Neurotrauma reports最新文献

A straightforward path to successful scientific translation remains uncharted, particularly in a complex progressive condition such as spinal cord injury (SCI), which affects multiple body functions simultaneously. Evolving regulatory requirements add to the complexity and expense of attaining a treatment that is both safe and efficacious. Although rare, there are examples of SCI scientists who have successfully navigated the "valley of death" from discovery science to completed clinical trials. This article reflects the translational journey of five SCI scientists who have encountered similar and different scenarios while striving to launch or complete a clinical trial. Learning from these experiences has identified lessons learned and gaps, particularly with respect to funding and support for SCI translation.

Traumatic spinal cord injury (TSCI) is a debilitating condition that can have significant effects on physical function and overall quality of life. Mechanisms of injury can vary from major trauma to low-energy falls. There has been a recent increase in the number of elderly patients with TSCI. A retrospective analysis of population-based hospital records linked with health care administrative datasets was conducted to measure age-standardized rates of TSCI over time. The study was conducted to describe the epidemiology and demographic characteristics of patients who experienced TSCI between 2001 and 2021 in the province of British Columbia, Canada. Demographic, clinical characteristics, and rates of TSCI were evaluated over time. Linear regression was used to assess changes over time. The study identified 3622 patients with TSCI. The average age at the time of injury was 51.1 (standard deviation [SD] 21.19) and 75.0% were males. The average annual age-standardized rate in this population was 35.4 per million. The overall rate remained stable throughout the study period. The mean age at injury increased from 41.9 to 57.5 over the study period of 2001-2021 (p < 0.001). The most frequent causes of injury were low-energy falls (49.9%) and motor vehicle injuries (36.6%). The proportion of injuries related to falls increased over the study period (p < 0.001). Motor and sensory complete TSCI were seen in higher rates among younger patients, and cervical spine injuries were most common among all age-groups. The rate of TCSI was consistent during the study period, though the demographic of patients and their injury mechanism changed considerably; elderly low-energy falls were an increasing proportion of cases. Continued vigilance in elderly fall prevention is needed to reduce the incidence of TCSI among the elderly.

Blast-induced traumatic ocular injury (bTOI) is a major cause of vision loss in military personnel involved in recent combat operations. However, its underlying mechanisms remain poorly understood, hindering the development of effective treatments. This study investigated the temporal expression patterns of key inflammatory markers in the retina after blast exposure using a ferret model. Ferrets (n = 40) were subjected to two tightly coupled blasts (20 psi) using an advanced blast simulator. Retinal tissues were collected at 4 h, 24 h, or 28 days post-blast. Differential mRNA expression of Toll-like receptors (TLRs: 1-9), cytokines (IL: 1β, 6, and 10), and cyclooxygenase enzymes (COX: 1 and 2) was assessed using quantitative real-time polymerase chain reaction after blast exposure and compared with sham controls. Our results revealed a rapid and sustained upregulation of multiple TLRs (1, 2, 4, 5, 7, and 8) in the retina following blast exposure, indicating a robust inflammatory response. This was accompanied by a significant increase in pro- and anti-inflammatory cytokines (IL-1β, IL-6 IL-10, and COX2) at 4 h post-blast, suggesting their involvement in the acute pathogenesis of bTOI. Our findings emphasize the critical role of early innate immune responses and the potential for chronic inflammation in bTOI, highlighting the importance of timely therapeutic interventions. Targeting these inflammatory pathways may offer therapeutic avenues for mitigating retinal damage and improving ocular function.

In the United States, data on outcomes in adults hospitalized with traumatic brain injury (TBI) and concomitant seizures are limited. Here, we report on a feasibility analysis to understand the prevalence and consequences of concomitant seizures in patients with TBI. A retrospective database study was conducted using the National Inpatient Sample 2016-2020. Hospitalizations in patients (≥18 years of age) with TBI were assessed and stratified into groups either with or without concomitant seizures. All patient data were stratified by age, sex, ethnicity, and payer type. The primary outcome was the prevalence of seizures or epilepsy among hospitalizations for TBI. Other outcome variables recorded were mean charges, length of hospital stay, and case fatality. Overall, 1,591,575 hospitalizations with TBI were assessed over the study period. TBI prevalence remained relatively constant throughout the study period and was higher in men and those aged ≥65 years. Concomitant seizures were observed in 12.2% of all patients and were highest for men, the 45-64 years age group, and Black and Native Americans. Mean charges were significantly higher and length of hospital stay was significantly longer in TBI hospitalizations with seizures compared with those without seizures across all study years. No significant difference in case fatality between patients with seizures compared with those without seizures was observed. Data from this analysis showed differences in demographics and outcomes for TBI hospitalizations with versus without concomitant seizures, highlighting potential disparities in health care for patients experiencing seizures that warrant further research.

Traumatic brain injury (TBI) is common among legally-impacted adults and has also been linked to negative outcomes throughout the criminal legal system. Despite this, relatively limited TBI research has focused on or even included legally-impacted adults. Existing literature in this population has used heterogeneous TBI definitions, populations, and measures when studying outcomes. This study therefore investigates the feasibility and acceptability of telephone-administered TBI common data elements (CDEs) and the Rehabilitation Needs Survey (RNS) in 85 legally-impacted community-dwelling adults. Regarding feasibility, completion rates across measures were high (88-100%), and noncompletion was most commonly due to participants declining to continue. Regarding acceptability, data collectors were able to administer and code most measures with relative ease. Reported difficulties related to measures requiring detailed data collector training to administer and code, such as the Brain Injury Screening Questionnaire (BISQ) and Brief Test of Adult Cognition by Telephone, or challenges inherent to self-report tests in general. In addition, data collectors recommended adding specific questions to the BISQ to query head injuries experienced during or as a result of their exposure to the criminal legal system. Overall, results support the use of telephone-administered TBI CDEs and the RNS in legally-impacted adults, and underscore the need for culturally-responsive training and technical assistance for TBI researchers engaging with this population.

Previous studies on restrictive versus liberal blood hemoglobin transfusion triggers in critically ill or cardiac surgery patients had established a paradigm favoring restrictive triggers. In contrast, the hemoglobin transfusion threshold in traumatic brain injury optimization and transfusion strategy in patients with acute brain injury trials (2024) suggest that a liberal hemoglobin (90-100 g/L) transfusion trigger is associated with better neuro-outcomes than a restrictive (70 g/L) trigger in anemic patients with acute brain injury. Increased blood oxygen content is one obvious possible reason for the observed superior neuro-outcomes with more liberal red blood cell transfusion. In this author's opinion, another plausible reason is that in replacing extracranial blood loss, which most of the patients in both trials had, avoidance of blood alternatives that could worsen intracranial hypertension might also have benefitted the liberal transfusion cohorts.

Abstract: Traumatic brain injury (TBI) is a leading cause of disability and death in children. Limited data exists on pediatric TBI in Southeast Asia, especially in low- and -middle-income countries. This study investigates the clinical characteristics and outcomes of pediatric TBI patients in a tertiary trauma center in the Philippines. This retrospective cohort study examined pediatric patients (18 years and under) with TBI admitted to a Philippine trauma center from 2021 to 2023. A total of 218 patients were included. Data on demographics, injury mechanisms, TBI severity, cranial imaging, surgical procedures, complications, and discharge outcomes were analyzed.

Abstract: Among the 218 patients, 75% were male, and most were aged 13-18. The primary mechanism of injury was motor vehicle crashes (MVCs), especially in older children (80%). For patients under 5, falls and MVCs were equally common. Most cases were mild (69%), and 40.8% had negative cranial imaging. Epidural hematoma (20%) was the most common abnormal finding. Of the patients, 8% required surgery, with craniotomy for epidural hematoma being the most frequent procedure. Half of those who underwent surgery had neurological deficits, and there was one recorded death. Overall, 86.7% of patients were discharged without complications, though only 34.6% of those with severe TBI had good outcomes. The overall complication rate was 8.7%, with mild neurological deficits being most common. The case fatality rate was 4.6%, with severe TBI showing a higher rate of 30.8%. The majority of patients were male teenagers involved in MVCs. Although most TBIs were mild, there was a notable incidence of severe TBI, particularly with epidural hematoma. These findings suggest higher-impact trauma in the Philippines. The complication and mortality rates align with other studies. Efforts should focus on road safety, traffic law enforcement, and public education. A multi-center prospective study is needed to better understand the factors influencing outcomes in pediatric TBI.

The Spinal Cord Outcomes Partnership Endeavors presented a clinical trials update (CTU) in collaboration with the International Spinal Research Trust as a precourse to their annual meeting. Selected trials adhered to a priori considerations, prioritizing novelty and a focus on neurorestorative approaches. The sessions featured 13 speakers, covering 4 in-preparation, 4 in-progress, and 4 recently completed trials. In addition to in-person attendance, individuals worldwide viewed a live stream of the presentations. Approximately 1600 participants, comprising clinicians, researchers, industry stakeholders, foundations, and individuals with lived experiences, engaged in the CTU through both in-person and virtual channels. Presentations represented a variety of approaches, including drug, biological, and device-based therapeutics. This summary provides high-level summaries of the trials presented and the resulting discussions including lessons learned. Rather than recapitulating published data, the presentations and discussions emphasized the novelty and strengths of each trial, practical aspects of translation, and lessons learned. Throughout the day, several discussion themes surfaced. These included reflections on the suitability of outcome measures and the distinction between statistically or clinically meaningful effects and meaningful changes in quality of life. Additional topics included novel trial designs, selection of inclusion criteria, recognizing the indispensable role of rehabilitation, tailoring approaches to individual needs, the importance of integrating lived experience, and emphasizing the importance of establishing robust pre-clinical data packages before venturing into clinical translation. Importantly, strategic directives are summarized to address these challenges, focusing resources and efforts to steer forthcoming trials effectively.

Sedatives play an important role in the management of patients with severe traumatic brain injury (sTBI) in the intensive care unit (ICU). Benzodiazepines are common for sedation (midazolam-based) but have been discouraged for non-brain-injured patients in the ICU. This study aimed to investigate the effect of midazolam-based sedation versus non-midazolam-based sedation on the need for intracranial pressure (ICP) lowering therapies in patients with sTBI in the ICU. We studied patients with sTBI (Glasgow Coma Sale ≤8) from 14 ICUs in Europe and Australia, who received ICP monitoring and continuous instrumental variable (IV) sedation for at least 24 h. We analyzed the association between sedation strategy and the need for ICP lowering therapies during the first 7 ICU days using a multivariable logistic regression model, adjusted for clinical markers of injury severity. We also analyzed the center as an IV in a random effects model to address potentially unmeasured confounding. Among 227 patients with sTBI, 152 (67%) received midazolam-based sedation. These patients had a lower age and higher median Glasgow Coma Scale on admission compared with 75 patients in the non-midazolam-sedated group. In logistic regression analyses, patients with midazolam-based sedation had higher odds of receiving hyperosmolar therapy (odds ratio [OR]: 3.4, 95% confidence intervals [CI]: 1.6-7.7). This effect could not be confirmed in the instrumental variable analysis (hyperosmolar therapy: OR: 1.3, 95% CI: 0.1-13.1). The mean ICU length of stay was significantly longer in the midazolam-based sedation group compared with the non-midazolam-based sedation group (19 vs. 13 days, hazards ratio 0.6, 95% CI: 0.4-0.8). Midazolam-based sedation was common for patients with sTBI without a significantly increased need for ICP therapies but an association with longer ICU stay. Larger prospective comparative effectiveness studies are needed regarding sedation strategies in critically ill patients with TBI.

Acute traumatic neural injury, also known as traumatic brain injury (TBI), is a leading cause of death. TBI treatment focuses on the use of sedatives, vasopressors, and invasive intracranial pressure (ICP) monitoring to mitigate ICP elevations and maintain cerebral perfusion pressure (CPP). While common sedatives such as propofol and fentanyl have significant side effects, ketamine is an attractive alternative due to its rapid onset and cardiovascular stability. Despite these benefits, ketamine's use remains controversial due to historical concerns about increasing ICP. Using high-frequency monitoring, this retrospective study compared cerebral pressure-flow dynamics in patients with moderate/severe TBI who received ketamine with those who did not. Statistical analysis included descriptive statistics, comparisons within and between patients receiving ketamine, and evaluation of physiological response around incremental dose changes in ketamine. Various cerebral physiological indices were analyzed, including ICP, CPP, regional cerebral oxygen delivery, intracranial compliance, and cardiovascular reactivity metrics. A total of 122 patients were studied, with 17 receiving ketamine (median age: 37 years) and 105 not receiving ketamine (median age: 42 years). Results indicated higher median ICP in the ketamine group compared with the no ketamine group (9.05 mmHg and 14.00 mmHg, respectively, p = 0.00017); however, this is likely due to differences in patient characteristics and injury severity between the groups. No significant differences were observed in any other index of cerebral pressure-flow dynamics or between any incremental dose change condition. These findings suggest that ketamine does not significantly impact cerebral pressure-flow dynamics, challenging historical concerns about its use in patients with TBI.