Hormonal basis of sex differences in anesthetic sensitivity.

General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, oophorectomy has no effect. To identify the neuronal circuits underlying sex differences, we performed whole brain c-Fos activity mapping under anesthesia in male and female mice. Consistent with a key role of the hypothalamus, we found fewer active neurons in the ventral hypothalamic sleep-promoting regions in females than in males. In humans, we demonstrate that females regain consciousness and recover cognition faster than males after identical anesthetic exposures. Remarkably, while behavioral and neurocognitive measures in mice and humans point to increased anesthetic resistance in females, cortical activity fails to show sex differences under anesthesia in either species. Cumulatively, we demonstrate that sex differences in anesthetic sensitivity are evolutionarily conserved and not reflected in conventional electroencephalographic-based measures of anesthetic depth. This covert resistance to anesthesia may explain the higher incidence of unintended awareness under general anesthesia in females.

Inequalities in Meningioma Survival: Results from the National Cancer Database.

Background Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of literature examining how healthcare, demographic, and socioeconomic factors impact patient outcomes. Methods We conducted a retrospective study of 65,812 patients from the National Cancer Database (NCDB; 2004-2012) who received treatment for their meningioma. Univariate and multivariate analyses were performed with the overall five-year survival as the primary outcome, and the following factors: facility type, geography, housing area, patient insurance, sex, ethnicity, race, income, and education. The multivariate model was adjusted for patient age, co-morbidity, tumor size, behavior, and treatment strategy. Results Diagnosis and treatment at an academic/research program, private insurance, female sex, Hispanic ethnicity, and high school diploma conferred a survival advantage on both univariate and multivariate analyses. Conclusions Disparities in survival outcomes in patients with meningiomas exist across multiple healthcare, demographic, and socioeconomic factors. Additional research is needed to elucidate the genetic and environmental factors driving these inequalities.

Growth of Lumbosacral Perineural (Tarlov) Cysts: A Natural History Analysis.

BACKGROUND: Tarlov cysts (TC) are commonly found spinal perineural cysts. Symptomatic TCs are rare, however, and there is no consensus on their pathogenesis and optimal management. OBJECTIVE: To characterize cyst growth in patients with symptomatic TCs. METHODS: This is a retrospective cohort study of 28 subjects, evaluated for symptomatic TCs (2011-2017). Each of the subjects had multiple magnetic resonance imaging (MRIs) across time and was included in a natural history analysis. RESULTS: A total of 42 TCs were identified across the 28 subjects, of which 7 cysts (17%) across 5 subjects demonstrated growth. Across a mean follow-up of 4.7 ± 1.8 years, TCs grew at a relative rate of 2.9 ± 2.6% in the anteroposterior, 4.3 ± 3.8% in the craniocaudal, and 1.4 ± 1.4% in the transverse dimensions per year. None of the cysts decreased in size between successive MRIs. Symptoms of cerebrospinal fluid (CSF) hypotension (positional headaches) were positive predictors of prior cyst growth on logistic regression (P = 0.02, odds ratio = 10). A total of 2 of the 5 subjects were initially asymptomatic from their TCs, and developed symptoms during the period of cyst growth, whereas 2 others experienced worsening of their symptoms during cyst growth. CONCLUSION: We report on the growth of TCs, which is consistent with a widely-held theory that hydrostatic and pulsatile forces of CSF along with a ball-valve phenomenon allow for continuous dilation of TCs.

Learning active sensing strategies using a sensory brain-machine interface.

Diverse organisms, from insects to humans, actively seek out sensory information that best informs goal-directed actions. Efficient active sensing requires congruity between sensor properties and motor strategies, as typically honed through evolution. However, it has been difficult to study whether active sensing strategies are also modified with experience. Here, we used a sensory brain-machine interface paradigm, permitting both free behavior and experimental manipulation of sensory feedback, to study learning of active sensing strategies. Rats performed a searching task in a water maze in which the only task-relevant sensory feedback was provided by intracortical microstimulation (ICMS) encoding egocentric bearing to the hidden goal location. The rats learned to use the artificial goal direction sense to find the platform with the same proficiency as natural vision. Manipulation of the acuity of the ICMS feedback revealed distinct search strategy adaptations. Using an optimization model, the different strategies were found to minimize the effort required to extract the most salient task-relevant information. The results demonstrate that animals can adjust motor strategies to match novel sensor properties for efficient goal-directed behavior.

Predictors of Neurological Outcome Following Subaxial Cervical Spine Trauma.

Background The treatment of traumatic subaxial cervical spine injuries remains controversial. The American Spinal Injury Association (ASIA) impairment scale (AIS) is a widely-used metric to score neurological function after spinal cord injury (SCI). Here, we evaluated the outcomes of patients who underwent treatment of subaxial cervical spine injuries to identify predictors of neurologic function after injury and treatment. Methods We performed a retrospective logistic regression analysis to determine predictors of neurological outcome; 76 patients met the inclusion criteria and presented for a three-month follow-up. The mean age was 50.6±18.7 years old and the majority of patients were male (n=49, 64%). Results The majority of patients had stable AIS scores at three months (n=56, 74%). A subset of patients showed improvement at three months (n=16, 21%), while a small subset of patients had neurological decline at three months (n=4, 5%). In our model, increasing patient age (odds ratio [OR] 1.39, 1.10-2.61 95% confidence interval [CI], P<0.001) and a previous or current diagnosis of cancer (OR 22.4, 1.25-820 95% CI, P=0.04) significantly increased the odds of neurological decline at three months. In patients treated surgically, we found that delay in surgical treatment (>24 hours) was associated with a decreased odds of neurological improvement (OR 0.24, 0.05-0.99 95% CI, P=0.048). Cervical spine injuries are heterogeneous and difficult to manage. Conclusion We found that increasing patient age and an oncologic history were associated with neurological deterioration while a delay in surgical treatment was associated with decreased odds of improvement. These predictors of outcome may be used to guide prognosis and treatment decisions.

Predictors of Failure of Nonoperative Management Following Subaxial Spine Trauma and Creation of Modified Subaxial Injury Classification System.

BACKGROUND: Subaxial cervical spine injuries may be treated with either nonoperative stabilization or surgical fixation. The subaxial injury classification (SLIC) provides 1 method for suggesting the degree of necessity for surgery. In the current study, we examined if the SLIC score, or other preoperative metrics, can predict failure of nonoperative management. METHODS: We performed a retrospective chart review to identify patients who presented with acute, nonpenetrating, subaxial cervical spine injury within our health system between 2007 and 2016. Patient demographics, medical comorbidities, injuries, and treatments were collected. Logistic regression analysis was used to determine potential predictors of failure of nonoperative management. RESULTS: During the study period, 40 patients met the inclusion criteria. A small subset of patients failed nonoperative management (n = 5, 12.5%). The mean SLIC score was 3.9 ± 1.9; however, 14 (35%) patients had scores >4. Neither total SLIC score (P = 0.68) nor SLIC subscores (morphology [P = 0.96], discoligamentous complex [P = 0.83], neurologic status [P = 0.60]) predicted failure of nonoperative treatment. Time to evaluation/treatment did predict failure of nonoperative management. Evaluation within 8 hours of injury was a negative predictor of failure (odds ratio = 0.03, P = 0.001) and evaluation 24 hours or more after injury was a positive predictor of failure (odds ratio = 66.00, P < 0.001). We created a modified SLIC score on the basis of these findings, which significantly predicted failure of nonoperative management (P = 0.044). CONCLUSIONS: Management of subaxial spine injuries is complex. In our cohort, SLIC scoring did not adequately predict odds of failure of nonoperative management. Time to evaluation, however, did. We created a modified SLIC score that significantly predicted failure of nonoperative management.

Outcome differences in adolescent blunt severe polytrauma patients managed at pediatric versus adult trauma centers.

BACKGROUND: Previous research suggests adolescent trauma patients can be managed equally effectively at pediatric and adult trauma centers. We sought to determine whether this association would be upheld for adolescent severe polytrauma patients. We hypothesized that no difference in adjusted outcomes would be observed between pediatric trauma centers (PTCs) and adult trauma centers (ATCs) for this population. METHODS: All severely injured adolescent (aged 12-17 years) polytrauma patients were extracted from the Pennsylvania Trauma Outcomes Study database from 2003 to 2015. Polytrauma was defined as an Abbreviated Injury Scale (AIS) score ≥3 for two or more AIS-defined body regions. Dead on arrival, transfer, and penetrating trauma patients were excluded from analysis. ATC were defined as adult-only centers, whereas standalone pediatric hospitals and adult centers with pediatric affiliation were considered PTC. Multilevel mixed-effects logistic regression models assessed the adjusted impact of center type on mortality and total complications while controlling for age, shock index, Injury Severity Score, Glasgow Coma Scale motor score, trauma center level, case volume, and injury year. A generalized linear mixed model characterized functional status at discharge (FSD) while controlling for the same variables. RESULTS: A total of 1,606 patients met inclusion criteria (PTC: 868 [54.1%]; ATC: 738 [45.9%]), 139 (8.66%) of which died in-hospital. No significant difference in mortality (adjusted odds ratio [AOR]: 1.10, 95% CI 0.54-2.24; p = 0.794; area under the receiver operating characteristic: 0.89) was observed between designations in adjusted analysis; however, FSD (AOR: 0.38, 95% CI 0.15-0.97; p = 0.043) was found to be lower and total complication trends higher (AOR: 1.78, 95% CI 0.98-3.32; p = 0.058) at PTC for adolescent polytrauma patients. CONCLUSION: Contrary to existing literature on adolescent trauma patients, our results suggest patients aged 12-17 presenting with polytrauma may experience improved overall outcomes when managed at adult compared to pediatric trauma centers. LEVEL OF EVIDENCE: Epidemiologic study, level III.

A Preliminary Analysis of Compassion Satisfaction and Compassion Fatigue With Considerations for Nursing Unit Specialization and Demographic Factors.

Compassion fatigue (CF), or vicarious traumatization, is a state of physical/emotional distress that results from caring for those experiencing pain. We sought to characterize levels of CF in intensive care unit (ICU) and oncology nursing populations with subanalyses comparing specific personal/professional demographic factors. The Professional Quality of Life (ProQOL) scale, a validated tool for assessing CF, burnout (BO), and compassion satisfaction (CS), was distributed to the ICU and oncology divisions of a community hospital. Demographic data and ProQOL scale scores were collected and compared within specialty and gender subgroups. Two-sample t tests and regression analyses were used to compare groups. Statistical significance was defined as p < .05. A total of 86 nurses submitted completed surveys able to be analyzed. Levels of CS were significantly lower (p = .023) and levels of BO were significantly higher (p = .029) in ICU nurses than in oncology nurses. Male nurses exhibited significantly higher CS (p = .001) and significantly lower BO (p = .021) and CF (p = .014) than female nurses. Intensive care unit nurses and female nurses from both ICU and oncology specialties may be at increased risk for developing a poorer overall ProQOL and CF.

An epidemiologic overview of 13 years of firearm hospitalizations in Pennsylvania.

BACKGROUND: Gun violence is a controversial public health issue plagued by a lack of recent research. We sought to provide a 13-y overview of firearm hospitalizations in Pennsylvania, analyzing trends in mode, intent, and outcome. We hypothesized that no adjusted change in mortality or functional status at discharge (FSD) would be observed for gunshot wound (GSW) victims over the study period. METHODS: All admissions to the Pennsylvania Trauma Outcome Study database from 2003 to 2015 were queried. GSWs were identified by external cause-of-injury codes. Collected variables included patient demographics, firearm type, intent (assault and attempted suicide), FSD, and mortality. Multilevel mixed-effects logistic regression models and ordinal regression analyses using generalized linear mixed models assessed the impact of admission year (continuous) on adjusted mortality and FSD score, respectively. Significance was set at P < 0.05. RESULTS: Of the 462,081 patients presenting to Pennsylvania trauma centers from 2003 to 2015, 19,342 were GSWs (4.2%). Handguns were the most common weapon of injury (n = 7007; 86.7%) among cases with specified firearm type. Most GSWs were coded as assaults (n = 15,415; 79.7%), with suicide attempts accounting 1866 hospitalizations (9.2%). Suicide attempts were most prevalent among young and middle-aged white males, whereas assaults were more common in young black males. Rates of firearm hospitalizations decreased over time (test of trend P = 0.001); however, admission year was not associated with improved adjusted survival (adjusted odds ratio: 0.99, 95% confidence interval: 0.97-1.01; P = 0.353) or FSD (adjusted odds ratio: 0.99, 95% confidence interval: 0.98-1.00; P = 0.089) while controlling for demographic and injury severity covariates. CONCLUSIONS: Temporal trends in outcomes suggest rates of firearm hospitalizations are declining in Pennsylvania; however, outcomes remain unchanged. To combat this epidemic, a multidisciplinary, demographic-specific approach to prevention should be the focus of future scientific pursuits.

Omega-3 Fatty Acid Supplementation and Warfarin: A Lethal Combination in Traumatic Brain Injury.

Polyunsaturated fatty acids such as omega-3 eicosapentaenoic acid and omega-6 docosahexaenoic acid, found in over-the-counter fish oil supplements, are often consumed for their beneficial, prophylactic, anti-inflammatory effects. Although the mechanisms of action are not fully known, a diet rich in polyunsaturated fats may reduce the risk of hyperlipidemia, atherosclerosis, high low-density lipoprotein cholesterol levels, hypertension, and inflammatory diseases. Masked by its many benefits, the risks of omega-3 fatty acid supplementation are often underappreciated, particularly its ability to inhibit platelet aggregation and promote bleeding in patients taking anticoagulant medications. The following details the clinical case of an elderly patient taking warfarin and fish oil supplementation whose warfarin-induced coagulopathy could not be reversed after suffering blunt head trauma.

Big children or little adults? A statewide analysis of adolescent isolated severe traumatic brain injury outcomes at pediatric versus adult trauma centers.

BACKGROUND: The appropriate managing center for adolescent trauma patients is debated. We sought to determine whether outcome differences existed for adolescent severe traumatic brain injury (sTBI) patients treated at pediatric versus adult trauma centers. We hypothesized that no difference in mortality, functional status at discharge (FSD), or overall complication rate would be observed between center types. METHODS: All adolescent trauma patients (aged 15-17 years) presenting with isolated sTBI (head Abbreviated Injury Scale [AIS] score ≥3; all other AIS body region scores ≤2) to accredited Levels I to II trauma centers in Pennsylvania from 2003 to 2015 were extracted from the Pennsylvania Trauma Outcome Study database. Dead on arrival, transfer, and penetrating trauma patients were excluded from analysis. Adult trauma centers were defined as non-pediatirc (PED) (n = 24), whereas standalone pediatric hospitals and adult centers with pediatric affiliation were considered Pediatric (n = 9). Multilevel mixed effects logistic regression models and a generalized linear mixed models assessed the adjusted impact of center type on mortality, overall complications, and FSD. Significance was defined as a p value less than 0.05. RESULTS: A total of 1,109 isolated sTBI patients aged 15 to 17 years presented over the 13-year study period (non-PED, 685; PED, 424). In adjusted analysis controlling for age, shock index, head AIS, Glasgow Coma Scale motor, trauma center level of managing facility, case volume of managing facility, and injury year, no significant difference in mortality (adjusted odds ratio, 0.82; 95% confidence interval [CI], 0.23-2.86; p = 0.754), FSD (coefficient, -0.85; 95% CI, -2.03 to 0.28; p = 0.136), or total complication rate (adjusted odds ratio, 1.21; 95% CI, 0.43-3.39; p = 0.714) was observed between center types. CONCLUSION: Although the optimal treatment facility for adolescent patients is frequently debated, patients aged 15 to 17 years presenting with isolated sTBI may experience similar outcomes when managed at pediatric and adult trauma centers. LEVEL OF EVIDENCE: Epidemiologic study, level III; therapeutic study, level IV.