Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Variation in neurosurgical management of traumatic brain injury

Funding/sponsors This study was funded by the European Union Seventh Framework Program (grant 602150) for Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Hersenstichting Nederland (Dutch Brain Foundation, grant PS2014-06) for The Dutch Neurotraumatology Quality Registry (Net-QuRe). There is no industry affiliation. 53 Institute of Medical Psychology and Medical Sociology, Universit\u00E4tsmedizin G\u00F6ttingen, G\u00F6ttingen, Germany. 54 Oxford University Hospitals NHS Trust, Oxford, UK. 55 Department of Neurosurgery, University of Pecs and MTA-PTE Clinical Neuroscience MR Research Group and Janos Szentagothai Research Centre, University of Pecs, Hungarian Brain Research Program (Grant No. KTIA 13 NAP-A-II/8), Pecs, Hungary. 56Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, UK. 57 Intensive Care Unit, CHR Citadelle, Li\u00E8ge, Belgium. 58 Intensive Care Unit, CHU, Li\u00E8ge, Belgium. 59 Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK. 60 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium. 61 Department of Anesthesia & Intensive Care, Maggiore Della Carit\u00E0 Hospital, Novara, Italy. 62 Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium. 63 Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands and Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands. 64 Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 65 Department of Neurology, Erasmus MC, Rotterdam, the Netherlands. 66 Division of Anaesthesia, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, UK. 67 Neurologie, Neurochirurgie und Psychiatrie, Charit\u00E9 \u2013 Universit\u00E4tsmedizin Berlin, Berlin, Germany. 68 Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. 69Department of Anaesthesiology and Intensive Therapy, University of P\u00E9cs, P\u00E9cs, Hungary. 70 Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark. 71National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand. 72 Department of Medicine, Azienda Ospedaliera Universit\u00E0 di Padova, Padova, Italy. 73 Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway. 74 Department of Neurosurgery, Hadassah-hebrew University Medical center, Jerusalem, Israel. 75 Fundaci\u00F3n Instituto Valenciano de Neurorrehabilitaci\u00F3n (FIVAN), Valencia, Spain. 76Department of Neurosurgery, Shanghai Renji hospital, Shanghai Jiaotong University/school of medicine, Shanghai, China. 89National Institute for Stroke & Applied Neurosciences of the AUT University, Auckland, New Zealand. 90Rehabilitation and Brain Trauma, Turku University Central Hospital and University of Turku, Turku, Finland. 91Helsinki University Central Hospital. 92Hungarian Brain Research Program - Grant No. KTIA 13 NAP-A-II/8, University of P\u00E9cs, P\u00E9cs, Hungary. 93Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 94Department of Psichiatry, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. 95Cyclotron Research Center, University of Li\u00E8ge, Li\u00E8ge, Belgium. 96Emergency Medicine Research in Sheffield, Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK. 97Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany. 98VP Global Project Management CNS, ICON, Paris, France. 99Department of Neurosurgery, Rambam Medical Center, Haifa, Israel. 100Department of Anesthesiology & Intensive Care, University Hospitals Southhampton NHS Trust, Southhampton, UK. 101icoMetrix NV, Leuven, Belgium. 102Cambridge University Hospitals, Cambridge, UK. 103Cologne-Merheim Medical Center (CMMC), Department of Traumatology, Orthopedic Surgery and Sportmedicine, Witten/Herdecke University, Cologne, Germany. 104Centrum f\u00FCr Schlaganfallforschung, Charit\u00E9 \u2013 Universit\u00E4tsmedizin Berlin, Berlin, Germany. 105Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK. 106Department of Neurological Surgery, University of California, San Francisco, California, USA. 107Department of Neurosurgery, CHU, Li\u00E8ge, Belgium. 108Department of Neurosurgery, The Walton centre NHS Foundation Trust, Liverpool, UK. 109Department of Medical Genetics, University of P\u00E9cs, P\u00E9cs, Hungary. 110National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia. 111Department Health and Prevention, University Greifswald, Greifswald, Germany. 112Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania. 113Centre Hospitalier Universitaire Vaudois. 114Department of Intensive Care, Elisabeth-Tweesteden Ziekenhuis, Tilburg, the Netherlands.Peer-reviewe

Effect of frailty on 6-month outcome after traumatic brain injury:a multicentre cohort study with external validation

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p&lt;0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03–1·06, p&lt;0·0001) compared with those admitted to the intensive care unit (1·02, 1·01–1·03 p&lt;0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0–0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03–1·08; p&lt;0·0001), but not in those admitted to the intensive care unit (1·01, 0·99–1·03; p=0·43). Interpretation: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury. Funding: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS–TRACK-TBI, US Department of Defense.</p

High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

International audienc

Correction: High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

status: Published onlin

Parsimonious immune-response endotypes and global outcome in patients with traumatic brain injuryResearch in context

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke

Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohortsResearch in context

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p < 0.001, I2 = 20.8%]. Although the MDD-PRS increased the risk of depression after TBI, it did not reach significance in the individual cohorts. However, in a combined analysis, the risk was significantly elevated with a pooled OR of 1.26 [95% CI 1.03–1.53, p = 0.02, I2 = 0%]. The addition of PRSs improved the proportion of outcome variance explained in the two study cohorts from 19.5% and 30.3% to 21.6% and 34.0% for PTSD; and from 11.0% and 22.5% to 12.8% and 22.6% for depression. Patients in the highest cognate PRS quintile had increased odds of 3.16 [95% CI 1.80–5.55] and 2.03 [95% CI 1.04–3.94] of developing PTSD or depression compared to the lowest quintile, respectively. Interpretation: Associations of PRSs with PTSD and depression following TBI are not disorder-specific. However, the overlap between MDD-PRS and depression following TBI is less robust compared to PTSD-PRS and PTSD. PRSs could improve risk prediction, and permit enrichment for interventional trials. Funding: This study was supported by funding by an FP7 grant from the European Union, Hannelore Kohl Stiftung, Integra LifeSciences Corporation, NeuroTrauma Sciences, US National Institutes of Health, US Department of Defense, National Football League Advisory Board, US Department of Energy, and One Mind