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Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

ObjectiveTo determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients and recorded new neurologic disorders and hospital outcomes.MethodsWe conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.ResultsOf 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17–1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63–0.85, p < 0.001).ConclusionsNeurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

IntroductionPredictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors.MethodsThe Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH.ResultsOut of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92).ConclusionIn patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Background and Purpose— The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods— We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score−24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score−24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95–100 and modified Rankin Scale score of 0–1), good 3-month functional outcome (modified Rankin Scale score of 0–2), and 3-month infarct volume. Results— There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P =0.045) but not median delta NIHSS (3 versus 2; P =0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month Barthel Index (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.75), excellent 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.74; ROC admission , 0.78), and good 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.78). Conclusions— In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Introduction: Stroke is the fifth leading cause of death in the US and a major cause of disability. Atrial fibrillation (AF) increases the risk of ischemic stroke fivefold. Cardioembolic stroke in patients with AF is associated with high mortality. The association of elevated cardiac troponin with mortality in patients with acute ischemic stroke has been studied previously; however, there is limited data in subgroups of ischemic stroke etiology. We sought to determine the association of troponin elevation at presentation with 90-day all-cause mortality in patients with acute ischemic stroke and AF. Methods: The I nitiation of A nticoagulation after C ardioembolic Stroke (IAC) study is a multicenter cohort drawn from eight US Stroke Centers. We included consecutive patients hospitalized with acute ischemic stroke and AF between 2015-2018, who had an initial baseline cardiac troponin I (bcTnI) obtained at presentation. The primary outcome was all-cause mortality at 90 days from stroke onset. We undertook multivariable logistic regression to determine the association between elevated bcTnl (≥0.1 ng/mL) and 90-day mortality. Results: Of the 2084 patients enrolled in IAC, 1889 patients had 90-day follow-up of which 1461 patients had bcTnI available. 239 of the included patients (16.4%) had an elevated bcTnl, and death within 90-days occurred in 323 patients (22.1%). Elevated bcTnI was associated with 90-day mortality in univariable analysis (49.4% vs 24.9%; OR 1.71, 95% CI 1.17-2.50, p Conclusion: In acute ischemic stroke patients with AF, elevated bcTnI was independently associated with 90-day all-cause mortality.

Introduction: Neurologic deterioration (ND) occurs in a quarter of acute lacunar infarcts and may lead to severe disability, but underlying pathophysiology of ND remains poorly understood. We sought to identify risk factors and clinical characteristics associated with ND. Methods: This retrospective observational study included consecutive patients with acute lacunar stroke admitted to New York University Langone Health and Brown University (NYU/Brown). Lacunar stroke was defined as a subcortical infarct 50%) in the parent vessel and no cardioembolic source. We defined ND as any neurologic deterioration referable to the lacunar stroke and not related to a medical or non-cerebrovascular neurological complication. We used logistic regression analyses to determine associations between ND and luminal stenosis ( Results: The NYU/Brown sample included 205 patients, of whom 41 (20%) had ND. In adjusted models, we found no definite association between luminal stenosis and ND (aOR 1.74, 95% CI 0.73-4.14). From CU, 361 total patients were included, of whom 59 (16%) had ND. In adjusted models, we found an association between luminal stenosis and ND (aOR 2.28 95% CI 1.15-4.50). Meta-analysis of both cohorts found luminal stenosis associated with ND (RR [95% CI]: 1.75 [1.23-2.49]). Conclusions: In this multi-center study, luminal stenosis (

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Objective: We aim to investigate infarct patterns and 90-day recurrence in patients with symptomatic intracranial atherosclerotic disease. Background: Large artery atherosclerosis subtype carries a high risk of early recurrent stroke despite medical management. Predictors of recurrence remain poorly understood. We hypothesized that border-zone infarcts are associated with a higher risk of recurrence. Design/Methods: We included consecutive patients admitted to NYU Langone Health (Manhattan and Brooklyn campuses) over 32-months with a diagnosis of acute ischemic stroke secondary to symptomatic intracranial or tandem atherosclerosis. Patients with purely extracranial stenosis were excluded. The primary predictor was infarct pattern (border-zone vs. non-border-zone infarction), defined in accordance to previous studies. We used univariate and multivariable cox-regression models to determine associations between infarct pattern and recurrent cerebrovascular events (RCVE) at 90-days. Results: Ninety-nine patients met the inclusion criteria; 95 were intracranial and 4 were tandem lesions. The mean age was 70 years, 58.6% were men, 15.1% Black and 16.1% Asian. The median symptom onset to arrival time was 1 day, nearly 74.7% of patients were treated with dual antiplatelet therapy and 99% were treated with high intensity statin. Within 90 days of follow up, 19.2% (19/99) had RCVE. In univariate analyses, the only factor associated with RCVE was border-zone infarct pattern when compared to non-border-zone infarct pattern (30.2% vs. 10.7%, p=0.02). In cox regression models, after adjusting for age and sex, border-zone infarct pattern was associated with increased risk of RCVE (adjusted HR 3.21 95% CI 1.21-8.51, p=0.019). Sensitivity analyses excluding patients with tandem lesions (n = 4) did not meaningfully change our findings (adjusted HR 3.04 95% CI 1.11-8.31, p=0.031). Conclusions: In real world post-SAMMPRIS medically treated patients with ICAD, infarct pattern was predictive of 90-day RCVE. Border-zone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for this high-risk cohort.

Background: Emergent treatment with intravenous thrombolysis and mechanical thrombectomy improved outcomes in patients with acute ischemic stroke. We aim to identify differences in acute stroke treatment trends between strokes occurring in the anterior versus posterior circulation. Methods: The IAC (Initiation of Anticoagulation after Cardioembolic stroke) study represents pooled data registry of 8 comprehensive stroke centers across the United States and included patients with cardioembolic stroke in the setting of AFib. In a post hoc analysis, we identified and separated patients into posterior circulation stroke (PCS) and anterior circulation stroke (ACS) groups based on imaging. Patients without infarct locations or those with multi-circulation infarcts were excluded. We compared baseline characteristics, stroke severity and the treatment trends with alteplase (tPA) and mechanical thrombectomy (MT) in PCS vs ACS using Fisher exact test, t-test and non-parametric tests. We then performed multivariable logistic regression adjusted for baseline differences to determine the associations between PCS and tPA or MT. Results: Of the 2084 patients in IAC cohort, 1589 met inclusion criteria for this study, in which 294 (22.7%) had PCS. Mean age was 76.8 years, 29.3% received tPA and 26.9% had MT. When compared to ACS, patients with PCS were more likely to be men (55.4% vs 45.6%, p=0.003), have diabetes (42.8% vs 29.8, p< 0.001) and lower median NIHSS score on admission (4 vs 8, p Conclusion: Posterior circulation strokes are half as likely to receive thrombolytic therapy and almost a third as likely to have thrombectomy, even after adjusting for baseline stroke severity scores. This is possibly due to difficulty in timely identification and diagnostic delays. There is need for better tools incorporating posterior circulation stroke signs and symptoms to allow for early detection and treatment.

Background: Perforator disease caused by parent artery atheromatous disease is one of the mechanisms implicated in the pathogenesis of lacunar infarcts, but there is limited data on its prevalence. We sought to determine the prevalence of parent vessel atheromatous disease in patients with lacunar infarcts. Methods: This is a retrospective study of consecutive patients with lacunar strokes admitted to NYU Langone Medical Center and Brown University from 2017-2019. Lacunar infarct was defined as subcortical infarct 50%) in the parent vessel and no cardioembolic source. Non-invasive imaging (CTA or MRA) was reviewed by a neuroradiologist or a vascular neurologist to determine the presence or absence of stenosis (< 50%) or luminal irregularity without stenosis in the stem artery segment at the location of the perforator corresponding to the infarct. Patients were divided into two groups: luminal irregularity/stenosis vs. none. We compared clinical and radiographic characteristics and rates of neurological deterioration between the two groups. Results: Among 208 patients with lacunar infarcts (mean age 68.9±11.9 years, 40.9% women, 61.1% White, 13.9% Black, and 12.5% Hispanic), 42 (20.2%) had luminal stenosis and 90 (43.3%) had luminal irregularity without stenosis. Baseline characteristics and prevalence of risk factors were similar between the two groups. Patients with luminal irregularity/stenosis had longer median infarct diameter (10.6 mm vs 8.7 mm, p=0.007). Other imaging variables such as the presence of prior lacunar infarcts and white matter disease burden assessed by Fazekas Score were not significantly different between the two groups. The rate of any neurological deterioration after admission was similar between the two groups (22.7% vs. 15.8%, p=0.283). Conclusion: In this multi-ethnic population, nearly two-thirds of patients with a lacunar infarct were found to have luminal irregularity or stenosis in the parent artery corresponding to the infarct, implying a potential atherosclerotic mechanism. Future studies are needed using advanced imaging of the stem artery to define plaque characteristics which may help determine the underlying mechanism.

Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60–0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44–0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted., Summery In this study of 3,473 hospitalized COVID-19 patients, treatment with zinc and an ionophore was associated with a 24% reduced risk of in-hospital mortality in multivariable Cox regression analysis. A sensitivity analysis in a propensity score-matched cohort supported this finding.

Supplemental Digital Content is available in the text., Objectives: Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. Design: Retrospective, multicenter, observational cohort study. Setting: Four New York City hospitals that are part of the same health network. Patients: Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. Interventions: None. Measurements and Main Results: Hyponatremia was categorized as mild (sodium: 130–134 mmol/L), moderate (sodium: 121–129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135–145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08–1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). Conclusions: Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.

Background and Purpose: In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage. Methods: We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. Results: We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01–7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63–2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29–0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22–1.48]). Conclusions: Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

Background and Purpose The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). Methods We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). Results A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 – 7.17, p = 0.021) Conclusion Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.

Background and Purpose: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. Methods: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). Results: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P =0.003) and historical controls (25.0%, P Conclusions: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

BACKGROUND AND PURPOSE Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome. METHODS We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-to-puncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge. RESULTS Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99; P = .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99; P = .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99; P = .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00; P = .16) and ASPECTS

Background: There is limited data on predictors of sICH in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. Methods: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke center over a 30-month period. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH to identify independent predictors of sICH with p Results: We identified 578 patients with acute ischemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: Thrombolysis in cerebral ischemia score, Alberta stroke program early computed tomography score (ASPECTS), and Glucose level, and using these predictors, we derived the weighted TAG score which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48-2.66, AUC=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22-1.79, AUC=0.69) cohorts. Conclusion: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Background/Aims: Guidelines suggest initiating anticoagulation after cardioembolic stroke within 4-14 days from the index event. Data supporting this suggestion did not account for important factors such as infarct burden or early hemorrhagic transformation. Methods: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with an acute cardioembolic stroke in the setting of atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and the primary outcome was the composite endpoint of recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), or major extracranial hemorrhage (ECH) within 90 days. Results: We enrolled 2090 patients from 8 comprehensive centers in the United States, 1325 met the inclusion criteria (362 were excluded due to non-composite endpoint related death within 90 days, 145 lost to follow up, and 258 were not started on oral anticoagulation or the timing was not reported). Anticoagulation (875 DOAC, 404 Warfarin) was initiated in 0-3 days in 49.7%, 4-14 days in 40.4%, and >14 days in 9.9%. The combined endpoint occurred in 10.7% (142) (98 ischemic events, 21 sICH, and 30 ECH) and did not differ between the three groups: 0-3 days (11.9%), 4-14 days (9.9%), >14 days (9.9%), p=0.525. After adjusting for confounders (such as infarct volume, bridging, CHADS2-Vasc, cardiac thrombus, and hemorrhage on 24-hr imaging), oral anticoagulation timing in the 4-14 day period (vs. >14) was not associated with a reduction in ischemic events (adjusted OR 0.74, p=0.438) and oral anticoagulation timing 4-14 days (vs. 0-3) was not associated with a reduction in sICH (OR 1.28, p=0.638). Factors associated with sICH were bridging (OR 5.36, p=0.001) and hemorrhage on 24-hr imaging (OR 7.26, p Conclusion: In this multicenter real world cohort, the recommended (4-14 days) timeframe to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required determine the optimal timing of anticoagulation initiation.

Background and Purpose: Previously we proposed a simple classification system of the left atrial appendage (LAA) morphology, with low risk (LAA-L) defined as one lobe with an acute angle bend arising from the proximal or middle portion and high risk (LAA-H) defined as all other morphologies. We aim to determine the association between LAA morphology (using both classification systems), LAA flow velocity, and stroke rates. Methods: We analyzed consecutive patients with atrial fibrillation (AF) selected for ablation who underwent cardiac CT angiography and transesophageal echocardiogram. The primary correlates were LAA-H and non-chicken wing (NCW) LAA morphology. The primary outcome was the composite endpoint of history of ischemic stroke/TIA or non-lacunar infarct on neuroimaging. Adjusting for CHADS2Vasc score, multivariable models were used to determine associations between LAA morphology and composite outcomes. Results: We identified 379 patients; the primary endpoint occurred in 32/379 patients (8.4%). LAA-H (adjusted OR 3.63, 95% CI 1.44-9.14) and NCW LAA morphology (adjusted OR 2.52, 95% CI 1.15-5.53) were associated with the primary endpoint. LAA flow velocity ≤20 cm/s was more common in LAA-H vs. LAA-L (9.6% vs. 2.8%, p = 0.019), but not in NCW vs. CW LAA morphology (9.7% vs. 3.7%, p = 0.054). Conclusion: The LAA H/L morphological classification system may be superior to the current system in risk stratifying patients with AF and correlates better with impaired LAA flow dynamics.

Introduction: The insular cortex controls several aspects of vital function including autonomic regulation, and strokes affecting the insula have been associated with dysautonomia, cardiac dysfunction, and arrhythmias. Previous studies have shown an association between insular strokes, elevated troponin levels, and atrial fibrillation (AF). In this study, we aim to determine the association between cardiac biomarkers and insular involvement of the infarct and hypothesize that insular involvement implicates a cardioembolic source. Methods: We abstracted data from a prospective comprehensive stroke center registry of consecutive patients with a discharge diagnosis of acute ischemic stroke who underwent brain imaging (CT or MRI) and work up to determine stroke mechanism. Data included demographics, clinical baseline variables, laboratory tests (including admission troponin level), and transthoracic echocardiographic variables (regional wall motion abnormalities, ejection fraction, and left atrial volume index), and stroke subtype. Multivariable logistic regression models were built to determine associations between AF, and cardiac biomarkers and insular infarcts. Results: We identified 1224 patients who met the inclusion criteria; 397 (32.4%) had insular involvement of the infarct. In multivariable models, insular infarcts were associated with AF (adjusted OR 1.73, 95% CI 1.23-2.43, p = 0.001) and left atrial volume index (adjusted OR per standard deviation increase 1.30, 95% CI 1.13-1.49, p = 0.001). There was a trend for association between insular involvement and positive troponin level (adjusted OR 1.45 95% CI 0.91-2.33, p = 0.122) but not with regional wall motion abnormalities (adjusted OR 1.13, 95% CI 0.69-1.84, p = 0.627). Insular involvement was associated with cardioembolic stroke subtype (45.8% vs. 26.7%, p Conclusion: The insular cortex is commonly involved in patients with atrial fibrillation and/or atrial dilation and maybe a neuroimaging biomarker of cardioembolic stroke. Larger studies are needed to confirm this association and test anticoagulation therapy in patients with insular infarcts.

Introduction: Large artery atherosclerosis subtype carries a high risk of early recurrent stroke despite medical management. Predictors of recurrence remain poorly understood. We hypothesized that borderzone infarcts are associated with a higher risk of recurrence. Objectives: We aim to investigate infarct patterns and 90-day recurrence in patients with symptomatic intracranial and/or extracranial atherosclerotic disease. Methods: We included consecutive patients admitted to NYU Langone Health (Manhattan and Brooklyn campuses) over 32-months with a diagnosis of acute ischemic stroke secondary to symptomatic intracranial or extracranial atherosclerosis. The primary predictor was infarct pattern (borderzone vs. non-borderzone infarction), defined in accordance to previous studies. Borderzone infarcts were divided into internal borderzone and cortical borderzone. We used univariate and multivariable cox-regression models to determine associations between infarct pattern and recurrent cerebrovascular events (RCVE) at 90-days. Results: Fifty-five patients met the inclusion criteria; 38 were intracranial, 3 tandem, 14 extracranial. Nearly 71% of patients were treated with dual antiplatelet therapy and 96% were treated with high intensity statin. The RCVE rate was 23.6%. In multivariable models, borderzone infarcts were associated with increased risk of RCVE (adjusted HR 9.8 95% CI 2.1-44.8, p=0.003). The risk of RCVE was highest among internal borderzone infarcts (47.3%) as opposed to cortical borderzone infarcts (33.3%) or non borderzone infarcts (18.8%). Conclusions: Borderzone (and particularly internal borderzone) infarcts are a surrogate marker of impaired distal blood flow and are associated with RCVE despite medical treatment. This highlights the need to develop alternate treatment strategies for this high-risk cohort.

Background and Purpose: The first of the 2 NINDS Stroke Study trials did not show a significant increase in early neurological improvement (ENI), defined as NIHSS improvement by ≥ 4, with alteplase treatment. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods: We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as [(admission NIHSS score–24-hour NIHSS score)x100/admission NIHSS score] and delta NIHSS as (admission NIHSS score–24-hour NIHSS score). We compared ENI using these definitions between alteplase vs. placebo patients. We also used receiver operating characteristic (ROC) curve to determine the predictive association of ENI with excellent 3-month functional outcomes [Barthel Index (BI) score 95 – 100 and modified Rankin scale (mRS) 0-1], good 3-month functional outcome (mRS 0-2) and 3-month infarct volume. Results: There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared to the placebo group (28% vs. 15%, p = 0.045) but not median delta NIHSS (3 vs. 2, p = 0.471). ROC curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month BI (ROC percent 0.83, ROC delta 0.76, ROS admission 0.75), excellent 3-month mRS (ROC percent 0.83, ROC delta 0.74, ROS admission 0.78), and good 3-month mRS (ROC percent 0.83, ROC delta 0.76, ROS admission 0.78). Percentage change had a stronger association with 90-day infarct volume than delta NIHSS score and both delta NIHSS and percent change in NIHSS were more pronounced with faster treatment times. Conclusion: In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Introduction: Previous studies have shown an elevated risk of MI (MI) in patients with symptomatic intracranial atherosclerotic disease (sICAD), but the mediators of increased risk of MI or death in these patients remain uncertain. We aim to determine risk factors associated with MI or death in patients with symptomatic ICAD. Methods: Patients enrolled in SAMMPRIS had sICAD and were randomized to aggressive medical management (AMM) vs. stenting and AMM. The primary outcome of this post-hoc analysis is MI or vascular death within 2 years of follow-up. We excluded patients who were lost to follow up, had a stroke during follow up, had non-vascular death or death within 30 days of stenting. Patients meeting the inclusion criteria were divided into two groups: those with vs. those without the primary outcome. We used binary logistic regression to determine predictors of incident MI or death within 2 years. Results: Of the 451 patients enrolled in SAMMPRIS, 350 patients met the inclusion criteria (reasons for exclusion: 4 deaths occurring within 30 days of stenting, 63 with ischemic stroke, 6 with symptomatic hemorrhage, 7 patients with non-cardiovascular death within 2 years, and 21 lost to follow up). At 2 years, 17 patients (4.9%) had MI/death; 10 patients had MI and 7 had cardiovascular deaths. In a multivariable model, factors associated with MI/death were: history of coronary artery disease (adjusted OR 3.19, 95% CI 1.14 - 8.93, p = 0.027) and systolic blood pressure (adjusted OR per 10 mm increase 1.20, 95% CI 0.98 - 1.44, p = 0.080). This risk was abut 24% with both predictors present and 2.8% with them absent (Figure). Conclusion: Higher systolic blood pressure and pre-existing cardiovascular disease were independently associated with incident MI or vascular death in patients with sICAD, despite medical management. Further studies are needed to confirm this association and test interventions to reduce this risk.

Background: Symptomatic vertebrobasilar (VB) atherosclerotic disease is associated with a high risk of recurrent stroke despite optimal medical therapy. Objective: In this study, we aim to examine the prognosis and associations between risk factors and recurrent major cardiovascular events (MACE) in patients with symptomatic VB stenosis randomized in the medical arm of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. Methods: Data from subjects in the medical arm of the SAMMPRIS trial with an infarct in the territory of vertebral or basilar arteries (n= 73) were analyzed. The primary outcome was MACE: defined as stroke, myocardial infarction, or other cardiovascular death during follow up. Mean risk factor values were compared between subjects who met the primary outcome at 2 years versus those who did not, using T-tests and χ2 tests. Results: Among 73 patients with VB stenosis randomized to medical treatment, 18 patients (24.6%) had recurrent MACE over a mean follow up of 2.8 years. This was significantly less than the rate of MACE in those with VB enrolled in the WASID trial (9.7 per 100-patient years vs. 20.9 per 100-patient years, p Conclusions: In patients with symptomatic VB disease, improvement of medical treatment over time led to a reduction in cardiovascular event rates but this risk remains elevated as nearly 1 in 5 patients had MACE within 2 years. Further risk factor optimization and lifestyle changes are needed to reduce the rates of MACE in this patient population.

Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography. Methods We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Results Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482). Interpretation In this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816.

Background and Purpose: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. Methods: Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). Results: Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). Conclusions: Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR

Introduction: Direct comparisons of stroke risk factors and rates of acute stroke treatment between Asians, Blacks and Whites are limited due to a lack of racial diversity in typical hospital catchment areas. Methods: Consecutive patients with ischemic or hemorrhagic stroke (intracerebral [ICH] or subarachnoid hemorrhage [SAH]) admitted to a single, comprehensive stroke center located in a racially diverse, underserved metropolitan area were prospectively enrolled in a registry between 9/2014-2/2017. Stroke risk factors, admission NIHSS, insurance status and acute stroke treatments (including IV tPA and/or mechanical thrombectomy) were compared between Asian, White and Black patients. Results: Of 1045 stroke patients, 170 (16%) were Asian, 226 (22%) were Black and 649 (62%) were White. Asians had significantly higher rates of ICH than Blacks or Whites (17% versus 6% and 8%, respectively, P Conclusions: In a single site study with minimal geographic/environmental heterogeneity, Asians and Blacks had higher rates of hemorrhagic strokes than Whites and higher rates of being underinsured. Rates of IV tPA utilization were lowest among Blacks, though rates of mechanical thrombectomy were similar across races. Lower rates of IV tpa use appear related to factors other than insurance status or treatment bias.

Introduction: Though some randomized trials of mechanical thrombectomy included octo- and nonagenarians, there is little data on outcomes among the oldest of the old. Methods: Consecutive patients with ischemic stroke admitted to a single, comprehensive stroke center were prospectively enrolled in a registry between 9/2014-2/2017. Rates of mechanical thrombectomy were compared over 10-year patient age epochs. Among those who underwent thrombectomy, recanalization rates, and discharge disposition were compared over age epochs after adjusting for admission NIHSS using multivariable logistic regression analysis. Cochrane-Armitage test of trend was used to assess for dose effect of age on discharge disposition. Good discharge disposition was defined as discharge to home, acute rehabilitation or outpatient physical therapy. Results: Of 1245 ischemic stroke patients, 221 (18%) underwent mechanical thrombectomy. Thrombectomy occurred in 13/75 (17%) aged 40-49, 23/176 (13%) aged 50-59, 41/274 (15%) aged 60-69, 53/289 (18%) aged 70-79, 55/287 (19%) aged 80-89, and 30/108 (28%) aged 90-99. There was no significant difference in thrombectomy rates per age epoch after adjusting for NIHSS. TICI2b-3 recanalization rates (85-93% of cases), IV tPA use (25/221, 11%), and withdrawal of life-sustaining therapy (7%) did not differ significantly across age epochs. However, after adjusting for admission NIHSS, the rates of good discharge disposition decreased proportionately, in a dose effect manner with each 10-year increase in age (Cochrane-Armitage 16.06, P Conclusions: Despite similarly excellent recanalization rates among stroke patients aged 80-99 years who underwent mechanical thrombectomy, good discharge disposition was significantly worse in the oldest of the old after adjusting for admission NIHSS. Nonetheless, nearly half of octogenarians and a third of nonagenarians who underwent mechanical thrombectomy were able to go home or to acute rehabilitation.

BackgroundThere is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation.MethodsWe evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ2 and t tests to identify independent predictors of sICH with pResultsWe identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, pConclusionHigh TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Introduction Scanning properties and analytic methodology of the 5-HT 2A receptor-selective positron emission tomography (PET) tracer 11 C-MDL100907 have been partially characterised in previous reports. We present an extended characterisation in healthy human subjects. Methods 64 11 C-MDL100907 PET scans with metabolite-corrected arterial input function were performed in 39 healthy adults (18–55 years). 12 subjects were scanned twice (duration 150 min) to provide data on plasma analysis, model order estimation, and stability and test–retest characteristics of outcome measures. All other scans were 90 min duration. 3 subjects completed scanning at baseline and following 5-HT 2A receptor antagonist medication (risperidone or ciproheptadine) to provide definitive data on the suitability of the cerebellum as reference region. 10 subjects were scanned under reduced 5-HT and control conditions using rapid tryptophan depletion to investigate vulnerability to competition with endogenous 5-HT. 13 subjects were scanned as controls in clinical protocols. Pooled data were used to analyse the relationship between tracer injected mass and receptor occupancy, and age-related decline in 5-HT 2A receptors. Results Optimum analytic method was a 2-tissue compartment model with arterial input function. However, basis function implementation of SRTM may be suitable for measuring between-group differences non-invasively and warrants further investigation. Scan duration of 90 min achieved stable outcome measures in all cortical regions except orbitofrontal which required 120 min. Binding potential (BP P and BP ND ) test–retest variability was very good (7–11%) in neocortical regions other than orbitofrontal, and moderately good (14–20%) in orbitofrontal cortex and medial temporal lobe. Saturation occupancy of 5-HT 2A receptors by risperidone validates the use of the cerebellum as a region devoid of specific binding for the purposes of PET. We advocate a mass limit of 4.6 μg to remain below 5% receptor occupancy. 11 C-MDL100907 specific binding is not vulnerable to competition with endogenous 5-HT in humans. Paradoxical decreases in BP ND were found in right prefrontal cortex following reduced 5-HT, possibly representing receptor internalisation. Mean age-related decline in brain 5-HT 2A receptors was 14.0 ± 5.0% per decade, and higher in prefrontal regions. Conclusions Our data confirm and extend support for 11 C-MDL100907 as a PET tracer with very favourable properties for quantifying 5-HT 2A receptors in the human brain.

Influenza is an acute viral respiratory infection that results in high morbidity and significant mortality in humans, producing significant health and economical burdens worldwide [1]. Annual vaccination has been the most effective strategy to reduce the impact of influenza virus infection [2]. As a consequence, significant effort has been made to produce effective vaccines that will reduce the incidence and severity of natural infections. In the United States, the use of intramuscular trivalent inactivated influenza vaccine (TIV) is recommended to induce protective immunity through the induction of serum antibodies. Recently, a live attenuated influenza vaccine (LAIV) delivered by intranasal spray was licensed [3–5]. LAIV induces an immune response that more closely resembles natural immunity than the response elicited by the intramuscular vaccine [6, 7]. This vaccine provides comparable levels of protection against laboratory-documented influenza in adults (85% efficacy), compared with TIV [8, 9], but the mechanism of action might be different. Lower serum hemagglutination-inhibition (HAI) titers are seen with LAIV, and they are accompanied by a higher level of immunoglobulin A (IgA) antibodies in nasal wash [8–11], suggesting that other immunological contributors may be involved in the protection following vaccination with LAIV. Although systems biology approaches have been used to predict the immunogenicity of the vaccine YF-17D against yellow fever [12] and, more recently, of TIV and LAIV against influenza [13], the latter study did not examine the mucosal response to LAIV. The present study extends what is known about the systemic response and provides information about the local response to LAIV. To identify factors associated with LAIV vaccination, we performed a study during the 2010–2011 influenza season. We developed a protocol to evaluate the immunological changes in systemic and local (upper respiratory tract) immune responses and collected blood samples and nasal secretions from 79 healthy adult subjects who were vaccinated with LAIV. Our study indicates that LAIV receipt induces a local inflammatory response, triggering nasal release of interferon (IFN) and granulocyte colony-stimulating factor (G-CSF) 2–3 days after vaccination, followed by specific IgA antibody production, with little changes in systemic immunity.

[ 11 C]PHNO is a recently introduced agonist to image DA D 2 -like receptors with Positron Emission Tomography (PET). In cats and humans, [ 11 C]PHNO revealed an atypical distribution compared to radiolabeled D 2 -like antagonists (such as [ 11 C]raclopride) or other D 2 -like agonists (such as [ 11 C]NPA), as it displayed unusual high binding in the globus pallidus (GP). The goal of this study was to assess the pharmacological nature of the binding of [ 11 C]PHNO in the GP in nonhuman primates. As previously reported in humans, [ 11 C]PHNO equilibrium specific to nonspecific equilibrium partition coefficients (V" 3 ) in baboons was much higher in GP (3.88 ± 1.15) than in the dorsal striatum (DST, 2.07 ± 0.43), whereas the reverse was true for [ 11 ]raclopride (1.48 ± 0.41 in GP, 2.56 ± 0.91 in DST) and [ 11 C]NPA (0.87 ± 0.19 in GP, 1.02 ± 0.13 in DST). Administration of unlabeled raclopride resulted in similar reductions of [ 11 C] PHNO V 3 " and [ 11 C]raclopride V" 3 in both the GP and the DST. This observation demonstrated that the [ 11 C]PHNO binding in the GP was specific to D 2 -like receptors. To evaluate the respective contribution of D 3 and D 2 receptors to the binding potential (BP) of [ 11 C]PHNO and [ 11 C]raclopride, experiments were carried out with the selective D 3 partial agonist l-(4(2-Napthoylamino)butyl)-4-(2-methoxyphenyl)-lA-piperazine HCL (BP897). BP897 reduced [ 11 C]raclopride V" 3 by 29% ± 9%, 19% ± 8%, and 10% ± 7% in GP, VST, and DST, respectively, a result consistent with expectation from postmortem studies (D 3 / D 2 ratio in GP > VST > DST). BP897 reduced [ 11 C]PHNO V" 3 by 57% ± 11%, 30% ± 11%, and 13% ± 8% in GP, VST, and DST, respectively, indicating that the D 3 receptor contribution to [ 11 C]PHNO signal is higher than that of [ 11 C]raclopride. From these experiments we conclude that [ 11 C]PHNO is a D 3 preferring agonist, and that this property explains the high GP signal not observed with [ 11 C]raclopride or [ 11 C]NPA. This property might contribute to its higher vulnerability to endogenous DA compared to [ 11 C]raclopride and [ 11 C]NPA.

Dopamine D2 receptors are configured in interconvertible states of high (D(2 high)) or low (D(2 low)) affinity for agonists. The in vivo proportion of sites in high-affinity state remains poorly documented. Previous studies have established the D2 agonist [11C]N-propyl-norapomorphine (NPA) as a suitable positron emission tomography radiotracer for imaging D(2 high) in the living brain. To elucidate the proportion of D2 receptors configured in D(2 high) states in vivo, imaging studies were conducted in three baboons with both [11C]NPA and the D2 receptor antagonist [11C]raclopride. These studies were performed under noncarrier- and carrier-added conditions, to compare the Bmax of [11C]NPA and [11C]raclopride in the same animals. [11C]raclopride in vivo KD and Bmax were 1.59 +/- 0.28 nM (n = 3) and 27.3 +/- 3.9 nM (n = 3), respectively. The in vivo KD of [11C]NPA was 0.16 +/- 0.01 nM (n = 3), consistent with its affinity for D(2 high) reported in vitro. The maximal density of sites for [11C]NPA was 21.6 +/- 2.8 nM (n = 3), i.e., 79% of the [11C]raclopride Bmax. This result suggested that 79% of D2 receptors are configured as D(2 high) in vivo. This large proportion of D(2 high) sites might explain the vulnerability of D2 radiotracers to competition by endogenous dopamine, and is consistent with a previous report that the in vivo binding of agonist radiotracer [11C]NPA is more vulnerable to competition by endogenous dopamine than that of antagonist radiotracer [11C]raclopride.