Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury

xloma.fota13 shared this article with you from Inoreader Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Traumatic brain injury (TBI) and hemorrhage remain the leading causes of death after trauma. We have previously shown that a dose of valproic acid (VPA) at (150 mg/kg) can decrease brain lesion size and hasten neurologic recovery. The current Food and Drug Administration–approved dose of VPA is 60 mg/kg. We evaluate neurologic outcomes and brain lesion size of a single dose of VPA at a level currently within Food and Drug Administration–approved dose in swine subjected to TBI and hemorrhagic shock. METHODS Swine (n = 5/group) were subjected to TBI and 40% blood volume hemorrhage. Animals remained in shock for 2 hours before randomization to normal saline (NS) resuscitation alone (control), NS-VPA 150 mg/kg (VPA 150), or NS-VPA 50 mg/kg (VPA 50). Neurologic severity scores (range, 0–32) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day (PID) 3. RESULTS Shock severity and laboratory values were similar in all groups. Valproic acid–treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs. VPA 150 mg/kg = 8 ± 7 or VPA 50 mg/kg = 6 ± 6; p = 0.02 and 0.003). Valproic acid–treated animals had significantly smaller brain lesion sizes (mean volume in mm3, control = 1,268.0 ± 241.2 vs. VPA 150 mg/kg = 620.4 ± 328.0 or VPA 50 mg/kg = 438.6 ± 234.8; p = 0.007 and 0.001). CONCLUSION In swine subjected to TBI and hemorrhagic shock, VPA treatment, in a dose that is approved for clinical use, decreases brain lesion size and reduces neurologic impairment compared with resuscitation alone. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interleukin 22 mitigates endothelial glycocalyx shedding after lipopolysaccharide injury

xloma.fota13 shared this article with you from Inoreader Interleukin 22 mitigates endothelial glycocalyx shedding after lipopolysaccharide injury Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The endothelial glycocalyx (EG) on the luminal surface of endothelial cells contributes to the permeability barrier of vessels and prevents activation of the coagulation cascade. Endothelial glycocalyx damage, which occurs in the shock state, results in endotheliopathy. Interleukin (IL)-22 is a cytokine with both proinflammatory and anti-inflammatory properties, and how IL-22 affects the EG has not been studied. We hypothesized that IL-22:Fc, a recombinant fusion protein with human IL-22 and the Fc portion of human immunoglobulin G1 (which extends the protein half-life), would not affect EG shedding in endothelium after injury. METHODS Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). Lipopolysaccharide-injured cells (n = 284) were compared with HUVECs with LPS injury plus 0.375 μg/mL of IL-22:Fc treatment (n = 293) for 12 hours. These two cohorts were compared with control HUVECs (n = 286) and HUVECs exposed to IL-22:Fc alone (n = 269). Cells were fixed and stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify EG. Total RNA was collected, and select messenger RNAs were quantified by real time - quantitative polymerase chain reaction (RT-qPCR) using SYBR green fluorescence. RESULTS Exposure of HUVECs to LPS resulted in degradation of the EG compared with control (5.86 vs. 6.09 arbitrary unit [AU], p = 0.01). Interleukin-22:Fc alone also resulted in degradation of EG (5.08 vs. 6.09 AU, p = 0.01). Treatment with IL-22:Fc after LPS injury resulted in less degradation of EG compared with LPS injury alone (5.86 vs. 5.08 AU, p = 0.002). Expression of the IL-22Ra1 receptor was not different for IL-22:Fc treated compared with LPS injury only (0.69 vs. 0.86 relative expression, p = 0.10). Treatment with IL-22:Fc after LPS injury resulted in less matrix metalloproteinase 2 (0.79 vs. 1.70 relative expression, p = 0.005) and matrix metalloproteinase 14 (0.94 vs. 2.04 relative expression, p = 0.02). CONCLUSIONS Interleukin-22:Fc alone induces EG degradation. However, IL-22:Fc treatment after LPS injury appears to mitigate EG degradation. This protective effect appears to be mediated via reduced expression of metalloproteinases. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Time to weigh in on obesity and associated comorbidities in combat-wounded amputees

xloma.fota13 shared this article with you from Inoreader Time to weigh in on obesity and associated comorbidities in combat-wounded amputees Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The Joint Trauma System database estimates that about 1,200 individuals have sustained a combat-related amputation during the Global War on Terror. Previous retrospective studies have demonstrated that combat-related amputees develop obesity and cardiovascular disease, but the incidence of obesity and associated comorbidities in this population is unknown. The objectives of this study are to determine the prevalence of obesity in the military amputee population and to compare this with the general population. METHODS This is a retrospective review of 978 patients who sustained a combat-related amputation from 2003 to 2014. Prevalence of obesity and comorbid conditions were determined. A multivariate logistic regression model was performed to identify risk factors for postamputation obesity. Kaplan-Meier curves were constructed using obesity as the event of interest. RESULTS A total of 1,233 charts were reviewed with 978 patients included for analysis. The median age of injury was 24 years. Median follow-up time was 8.7 years, ranging from 0.5 years to 16.9 years. The average Injury Severity Score was 23.3. The average body mass index preinjury was 25.6 kg/m2, and the average most recent corrected body mass index was found to be 31.4 kg/m2. Prevalence of comorbidities was higher in the amputee population. Fifty percent of patients who progressed to obesity did so within 1.3 years. CONCLUSION There is a notable prevalence of obesity that develops in the amputee population that is much higher than the general population. We determined that the amputee population is at risk, and these patients should be closely monitored for 1 to 2.5 years following injury. This study provides a targeted period for which monitoring and intervention can be implemented. LEVEL OF EVIDENCE Retrospective, basic science, outcomes analysis, level III/IV. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Long-term outcomes of psychoactive drug use in trauma patients: A multicenter patient-reported outcomes study

xloma.fota13 shared this article with you from Inoreader Long-term outcomes of psychoactive drug use in trauma patients: A multicenter patient-reported outcomes study Via Journal of Trauma and Acute Care Surgery - Current Issue INTRODUCTION Psychoactive drug use (PDU) is reported in up to 40% of trauma patients and is associated with a higher rate of in-hospital complications. However, little is known about its long-term impact on trauma patients. We aimed to assess the long-term functional, mental, and psychosocial outcomes of PDU in trauma patients 6 to 12 months after injury. METHODS Trauma patients with moderate to severe injuries (Injury Severity Score, >9) who had a toxicology screen upon admission to one of three level 1 trauma centers were contacted by phone 6 to 12 months postinjury. Psychoactive drug use was defined as the presence of a psychoactive, nonprescribed substance on toxicology screen including amphetamine, barbiturate, benzodiazepine, cannabinoid, methamphetamine, methadone, opioid, oxycodone, methylenedioxymethamphetamine (ecstasy), phencyclidine, tricyclic antidepressant, and cocaine. The interviews systematically evaluated functional limitations, social functioning, chronic pain, and mental health (posttraumatic stress disorder, depression, anxiety). Patients with a score of ≤47 on the Short-Form Health Survey version 2.0 social functioning subdomain were considered to have social dysfunction. Multivariable regression models were built to determine the independent association between PDU and long-term outcomes. RESULTS Of the 1,699 eligible patients, 571 (34%) were included in the analysis, and 173 (30.3%) screened positive for PDU on admission. Patients with PDU were younger (median age [interquartile range], 43 [28–55] years vs. 66 [46–78] years, p View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnostic accuracy of prehospital triage tools for identifying major trauma in elderly injured patients: A systematic review

xloma.fota13 shared this article with you from Inoreader Diagnostic accuracy of prehospital triage tools for identifying major trauma in elderly injured patients: A systematic review Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Older adults with major trauma are frequently undertriaged, increasing the risk of preventable morbidity and mortality. The aim of this systematic review was to evaluate the diagnostic performance of prehospital triage tools to identify suspected elderly trauma patients in need of specialized trauma care. METHODS Several electronic databases (including MEDLINE, EMBASE, and the Cochrane Library) were searched from inception to February 2019. Prospective or retrospective diagnostic studies were eligible if they examined prehospital triage tools as index tests (either scored theoretically using observed patient variables or evaluated according to actual paramedic transport decisions) compared with a reference standard for major trauma in elderly adults who require transport by paramedics following injury. Selection of studies, data extraction, and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool were undertaken independently by at least two reviewers. Narrative synthesis was used to summarize the findings. RESULTS Fifteen studies met the inclusion criteria, with 11 studies examining theoretical accuracy, three evaluating real-life transport decisions, and one assessing both (of 21 individual index tests). Estimates for sensitivity and specificity were highly variable with sensitivity estimates ranging from 19.8% to 95.5% and 57.7% to 83.3% for theoretical accuracy and real life triage performance, respectively. Specificity results were similarly diverse ranging from 17.0% to 93.1% for theoretical accuracy and 46.3% to 78.9% for actual paramedic decisions. Most studies had unclear or high risk of bias and applicability concerns. There were no obvious differences between different triage tools, and findings did not appear to vary systematically with major trauma prevalence, age, alternative reference standards, study designs, or setting. CONCLUSION Existing prehospital triage tools may not accurately identify elderly patients with serious injury. Future work should focus on more relevant reference standards, establishing the best trade-off between undertriage and overtriage, optimizing the role prehospital clinician judgment, and further developing geriatric specific triage variables and thresholds. LEVEL OF EVIDENCE Systematic review, level III. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Roadway features associated with elderly drivers in motor vehicle crashes

xloma.fota13 shared this article with you from Inoreader Roadway features associated with elderly drivers in motor vehicle crashes Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND As the number of older US drivers has increased over the past decades, so has the number of injuries, hospitalizations, and deaths from motor vehicle crashes (MVCs) involving elderly drivers. We seek to identify personal, environmental, and roadway features associated with increased crashes involving elderly drivers. We hypothesize that elderly drivers are more likely to be involved in MVCs at intersections with more complex signage and traffic flow. METHODS This is a retrospective observational study using 2015 to 2019 police traffic crash reports and a Department of Public Health database of built-environment variables from a single urban center. Demographics and environmental/road features were compared for vehicle-only MVCs involving elderly (≥65 years) and younger drivers. χ2 and nonparametric tests were used to analyze 36,168 drivers involved in MVCs. RESULTS There were 2,575 (7.1%) elderly drivers involved in MVCs during the study period. Left turns and all-way stop signs were associated with increased crash risk among elderly drivers compared with younger drivers. Elderly-involved MVCs were less likely to occur at intersections with left-turn restrictions, traffic lights, only one-way streets, and bike lanes compared with MVCs with younger drivers. Elderly drivers were more likely to be involved in MVCs on weekdays, less often intoxicated at the time of the crash, and less frequently involved in fatal MVCs compared with younger drivers. However, elderly drivers were more frequently the at-fault party, especially after the age of 75 years. CONCLUSION Updates to roadway features have potential to decrease injury and death from MVCs involving elderly adults. Left turn restrictions or other innovative safety treatments at all-way stops or where left turns are permitted may mitigate road crashes involving older adults. Education may increase awareness of higher-risk driving tasks such as turning left, and driving alternatives including public transportation/paratransit may offer alternate means to maintain activities of daily living. LEVEL OF EVIDENCE Prognostic/Epidemiological, level IV. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A meta-analysis of the diagnostic accuracy of chest ultrasound for the diagnosis of occult penetrating cardiac injuries in hemodynamically stable patients with penetrating thoracic trauma

xloma.fota13 shared this article with you from Inoreader A meta-analysis of the diagnostic accuracy of chest ultrasound for the diagnosis of occult penetrating cardiac injuries in hemodynamically stable patients with penetrating thoracic trauma Via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND We performed a systematic review (SR) and meta-analysis (MA) to determine the diagnostic accuracy of chest ultrasound (US) compared with a pericardial window (PW) for the diagnosis of occult penetrating cardiac injuries in hemodynamically stable patients with penetrating thoracic trauma. METHODS A literature search in five databases identified relevant articles for inclusion in this SR and MA. Studies were eligible if they evaluated the diagnostic accuracy of chest US, compared with a PW, for the diagnosis of occult penetrating cardiac injuries in hemodynamically stable patients presenting with penetrating thoracic trauma. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for final analysis. Methodological quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2. We performed a MA of binary diagnostic test accuracy within the bivariate mixed-effects logistic regression modeling framework. RESULTS We included five studies in our SR and MA. These studies included a total of 556 trauma patients. The MA found that, compared with PW, the US was 79% sensitive and 92% specific for detecting occult penetrating cardiac injuries in hemodynamically stable patients. The presence of a concomitant left hemothorax was frequent in patients with false-negative results. CONCLUSION This SR and MA found that, compared with PW, US was 79% sensitive and 92% specific for detecting occult penetrating cardiac injuries in hemodynamically stable patients with penetrating thoracic trauma. Caution interpretation of pericardial US results is suggested in the presence of left hemothorax. In these cases, a second diagnostic test should be performed. LEVEL OF EVIDENCE Systematic Review and Meta-analysis, level II. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.