A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator

In November 2017, the Lancet Neurology Commission on Traumatic Brain Injury (TBI) highlighted existing deficiencies in epidemiology, patient characterization, identifying best practice, outcome assessment, and evidence generation. The Commission concluded that C needed to address deficiencies in prevention , and made a recommendation for large collaborative studies which could provide the framework for precision medicine and comparative effectiveness research (CER).

In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22), moderate (moTBI; n = 14) or mild TBI (mTBI; n = 108) according to Glasgow Coma Scale. The control group (n = 28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23), moTBI (n = 7), mTBI (n = 37) patients and controls (n = 27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

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Our aim was to create simple and largely scalable machine learning-based algorithms that could predict mortality in a real-time fashion during intensive care after traumatic brain injury. We performed an observational multicenter study including adult TBI patients that were monitored for intracranial pressure (ICP) for at least 24 h in three ICUs. We used machine learning-based logistic regression modeling to create two algorithms (based on ICP, mean arterial pressure [MAP], cerebral perfusion pressure [CPP] and Glasgow Coma Scale [GCS]) to predict 30-day mortality. We used a stratified cross-validation technique for internal validation. Of 472 included patients, 92 patients (19%) died within 30 days. Following cross-validation, the ICP-MAP-CPP algorithm’s area under the receiver operating characteristic curve (AUC) increased from 0.67 (95% confidence interval [CI] 0.60–0.74) on day 1 to 0.81 (95% CI 0.75–0.87) on day 5. The ICP-MAP-CPP-GCS algorithm’s AUC increased from 0.72 (95% CI 0.64–0.78) on day 1 to 0.84 (95% CI 0.78–0.90) on day 5. Algorithm misclassification was seen among patients undergoing decompressive craniectomy. In conclusion, we present a new concept of dynamic prognostication for patients with TBI treated in the ICU. Our simple algorithms, based on only three and four main variables, discriminated between survivors and non-survivors with accuracies up to 81% and 84%. These open-sourced simple algorithms can likely be further developed, also in low and middle-income countries.

GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities.

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