bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP211: Ethnic Differences in Cognitive Recovery 3 Months Following Stroke
Authors: Briceño Emily M , Dong Liming , Lisabeth Lynda D , Morgenstern Lewis B
Published: June 2021

Introduction:
Mexican Americans (MA) have worse cognitive outcomes following stroke relative to non-Hispanic whites (NHW). In a population-based study we examined whether MAs and NHWs have different cognition just after stroke (baseline) and different cognitive trajectories at 90 days post stroke.

Methods:
The sample included 598 participants from the Brain Attack Surveillance in Corpus Christi Project who had ischemic stroke between 2008-2013. Cognitive assessment was the 3MSE (English or Spanish). A change score was calculated (3MSE at 90 days minus 3MSE at baseline). Robust regression was used to examine ethnic differences in cognitive outcomes adjusted for sociodemographics, pre-stroke factors, and clinical stroke characteristics; missing covariate values were imputed with multiple imputation.

Results:
The sample was 57% MA, 35% NHW, and 8% other race/ethnicity. MAs were younger, had lower educational attainment, and were less likely to have health insurance than NHWs (all p<0.01). MAs showed lower cognitive function at baseline (Table 1) and less cognitive recovery 90 days following stroke compared with NHWs (Table 2), which remained significant after accounting for all covariates (Model 5, Tables 1 and 2).

Conclusions:
MAs have worse post-stroke baseline cognition and less robust cognitive recovery 90 days following stroke than NHWs. This disparity should be addressed through rehabilitation or other interventions.
Abstract WP214: Risk Factors for Recurrence of Vascular Events in Middle-Aged Stroke Survivors
Authors: Vanent Kevin N , Leasure Audrey C , Kuohn Lindsey R , Benavente Oscar R , Shoamanesh Ashkan , Biffi Alessandro , Sheth Kevin N , Falcone Guido J
Published: June 2021

Background:
Stroke in middle-aged persons is emerging as a distinct entity from previously described "stroke in the young.” Risk factors for recurrence of vascular events in middle-aged stroke survivors have not been well described in a large, racially diverse US-based population.

Methods:
We performed a retrospective longitudinal analysis of claims data from all hospitalizations in California (2005-2011), Florida (2005-2014), and New York (2005-2014). We included survivors of first-ever ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH). We used validated ICD-9 codes to identify recurrent vascular events, defined as a readmission with a primary diagnosis of IS, ICH, or myocardial infarction (MI). We used survival analysis and Cox proportional hazards regression to determine factors associated with recurrence risk in middle-aged (40-60 years) versus older (>60 years) adults.

Results:
We identified 123,212 non-fatal hospitalizations for first-ever IS or ICH in middle-aged adults. There were 14,721 readmissions for recurrent vascular events (11.9%) over a mean follow-up of 4.0 years (standard deviation [SD] 2.8 years). The 1-year and 10-year recurrence rates were 5.5% (95% confidence interval [CI], 5.3%-5.6%) and 19.4% (95% CI, 19.0%-19.8%) respectively. In multivariable analysis, black (hazard ratio [HR] 1.44; 95% CI, 1.39-1.50; p<0.001) and Hispanic race (HR 1.10; 95% CI, 1.05-1.16; p<0.001), diabetes (HR 1.76; 95% CI, 1.70-1.82; p<0.001), smoking (HR 1.22; 95% CI, 1.18-1.27; p<0.001), hyperlipidemia (HR 1.08; 95% CI, 1.04-1.12; p<0.001), and hypertension (HR 1.06; 95% CI, 1.03-1.10; p<0.001) were associated with increased risk. The associations of black race and diabetes were modified by age category (both multivariable interactions p<0.001). Black race and diabetes were associated with greater increases in risk in middle-aged versus older adults (in older adults: black race HR 1.28; 95% CI, 1.25-1.31; p<0.001; diabetes HR 1.27; 95% CI, 1.25-1.30; p<0.001).

Conclusions:
Black race and diabetes were the strongest risk factors for recurrence of vascular events in a middle-aged population. Further study of interventions to reduce recurrence and resulting disability in this younger, higher risk population is needed.
Abstract WP222: Patient Factors Influencing Oral Anticoagulant Prescribing for Atrial Fibrillation After Stroke
Authors: Sterling Kadieann , Langhorne Peter , Macleod Mary J , Turner Melanie
Published: June 2021

Introduction:
Several studies have observed suboptimal prescribing of oral anticoagulants (OAC) in patients with atrial fibrillation (AF). This occurs especially in older patients, despite higher risk for first or recurrent stroke. The decision not to recommend anticoagulation may be influenced by a wide range of factors.

Aims:
To determine the patient factors (age, gender, living circumstances and comorbidities) associated with post-stroke OAC prescribing in a national cohort of stroke survivors with atrial fibrillation.

Methods:
A retrospective cohort observational study, using a linked dataset of the Scottish Stroke Care Audit (2010-15), Prescribing Information System and the Scottish Morbidity Record. Multivariate logistic regression analysis was done to calculate the odds of OAC prescribing within six months post-stroke, adjusting for the following patient factors: age, gender, deprivation, year of admission, stroke subtype, stroke severity (six simple variables), comorbidity count and concomitant medication use.

Results:
Overall, 8129 stroke survivors had confirmed AF; 4817 (59.3%) were prescribed OAC within the six months post-stroke. Older patients were less likely to be prescribed an OAC (adjusted Odds Ratio (aOR) 0.97, 95% Confidence Interval (CI) 0.96-0.98). There was no significant difference between male and female OAC prescribing (aOR 0.92, CI 0.79 - 1.07) or whether living alone before stroke (aOR 0.928, CI 0.78 - 1.08). Independent in activities of daily living before stroke (aOR 2.09, CI 1.69 - 2.59) and orientated at baseline assessment (aOR 1.51, CI 1.25 - 1.84) were both associated with more OAC prescriptions. Patients who lived in less deprived areas were more likely to be prescribed an OAC. Number of comorbidities significantly influenced prescribing; patients with 1-3 comorbidities (aOR 0.71, CI 0.60 - 0.84), and ≥ 4 comorbidities (aOR 0.46, CI 0.34 - 0.625) respectively were less likely to be prescribed an OAC compared to patients with no comorbidities.

Conclusions:
Lower OAC prescribing in older age may also reflect prior dependence, social deprivation and multiple comorbidities. Promoting appropriate stroke prevention in higher risk patients who may still benefit from OAC requires ongoing attention.
Abstract WP223: Evolution of Ischemic Stroke Subtypes: An Observational Study Over 15 Years
Authors: Ip Yiu Ming Bonaventure , Soo Oi Yan Yannie , Leung Wai Hong Thomas
Published: June 2021

Introduction:
In the face of population ageing and contemporary cardiovascular risk factor control, understanding the evolution of ischemic stroke mechanisms may inform stroke prevention strategy and guide resources allocation.

Method:
Through a registry-based observational study in a regional hospital in Hong Kong, we studied the evolution of stroke mechanisms by TOAST classification over a 15-year period (2004-2018). We retrieved demographic data, pre-defined cardiovascular risks, use of medications, intensity of risk factor control and clinical outcomes (2-year recurrence and 3-month mortality and disability) from the stroke registry. We defined stroke mechanisms by clinical signs and symptoms, cardiovascular risk profile and infarct topography. We compared the trends of stroke mechanisms by Chi-square test for trend and continuous variables by one-way ANOVA test with post-hoc Bonferroni test. Interobserver reliability was assessed by kappa statistics.

Results:
We included 5982 patients over the 15-year period. The number of atrial fibrillation (AF)-related stroke increased by 213% (p<0.001) and large-artery-disease (LAD)-related stroke decreased by 47.7% (p<0.001). AF-related stroke had the highest mean age (77.4±11, p<0.001) and National Institute of Health Stroke Scale on admission (14.8±10.8, p<0.001). Within the AF-related stroke patients, the number of strokes as first presentation of AF increased by 200%. 2-year recurrence of stroke or transient ischemic attack of patients with symptomatic intracranial atherosclerosis (ICAS) decreased from 20.7% to 9.3%.

Conclusion:
We observed a huge increase in AF-related stroke and newly diagnosed AF at presentation. Our results demanded an enhanced surveillance in detecting AF, primary prevention and thrombectomy facilities given the high morbidity and mortality associated with AF-related strokes. The decline in ICAS-related stroke and its recurrence may underscore the importance of intensive risk factor management in the Asia-Pacific region where ICAS remained prevalent.
Abstract WP241: Prevalence of Subclinical Extracranial Carotid Atherosclerosis Detected by Ultrasound Among Amerindians: A Population Study in Rural Ecuador
Authors: Del Brutto Victor J , Romano Jose G , Mera Robertino M , Amodio Jonathan P , Rundek Tatjana , Del Brutto Oscar H
Published: June 2021

Background:
Epidemiological information on extracranial carotid atherosclerosis (ECA) among Amerindians is limited. We aim to determine the prevalence of subclinical ECA and its correlation with cardiovascular risk factors in community-dwelling adults of Amerindian ancestry living in a rural Ecuadorian village.

Methods:
Utilizing a population-based design, stroke-free individuals aged ≥40 years were invited to undergo carotid ultrasound. Subclinical ECA was defined as an intima-media thickness (cIMT) >1mm and/or the presence of carotid plaques (focal intima thickening >1.5mm that protrudes into the lumen). Degree of luminal stenosis was calculated and considered significant if >50%. We investigated the association between these biomarkers and cardiovascular risk factors.

Results:
Of 728 candidates, 559 (77%) stroke-free individuals underwent carotid sonographic evaluation and were included. The mean age was 62.3 ±12.5 and 238 (43%) were men. The mean value of the cIMT was 0.85 ± 0.17mm (median cIMT: 0.83mm; IQ range: 0.74-0.92 mm). The prevalence of increased cIMT, carotid plaques, and increased cIMT and/or carotid plaques were 14%, 23.8%, and 26.1%, respectively. Table depicts the association of these biomarkers with cardiovascular risk factors. A multinomial logistic regression model, using individuals with normal carotids as the referent category, showed significant associations of ECA with increasing age, male gender, smoking and high blood pressure. Significant carotid stenosis was found in 19 subjects (3.4%).

Conclusions:
About one-fourth of Amerindians living in a rural setting have subclinical ECA. Increasing age, male gender, smoking and high blood pressure were independent determinants of the burden of ECA, while elevated glucose and total cholesterol showed no significant association. Obesity was inversely associated with ECA in univariate analysis, but such association disappeared in the multivariate model.
Abstract WP250: Diurnal Temperature Range as a Risk Factor for Ischemic Stroke Severity in Summer
Authors: Kang Minkyung , Lee Eung-Joon , Jeong Hae Bong , Jeong Han-Yeong , Kim Tae Jung , Ko Sang-Bae , Yoon Byung-Woo
Published: June 2021

Introduction:
Temperature affects human health. It is widely known that mean ambient temperature with both short-term and cumulative lagged effect, is the exposure measure for ischemic stroke. Recently, not only mean temperature, larger diurnal temperature range (DTR, difference between high- and low-daily temperature) was associated with coronary heart disease mortality and ischemic stroke hospitalizations. We hypothesized that a larger DTR results in environmental stress to the human cardiovascular system, thereby increasing the risk for acute ischemic stroke severity.

Methods:
We used both time-series and case-crossover approaches to assess the relation between DTR and ischemic stroke severity between summer of 2016 and 2018 in Korea. Data were obtained from Korean Stroke Registry and Korean Meteorological Administration. We used exposures averaged over periods varying from 1 to 14 days to assess the effects of DTR on stroke severity. We estimated the relation between DTR and ischemic stroke severity after adjustment for classical stroke risk factor and weather conditions of stroke index day.

Results:
A 9,249 patients were included in both time-series and case-crossover analyses. The results showed that DTR was significantly associated with stroke severity. The lag effect of DTR was stabilized at about 3-4 days. A 5 °C increase of three-day moving average of DTR corresponded to a 1.67 (95% Confidential Interval, CI 1.64-1.70, p<0.001) and a 5°C increase of DTR of stroke onset day corresponded to a 1.09 (95% CI 1.07-1.12, p<0.001) increase of NIHSS with unidirectional case-crossover analysis after adjustment for classical stroke risk factor and meteorological factor.

Discussion:
The current study supported our hypothesis that diurnal temperature variation could be a new severity factor for acute ischemic stroke. Moreover, the two different methods we used provided relatively similar results, suggesting that the association between DTR and stroke

severity was reasonably robust. Our data added additional evidence that exposure to large DTR was associated with increased burden of stroke. This findings would contribute public health program to prevent unstable thermal environments.
Abstract WP265: Association Between Brachial-Ankle Pulse Wave Velocity and Aortic Atheroma in Acute Ischemic Stroke
Authors: Jeong Jaewook , Choi Jin Kyo , Kim Young Dae , Heo Ji Hoe , Nam Hyo Suk
Published: June 2021

Background and Purpose:
Aortic plaques are associated with both larger artery and small artery atherosclerosis. However, association between aortic plaque and aortic stiffness in ischemic stroke is unknown. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive technique to measure aortic stiffness. In the present study, we hypothesized that presence of aortic plaques is associated with increased baPWV.

Methods:
We reviewed 1099 patients diagnosed with acute ischemic stroke, who had both transesophageal echocardiography (TEE) and brachial-ankle pulse wave velocity (baPWV) measurements. Aortic plaques were classified as complex aortic plaques (CAP) or simple aortic plaques (SAP). CAP were defined as plaques protruding into the lumen ≥4 mm and of mobile lesions located in the proximal aorta. SAP represented plaques <4 mm in the proximal aorta and plaques located in the descending aorta of any sizes. Patients were classified into 4 groups; patients who have CAP only, those who have SAP only, those who have both CAP and SAP, and those without aortic plaques.

Results:
Among the 1099 patients, aortic atheroma was found in 689 (62.7%) patients. Twenty one (1.9%) patients had only CAP, 142 (12.9%) patients had both SAP and CAP, while 526 (47.9%) patients had SAP without CAP. Mean value of baPWV was 1982±580 cm/sec. baPWV was significantly increased in patients with any aortic atheromas than those without atheromas (2095±577 cm/sec vs. 1793±535 cm/sec, p <0.001). Analysis of variance showed that baPWV was significantly increased in patients with SAP only (p<0.001) and SAP and CAP (p<0.001) compared to those without any aortic atheroma, whereas CAP only patients were not associated with baPWV (p = 0.131).

Conclusion:
We found that baPWV was associated with SAP but not CAP in acute ischemic stroke patients. These feature suggests that SAP represent generalized atherosclerosis and aortic stiffness, whereas CAP represent the sole mechanism of stroke.
Abstract WP267: Association Between Arterial Resistance and Subtypes of Cerebral Small Vessel Disease
Authors: LEE Yongseok , Nam Ki-Woong , Kwon Hyung-Min
Published: June 2021

Introduction:
Increased arterial resistance is a potential pathophysiological mechanism in the pathogenesis of cerebral small vessel disease (cSVD). In this study, we aimed to investigate the association between puslatility index (PI) representing cerebral arterial resistance and subtypes of cSVD in patients with stroke due to small vessel occlusion (SVO).

Hypothesis:
Pattern of increased arterial resistance may be different between individual subtypes of cSVD.

Methods:
We included consecutive patients with SVO between 2010 and 2013. White matter hyperintensity (WMH) volume was rated using semi-automated quantitative methods. And the presence of old lacunar infarct (OLI), cerebral microbleed (CMB), or enlarged perivascular space (EPVS) was also evaluated. The relationship between PI, measured with transcranial Doppler sonography in each middle cerebral artery, and subtypes/burden of cSVD was analyzed in the relevant hemisphere.

Results:
A total of 206 patients with 412 hemispheres were included (mean age: 64 years, male: 68%). In multivariable analysis, PI was positively associated with the WMH volume [beta = 1.372, 95% confidence interval (CI) = 0.624 to 2.120,
P
< 0.001] after adjusting confounders. PI was also related to the presence of OLI (adjusted odds ratio = 11.37, 95% CI = 2.55-48.56,
P
= 0.001), however this relationship was not significant in CMB or EPVS. Regarding to the cSVD burden, PI increased according to the WMH tertiles (
P
for trend < 0.001), and burden of OLI (
P
for trend = 0.004) in a dose-response manner.

Conclusion:
Association of cerebral arterial resistance is different between subtypes of cSVD, which is suggestive of underlying pathophysiological difference. Simple measure of PI seems to be useful to estimate the arterial resistance and the burden of cSVD.
Abstract WP269: Automatic Segmentation of Cerebral Arteries in MRA TOF Using Deep Learning
Authors: Yeo Leonard L , Engin Melih , Lange Robin , Boopathy Sethu R , Cunli Yang , Tang David K , Mohammadzadeh Milad , Monajemi Sadaf , Goh Chin Kong , Tu Tian Ming , Sharma Vijay K
Published: June 2021

Purpose:
Time-of-Flight (TOF) MRA is commonly used for grading cerebrovascular diseases. Analysis of cerebral arteries in MRA TOF is a challenging and time consuming task that would benefit from automation. Established image processing methods for automatic segmentation of cerebral arteries suffer from common artefacts such as kissing vessels (when two nearby vessels touch) and signal intensity drop (especially in the presence of pathology). Artificial intelligence models are promising candidates for resolving such artefacts. Here, we propose and assess the performance of a deep learning model for automatic segmentation of cerebral arteries in MRA TOF which is robust to common MRI artefacts.

Methods:
A 3D convolutional neural network (CNN) is proposed for automatic segmentation of intracranial arteries in MRA TOF. The neural network is trained with a custom loss function and residual blocks to penalize the occurrence of common artefacts such as kissing vessels. The model is trained and tested on a dataset consisting of 82 subjects (50 healthy volunteers and 32 patients with intracranial stenosis) following a 3-fold cross-validation method, i.e. 3 models are trained where each model is blind to one-third of the data in the training process to avoid bias. Manual segmentation of the arteries done by an expert reader are used as ground-truth for training and testing the model.

Results:
The proposed deep learning model achieved excellent accuracy compared against the ground truth (Dice score 0.89). Our proposed deep learning model outperformed a state-of-the-art neural network for image segmentation (3DU-Net, Dice score 0.85) and resulted in considerably less occurences of artefacts such as kissing vessels (9% of cases had segmentation artefacts for our model vs 16% for 3D U-Net). The proposed deep learning model was fast, taking only 2 seconds to produce a 3D model of the arteries on a laptop with a dedicated GPU.

Conclusion:
The proposed deep learning model accurately segments intracranial arteries in MRA TOF and is robust to common artefacts of MR imaging thanks to implementation of a custom loss function. The model can potentially increase the accuracy and speed of grading cerebrovascular diseases.
Abstract WP281: Pharmacists Improve Door to Needle Times in the Emergency Department
Authors: Phan Kevin , Degener Megan
Published: June 2021

Background:
An estimated two million brain cells die every minute cerebral perfusion is impaired. The best outcomes for acute ischemic strokes are achieved by decreasing the time from emergency department (ED) arrival to thrombolytic therapy. Alteplase, a high risk medication, was dosed and prepared in the pharmacy. This contributed to prolonged door to needle (DTN) times.

Purpose:
To describe the impact of pharmacist interventions on DTN times in the ED.

Methods:
All patients who received alteplase for acute ischemic stroke from January 2012 to April 2019 were reviewed. In November 2012, the ED pharmacy program began with a dedicated ED pharmacist for 8 hours a day and expanded to 13 hours a day in September 2014. During those hours alteplase was prepared at bedside in the ED. In November 2015, all pharmacists were trained on the ED code stroke process. Monthly case reviews and DTN times were reported to the stroke coordinators starting January 2017. Alteplase preparation and administration in the computed tomography (CT) room started April 2017. Following comprehensive stroke center certification, routine stroke competency exams were administered to pharmacists in 2018. In 2019, pharmacists started reporting DTN times at neuroscience core team meetings.

Results:
During this time frame, a total of 407 patients received alteplase. Average DTN times decreased from a baseline of 130.9 minutes to 45.3 minutes. Interventions that resulted in the largest decrease in average DTN times were the expanded ED service hours (34.6 minutes) and pharmacist preparation of alteplase in the CT room (21.9 minutes).

Conclusions:
Pharmacists directly impacted stroke care in the ED by decreasing DTN times. Presence of a pharmacist in the ED enabled fast and safe delivery of alteplase by ensuring accurate dosing and preparation. Pharmacists also performed rapid medication reconciliation and expedited antihypertensive therapies. In conclusion, having pharmacists as part of the stroke team is a model that could be adopted by hospitals to enhance stroke care.
Abstract WP289: Increasing Emergency Department Use of Advanced Neuroimaging in the Mechanical Thrombectomy Era
Authors: Mamer Lauren E , Kocher Keith E , Cranford James , Scott Phillip A
Published: June 2021

Introduction:
Data supporting mechanical thrombectomy substantially expanded both the time available for treatment and need for advanced neuroimaging in patients with suspected stroke. These factors potentially increase emergency department (ED) use of neuroimaging resources, though the existence and magnitude of effect is unknown, particularly in a broad hospital population including non-stroke center emergency departments.

Hypothesis:
ED use of CT-angiography (CTA) and CT-Perfusion (CTP) imaging is both increasing and accelerating from 2013 to 2018.

Methods:
Prospective, longitudinal, single-state cohort study of ED visits using existing California OSHPD dataset (a mandatory reporting database of all CA-licensed, non-federal, emergency department encounters either discharged or transferred) from 2013 to 2018. NCHCT (CPT 70450), CTA Head (CPT 70496), CTP (CPT 0042T) and MRI Brain (CPT 70553) use in the data set, as determined by Common Procedural Terminology (CPT) codes, was analyzed using descriptive statistics and tests of comparison.

Results:
All advanced neuroimaging increased during the period. Use of NCHCT increased 61% over the study period, from 2,432 to 3,922 per 100,000 ED visits (p trend < .001). Use of CTA increased 405%, from 39 to 197 per 100,000 encounters (p trend < .001). Use of CTP increased 230%, from 3 to 10 per 100,000 encounters (p trend < .001). Use of MRI Brain increased 19%, from 52 to 62 per 100,000 encounters (p trend < .001). On a year-over-year basis, both CTA and CTP use is accelerating, with substantial increases noted between 2017 and 2018.

Conclusions:
We identified recent, substantial, temporal changes in CTA and CTP neuroimaging acquisition among CA emergency departments in the nascent mechanical thrombectomy era. Dramatic changes in CTA and CTP use suggest that changes are occurring in ED evaluation of neurological emergencies. If true, this differs substantially from the speed of ED acceptance of rt-PA for stroke treatment. Further analysis from the CA OSHPD and other (NEDS) datasets is planned to better understand the patient, hospital, and clinical factors driving these neuroimaging trends in the ED.
Abstract WP299: Current Trends in Telestroke Utilization by Spoke Sites Using Distributed Provider Service Organizations via a Commercial Vendor Platform: Data From 2013 to 2019
Authors: Zachrison Kori S , Sharma Richa , Mehrotra Ateev , Schwamm Lee H
Published: June 2021

Background:
Most data on telestroke utilization come from single academic hub-and-spoke telestroke networks. Our objective was to describe trends in telestroke consultations among a national sample of telestroke sites using a common commercial vendor platform.

Methods:
A major commercial telestroke vendor (InTouch Health) provided data on all telestroke consultations by two provider service organizations from 2013-2019. Kendall’s τ β nonparametric test was utilized to assess time trends and generalized linear models assessed the link between hospital consult utilization and alteplase (tPA) performance adjusting for hospital characteristics.

Results:
Among 67,736 telestroke consultations to 132 spoke sites, most occurred in the emergency department (90%) and for stroke indications (TIA 13%, ischemic stroke (IS) 39%, hemorrhagic stroke 2%, other 46%).Median NIHSS was low (2 (IQR 0-6). tPA was recommended for 23% of IS patients. From 2013 to 2019, times from ED arrival to NIHSS, CT scan, imaging review, consult, and tPA administration all decreased (p<0.05 for all), while times from consult start to tPA recommendation and bolus increased (p<0.01 for both). Transfer was recommended for 8% of IS patients diagnosed. Number of patients treated with tPA per hospital was significantly associated with number of consults, size and US region in unadjusted and adjusted analyses (Table). After accounting for hospital characteristics, only duration of hospital participation in the network was associated with shorter hospital median door-to-needle time for tPA delivery (39 minutes shorter per year, p=0.04).

Conclusion:
In this network, times to consult start and tPA bolus decreased over time, though performance varied by telestroke consult volume and region. Duration of telestroke participation was associated with faster tPA delivery, suggesting practice improves performance. Commercial telestroke networks appear to behave similarly to academic networks.
Abstract WP300: Optimal Prehospital Stroke Triage is Highly Dependent on Individual Hospital Reperfusion Times
Authors: Zachrison Kori S , Truong Han Q , Eschenfeldt Patrick C , Ingram Myles A , Ali Ayman , Hur Chin , Schwamm Lee H
Published: June 2021

Background:
Prehospital routing decisions for patients with suspected stroke depends on many factors. Past decision modeling analyses have incorporated patient and hospital characteristics such as age, stroke severity, and average door-to-reperfusion times. However, these models do not include actual hospital performance data. We sought to determine whether inclusion of actual hospital data for door-to-needle and door-to-puncture times for thrombolysis (tPA) and thrombectomy (EVT) affects optimal routing destinations.

Methods:
Our previously published simulation model incorporates geographic, patient, and hospital data to determine optimal transport destination, using a standard distribution of tPA and EVT times by hospital type (PSC vs CSC). We enhanced the model using actual hospital performance data on tPA and EVT treatment times from all Northeast Get with the Guidelines Stroke hospitals. We used 1000 patient locations based on census density with 10 levels of stroke severity at each location, running 2,000 simulations for each hypothetical scenario (20 million simulations per model version) to determine the optimal treatment destination. We compared model recommendations from the 2 versions to determine if the results changed with use of actual hospital data. Potential gains to patients were calculated using quality-adjusted life years.

Results:
Of the 10,000 simulated scenarios, 2170 scenarios (21.7%) had the same optimal destination in both model versions. Of the 7830 scenarios with changed recommendations, 542 (6.9%) scenarios had a change from PSC to CSC recommendation, 2927 (37.3%) from CSC to PSC, and 4361 (55.7%) changed within group from one PSC to another, or from one CSC to another. Likelihood and type of recommendation change did not vary significantly by stroke severity. Optimized hospital destination led to gains of up to 78 quality-adjusted days relative to the baseline model.

Conclusion:
Prehospital routing models for patients with suspected stroke may benefit from inclusion of actual hospital performance characteristics. In our model, this resulted in more than a third of patients switching from CSC to PSC and keeping initial care local. Further replication is needed to avoid patient harm and potential overtriage to CSC.
Abstract WP303: Laying the Groundwork for Stroke Care in Armenia. Assessment of Ambulance Services in the Republic of Armenia: Current State of Care, Public Perception and Opportunities for Strengthening the Emergency Medical System
Authors: Chekijian Sharon , Truzyan Nune , Grigoryan Mikayel , Babikian Viken
Published: June 2021

Background:
The recent creation of the Armenian National Stroke Program has stipulated that all links in the Stroke Chain of Survival are examined and remediated including Emergency Medical Systems (EMS). EMS forms the second link in the chain of survival after early recognition of stroke symptoms by the general public. This study describes the perception of and performance of EMS in Armenia’s capital, Yerevan, and provides the groundwork for nascent stroke care in Armenia.

Methods:
We used mixed methods to derive a comprehensive picture of the state of Emergency Medical Systems. We administered a survey using random digit telephone number generator to 384 households at three intervals over a 5 year period in 2005, 2009 and 2010. A trend analysis was performed for six questions regarding EMS. We queried knowledge of the 911-equivalent access number, perception of accessibility of emergency services, perception of anticipated care, and financial concerns. The surveys had a 96% response rate. We also performed key stakeholder interviews and focus groups to describe the state and evolution of emergency care in Armenia.

Results and Discussion:
Appropriate and timely stroke care relies on activation of EMS. EMS in Armenia remains an ambulance-based service following the Franco-German model where ambulances are staffed by a physician, nurse and driver. Utilization of EMS in Armenia is one of the highest in the world. Eighty percent of calls are treated on scene and 20% are transported to surrounding hospitals. There is currently minimal hospital-based emergency care. Over the three survey periods there was a trend towards increased trust in the EMS system. The idea that the ambulance will respond in a timely manner and not request payment before accepting the call (p=0.04) gained traction. Increased trust means more people will wait for the ambulance than drive the patient to the hospital themselves (p=0.01), a key factor for prompt stroke care. Since February of 2019, stroke patients are transferred to two stroke referral centers in Yerevan. EMS systems strengthening starting with public education and trust-building, emergency medicine residency, ambulance and helicopter protocols and tele-stroke development is key in providing timely and quality stroke care.
Abstract WP310: PRIMED Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies
Authors: Bahr Hosseini Mersedeh , Bikosn Marom , Iacoboni Marco , Carmichael Stanley Thomas , Saver Jeffrey L
Published: June 2021

Introduction:
Multiple neuroprotective therapies (NPT’s) for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous quality assessment of all the cumulative preclinical evidence supporting an NPT prior to conducting human trials. There is a need for an updated translational readiness assessment tool to assess candidate therapies that combines desirable elements of existing instruments (STAIR 2.0, CAMARADES, RoB2) and include additional important elements.

Methods:
Candidate items for the intervention translational readiness scale, based on prior instruments, were rated by importance, reliability, and feasibility. For illustrative purposes, the assessment tool was applied to four NPT in current development, including two pharmacologic agents [uric acid (UA) and trans sodium crocetinate (TSC)] and two neuromodulatory device interventions [cathodal direct current stimulation (C-DCS) of ischemic hemisphere and fastigial nucleus stimulation (FSN)].

Results:
The final Preclinical evidence of Readiness In stroke Models Evaluating Drugs/Devices (PRIMED) assessment tool rates evidence available from all reported animal studies in 10 domains (Fig1). Among the four assessed candidate NPT’s, the scores for two pharmacologic NPT’s indicated high translational readiness (UA and TSC 17) and the two neuromodulatory NPT’s had intermediate readiness-for-translation (C-DCS 12, FNS 8).

Conclusion:
The PRIMED assessment tool is an updated, multidimensional tool that provides a detailed assessment of multiple important readiness features across all preclinical experiments testing an NPT to assess readiness for translation, applicable to both pharmocologic and device therapies for acute stroke, providing both qualitative profiling of agent strengths and weaknesses and a quantitative summary score. Based on this tool, translational readiness is high for UA and TSC and intermediate for C-DCS and FNS.
Abstract WP316: Effects of Different Phenotypes of Microglia-Derived Exosomes on Ischemia-Reperfusion Injury
Authors: Cao Xiang , Chen Fangyu , Liu Pinyi , Xu Yun
Published: June 2021

Introduction:
Microglia are the main type of resident immune cells in the brain. Under different stimuli, microglia exhibit two entirely different functional activated states, termed the pro-inflammatory (M1) phenotype and the anti-inflammatory (M2) phenotype. Almost all cell types can release exosomes, which are considered as important mediators in cell-to-cell communication. Cell-derived exosomal cargo contains a variety of proteins and nucleic acids, which can work locally or stably transferred to recipient cells. Here, we explored the effects of different phenotypes of microglia-derived exosomes on ischemia-induced brain injury.

Methods:
Primary microglial cells (PMGs) were treated with LPS or IL-4 to induce the M1 or M2 phenotype, respectively. Exosomes were isolated from the cell culture supernatant. Neuronal apoptosis was examined after oxygen-glucose deprivation (OGD) treatment with different exosomes. Transient middle cerebral artery occlusion (MCAO) was used as the in vivo ischemic stroke model to observe the effects of different phenotypes of microglia-derived exosomes on brain injury. Protein profiles were investigated to screen the candidate molecules that mediate distinct functions.

Results:
Exosomes derived from different phenotypes of microglia have similar diameter, density and exosomal markers. PMGs-derived exosomes can be taken up by neurons. M1 microglia-derived exosomes increased neuronal apoptosis after OGD treatment than OGD alone, while M2 microglia-derived exosomes attenuated neuronal apoptosis. In vivo results revealed that M2 microglia-derived exosomes alleviated brain infarct size and neurological deficits. Besides, M1 microglia-derived exosomes aggravated brain damage. Proteomic analysis showed that the expression of complement-related proteins in M1 microglia-derived exosomes was significantly upregulated than that of M2 microglia-derived exosomes, while the underlying mechanism mediated by specific proteins needs further verification.

Conclusions:
We demonstrated that M1 microglia-derived exosomes could aggravate ischemic brain injury, while M2 microglia-derived exosomes attenuated this phenomenon. We will explore the detailed mechanisms in the future.
Abstract WP322: Do Mural Cells Differentiate Into Microglia-Like Cells After Ischemic Stroke?
Authors: Yao Yao , Nirwane Abhijit
Published: June 2021

Introduction:
Controversial results exist on whether mural cells can differentiate into microglia-like cells after ischemic stroke. This discrepancy can be due to different experimental methods (immunostaining versus lineage tracing) and/or distinct transgenic animals (RGS5
GFP
versus Tbx18-CreERT mice).

Methods:
To determinate whether mural cells are able to differentiate into microglia-like cells after ischemic stroke, we permanently labeled mural cells with tdTomato by crossing PDGFRβ-Cre and PDGFRβ-CreERT with Ai14 reporter mice. The resulting Ai14:PDGFRβ-Cre
+
and Ai14:PDGFRβ-CreERT
+
mice were subjected to 45 minutes of middle cerebral artery occlusion (MCAO) followed by reperfusion. At various time points after injury, the proliferation, apoptosis, and differentiation of PDGFRβ
+
cells were examined.

Results:
In both Ai14:PDGFRβ-Cre
+
and Ai14:PDGFRβ-CreERT
+
mice, we observed a substantial reduction of PDGFRβ
+
cells at day 2 after ischemic stroke and a subsequent repopulation (mainly due to proliferation) of PDGFRβ
+
cells at day 7 after ischemic stroke. We also showed that PDGFRβ
+
cells changed their morphology and differentiated into microglia-like cells at day 7 after injury, suggesting that PDGFRβ
+
cells can indeed differentiate into microglia-like cells after ischemic stroke. In addition, we noted that PDGFRβ also labeled Col1α1
+
fibroblasts in the brain. Interestingly, high numbers of PDGFRβ
+
Col1α1
+
cells were found in both Ai14:PDGFRβ-Cre
+
and Ai14:PDGFRβ-CreERT
+
mice at day 7 after ischemic injury.

Conclusions:
These results suggest that PDGFRβ is not an ideal marker for mural cells in pathological conditions that involve fibroblast activation. It remains unclear whether mural cells or fibroblasts differentiate into microglia-like cells after ischemic stroke. Future research should focus on answering this important question.
Abstract WP332: Recurrent Ischemic Stroke: Patient Characteristics, Hospital Arrival Mode, And Outcomes, Paul Coverdell National Acute Stroke Program 2016-18
Authors: Coleman King Sallyann , Odom Erika , Tong Xin
Published: June 2021

Introduction:
Better characterizing patients with recurrent ischemic stroke, whether they are more likely to arrive by ambulance, and their outcomes is important to reinforcing prevention practices and identifying disparities.

Method:
We identified 226,974 admissions with a clinical diagnosis of ischemic stroke, age≥18 years, from 463 participating hospitals in the PCNASP from 2016-2018, 58,505 or 25.8% of which had a recurrent stroke. We compared descriptive and clinical features of those with a first stroke with those having recurrent stroke.

Results:
A higher proportion of recurrent stroke admissions was found among black (vs. white) patients: 32.2% vs 24.3%). Recurrent stroke patients were more likely to arrive by ambulance (52.8% vs 45.0%), suffer a more severe stroke (mean NIHSS 6.8 vs 5.9) and less likely to receive alteplase (7.9% vs 10.9%) than those with their first stroke. In addition, those with a recurrent stroke were also more likely to have worse outcomes with fewer recurrent stroke patients being discharged home (42.7% vs 51%). Small differences were seen in the proportion of recurrent stroke patients who were able to ambulate with assistance before their stroke but were then unable to ambulate at discharge (2.2% vs 0.9% for first stroke patients). There were no significant differences seen for in-hospital death.

Conclusion:
Black patients with ischemic strokes had a higher proportion of recurrent events. Recurrent stroke patients were more likely to arrive by ambulance, and suffer a more severe stroke and have worse outcomes. Understanding disparities among those with recurrent stroke may support public health practitioners and health care professionals intervene to prevent or manage recurrent stroke.
Abstract WP340: Impact of Increasing Primary Stroke Center Transfers on Comprehensive Stroke Center Capacity
Authors: Holl Jane , Cai Andy , Ha Lauren , Hulli Alin , Paan Melina , Paras Matthew , Perry Ohad , Ankenman Bruce , Richards Christopher , Parnianpour Zahra , Khorzad Rebeca , Prabhakaran Shyam
Published: June 2021

Introduction:
Given the time-sensitive benefits of acute stroke (AS) treatments, stroke systems of care must balance reducing door-in-door-out (DIDO) time at primary stroke centers (PSCs) with capacity limits at comprehensive stroke centers (CSCs). For example transferring more AS patients earlier in the process (e.g., prior vascular imaging for large vessel occlusion) from PSCs would result in more inappropriate transfers to CSCs that could overburden these centers.We conducted a simulation to estimate the balance between increased AS transfers from PSCs to CSCs and the percent of CSC time on “bypass” (inability to accept transfers to neuro-ICU).

Methods:
Clinicians from 3 Chicago-area CSCs and 3 affiliated PSCs and the Chicago Emergency Medical Services (EMS) created a PSC DIDO process map. We assumed CSC time on bypass is affected by AS and non-AS admissions from the CSC and from the affiliated PSCs. Input data were obtained fromtheChicago region registry (e.g., # PSC to CSC transfers), peer reviewed literature (US average transfer rate of AS patients to CSCs), EMS (PSC-CSC affiliations), and CSCs (e.g., average bed occupancy rates). CSC size was estimated by #neuro-ICU beds: small (12 beds), medium (23 beds), and large (28 beds). The simulation output was % time of CSC on “bypass”.

Results:
Table shows % time of CSC on bypass by varying PSC AS transfer rates for each category of CSC size. Larger increases in PSC transfer rates resulted in modest increases in CSC bypass rates, particularly for medium and large CSCs. Validation with data from one CSC showed < 4% overestimate of CSC % time on bypass.

Conclusion:
CSCs with more beds have efficiencies of scale leading to lower % time on bypass, even with increases in PSC AS transfer rates proportionate to CSC size. This model allows stroke systems of care to compute regional CSCs’ % time on bypass based on actual PSCs’ transfer rates and CSC size.
Abstract WP343: Machine Learning Predicts Sex Difference in Acute Ischemic Stroke
Authors: Lai Yun-Ju , Blixt Frank W , McCullough Louise D
Published: June 2021

Introduction:
Stroke is a common cause of physical disability. Women generally suffer from more severe strokes, have poorer stroke outcomes, and higher mortality than that of men. Cytokines play an important role in post-stroke inflammation. Prior studies have examined differences in individual cytokine levels in patients with acute ischemic stroke (AIS), but comprehensive cytokine expression profiling across different sex and clinical characteristics are lacking.

Hypothesis:
Stroke is a sexually dimorphic disease with well-known sex differences in immune cell prevalence, cytokine expression, and outcome. A comprehensive cytokine and immune cell network may help identify sex-specific immune response and further provide guidance for stroke research in females.

Methods:
Patients with AIS were recruited from 2011-2015 at a Comprehensive Stroke Center. Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 30 common cytokines. Data were analyzed with SPSS 26.0 (IBM) and machine learning algorithms. Spearman’s correlation, Mann-Whitney U test, and two-way ANOVA analyses were used to determine the relationships among the variables. The network between cytokines and immune cell types was predicted by CIBERSORT and modified ssGSEA in R package.

Results:
We examined sex differences in serum cytokine profiles on stroke severity and immune cells profiles using 144 patients with AIS. Among 30 cytokines, IFN-A2, IFNγ, IL-1RA, IL-6, IL-8, IP-10, RANTES, TNFα, and VEGF were found to have statistically significant differences between male and female. Additionally, female survivors with higher admission NIHSS exhibited higher levels of IFN-A2, IFNγ, IL-6, and IL-8 (F=2.722, p=.011; F=2.245, p=.034; F=7.626, p<.001; F=4.599, p<.001, respectively). A cytokine-immune cell network was created using computer algorithms resulting in identification of an upregulation of Th22 in the female. Sex-specific expression of Th22 cells was then validated in human PBMC.

Conclusion:
Our study suggests sex is an important factor which determines clinical outcome. Reducing Th22 may improve stroke recovery in females. Analyzing clinical data using machine learning algorithms can identify prognostic indicators of stroke.
Abstract WP346: Factors Associated With TPA Refusal via Telestroke
Authors: Malazarte Rene , Jagolino-Cole Amanda , Ankrom Christy , Zhu Liang , Joseph Michele , Trevino Alyssa , Zha Alicia , Cossey TC , Savitz Sean , Wu Tzu Ching , Rosero-Enriquez Adriana
Published: June 2021

Introduction:
tPA refusal occurs 4-8% when offered in-person for acute ischemic stroke (AIS). Telestroke (TS) has increased tPA use for AIS, but entails non-traditional patient-physician interaction. Refusal accounts for 16-18% of reasons patients do not receive tPA via TS. We report tPA refusal incidence and associated factors in our TS network.

Methods:
We identified patients in our TS registry (9/2015-12/2018) who were offered tPA for suspected AIS within 4.5 hrs of symptom onset. We compared demographics, clinical characteristics, and outcomes associated with tPA refusal.

Results:
Of 1242 patients offered tPA in our TS network, 101 (8%) refused. Of 1376 patients that did not receive tPA, refusal accounted for 7% (101/1376). Patients refusing tPA were younger than those that accepted (median age 61 vs 66, p=0.01) (Table 1). Male patients were less likely to decline tPA (OR 0.65, CI 0.43-0.98), and non-Hispanic black patients were more likely (OR 1.86, CI 1.18-2.93). tPA refusal was associated with mild stroke (median NIHSS 3 vs 7, p<0.0001) and prior ischemic stroke (OR 1.66, CI 1.06-2.60). Patients with final diagnosis of stroke vs stroke mimic were less likely to refuse tPA (OR 0.23, CI 0.15-0.36). Insurance status and baseline functional status were similar among patients who accepted and refused tPA. Patients who accepted tPA were more likely discharged to inpatient rehab. tPA was primarily refused for risk of adverse effects and mild/improving symptoms.

Conclusion:
Refusal contributes to lower utilization of tPA. Our incidence of refusal was comparable to historical data in non-TS settings. While some factors associated with tPA refusal via TS are consistent with historical data on tPA refusal in-person, differences in patient age, gender, and race/ethnicity still warrant further investigation. Specifically, studies are needed to understand if tPA refusal is related to care delivered via TS, or if patients are more reluctant due to perceived risks of tPA via TS.