bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3384: Effectiveness of the FAST Program Targeting African American Middle School Teachers
Authors: Miller Elaine T , King Keith , Miller Rosemary
Published: July 2021

Significance and Purpose:
During the school year, teachers interact with middle students almost half of their waking hours and have a unique opportunity to positively affect their own health as well as their students. The purpose of this pilot study performed in a predominantly African American middle school was to evaluate the effectiveness of the 3 month long FAST Stroke Education Program designed for teachers that used Social Cognitive Theory as the underlying framework. The program objectives were to: (1) increase the teachers’ knowledge of the major stroke risk factors, stroke warning signs, and treatment seeking behaviors (call 911); (2) improve the teachers self-efficacy related to improving one of their own modifiable stroke risk factors; and (3) achieve their self-identified goal to reduce a modifiable stroke risk factor.

Methodology:
After obtaining consent, the teachers received a pretest survey that assessed their stroke knowledge and self-efficacy related to stroke. Following this pretest, the teachers received a 45 minute educational intervention that included interaction with a stroke survivor and taking an immediate posttest. As part of this session, the teachers also identified one personal objective for the next 3 months (i.e., exercise 30 minutes 3 times/day) and listed 2-3 feasible actions to achieve this objective. Six weeks later, they were mailed their objective, action plan, and stroke related educational materials in a self-addressed envelope. At three months, teachers received a long-term posttest that also determined if they had achieved their self-identified modifiable stroke risk factor.

Findings:
The study’s convenience sample consisted of 29 full-time teachers who were mostly male (n = 18, 62%) and African American (n=19, 65.5%). Risk factor knowledge scores were significantly higher at immediate posttest than at pretest, t = 2.25, p = .03 and was maintained at 3 months. Regarding stroke warning signs, there was a significant difference between pretest and posttest with a t=2.52, p = .015,but this knowledge wasn’t maintained. Subjects improved and maintained their stroke self-efficacy from pretest to long-term posttest and 31% of the teachers achieved their health objective. Another 58.6% stated they made some progress in achieving their stroke reduction objective.

Conclusions and Practice Implications:
Pilot results reveal some positive stroke outcomes involving middle school teachers. Additional refinements in the FAST program and educational strategies will occur to further enhance information retention and achievement of personal health outcomes prior to testing with a larger sample.
Abstract 3420: High-sensitivity Troponin T Improves Cardiovascular Risk Prediction In Patients With Cerebral Ischemia
Authors: Stahrenberg Raoul , Niehaus Cord F , Weber-Krüger Mark , Mende Meinhard , Hasenfuβ Gerd , Gröschel Klaus , Wachter Rolf
Published: July 2021

Background
Patients with a cerebral ischemic event are at high risk of recurrent ischemia and other cardiovascular events. Clinical scores are recommended to predict cardiovascular risk in patients with cerebral ischemia to inform secondary preventive measures. Biomarkers may improve risk prediction beyond clinical scores and therefore secondary prevention.

Methods
Within the observational Find-AF trial (ISRCTN 46104198), 197 patients aged >18 years with cerebral ischemia and without atrial fibrillation had blood sampled at baseline and completed 1-year follow-up. Predictive value of 5 novel cardiovascular biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2), National Institutes of Health Stroke Scale (NIH-SS) and Modified Rankin Scale (MRS).

Results
There were 23 vascular events (11.7%) and 13 deaths (6.6%) during 1 year. In multivariate analyses of all 5 markers, only high-sensitivity Troponin T (hs-TropT) remained significantly predictive of vascular events (p=0.045) and all-cause mortality (p=0.004). Hs-TropT was higher in patients with a vascular event (median 12.7 [6.8; 49.6] ng/mL vs. 5.1 [1.5; 11.7] ng/mL) and patients with hs-TropT above the median of 6.15 ng/mL were more likely to have a vascular event (Hazard Ratio 4.0, p=0.006 on log-rank test). For prediction of vascular events as well as all-cause mortality, hs-TropT significantly contributed to multivariate Cox-regression models with ESRS, SPI-2, or each combined with NIH-SS or MRS as covariates. C-statistic increased numerically from 0.689 (ESRS) to 0.743 (ESRS+hs-TropT) and 0.696 (SPI-2) to 0.758 (SPI-2+hs-TropT) (p=n.s.). Areas under the receiver-operator characteristics curves for vascular events were 0.694 (SPI-2), 0.712 (ESRS), 0.743 (ESRS+hs-TropT), 0.755 (hs-TropT) and 0.760 (SPI-2+hs-TropT). No patient with a low-risk ESRS ≤2 and a hs-TropT below the median had a vascular event during 1 year follow-up.

Conclusion
Hs-TropT is predictive of major vascular events and all-cause mortality in patients with cerebral ischemia and improves prediction by established clinical scores.
Abstract 3450: Low Education as a Predictor Of Poor 1-year Stroke Survival In The Emma Study (study Of Stroke Mortality And Morbidity In Adults), Brazil
Authors: Goulart Alessandra C , Fernandes Tiotrefis G , Alencar Airlane P , Fedeli Ligia M , Benseñor Isabela M , Lotufo Paulo A
Published: July 2021

Low education as a predictor of poor 1-year stroke survival in the EMMA Study (Study of Stroke Mortality and Morbidity in Adults), Brazil Background and purpose-socioeconomic status plays an important role in stroke trends. This study aimed to investigate educational level as a surrogate to explain differences in stroke survival.

Hypothesis:
to verify if stroke survival is influenced by educational level. Methods-we prospectively ascertained 430 consecutive first-ever stroke patients (ischemic and haemorrhagic) enrolled in the Stroke Mortality and Morbidity Study (The EMMA study) between April 2006 and December 2008 in a community hospital in São Paulo, Brazil, and stratified them according to educational level (illiterate, 1-7 years, ≥8 years). Results- stroke survival rate was 74.9% at one-year follow-up. The risk for fatal stroke inversely correlated with years of education (multivariate hazard ratio comparing non educated group with ≥8 years of education group = 2.06; 95% CI, 1.18-3.60,
P
for trend=0.01). The gradient was more pronounced for ischemic stroke (hazard ratio=2·32; 95%CI, 1.26-4.27,
P
=0.01). This association was even stronger after adjusting by sociodemographic, cardiovascular risk factors and in the full model (hazard ratio = 2.67, 2.43, and 2.65, respectively). No education was associated with an increased risk of fatal stroke for patients who were less than 68 years old (hazard ratio=3.67; 95% CI, 1.10-12.45), female (hazard ratio=3.42; 95% IC, 1.10-12.45), lived alone (hazard ratio=2.78; 95% CI, 1.16-6.66) and smoked (hazard ratio=4.27; 95% IC, 1.28-14.19).Conclusions-stroke survival was directly related to years of education, especially for ischemic stroke. Absence of education was a significant marker of fatal stroke in persons under age 68 years, who live alone, and who smoked.
Abstract 3471: Emergent Carotid Artery Stenting: Outcomes on a National Level
Authors: Alshekhlee Amer , Vora Nirav , Feen Eli , Edgell Randall C , Piriyawat Paisith , Callison R C , Kitchener Jacob , Kaushal Ritesh , Mehta Sonal , Cruz-Flores Salvador
Published: July 2021

Background:
Emergent carotid artery stenting (CAS) is sometimes performed in the setting of acute cerebral ischemia. In this study, we assess outcomes associated with CAS when performed emergently.

Methods:
A cohort of patients with CAS was identified from the National Inpatient Sample database using the procedure codes (00.63) for the years 2004 through 2007. The type of admission (elective or emergent) for each patient was clarified in the database. Patients with missing admission type were eliminated. We further ascertained the emergent hospitalization by including only patients who were admitted through the Emergency Department. Primary outcomes include stroke (ischemic or hemorrhagic), myocardial infarction or death occurring during the same hospitalization. Multivariate logistic regression analyses were used to assess covariates associated with the primary outcome and hospital mortality.

Results:
In this analysis, 9001 patients were admitted and treated with CAS; 822 patients (9.13%) had the procedure performed emergently and the rest had elective CAS. The mean age (69.0 ± 13.2 vs. 70.6 ± 10.2) and gender (females 40.4% vs. 39.8%) were similar in both groups. Risk factors included higher rates of congestive failure and chronic lung disease in the emergent group. In addition, emergent CAS had more severe Charlson comorbidity index (4.0% vs. 1.76%; p < 0.0001). Unadjusted analysis showed higher rate of any stroke, myocardial infarction or death in the emergent group (12.3% vs. 3.37%; OR 4.0; 95% CI 3.15, 5.10). Adjusted analysis for the basic demographic, risk factors and the comorbidity index revealed a higher risk of any stroke, myocardial infarction and death when CAS performed emergently (OR 3.27; (95% CI, 2.54, 4.21). Secondary outcomes of hospital mortality (5.11% vs. 0.67%), myocardial infarction (5.47% vs. 1.11%) and intracerebral hemorrhage (2.07% vs. 0.35%) were higher in the emergent CAS group (P < 0.0001). Post-operative stroke rates were similar (1.92% vs. 1.82%; P= 0.85). Intracerebral hemorrhage was the strongest predictor of mortality (OR 64.0; 95% CI 32.1, 127.7). Other predictors of mortality include congestive heart failure, myocardial infarction and the use of thrombolytic.

Conclusion:
CAS is associated with higher risk of stroke, myocardial infarction and death when performed emergently. Despite the low rate of intracerebral hemorrhage when CAS performed emergently, intracerebral hemorrhage remains the strongest predictor of mortality.
Abstract 3482: Increased Matrix Metalloproteinase-9 Expression is Correlated with Carotid Intraplaque hemorrhage in a Swine Model
Authors: Shi Zhong-Song , Jiang Xiao-Bing , Wang Jin-Shan , Yuan Wei-Si , Liu Dong-Hong
Published: July 2021

Purpose:
The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model.

Materials and Methods:
Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed.

Results:
One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal (
P
<0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for MMP-9 tended to be greater in the vulnerable plaque than in the stable plaque (8.69 ± 0.73% vs. 7.04 ± 0.94%, p=0.35). Areas positive for MMP-9 were significantly greater in the plaque with intraplaque hemorrhage than in the plaque without intraplaque hemorrhage (11.84 ± 1.22% vs. 6.63 ± 0.59%, p<0.001). On multivariate analysis, positive expression of MMP-9 was an independent predictor of intraplaque hemorrhage (p=0.007).

Conclusion:
Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.
Abstract 3511: Potential Physiological Pathway Through Which PGD
2
DP1 Receptor Is Preventing Ischemic Brain Damage
Authors: Ahmad Abdullah , Maruyama Takayuki , Narumiya Shuh , Dore Sylvain
Published: July 2021

Background and Purpose:
Being the most abundant prostaglandin in brain, PGD
2
serves as a prime candidate to be investigated in neurologic conditions. Previously we have shown that DP1
-/-
mice have greater brain damage after middle cerebral artery occlusion (MCAO) and NMDA-induced acute excitotoxicity. Characterization of cerebral vessels in C57BL/6 wildtype (WT) and DP1
-/-
mouse brain shows no major differences. In the present study we are testing whether post-treatment with DP1 agonist BW245C improves cerebral blood flow (CBF), and minimizes brain damage and behavioral deficits after MCAO.

Methods:
To determine if BW245C can change basal CBF, WT and DP1
-/-
mice were anesthetized with isoflurane and a laser Doppler flow (LDF) probe was affixed to the skull to record CBF. Once the baseline was obtained, mice were given a single i.p. injection of vehicle or 0.2mg/kg BW245C, and CBF was recorded for 2h at 10min intervals. To determine if BW245C can prevent brain damage after MCAO, separate cohorts of WT and DP1
-/-
mice were subjected to 60min MCAO and 96h reperfusion. Immediately at reperfusion, mice were given a single i.p. injection of vehicle or 0.2mg/kg BW245C. These mice were also tested for (a) open field activity, (b) cylinder test, (c) hanging wire test, and (d) neurologic deficit. Finally to determine the selectivity of BW245C, DP1
-/-
mice were subjected to MCAO and immediately at reperfusion vehicle or 0.2mg/kg BW245C was given i.p. and brains were harvested at 96h.

Results:
BW245C treatment increased the CBF significantly in WT and in DP1
-/-
it remained unchanged. The infarction volume was significantly reduced to 38.7±8.1% in BW245C treatment group (n=8) as compared with the control group (51.2±7.1%; n=13) and vehicle group (52.7±8.6%; n=8). The attenuation in cerebral infarction by BW245C correlated with significant improvement in behavioral deficit outcomes. Moreover, the results were extended in the DP1
-/-
where we found a significant increase in infarction volume (66.3±11.4%) as compared with the WT control mice (51.2±7.1%; n=13). Furthermore, the pharmacologic effects of BW245C were found to be absent in DP1
-/-
suggesting that the protective effect of BW245C is through DP1 receptor.

Conclusions:
Overall the data suggests that stimulation of the DP1 receptor improves CBF, and minimizes brain damage and functional deficits after ischemia. This ongoing work is enabling us to provide mechanisms through which DP1 receptor is exerting its neuroprotective effects. Further work is underway to determine the PGD
2
DP1 action in regulating the vascular unit.
Abstract 3535: CD36 Impacts Stroke Injury In Hyperlipidemia Through MCP-1/CCR2 Axis.
Authors: Kim Eunhee , Febbraio Maria , Bao Yi , Tolhurst Aaron T , Cho Sunghee
Published: July 2021

Hyperlipidemia increases ischemic injury. The exacerbation is associated with elevated expression of CD36, a class B scavenger receptor, in peripheral monocytes/macrophages as well as ischemic brain (Kim et al., 2008). This study investigates whether and how peripheral and brain CD36 contribute to stroke-induced brain injury in hyperlipidemia. Bone marrow cells (BM) were exchanged between CD36-expressing (AKO) and CD36-deficient (DKO) mice. The experimental mice were fed a high fat diet for 11 weeks and then subjected to transient ischemic stroke by middle cerebral artery occlusion. Ischemic outcome, MCP-1, CCR2 in the brain, and plasma MCP-1 levels were determined at 3 days post-ischemia. Compared to AKO mice received AKO
BM
(control transplant), the AKO mice received DKO
BM
resulted in 30% reduction in infarct volume (IV) (
n
=12-14, p<0.05,
Fig. 1
left), 27% in MCP-1 (p<0.05) and 35% CCR2 (p<0.05) mRNA levels. In contrast, DKO mice received AKO
BM
did not increase IV (
Fig. 1
right), MCP-1 or CCR2 mRNA levels compared to DKO mice received DKO
BM
(
n
=11-15,
ns
). Correlation analyses of MCP-1 vs IV or CCR2 vs IV showed significant reductions in slope elevations in DKO mice compared to AKO (MCP-1 vs IV, p<0.05; CCR2 vs IV, p<0.01,
n
=23-25/group). In spite of blunted MCP-1 expression in ischemic brain, plasma MCP-1 levels were significantly higher in DKO mice (DKO, 441.5±33.6pg/ml
vs
AKO, 235.8±15.9pg/ml,
n
=25, p<0.001). We further addressed
in vitro
the importance of CD36 in splenocytes for CCR2 expression. In a given AKO or DKO serum, CCR2 expression was higher in AKO splenocytes compared to DKO splenocytes (
Fig. 2
). This study demonstrates several findings;
i)
peripheral CD36 contributes ischemic injury in hyperlipidemia;
ii)
brain (host) CD36 is additionally required for the peripheral CD36 effect take place
iii)
DKO host displays reduced MCP-1/CCR2 expression in the post-ischemic brain but higher plasma MCP-1 levels
iv)
CD36 regulates CCR2 expression in splenocytes. The findings suggest that host and peripheral CD36 synergistically regulates immune cells trafficking through modulating MCP-1/CCR2 axis. Thus, targeting CD36 may serve as a novel neuro-immune strategy to achieve neuroprotection from stroke-induced acute brain injury in hyperlipidemia.
Abstract 3542: Novel Differences in a Mouse Model of Hyperglycemia after Cerebral Ischemia
Authors: Li Sean S , Guzik Amy K , Annex Brian H , Worrall Bradford B
Published: July 2021

Background:
Stroke is a leading cause of serious long-term adult disability in the United States. Hyperglycemia has consistently been associated with worse clinical outcomes from ischemic stroke. Animal studies utilizing genetic models of type II diabetes have shown greater ischemic injury in the setting of hyperglycemia. However, these models may not well represent all physiological aspects of human type II diabetes and post-stroke hyperglycemia. Diet induced diabetes may prove more analogous to human disease. The high fat diet mouse model of type II diabetes reliably creates a subacute hyperglycemic state. We evaluated normal and high fat diet (HFD) fed mice following middle cerebral artery occlusion (MCAO) to determine if post-ischemic functional status is influenced by hyperglycemia in this model.

Methods:
C57BL/6 male mice (12-18 weeks) fed either normal diet or HFD (60%kCal fat) were subjected to 60 minutes of transient MCAO via 6-0 monofilament. Triphenyltetrazolium chloride staining confirmed infarction in a subset of mice. A glucose tolerance test was performed, and fasting blood sugar was tested prior to surgery to verify hyperglycemia. Neurologic deficit score (NDS) was measured before and after surgery, and 24 hours post MCAO.

Results:
HFD fed mice demonstrated worse NDS following ischemia compared to normal fed mice. This was significant at 24 hours post MCAO (p<0.0001). Normal fed mice showed improvement in functional score 24 hours post MCAO (p<0.05), but HFD fed mice demonstrated no improvement.

Conclusion:
Our data show that HFD fed mice have worse outcomes post-MCAO and without the recovery in functional scores seen in normal fed mice. This mirrors the human condition, where worse clinical outcomes are seen in hyperglycemic patients with ischemic stroke. This model provides an opportunity to investigate mechanisms underlying differential recovery in the setting of hyperglycemia and to test if insulin treatment can prevent the adverse recovery in HFD animals as has been postulated in humans. We are conducting gene expression experiments to test candidates that may mediate ischemic damage and recovery and to identify novel therapeutic targets.
Abstract 3546: Genetic Variables Contributing To Aspirin Resistance: A Genome-Wide Association Study
Authors: Malik Shaneela , Chen Fang , Kramer Jamie , Chen Wei-Min , Hsu Fang-Chi , Southerland Andrew M , Adams Marcia , Doheny Kimberly , Gogarten Stephanie , Laurie Cathy , Udren Jenna , Bookman Ebony , Ramoni Marco , Sale Michele M , Worrall Bradford B
Published: July 2021

Background:
Aspirin reduces risk of vascular events by 15-30% in patients with ischemic stroke, but recurrent vascular events occur in up to 45% on aspirin therapy. Understanding factors contributing to aspirin resistance is important in secondary stroke prevention. Several clinical and genetic factors have been implicated. We sought to use GWAS data from the Vitamin Intervention for Stroke Prevention (VISP) trial to evaluate genetic factors that may contribute to aspirin resistance.

Methods:
We conducted a case-control analysis in participants in the VISP study. We included all individuals on aspirin at the time of enrollment. Patients on combination antiplatelet and/or anticoagulation therapy were excluded. We conducted a survival analysis of 960 individuals using Cox proportional hazards model with multiple clinical, demographic and genetic covariates. Demographic factors include sex, age and 10 principle components from population structure analysis. A total of 11 clinical factors and 14 genes (319 single nucleotide polymorphisms (SNPs)) were analyzed (

Table

).

Results:
The top SNPs were rs12603582 in the integrin beta 3 (platelet glycoprotein IIIa) gene (ITGB3) on Chromosome 17 (p=0.0056); rs9472831 in the phospholipase A2 gene (PLA2G7) on Chromosome 6 (p=0.0079), and rs5985 in the coagulation factor XIII gene (F13A1) on Chromosome 6 (p=0.0080). Of the 16 SNPs with p-values less than 0.05, 5 were in phospholipase A2, group IVA (PLA2G4A), 2 were in the coagulation factor XIII (F13B), 3 were in F13A1, 1 was in PLA2G7, and 5 were in ITGB3.x

Conclusion:
No individual genetic factor was significantly associated with recurrent stroke or MI in the VISP population after correction for multiple comparisons. Our study had limited power to detect associations due to a small sample size. A Bayesian network has been used to develop a predictive model for stroke in sickle cell patients. We will apply a similar approach to develop a model for genetic and clinical variables (

Table

). We also will expand our sample by inclusion of cases from the Women’s Health Initiative. With further study and analysis we hope to identify additional genetic factors that may predispose patients to aspirin resistance.
Abstract 3548: Neuroimaging Modalities Predict Robust Collaterals For Optimal Intraarterial Acute Stroke Therapy
Authors: Kaushal Ritesh , Kitchner Jacob , Amer Alshekhlee , Mehta Sonal , Chibnall John , Piriyawat Paisith , Feen Eliahu , Cruz-Flores Salvador , Callison Richard , Edgell Randall , Vora Nirav
Published: July 2021

BACKGROUND:
Collaterals during intra-arterial (IA) therapy have been shown to impact outcome. We sought to identify pre-treatment predictors of robust collaterals to improve patient selection for this therapy.

METHODS:
With institutional review board approval, we retrospectively reviewed patients from a single center receiving IA therapy for internal carotid artery (ICA) and middle cerebral artery (MCA) M1 segment occlusions from January 2009 to June 2011. We collected the following clinical data: age, gender, stroke score, and risk factors. Radiologic parameters included the pre-treatment Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast CT (NCCT) and CT Perfusion (CTP) cerebral blood volume maps and site of occlusion. All patients had complete diagnostic angiography prior to IA therapy. Collateral circulation of the symptomatic MCA territory was based on a previously published protocol in which any collateral filling of the MCA M1 segment was scored 1, any filling up to the M2 segments was scored 2, any filling up to the M3 segments was scored 3, any filling up to the M4 segments was scored 4. Absent collaterals were scored 5. The endpoint was robust collaterals defined as a score < 4. Associations between demographic, clinical, and radiologic parameters and robust collaterals were determined using chi-squared analysis. Receiver-operating characteristic (ROC) curves determined sensitivities and specificities for significant predictors.

RESULTS:
Fifty-three patients were identified (mean age of 66 %/- 11 years, median stroke score of 16.5). Occlusions occurred in the MCA M1 segment (37), ICA origin (2), intracranial ICA (9), and tandem ICA origin with intracranial ICA or M1 MCA (5). Robust collaterals were identified in 42 patients and predicted by 2 correlates on multivariate analysis: NCCT ASPECTS > 8 (p = .011), where 89.2% of patients with NCCT ASPECTS > 8 had robust collaterals, compared to 56.3% of patients with NCCT ASPCECTS ≤ 8; and CTP ASPECTS > 7 (p < 0.001), where 100% of patients with CTP ASPECTS > 7 had robust collaterals, compared to 45.5% of patients with CTP ASPCECTS ≤ 7. NCCT ASPECTS > 8 had a sensitivity of 79% and a specificity of 64% in predicting robust collateral circulation. CTP ASPECTS > 7 had a sensitivity of 83% and a specificity of 100%.

CONCLUSIONS:
Higher ASPECT scores on baseline CT and CTP reflects presence of robust collaterals and can aid in patient selection for IA therapy. In addition, a protocol using CTP may further increase the selection accuracy.
Abstract 3549: Sex-Independent Down-regulation of MMP-9 with Minocycline after Experimental Embolic Stroke
Authors: Hoda Md Nasrul , Li Weiguo , Ahmad Ajmal , Ogbi Safia , Zemskova Marina A , Johnson Maribeth H , Ergul Adviye , Hill William D , Hess David C , Sazonova Irina Y
Published: July 2021

Background and Purpose -
Minocycline provides neurovascular protection reducing acute cerebral injury. However, it is unclear whether minocycline is effective in females. We tested minocycline in both sexes and aged animals using an embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans. The aim was to determine if there is a sex-specific change in MMP-9 levels.

Methods -
In the context of the revised preclinical STAIR criteria call for testing of neuroprotective agents in female mice and aged mice, minocycline was tested in five groups of mice subjected to thromboembolic stroke: adult males, aged males, adult females, aged females, and adult ovariectomized females (n=9-23 animals/group). Behavioral outcomes, infarct volumes, and cerebral blood flow as well as expression and activity of MMP-9 were assessed. Statistical ANOVA analyses were performed using SAS® 9.2.

Results -
The model resulted in reproducible infarct in the experimental groups. As expected, adult females were significantly more resistant to cerebral ischemic injury than males. This advantage was abolished by aging and ovariectomy. Minocycline significantly reduced the infarct volume (P=0.0001) and also improved neurologic score (P<0.0001) in all groups. Moreover, minocycline treatment significantly reduced mortality at 24 hours post stroke (P=0.037) for aged mice (25% versus 54%). Stroke up-regulated MMP-9 level in the brain and acute minocycline treatment reduced its expression in both genders (P<0.0001).

Conclusion -
In a thromboembolic stroke model minocycline is neuroprotective inhibiting MMP-9 irrespective of mouse sex and age.
Abstract 3550: Temporal Trends, Risk Factors, and Hospital Costs of the Adult Respiratory Distress Syndrome (ARDS) after Acute Ischemic Stroke in the United States
Authors: Rincon Fred , Maltenfort Mitchell , Vibbert Matthew , Urtecho Jacqueline , McBride William , Moussouttas Michael , Jallo Jack , Bell Rodney
Published: July 2021

Background.
We sought to determine the prevalence and risk factors of ARDS, and its impact on hospital length of stay (LOS) and cost, after acute ischemic stroke (AIS) in the U.S.

Methods.
Data were derived from the National Inpatient Sample from 1998-2008. We searched for admissions of patients >18 years, with a diagnosis of AIS and ARDS. Definitions were based on ICD9-CM codes. Prevalence proportions, and hospital LOS and cost were calculated. Multivariate logistic regression models were then fitted to determine odds ratios (OR) and 95% confidence intervals (CI) for determinants of ARDS and to assess for its impact on hospital LOS and cost.

Results.
Over the 10-year period, we identified 4,066,043 admissions that corresponded to a primary diagnosis of AIS of which 157,464 had ARDS for a cumulative prevalence of 4%. Cases of ARDS after AIS increased from 13,395 (3.6%) in 1998 to 17,222 (4%) in 2008. ARDS was more common among old (OR 0.9; 95%CI 0.9-0.98), men (OR 1.2; 95%CI 1.2-1.21), blacks (OR 1.2; 95%CI 1.1-1.2), urban-academic centers (OR 1.4; 95%CI 1.3-1.5); and in sepsis (OR 8.0; 95%CI 7.6-8.4), cardiovascular dysfunction (OR 3.5; 95%CI 3.3-3.7), respiratory dysfunction(OR 2.3; 95%CI, 2.2-2.4), hepatic dysfunction (OR 2.9; 95%CI 2.4-3.4), hematological dysfunction (OR 1.9; 95%CI, 1.8-2.1), and after thrombolysis (OR 3.8; 95%CI, 3.6-4.0). The median hospital LOS for ARDS was 8 days Inter-Quartile range [IQR] 14-23 vs. 3 days IQR 5-7, p<0.001. Median hospital cost for ARDS was $56,990 IQR $29,360-$111,900 vs. $17,240 IQR $10,760-$28,620, p<0.001. ARDS independently predicted higher hospital LOS (OR 2.4, 95% CI, 2.4-2.5) and higher costs (OR 2.6, 95% CI 2.5-2.6).

Conclusion.
Our analysis demonstrates an increase in the prevalence of ARDS after AIS in U.S. ARDS is associated with significant increase in hospital LOS and overall costs.
Abstract 3572: Clinical Outcomes of the “Stroke100 Club”
Authors: Guzik Amy K , Raman Rema , Ernstrom Kain , Meyer Dawn M , Sodhi Ajeet , Ovbiagele Bruce , Hemmen Thomas , Pancioli Arthur M , Meyer Brett C
Published: July 2021

Background:
Patients with advanced age or high NIHSS have poorer tPA outcomes. When combined, old age (≥80yo) and elevated NIHSS (≥20) may have an even worse outcome. Patients who are also in this “Stroke100 Club” (any combination of age and NIHSS ≥100) by other means, have not been fully assessed. We evaluated discharge destination, 90-day mRS, sICH and death in treated and untreated Stroke100 Club patients. We further compared patients with age ≥ 80 and NIHSS ≥ 20 (“80/20s”), those who reached 100 without both characteristics (“non80/20s”) and ‘controls’.

Methods:
The UCSD SPOTRIAS prospectively collected database was analyzed for AIS patients (with and without tPA). Multivariable regression models including the Stroke100 group as an independent variable was used. Outcomes were adjusted for baseline mRS. For comparing categorical outcomes between controls, “80/20s” and “non80/20s” subgroups, a Fisher’s exact was used.

Results:
The IV tPA subset included 257 patients (mean age 71, 52% male, 85% white, mean NIHSS 12). 53 were in the “Stroke100 Club” (28 80/20, 25 non80/20), with more women (68% p= 0.002), higher NIHSS (22.5 p<0.0001), older age (mean age 86.4 p<0.0001), higher pre stroke mRS (34.6% mRS 3-6 vs 7.84%, p<0.0001), more HTN (p=0.045) and more afib (p= 0.008). There were 284 non tPA patients (mean age 69.52, 54% male, 85% white, mean NIHSS 5.92). 21 were in the “Stroke100 Club” (14 80/20, 7 non80/20), with higher NIHSS (23 p<0.0001), older age (mean 86.2 p<0.0001), higher pre stroke mRS (45.5% 3-6 vs 9.5%, p= 0.0001), and more afib (p= 0.0002). Stroke100 Club 90day mRS(3-6) outcomes were worse in both tPA treated patients (OR=6.77, p= 0.0001) and nontreated patients (OR 31.57, p= 0.001). sICH rates (in tPA subjects) were not different (3.8% vs 3.4%, p> 0.99).

Conclusions:
There is a question of treatment outcome in patients with various permutations of stroke severity and advanced age. Our data corroborates the concern of poor outcomes for Stroke100 Club patients, but notes no increased sICH with tPA. Though outcome may be poor, withholding tPA should be discouraged as worse outcomes were not due to sICH. Young patients with severe strokes or old patients with mild strokes may have outcomes similar to the standard “80/20” Stroke100 patients, however further adjusted analysis is ongoing. In addition, further analyses are being done to compare tPA to non tPA patients.
Abstract 3577: Lesions in White Matter Tracts Contralateral to the Ischemic Vascular Injury
Authors: Paraguay Isabela B , Magalhães Daniel S , Lima Fabricio O , Ribeiro Fádua H , Pereira Fabrício R , Avelar Wagner M , Yoshida Hlio M , Fernandes Paula T , Cendes Fernando , Li Li M
Published: July 2021

Background:
The phenomenon of diaschisis, with wallerian degeneration, can increase the brain lesion burden in unilateral vascular ischemic lesion leading to contralateral damage. Diffusion tensor imaging (DTI) allows the visualization and measurement of white matter lesions. We tested the hypothesis that there are white matter tracts lesions in the hemisphere contralateral to the ischemic lesion.

Methods:
Patients with unilateral ischemic lesions, who had performed a diagnostic MRI including DTI sequence (Philips Achieva 3T, Best, Netherlands) from August 2009 to April 2010 were selected. A neuroradiologist analyzed the images and selected the ones with unilateral ischemic lesion on middle cerebral artery territory. For comparisons, images of healthy-control subjects with similar age, from the local neuroimaging laboratory, were used. The DTI images (TR=8500, TE=61, 2mm of slice thickness, 32 directions, b-factor 1000) were analyzed using a tract based statistical study (TBSS, fMRIB software library, Oxford, UK). After image alignment and mapping, the fractional anisotropy values were compared in order to detect possible differences in the white matter tracts between patients and controls. P values < 0.05 were considered as statistically significant.

Results:
Thirty seven patients (11 women) with mean age of 60 years (range, 25- 79 years) and 24 controls (11 women) with mean age of 58 years (range, 49- 70) were studied. Twenty of the 37 patients had ischemic lesions on the right hemisphere. Leukoaraiosis was present in all stroke patients. Differences of fractional anisotropy between patients and controls were detected on the ipsilateral hemisphere but also in the hemisphere contralateral to the ischemic lesion and outside the middle cerebral artery territory (p < 0.05).

Conclusions:
Patients with unilateral ischemic lesions present changes of the white matter integrity in both hemispheres. Contralateral white matter lesions are seen beyond ipsilateral middle cerebral artery territory, which suggests a diaschisis phenomenon or a diffuse microvascular involvement.
Abstract 3594: A Pilot Feasibility Study of Community Engaged Stroke Preparedness: The ASPIRE Project
Authors: Boden-Albala Bernadette , Wing Jeffrey J , St Clair Shauna , Fernandez Stephen , Gibbons M. C , Morgenstern Lewis , Edwards Dorothy F , Kidwell Chelsea
Published: July 2021

BACKGROUND:
Lack of culturally appropriate education about stroke may prevent people from recognizing symptoms and/or seeking immediate care. The Stroke Warning Information and Faster Treatment (SWIFT) intervention reports increasing the proportion of prevalent stroke/TIA cases arriving under 4.5 hours using culturally tailored strategies, but few interventions have rigorously evaluated preparedness strategies in community settings. ASPIRE is a multi-dimensional program with a three-pronged approach (community, hospital, EMS) to acute stroke preparedness targeted to increased IV tPA utilization in underserved black communities in the DC metro area.

METHODS:
Using community engaged methodology, a skill-based approach to teaching community members to recognize acute stroke, call 911 and navigate the ER setting was developed. In the pilot phase, 50 education sessions were conducted in church, civic, educational and work organizations over a six month period in Ward 7 of the DC Metro area. Local ER and EMS staff were also in-serviced. We prospectively identified all hospital stroke admissions and EMS utilization information including acute stroke parameters for the 6 month pre and post intervention periods. Pre-post pilot intervention acute ischemic stroke parameters were compared.

RESULTS:
In the pre-intervention period, we identified 142 ischemic strokes in Ward 7: mean age 63 yrs; 63% male; 96% blacks. Fifty-six percent arrived via EMS, with a mean and median time to arrival of 1600 minutes (27.0 hours), and 890 minutes (14.8 hours), respectively. Following the intervention we identified 115 ischemic stroke cases: 66 yrs; 47% male; 89% black. Fifty percent arrived via EMS, mean and median time to arrival was 1423 min (23.7 hours) and 815 min (13.6 hours). In addition to this modest decrease in overall arrival times, an increased proportion of cases arriving in the 4.5 hours group was noted [pre 25% vs. post 28%, p=NS]. We were also able to match 104 ischemic stroke cases to EMS utilization sheets demonstrating feasibility for larger evaluation.

CONCULSION:
The ASPIRE pilot demonstrates feasibility of the multilevel community education intervention as well as feasibility of linking EMS and hospital records on a city wide scale. Despite the small number of ischemic strokes in this pilot phase, a modest reduction in hospital arrival times occurred in the post intervention phase. A city-wide intervention aimed at increasing the proportion of stroke patients treated with IV tPA is currently underway.
Abstract 3596: National Estimates of Down Syndrome Prevalence in Patients with Moyamoya Disease
Authors: Kainth Daraspreet S , Chaudhry Saqib A , Kainth Hunar , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background:
An association between Moyamoya disease and Down syndrome appears to exist based on reported anectdotal cases in the literature.

Objective:
We performed this study to determine the prevalence of Down syndrome associated with Moyamoya disease in inpatients and to identify the clinical features of Moyamoya disease that may be unique when associated with Down syndrome.

Methods:
We analyzed data from patients entered in the Nationwide Inpatient Sample between 2002 and 2009, using International Classification of Diseases codes for Moyamoya disease and Down syndrome for patient identification. Data including patient age, gender, ethnicity, secondary diagnosis, medical complications, hospital costs, and patient outcomes was obtained.

Results:
From 2002 to 2009, an estimated 518 patients (mean age [±SD] 16.2 [± 1.68] years) with co-existing Moyamoya disease and Down syndrome were admitted as inpatients. The estimated prevalence was 3.76% (3760 per 100,000) among patients admitted with Moyamoya disease and 10.6% (10,600 per 100,000) among patients aged under 15 years. Patients admitted with Moyamoya disease and Down syndrome were most frequently Caucasian and Hispanic (p=0.015). They were more likely to present with symptoms of ischemic stroke and less commonly with hemorrhagic stroke, 15.3% and 2.7%(p < 0.05), respectively. The average length of hospital stay was 8.7 days (3.0 - 14.4). The majority were discharged home, 6.9% to nursing facilities, and 1.8% died in the hospital.

Conclusion:
This is the first study to estimate the prevalence of Down syndrome in patients with Moyamoya disease. The 300 fold greater prevalence of Down syndrome in patients with Moyamoya disease compared with prevalence among live births (12 per 100,000) highlight the need for better understanding of common pathophysiology of both conditions .
Abstract 3632: Secondary Vascular Events and Sleep Adequacy: the SWIFT Study
Authors: EVENSEN LAURA , Liu Nan , Wang Yijun , Boden-Albala Bernadette
Published: July 2021

Objective:
To describe the relationship between sleep problems, measured by the Medical Outcomes Sleep scale (MOS) at baseline, in ischemic stroke and TIA (IS/TIA) patients and the likelihood of having a recurrent event, leading to vascular death.

Background:
Among IS/TIA patients, there is increased risk for recurrent vascular events, including stroke, MI and vascular death. While history of stroke is a major predictor of recurrent events, there may be unidentified factors in play. Sleep quality may predict recurrent vascular events, but little is known about the relationship between sleep and recurrent events in IS/TIA patients.

Methods:
The Stroke Warning Information and Faster Treatment (SWIFT) Study is an NINDS SPOTRIAS funded randomized trial to study the effect of culturally appropriate, interactive education on stroke knowledge and time to arrival after IS/TIA. Sleep problems and recurrent event information were collected among consentable IS/TIA patients. Cox proportional hazards models were used to describe relationships between sleep and recurrent vascular events in IS/TIA patients. The MOS, a 12 item sleep assessment, measures 6 dimensions of sleep: initiation, maintenance, quantity, adequacy, somnolence and respiratory impairment.

Results:
Over 5 years, the SWIFT study cohort of 1198 [77% IS; 23% TIA] patients were prospectively enrolled. This cohort was 50% female; 50% Hispanic, 31% White and 18% Black, with a mean NIHSS of 3.2 [SD ±3.8]. 750 subjects completed the MOS scale at baseline. In a multivariate analysis, after adjusting for demographics and vascular risk factors: gender, age, race ethnicity, NIHSS, stroke history, qualifying event type, hypertension, diabetes, smoking and family stroke history, longer sleep initiation is associated with combined outcome of IS/TIA, MI and vascular death [p=0.1, HR=1.09]. Significant predictors of vascular death included: trouble falling asleep (initiation) [p=0.05, HR=1.15]; not ‘getting enough sleep to feel rested’ and not ‘getting the amount of sleep you need’ (adequacy) [p=0.06, HR=1.18 and p=0.03, HR=1.18, respectively]; shortness of breath or headache upon waking (respiratory impairment) [p=0.003, HR=1.33]; restless sleep [p=0.07, HR=1.15] and waking at night with trouble resuming sleep [p=0.004, HR=1.23] (maintenance); daytime drowsiness [p=0.05, HR=1.18] and trouble staying awake [p=0.01, HR=1.25] (somnolence); and taking naps (quantity) [p=0.03, HR=1.22].

Conclusions:
Sleep problems represent diverse, modifiable risk factors for secondary vascular events, particularly vascular death. Exploring sleep dimensions may yield crucial information for reduction of secondary vascular events in IS/TIA patients. Further investigation is needed to fully understand the effects of sleep on secondary vascular event incidence.
Abstract 3645: Omeprazole, A Potent Cyp 2c19 Inhibitor, Does Not Alter The Pharmacokinetics Or Platelet Aggregation Of Asa And Dipyridamole In Combination
Authors: Offman Elliot , Rolf-Stefan Rolf , Vandermaelen Cam , Schobelock Michael , Eisert Wolfgang
Published: July 2021

Antiplatelet therapies such as aspirin (ASA), clopidogrel or a combination of ASA and extended-release dipyridamole (ASA/DP) are recommended therapeutic options for reducing the risk of stroke in patients with prior stroke or TIA. The clinical benefit of clopidogrel is highly dependent on the bioactivation of clopidogrel to its active metabolite by CYP 2C19. Omeprazole (OME), a frequently used gastric acid suppressant, is a potent inhibitor of CYP2C19, and has been identified as having a clinically significant interaction with clopidogrel. It was unclear whether ASA/DP would be subject to the same interaction risk when concomitantly administered with OME. This study formally tests whether multiple daily doses of OME 80 mg alters the pharmacokinetics of dipyridamole or the inhibition of platelet aggregation (IPA) of ASA/DP. This study was performed in 60 healthy volunteers as a multiple-dose, open-label, randomized, crossover trial with 4 treatments within 2 treatment sequences. The endpoints included the steady-state Cmax and AUC of DP as well as IPA at 4 and 12 hours postdose. The mean plasma DP concentration time profile for all treatments is displayed in
Figure 1
. The 90% confidence interval for DP Cmax and AUC was fully contained within 80-125% bounds indicating no clinically significant interaction between ASA/DP and OME. Moreover, concomitant administration of ASA/DP with OME had no effect on the inhibition of arachidonic acid induced platelet aggregation over the normal dosing interval at steady-state (
Table 1
). There was no difference detected regardless of whether subjects were pre-treated with OME alone or ASA/DP and OME. In conclusion, concurrent administration of OME with ASA/DP does not alter the steady-state pharmacokinetics of DP nor the inhibition of platelet aggregation of ASA/DP, regardless of the order of treatment administration. All treatments were well tolerated. [
Table 1
.]

Table Notes: A: ASA/DP alone B: ASA/DP + Omeprazole following ASA/DP alone C: Omeprazole alone D: ASA/DP + Omeprazole following Omeprazole alone
Abstract 3664: Comparison of the Short-Form 12 to the Modified Rankin Scale Score at 3 and 12 Months Post Intracerebral Hemorrhage
Authors: Kleinman Jonathan T , Snider Ryan W , Thai Demi , Nguyen Haihong , Eyngorn Irina , Wijman Christine A
Published: July 2021

Background:
The modified Rankin Scale score (mRS) is routinely used to evaluate functional outcome following stroke. The Short Form 12 version 2 (SF-12v2) is a 2 minute physical and mental health survey that measures 8 domains of health and is: widely used, norm-based, and comprehensive. We sought to compare physical component summary (PCS) scores, mental component summary (MCS) scores, and their sub-scores to the mRS scores. Each metric provides unique and relevant health information.

Methods:
Consecutive ICH patients were prospectively enrolled in the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study. Three month evaluations were done in clinic when possible, while 1-year evaluations were obtained via semi-structured telephone interviews. Responses were adjusted for age and gender based on published data. Physical functioning ([PF] ability to perform activities), limitation in the amount and types of physical activities to the point that less is accomplished than desired (role physical [RP]), mental health ([MH] feelings of anxiety and depression), and PCS scores were compared to the mRS and to each other as they have the highest internal consistency based on published data. Significant depressive symptoms was defined as >10 points (1 standard deviation) below the mean.

Results:
Seventy-nine ICH patients had the SF12v2 and mRS available for assessment: mean age 59±17 years and ICH volume 22±27cc. Physical functioning at 3 months was correlated with mRS as assessed by: the PCS (R
2
=0.39); PF (R
2
=0.56); and RP (R
2
=0.52). At 12 months the mRS was more correlated with each sub component score and the PCS (R
2
=0.53). Feelings of anxiety and depression were not correlated with either 3 or 12 month mRS (R
2
= 0.06 and 0.15 respectively). At 3 months 6 (14%) patients with a mRS ≤2 had signs of depression and 6 (19%) of patients with mRS 3-4 had signs of depression as assessed by MH. More patients with mRS ≥2 had depressive symptoms (22% vs 4%, p=0.09) at 3 months and at 12 months (14% vs 0%, χ
2
=4.7, p=0.04) compared to those with a mRS of 0-1.

Conclusions:
The self reported physical components of the SF12v2 have only a fair correlation with the mRS at 3 and 12 months after intracerebral hemorrhage. Feelings of depression do not have a linear relationship with mRS, but a higher proportion of patients with increased mRS have significant depressive symptoms at one year.