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Traumatic brain injury (TBI), ranging from mild concussion to severe penetrating wounds, can involve brain regions that contain damaged or lost synapses in the absence of neuronal death. These affected regions significantly contribute to sensory, motor and/or cognitive deficits. Thus, studying the mechanisms responsible for synaptic instability and dysfunction is important for protecting the nervous system from the consequences of progressive TBI. Our controlled cortical impact (CCI) injury produces ~20% loss of synapses and mild changes in synaptic protein levels in the CA3-CA1 hippocampus without neuronal losses. These synaptic changes are associated with functional deficits, indicated by > 50% loss in synaptic plasticity and impaired learning behavior. We show that the receptor tyrosine kinase EphB3 participates in CCI injury-induced synaptic damage, where EphB3−/− mice show preserved long-term potentiation and hippocampal-dependent learning behavior as compared with wild type (WT) injured mice. Improved synaptic function in the absence of EphB3 results from attenuation in CCI injury-induced synaptic losses and reduced d-serine levels compared with WT injured mice. Together, these findings suggest that EphB3 signaling plays a deleterious role in synaptic stability and plasticity after TBI.

BackgroundThe effects of white matter hyperintensity volume and subclinical brain infarcts on the risk of incident stroke, its ischemic subtypes, and mortality require further study in diverse samples.Methods and ResultsStroke‐free participants in the Northern Manhattan Study underwent magnetic resonance imaging (N=1287; mean age 71±9 years, 60% women, 15% non‐Hispanic white, 17% non‐Hispanic black, 68% Hispanic) and were followed for a median of 8 years (interquartile range: 6–9 years). Cox models estimated proportional hazards of incident stroke of all types, ischemic stroke (and its subtypes), and mortality and stratified by race/ethnicity. In total 72 participants (6%) had incident strokes and 244 died (19%). In fully adjusted models, those with larger white matter hyperintensity volume had greater risk of all stroke types (hazard ratio [HR]: 1.4; 95% CI, 1.1–1.9), ischemic stroke (HR: 1.3; 95% CI, 1.0–1.8), and cryptogenic stroke (HR: 2.2; 95% CI, 1.1–4.4). White and black but not Hispanic participants had increased stroke risk (P<0.05 for heterogeneity for all and ischemic stroke). Those with subclinical brain infarct had greater risk for all stroke types (HR: 1.9; 95% CI, 1.1–3.3), ischemic stroke (HR: 2.2; 95% CI, 1.3–3.8), lacunar (HR: 4.0; 95% CI, 1.3–12.3), and cryptogenic stroke (HR: 3.6; 95% CI, 1.0–12.7), without significant heterogeneity across race/ethnic groups. Greater white matter hyperintensity volume increased both vascular (HR: 1.3; 95% CI, 1.1–1.7) and nonvascular (HR: 1.2; 95% CI, 1.0–1.5) mortality among Hispanic and white but not black participants (P=0.040 for heterogeneity). Subclinical brain infarct was associated with increased vascular mortality among Hispanic participants only (HR: 2.9; 95% CI, 1.4–5.8).ConclusionsIn this urban US sample, subclinical cerebrovascular lesions increased the risk of clinical stroke and vascular mortality and varied by race/ethnicity and lesion type.

Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race‐ethnic and sex differences in door‐to‐CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator‐treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator‐treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race‐ethnic disparities persist and require further efforts to improve performance and reduce these disparities.

Background: Sex is a contributing factor to inequalities in stroke care. In line with the aims of the FL-PR CReSD Study to assess Get With The Guidelines-Stroke (GWTG-S) quality improvement data, we sought to compare stroke performance metrics by sex among 9 GWTG-S participating Puerto Rico hospitals from 2010-2014. Methods: Age and NIHSS-adjusted hierarchical generalized linear models, stratified by sex, were evaluated for the following GWTG-S performance metrics: IV tPA treatment, early antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy for atrial fibrillation (AF) at discharge, statin medication at discharge, smoking cessation counseling, defect-free care (compliance with all performance measures), in addition to CT scan ≤25 minutes and door-to-IV tPA administration ≤60 minutes of hospital arrival. Results: Among 3,277 acute ischemic stroke cases, 48% were women. As compared to men, women were older (72±14 vs. 68±13 years, P<0.0001) with higher NIHSS scores (10±8.5 vs. 9±7.7, P=0.005). Women were less likely to receive IV tPA ≤ 4.5 hours among eligible patients arriving ≤ 3.5 hours (OR 0.71, 95% CI 0.51-0.98, P=0.04), early antithrombotic therapy (OR 0.86, 95% CI 0.75-0.97, P=0.02), DVT prophylaxis (OR 0.93, 95% CI 0.88-0.99, P=0.03), statin medication at discharge (OR 0.85, 95% CI 0.78-0.93, P=0.0001), and anticoagulation for AF at discharge (OR 0.67, 95% CI 0.49-0.92, P=0.01) despite having higher rates of AF at admission (11% vs. 7%, P=0.001). Rates of IV tPA for patients arriving ≤ 2 hours, antithrombotic therapy at discharge, and smoking cessation counseling showed no sex differences. While women were less likely to have a CT scan ≤ 25 minutes of hospital arrival compared to men (OR 0.83, 95% CI 0.74-0.93, P=0.002), no difference was found in door-to-IV tPA administration ≤ 60 minutes. Although an overall temporal improvement in defect-free care was observed from 2010-2014 (31% to 63%, P<.0001), women were less likely to receive this measure than men (OR 0.91, 95% CI 0.85-0.97, P=0.007). Conclusions: Overall, stroke care remains lower for Puerto Rican women than men. Continued adoption of the GWTG-S quality improvement program may help reduce sex disparities in quality of care across the island.

Background and Purpose In the US, about half of acute ischemic stroke patients treated with tissue plasminogen activator (tPA) receive treatment within 60 minutes of hospital arrival. We aimed to determine the proportion of patients receiving tPA within 60 minutes (DTNT≤60) and 45 minutes (DTNT≤45) of hospital arrival by race/ethnicity and sex and to identify temporal trends in DTNT≤60 and DTNT≤45. Methods Among 65,654 AIS admissions in the NINDS-funded FL-PR Collaboration to Reduce Stroke Disparities (CReSD) Study from 2010–2015, we included 6,181 IV tPA-treated cases (9.4%). Generalized estimating equations were used to determine predictors of DTNT≤60 and DTNT≤45. Results DTNT≤60 was achieved in 42% and DTNT≤45 in 18% of cases. After adjustment, women less likely received DTNT≤60 (OR=0.81, 95% CI 0.72–0.92) and DTNT≤45 (OR=0.73 95% CI 0.57–0.93). Compared to whites, Blacks less likely had DTNT≤45 during off hours (OR= 0.68, 95% CI 0.47–0.98). Achievement of DTNT≤60 and DTNT≤45 was highest in South Florida (50%, 23%) and lowest in West Central Florida (28%, 11%). Conclusions In the FL-PR Collaboration to Reduce Stroke Disparities, achievement of DTNT≤60 and DTNT≤45 remains low. Compared to Whites, Blacks less likely receive tPA treatment within 45 minutes during off hours. Treatment within 60 and 45 minutes is lower in women compared to men and lowest in West Central Florida compared to other Florida regions and Puerto Rico. Further research is needed to identify reasons for delayed thrombolytic treatment in women and Blacks and factors contributing to regional disparities in DTNT.

Background: Racial and ethnic disparities in stroke care are known to contribute to inequality in stroke outcomes. The goal of the FL-PR CReSD Study is to assess and evaluate Get With The Guidelines-Stroke (GWTG-S) quality improvement data collected among Florida and Puerto Rico hospitals to evaluate for race-ethnic, sex, and regional disparities in stroke performance metrics. We sought to analyze the temporal trends in stroke performance metrics among the 9 hospitals located in Puerto Rico from 2010 to 2013. Methods: Age-adjusted temporal trends were evaluated in the following GWTG-S pre-defined performance measures (IV tPA treatment within 3 hours among eligible patients arriving in 2 hours, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, and smoking cessation counseling) and defect-free care (compliance with all 7 performance measures). Results: The mean age of 3,094 registered stroke cases was 69.5 ± 14.0 years, 50% were men, and 2,184 (71%) were diagnosed as ischemic strokes. Defect-free care occurred in 60% of ischemic stroke patients. Lower performance metrics were found for IV tPA treatment (78%), DVT prophylaxis (64%), and statin medication at discharge (83%). An additional IV tPA measure of treatment by 4.5 hours when arriving by 3.5 hours was observed in 65% of patients. The performance metrics that significantly improved over time from 2010 to 2013 included: IV tPA treatment within 3 hours (64% to 87%, p=0.04), DVT prophylaxis (33% to 87%, p<0.0001), statin medication at discharge (78% to 87%, p=0.01), and defect-free care (37% to 79%, p<0.0001). Conclusions: In only four years, Puerto Rico hospitals participating in GWTG-S showed significant improvement across all pre-defined acute stroke performance measures. Wider implementation of quality improvement programs like GWTG-S among the 3.7 million inhabitants of Puerto Rico could further improve acute stroke care.

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