Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the ‘signature injury’ of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague–Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan’s blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan’s blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t=4.808, p<0.05), and a reduction back toward control levels when bryostatin-1 was administered (t=5.113, p<0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t=4.559, p<0.01) and increased the neuroprotective isozyme PKCε (t=6.102, p<0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

Background Undertriage of older trauma patients is implicated as a cause for outcome disparities. Undertriage is defined by an Injury Severity Score (ISS) ≥16 without full trauma activation. We hypothesized that in patients ≥65 years, undertriage is associated with unfavorable discharge. Methods This is a retrospective study of patients ≥65 years admitted at a Level 1 Trauma Center between July 2016 and June 2018 with blunt trauma. The Matrix method was used to determine the undertriage rate, and outcomes were compared between undertriaged and fully activated patients with ISS ≥16. Favorable outcomes in undertriaged patients instigated further analyses to determine factors that predicted unfavorable discharge condition, defined by discharge from the hospital with severe disability, persistent vegetative state, and in-hospital death. Results The undertriage rate was 7.9%. When compared to fully activated patients with ISS ≥16, a lower percentage of undertriaged patients were discharged in an unfavorable condition (16.6% vs 64.7%, P < .001). On the multivariate analysis, male sex (OR = 1.52), preexisting coronary artery disease (OR = 1.86), age >90 years (OR = 2.31), ISS 16-25 (OR = 3.50), Glasgow Coma Score (GCS) ≤14 (OR = 6.34), and ISS >25 (OR = 9.64) were significant independent risk factors for unfavorable discharge. Discussion The undertriage rate in patients ≥65 years was higher than the accepted standard (5%). However, undertriaged patients had better outcomes than those fully activated with ISS ≥16. Factors more predictive of unfavorable discharge condition were GCS ≤14 and ISS >25. These data suggest that ISS alone is a poor marker for assessing undertriage in older patients. Additional parameters established in this study should be considered as potential markers for better predicting outcomes in older trauma patients.

Background At our hospital, acute surgical care of children aged 6 and older is managed by adult acute care surgeons. Previously published data from a 10-year experience with this model demonstrated no differences in outcomes when compared with pediatric surgical benchmark data. This study assesses for the effects of a learning curve in the care of pediatric patients by comparing outcomes of patients treated in the first three years with those treated in the last 3 years during a 10-year experience with this model. Design This was a retrospective study of pediatric patients aged 6 and older who underwent an emergent or urgent, nontrauma surgical procedure by a general surgeon. Data was obtained via chart review and descriptive statistics were compared between patients operated on between January 1, 2009-January 1, 2012 and January 1, 2016-January 1, 2019. Results In all, 208 cases were performed in the early cohort and 192 cases in the late cohort. Appendectomy was the most common procedure in both intervals (88% early, 94.8% late). Although there was a significant decrease in open procedures in the later cohort (22.6% vs 4.7%, P < .001), there was no significant change in disease-specific complications or negative appendectomies. No consults to a fellowship-trained pediatric surgeon were required during either time period, although one was available if needed. Conclusions Our data demonstrated a decrease in the number of open procedures in the later cohort. This may be due to an increased comfort level with pediatric laparoscopy over time. However, no significant changes in outcomes were observed. This study supports that acute care general surgeons can provide comparable care to pediatric patients within this age demographic and that although a learning curve, appears to exist with respect to pediatric laparoscopy, it is insignificant in terms of its effect on overall outcomes.

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