Search Results (1,163)

Traumatic Brain Injury (TBI) is a major global health concern and a leading cause of death and disability, especially in young adults. It triggers complex secondary injury cascades, e.g., calcium dysregulation, mitochondrial dysfunction and protease activation, that extend well beyond the initial mechanical insult to drive ongoing neurodegeneration. The calcium-dependent protease calpain has emerged as a central mediator of TBI cellular pathology. Calpain cleaves a broad range of cytoskeletal and regulatory proteins across neuronal compartments, disrupting axonal integrity, synaptic function and calcium homeostasis. Despite decades of research, calpain remains an elusive therapeutic target. In this review, we examine the spatial and temporal patterns of calpain activation in the traumatically injured brain, categorize key calpain substrates by structure and location, and assess their mechanistic roles in TBI pathology. We also review recent advances in next-generation calpain-2 selective inhibitors with enhanced specificity and preclinical efficacy and discuss the emerging use of calpain-cleaved protein fragments such as SBDP145 and SNTF as candidate biomarkers for TBI diagnosis and progression. Drawing on molecular, preclinical, and clinical data, we argue that calpain warrants renewed attention as both a therapeutic target and mechanistic biomarker in TBI. It may be time for Cinderella to leave the basement. Full article

Diffuse axonal injury (DAI) is one of the most severe consequences of traumatic brain injury (TBI), characterized by widespread axonal damage in the cerebral white matter. DAI plays a crucial role in determining clinical outcomes, significantly contributing to long-term disability and mortality in severe cases. Despite advancements in neuroscience and clinical management, the diagnosis and prognosis of DAI remain challenging due to its complex pathophysiology and the difficulty of detecting axonal damage in its early stages. This study critically analyzes the clinical and post-mortem methodologies used to assess DAI, highlighting their strengths and limitations. Traditional histopathological grading systems provide valuable insights into disease progression, yet their correlation with long-term functional outcomes remains controversial. Advanced neuroimaging techniques, such as diffusion-weighted MRI, have improved lesion detection, although their routine clinical application is still limited. Additionally, emerging approaches involving biomarkers and artificial intelligence-based models hold promise for enhancing diagnostic accuracy and prognostic predictions. By synthesizing current knowledge on DAI, this work aims to outline a comprehensive framework for improving diagnosis and outcome assessment. Furthermore, it seeks to foster collaboration among clinicians and researchers, ultimately advancing the understanding of DAI and refining strategies to improve patient care. Full article

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Patient disposition following TBI has been shown to interact with factors such as age, sex, and injury severity to impact clinical outcomes. Discharge home is associated with better functional outcomes and lower mortality, while discharge to rehabilitation or long-term care facilities is linked to greater injury severity, older age, and higher comorbidity burden. The aim of this study was to further correlate clinical outcomes with discharge dispositions in patients with severe TBI. Methods: This is a retrospective study (2020–2023) of dispositions in patients with severe TBI with AIS (head) ≥ 3. We investigated the relationship between patient disposition and a range of clinical variables, using both parametric (ANOVA) and non-parametric (Kruskal–Wallis, Wilcoxon, Van der Waerden, Savage, Kolmogorov–Smirnov, and Cramer–von Mises) statistical tests. Variables significant in univariate analysis were entered into a multinomial logistic regression model, with discharge home as the reference group. Results: In a cohort of 824 patients, 25.1% were female (n = 207) and 74.9% were male (n = 617). The mean age was 64.1 years for females and 48.9 years for males. Those admitted for severe TBI were included in our analysis. Most patients were discharged home (52.8%), followed by death (12.4%), inpatient rehab (5.1%), and home with services (5.6%). Significant associations were found between disposition and sex, with both males and females most likely to be discharged home (p = 0.0174), as well as between disposition and injury type (p = 0.0186). Disposition was significantly associated with most major clinical variables: hospital length of stay (HLOS), vent days, Glasgow Coma Scale (GCS), and Injury Severity Score (ISS), with p-values < 0.0001 for ANOVA and non-parametric tests. Longer HLOS and ICULOS were associated with discharge to skilled nursing facilities (SNF) most frequently. Days on mechanical ventilation correlated most strongly with discharge to SNF. Lower GCS scores and higher AIS and ISS scores were linked to death or brain death. Prolonged EDLOS was predominantly associated with psychiatric admissions. Higher levels of ETOH were associated with discharge to police custody, followed by homelessness. Conclusions: Our study supports existing evidence that discharge disposition following severe TBI is influenced by several factors, such as injury severity, age, sex, and clinical variables, such as length of stay and ventilator days. Full article

Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article

Background: Pelvic fractures are complex injuries often associated with significant morbidity and mortality, requiring multidisciplinary management. This case series highlights the presentation, management strategies, and outcomes of patients with pelvic fractures treated at our institution. Methods: The medical records of 13 patients diagnosed with pelvic fractures from 1 January 2020 through 31 December 2023 were retrospectively reviewed. Demographic data, mechanism of injury, fracture pattern, associated injuries, treatment modalities, and outcomes were analyzed. Results: A total of 13 patients were included in the study, with ages ranging from 18–95 years. Six of the patients were male and seven were female. The most common mechanisms of injury were falls and pedestrians struck by vehicles. Associated injuries included traumatic brain injury (TBI), fractures including extremities, ribs, and vertebrae, visceral injury, and spinal cord injury. Treatment strategies ranged from conservative, non-surgical management to operative intervention, including interventional radiology embolization, external traction, open reduction and internal fixation (ORIF), and percutaneous screw stabilization. Additional interventions included chest tube placement, exploratory laparotomy, and craniectomy. Two patients died while in the hospital, one was discharged to a shelter, and the remaining 10 were discharged to various inpatient rehab facilities. Conclusions: Pelvic fractures pose significant clinical challenges due to their complexity and associated injuries. This case series underscores the importance of multidisciplinary intervention and treatment strategies in optimizing outcomes. Further studies should focus on the effectiveness of interventions, utilization of new technology, and multidisciplinary team planning. Full article

Objectives: Early death after trauma has been described several times. Little is known about it after traumatic brain injury (TBI) and decompressive craniectomy (DC). The aim of this study was to characterize patients who die after a TBI and DC during their in-hospital stay. Methods: In a subgroup analysis of a retrospective, multicenter, and observational study, non-survivors from in-hospital stays treated for severe TBI and DC were included. Propensity score matching (PSM) was used. Results: A total of 223 patients with severe TBI were treated with DC, and there were 65 (29.1%) patients who did not survive. Of these, 22 (33.8%) died within the first 24 h. Non-survivors were older (p = 0.010), and pupillomotor dysfunction and a higher heart rate on admission were more common (p < 0.001). PSM patients for overall survival (41, 18.4%) differed in mean heart rate from the deceased (p = 0.030). In a multivariate model, age (OR: 1.045, p = 0.013, CI95%: 1.010 to 1.082), Quick value (OR: 0.965, p = 0.049, CI95%: 0.931 to 1.000), and heart rate (OR: 1.099, p = 0.030, CI95%: 1.009 to 1.197) were confirmed as predictive factors. Conclusions: Even after DC, known factors, such as chronological age and comorbidities, have a significant influence on mortality. The value of DC in an aging society for a particular severity of TBI should be further assessed on the basis of prospective studies. Full article

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Functional recovery after traumatic brain injury (TBI) is hindered by progressive neurodegeneration resulting from neuroinflammation and other secondary injury processes. Dexamethasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but its systemic administration can cause a myriad of other medical issues. We aim to provide a local, sustained treatment of DX for TBI. Previously, we demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and improved motor functional recovery at 7 days post-injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel disks were placed on the surface of the injured cortex. Cognitive function was evaluated using the Morris Water Maze test, and secondary injury was evaluated by histological analysis. The hydrogel treatment group demonstrated significantly shorter latency to target, decreased distance to find the hidden target, increased number of target crossings, increased number of entries to the platform zone, and decreased latency to first entry of target zone compared to untreated TBI rats for probe test. We also observed reduced lesion volume, inflammatory response, and apoptosis in the hydrogel treatment group compared to the untreated TBI group. Full article

Background: Achieving meaningful community integration (engagement in meaningful activity, independent living, and social connectedness) after a traumatic brain injury (TBI) requires addressing persistent barriers limiting its fulfillment. This qualitative study explored the perceptions and experiences of community integration for individuals living with TBI in the community. Methods: Using semi-structured interviews, four focus groups of individuals with TBI were conducted. Data were analyzed using codebook thematic analysis. Findings: There were 13 participants between the ages of 25 and 64, who had acquired their injury at least three years earlier. Community integration was illustrated through three themes: (1) ‘Am I left on my own?’ explored the support systems after TBI, (2) ‘One size fits all’ described the response of society to TBI, and (3) ‘Adapting to a new normal’ highlighted responses to a changed reality. Conclusions: Individuals with TBI reported decreased community integration in multiple facets of life. Understanding the experiences of community integration after TBI can create room for future rehabilitation interventions that consider new abilities and adaptation to barriers. Full article

Objective: Potassium levels (KLs) influence clinical outcomes in severe traumatic brain injury (TBI). This study investigates the relationship between KLs and clinical outcomes to improve prognosis and guide management. Method: A retrospective study was conducted at a level 1 trauma center in Queens, New York, from January 2020 to December 2023. Patients with an AIS score of 3 or higher were included. KLs were measured at the time of hospital admission, ICU admission, ICU discharge, hospital discharge, and death, if applicable. Clinical outcomes such as age, race, length of hospital stay (H LOS), ICU length of stay (ICU LOS), ventilation days (VDs), Glasgow Coma Scale (GCS), and mortality were assessed. Results: KLs were categorized into five groups: extreme hypokalemia (<2.5 mEq/L), hypokalemia (2.6–3.5 mEq/L), normokalemia (3.5–5.2 mEq/L), hyperkalemia (5.2–7.0 mEq/L), and extreme hyperkalemia (>7.0 mEq/L). Significant correlations were observed between KLs at hospital admission and age (p = 0.0113), race (p = 0.003), and H LOS (p = 0.079). ICU KLs showed positive correlations with AIS head score (p = 0.038), ISS (p = 7.84 × 10⁻⁶), and GCS (p = 2.6 × 10⁻⁶). ICU KLs were also associated with LOS in the Emergency Department (ED) (p = 6.875 × 10⁻⁶) and ICU (p = 1.34 × 10⁻²¹), as well as VDs (p = 7.19 × 10⁻⁷). ICU discharge KLs correlated with ISS (p = 2.316 × 10⁻³), GCS (p = 2.201 × 10⁻³), ED LOS (p = 3.163 × 10⁻⁴), and VDs (p = 7.44 × 10⁻⁴). KLs at discharge were linked with mortality (p < 0.0001) and H LOS (p = 0.0091). Additionally, KLs at the time of death were correlated with ISS (p = 0.01965), GCS (p = 0.01219), ED LOS (p = 0.00594), ICU LOS (p = 0.049), VDs (p = 0.00005), and mortality (p < 0.0001). Conclusions: Potassium imbalances, especially hypokalemia, significantly affect outcomes in severe TBI patients. Monitoring and managing KLs may improve prognosis. Full article

Traumatic brain injury (TBI) initiates a complex cascade of pathophysiological events that have far-reaching consequences beyond the initial injury. This review examines the current state of the literature on the mechanisms underlying neurotrauma and neuroinflammation, with particular emphasis on the molecular cross-talk between these disparate pathways that ultimately precipitates the development of chronic traumatic encephalopathy (CTE). We integrate this mechanistic knowledge with potential diagnostic biomarkers, such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and advances in neuroimaging and machine learning-based predictive tools. Finally, we discuss the current therapeutic approaches under investigation, and highlight which molecular targets have yet to be explored for potential therapeutic development. Full article

Background/Objectives: Traumatic brain injury (TBI) is a global public health concern, affecting over 60 million people annually. It is associated with high rates of mortality and disability, particularly among young and economically active individuals, and remains the leading cause of death in people under 40 years of age. Although computed tomography (CT) is the standard method for excluding intracranial bleeding (ICB), it is frequently unavailable in resource-limited settings where the burden of TBI is greatest. The InfraScanner 2000 is a near-infrared spectroscopy (NIRS) device designed to detect ICB and may serve as a triage tool in environments without access to CT imaging. This study aimed to evaluate the diagnostic performance of the InfraScanner 2000 for detecting ICB in the emergency department (ED) of a trauma center in a cohort of Colombian patients with TBI. Methods: This prospective study was conducted in Cali, Colombia, between December 2019 and February 2021. Adult patients presenting to the ED with blunt TBI were enrolled. InfraScanner assessments were performed according to a standardized protocol, and all participants underwent head CT within 6 h of injury. Results: A total of 140 patients were included. Of these, 66% were male and 34% were female. Most patients (63.57%) were between 18 and 39 years old, with a median age of 39 years (IQR: 18–86). The InfraScanner demonstrated a sensitivity of 60.0% (95% CI: 32.5–84.8), specificity of 78.4% (95% CI: 71.2–85.6), positive predictive value (PPV) of 25.0%, and negative predictive value (NPV) of 94.2% for detecting ICB. Conclusions: The InfraScanner 2000 showed good specificity and high NPV in identifying ICB among Colombian patients with TBI. These findings suggest it could serve as a useful triage tool to support decision-making in emergency settings with limited access to CT imaging. Full article

Objective: The primary objective was to identify whether there were differences in performance for the individual subcomponents of the instrumented timed “Up and Go” (iTUG) between adults with traumatic brain injury (TBI) and healthy controls. Methods: Fifteen adults with moderate-to-severe TBI and fifteen age- and sex-matched controls completed two separate trials of the iTUG. Paired t-tests or Wilcoxon signed rank tests were used to determine the differences between groups. Results: Adults with moderate-to-severe TBI took more time to complete the iTUG (14.50 ± 2.36 s vs. 9.85 ± 1.71 s; p-value = 0.0002), had slower chest flexion angular velocities (63.52 ± 23.25 s vs. 88.19 ± 29.20 s; p-value = 0.0486) and vertical acceleration (2.22 [1.23–2.74] s vs. 3.89 [3.36–5.02] s; p-value = 0.0005) during the sit-to-stand movements, and had slower angular velocities during the turns (p-value < 0.05 for both mean and peak turn angular velocities) compared with the controls. Conclusions: Adults with moderate-to-severe TBI completed the iTUG more slowly than healthy controls. Significant differences were noted in the sit-to-stand and turn subcomponents for adults with moderate-to-severe TBI compared with healthy controls, which would not be apparent from evaluating the total time taken alone. Full article

Introduction: Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with the Glasgow Coma Scale (GCS) serving as a tool to measure injury severity. This study aimed to investigate the relationship between GCS admission scores and various socio-demographic, clinical, injury-related, and hospital-related variables in patients with TBI across two tertiary care centers in Eastern Europe, a region that remains underrepresented in the literature. Methods: A retrospective observational study was conducted using data from 119 TBI patients admitted between March 2020 and June 2023 at Cluj County Emergency Hospital (Romania) and Saint Vincent Hospital (Poland). GCS scores were analyzed as both categorical and continuous variables. Statistical analyses included Wilcoxon and Kruskal–Wallis tests for group comparisons and Spearman correlations for continuous variables. Results: Most patients included suffered a mild TBI (GCS score between 13 and 15). There were significant associations between GCS scores and post-traumatic amnesia (p < 0.05), discharge status (p < 0.01), discharge destination (p < 0.01), and education level (p < 0.01). GCS scores at admission were linked to survival, absence of post-traumatic amnesia, higher education levels, and home discharge. No significant differences observed across sex, residence, employment status, injury type, cause, or mechanism of injury. A weak but significant negative correlation was observed between GCS and length of hospital stay (rho = −0.229, p > 0.05), while age showed a non-significant correlation. Conclusions: The GCS score at admission is significantly associated with various clinical and socio-demographic outcomes in TBI patients, supporting the utility of the GCS score as a prognostic tool. The predominance of mild cases and the absence of radiological data, such as cerebral contusions or epidural or subdural hematomas, limit the generalizability of the findings. Further studies with larger samples and comprehensive imaging data are necessary to validate these findings. Full article