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).

No abstract

Background and Purpose-ABC/2 is still widely accepted for volume estimations in spontaneous intracerebral hemorrhage (ICH) despite known limitations, which potentially accounts for controversial outcome-study results. The aim of this study was to establish and validate an automatic segmentation algorithm, allowing for quick and accurate quantification of ICH. Methods-A segmentation algorithm implementing first-and second-order statistics, texture, and threshold features was trained on manual segmentations with a random-forest methodology. Quantitative data of the algorithm, manual segmentations, and ABC/2 were evaluated for agreement in a study sample (n=28) and validated in an independent sample not used for algorithm training (n=30). Results-ABC/2 volumes were significantly larger compared with either manual or algorithm values, whereas no significant differences were found between the latter (P<0.0001; Friedman+Dunn's multiple comparison

Eps8 controls actin dynamics directly through its barbed end capping and actin-bundling activity, and indirectly by regulating Rac-activation when engaged into a trimeric complex with Eps8- Abi1-Sos1. Recently, Eps8 has been associated with promotion of various solid malignancies, but neither its mechanisms of action nor its regulation in cancer cells have been elucidated. Here, we report a novel association of Eps8 with the late endosomal/lysosomal compartment, which is independent from actin polymerization and specifically occurs in cancer cells. Endogenous Eps8 localized to large vesicular lysosomal structures in metastatic pancreatic cancer cell lines, such as AsPC-1 and Capan-1 that display high Eps8 levels. Additionally, ectopic expression of Eps8 increased the size of lysosomes. Structure–function analysis revealed that the region encompassing the amino acids 184–535 of Eps8 was sufficient to mediate lysosomal recruitment. Notably, this fragment harbors two KFERQ-like motifs required for chaperone-mediated autophagy (CMA). Furthermore, Eps8 co-immunoprecipitated with Hsc70 and LAMP-2, which are key elements for the CMA degradative pathway. Consistently, in vitro, a significant fraction of Eps8 bound to (11.9± 5.1%) and was incorporated into (5.3± 6.5%) lysosomes. Additionally, Eps8 binding to lysosomes was competed by other known CMA-substrates. Fluorescence recovery after photobleaching revealed that Eps8 recruitment to the lysosomal membrane was highly dynamic. Collectively, these results indicate that Eps8 in certain human cancer cells specifically localizes to lysosomes, and is directed to CMA. These results open a new field for the investigation of how Eps8 is regulated and contributes to tumor promotion in human cancers

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 Ն5) 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 ). 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. C...

OBJECTIVE In this analysis, the authors sought to identify variables triggering an additional resection (AR) and determining residual intraoperative tumor volume in 1.5-T intraoperative MRI (iMRI)-guided glioma resections. METHODS A consecutive case series of 224 supratentorial glioma resections (WHO Grades I–IV) from a prospective iMRI registry (inclusion dates January 2011–April 2013) was examined with univariate and multiple regression models including volumetric data, tumor-related, and surgeon-related factors. The surgeon's expectation of an AR, in response to a questionnaire completed prior to iMRI, was evaluated using contingency analysis. A machine-learning prediction model was applied to consider if anticipation of intraoperative findings permits preoperative identification of ideal iMRI cases. RESULTS An AR was performed in 70% of cases after iMRI, but did not translate into an accumulated risk for neurological morbidity after surgery (p = 0.77 for deficits in cases with AR vs no AR). New severe persistent deficits occurred in 6.7% of patients. Initial tumor volume determined frequency of ARs and was independently correlated with larger tumor remnants delineated on iMRI (p < 0.0001). Larger iMRI volume was further associated with eloquent location (p = 0.010) and recurrent tumors (p < 0.0001), and with WHO grade (p = 0.0113). Greater surgical experience had no significant influence on the course of surgery. The surgeon's capability of ruling out an AR prior to iMRI turned out to incorporate guesswork (negative predictive value 43.6%). In a prediction model, AR could only be anticipated with 65% accuracy after integration of confounding variables. CONCLUSIONS Routine use of iMRI in glioma surgery is a safe and reliable method for resection guidance and is characterized by frequent ARs after scanning. Tumor-related factors were identified that influenced the course of surgery and intraoperative decision-making, and iMRI had a common value for surgeons of all experience levels. Commonly, the subjective intraoperative impression of the extent of resection had to be revised after iMRI review, which underscores the manifold potential of iMRI guidance. In combination with the failure to identify ideal iMRI cases preoperatively, this study supports a generous, tumor-oriented rather than surgeon-oriented indication for iMRI in glioma surgery.

Purpose The incidence of acute subdural hematomas (aSDH) is rising. However, beneficial effects of surgery for the oldest aSDH patients remain unclear. We hence describe the postoperative outcome of octa- and nonagenarians with aSDH in comparison to a younger patient cohort. Methods Patients aged ≥ 80 years surgically treated for traumatic aSDH at a single institution between 2006 and 2016 were retrospectively reviewed. Clinical and imaging variables were assessed, and univariate analysis was performed to identify factors predicting outcome at discharge. Results were compared to a cohort of younger aSDH patients and statistical analysis was performed. Long-term outcome was prospectively evaluated with the GOSE and QOLIBRI. Results 27 aSDH patients aged ≥ 80 years were identified. On admission, 41% were in a comatose state and in-hospital mortality was 33%. At discharge, 22% had a favorable outcome (GOS 4 + 5). In univariate statistical analysis, better neurological status (GCS > 8), ≤ 1 comorbidity and smaller aSDH volumes were significant predictors for a favorable outcome. Comparison to 27 younger aSDH patients revealed significant differences in the prevalence of comorbidities and antithrombotics. At long-term follow-up, quality of life of aSDH patients was reduced (median QOLIBRI 54%). Conclusion Outcome after surgical treatment of aSDH in octa- and nonagenarians is not detrimental per se. Predictors for a favorable outcome are a non-comatose state on admission (GCS > 8), ≤ 1 preexisting comorbidity and a lower aSDH volume in patients aged ≥ 80 years. In individual patients, surgical evacuation of aSDH might remain a treatment option even in high ages.