bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP180: Lifelong Cerebrovascular And Neurological Disease Burden Among Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts And Leukoencephalopathy (cadasil): Analysis Of 914 Cadasil Patients From A Global Research Network
Authors: Pan Alan P , Meeks Jennifer , Potter Thomas , Bako Abdulaziz , Tannous Jonika , Johnson Carnayla , Baig Eman , Khan Osman , Dubey Prachi , Ahmed Wamda O , Misra Vivek , Vahidy Farhaan S
Published: February 2022

Background:
We evaluated the cerebrovascular and neurological disease (CVND) burden among patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Methods:
Harmonized electronic medical record data from a global research network were utilized to identify diagnosed CADASIL patients. We compared demographics, risk factors, co-existing conditions, and outcomes for CADASIL patients with and without stroke sub-types (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH] and transient ischemic attack [TIA]). Likelihood of stroke incidence and overall mortality associated with sex were computed. Odds ratios (OR) and 95% confidence intervals (CI) are reported.

Results:
Between 2018 and 2020, 914 CADASIL patients were identified (Median (IQR) age: 60 (50 - 69) years, 61.3% females); of whom 596 (65.2%) had a stroke diagnosis. Among all CADASIL-Stroke patients, 89.4% had IS, which co-existed with TIAs in 27.7% and ICH / SAH in 6.2% (Figure). Among 30% and 71% of CADASIL-Stroke patients, the initial stroke event occurred before 50 and 65 years of age, respectively. In addition to a higher burden of hypertension, atrial fibrillation, hyperlipidemia, and diabetes; a higher proportion of CADASIL-Stroke patients (vs CADASIL-non-Stroke) had other co-existing neurological conditions, including migraines (36.7% vs 29.9%), cognitive impairment (38.8% vs 24.2%), epilepsy / seizures (18.6% vs 11.6%), and mood disorders (52.9% vs 40.9%). Adjusted for age and commodities, males had a higher risk of stroke (OR, CI: 1.37, 1.01 - 1.86) and also demonstrated higher overall mortality in a separate model additionally adjusted for stroke diagnoses (OR, CI: 2.72, 1.53 - 4.84).

Conclusion:
Given the high CVND burden; early genetic screening and targeted preventive strategies are warranted among patients with suspected CADASIL and other hereditary cerebral small vessel diseases.
Abstract WP181: Statin Usage Increases White Matter Hyperintensities: A Post-hoc Analysis Of SPRINT-MIND
Authors: Goldstein Eric , Garg Gauri , Navarro Kayla , Wolcott Zoe , Yaghi Shadi , Wong Ka-ho , de Havenon Adam H
Published: February 2022

Introduction:
White matter hyperintensity (WMH), a radiographic marker of cerebral small vessel disease, is typically treated by modification of conventional cerebrovascular risk factors. However, the influence of dyslipidemia and the impact of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) on WMH is less certain. The goal of this study was to evaluate the influence of statins on progression of WMH over a four-year interval.

Methods:
We performed a post-hoc analysis of the SPRINT-MIND database for participants who had completed a baseline and a 4-year follow-up brain MRI with volumetric WMH calculations. Follow-up visits within this time window included data on medications, including statins. We defined statin usage as no therapy (0% of visits), partial therapy (1 - 99% of visits) or full therapy (100% of visits) based on this self-reported data. WMH progression was calculated as the difference in WMH volume between the two scans and then segmented into tertiles. ANOVA and chi-squared tests were used for continuous and categorical variables with adjustments made for variables known to influence WMH development.

Results:
425 individuals were included in this study: 53% (226/425) without statins use, 27% (115/425) with partial use and 20% (84/425) and full use. Demographic characteristics and baseline WMH volumes were similar amongst the cohort. With increasing statin use, a significant reduction in LDL was identified. Those with full statin use were significantly more likely to be in the top tertile of worse WMH progression (adjusted OR 2.30, 95% CI 1.11 - 4.77, p = 0.025).

Conclusion:
SPRINT-MIND participants prescribed a statin were nearly 2.5 times more likely to be within the top tertile of WMH progression over four years, despite adjustment for synergistic risk factors and improvement in LDL.
Abstract WP188: Temporal Trends And Sociodemographic Factors In Blood Pressure Awareness, Treatment, And Control Among U.S. Stroke Survivors
Authors: Oh Daniel , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: February 2022

Background:
Blood pressure (BP) control is crucial for secondary stroke prevention. Previous studies have shown that one in five stroke survivors have unrecognized hypertension and one in three have poorly controlled BP. Little is known regarding recent trends in BP awareness, treatment, and control among stroke survivors in the U.S.

Methods:
Among adults (age>=18 years) with self-reported stroke who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we assessed temporal trends in BP awareness, treatment and control by age group, sex, race/ethnicity, education, and poverty income ratio (PIR). BP control was defined as Systolic Blood Pressure (SBP) <140/90 mm Hg. Factors associated with BP control were assessed with Poisson regression models adjusting for sociodemographic factors and antihypertensive use.

Results:
Among individuals with self-reported stroke (n=1,883), the age-adjusted proportion of individuals with BP awareness increased from 87% (82-91%) in 1999-2002 to 96% (93-98%) in 2007-2010, then decreased to 92% (88-95%) in 2015-2018 (
P
=0.005, quadratic trend). For those with hypertension, antihypertensive use increased from 87% (76-93%) in 1999-2002 to 97% (93-98%) in 2007-2010 and 96% (93-98%) in 2015-2018 (
P
=0.013, quadratic trend). BP control significantly increased from 40% (29-52%) in 1999-2002 to 63% (65-81%) in 2007-2010, then decreased to 58% (50-66%) in 2015-2018 (
P
=0.014, quadratic trend). Factors associated with poorly controlled BP in 2011-2018 were age 75+ years (vs. 18-44) [PR 0.60 (0.44-0.82),
P
≤0.01], female sex [PR 0.79 (0.66-0.94),
P
≤0.01], Black race (vs. Non-Hispanic White race) [PR 0.79,
P
=0.01], and lack of health insurance (vs. Medicare) [PR 0.53 (0.33-0.86),
P
=0.01].

Conclusion:
While BP awareness, treatment, and control among stroke survivors increased from 1999 to 2010, the trend reversed in 2011-2018. Future work could help identify reasons for the worrisome trends and target vulnerable stroke survivors for sustained optimal BP control.
Abstract WP198: Hematological And Embolic Biomarkers And Clinical Outcomes In Patients With Cancer And Ischemic Stroke
Authors: Navi Babak B , Zhang Cenai , Sherman Carla , Genova Richard , LeMoss Natalie M , Kamel Hooman , Tagawa Scott T , Saxena Ashish , Ocean Allyson J , Kasner Scott E , Cushman Mary , Elkind Mitchell S , Peerschke Ellinor , DeAngelis Lisa M
Published: February 2022

Introduction:
We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS.

Methods:
In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes.

Results:
Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS.

Conclusion:
Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.
Abstract WP201: Increasing Mortality From Ischemic Stroke In The US, Racial And Etiological Analysis
Authors: Fadhil Ali , Delozier Sarah , Sundararajan Sophia
Published: February 2022

Background:
Ischemic stroke is the fifth leading cause of death in the United States. In spite of the recent advances in the management of ischemic stroke, mortality rates remain high and have increased in recent years. Importantly, mortality differs by race, with African Americans more likely to die from stroke. To better understand stroke mortality we examined data from 1999 through 2018 with respect to both race and stroke subtype.

Methods:
Using the Multiple Cause Of Death Database, we identified all patients who died of cerebral infarction (CI) using the International Classification of Diseases, 10th revision code I63. Age-adjusted mortality rates (AAMR) standardized to the 2000 US census data were used. Data for continuous variables were examined using simple linear regression models and multivariable linear regression models controlling for relevant covariates. All tests were two-tailed and p < 0.05 was considered significant.

Results:
A total of 201,157 CI deaths were identified between 1999 and 2018. AAMR showed a U-shaped trend, such that compared to 1999-2004 (4.52±0.60) AAMR decreased from 2005-2014 (2.06±0.20), p < 0.001, and increased from 2015-2018 (3.63±1.32), p < 0.001. AAMR differed significantly by race, p = 0.045. Rates were 3.05+1.26 for Caucasians and 4.04+1.74 for African Americans. AAMR decreased between 1999 and 2018 for thrombotic strokes, p < 0.001, while AAMR increased over this time for embolic stroke, p < 0.001. Amongst Caucasians, there was no significant differences in AAMR for each stroke subtype from 1999 to 2018, p = 0.081. However, for African Americans, there was a significantly higher AAMR for thrombotic strokes (0.56±0.33) compared to embolic strokes (0.33±0.15), p = 0.006.

Conclusion:
Despite recent advances in ischemic stroke management, AAMR has increased in the last 4 years by 1.8 times. AAMR in African Americans is 1.3 times that of Caucasians with African American mortality from thrombotic stroke being 1.7 times higher than from embolic stroke. Mortality from CI caused by embolism increased by 2.8 times over the study period while that due to thrombosis decreased by 5 times. Further studies are needed to clarify the reasons behind the recent increase in AAMR.
Abstract WP203: Effects Of Oral Factor Xa Inhibitors On Ischemic Stroke In Patients Without Atrial Fibrillation: Systematic Review Of Randomized Clinical Trials
Authors: Katsanos Aristeidis , Perera Kanjana , Eikelboom John W , HART Robert G
Published: February 2022

Background and Purpose:
To assess the effects of oral factor Xa inhibitors for prevention of ischemic stroke in patients without a history of atrial fibrillation.

Methods:
Systematic review of randomized clinical trials (RCTs) testing oral factor Xa inhibitors in patients without a history of atrial fibrillation that reported ischemic stroke.

Results:
Twenty-two RCTs reported 1194 ischemic strokes: five RCTs testing apixaban (75 ischemic strokes), one RCT each testing betrixaban (52 ischemic strokes) and edoxaban (1 ischemic stroke), and 15 RCTs testing rivaroxaban (1066 ischemic strokes). Three double-blinded RCTs reported statistically significant reductions in ischemic stroke: Two comparing rivaroxaban 2.5mg twice daily versus placebo in patients with cardiovascular disease (COMPASS, hazard ratio (HR) 0.51, 95%CI 0.38-0.68 and COMMANDER-HF, HR 0.64, 95%CI 0.43-0.95), and a third trial compared betrixaban 80mg daily with enoxaparin followed by placebo in patients hospitalized for acute medical illness (APEX, relative risk 0.53, 95%CI 0.30-0.94). Compared with aspirin, rivaroxaban 5mg twice daily significantly reduced ischemic stroke in patients with chronic atherosclerosis in COMPASS (HR 0.69, 95%CI 0.53-0.90), but in contrast rivaroxaban 15mg daily vs. aspirin showed no reduction in ischemic stroke in patients with recent embolic stroke in the large NAVIGATE ESUS trial (HR 1.01, 95%CI 0.81-1.26). Comparisons from 18 other RCTs were inconclusive, although trends consistently showed numerically fewer ischemic strokes among those assigned oral fXa inhibitors compared with placebo.

Conclusions:
There is convincing evidence that oral factor Xa inhibitors reduce ischemic stroke in patients without a history of atrial fibrillation. The strongest evidence was for rivaroxaban 2.5mg twice daily when given with aspirin in patients with cardiovascular disease. Reduction in ischemic stroke by other dosages, by other factor Xa inhibitors, and when given without antiplatelet agents is less certain. The contribution of atrial fibrillation-related stroke unlikely accounts for the observed reductions.
Abstract WP212: Racial Disparities In Perioperative Stroke And Mortality Following Stroke In Adult Cardiac Transplant Recipients
Authors: Liou Lathan , Lehman Laura L , Salia Soziema , Gupta Suruchi , Barrera Francisco , Mostofsky Elizabeth , Murray Mittleman Murray A
Published: February 2022

Introduction:
In the general US population, Black adults have a higher stroke incidence and mortality rate after stroke compared to white adults. Among heart transplant recipients, Black adults also have a higher mortality rate beginning 6-12 months post-transplant. Whether there are racial disparities in perioperative stroke incidence and all-cause mortality following perioperative stroke among cardiac transplant recipients is unknown.

Methods:
Using the Scientific Registry of Transplant Recipients, we examined all adults in the United States who received their first heart transplant between January 2008 - December 2018. We used multivariable conditional logistic regression to assess the association between race and perioperative stroke. We used multivariable Cox proportional hazard regression to examine the association between race and mortality among adults who survived a perioperative stroke. In both models, we included age, sex, hospitalization status, prior ventricular assist device (VAD) implantation, extracorporeal membrane oxygenation (ECMO), calendar year, etiology of heart disease, bilirubin, and functional status as covariates.

Results:
Among 20,912 adults, 428 (2.7%) white recipients and 126 (2.4%) Black recipients had a perioperative stroke. In a multivariable model, there was 11% lower odds of perioperative stroke in Black recipients compared to white recipients (OR = 0.89, 95% CI: 0.71, 1.12). Among perioperative stroke survivors, mortality rates were similar between Black and white recipients within 6 months (HR = 1.02, 95% CI: 0.70, 1.49) and in long-term follow up (HR = 0.95, 95% CI: 0.52, 1.73). However, our regression results were imprecise. Further adjustment for health behaviors and socioeconomic position did not alter the results.

Conclusion:
Black recipients experienced a lower incidence of perioperative stroke; however, mortality rates were similar between Black and white recipients following perioperative stroke. These unexpected findings warrant further research.
Abstract WP214: Levels And Dynamics Of Estimated Glomerular Filtration Rate And Clinical Outcomes In Patients With Stroke Or Tia -
Results Of The Mondafis Trial
Authors: Tuetuencue Serdar , Olma Manuel , Kunze Claudia , Krämer Michael , Dietzel Joanna , Schurig Johannes , Pfeilschifter Waltraud , Hamann Gerhard F , Büttner Thomas , Heuschmann Peter U , Kirchhof Paulus , Laufs Ulrich , Nabavi Darius , Röther Joachim , Thomalla Goetz , Veltkamp Roland , Eckardt Kai-Uwe , Häusler Karl Georg , Endres Matthias
Published: February 2022

Background:
Impaired kidney function increases the risk of vascular events in stroke patients, when assessed by single measurements of serum creatinine and estimated glomerular filtration rate (eGFR). Whether repeated measurements improve risk prediction in acute stroke patients is unknown.

Methods:
The investigator-initiated, prospective, multicenter
Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke
study randomized 3,465 acute ischemic stroke patients without known AF to usual diagnostic procedures for detecting AF or an additive Holter-ECG. eGFR was estimated by the CKD-Epi formula. Dynamics of eGFR during hospitalization was categorized as “stable ≥60ml/min”, “rising” (by at least 15% from any baseline value), “falling” (by at least 15% and baseline eGFR≥60ml/min) and “stable <60ml/min”. Recurrent stroke, major bleed, myocardial infarction, and all-cause death within 24 months were assessed as a composite endpoint. We estimated hazard ratios in confounder adjusted models.

Results:
The dynamics of eGFR were available in 1,623 patients. In 1,001 (61.7%) eGFR was “stable≥60ml/min”, in 231 (6.7%) “rising”, in 74 (4.6%) “falling”, and in 317 (19.5%) “stable<60ml/min”. After Adjusting for age, stroke severity, cardiovascular risk factors, and randomization, “falling” (HR 1.79; 95%CI 1.07-2.99) and “stable<60ml/min” eGFR (HR 1.64; 95%CI 1.20-2.24) correlated significantly with the composite endpoint, while only “falling” eGFR was associated with all-cause death (HR 3.12; 95%CI 1.63-5.98).

Conclusions:
Hospitalized ischemic stroke patients with a falling eGFR (of at least 15%, baseline ≥60ml/min) are at similar risk for recurrent vascular events or death and at higher risk for death as stroke patients with constantly reduced kidney function. Repeated estimates of eGFR may therefore improve risk prediction.
Abstract WP224: Trends In Self-reported Stroke And Myocardial Infarction Prevalence And Associated Modifiable Risk Factors Within Race/ethnicity Strata In The United States From 2011-2019
Authors: de Havenon Adam H , Heath Tyria , Johnston Karen C , Sharma Richa , Wong Ka-ho , Yaghi Shadi , NEY JOHN , Sheth Kevin N
Published: February 2022

Background:
Stroke and myocardial infarction (MI) prevalence varies by race/ethnicity, as do the risk factors.

Methods:
We included biyearly data from the 2011-2019 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of self-reported stroke and MI by race and ethnicity. We also describe the prevalence of modifiable vascular risk factors in patients with stroke and MI.

Results:
The weighted number of U.S. participants represented in BRFSS surveys increased from 237,404,549 in 2011 to 251,703,709 in 2019. Stroke prevalence increased from 2.9% in 2011 to 3.4% in 2019 (<0.001), while MI prevalence did not change over time (4.3% in 2011; 4.2% in 2019). The prevalence of stroke and MI was highest in American Indian/Alaskan Natives (AI/AN) at 5.6% and 7.5% in 2011 and 2019, respectively, compared to 3.2% and 4.8% for whites (p<0.001). Prevalence trends by race/ethnicity are in Figure 1. Modifiable risk factors are in Tables 1&2, which show that AI/AN consistently have the highest or second highest proportion with ≥4 risk factors.

Conclusion:
Prevalence of self-reported stroke, but not MI, is increasing in the United States. AI/AN consistently had the highest prevalence from 2011-2019 and the highest overall burden of modifiable vascular risk factors, rendering this group more vulnerable to a recurrent vascular event.
Abstract WP23: Determining The Association Between Atrial Cardiopathy And Cerebral Microbleeds In Ischemic Stroke Patients
Authors: Zhao David , Gootee Emma , Gottesman Rebecca F , Johansen Michelle C
Published: February 2022

Introduction:
Cerebral microbleeds (CMB) are frequently found in individuals with atrial fibrillation (AF) or ischemic stroke (IS), but whether atrial cardiopathy among IS patients is associated with CMB is unknown. We hypothesize that atrial cardiopathy is associated with increased risk of CMB.

Methods:
Inclusion criteria were IS patients admitted to Johns Hopkins (2015-2019) with transthoracic echocardiography, and electrocardiography. CMB were defined per established criteria as small, round hypo-intensities on T2* susceptibility weighted imaging or gradient recalled echo MRI sequences. Atrial cardiopathy was defined as the presence of ≥1: left atrium (LA) diameter >4.0 cm (males) or >3.8 cm (females), PR interval >200 ms, or NT-pro BNP >250 pg/mL. Multivariable or multinomial logistic regression was used to determine the association between atrial cardiopathy, and CMB presence or number, each, adjusted for potential confounders.

Results:
Patients (N=150) were mean age 61 years (range 22-98), 42% female, 59% black, and 42% were on anti-thrombotic medications. 54 (36%) participants had ≥1 CMB (range 0-10, IQR 0-7). 65 (43%) patients had atrial cardiopathy (46 with enlarged LA diameter, 15 with elongated PR interval, 16 with elevated NT-pro BNP). Age (67 years vs. 57 years, p<0.001) and AF (N=18 vs. N=12, p=0.032) differed based on atrial cardiopathy status. Atrial cardiopathy was associated with higher odds of any CMB (OR 2.41, 95% CI 1.22-4.79) but not after adjustment (Table 1). Atrial cardiopathy was associated with lobar CMB (OR 2.33, 95% CI 1.01-5.37, Model 3) but not with deep (OR 0.45, 95% CI 0.13-1.54, Model 3). There was a non-statistically significant higher relative risk of having 1 or >1 CMBs (vs. none) among those with atrial cardiopathy.

Conclusion:
In this study, we found a significant association between atrial cardiopathy and lobar CMB in IS patients, suggesting that atrial cardiopathy may increase subclinical embolic risk.
Abstract WP235: Docosanoids Protect Inflammation-induced Brain Damage And Lead To Neurological Recovery In Experimental Stroke
Authors: Bazan Nicolas G , Mukherjee Pranab K , Reid Madigan M , Obenaus Andre , Khoutorova Larissa , Roque Cassia R , Desai Neehar N , Simons Tyler , Ji Jeff , Oria Reinaldo B , Belayev Ludmila
Published: February 2022

Objective:
Cerebral ischemia initiates lipid peroxidation, uncompensated oxidative stress, and neuronal damage. We investigated the neuroprotective bioactivity of docosanoid (DOC) mediators: Neuroprotectin D1 (NPD1), Resolvin D1 (RvD1), and their combination (NPD1+RvD1) against experimental ischemic stroke. These lipid mediators are biosynthesized “on-demand” in response to stroke onset to resolve neuroinflammation and restore homeostasis. This study investigated the dose-response and therapeutic window in a model of focal cerebral ischemia.

Methods:
Male SD rats received 2h of middle cerebral artery occlusion (MCAo). Neurological score was evaluated on days 1, 2, 3, and 7, followed by an
ex vivo
MRI on day 7. In dose-response study, rats were treated with NPD1 (111, 222, and 333μg/kg), RvD1 (111, 222, and 333μg/kg), NPD1 + RvD1 or vehicle (n=4-5 per group). All treatments were administered IV at 3h after the onset of MCAo. In the therapeutic window study, vehicle, NPD1 (222 μg/kg), RvD1 (222 μg/kg), NPD1+RvD1 were administered IV at 3, 4, 5, and 6 h after onset of MCAo.

Results:
No adverse behavioral side effects were observed after drugs administration. NPD1 (111, 222, and 333μg/kg) treatment alone greatly improved neurological scores (by 32-35%) and RvD1 (111, 222, and 333μg/kg) alone (by 31-35%) vs vehicle group on day 7. The neuroprotective effect was enhanced using the NPD1+ RvD1, which improved total neurological scores on days 1-7 by 25-40% vs vehicle. Ischemic core, penumbra, and total lesion volumes (computed from T2WI) were reduced with NPD1+RvD1 by 69, 70, and 67% vs vehicle. Therapeutic window: treatments with NPD1 and RvD1 alone when administered at 3h improved behavior on day 7 by 35%. Combinatory NPD1+RvD1 treatment improved behavior when administered at 3h (by 56%), 4h (by 23%), 5h (by 26%), and 6 h (by 28%), vs vehicle.

Conclusion:
We show that NPD1, RvD1 alone provides high-grade neuroprotection against inflammation and elicit neurological recovery in the MCAo model. Combination therapy with NPD1 and RvD1 is more effective than the single therapy when administered up to 6h after focal cerebral ischemia in rats. Thus, we hypothesize that these treatments may potentially be used in treating focal ischemic stroke in the clinical setting.
Abstract WP238: Novel Mirnas In Plasma And Cerebrospinal Fluid Of Intracerebral Hemorrhage
Authors: Erkilinc Busra , Tran Vi , Lindsay Michael , Warren Jasmine , nguyen doan , Iwuchukwu Ifeanyi O
Published: February 2022

Introduction:
microRNAs (miRNAs) profiles in plasma and cerebrospinal fluid change in relation to cerebrovascular diseases and may serve as biomarkers or therapeutic targets of intracerebral hemorrhage (ICH). In this study, we examined the expression of novel and previously unreported miRNAs in ICH in plasma and cerebrospinal fluid (CSF) identified from miRNA sequencing.

Methods:
Patients with acute spontaneous ICH (n=8) were consented and peripheral whole blood were collected within 48 hours of ICH onset and processed for plasma and peripheral blood mononuclear cells (PBMC). CSF was obtained from an external ventricular drain (EVD). Six novel miRNAs were selected from miR-Seq analysis and further validated for their expression in ICH plasma/CSF, PBMC RNA and normal control plasma/CSF. Total RNA was used for real-time PCR validation of novel miRNAs using custom locked-nucleic acid (LNA) assay. Demographic and clinical data were collected.

Results:
miRNA-seq comparison between ICH plasma and CSF identified 19 and 30 differentially expressed miRNA (p<0.05), of which 9 and 7 novel miRNAs were identified in plasma and CSF, respectively. PC-5p-218_26568 was identified in ICH CSF, ICH PBMC and weakly in ICH plasma and normal plasma, but not in normal CSF. PC-5p-585_8337 was identified in ICH CSF and plasma, but not in normal CSF, plasma or ICH PBMC. PC-3p-4244_570 was found in CSF and plasma ICH patients and normal controls, exhibiting a 4-fold and 11-fold higher in ICH CSF and plasma than normal controls. It was also identified in ICH PBMC. PC-5p-1115_3460 was detected in normal plasma but not in ICH plasma, whereas PC-5p-6497_338 was found in ICH plasma but not in normal plasma and CSF. Lastly, PC-3p-3144_857 was found in ICH plasma and ICH PBMC and not in CSF.

Conclusion:
We identified distinct differences in miRNAs expression in healthy and ICH plasma and CSF. Further studies are underway on the gene targets and utility of these miRNAs as therapeutic targets or biomarkers of ICH.
Abstract WP24: Pharmacological Hypothermia (PH) Promotes Plasticity Through RNA Binding Motif 3 (RBM3)-Mediated Cold Shock Pathway Following Ischemic Stroke
Authors: Jiang Qian , Geng Xiaokun , Ding Yuchuan
Published: February 2022

Background:
Phenothiazine, including chlorpromazine and promethazine (C+P), induce hypothermia and neuroprotection after stroke. Immediately after stroke onset, there is a neuroplasticity window within which rehabilitation is especially effective. Recent studies have indicated that hypothermia-induced neuroplasticity involves the RBM3-mediated cold shock pathway, but it is unknown whether this pathway participates in neuroprotection and neuroplasticity in the context of pharmacological hypothermia (PH) induced by C+P after stroke.

Methods:
Adult Sprague-Dawley rats were divided in 3 groups: (1) sham; (2) stroke; (3) stroke treated with C+P before reperfusion. Long-term functional outcomes were determined by grid walk tests, rota-rod tests, beam balance tests, forelimb placing tests, adhesive tape touch and adhesive tape removal at 7 through 28 days. mRNA and protein quantities of cold shock pathway [RBM3, eukaryotic initiation factor 2 alpha (eIF2α), and reticulon 3 (RTN3)] and neuroplasticity [synaptophysin (SYN), post-synaptic density protein-95 (PSD-95), Tau, and recombinant growth associated protein 43 (GAP43)] were assessed by real-time PCR and western blot at day 1, 7 and 28 after reperfusion. Additionally, expression of RTN3 and eIF2α, and the co-localization of SYN and PSD95 was measured in primary neurons which subjected to oxygen/glucose deprivation (OGD) with RBM3 knockdown.

Results:
PH significantly improved functional outcomes at day 7 and 28. At day 1, mRNA and protein expression of RBM3 and RTN3 were significantly increased, and eIF2α was dephosphorylated by PH after stroke. mRNA and protein levels of SYN, Tau and GAP43 were all increased by PH at day 7 and 28. Furthermore, in OGD with shRBM3 group, levels of RTN3 and eIF2α dephosphorylation were significantly decreased, and the co-localization of SYN and PSD95 were significantly reduced compared with OGD group at 24 h without shRBM3.

Conclusion:
Our study has provided evidence, for the first time, for a novel mechanism underlying hypothermia in which the neuroplasticity and rehabilitation were achieved after ischemic stroke. Our findings suggest that the RBM3-induce cold shock pathway is a potential target of hypothermia for neuroprotection and neurorehabilitation.
Abstract WP251: Long Term Outcome Prediction After Ischemic Stroke Using Gene Expression
Authors: Amini Hajar , Knepp Bodie , Rodriguez Fernando , Carmona Paulina , Khoury Jane C , Pancioli Arthur , Broderick Joseph P , Ander Bradley , Sharp Frank R , Stamova Boryana
Published: February 2022

Objective:
Prediction of the long-term outcome in Ischemic Stroke (IS) patients can have a significant impact on design of clinical trials and on patients’ care. We studied gene expression (GE) as a novel biomarker to provide an accurate prediction of 90-day outcome in IS patients.

Methods:
RNA from 72 samples from 2 peripheral blood draws (at ≤3 and 24 hrs post IS onset) was analyzed on Affymetrix U133 Plus 2.0 microarrays. These represented samples from 36 CLEAR trial IS patients that had blood drawn within 3 hrs of stroke onset and were then treated with tPA with or without eptifibatide. The samples were split into derivation (n=25) and validation (n=11) sets. We identified the differential GE in blood at 24 hrs and the difference in GE between 24 hrs and 3 hrs post IS that was associated with 90-day post stroke outcome using the model: GE = μ + NIHSS_24hr+mRS_90day+ ε. Good outcome was defined as mRS 0-2; Poor - as mRS 3-5. Logistic regression was used to derive a biomarker classifier.

Results:
Using 24 hrs GE, we identified 14 probesets (12 genes) with the highest discriminative power for predicting outcome. The model achieved recall (the probability of correctly identifying the patients with Good outcome) of 0.88 and specificity (the probability of correctly identifying the patients with Poor outcome) of 0.67 in the validation set (The AUC-ROC = 0.88). The biomarker genes were enriched in immune responses such as IL and cytokine signaling. Among the predictors were genes important for stroke and repair after stroke (e.g.,
MACC1
,
GDF11
).
MACC1
has been considered as a potential treatment target for IS with a protective role in hypoxia-induced human brain microvascular endothelial cells.
GDF11
plays a role in brain repair after IS. We also determined how the change of GE from 3 hrs to 24 hrs would predict the 90-day outcome. A panel of ten genes was able to predict outcome in the validation set (recall= 1, specificity = 0.67, AUC-ROC=0.88). These included
AVPR1A
, which mediates platelet aggregation and release of coagulation factors and exacerbates brain inflammatory response to injury.

Conclusion:
This pilot study suggests gene expression can be used to predict stroke outcome. Some of the genes may serve as potential therapeutic targets.
Abstract WP255:
Cyfip2
Genotype Contributes To Variation In Stroke Vulnerability Among C57BL/6 Mouse Substrains
Authors: Zhao Liang , Mulligan Megan K , Kumar Vivek , Nowak Thaddeus S
Published: February 2022

C57BL/6 mouse substrains of the N lineage derived from the NIH colony later than the separation of the Bailey line in the early 1960s show increased stroke vulnerability relative to C57BL/6J. A missense mutation in
Cyfip2
, encoding cytoplasmic FMR1 interacting protein 2, is one of several known variants with a corresponding substrain distribution. This study evaluated reciprocal mouse lines in which the N
Cyfip2
variant had been either introduced into C57BL/6J (J-
Cyfip2
) or corrected in C57BL/6NJ (NJ-
Cyfip2
) by CRISPR-Cas9 editing. Stroke was produced by permanent surgical occlusion of the middle cerebral and ipsilateral common carotid arteries under isoflurane anesthesia, and infarct volume was measured as the region of pallor in brain slices incubated with triphenyltetrazolium chloride at 24 hours. Figure illustrates mean ± SEM (group sizes in parentheses) for mice of the current study, along with prior data for parent substrains. Introduction of the N-lineage mutation markedly increased infarct size in both males and females (†) while maintaining the sex difference seen in J mice (*). Correction of the mutation in NJ had no significant effect. At face value these results establish
Cyfip2
genotype as an important determinant of stroke vulnerability since the variant alone is sufficient to increase infarct volume in the J background. However, it is not the sole basis for differing stroke outcome among substrains, and at least one other variant must underlie the heterogeneity in sex difference.
Cyfip2
encodes a protein with recognized functional roles in brain and the immune system, but the precise intersection with stroke pathology remains to be established.
Abstract WP28: Thromboembolic Clot Perviousness In Covid-19: A Case-control Study
Authors: McNally J. Scott , de Havenon Adam H , Wolcott Zoe , Goldstein Eric
Published: February 2022

Background:
Large vessel occlusion (LVO) is the most common stroke subtype for those patient’s presenting with COVID-19. Clot perviousness, or a clot’s permeability to iodinated contrast, provides insight to an individual’s responsiveness of hyperacute revascularization, clot origin and functional post-stroke outcomes. We aimed to calculate LVO perviousness for those with and without COVID-19 and its association with revascularization and outcomes.

Methods:
This is a retrospective case-control study for individuals presenting with middle cerebral artery (MCA) LVO with and without COVID-19 positivity. Clot perviousness was calculated by a blinded experienced neuroradiologist. Perviousness scores were compared with demographic and comorbidity information as well as revascularization and functional outcomes.

Results:
18 individuals with a MCA LVO (9 COVID-19 infected) were included. Those with COVID-19 were significantly more likely to have diabetes mellitus [67% (6/9) versus 11% (1/9),
p
= 0.05] and hypertension [89% (8/9) versus 22% (2/9),
p
= 0.02]. Clot perviousness trended lower in the COVID-19 group [11.0 (8.2 - 26.4) versus 31.7 (30.4 - 39.2), p = 0.10]. Those with COVID-19 infection tended to have a lower clot pervious score, [22% (2/9) versus 78% (7/9), p =0.057]. The majority of those presenting with COVID-19 died during the hospitalization.

Conclusions:
Our data suggests for those with COVID-19 and MCA LVO, clots tended to be more impermeable to iodinated contrast. This finding may be due to the underlying coagulopathy of COVID-19, namely alternations in fibrin homeostasis.
Abstract WP31: Really, Did A Code Stroke Simulation Improve Compliance In Patient Care Requirements?
Authors: Rhew Denise , Upham Jason E
Published: February 2022

Purpose:
Enhance the care of ischemic stroke patients by improving compliance with implementation of appropriate order sets, following protocols addressing assessment of vital signs, neuro checks, and lowering door to needle times.

Method:
ED nurses were required to attend one of five simulation skills fair offered over a nine month period. A stroke simulation scenario was provided in the simulation lab. Groups of nurses performed each step in the care of a code stroke patient. An ED nurse facilitated each step to assure the staff had an understanding of time related events such as calling code stroke, identifying the exact time of last seen well, obtaining CT, vital signs, labs, neuro checks, scoring the patient, and administration of Alteplace, if applicable.

Results/Outcomes:
Metrics for fiscal year were compared to the statistics collected for the last quarter of fiscal year. Implementation of the stroke order set rose 56.4%, from 43.6% to 100%. Compliance with the protocol, neuro checks improved 40% to 90% and documentation of vital signs per protocol rose from 90% to 97%. Door to needle time improved by 11 minutes.

Implications:
The simulation educational intervention proved to show a significant improvement in compliance in performing vital signs, neuro checks, using stroke order sets and especially door to needle times. The ED leadership team has recognized the significant impact to our patient care outcomes and compliance resulting from providing this simulation education. The simulation also identified that the majority of the staff did not understand how to correctly perform neuro checks and were not placing the correct code stroke order sets that included the orders to do vital signs and neuro checks per protocol.
Abstract WP33: Improving Activation Of The Inpatient Stroke Response Team - A Two Decade Experience
Authors: Beland Dawn K , Panza Gregory , Nouh Amre
Published: February 2022

Inpatient acute stroke may go unrecognized and missed treatment opportunities are often related to not activating an inpatient stroke response team (SRT). An inpatient stroke response protocol was implemented at our institution in 2001. Since implementation, several interventions have been tried to improve stroke recognition and increase the volume of SRT calls. Objective Describe the relationship between the interventions and change in stroke call volume aimed to support an inpatient SRT.

Methods:
We performed a retrospective review of all inpatient stroke calls at an urban university-affiliated Comprehensive Stroke Center. A descriptive analysis examined the change in call volume over 20 years as a result of various interventions to support inpatient stroke calls. Unit-based education, focused cardiology nursing unit education, all employee mandatory computer-based stroke education, addition of stroke unit nurses to the inpatient SRT, call process changes analogous to cardiac or respiratory alerts and treatment protocol updates were implemented. Previous interventions were continued as new ones were added.

Results:
A positive linear relationship between the interventions and call volume was noted. The average increase in annual call volume following an intervention was 47.95±42.39 calls. The average annual percent growth in call volume following an intervention was 134.79±134.58 percent. Continued nursing education led to the greatest increases in annual average call volume (Table).

Conclusions:
The results suggest that once implemented, supportive interventions positively impact the utilization of an inpatient SRT. Focused and frequent education regarding the inpatient stroke response protocols through annual education and activities related to program certification had the most impact on inpatient stroke team call volume at our center. These results may be beneficial to other stroke programs as they develop inpatient stroke protocols.
Abstract WP40: Improving Novices Stroke Nurses’ Education To Improve Patient Outcomes
Authors: Warren Kimberly S
Published: February 2022

Problem:
Stroke care is a lifelong chronic disease process that is constantly evolving for patients and the hospitals that care for them. Today's evidence-based care of stroke patients is time-sensitive and time-intensive for the registered nurse (RN). With the growing incidence of stroke, there is an emerging need for nurses’ education and timely bedside assessment. Eighty percent of strokes are preventable through risk factor management, and twenty percent of stroke patients will have a recurrence. Nurses are primarily responsible for providing this education. However, new stroke nurses in the Emergency Room or on the stroke unit may not have this foundation of knowledge or know the current evidence-based practice, which is often not taught in school.

Purpose:
The purpose of this study is to evaluate nursing knowledge and performance at baseline, post education intervention, and again two months after implementation to determine if providing several different education techniques improves knowledge, performance, and retention during a quality improvement project. EBP Questions: RQ1: Is there a significant difference between stroke knowledge test scores before, immediately after, and two months after receiving an evidence based educational intervention. • RQ2: Is there a significant difference in stroke code simulation scores before, immediately after, and two months after receiving an evidence based educational intervention. • RQ3: Is there a correlation between nurse’s stroke code simulation scores at two months and their years of experience as a nurse?

Methods:
A quasi-experimental design will be used to compare the knowledge novice stroke nurses at baseline. Again, after a four-hour lecture. Finally, after simulation they will again be tested for knowledge.

Outcome:
The expected outcome is that staff knowledge will increase with each simulation. As the nurses continue to learn and practice, they should increase awareness of stroke signs and symptoms for patients arriving in the emergency room through triage or EMS.

Significance:
This study will contribute to evidence-based research to determine if multi-faceted education techniques are best when training novice nurses to new time sensitive processes in this critical access hospitals.
Abstract WP41: Mobile Stroke Unit Operational Performance: A Retrospective Single Institution Analysis And Meta-Analysis
Authors: Ellens Nathaniel R , Schartz Derrek , Rahmani Redi , Akkipeddi Sajal M , Kelly Adam G , Benesch Curtis , Burgett Jason , Lesperance Joshua , Proper Diana , Mattingly Thomas , Pilcher Webster , Bhalla Tarun , Bender Matthew
Published: February 2022

Introduction:
Mobile stroke units (MSU) have become increasingly common and now span a diverse range of communities. Reporting has previously focused on clinical outcomes, and metrics reporting the operational performance of MSUs have not been standardized. The aim of this study was to establish normalized metrics to evaluate MSUs and to a complete a meta-analysis of the current literature on MSU performance.

Methods:
Our MSU serves a population of 741,000 people in upstate New York. Data was prospectively collected and retrospectively analyzed from its inception in October of 2018 through March of 2021. We report rates of transportation/dispatch and MSU utilization rates. MEDLINE and Cochrane Library databases were utilized to perform a meta-analysis. Pooled rates of tPA/dispatch, tPA/day, mechanical thrombectomy (MT)/dispatch and MT/day were calculated. An assessment of inter-study heterogeneity was also completed.

Results:
In 606 days, our MSU was dispatched 1,719 times for an average rate of 2.8 dispatches/day. 324 patients (18.8%) were transported to the hospital by the MSU. Intravenous tPA was administered in 64 patients (3.7% of all dispatches) and the rate of tPA/day was 0.317 (95% CI 0.150 to 0.567). MT was performed in 24 patients (1.4% of dispatches) for a MT/day rate of 0.119 (95% CI 0.074 to 0.163). Of the 290,760 total minutes the MSU was available, it was in use for 38,742 minutes (13.3% utilization rate). Our meta-analysis included 18 total articles. Eight studies were included in the pooled analysis of tPA/dispatch (342/5,862) for a rate of 7.2% (95% CI 4.8% to 9.5%, I2 = 92%) and nine were included in the analysis of tPA/day (785/1,998) for a rate of 0.359 (95% CI 0.150 to 0.567, I2 = 99%). Seven studies met criteria for analysis of MT/dispatch (102/5,335) for a rate of 2.0% (95% CI 1.2% to 2.8%, I2 = 67%) and for MT/day (103/1,249) for a rate of 0.092 (95% CI 0.046 to 0.138, I2 = 91%).

Conclusions:
Future studies investigating MSUs should focus on the following normalized metrics: tPA/dispatch, tPA/day, MT/dispatch, MT/day, and the newly described utilization rate. These normalized metrics are also useful at an institutional level when evaluating the overall utilization and efficacy of an MSU.
Abstract WP46: Patterns Of Emergency Medical Transport For Suspected Acute Stroke, Acute Myocardial Infarction, And Other Diagnoses During The Covid-19 Pandemic: A Retrospective Analysis Of A Large Hospital-based Emergency Medical Services (EMS) Agency
Authors: Koneru Sitara , Nogueira Raul G , Moore Shawn , Moran Timothy , Fleming Carol , Kumar Lekshmi , Haussen Diogo C , Bianchi Nicolas , Frankel Michael , Bhatt Nirav
Published: February 2022

Introduction:
During the initial peak of the COVID-19 pandemic, many centers globally reported a significant decrease in volumes of emergencies including acute stroke (AS) and acute myocardial infarction (AMI). While the reason for this remains unknown, pandemic-driven anxiety among patients may have resulted in unwarranted refusals to transport when deemed necessary by EMS (Emergency Medical Services) providers. We sought to study the impact of COVID-19 pandemic on the patterns of Emergency Medical transport (EMTr) and patient refusals to transport when serious medical conditions were suspected by EMS personnel.

Methods:
In this retrospective, observational study of Grady Health System’s EMS, we compared the rates of EMTr and refusals for adult patients with suspected diagnoses of AS, AMI, and other medical conditions in the first year of the pandemic (Y1, Mar 2020-Feb 2021) with the corresponding period in the year prior (Y0). We also compared the temporal trends for these variables across the different pandemic waves (1
st
, Mar-May 2020; 2
nd
, Jun-Aug 2020; 3
rd
, Sep 2020-Feb 2021) with the corresponding periods in the year before.

Results:
Grady EMS responded to 207,888 calls in Y1 compared to 201,968 in Y0. The overall rate of refusals for all diagnoses was 15.5% in Y1 vs 14.1% in Y0, that for AS was 2.25% in Y1 vs 1.77% in Y0 and 7.5% in Y1 vs 5.67% in Y0 for AMI (Figure).

Conclusion:
There were more refusals in the first two waves of the pandemic. While refusals were higher for AS and AMI, this was not statistically significant. Our study provides valuable insight into the behavioral patterns of patients seeking emergency care during the pandemic and emphasizes a need for public education and more research.