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Statins, drugs known for lipid lowering capabilities and reduction of cardiovascular disease, have demonstrated neuroprotective effects following ischemic stroke in retrospective clinical and animal studies. However, dosing (methods, time, type of statin, and quantity) varies across studies, limiting the clinical applicability of these findings. Furthermore, a comprehensive review of statins in edema and blood-brain barrier (BBB) breakdown is needed to provide insight on diverse, less explored neuroprotective effects. In the present study, we conduct a meta-analysis of publications evaluating statin administration in animal models of ischemic stroke. We review statins' most effective dosing regimen in four outcomes-infarct, edema, BBB breakdown, and functional outcome-to characterize several parameters of benefit associated with statin administration. A search term was constructed to identify experimental murine studies exploring statin use after transient middle cerebral artery occlusion (tMCAO) in PubMed, Web of Science, and Embase. Extracted data included statin type, dose, time and method of administration, and the four predetermined outcomes (functional outcome, edema, BBB breakdown, and infarction). A meta-analysis and stratified meta-regression were conducted using the standardized mean difference (SMD) method for continuous measurements. Included publications were assessed for bias using SYRCLE's RoB tool for animal studies. A total of 24 studies were included. Statin administration significantly reduced infarct volume (p < 0.0001), edema volume (p < 0.002), and neurological deficit (p < 0.0001). Simvastatin and pravastatin were most effective in reducing infarct volume when compared with atorvastatin (p = 0.0475, p = 0.0004) and rosuvastatin (p = 0.0036, p < 0.0001). Pravastatin outperformed all others in functional outcome. Subcutaneous (SC) injection was most effective in all outcomes. Statin therapy reduced BBB breakdown according to our systematic review. Mean study quality was 4.6/10. While statin therapy evidently improves neurological outcome following ischemic stroke, this analysis adds to our understanding of dosing and statins' effects on edema and BBB breakdown. These findings will aid the design of future studies investigating statin use and have larger implications for the clinical care of ischemic stroke patients.

OBJECTIVEPostoperative surgical site infections (SSIs) in neurosurgical patients carry a significant risk of increased morbidity and mortality. With SSIs accounting for approximately 20% of nosocomial infections and costing approximately $1.6 billion USD annually, there is a need for additional prophylaxis to improve current standards of care. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. A randomized controlled trial assessing its efficacy in the general neurosurgical population is currently underway. Here, the authors report their initial impressions of topical vancomycin safety among patients enrolled during the 1st year of the trial.METHODSThis prospective, multicenter, patient-blinded, randomized controlled trial will enroll 2632 patients over 5 years. Here, the authors report the incidence of adverse events, the degree of systemic vancomycin absorption in treated patients, and pattern changes of antibiotic-resistant profiles of Staphylococcus aureus flora among patients enrolled during the 1st year.RESULTSThe topical vancomycin treatment group comprised 257 patients (514 total enrolled patients), of whom 2 exhibited weakly positive serum levels of vancomycin (> 3.0 mg/dl). S. aureus was detected preoperatively in the anterior nares of 35 (18.1%) patients and the skin near the surgical site of 9 (4.7%). Colonization in the nares remained for many patients (71.4%) through postoperative day 30. The authors found a significant association between preoperative S. aureus colonization and postoperative colonization. Seven methicillin-resistant isolates were detected among 6 different patients. Two isolates were detected preoperatively, and 5 were de novo postoperative colonization. No adverse responses to treatment have been reported to date.CONCLUSIONSThe authors’ data indicate that the use of topical vancomycin is safe with no significant adverse effects and minimal systemic absorption, and no development of vancomycin-resistant microorganisms.Clinical trial registration no.: NCT02284126 (clinicaltrials.gov)

Study Objectives Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI. Methods In an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury. Results In the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, x̅ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency (x̅ = 18.0 vs 21.0, p = 0.0005, d = –0.65) and stop-go tests (x̅ = 30.1 vs 31.1, p = 0.024, d = –0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (beta = 0.22, p = 0.00002) and tau (beta = 0.14, p = 0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores (x̅ = 3.8 vs 2.7, p = 0.0005), raising the possibility that the PSQI might be partly secondary to OSA. Conclusions Poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.

BACKGROUND/PURPOSE: Blood type has become an increasingly recognized risk factor for coagulopathy. We explored the association between blood type and hematoma expansion (HE) after intracerebral hemorrhage (ICH). METHODS: Spontaneous ICH patients prospectively enrolled in an ongoing ICH cohort study at Columbia University Irving Medical Center from 2009 to 2016 were evaluated. Primary ICH patients with admission blood type testing were evaluated for HE differences, defined as > 33% relative HE. The association of blood type with radiographic HE outcomes was assessed using multivariable logistic regression models. The association of blood type and poor clinical outcomes using modified Rankin Scale (mRS 4–6) was additionally explored. RESULTS: Of 272 ICH patients with blood type data and neuroimaging available to determine HE, there were 146 (54%) type-O, 82 (30%) type-A, 34 (13%) type-B, and 10 (3%) type-AB patients. No significant baseline demographic, clinical, or radiographic differences were noted between blood types. Type-B blood was associated with more HE compared to other blood types (OR 2.82; 95% CI 1.23–6.45) after adjusting for known covariates of HE (anticoagulant use, time to admission computed tomography scan, and baseline hematoma volume). No associations with blood type and poor 3 month mRS were identified, but these analyses were limited secondary to our smaller cohort. CONCLUSIONS: There may be differences in HE after ICH in patients with different blood types. Further work is required to replicate these findings and identify the pathophysiologic mechanisms behind coagulopathy between blood types after ICH.

With the rise of great power competition in the Indo-Pacific, Global Health Engagement can facilitate positive foreign relations. Increasing military medical outreach in American Samoa will provide improved health care in the territory, offer relevant medical training in resource-limited environments, and build connections with a community that has many uniformed members.

Introduction Disordered sleep is a critical issue facing the US military due to its negative impact on maintaining force readiness, health, and well-being. Traumatic brain injury (TBI) is highly prevalent among military personnel and commonly co-occurs with disturbed sleep: up to 89% of military service members with TBI report poor sleep quality. Disturbed sleep is a hallmark of post-traumatic stress disorder (PTSD), which often coexists with TBI, with upward of 90% of patients with PTSD reporting some form of sleep disturbance. The pathophysiological mechanisms underlying sleep disturbances in TBI patients remain elusive. Exosomal microRNA (exomiRs), which are implicated in intracellular communication, may provide novel insight into molecular networks related to sleep disturbances in TBI patients. Methods ExomiR was extracted from plasma samples of 108 post-9/11 military personnel, and veterans with a history of mild TBI enrolled in a multicenter prospective longitudinal study. ExomiR profiling analysis was conducted using nCounter Human v3 miRNA Expression Panel with 798 microRNA probes. Sleep quality was assessed using the global score on the Pittsburgh Sleep Quality Index (PSQI), and symptoms of PTSD were measured with the PTSD Checklist for DSM-5 (PCL-5). Generalized linear models and Spearman’s correlations were constructed to analyze the relationship between levels of exomiR and global PSQI score. Results We found 17 exomiR that were significantly (P < 0.05) associated with sleep quality and 11 exomiR significantly associated with PTSD symptoms. Two exomiR, has-miR-1268a and has-miR-139-5p, were significantly associated with both sleep quality and PTSD symptoms. The top three significant exomiR associated with sleep quality were hsa-miR-1250-5p (r = 0.2295, p = 0.0171), hsa-miR-3615(r = 0.2207, p = 0.0229), and hsa-miR-122-5p(r = 0.2069, p = 0.0132). Conclusion Overall, these findings suggest that analysis of exosomal miRNA expression may provide novel insights into the underlying pathobiology of sleep quality in military personnel with mild TBI, independent of PTSD symptoms. Further research is needed to understand the biological underpinnings of poor sleep quality in individuals with TBI and to determine causal links. Support (if any) Intramural Research Program at the NINR, Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.

Introduction Mild traumatic brain injury (mTBI) and sleep disorders are independently associated with inflammation. Following mTBI, elevated levels of cytokines, such as interleukin-6 (IL-6), 10 (IL-10) and tumor necrosis factor alpha (TNFα), have been observed. These signals are also known to modulate sleep homeostasis. IL-6, IL-10 and TNFα concentrations are typically measured in plasma, but recent work has shown that their measurement in extracellular vesicles (EVs) may hold additional value, as they are shielded from degradation and may be more biologically relevant. We hypothesized that inflammatory biomarkers in chronic mTBI patients would be elevated in poor sleepers. Methods In a cross-sectional cohort of warfighters (n=137 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with EV and plasma IL-6, IL-10, TNFα. Protein quantification was performed with Simoa. Two-tailed tests were used with a type I error of p Results In the mTBI cohort, poor sleepers (PSQI>=10, a published military cutoff) had elevated IL-6 vs. good sleepers (mean [SD] pg/mL, EV: 0.47 [0.63] vs 1.01 [1.54], p=0.04, d=0.44; plasma: 5.00 [13.31] vs 6.88 [13.51], p=0.03, d=0.14). Poor sleepers with mTBI had less EV IL-10 (1.71 [8.18] vs 0.30 [0.54], p=0.017). Comparisons of plasma IL-10 were not significant. No differences in TNFα were observed in mTBI groups. In our model, PSQI was the strongest predictor of EV IL-6 (βstd=0.27, p=0.03) in mTBI patients, whereas only BMI predicted IL-6 in controls. EV IL-6, IL-10, and TNFα correlated with PSQI (R=0.21, p=0.019; R=0.21, p=0.014; R=0.22, p=0.013, respectively), but these relationships were not found with plasma. In controls, no correlations or differences in any biomarker were observed between groups. Conclusion Warfighters who report poor sleep had significantly elevated inflammatory biomarkers after chronic mTBI. Cytokine levels in EVs had greater effect sizes between groups compared to plasma levels suggesting EV measurements may have improved signal. Poor sleep and its association with inflammatory cytokines after mTBI may have therapeutic implications. Support (if any) DoD: Contract W91YTZ-13-C-0015/ HT0014-19-C-0004 with VHA Central Office VA TBI Model Systems Program of Research/DHA Contracting Office (CO-NCR) HT0014

Background: Nicotine may have neuroprotective effects on the injured brain through modulation of the cholinergic anti-inflammatory pathway. Aims: This study aimed to evaluate the relationship between cigarette smoking and outcomes in patients with spontaneous intracerebral hemorrhage (ICH). Methods: This was a retrospective review of consecutive ICH patients enrolled in the ICH Outcomes Project from 2009 to 2017. Patients with age ≥18 years and baseline modified Rankin Scale (mRS) score 0-2 were included. Smoking patterns were categorized as recent smoker (≤30 days prior to ICH) and not recent smoker (>30 days prior to ICH). Not recent smokers were further categorized into former smokers and nonsmokers. The primary outcome was good outcome (90-day mRS ≤ 2). Secondary outcomes were excellent outcome (90-day mRS 0-1), 90-day Barthel Index, and in-hospital and 90-day mortality. Results: The study cohort comprised 545 patients, including 60 recent smokers and 485 not recent smokers. Recent smokers had higher rates of good (35% versus 23%; odds ratio [OR] = 1.787, P = .047) and excellent (25% versus 13%; OR = 2.220, P = .015) outcomes compared to not recent smokers. These differences were not significant after baseline adjustments. Recent smokers had higher rates of good (36% versus 24%; OR = 1.732, P = .063) and excellent (25% versus 13%; OR = 2.203, P = .018) outcomes compared to nonsmokers. These differences were not significant after baseline adjustments. A 90-day Barthel Index, in-hospital, and 90-day mortality were comparable between recent and not recent smokers, recent and nonsmokers, and former and nonsmokers. Conclusions: Despite potential neuroprotective effects of nicotine found in cigarettes, these may be outweighed by the detrimental effects of cigarette smoking on health outcomes.

Objectives Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH. Patients and Methods This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months. Results The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p = 0.087). Gender did not affect PTSD symptom development, (t = 1.34, p = 0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01). Conclusion Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD.

Intro: Elevated SBP is common after ICH. Continuous infusions of IV antihypertensive agents are often utilized to quickly correct SBP requiring ICU level care. It is difficult to predict SBP response to these treatments and subsequent medication weaning strategies, as SBP elevation can be the result or etiology of ICH. Identifying patients with a history of uncontrolled hypertension may help tailor SBP treatment. Left ventricular hypertrophy (LVH) on echocardiogram (echo) is a tool to assess for uncontrolled hypertension. Hypothesis: ICH patients with LVH require longer times of continuous infusions of antihypertensive medications (labetalol/nicardipine) compared to those without LVH. Methods: Admission demographics, medical history, continuous infusions of anti-hypertensives, echo data, ICH characteristics and medical/surgical interventions were prospectively collected for primary-ICH patients between 2009-2015. Patients without admission echo were excluded. LVH presence was evaluated as a binary variable and intergroup differences were evaluated using Mann-Whitney U or Student’s t- test for continuous variables and χ2 or Fisher exact test for categorical variables. Association of LVH presence and total duration of labetalol/nicardipine (in hours) within 72 h of ICU admission was evaluated using linear regression analysis after adjusting for age, race, ICH score and surgical intervention. Results: 370 primary-ICH patients with admission echo were identified. Of these patients, 252 (68%) patients had LVH. ICH patients with LVH were significantly younger (64 vs 69yo), had higher prevalence of pre-morbid hypertension (84 vs 64%), and higher ED and NICU admission SBP (189 vs 174mmHg; 158 vs 147mmHg). No intergroup differences in ICH score, surgical interventions or standing oral anti-hypertensive medication use was seen. Linear regression revealed ICH patients with LVH had longer times on continuous anti-hypertensive infusions compared to those without (20 vs 10h; β=0.11; p=0.04) after adjusting for aforementioned covariates. Conclusions: Our findings suggest that ICH patients with LVH on echo present with elevated SBP that is difficult to control. Early identification of this group may allow for earlier, tailored treatments.

Intracerebral hemorrhage (ICH) is one of the most common classes of stroke. Indications for surgery in patients with ICH are largely dependent on patient age, level of consciousness, time elapsed since ICH onset, and the site and size of hemorrhage; however, research in ICH approach, management, surgical indications, and technical management have not completely addressed some of the most common complications of this condition. In this chapter we review the efficacy of craniotomy and hematoma evacuation in various presentations following ICH. We also discuss current guidelines by which endoscopic evacuation can be considered, conclusions from a number of trials involving stereotactic catheter aspiration with fibrinolytic agents, and the use of decompressive craniectomy. We conclude that the standard of care should continue to be refined as new evidence becomes available, specifically that which is concerned with hemorrhage type and location.

Three-dimensional (3D) printers are a developing technology penetrating a variety of markets, including the medical sector. Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics. With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well. Digital Imaging and Communication in Medicine (DICOM) can be translated into Stereolithography (STL) files, which are then read and methodically built by 3D Printers. Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients. Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research. In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, we outline the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery, their applications, and the limitations that need to be overcome if 3D printers are to become common practice in the neurosurgical field.