longitudinal analyses of the reciprocity of depression and anxiety after traumatic brain injury and its clinical implications. Journal of Clinical Medicine. ISSN 2077-0383. 10(23). doi: 10.3390/jcm10235597. Full text in Research Archive
• Svendsen, Henrik Aasrum; Meling, Torstein Ragnar; Nygaard, Vigdis; Waagene, Stein; Russnes, Hege Elisabeth Giercksky & Juell, Siri [Show all 11 contributors for this article] (2021). Novel human melanoma brain metastasis models in athymic nude fox1^nu mice: Site-specific metastasis patterns reflecting their clinical origin. Cancer Medicine. ISSN 2045-7634. 10(23), p. 8604–8613. doi: 10.1002/cam4.4334. Full text in Research Archive
• Andersson, Helene; Jablonski, Greg Eigner; Nordahl, Stein Helge Glad; Nordfalk, Karl; Helseth, Eirik & Martens, Camilla [Show all 8 contributors for this article] (2021). The Risk of Benign Paroxysmal Positional Vertigo After Head Trauma. The Laryngoscope. ISSN 0023-852X. 132(2), p. 443–448. doi: 10.1002/lary.29851. Full text in Research Archive
• Rizvi, Syed Ali Mujtaba; Helseth, Eirik; Aarhus, Mads; Harr, Marianne Efskind; MIRZAMOHAMMADI, JALAL & RØNNING, PÅL ANDRE [Show all 8 contributors for this article] (2021). Favorable prognosis with nonsurgical management of type III acute odontoid fractures: a consecutive series of 212 patients. The spine journal. ISSN 1529-9430. 21(7), p. 1149–1158. doi: 10.1016/j.spinee.2021.02.003. Full text in Research Archive
• Tverdal, Cathrine Buaas; Andelic, Nada; Helseth, Eirik; Brunborg, Cathrine; RØNNING, PÅL ANDRE & Hellstrøm, Torgeir [Show all 8 contributors for this article] (2021). In the aftermath of acute hospitalization for traumatic brain injury: Factors associated with the direct pathway into specialized rehabilitation. Journal of Clinical Medicine. ISSN 2077-0383. 10(16), p. 1–14. doi: 10.3390/jcm10163577. Full text in Research Archive
• Andelic, Nada; Røe, Cecilie; Tenovuo, Olli; Azouvi, Philippe; Dawes, Helen & Majdan, Marek [Show all 56 contributors for this article] (2021). Unmet Rehabilitation Needs after Traumatic Brain Injury across Europe: Results from the CENTER-TBI Study. Journal of Clinical Medicine. ISSN 2077-0383. 10(5). doi: 10.3390/jcm10051035. Full text in Research Archive
• Rootwelt, Rebecca; Vik-Mo, Einar Osland; Yri, Olav Erich; Aass, Nina Kathrine; Kaasa, Stein & Skovlund, Eva [Show all 8 contributors for this article] (2021). Surgery for brain metastases – real-world prognostic factors’ association with survival. Acta Oncologica. ISSN 0284-186X. 60(9), p. 1161–1168. doi: 10.1080/0284186X.2021.1930150. Full text in Research Archive
• Hellstrøm, Torgeir; Andelic, Nada; de Lange, Ann-Marie Glasø; Helseth, Eirik; Eiklid, Kristin Louise & Westlye, Lars Tjelta (2021). Apolipoprotein ɛ4 Status and Brain Structure 12 Months after Mild Traumatic Injury: Brain Age Prediction Using Brain Morphometry and Diffusion Tensor Imaging. Journal of Clinical Medicine. ISSN 2077-0383. 10(3). doi: 10.3390/jcm10030418. Full text in Research Archive
• Robertsen, Annette; Helseth, Eirik & Førde, Reidun (2021). Inter-physician variability in strategies linked to treatment limitations after severe traumatic brain injury; proactivity or wait-and-see. BMC Medical Ethics. ISSN 1472-6939. 22(1). doi: 10.1186/s12910-021-00612-8. Full text in Research Archive
• Søberg, Helene Lundgaard; Moksnes, Håkon Øgreid; Anke, Audny; Røise, Olav; Røe, Ellen-Cecilie Treu & Aas, Eline [Show all 20 contributors for this article] (2021). Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study. JMIR Research Protocols. ISSN 1929-0748. 10(4), p. 1–10. doi: 10.2196/25980. Full text in Research Archive
• Borgen, Ida Maria Henriksen; Røe, Cecilie; Brunborg, Cathrine; Tenovuo, Olli; Azouvi, Philippe & Dawes, Helen [Show all 50 contributors for this article] (2021). Care transitions in the first 6 months following traumatic brain injury: Lessons from the CENTER-TBI study. Annals of Physical and Rehabilitation Medicine. ISSN 1877-0657. 64(6). doi: 10.1016/j.rehab.2020.10.009. Full text in Research Archive Show summary

  Background: No large international studies have investigated care transitions during or after acute hospitalisations for traumatic brain injury (TBI). Objectives: To characterise various TBI-care pathways and the number of associated transitions during the first 6 months after TBI and to assess the impact of these on functional TBI outcome controlled for demographic and injury-related factors. Methods: This was a cohort study of patients with TBI admitted to various trauma centres enrolled in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Number of transitions and specific care pathways were identified. Multiple logistic regression analyses were used to assess the impact of number of transitions and care pathways on functional outcome at 6 months post-injury as assessed by the Glasgow Outcome Scale-Extended (GOSE). Results: In total, 3133 patients survived the acute TBI-care pathway and had at least one documented in-hospital transition at 6-month follow-up. The median number of transitions was 3 (interquartile range 2-3). The number of transitions did not predict functional outcome at 6 months (odds ratio 1.08, 95% confidence interval 1.09-1.18; p = 0.063). A total of 378 different care pathways were identified; 8 were identical for at least 100 patients and characterized as "common pathways". Five of these common care pathways predicted better functional outcomes at 6 months, and the remaining 3 pathways were unrelated to outcome. In both models, increased age, violence as the cause of injury, pre-injury presence of systemic disease, both intracranial and overall injury severity, and regions of Southern/Eastern Europe were associated with unfavourable functional outcomes at 6 months. Conclusions: A high number of different and complex care pathways was found for patients with TBI, particularly those with severe injuries. This high number and variety of care pathway possibilities indicates a need for standardisation and development of "common data elements for TBI care pathways" for future studies.

• van Veen, Ernest; van der Jagt, Mathieu; Citerio, Guiseppe; Stocchetti, Nino; Epker, Jelle & Gommers, Diederik [Show all 50 contributors for this article] (2020). End-of-life practices in traumatic brain injury patients: Report of a questionnaire from the CENTER-TBI study. Journal of critical care. ISSN 0883-9441. 58, p. 78–88. doi: 10.1016/j.jcrc.2020.04.001. Full text in Research Archive
• Timmers, Marjolein; van Dijck, Jeroen T. J. M.; van Wijk, Roel P J; Legrand, Valerie; van Veen, Ernest & Maas, Andrew I.R. [Show all 50 contributors for this article] (2020). How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study. BMC Medical Ethics. ISSN 1472-6939. 21:36(1). doi: 10.1186/s12910-020-00480-8. Full text in Research Archive
• Mikolic, Ana; van Klaveren, David; Oude Groeniger, Joost; Wiegers, E; Lingsma, Hester F & Zeldovich, Marina [Show all 50 contributors for this article] (2020). Differences between Men and Women in Treatment and Outcome after Traumatic Brain Injury. Journal of Neurotrauma. ISSN 0897-7151. 38(2), p. 235–251. doi: 10.1089/neu.2020.7228. Full text in Research Archive
• Mikolic, Ana; Polinder, Suzanne; Steyerberg, Ewout W; Retel Helmrich, Isabel; Giacino, Joseph T. & Maas, Andrew I.R. [Show all 51 contributors for this article] (2020). Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury: External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study. Journal of Neurotrauma. ISSN 0897-7151. 38(2), p. 196–209. doi: 10.1089/neu.2020.7074. Full text in Research Archive
• Mathieu, Francois; Güting, Helge; Gravesteijn, Benjamin; Monteiro, Miguel; Glocker, Ben & Kornaropoulos, Evgenios [Show all 51 contributors for this article] (2020). Impact of Antithrombotic Agents on Radiological Lesion Progression in Acute Traumatic Brain Injury: A CENTER-TBI Propensity-Matched Cohort Analysis. Journal of Neurotrauma. ISSN 0897-7151. 37(19), p. 2069–2080. doi: 10.1089/neu.2019.6911.
• Gravesteijn, BY; Sewalt, Charlie; Stocchetti, Nino; Citerio, Giuseppe; Ercole, Ari & Lingsma, Hester F [Show all 54 contributors for this article] (2020). Prehospital Management of Traumatic Brain Injury across Europe: A CENTER-TBI Study. Prehospital Emergency Care. ISSN 1090-3127. doi: 10.1080/10903127.2020.1817210. Full text in Research Archive
• Dijkland, Simone; Retel Helmrich, Isabel; Nieboer, Daan; van der Jagt, Mathieu; Dippel, Diederik W.J. & Menon, David K [Show all 50 contributors for this article] (2020). Outcome Prediction after Moderate and Severe Traumatic Brain Injury: External Validation of Two Established Prognostic Models in 1742 European Patients. Journal of Neurotrauma. ISSN 0897-7151. doi: 10.1089/neu.2020.7300.
• Vande Vyvere, Thijs; De La Rosa, Ezequiel; Wilms, Guido; Nieboer, Daan; Steyerberg, Ewout & Maas, Andrew I.R. [Show all 51 contributors for this article] (2020). Prognostic Validation of the NINDS Common Data Elements for the Radiologic Reporting of Acute Traumatic Brain Injuries: A CENTER-TBI Study. Journal of Neurotrauma. ISSN 0897-7151. 37(11), p. 1269–1282. doi: 10.1089/neu.2019.6710.
• Huijbers, Jilske; Wiegers, E; Lingsma, Hester F; Citerio, Giuseppe; Maas, Andrew I.R. & Menon, David K [Show all 51 contributors for this article] (2020). Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis. Intensive Care Medicine. ISSN 0342-4642. 46(5), p. 995–1004. doi: 10.1007/s00134-020-05965-z. Full text in Research Archive Show summary

  Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01). Conclusions: Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources.

• Czeiter, Endre; Amrein, Krisztina; Gravesteijn, BY; Lecky, Fiona; Menon, David K & Mondello, Stefania [Show all 50 contributors for this article] (2020). Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. ISSN 2352-3964. 56. doi: 10.1016/j.ebiom.2020.102785. Full text in Research Archive Show summary

  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.

• van Wijk, Roel P J; van Dijck, Jeroen T. J. M.; Timmers, Marjolein; van Veen, Ernest; Citerio, Giuseppe & Lingsma, Hester F [Show all 50 contributors for this article] (2020). Informed consent procedures in patients with an acute inability to provide informed consent: Policy and practice in the CENTER-TBI study. Journal of critical care. ISSN 0883-9441. 59(15), p. 6–15. doi: 10.1016/j.jcrc.2020.05.004. Show summary

  Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.

• Riemann, Lennart; Zweckberger, Klaus; Unterberg, Andreas; El Damaty,, Ahmed; Younsi, Alexander & Andelic, Nada [Show all 50 contributors for this article] (2020). Injury Causes and Severity in Pediatric Traumatic Brain Injury Patients Admitted to the Ward or Intensive Care Unit: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study. Frontiers in Neurology. ISSN 1664-2295. 11. doi: 10.3389/fneur.2020.00345. Full text in Research Archive Show summary

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

• Wilson, Lindsay; Horton, Lindsay; Kunzmann, Kevin; Sahakian, Barbara J.; Newcombe, Virginia & Stamatakis, E [Show all 50 contributors for this article] (2020). Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury . Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. doi: 10.1136/jnnp-2020-324492. Full text in Research Archive Show summary

  Objective: 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. Methods: 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. Results: Overall effect sizes were small to medium, and greatest for tests involving processing speed (ηp2 0.057–0.067) and learning and memory (ηp2 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 (ηp2 0.111), mental health (ηp2 0.131) and physical health (ηp2 0.252). Conclusions: 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.

• Tønne, Elin; Due-Tønnessen, Bernt Johan; Wiig, Ulrikke Straume; Stadheim, Barbro; Meling, Torstein Ragnar & Helseth, Eirik [Show all 7 contributors for this article] (2020). Epidemiology of craniosynostosis in Norway. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 26(1), p. 68–75. doi: 10.3171/2020.1.PEDS2051. Full text in Research Archive
• Böhm, JK; Güting, Helge; Thorn, S; Schäfer, Nadine; Rambach, V & Schöchl, Herbert [Show all 50 contributors for this article] (2020). Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI): A CENTER-TBI Analysis. Neurocritical Care. ISSN 1541-6933. doi: 10.1007/s12028-020-01151-7. Full text in Research Archive Show summary

  Background: 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. Methods: 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. Results: 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. Conclusion: Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.

• Rizvi, Syed Ali Mujtaba; Helseth, Eirik; Harr, Marianne Efskind; MIRZAMOHAMMADI, JALAL; Rønning, Pål Andre & Mejlænder-Evjensvold, Magnus [Show all 7 contributors for this article] (2020). Management and long-term outcome of type II acute odontoid fractures: a population-based consecutive series of 282 patients. The spine journal. ISSN 1529-9430. p. 1–11. doi: 10.1016/j.spinee.2020.11.012. Full text in Research Archive
• Tønne, Elin; Due-Tønnessen, Bernt Johan; Mero, Inger-Lise; Wiig, Ulrikke Straume; Kulseth, Mari Ann & Vigeland, Magnus Dehli [Show all 12 contributors for this article] (2020). Benefits of clinical criteria and high-throughput sequencing for diagnosing children with syndromic craniosynostosis. European Journal of Human Genetics. ISSN 1018-4813. 00(0), p. 1–10. doi: 10.1038/s41431-020-00788-4. Full text in Research Archive Show summary

  An accurate diagnosis of syndromic craniosynostosis (CS) is important for personalized treatment, surveillance, and genetic counselling. We describe detailed clinical criteria for syndromic CS and the distribution of genetic diagnoses within the cohort. The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve individuals with syndromic CS born between 1 January 2002 and 30 June 2019. All individuals were assessed by a clinical geneticist and classified using defined clinical criteria. A stepwise approach consisting of single-gene analysis, comparative genomic hybridization (aCGH), and exome-based high-throughput sequencing, first filtering for 72 genes associated with syndromic CS, followed by an extended trio-based panel of 1570 genes were offered to all syndromic CS cases. A total of 381 individuals were registered with CS, of whom 104 (27%) were clinically classified as syndromic CS. Using the single-gene analysis, aCGH, and custom-designed panel, a genetic diagnosis was confirmed in 73% of the individuals (n = 94). The diagnostic yield increased to 84% after adding the results from the extended trio-based panel. Common causes of syndromic CS were found in 53 individuals (56%), whereas 26 (28%) had other genetic syndromes, including 17 individuals with syndromes not commonly associated with CS. Only 15 individuals (16%) had negative genetic analyses. Using the defined combination of clinical criteria, we detected among the highest numbers of syndromic CS cases reported, confirmed by a high genetic diagnostic yield of 84%. The observed genetic heterogeneity encourages a broad genetic approach in diagnosing syndromic CS.

• Døving, Mats; Galteland, Pål; Eken, Torsten; Sehic, Amer; Utheim, Tor Paaske & Skaga, Nils Oddvar [Show all 8 contributors for this article] (2020). Dentoalveolar injuries, bicycling accidents and helmet use in patients referred to a Norwegian Trauma Centre: A 12‐year prospective study. Dental Traumatology. ISSN 1600-4469. p. 1–7. doi: 10.1111/edt.12627. Full text in Research Archive
• Næss, Ingar; Galteland, Pål; Skaga, Nils Oddvar; Eken, Torsten; Helseth, Eirik & Ramm-Pettersen, Jon-Terje (2020). The number of patients hospitalized with bicycle injuries is increasing - A cry for better road safety. Accident Analysis and Prevention. ISSN 0001-4575. 148:105836, p. 1–7. doi: 10.1016/j.aap.2020.105836. Full text in Research Archive
• Rizvi, Syed Ali Mujtaba; Helseth, Eirik; Rønning, Pål André; MIRZAMOHAMMADI, JALAL; Harr, Marianne Efskind & Brommeland, Tor [Show all 13 contributors for this article] (2020). Odontoid fractures: impact of age and comorbidities on surgical decision making. BMC Surgery. ISSN 1471-2482. 20(236), p. 1–10. doi: 10.1186/s12893-020-00893-7.
• Skansaar, Ola Fougner; Tverdal, Cathrine Buaas; Rønning, Pål André; Skogen, Karoline; Brommeland, Tor & Røise, Olav [Show all 9 contributors for this article] (2020). Traumatic brain injury—the effects of patient age on treatment intensity and mortality. BMC Neurology. ISSN 1471-2377. 20:376, p. 1–10. doi: 10.1186/s12883-020-01943-6. Full text in Research Archive
• Robba, Chiara; Rebora, Paola; Banzato, Erika; Wiegers, E; Stocchetti, Nino & Menon, David [Show all 50 contributors for this article] (2020). Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury: Analysis of a Large, Multicenter, Prospective, Observational Longitudinal Study . Chest. ISSN 0012-3692. 158(6), p. 2292–2303. doi: 10.1016/j.chest.2020.06.064.

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• Storvig, Gøril; Sødal, Hild Flatmark; Robinson, Hilde Stendal; Tverdal, Cathrine Buaas; Helseth, Eirik & Taubøll, Erik (2022). Tidlig post-traumatiske epileptiske anfall hos pasienter med traumatisk hjerneskade.
• Søberg, Helene L.; Moksnes, Håkon Øgreid; Anke, Audny Gabriele Wagner; Røise, Olav; Røe, Cecilie & Aas, Eline [Show all 20 contributors for this article] (2022). Erratum: Rehabilitation Needs, Service Provision, and Costs in the First Year following Traumatic Injuries: Protocol for a Prospective Cohort Study ((JMIR Res Protoc (2021) 10: 4 (e25980) DOI: 10.2196/25980). JMIR Research Protocols. ISSN 1929-0748. 11(3). doi: 10.2196/37723.
• Weber, Clemens; Myrseth, Erling; Kurz, Kathinka Dæhli; Frič, Radek; Ingebrigtsen, Tor & Helseth, Eirik [Show all 8 contributors for this article] (2021). MR av nakke i vektbærende stilling? Tidsskrift for Den norske legeforening. ISSN 0029-2001. 141(11), p. 1–3. doi: 10.4045/tidsskr.21.0284.
• Andelic, Nada; Røe, Cecilie; Brunborg, Cathrine; Zeldovich, Marina; Løvstad, Marianne & Løke, Daniel [Show all 19 contributors for this article] (2020). Correction to: Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study (Journal of Neurology, (2020), 10.1007/s00415-020-10022-2). Journal of Neurology. ISSN 0340-5354. 268, p. 74–76. doi: 10.1007/s00415-020-10174-1.
• Sundstrøm, Terje; Helseth, Eirik & Wester, Knut (2020). Subacute Surgery in Neurointensive Care. In: Sundstrøm T., Grände PO., Luoto T., Rosenlund C., Undén J., Wester K. (eds) Management of Severe Traumatic Brain Injury. Springer, Cham. In Sundstrøm, Terje; Grände, Per-Olof; Luoto, Teemu; Rosenlund, Christina; Undén, Johan & Wester, Knut Gustav (Ed.), Management of Severe Traumatic Brain Injury Evidence, Tricks, and Pitfalls. Springer. ISSN 978-3-030-39383-0. doi: 10.1007/978-3-030-39383-0_57.
• Sundstrøm, Terje; Helseth, Eirik & Wester, Knut (2020). Surgical Management of Penetrating Brain Injuries. In: Sundstrøm T., Grände PO., Luoto T., Rosenlund C., Undén J., Wester K. (eds) Management of Severe Traumatic Brain Injury. Springer, Cham. . In Sundstrøm, Terje; Grände, Per-Olof; Luoto, Teemu; Rosenlund, Christina; Undén, Johan & Wester, Knut Gustav (Ed.), Management of Severe Traumatic Brain Injury Evidence, Tricks, and Pitfalls. Springer. ISSN 978-3-030-39383-0. doi: 10.1007/978-3-030-39383-0_25.
• Sundstrøm, Terje; Helseth, Eirik & Wester, Knut (2020). Surgical Management of Traumatic Intracranial Haematomas. In: Sundstrøm T., Grände PO., Luoto T., Rosenlund C., Undén J., Wester K. (eds) Management of Severe Traumatic Brain Injury. Springer, Cham. . In Sundstrøm, Terje; Grände, Per-Olof; Luoto, Teemu; Rosenlund, Christina; Undén, Johan & Wester, Knut Gustav (Ed.), Management of Severe Traumatic Brain Injury Evidence, Tricks, and Pitfalls. Springer. ISSN 978-3-030-39383-0. doi: 10.1007/978-3-030-39383-0_24.
• Sundstrøm, Terje; Helseth, Eirik & Wester, Knut (2020). Basic Trauma Craniotomy. In: Sundstrøm T., Grände PO., Luoto T., Rosenlund C., Undén J., Wester K. (eds) Management of Severe Traumatic Brain Injury. Springer, Cham. . In Sundstrøm, Terje; Grände, Per-Olof; Luoto, Teemu; Rosenlund, Christina; Undén, Johan & Wester, Knut Gustav (Ed.), Management of Severe Traumatic Brain Injury Evidence, Tricks, and Pitfalls. Springer. ISSN 978-3-030-39383-0. doi: 10.1007/978-3-030-39383-0_23.

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