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Abstract Outcome after traumatic brain injury (TBI) is typically assessed using the Glasgow outcome scale extended (GOSE) with levels from 1 (death) to 8 (upper good recovery). Outcome prediction has classically been dichotomized into either dead/alive or favorable/unfavorable outcome. Binary outcome prediction models limit the possibility of detecting subtle yet significant improvements. We set out to explore different machine learning methods with the purpose of mapping their predictions to the full 8 grade scale GOSE following TBI. The models were set up using the variables: age, GCS-motor score, pupillary reaction, and Marshall CT score. For model setup and internal validation, a total of 866 patients could be included. For external validation, a cohort of 369 patients were included from Leuven, Belgium, and a cohort of 573 patients from the US multi-center ProTECT III study. Our findings indicate that proportional odds logistic regression (POLR), random forest regression, and a neural network model achieved accuracy values of 0.3–0.35 when applied to internal data, compared to the random baseline which is 0.125 for eight categories. The models demonstrated satisfactory performance during external validation in the data from Leuven, however, their performance were not satisfactory when applied to the ProTECT III dataset.

How to accurately design a personalized matching implant that can induce skull regeneration is the focus of current research. However, the design space for the porous structure of implants is extensive, and the mapping relationships between these structures and their mechanical and osteogenic properties are complex. At present, the forward design of skull implants mainly relies on expert experience, leading to high cost and a lengthy process, while the existing inverse design approaches face challenges due to data dependence and manufacturing process errors. This study presents an efficient inverse design method for personalized multilevel structures of skull implants using a machine learning pipeline composed of a finite element method, topological optimization, and neural networks. Based on the mechanical response of the human body falls, this method can tailor multi-level structures for implants in various defect positions. The results show that the proposed method establishes a bidirectional relationship between topological parameters and mechanical properties, enabling the customization of mechanical behavior at low computational cost while accounting for manufacturing errors in the 3D printing process. Additionally, the design results are also mutually consistent with analytical relationships between lattice parameters and the elastic modulus obtained from experiments and finite element simulations. Thus, this study provides a general and practical approach to rapidly design skull osteoinductive implants. [ABSTRACT FROM AUTHOR]

Purpose of Review: Critically ill children are at risk of neurologic dysfunction and acquiring primary and secondary brain injury. Close monitoring of cerebral function is crucial to prevent, detect, and treat these complications., Recent Findings: A variety of neuromonitoring modalities are currently used in pediatric and neonatal ICUs. These include noninvasive modalities, such as electroencephalography, transcranial Doppler, and near-infrared spectroscopy, as well as invasive methods including intracranial pressure monitoring, brain tissue oxygen measurement, and cerebral microdialysis. Each modality offers unique insights into neurologic function, cerebral circulation, or metabolism to support individualized neurologic care based on a patient's own physiology. Utilization of these modalities in ICUs results in reduced neurologic injury and mortality and improved neurodevelopmental outcomes., Summary: Monitoring of neurologic function can significantly improve care of critically ill children. Additional research is needed to establish normative values in pediatric patients and to standardize the use of these modalities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) is a major global health problem that disproportionally affects low- and middle-income countries. The needs for patients with TBI therefore may differ between levels of national development. We aimed to describe differences in epidemiology and acute care provision of TBI between India and Europe., Methods: We used data from two prospective observational registry studies - the Collaborative Indian NeuroTrauma Effectiveness Research in TBI (CINTER-TBI) and the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI), which included TBI patients with an indication for brain CT-scan presenting to 65 centres across Europe and Israel and two trauma centres in India. We performed descriptive analyses of demographic, injury, and treatment characteristics and used random-effects logistic regression with covariate adjustment to examine the likelihood of acute neurosurgical interventions and in-hospital mortality., Results: We included 22 849 patients from CENTER-TBI and 3904 from CINTER-TBI. The median age in Europe was 55 years (IQR = 32-76) compared to 27 years (IQR = 18-40) in India. The most common cause of TBI in Europe were falls (n = 12150 (53%), while traffic incidents predominated in India (n = 2130 (55%)). The proportion of patients with severe TBI was higher in India (n = 867 (22%)) than in Europe (n = 1661 (7%). Professional pre-hospital care involving ambulance service was utilised by three-fourths (n = 17203 (75%)) of European and less than a one-tenth (n = 224 (6%)) of Indian patients in our sample. Patients with severe TBI were more likely to undergo surgical contusion/haematoma evacuation in India compared to Europe (OR = 2.0; 95% CI = 1.7-2.5) and Indian patients had higher odds of undergoing intracranial pressure monitor placement (OR = 2.3; 95% CI = 2.0-2.7). A primary decompressive craniectomy was likewise more often performed in the Indian cohort (OR = 5.1; 95% CI = 3.5-7.5). Discharge destinations in Europe included rehabilitation centres (n = 1261 (6%)) or nursing homes (n = 1208 (5%)), which was rarely the case in India (n = 13 (0%) and n = 9 (0%), respectively)., Conclusions: Substantial disparities between India and Europe exist along the neurotrauma care chain, with both systems being likely to face unique features and challenges in the future., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Traumatic brain injury (TBI) can come with long term consequences for functional outcome that can complicate return to work., Objectives: This study aims to make accurate patient-specific predictions on one-year return to work after TBI using machine learning algorithms. Within this process, specific research questions were defined: 1 How can we make accurate predictions on employment outcome, and does this require follow-up data beyond hospitalization? 2 Which predictors are required to make accurate predictions? 3 Are predictions accurate enough for use in clinical practice?, Methods: This study used the core CENTER-TBI observational cohort dataset, collected across 18 European countries between 2014 and 2017. Hospitalized patients with sufficient follow-up data were selected for the current analysis (N = 586). Data regarding hospital stay and follow-up until three months post-injury were used to predict return to work after one year. Three distinct algorithms were used to predict employment outcomes: elastic net logistic regression, random forest and gradient boosting. Finally, a reduced model and corresponding ROC-curve was created., Results: Full models without follow-up achieved an area under the curve (AUC) of about 81 %, which increased up to 88 % with follow-up data. A reduced model with five predictors achieved similar results with an AUC of 90 %., Conclusion: The addition of three-month follow-up data causes a notable increase in model performance. The reduced model - containing Glasgow Outcome Scale Extended, pre-injury job class, pre-injury employment status, length of stay and age - matched the predictive performance of the full models. Accurate predictions on post-TBI vocational outcomes contribute to realistic prognosis and goal setting, targeting the right interventions to the right patients., (Copyright © 2024. Published by Elsevier Inc.)

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., Competing Interests: Declaration of interests CENTER-TBI was funded by the European Commission (EC grant 602,150) which was part of its 7th Framework Programme (FP7) for research, Hannelore Kohl Stiftung (Germany); Integra LifeSciences Corporation (USA); OneMind (USA); NeuroTrauma Sciences LLC (USA). The research reported in this manuscript also made use of resources provided by the TBI-REPORTER Project, supported by a multi-funder consortium (UK Research and Innovation; National institute for Health and Care Research UK; UK Department of Health and Social Care; UK Ministry of Defence, and Alzheimer’s Research UK). The TRACK-TBI consortium was supported by US Department of Defense (TBI Endpoints Development Initiative (Grant No. W81XWH-14-2-0176)); US Department of Defense (TRACK-TBI Precision Medicine (Grant No. W81XWH-18-2-0042)); US Department of Defense/MTEC (TRACK-TBI NETWORK (Grant No. W81XWH-15-9-0001)); NIH-NINDS (TRACK-TBI (Grant No.U01NS086090)); National Football League Scientific Advisory Board (TRACK-TBI LONGITUDINAL); United States Department of Energy (funding for a precision medicine collaboration); NeuroTrauma Sciences LLC (funding for TRACK-TBI data curation); One Mind (funding for TRACK-TBI patients stipends and support to clinical sites). KKWW is a shareholder of Gryphon Bio Inc. AH reports grants from the Medical Research Council, UK; fees from Coroner, Civil Courts UK and Cambridge Leadership Forum unrelated to this manuscript; travel grants from the University of Pennsylvania; membership of the BONANZA trial data safety monitoring board; involvement with the National Neurosurgical Audit programme and Holomedicine Association, both unpaid. ERZ reports membership of the TBI-Reporter Advisory Board, InTBIR executive committee and is Vice President of the European Neuotrauma Organization, all are unpaid. OT reports grants from the Sigrid Juselius Foundation, unrelated to this work; fees from Abbott Inc and Neurotrauma Sciences Ltd; fees for legal testimony unrelated to this work; participation on an advisory board for Neurotrauma Sciences Ltd. GTM reports grants from US Department of Defense/Medical Technology Enterprise Consortium and grants from the US Department of Defense, National Institute of Neurological Disorders and Stroke, and National Football League Scientific Advisory Board during the conduct of the study and funding from NeuroTrauma Sciences LLC and One Mind. AIRM declares consulting fees from PresSura Neuro, Integra Life Sciences, Gryphon Bio and NeuroTrauma Sciences. DKM reports grants from the NIHR, Brain Research UK, during the conduct of the study; grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from Neurotrauma Sciences, personal fees from Lantmaanen AB, personal fees from Pressura, personal fees from Pfizer, outside the submitted work., (Copyright © 2024. Published by Elsevier B.V.)

Poor outcome following traumatic acute subdural hematoma (ASDH) is associated with the severity of the primary injury and secondary injury including cerebral edema and ischemia. However, the underlying secondary injury mechanism contributing to elevated intracranial pressure (ICP) and high mortality rate remains unclear. Cerebral edema occurs in response to the exposure of the intracellular fixed charge density (FCD) after cell death, causing ICP to increase. The increased ICP from swollen tissue compresses blood vessels in adjacent tissue, restricting blood flow and leading to ischemic damage. We hypothesize that the mass occupying effect of ASDH exacerbates the ischemic injury, leading to ICP elevation, which is an indicator of high mortality rate in the clinic. Using FEBio (febio.org) and triphasic swelling biomechanics, this study modeled clinically relevant ASDHs and simulated post-traumatic brain swelling and ischemia to predict ICP. Results showed that common convexity ASDH significantly increased ICP by exacerbating ischemic injury, and surgical removal of the convexity ASDH may control ICP by preventing ischemia progression. However, in cases where the primary injury is very severe, surgical intervention alone may not effectively decrease ICP, as the contribution of the hematoma to the elevated ICP is insignificant. In addition, interhemispheric ASDH, located between the cerebral hemispheres, does not significantly exacerbate ischemia, supporting the conservative surgical management generally recommended for interhemispheric ASDH. The joint effect of the mass occupying effect of the blood clot and resulting ischemia contributes to elevated ICP which may increase mortality. Our novel approach may improve the fidelity of predicting patient outcome after motor vehicle crashes and traumatic brain injuries due to other causes., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The large amount of training samples required to develop a deep learning brain injury model demands enormous computational resources. Here, we study how a transformer neural network (TNN) of high accuracy can be used to efficiently generate pretraining samples for a convolutional neural network (CNN) brain injury model to reduce computational cost. The samples use synthetic impacts emulating real-world events or augmented impacts generated from limited measured impacts. First, we verify that the TNN remains highly accurate for the two impact types (N = 100 each; R 2 of 0.948-0.967 with root mean squared error, RMSE, ~ 0.01, for voxelized peak strains). The TNN-estimated samples (1000-5000 for each data type) are then used to pretrain a CNN, which is further finetuned using directly simulated training samples (250-5000). An independent measured impact dataset considered of complete capture of impact event is used to assess estimation accuracy (N = 191). We find that pretraining can significantly improve CNN accuracy via transfer learning compared to a baseline CNN without pretraining. It is most effective when the finetuning dataset is relatively small (e.g., 2000-4000 pretraining synthetic or augmented samples improves success rate from 0.72 to 0.81 with 500 finetuning samples). When finetuning samples reach 3000 or more, no obvious improvement occurs from pretraining. These results support using the TNN to rapidly generate pretraining samples to facilitate a more efficient training strategy for future deep learning brain models, by limiting the number of costly direct simulations from an alternative baseline model. This study could contribute to a wider adoption of deep learning brain injury models for large-scale predictive modeling and ultimately, enhancing safety protocols and protective equipment., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Computational methods for the optimization of synthetic as well as processing parameters for the fabrication of polymeric foams based on styrene and methyl methacrylate are introduced in the current study. Small scale experiments are utilized to develop a synthetic procedure for polymers with desired chain length and composition. After the upscaling of these experiments, the optimal processing parameters for autoclave foam production are determined applying Bayesian optimization, active learning algorithms and random sampling as well as exploitation-based algorithms (Greedy). By these experiments the power of such a systematic approach is shown and the foamability of styrene-methyl methacrylate-based copolymers is investigated. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury., Methods: Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates., Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively., Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity., Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust., Competing Interests: Declaration of interests Data were obtained in CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA). Data for the CENTER-TBI study has been collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). VFJN holds a NIHR Rosetrees Trust Advanced Fellowship, NIHR302544, which is funded in partnership by the NIHR and Rosetrees Trust. DKM reports grants, personal fees, and non-financial support from GlaxoSmithKline outside the submitted work; personal fees from Neurotrauma Sciences, Lantmannen AB, PressuraNeuro, CSL Behring, and Invex Ltd, outside of the submitted work. Dr Maas reports receiving personal fees from NeuroTrauma Sciences, and PressuraNeuro outside the submitted work. VFJN reports a grant with ROCHE Pharmaceuticals outside the submitted work, and personal fees from Integra outside the submitted work. Dr Wilson reports receiving personal fees from Novartis, Neurotrauma Sciences, and Mass General Brigham outside the submitted work. No other disclosures were reported., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The study investigated the effectiveness of low-frequency sampling in detecting alterations in cerebrovascular reactivity (CVR) associated with changes in intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across different age groups. The primary objective was to investigate an ICP threshold that indicates a decrease in CVR as evidenced by a significant increase in the ultra-low-frequency pressure reactivity index (UL-PRx). Additionally, the study aimed to develop an age-based categorization method for patients with TBI to investigate the differences between these ICP thresholds in different age groups., Methods: In this retrospective analysis, data from 263 patients with TBI were prospectively collected. ICP and mean arterial pressure were extracted from the hospital database at 5-min intervals. Demographic details, clinical presentation, computed tomography scans, neurosurgical interventions, and 12-months outcome were recorded. ICP versus UL-PRx values were categorized into ICP bins and graphically represented with boxplots for each age group, illustrating how as ICP values rise, there is a bin (age-tailored ICP [AT-ICP]) beyond which UL-PRx shows a sudden increase, indicating CVR loss. Homogeneous age groups were established to obtain a consistent AT-ICP threshold. The discriminatory ability of the AT-ICP thresholds was compared with the guideline-recommended thresholds by calculating the area under the Receiver Operating Characteristic curve of the ICP-derived indices (dose above threshold, and the hourly dosage above threshold)., Results: Age groups 0-5, 6-20, 21-60, 61-70, and 71-85 years were the best age subdivisions, corresponding to AT-ICP thresholds of 20, 30, 35, 25, and 30 mmHg, respectively. The AT-ICP thresholds exhibited better discriminative ability compared with the guideline-recommended thresholds., Conclusions: The AT-ICP thresholds offer a novel approach for estimating CVR impairment and the developed method represents an alternative solution to address the age stratification issue in patients with TBI., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Given the complexity of cerebral pathology in patients with acute brain injury, various neuromonitoring strategies have been developed to better appreciate physiologic relationships and potentially harmful derangements. There is ample evidence that bundling several neuromonitoring devices, termed "multimodal monitoring," is more beneficial compared to monitoring individual parameters as each may capture different and complementary aspects of cerebral physiology to provide a comprehensive picture that can help guide management. Furthermore, each modality has specific strengths and limitations that depend largely on spatiotemporal characteristics and complexity of the signal acquired. In this review we focus on the common clinical neuromonitoring techniques including intracranial pressure, brain tissue oxygenation, transcranial doppler and nearinfrared spectroscopy with a focus on how each modality can also provide useful information about cerebral autoregulation capacity. Finally, we discuss the current evidence in using these modalities to support clinical decision making as well as potential insights into the future of advanced cerebral homeostatic assessments including neurovascular coupling. [ABSTRACT FROM AUTHOR]

Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury ( n = 21) to that of single injury ( n = 21) and healthy controls ( n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury., Competing Interests: D.K.M. reports grant support from the National Institute for Health Research (UK), Medical Research Council (UK), Canadian Institute for Advanced Research and the European Union. He is in receipt of collaborative research grant funding with Lantmannen AB, GlaxoSmithKline Ltd and Cortirio Ltd and personal fees from Calico LLC, GlaxoSmithKline Ltd, Lantmannen AB and Integra Neurosciences. All other authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Objectives: Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery., Methods: This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling., Results: In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died., Conclusion: Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Objective: The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI)., Methods: The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale-Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC., Results: Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61-1.21 and 0.88, 95% CI 0.48-1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2-16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7-4.7) and QOLIBRI scores (β -1.9, 95% CI -9.1 to 9.6) were similar between the two groups., Conclusions: Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient's chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus. Clinical trial registration nos.: CENTER-TBI, NCT02210221 (clinicaltrials.gov); Net-QuRe, NTR6003 (trialsearch.who.int) and NL5761 (onderzoekmetmensen.nl).

Additive manufacturing allows the tailoring of the structure of energy-absorbing materials. It is thus feasible now to use light, printed structures instead of other materials such as foams and honeycombs, signifying greater possibilities for customization. Some of these structures are triply periodic minimal-surface structures that is a family of different structures like the gyroid one. Another benefit of additively manufactured graded structures, which foams or honeycombs lack, is the flexibility to vary the internal parameters along one or more directions. This study focuses on the comparative analysis of graded and non-graded gyroid structures for four common thermoplastic materials used in additive manufacturing. These structures are compared with each other under quasi-static compression testing, as well as with expanded polystyrene foam and solid samples of the thermoplastic materials. The analysis includes investigation of the stress–strain and specific stress–strain curves, capability of absorbing energy per unit weight and per unit volume, ideality, total efficiency, and normalized energy vs. normalized stress characteristics. We also analyze the internal fracture mechanism of the structures. The objective is to obtain more extensive knowledge of the behavior of non-graded structures. [ABSTRACT FROM AUTHOR]

The development of additive manufacturing and lattice structures has created opportunities for the development of lightweight impact–absorption structures that can overcome most constraints of previously used materials such as expanded polystyrene foams. However, for the successful application of such structures, the effects of their variables in their mechanical performance must be established. In this study, the mechanical properties and energy absorption of thermoplastic sheet gyroid structures were investigated and compared with the performance of current materials. Consequently, the specimens were tested after changing the main variables, i.e., cell size and volume fraction, of various thermoplastic materials such as acrylonitrile butadiene styrene, polylactic acid, thermoplastic polyurethane, and polyamide 12. Finally, they were tested in a quasi-static compression test and their deformation stages were photographed. The stress–strain curves of all materials changed after adopting the sheet gyroid structure, exhibiting three distinct regions: linear elastic, long collapse plateau, and densification that made them particularly applicable for energy absorption. Volume fraction affected the layer collapse. The elastic geometrical stiffness increased for higher volume fractions and smaller cells. In addition, the peak and plateau stresses increased at higher volume fractions, and while smaller cells were not directly affected. Additionally, the area under the curves increase with the volume fraction; hence, for most materials, specific energy absorption was larger for higher volume fractions. The constituent material properties contributed significantly to the structural behavior, exhibiting three primary deformation mechanisms, i.e., elastomeric, elastic–plastic, and elastic–brittle, resulting in a wide spectrum of properties for each application requirement. The comparison of the optimal properties with the expanded polystyrene demonstrated the ability of sheet gyroid structures to overcome most of its challenges, exhibiting a superior specific energy absorption, ability to withstand various impacts, letting air flow in its all axes, and being recyclable. Thus, sheet gyroid structures can be considered promising alternatives. [ABSTRACT FROM AUTHOR]

Many studies indicate that wearing a bicycle helmet significantly reduces the risk of accident-related head injuries. Less is reported, however, about bicycle helmet use, about preventing facial injury. Epidemiological studies typically report incidences of 'head injury,' though rarely categorize head, brain, and facial injuries separately. Studies that do focus on facial injury suggest that helmets do not provide adequate protection. A 3D biofidelic child head form and two conventional bicycle helmets (that is," open face") were created in MSC ADAMS™ computer modelling and simulation software. Peak force and linear accelerations were measured for a series of head form impact simulations corresponding to an established testing standard and a newly proposed series of tests derived from modified motorcycle standards, incorporating injury thresholds from the facial bone impact tolerance literature. Almost all impact simulations exceeded the threshold for fracture, soft tissue, and dental trauma. An observational study was conducted using MSC ADAMS™ to assess a helmeted headform's face exposure during impact simulations. Helmets failed to reduce face impact exposure, during all simulations, except for perpendicular cheek impacts. International test standards, therefore, require urgent revision to ensure that face protection is included. [ABSTRACT FROM AUTHOR]

Background: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury., Methods: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors., Results: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury., Conclusions: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache., Trial Registration: ClinicalTrials.gov NCT02210221., (© 2024. The Author(s).)

Importance: The optimal timing for fixation of extremity fractures after traumatic brain injury (TBI) remains controversial., Objective: To investigate whether patients who underwent extremity fixation within 24 hours of TBI experienced worse outcomes than those who had the procedure 24 hours or more after TBI., Design, Setting, and Participants: This cohort study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Patients 16 years or older with TBI who underwent internal extremity fixation met inclusion criteria. To compare outcomes, patients who underwent the procedure within 24 hours were propensity score matched with those who underwent it 24 hours or later. Patients were treated from December 9, 2014, to December 17, 2017. Data analysis was conducted between August 1, 2022, and December 25, 2023., Main Outcomes and Measures: The primary outcome was an unfavorable functional status at 6 months (Glasgow Outcome Scale-Extended [GOSE] score ≤4)., Results: A total of 253 patients were included in this study. The median age was 41 (IQR, 27-57) years, and 184 patients (72.7%) were male. The median Injury Severity Score (ISS) was 41 (IQR, 27-49). Approximately half of the patients (122 [48.2%]) had a mild TBI while 120 (47.4%) had moderate to severe TBI. Seventy-four patients (29.2%) underwent an internal extremity fixation within 24 hours, while 179 (70.8%) had the procedure 24 hours or later. At 6 months, 86 patients (34.0%) had an unfavorable functional outcome. After propensity score matching, there were no statistically significant differences in unfavorable functional outcomes at 6 months (odds ratio [OR], 1.12 [95% CI, 0.51-1.99]; P = .77) in patients with TBI of any severity. Similar results were observed in patients with mild TBI (OR, 0.71 [95% CI, 0.22-2.29]; P = .56) and moderate to severe TBI (OR, 1.08 [95% CI, 0.32-3.70]; P = .90)., Conclusions and Relevance: The outcomes of extremity fracture fixation performed within 24 hours after TBI appear not to be worse than those of procedures performed 24 hours or later. This finding suggests that early fixation after TBI could be considered in patients with mild head injuries.

Purpose: We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI)., Methods: From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]., Results: Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001)., Conclusion: Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings., (© 2024. The Author(s).)

This study aims to facilitate intracranial simulation of traumatic events by determining the mechanical properties of different anatomical structures of the brain. Our experimental indentation paradigm used fresh, post-operative human tissue, which is highly advantageous in determining mechanical properties without being affected by postmortem time. This study employed an inverse finite element approach coupled with experimental indentation data to characterize mechanical properties of the human hippocampus (CA1, CA3, dentate gyrus), cortex white matter, and cortex grey matter. We determined that an uncoupled viscoelastic Ogden constitutive formulation was most appropriate to represent the mechanical behavior of these different regions of brain. Anatomical regions were significantly different in their mechanical properties. The cortex white matter was stiffer than cortex grey matter, and the CA1 and dentate gyrus were both stiffer than cortex grey matter. Although no sex dependency was observed, there were trends indicating that male brain regions were generally stiffer than corresponding female regions. In addition, there were no statistically significant age dependent differences. This study provides a structure-specific description of fresh human brain tissue mechanical properties, which will be an important step toward explicitly modeling the heterogeneity of brain tissue deformation during TBI through finite element modeling., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Importance: Exposure to traumatic brain injury (TBI) has raised widespread concern over participation in sports, particularly over possible long-term consequences. However, little is known about the outcomes of individuals presenting to hospitals with sports-related TBI., Objective: To compare the characteristics and outcomes of individuals presenting to hospitals with sports-related and non-sports-related TBI., Design, Setting, and Participants: The CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) observational cohort study was conducted at hospitals in 18 countries. The study enrolled 4509 patients who had TBI and had an indication for computed tomography (CT), of whom 4360 were 16 years or older. Outcomes were assessed at 3 and 6 months, and groups were compared using regression analyses adjusting for clinical and demographic differences. Data were collected between December 9, 2014, and December 17, 2017, and analyzed from August 2022 to March 2023., Exposure: Sports-related and non-sports-related TBI with subgroups selected by severity of injury., Main Outcomes and Measures: The main outcome was the Glasgow Outcome Scale-Extended (GOSE) at 6 months, with secondary outcomes covering postconcussion symptoms, health-related quality of life, and mental health., Results: A total of 4360 patients were studied, including 256 (6%) with sports-related TBI (mean [SD] age, 38.9 [18.1] years; 161 [63%] male) and 4104 with non-sports-related TBI (mean [SD] age, 51.0 [20.2] years; 2773 [68%] male). Compared with patients with non-sports-related TBI, patients with sports-related TBI were younger, more likely to have tertiary education, more likely to be previously healthy, and less likely to have a major extracranial injury. After adjustment, the groups did not differ in incomplete recovery (GOSE scores <8) at 6 months (odds ratio [OR], 1.27; 95% CI, 0.90-1.78; P = .22 for all patients; OR, 1.20; 95% CI, 0.83-1.73; P = .34 for those with mild TBI; and OR, 1.19; 95% CI, 0.74-1.92; P = .65 for those with mild TBI and negative CT findings). At 6 months, there was incomplete recovery in 103 of 223 patients (46%) with outcomes in the sports-related TBI group, 65 of 168 (39%) in those with mild sports-related TBI, and 30 of 98 (31%) in those with mild sports-related TBI and negative CT findings. In contrast, at 6 months, the sports-related TBI group had lower prevalence of anxiety, depression, posttraumatic stress disorder, and postconcussion symptoms than the non-sports-related group., Conclusions and Relevance: In this cohort study of 4360 patients with TBI, functional limitations 6 months after injury were common after sports-related TBI, even mild sports-related TBI. Persisting impairment was evident in the sports-related TBI group despite better recovery compared with non-sports-related TBI on measures of mental health and postconcussion symptoms. These findings caution against taking an overoptimistic view of outcomes after sports-related TBI, even if the initial injury appears mild.

Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU., Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated., Findings: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved., Interpretation: First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice., Funding: European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences., Competing Interests: Declaration of interests DKM reports grants, personal fees, and non-financial support from GlaxoSmithKline; personal fees from Neurotrauma Sciences, Lantmannen, Pressura, and Pfizer, outside of the submitted work. SB reports grants from the Gates Cambridge foundation fellowship during the conduct of this study. PS receives parts of licensing fee for the ICM+ software from Cambridge Enterprise, UK, during the conduct of this study. ES receives royalties from Springer during the conduct of this study. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

During deep brain stimulation of the sub-thalamic nucleus (STN-DBS), frequently adjusting the position of the cannula may lead to changes in tissue viscoelasticity. To investigate the mechanical properties of tissue on implant path at repeated loads, three cyclic tension and relaxation tests were carried out at 10 % and 20 % strains. Results indicated that white matter was about 25 %–140 % stiffer than gray matter. Within 20 % strain, the natural viscoelasticity of tissue was not affected by the repeated tension. Whereas at 20 % strain, irreversible internal structure rearrangements occurred at the first relaxation due to the persistent strain action, and almost 60 % of the attenuation modulus generated in the initial 5 s of the process, which leads to a softer transformation of the tissue. Further simulated puncture experiments revealed that an irreversible depression occurred when the cerebral hemisphere was subjected to a constant pressure of cannula for 5 s. [ABSTRACT FROM AUTHOR]