Traumatic Brain Injury Research Research Articles

Experimental animal models in traumatic brain injury research: a comprehensive review of methods and outlook

Traumatic brain injury (TBI) remains a significant public health concern worldwide, necessitating effective research models to elucidate its pathophysiology and develop therapeutic interventions. Animal models play a crucial role in TBI research, offering valuable insights into injury mechanisms and potential treatments. However, selecting the appropriate model can be challenging due to diverse array of available options and their respective advantages and limitations. In this comprehensive review, we examine four commonly used animal models of TBI: the weight drop, fluid percussion, cortical impact, and blast injury models. Each model is characterized by distinct injury mechanisms, allowing researchers simulate various aspects of TBI pathology. We discuss the unique advantages and disadvantages of each model, providing insights into their applications and considerations for model selection based on research objectives and outcome measures. Furthermore, we highlight emerging directions in TBI modelling, emphasizing the importance of refining and innovating models to replicate the complexity of human TBI. By critically evaluating and understanding the subtlety of different TBI models, researchers can make informed decisions to enhance the translational potential of preclinical TBI research and ultimately improve clinical outcomes for TBI patients.

Recovery Potential in Patients Who Died After Withdrawal of Life-Sustaining Treatment: A TRACK-TBI Propensity Score Analysis.

Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.

A Proof-of-Concept Study Demonstrating How FITBIR Datasets Can be Harmonized to Examine Posttraumatic Stress Disorder-Traumatic Brain Injury Associations

Background: Although posttraumatic stress disorder (PTSD) is common following traumatic brain injury (TBI), the specific associations between these conditions is difficult to elucidate in part due to the diverse methodologies, small samples, and limited longitudinal data in the extant literature. Objective: Conduct a proof-of-concept study demonstrating our ability to compile patient-level TBI data from shared studies in the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System to address these shortcomings and improve our understanding of TBI outcomes including the rates PTSD comorbidity. Method: We searched the FITBIR database for shared studies reporting rates of probable PTSD among participants with no TBI, history of mild TBI, or history of moderate/severe TBI. We merged and harmonized data across the relevant studies and analyzed rates of probable PTSD across TBI history and severity categories. Results: Four FITBIR studies with 2,312 participants included PTSD outcome data. The final sample for comparative analyses comprised 1,633 participants from two studies with TBI group comparison data. Approximately 79% had a history of mild TBI and 32-37% screened positive for probable PTSD. Participants with a history of mild TBI had 2.8 greater odds of probable PTSD compared to those without TBI (95% CI: 2.0, 3.7). Conclusions: Only two FITBIR studies reported data examining PTSD outcomes for mild TBI as of January 2021. The analyses are consistent with prior literature, suggesting mild TBI is associated with higher rates of probable PTSD than no TBI. This study developed the methods, shared the harmonization and analysis code, and publicly shared the TBI and PTSD meta-dataset back to FITBIR for dissemination through their website, allowing future research teams to update these and other, related analyses as more studies are contributed to and shared via the FITBIR platform.

The recent two decades of traumatic brain injury: a bibliometric analysis and systematic review.

Traumatic brain injury (TBI) is a serious public health burden worldwide, with a mortality rate of 20%-30%; however, reducing the incidence and mortality rates of TBI remains a major challenge. This study provides a multidimensional analysis to explore the potential breakthroughs in TBI over the past two decades. We used bibliometric and Latent Dirichlet Allocation (LDA) analyses to analyze publications focusing on TBI published between 2003 and 2022 from the Web of Science Core Collection (WOSCC) database to identify core journals and collaborations among countries/regions, institutions, authors, and research trends. Over the past 20 years, 41,545 articles on TBI from 3,043 journals were included, with 12,916 authors from 20,449 institutions across 145 countries/regions. The annual number of publications has increased ten-fold compared to previous publications. This study revealed that high-income countries, especially the United States, have a significant influence. Collaboration was limited to several countries/regions. The LDA results indicated that the hotspots included four main areas: "Clinical finding", "Molecular mechanism", "Epidemiology", and "Prognosis". Epidemiological research has consistently increased in recent years. Through epidemiological topic analysis, the main etiology of TBI has shifted from traffic accidents to falls in a demographically aging society. Over the past two decades, TBI research has developed rapidly, and its epidemiology has received increasing attention. Reducing the incidence of TBI from a preventive perspective is emerging as a trend to alleviate the future social burden; therefore, epidemiological research might bring breakthroughs in TBI.

Comparing Randomized Controlled Trials of Moderate to Severe Traumatic Brain Injury in Lower to Middle Income Countries Versus High Income Countries.

Outcomes from traumatic brain injury (TBI) including death differ significantly between high-, middle-, and low-income countries. Little is known, however, about differences in TBI research across the globe. The objective of this article was to examine randomized controlled trials (RCTs) of moderate-to-severe TBI in high-income countries (HICs) compared with low- and middle-income countries (LMICs), as defined by the World Bank income per capita cutoff of $13,205 US dollars. A systematic review was conducted for articles published in the English language to December 2022 inclusive using MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria: (1) human participants with a mean age of ≥18 years; (2) ≥50% of the sample had moderate to severe TBI; and (3) the study design was a RCT. Data extracted included author, year, country, sample size, primary focus (medical/surgical management or rehabilitation), injury etiology, time post-injury, and indicator(s) used to define TBI severity. There were 662 RCTs (published 1978-2022) that met inclusion criteria comprising 91,946 participants. There were 48 countries represented: 30 HICs accounting for 451 RCTs (68.1%) and 18 LMICs accounting for 211 RCTs (31.9%). The 62.6% of RCTs from LMICs were conducted in the acute phase post-injury (≤1 month) compared with 42.1% of RCTs from HICs. Of RCTs from LMICs, 92.4% focused on medical/surgical management compared with 52.5% from HICs. Since 2016, more RCTs have been conducted in LMICs than in HICs, indicating the importance of better understanding this pattern of research output.

A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

Early versus delayed cranioplasty after decompressive craniectomy in traumatic brain injury: a multicenter observational study within CENTER-TBI and Net-QuRe.

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). 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. 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. 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).

120 Outcome Related Thresholds of Near Infrared Spectroscopy Based Cerebrovascular Reactivity Metrics in Moderate Severe TBI: A Canadian High Resolution-TBI (CAHR-TBI) Cohort Study

INTRODUCTION: Dysfunctional cerebrovascular reactivity (CVR)/autoregulation contributes to secondary injury following traumatic brain injury (TBI). Currently, monitoring of CVR relies on intracranial pressure (ICP) monitoring and has known thresholds at which outcomes worsen. Interest has shifted to less invasive near infrared spectroscopic (NIRS) regional cerebral oxygen saturation (rSO2) based measures of CVR. However, threshold levels at which outcomes worsen have not yet been determined for these indices. METHODS: A retrospective multi-institutional cohort study utilizing the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative database was performed. The cohort included TBI patients with ICP, arterial blood pressure (ABP), and rSO2 monitoring treated in adult intensive care units (ICU). COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and ABP) were calculated for each subject as the rSO2 based indices of CVR. 2 x 2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated and the threshold producing the highest value was identified as providing the best discriminative value. RESULTS: A total of 129 patients were included. For both COx and COx_a an optimal threshold value of 0.2 was identified for both survival (χ2 = 9.57, p = 0.0020; χ2 = 13.04, p = 0.0003 respectively) and favorable outcomes (χ2 = 5.98, p = 0.0145; χ2 = 8.94, p = 0.0028 respectively) with values above this associated with worse outcomes. Notably, there was no identifiable threshold for raw rSO2 values at which outcomes were identified to worsen. CONCLUSIONS: In this multi-institutional cohort study, COx and COx_a were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI

BackgroundHeadache 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.MethodsA 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.ResultsA 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.ConclusionsHeadache 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 registrationClinicalTrials.gov NCT02210221.

Harmonizing federal interagency traumatic brain injury research data to examine depression and suicide-related outcomes.

This proof-of-concept study was conducted to establish the feasibility of compiling Federal Interagency Traumatic Brain Injury Research (FITBIR) data pertaining to depression and suicide risk, with the secondary goal of improving understanding regarding these outcomes. FITBIR is a national repository of participant-level traumatic brain injury (TBI) data designed to address methodological limitations (e.g., small sample size, heterogeneity of injuries). FITBIR studies with TBI severity and measures related to depression and suicidal ideation were identified. Data were harmonized across relevant studies and grouped to identify "probable depression" and suicidal ideation, resulting in a large, combined sample. Rates of probable depression and suicidal ideation were described across the available studies, considering the influence of demographic and/or injury-related factors on outcomes. Cross-sectional studies meeting criteria included four studies with depression outcomes and two with suicidal ideation outcomes. Two studies reported data appropriate for comparative analyses on depression. Combined results suggested that approximately 71% of participants were categorized as having probable depression. Participants with a history of mild TBI had 2.54 greater odds of probable depression (95% confidence interval [1.93, 3.34]) than those without a history of TBI. Methods, harmonization code, and meta-databases related to TBI, probable depression, and suicidal ideation are now publicly available on the FITBIR website. Even with limited data, harmonization of FITBIR studies can serve as the basis for ongoing TBI and mental health research. Analyses will be more robust in the future as more studies with relevant outcome data are added to the FITBIR database. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Imaging Findings in Acute Traumatic Brain Injury: a National Institute of Neurological Disorders and Stroke Common Data Element-Based Pictorial Review and Analysis of Over 4000 Admission Brain Computed Tomography Scans from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.

In 2010, the National Institute of Neurological Disorders and Stroke (NINDS) created a set of common data elements (CDEs) to help standardize the assessment and reporting of imaging findings in traumatic brain injury (TBI). However, as opposed to other standardized radiology reporting systems, a visual overview and data to support the proposed standardized lexicon are lacking. We used over 4000 admission computed tomography (CT) scans of patients with TBI from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study to develop an extensive pictorial overview of the NINDS TBI CDEs, with visual examples and background information on individual pathoanatomical lesion types, up to the level of supplemental and emerging information (e.g., location and estimated volumes). We documented the frequency of lesion occurrence, aiming to quantify the relative importance of different CDEs for characterizing TBI, and performed a critical appraisal of our experience with the intent to inform updating of the CDEs. In addition, we investigated the co-occurrence and clustering of lesion types and the distribution of six CT classification systems. The median age of the 4087 patients in our dataset was 50 years (interquartile range, 29-66; range, 0-96), including 238 patients under 18 years old (5.8%). Traumatic subarachnoid hemorrhage (45.3%), skull fractures (37.4%), contusions (31.3%), and acute subdural hematoma (28.9%) were the most frequently occurring CT findings in acute TBI. The ranking of these lesions was the same in patients with mild TBI (baseline Glasgow Coma Scale [GCS] score 13-15) compared with those with moderate-severe TBI (baseline GCS score 3-12), but the frequency of occurrence was up to three times higher in moderate-severe TBI. In most TBI patients with CT abnormalities, there was co-occurrence and clustering of different lesion types, with significant differences between mild and moderate-severe TBI patients. More specifically, lesion patterns were more complex in moderate-severe TBI patients, with more co-existing lesions and more frequent signs of mass effect. These patients also had higher and more heterogeneous CT score distributions, associated with worse predicted outcomes. The critical appraisal of the NINDS CDEs was highly positive, but revealed that full assessment can be time consuming, that some CDEs had very low frequencies, and identified a few redundancies and ambiguity in some definitions. Whilst primarily developed for research, implementation of CDE templates for use in clinical practice is advocated, but this will require development of an abbreviated version. In conclusion, with this study, we provide an educational resource for clinicians and researchers to help assess, characterize, and report the vast and complex spectrum of imaging findings in patients with TBI. Our data provides a comprehensive overview of the contemporary landscape of TBI imaging pathology in Europe, and the findings can serve as empirical evidence for updating the current NINDS radiologic CDEs to version 3.0.

Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study.

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to a United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. The GFAP provided good discrimination in the overall cohort at days 1 (AUC = 0.82) and 14 (AUC = 0.72), and in the hospitalized subgroup at days 1 (AUC = 0.84), 3 (AUC = 0.88), 5 (AUC = 0.82), and 14 (AUC = 0.74). The UCH-L1, NSE, and S100B did not perform well (AUC = 0.51-0.57 across time points). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h time frame in patients with TBI who have a GCS 13-15.

Changes in neurologic status after traumatic brain injury in the Resuscitation Outcomes Consortium Hypertonic Saline trial.

Traumatic brain injury (TBI) is an important public health problem resulting in significant death and disability. Emergency medical services (EMS) personnel often provide initial treatment for TBI, but only limited data describe the long-term course and outcomes of this care. We sought to characterize changes in neurologic status among adults with TBI patients enrolled in the Resuscitation Outcomes Consortium Hypertonic Saline (ROC-HS) trial. We used data from the TBI cohort of the ROC-HS trial. The trial included adults with TBI, with Glasgow Coma Scale (GCS) ≤8, and excluded those with shock (systolic blood pressure [SBP] ≤70 or SBP 71-90 with a heart rate [HR] ≥108). The primary outcome was Glasgow Outcome Scale-Extended (GOS-E; 1=dead, 8=no disability) determined at (a) hospital discharge and (b) 6-month follow-up. We assessed changes in GOS-E between hospital discharge and 6-month follow-up using descriptive statistics and Sankey graphs. Among 1279 TBI included in the analysis, GOS-E categories at hospital discharge were as follows: favorable (GOS-E 5-8) 220 (17.2%), unfavorable (GOS-E 2-4) 664 (51.9%), dead (GOS-E 1) 321 (25.1%), and missing 74 (5.8%). GOS-E categories at 6-month follow-up were as follows: favorable 459 (35.9%), unfavorable 279 (21.8%), dead 346 (27.1%), and missing 195 (15.2%). Among initial TBI survivors with complete GOS-E,>96% followed one of three neurologic recovery patterns: (1) favorable to favorable (20.0%), (2) unfavorable to favorable (40.3%), and (3) unfavorable to unfavorable (36.0%). Few patients deteriorated from favorable to unfavorable neurologic status, and there were few additional deaths. Among TBI receiving initial prehospital care in the ROC-HS trial, changes in 6-month neurologic status followed distinct patterns. Among TBI with unfavorable neurologic status at hospital discharge, almost half improved to favorable neurologic status at 6 months. Among those with favorable neurologic status at discharge, very few worsened or died at 6 months. These findings have important implications for TBI clinical care, research, and trial design.

Early vs Late Fixation of Extremity Fractures Among Adults With Traumatic Brain Injury

The optimal timing for fixation of extremity fractures after traumatic brain injury (TBI) remains controversial. 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. 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. The primary outcome was an unfavorable functional status at 6 months (Glasgow Outcome Scale-Extended [GOSE] score ≤4). 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). 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.

Mapping knowledge of the stem cell in traumatic brain injury: a bibliometric and visualized analysis.

Traumatic brain injury (TBI) is a brain function injury caused by external mechanical injury. Primary and secondary injuries cause neurological deficits that mature brain tissue cannot repair itself. Stem cells can self-renewal and differentiate, the research of stem cells in the pathogenesis and treatment of TBI has made significant progress in recent years. However, numerous articles must be summarized to analyze hot spots and predict trends. This study aims to provide a panorama of knowledge and research hotspots through bibliometrics. We searched in the Web of Science Core Collection (WoSCC) database to identify articles pertaining to TBI and stem cells published between 2000 and 2022. Visualization knowledge maps, including co-authorship, co-citation, and co-occurrence analysis were generated by VOSviewer, CiteSpace, and the R package "bibliometrix." We retrieved a total of 459 articles from 45 countries. The United States and China contributed the majority of publications. The number of publications related to TBI and stem cells is increasing yearly. Tianjin Medical University was the most prolific institution, and Professor Charles S. Cox, Jr. from the University of Texas Health Science Center at Houston was the most influential author. The Journal of Neurotrauma has published the most research articles on TBI and stem cells. Based on the burst references, "immunomodulation," "TBI," and "cellular therapy" have been regarded as research hotspots in the field. The keywords co-occurrence analysis revealed that "exosomes," "neuroinflammation," and "microglia" were essential research directions in the future. Research on TBI and stem cells has shown a rapid growth trend in recent years. Existing studies mainly focus on the activation mechanism of endogenous neural stem cells and how to make exogenous stem cell therapy more effective. The combination with bioengineering technology is the trend in this field. Topics related to exosomes and immune regulation may be the future focus of TBI and stem cell research.

Exploiting Natural Language Processing to Unveil Topics and Trends of Traumatic Brain Injury Research.

Traumatic brain injury (TBI) has evolved from a topic of relative obscurity to one of widespread scientific and lay interest. The scope and focus of TBI research have shifted, and research trends have changed in response to public and scientific interest. This study has two primary goals: first, to identify the predominant themes in TBI research; and second, to delineate "hot" and "cold" areas of interest by evaluating the current popularity or decline of these topics. Hot topics may be dwarfed in absolute numbers by other, larger TBI research areas but are rapidly gaining interest. Likewise, cold topics may present opportunities for researchers to revisit unanswered questions. We utilized BERTopic, an advanced natural language processing (NLP)-based technique, to analyze TBI research articles published since 1990. This approach facilitated the identification of key topics by extracting sets of distinctive keywords representative of each article's core themes. Using these topics' probabilities, we trained linear regression models to detect trends over time, recognizing topics that were gaining (hot) or losing (cold) relevance. Additionally, we conducted a specific analysis focusing on the trends observed in TBI research in the current decade (the 2020s). Our topic modeling analysis categorized 42,422 articles into 27 distinct topics. The 10 most frequently occurring topics were: "Rehabilitation," "Molecular Mechanisms of TBI," "Concussion," "Repetitive Head Impacts," "Surgical Interventions," "Biomarkers," "Intracranial Pressure," "Posttraumatic Neurodegeneration," "Chronic Traumatic Encephalopathy," and "Blast Induced TBI," while our trend analysis indicated that the hottest topics of the current decade were "Genomics," "Sex Hormones," and "Diffusion Tensor Imaging," while the cooling topics were "Posttraumatic Sleep," "Sensory Functions," and "Hyperosmolar Therapies." This study highlights the dynamic nature of TBI research and underscores the shifting emphasis within the field. The findings from our analysis can aid in the identification of emerging topics of interest and areas where there is little new research reported. By utilizing NLP to effectively synthesize and analyze an extensive collection of TBI-related scholarly literature, we demonstrate the potential of machine learning techniques in understanding and guiding future research prospects. This approach sets the stage for similar analyses in other medical disciplines, offering profound insights and opportunities for further exploration.

Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes—an analysis of CENTER-TBI data

PurposeWe 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).MethodsFrom 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)].ResultsAmong 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).ConclusionThough 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.

Association Between Early External Ventricular Drain Insertion and Functional Outcomes 6 Months Following Moderate-to-Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading global cause of morbidity and mortality. Intracranial hypertension following moderate-to-severe TBI (m-sTBI) is a potentially modifiable secondary cerebral insult and one of the central therapeutic targets of contemporary neurocritical care. External ventricular drain (EVD) insertion is a common therapeutic intervention used to control intracranial hypertension and attenuate secondary brain injury. However, the optimal timing of EVD insertion in the setting of m-sTBI is uncertain and practice variation is widespread. Therefore, we aimed to assess if there is an association between timing of EVD placement and functional neurological outcome at 6 months post m-sTBI. We pooled individual patient data for all relevant harmonizable variables from the Erythropoietin in Traumatic Brain Injury (EPO-TBI) and Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomized control trials, and the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) Core Study version 3.0 and Australia-Europe NeuroTrauma Effectiveness Research in TBI (Oz-ENTER) prospective observational studies to create a combined dataset. The Glasgow Coma Scale (GCS) score was used to define TBI severity and we included all patients admitted to an intensive care unit with a GCS ≤12, who were 15 years or older and underwent EVD placement within 7 days of injury. We used hierarchical multi-variable logistic regression models to study the association between EVD insertion within 24 h of injury (early) compared with EVD insertion more than 24 h after injury (late) and 6-month functional neurological outcome measured using the Glasgow Outcome Score Extended (GOSE). In total, 2536 patients were assessed. Of these, 502 (20%) underwent early EVD insertion and 145 (6%) underwent late EVD insertion. Following adjustment for the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) score extended (Core + CT), sex, injury severity score, study and treatment site, patients receiving a late EVD had higher odds of death or severe disability (GOSE 1-4) at 6 months follow-up than those receiving an early EVD adjusted odds ratio; 95% confidence interval, 2.14; 1.22-3.76; p = 0.008. Our study suggests that in patients with m-sTBI where an EVD is needed, early (≤ 24 h post-injury) insertion may result in better long-term functional outcomes. This finding supports future prospective investigation in this area.

Development of a Multimodal Machine Learning-Based Prognostication Model for Traumatic Brain Injury Using Clinical Data and Computed Tomography Scans: A CENTER-TBI and CINTER-TBI Study.

Computed tomography (CT) is an important imaging modality for guiding prognostication in patients with traumatic brain injury (TBI). However, because of the specialized expertise necessary, timely and dependable TBI prognostication based on CT imaging remains challenging. This study aimed to enhance the efficiency and reliability of TBI prognostication by employing machine learning (ML) techniques on CT images. A retrospective analysis was conducted on the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) data set (n = 1016). An ML-driven binary classifier was developed to predict favorable or unfavorable outcomes at 6 months post-injury. The prognostic performance was assessed using the area under the curve (AUC) over fivefold cross-validation and compared with conventional models that depend on clinical variables and CT scoring systems. An external validation was performed using the Comparative Indian Neurotrauma Effectiveness Research in Traumatic Brain Injury (CINTER-TBI) data set (n = 348). The developed model achieved superior performance without the necessity for manual CT assessments (AUC = 0.846 [95% CI: 0.843-0.849]) compared with the model based on the clinical and laboratory variables (AUC = 0.817 [95% CI: 0.814-0.820]) and established CT scoring systems requiring manual interpretations (AUC = 0.829 [95% CI: 0.826-0.832] for Marshall and 0.838 [95% CI: 0.835-0.841] for International Mission for Prognosis and Analysis of Clinical Trials in TBI [IMPACT]). The external validation demonstrated the prognostic capacity of the developed model to be significantly better (AUC = 0.859 [95% CI: 0.857-0.862]) than the model using clinical variables (AUC = 0.809 [95% CI: 0.798-0.820]). This study established an ML-based model that provides efficient and reliable TBI prognosis based on CT scans, with potential implications for earlier intervention and improved patient outcomes.