bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP188: A Damage-Associated Molecular Pattern (DAMP) and Neutrophil Count are Associated with Plasma MMMP-9 Concentration After Acute Ischemic Stroke
Authors: Batra Ayush , Wolcott Zoe C , Pham Ly , Hales Riley , Kimberly William T
Published: June 2021

Introduction/Hypothesis:
The sterile inflammatory response involves activation of the immune system in the absence of infection following trauma, ischemia, or toxins. Matrix metalloproteinase-9 (MMP-9) is a neuro-inflammatory zinc metalloproteinase implicated in secondary injury after acute ischemic stroke. In order to determine whether MMP-9 was associated with a sterile inflammatory response, we examined the association between circulating MMP-9 and extracellular ATP [a marker of a damage-associated molecular pattern (DAMP)] and acute neutrophil count.

Methods:
We measured plasma MMP-9 and ATP levels in 338 patients who presented to two institutions with acute ischemic stroke and were enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) study. Plasma samples and admission leukocyte subsets were collected at 7.0 ± 3.0 hours and 47.7 ± 7.3 hours from stroke onset. ATP was measured using a liquid chromatography-tandem mass spectrometry metabolomics assay. MMP-9 levels were measured by ELISA using a commercially available assay.

Results:
338 acute stroke patients were available for analysis. MMP-9 was associated with plasma ATP on admission (Pearson r = 0.24, P<0.0001) and at 48 hours (Pearson r = 0.21, P = 0.0028). MMP-9 levels were also associated with total leukocyte count on admission (Pearson r=0.32, P<0.0001) and at 48 hours (Pearson r=0.39, P<0.0001). Absolute neutrophil counts were the only leukocyte subsets to be associated with MMP-9 on both admission (Pearson r=0.31, P<0.001) and at 48 hours (Pearson r=0.34, P<0.0001).

Conclusions:
MMP-9 is associated with markers of the sterile inflammatory response, including circulating plasma ATP levels and absolute neutrophil count. In vitro studies have demonstrated that an initial rise in extracellular ATP is associated with increased neutrophil-mediated MMP-9 release. These findings suggest that ATP may be functioning as a DAMP in response to acute ischemia, and is associated with MMP-9 acutely in patients. This study marks the first clinical cohort to begin to characterize determinants of the sterile inflammatory response in acute ischemic stroke.
Abstract WP19: Transfer Selection for Endovascular Therapy of Ischemic Stroke within A Collaborative Network: Off-site Versus On-site Neurology Service
Authors: Winzer Simon M , Barlinn Kristian , Gerber Johannes , Siepmann Timo , Pallesen Lars-Peder , Prakapenia Alexandra , Koehler Anne , Bodechtel Ulf , Linn Jennifer , Reichmann Heinz , Puetz Volker , Barlinn Jessica
Published: June 2021

Introduction:
Selection of patients for endovascular therapy (EVT) may depend on the hospital providing first line assessment. In our collaborative stroke network, we aimed to compare clinical characteristics and outcomes in ischemic stroke patients undergoing EVT who were transferred from telestroke hospitals following teleconsultation and in those transferred from hospitals providing on-site neurology service.

Methods:
We analyzed prospectively collected data from consecutive ischemic stroke patients who underwent emergent EVT at our comprehensive stroke center (01/2010 to 12/2014) after acute transfer from either telestroke hospitals or non-telestroke hospitals with on-site neurology service. We compared baseline characteristics, onset-to-EVT time, symptomatic intracranial hemorrhage (sICH), favorable functional outcome (mRS 0-2) at discharge and in-hospital mortality.

Results:
Among 133 transferred patients who underwent emergent EVT: median age 67 years (IQR, 15); 56% men; median NIHSS score 17 (21); 52% had anterior and 48% posterior circulation stroke. Sixty-five patients (49%) were transferred from telestroke and 68 (51%) from non-telestroke hospitals. Telestroke patients were less severely affected (median NIHSS scores: 15 [7] vs. 22 [20]; p=.0005) and more likely to have anterior circulation stroke (69% vs. 35%; p<.0001) compared with non-telestroke patients. No between-group differences were present with regard to demographics, vascular risk factors, intravenous tPA rate and onset-to-EVT time. In-hospital mortality was lower among telestroke compared with non-telestroke patients (11% vs. 26%; p=.026). There were no differences in sICH (5% vs. 4%; p=1.0) and favorable functional outcome (17% vs. 18%; p=1.0).

Conclusions:
Patients transferred from telestroke hospitals were twice as often treated for anterior circulation stroke than those from non-telestroke neurological hospitals within our stroke network. This might be explained by more conservative selection of patients potentially amenable for EVT in hospitals harboring on-site neurology service but no EVT-capability. As our data was acquired prior to evidence from the positive EVT trials, further research is warranted to elaborate these findings.
Abstract WP195: Home Time by Stroke Type: a Population-based Study to Evaluate Functional Outcome After a Cerebrovascular Event
Authors: Yu Amy Y , Rogers Edwin , Smith Eric E
Published: June 2021

Introduction:
Home time has been proposed as a surrogate for functional outcome in ischemic stroke, and is also a highly valued patient-centered outcome that reflects resource utilization. In prospective cohort studies and clinical trials, higher home time has been correlated with lower disability; however, the requirement for informed consent results in selection bias. Therefore, the population distributions of home time after stroke are currently unknown. Additionally, home time distributions have not been reported in hemorrhagic stroke and transient ischemic attack (TIA). We developed a novel administrative data algorithm to compare home time distributions after hospital admission for cerebrovascular events in the population of Alberta, Canada.

Methods:
Home time was defined as the number of nights not spent in an institution, including acute-care, inpatient rehabilitation facilities, and long-term care, in the 90 days after admission for a cerebrovascular event. Community-dwelling residents of Alberta, Canada with a valid healthcare number admitted for a cerebrovascular event between April 2012 and June 2015 were included. We used the Kruskal-Wallis test to compare the median home-times according to stroke type: ischemic stroke (IS), TIA, or hemorrhagic stroke (HS), including intracerebral and subarachnoid hemorrhage. We correlated admitting age and home time with Spearman correlations and assessed sex and home time with Wilcoxon Rank Sum.

Results:
A total of 12520 admissions were identified, the median age was 74 years (IQR 22), and 53% were male. There were 8482 (68%) IS, 2434 (19%) TIA, and 1604 (13%) HS. The median (IQR) home time by stroke type was 72 nights (85) for IS, 87 nights (6) for TIA, and 29 nights (79) for HS (p<0.001). For each stroke type, lower home time was correlated with higher age (IS: r=-0.35; TIA: r=-0.31; HS: r=-0.33; p<0.001 for each comparison) and female sex (p≤0.001).

Conclusion:
In this population with universal healthcare access, TIA had the highest home time (i.e. best outcomes) whereas hemorrhagic stroke had the lowest, consistent with expected functional outcomes based on prospective cohort studies. Home time may be a useful metric to track patient outcomes and healthcare utilization based on administrative health data.
Abstract WP203: Glycemic Control on Admission and During First Year Follow-Up in Stroke Patients
Authors: Kamal Eman K , Mominkhan Heba J , Al Amoudi Rana A , Rammal Seba A , Almekhlafi Mohammed A
Published: June 2021

Introduction:
The increasing incidence of stroke in the developing countries has been attributed to the poor control of prevalent risk factors including diabetes. We aimed to evaluate the degree of glycemic control and its temporal changes in a cohort of stroke patients and whether these levels impacted patients outcomes.

Methods:
This a longitudinal retrospective cohort of all stroke patients admitted to a single tertiary center between Jan 2010 to December 2014. Clinical, radiographic, and outcome data were collected. Admission and follow-up levels of Glycosylated Hemoglobin (HbA1c) were recorded. The WHO definitions of diabetics and pre-diabetics were used to define cases (Normal if HbA1c is less than 5.7%, Prediabetes 5.7% to 6.4% , Diabetes 6.5% or higher).

Results:
A total of 548 patients were admitted during the study period. The mean age of the patients was 62.9 years (SD 16.9) and 42.1% were females. Saudi nationals represented 36.1% of all cases. Hemorrhagic stroke was diagnosed in 9.9%.

The admission HbA1c was checked in 332 (60.6%) patients. The mean level was 8.2% (Median 7.6%, range 4.9 to 15.1). Patients meeting the WHO definition of diabetes represented 16.3% while pre diabetics were 6.1%. At least one follow-up HbA1c reading was obtained in 101 patients who meet the WHO criteria for diabetes on stroke admission. Out of those, 30 patients (29.7%) had no change or worsening of the glycemic control with a mean increase in HbA1c of 1.1% compared to the stroke admission HbA1c (median increase of 0.9, range 3.9 to 0.1). The remaining 89 patients (70.3%) had better glycemic control with a mean drop of their HbA1c of 1.6% (median drop of 1.2, range 0.02 to 7.4).

Conclusion:
Poor glycemic control was prevalent in patients admitted with stroke. Although the majority of patients had better glycemic control on subsequent follow-up, a third of tested patients had no change or worsening of their baseline HbA1c. This calls for the continued improvement of diabetes education and intervention clinics.
Abstract WP205: Pipeline for Automated White Matter Hyperintensity Segmentation in Patients With Acute Ischemic Stroke: The MRI-GENIE Study
Authors: Schirmer Markus D , Dalca Adrian V , Sridharan Ramesh , Giese Anne-Katrin , Broderick Joseph P , Jimenez-Conde Jordi , Holmegaard Lukas , Kissela Brett M , Kleindorfer Dawn O , Lemmens Robin , Lindgren Arne , Meschia James F , Rundek Tatjana , Sacco Ralph L , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Thijs Vincent , Woo Daniel , Worrall Bradford B , Kittner Steven J , Rosand Jonathan , Wu Ona , Golland Polina , Rost Natalia S
Published: June 2021

Introduction:
White matter hyperintensity volume (WMHv) is an important and highly heritable cerebrovascular phenotype; however, manual or semi-automated approaches to clinically acquired MRI analysis hinder large-scale studies in acute ischemic stroke (AIS). In this work, we develop a high-throughput, fully automated WMHv analysis pipeline for clinical fluid-attenuated inversion recovery (FLAIR) images to facilitate rapid genetic discovery in AIS.

Methods:
Automated WMHv extraction from multiple subjects relies on significant pre-processing of medical scans, including co-registration of the images. To reduce the effects of anisotropic voxel sizes, each FLAIR image is upsampled using bi-cubic interpolation. Brain extraction is performed using RObust Brain EXtraction (ROBEX). Images are then registered to an in-house FLAIR template using Advanced Normalization Tools (ANTs). The spatial covariation of WMH is learned through principal component analysis (PCA) of manual outlines from 100 subjects. Areas of leukoaraiosis are identified and separated from other lesions using the PCA modes. Volumes are then computed using non-interpolated slices for each subject. Standard deviation (SD) in WMHv (9 subjects; 6 raters each) is calculated as a measure of variability. Good agreement between automated and manual outlines is assessed in 358 subjects (automated WMHv within 3SD of manual WMHv).

Results:
As part of the
MRI
-
Gen
etics
I
nterface
E
xploration (MRI-GENIE) study, WMHv were calculated on a set of 2703 FLAIR images of patients from 12 independent AIS cohorts (sites). Results are shown in Figure 1. Comparing manual and automated WMHv shows that 88% of the automated WMHv fall within 3 SD from the manual WMHv, suggesting good agreement.

Conclusion:
WMHv segmentation using a fully-automated pipeline for analysis of clinical MRIs is both feasible and accurate. Ongoing analysis of the extracted WMHv is expected to advance current knowledge of risks and outcomes in AIS.
Abstract WP206: Risk of Recurrent Stroke in Patients Diagnosed with Comorbid Depression at the Time of Transient Ischemic Attack
Authors: Lerario Michael P , Navi Babak B , Merkler Alexander E , Ferretti Casara J , Allen Nicole C , Koyfman Feliks , Bernardini Gary L , Kamel Hooman
Published: June 2021

Introduction:
Although rates of depression are increased in patients with transient ischemic attack (TIA), the effect of depression on recurrent cerebrovascular events is uncertain. Therefore, we aimed to calculate the risk of subsequent stroke in patients with comorbid depression at the time of TIA.

Methods:
We used all-payer claims data on all nonfederal acute care hospitalizations in New York, California, and Florida from 2005-2013. Our cohort comprised all patients hospitalized for TIA (
ICD-9-CM
435.x). The predictor variable was a diagnosis of depression (
ICD-9-CM
296.20-.25, 296.30-.35, 300.4, 311 in any diagnosis code position) during the index hospitalization for TIA. Kaplan-Meier survival statistics were used to calculate cumulative rates of our primary composite outcome of ischemic and hemorrhagic stroke (
ICD-9-CM
431, 433.x1, 434.x1, or 436 without concomitant trauma or rehabilitation codes). Cox proportional hazard analysis was used to examine the association between depression and stroke.

Results:
We identified a total of 1,817,842 TIA patients, among whom 223,311 (12.3%) were discharged from their index TIA visit with a comorbid depression diagnosis. Over a mean follow-up of 4.2 (+/- 2.1) years, 227,501 patients were diagnosed with subsequent stroke. The 1-year cumulative rate of stroke was 3.5% in both patients with depression (95% CI, 3.3-3.7%) and without depression (95% CI, 3.5-3.6%). The 5-year cumulative rate of stroke was 8.5% (95% CI, 8.2-8.9%) in those with depression compared to 8.9% (95% CI, 8.7-9.0%) in patients without depression at the time of their TIA diagnosis. After adjusting for demographics and vascular risk factors, depression was not associated with subsequent stroke (hazard ratio, 1.0; 95% CI, 1.0-1.1;
p
=0.7). To reduce any misclassification error, these results were unchanged in a sensitivity analysis which included only those patients who underwent brain magnetic resonance imaging during their index hospitalization for TIA.

Conclusions:
A comorbid diagnosis of depression at the time of TIA is not associated with an increased risk of subsequent stroke. Future research should evaluate whether incident depression diagnosed after hospital discharge for TIA is associated with heightened stroke risk.
Abstract WP225: What Do Kids Know? An Assessment of Stroke Awareness in School-aged Children
Authors: Kabbani Mouhammed R , Smith Angela L , Borgert Andrew J , Ramirez Luis D , Schossow Andrea J
Published: June 2021

Introduction:
Half of grade school-age children in the U.S. receive after school care from their grandparents or another adult family member. Yet, few studies have investigated if educating youth about stroke is an effective vehicle for spreading stroke knowledge to their families and the impact on onset-to-door time.

Objective:
To assess the level of knowledge about stroke warning signs and behavioral actions in school-aged children.

Methods:
Surveys differentiated to each school level- elementary (K-5), middle (6-8) and high school (9-12) - were administered to students in 3 community school districts. 6-8 and 9-12 grade students completed the surveys via an online tool, while K-5 students were guided through a picture-based survey. Topics included identifying the signs and symptoms of a stroke, risk factors for stroke and what action to take if the student thought someone was having a stroke.

Results:
Among 3 participating school districts, 3,425 elementary, 1,239 middle school and 1,594 high school students were surveyed. Less than half (43.7%) of K-5 students recognized 3 main signs of stroke (face, arm and speech). Stroke knowledge level is low among all students in elementary, middle and high school (Figure 1). Previous education was reported in 22% of K-5, 53% in 6-8 and 15% in 9-12 students. Those noting previous stroke education had increased knowledge at all 3 levels (p<0.001, p=0.002 and p<0.001). Total previous education occurring in school was reported at 11%.

Conclusions:
Children know how to respond to a medical emergency, yet their knowledge about the signs of a stroke is low. Educating youth increases their awareness regardless of age, making the student population a prime target for educational efforts. We plan to partner with school districts to develop curriculum appropriate for the elementary, middle and high school as the next step to increasing awareness about stroke.
Abstract WP232: Biomarkers of Atrial Cardiopathy and Atrial Fibrillation Detection on Mobile Continuous Outpatient Telemetry After Cryptogenic Stroke
Authors: Sebasigari Denise , Merkler Alexander , Yang Guo , Kummer Benjamin , Gialdini Gino , Cutting Shawna , Elkind Mitchell S , Kamel Hooman , Furie Karen L , Yaghi Shadi
Published: June 2021

Background:
In population-based studies, biomarkers of atrial dysfunction or “cardiopathy” have been shown to be associated with embolic stroke risk. However, it is unclear if this risk is mediated by undiagnosed paroxysmal atrial fibrillation or flutter (AF). We aim to determine whether atrial cardiopathy biomarkers predict atrial fibrillation on continuous heart-rhythm monitoring after embolic stroke of undetermined source (ESUS).

Methods:
This was a single-center retrospective study including all patients who met consensus criteria for ESUS and who underwent 30 days of ambulatory heart-rhythm monitoring looking for AF between Jan 1
st
, 2013 and Dec 31
st
, 2015. We reviewed medical records for clinical, radiographic, and cardiac variables. The primary outcome was new diagnosis of AF detected during heart-rhythm monitoring. The primary predictors were atrial biomarkers: left atrial diameter on echocardiography, P-wave terminal force in ECG lead V1 , and PR interval on ECG. Multiple logistic regression was used to assess the relationship between atrial biomarkers and AF detection.

Results:
Among 196 eligible patients, 23 (11.7%) were diagnosed with AF. In unadjusted analyses, patients with AF were older (72.4 vs. 61.4 years, p < 0.001) and had larger left atrial diameter (39.2 vs. 35.7 mm, p = 0.03). In a multivariable model including variables significant on univariate analyses, the only predictor of AF was age ≥ 60 years (odds ratio, 3.0; 95% CI, 1.06-8.5; p = 0.04). Atrial biomarkers were not associated with AF detection.

Conclusion:
Atrial biomarkers were not associated with AF after ESUS. This suggests that previously reported associations between these markers and stroke may reflect independent cardiac pathways leading to stroke. Prospective studies are needed to investigate these mechanisms and study anticoagulation versus antiplatelet treatment for secondary stroke prevention in patients with ESUS and atrial cardiopathy.
Abstract WP239: Real Time Prospective Measurement of aPTT Predicts Paradoxical Embolism in Cryptogenic Stroke
Authors: Song Bo , Deng Wenjun , Fisher Lindsay , Chou I-ying , Oyer Max , McMullin David , Lo Eng H , Xu Yuming , Buonanno Ferdinando S , Ning Mingming
Published: June 2021

Patent foramen ovale (PFO) is an important underlying source of cryptogenic stroke (CS) associated with hematologic procoagulability. However, the association of genetically identified hyperocagulability and paradoxical embolism has been difficult to establish due to retrospective analysis and the limited numbers of of known genetically identified hypercoagulable conditions. In this study, we explored the utility of conventional coagulation status in PFO related stroke, as the patients may harbor genetically unidentified hyperocoagulable conditions.

Method:
Eligible pts were prospectively recruited in accordance with IRB, and underwent conventional coagulation testing (PT/PTT) testing within 12 hours of stroke. All patients underwent full cryptogenic workup such as MRI/MRA, mobile cardiac outpatient telemetry (>30 days), cardiac echo, and hypercoagulable testing.

Results:
We screened 4,831 pts admitted with acute neurologic diseases, and recruited 358 eligible acute ischemic stroke pts. 54 (15.1%) pts had CS and 32 pts had PFO related stroke. While there is no difference between PFO-related CS and PFO-unrelated CS on full hypercaogulable screen (protein S, protein C, FVL, PTGM, ATIII, APLAb, LA, hcy), aPTT was statistically significantly shortened in PFO-related stroke patients (PFO CS vs. non-PFO CS: aPTT 27.2±4.1s vs. 29.9±2.3s). ROC curve indicates early shortened aPTT can predict PFO related stroke (sensitivity 70%, specificity 81.5%, p=0.017) (see Figure).

Conclusion:
We found real time aPTT to be significantly shortened in patients eventually diagnosed with paradoxical embolism related to PFO. While studies in larger pt cohorts accounting for other potential confounders are underway, this proof-of-concept study demonstrates the importance and utility of early conventional coagulation testing in identifying paradoxical embolism. Pts with shortened aPTT may need additional workup for other underlying hypercoagulable conditions.
Abstract WP24: The Middle Cerebral Artery Occlusion, Anatomy Study and Pitfalls in the Design and Classification of Its Segment Occlusions in the Clinical Trials
Authors: Qureshi Mohtashim A , Afzal Mohammad R , Qureshi Ihtesham A , Ghatali Mohammad , Piriyawat Paisith , Maud Alberto , Cruz-Flores Salvador , Rodriguez Gustavo J
Published: June 2021

Objective:
The middle cerebral artery (MCA) occlusion is the most commonly treated vessel with mechanical thrombectomy. The MCA is defined in segments. The M1 segment is classically defined as the horizontal segment extending from the internal carotid artery bifurcation to the Sylvian fissure. It is assumed that the MCA bifurcation occurs in the M1-2 junction, and terms M2 occlusion and division occlusion are used indistinctly, however it is not known how often the MCA bifurcation occurs within the M1 segment.

Methodology:
Consecutive patients undergoing cerebral angiograms were selected between 2011 and 2015. The anatomy of the MCA was classified as classical, when the bifurcation occurs at the M1-2 junction and non-classical when the bifurcation occurs within the M1 segment, having the M1 segment a pre-bifurcation (main trunk) and a post-bifurcation (division) occlusion. Demographics and vascular risk factors were also collected.

Results:
A total of 500 patients underwent a cerebral angiogram and were studied. The classical pattern was found in 47.5% patients on the left and 53.5% patients on the right. There were no differences between the classical and non-classical anatomical pattern when demographics or vascular risk factors were compared.

Conclusion:
In our series of patients the non-classical pattern was found in almost 50.0% of the patients undergoing a cerebral angiogram. In the endovascular treatment of acute ischemic stroke, it is necessary to develop a new classification as an M1 occlusion could relate to a post-bifurcation (division) or a pre-bifurcation (main trunk) occlusion and comparison of these groups may lead to confounding results.
Abstract WP251: Telestroke 2.0 in Catalonia: More Patients Treated and Secondary Transfers Reduced
Authors: Gomis Meritxell , López-Cancio Elena , Perez de la Ossa Natalia , Cardona Pere , Ribó Marc , Serena Joaquin , Purroy Francisco , Garcés Moisés , López Mercè , Soteras Iñigo , Aragonés Josep Maria , Cocho Dolores , Palomeras Ernest , Villagrasa David , Puiggrós Elsa , Catena Ester , Sanjurjo Eduard , López Claverol Núria , Carrión Dolors , Abilleira Sònia , Dávalos Antoni
Published: June 2021

Objetive:
To describe the main results from the implementation of Telestroke 2.0 in Catalonia.

Methods:
The network consists of 12 community hospitals and an expert stroke neurologist 24h/7d, covering a population of 1.3 million inhabitants. It includes a two-way videoconferencing system and visualization of neuroimaging on a web platform. The neurologist evaluates the patient and decides the therapeutic approach and/or transfer the patient to another facility, entering these data in a mandatory registry (TICAT). Simultaneously, all patients treated locally with reperfusion therapies in all centers of Catalonia are also prospectively recorded in a mandatory registry (SONIIA).

Results:
From March-2013 to December-2015, 1206 patients were evaluated through Telestroke network. Final diagnosis was: 951 ischemic, 51 TIA, 85 intracranial hemorrhages and 119 with a diagnosis different from stroke. Transfer to another center was avoided in 46.8% of ischemic, 76.5% of TIAs and 23.5% of hemorrhages. A total of 322 patients received rtPA (33.8% of ischemic). Compared with those who received rtPA locally (2897 patients in the same period in Catalonia), the door-to-needle time(minutes) was longer in treated through Telestroke (55[45-70] versus 44[32-59]), and this time was progressively reduced from 2013 to 2015 (59[53- 82] to 40[50-60], p<0.001). Baseline and 24h NIHSS, rate of symptomatic hemorrhage, mRS at 3m and percentage of patients receiving rescue thrombectomy were similar in both groups. Population rate of fibrinolysis /100.000 inhabitants in Catalonia increased progressively from 2012 to 2015.

Conclusions:
Telestroke favors fibrinolysis therapy safely and effectively, avoiding a large number of secondary transfers to other centers
Abstract WP259: Simulation Based Medical Education in Interprofessional Education: Acute Stroke Management Model
Authors: Johnson Brett , Horsley Leann , Reed Trent , Quinones Donna , Siddall Viva , Balasubramanian Neelam , Ray Jessica , Friend Patricia , Muccino Keith , Ruland Sean
Published: June 2021

Introduction:
Simulation-based medical education (SBME) is an established tool for training and certifying providers for critical situations such as ACLS. Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) is a program developed by the Agency for Healthcare Research and Quality and the Department of Defense to improve teamwork. Previous work has demonstrated the effectiveness of SBME in stroke team performance among neurology residents and ICU nurses. Our aim was to develop an SBME interprofessional education (IPE) program for nursing and medical students on stroke team performance.

Method:
Using a quantitative descriptive one group pretest/posttest design, acute stroke care (14 items), TeamSTEPPS knowledge (14 items) and attitudes toward IPE (16 items) were assessed. After the initial survey, students were given modules on acute stroke care and TeamSTEPPS. Students were randomly assigned into small mixed groups before participating in 2 high-fidelity simulations: an IV tPA-eligible ischemic stroke and a warfarin-associated ICH requiring INR reversal. During each case, trained faculty assessed students using a standardized checklist focusing on stroke management and teamwork. Faculty underwent inter-rater reliability and recalibration training prior to participation. A standardized debriefing was conducted immediately after each case. A 1-hour reinforced learning session was provided by physician and nursing experts in stroke and TeamSTEPPS between cases.

Result:
65 nursing and 26 medical students participated. Improvement was seen in the cognitive assessment (
p
<0.0001 for composite score) and each affective item (
p
<0.0001) after SBME. Psychomotor scores improved (
p
<0.01) in most items on the team performance checklist and improved for 5 items on the stroke task checklist.

Conclusion:
SBME is feasible and effective for supporting IPE in team-based stroke training among nursing and medical students. Although impact on real-world metrics such as door-to-needle time and protocol deviation remains uncertain, SBME using TeamSTEPPS principles should be incorporated within stroke education curricula. Moreover, a stroke code certification process similar to ACLS should be contemplated.
Abstract WP275: Much Work to Do: Analysis of Potential Performance Measures for Patients Transferred for Acute Endovascular Thrombectomy
Authors: Shkirkova Kristina , Starkman Sidney , Liebeskind David , Duckwiler Gary , Tateshima Satoshi , Szeder Viktor , Jahan Reza , Sharma Latisha , Rao Neal , Hinman Jason D , Raychev Radoslavc , Arch Alison , Chhraba Arun , Frischmann Lindsey , Malhotra Konark , Chatfield Fiona , Saver Jeffrey
Published: June 2021

Background:
Potential performance measures to assess care of acute ischemic stroke patients transferred from initial hospitals to interventional centers for thrombectomy include: 1) door-in to door-out (DIDO) time (time from arrival to discharge at first hospital, and 2) first imaging at referral hospital to first arterial access at endovascular hospital (FIFA) (time from qualifying CT/MR imaging at initial hospital to arterial puncture at endovascular hospital).

Methods:
In a prospectively maintained registry, we analyzed consecutive patients transferred from regional referral hospitals to receive thrombectomy at an academic medical center, January 2015 to March 2016.

Results:
Among 35 patients, transferred from 10 referral hospitals, with documented time intervals, mean age was 52.8 (±12.2), 37% female, mean NIHSS 12.3 (±8.3). Initial hospital imaging was NCCT alone in 49%, and NCCT with CTA or MRA in 51%. Overall, 20 (57%) received IV tPA at the initial hospital, and 14 (40%) thrombectomy at the interventional hospital. Door-in door-out times were median 153 min (IQR 99-220). For candidate target DIDO performance metric intervals: <60m was achieved in 6%; <90m in 20%. Interfacility travel was by air in 34% (median distance 65, IQR 50-65, miles] and ground in 66% (median 16, IQR 12-16, miles), and travel times were similar for air v ground, 58 min (IQR 37-87) v 51 min (IQR 40-70), p=0.52. First (outside) imaging to first arterial access times were median 261 min (IQR 190-315). For candidate target FIFA performance metric intervals: <90m (SNIS “ideal”) was achieved in 3%; <120m in 6%. Additional intervals were: onset to first door, 52 min (IQR 33-156); onset to second door, 304 min (IQR 240-434); onset to puncture, 355 min (IQR 312-447); and onset to substantial reperfusion, 412 min (IQR 342-529).

Conclusion:
Substantial opportunities exist to expedite thrombectomy for patients presenting to referral hospitals and transferred to interventional centers. National programs to improve achievement of DIDO and FIFA performance measure targets would benefit acute stroke patients in developing regional acute stroke care networks
Abstract WP277: Race Score is Scalable to Other Ems Systems; A Sensitivity Analysis
Authors: Panjwani Sharjeel , Shawver Julie , Zaidi Syed F , Jumaa Mouhammad A
Published: June 2021

Back Ground:
Rapid Arterial Occlusion Evaluation Scale (RACE) was first instituted in Barcelona and described in 2014 to successfully assess stroke severity and identify patients with acute stroke with large vessel occlusion (LVO) at pre-hospital setting by medical emergency technicians.

Objective:
We instituted Rapid Arterial Occlusion Evaluation Scale (RACE) hospital bypass protocol (RA) in Lucas county, Ohio since July 2015. Our aim in this study is to evaluate the sensitivity of our RACE protocol in identifying cerebro-vascular accidents and furthermore to identify ischemic CVAs from the cohort.

Method:
All county EMS personnel (N=464) underwent training in the Rapid Arterial Occlusion Evaluation (RACE) score. The RACE Alert (RA) protocol, whereby patients with stroke symptoms, who were last seen normal less than 12 hours and had a RACE score ≥5 were taken to a facility that has neuro-interventional capacity, was implemented in July 2015. An IRB approved prospective DB was maintained during that period. Patient’s stroke characteristics, type of acute treatment and final diagnosis on discharge were reviewed for the purpose of this abstract. Our results were comparable to the Spanish study done in Barcelona in 2014.

Results:
Between Jul 2016-Jun 2016 186 RAs were activated. The discharge diagnoses included ischemic stroke N=91 (49%), ICH N=26 (14%) and TIA N=17(9%). The rate of stroke mimic was N=52 (28%) of the total RACE alerts. These included seizures (12%), metabolic encephalotpathy (12%) and others including sepsis and migraines. Of the patients presenting as RA, 33% underwent IV tPA treatment ± mechanical thrombectomy.

Conclusion:
Results from our prospective county wide data is comparable to prior studies. RACE score may be scalable to other EMS systems to triage potential LVOs for direct transfer to centers with interventional capabilities.
Abstract WP279: Concordance of Paramedic and Hospital Documented Last Known Well Times for EMS Transported Acute Ischemic Stroke Patients
Authors: Ramirez Lucas , Bosson Nichole , Gausche-Hill Marianne , Saver Jeffery L , Starkman Sid , Liebeskind David S , Lyden Patrick , Sanossian Nerses
Published: June 2021

Background:
Last known well time (LKWT) is increasingly used by EMS systems to identify acute stroke patients appropriate for direct routing to Stroke Centers. However, determining LKWT in the field is challenging, as patients may be aphasic, witnesses may not be available on scene, and rapid departure from the scene is desirable.

Objective:
To characterize the concordance and degree of discordance between prehospital-determined LKWT and final LKWT documented at the hospital.

Methods:
This is a retrospective analysis of consecutive patients with positive prehospital stroke screens transported to an approved stroke center in a large metropolitan system from January 2011 to December 2014. Data was abstracted from the regional EMS Agency stroke database. Patients with missing prehospital or hospital documentation of LKWT were excluded. The percent concordance and the median difference were calculated for prehospital versus final hospital documented LKWT. The effect of patient characteristics on discordance was also explored via multivariate regression analysis.

Result:
Among the 9,810 patients transported for suspected stroke, the median age was 75 (Interquartile range [IQR] 62-85) years, 53% were women, 67% White, 11% Asian, 9% Black and 27% Hispanic. The median NIHSS was 11 (IQR 4 to 20). 83% had a cerebrovascular final diagnosis, ischemic stroke (IS) being the most common (n=5160, 53%), whereas 17% had a non-stroke-related diagnosis. There were 6873 patients missing either prehospital or hospital documentation of LKWT leaving 9810 patients for the analysis. Prehospital and hospital documented LKWTs were exactly equal in 42% of patients (36% for IS), within 15 minutes in 53% (48% for IS), within 1 hour in 66% (63% in IS) and within 2 hours in 70% (68% in IS). The median difference in LKWT between documented prehospital and hospital values was 0 minutes (IQR -6 to 18). The degree of discordance in LKWT did not vary with patient sex, race, or Hispanic ethnicity.

Conclusions:
Paramedic-documented LKWT was within 15 minutes of the final hospital documented LKWT in just over half of acute stroke EMS transports and within 1 hour in two-thirds.. As accurate LKWT determination in the field is challenging, time of symptom onset should be confirmed after hospital arrival.
Abstract WP280: Barriers to the Early Management of Patients With Transient Ischemic Attack in Low and Middle Income Countries
Authors: Teixeira Fernanda J , Portal Bernardo C , Tomasi Gustavo H , Gasperin Paula C , Vedana Viviane M , Martins William A , Cristovam Rafael A , Zandoná Manuella E , Federizzi Bianca B , Marrone Luiz C , Massaro Ayrton R , da Costa Jaderson C
Published: June 2021

Background:
Although much progress has been made in the acute ischemic stroke care in low- and middle-income countries (LMIC), there is a paucity of specific data on the early management of TIA patients. Patients with TIA present a substantial risk of stroke during the first few hours of symptom onset, when secondary prevention therapies should be urgently initiated. Therefore, hospital admission may offer some advantages for early management. Our aim was to evaluate the benefit of hospital admission of TIA patients in a LMIC.

Methods:
All TIA patients who arrived at our emergency room (ER) between March 2015 to March 2016 were admitted to the hospital. All patients were submitted to the following diagnostic protocol: brain imaging, intra and extracranial vascular imaging, echocardiography (TT and or TEE) and ECG. Baseline, imaging characteristics and early outcome were analyzed.

Results:
Among 845 consecutive stroke patients evaluated at our ER, 12.8% were diagnosed as TIA. Although vascular risk factors and presentation with weakness or speech disturbances were frequent findings among our TIA patients, only 1 in 5 patients (17.4%) required specific treatment (anticoagulation or carotid revascularization). In addition, half of our patients were classified as cryptogenic TIA. The average length of stay was 7.03 and there were no in-hospital stroke or death. We did not detect significant differences in demographics, risk factors and imaging features between patients that received standard vs. specific treatment.

Conclusions:
Many TIA patients with mild symptoms may not have reached our ER and among those who were evaluated some may not have required hospital admission. Clustering of risk factors among TIA patients may not be a variable helpful to identify high-risk patients in LMIC. A 24/7 emergency TIA clinic may be an option to improve urgent treatment and reduce acute care cost.
Abstract WP286: ONO-8610539, an Injectable Small-Molecule Inhibitor of Blood Coagulation Factor XIa, Improves Cerebral Ischemic Injuries Associated with Photothrombotic Occlusion of Rabbit Middle Cerebral Artery
Authors: Sakimoto Shinya , Hagio Tetsuya , Yonetomi Yasuo , Ono Takehiro , Koyama Sho , Hashimoto Ai , Gohda Masashi , Sakai Masaru , Nishiyama Taihei , Tanaka Kenji , Matsuya Hidekazu , Imagawa Akira , Hirota Yasushi , Kawabata Kazuhito , Habashita Hiromu
Published: June 2021

Background and Purpose:
High levels of blood coagulation factor XI (FXI) are an established risk factor for acute ischemic stroke and thrombosis. Patients with severe FXI deficiency have a low risk of ischemic stroke. In addition, FXI-deficient or anti-FXI antibody-treated mice are protected against cerebral ischemic injury and bleeding is not observed. Therefore, FXI is considered to be a promising drug target for the treatment and secondary prevention of ischemic stroke that would not increase the risk of bleeding. ONO-8610539 is a potent, injectable small-molecule inhibitor of activated FXI. The objective of this study was to elucidate the effects of ONO-8610539 on preventing ischemic brain injury in an experimental stroke model.

Methods:
The preventive and hemorrhagic effects of ONO-8610539 were compared with those of argatroban, a direct thrombin inhibitor, in a rabbit middle cerebral artery (MCA) occlusion model. To occlude the MCA photothrombotically, rose bengal was administered, followed by irradiation with green light for 30 minutes. The intravenous administration of ONO-8610539 or argatroban was then initiated and continued for 23.5 hours. The effects of these compounds on neurological function, infarcted brain volume, and cerebral hemorrhage volume were evaluated in a blinded manner. Blood was collected to measure activated partial thromboplastin time (APTT) and prothrombin time (PT) before and at 24 hours after photothrombosis.

Results:
ONO-8610539 at doses of 0.3 and 1 mg/kg/h significantly attenuated neurological deficits and infarct volumes in the cortex. Even at a dose of 1 mg/kg/h, ONO-8610539 did not increase cerebral hemorrhage volume. The APTT ratios increased by 1.9-fold from baseline at the 0.3 mg/kg/h dose and increased by 4.4-fold at 1 mg/kg/h, while changes in PT were not observed at either doses. Argatroban also prevented ischemic neuronal injuries at 0.3 mg/kg/h; however, these effects were attenuated at 1 mg/kg/h. Moreover, argatroban significantly exacerbated cerebral hemorrhage at 1 mg/kg/h.

Conclusion:
ONO-8610539 is expected to be a novel potent anticoagulant for the treatment and prevention of ischemic stroke that does not increase bleeding risk.
Abstract WP29: Temporal Trends of Intravenous Recombinant Tissue Plasminogen Activator Infusion and Endovascular Treatment for Acute Ischemic Stroke in Japan: J-ASPECT Study
Authors: Kurogi Ai , Onozuka Daisuke , Hagihara Akihito , Kada Akiko , Nishimura Kunihiro , Kamitani Satoru , Ogasawara Kuniaki , Ono Junichi , Shiokawa Yoshiaki , Aruga Toru , Toyoda Kazunori , Nakagawara Jyoji , Miyachi Shigeru , Yoshimura Shinichi , Okuchi Kazuo , Nagata Izumi , Matsuda Shinya , Nakamura Fumiaki , Suzuki Akifumi , Ido Keisuke , Kurogi Ryota , Nishimura Ataru , Arimura Kouichi , Sayama Tetsuro , Iihara Koji
Published: June 2021

Objective:
This study aimed to investigate recent nationwide trends in the epidemiology of acute ischemic stroke (AIS) in Japan.

Methods:
We analyzed 328,147 acute ischemic stroke patients in 350 certified training hospitals in Japan using data obtained from the Japanese Diagnosis Procedure Combination Database. Data between the period April 1, 2010 and May 31, 2014 were used. We divided patients into three treatment groups: medical treatment only (group M), intravenous t-PA infusion only (group IVT), and endovascular treatment (group ET). Outcome was assessed by in-hospital mortality and modified Rankin Scale (mRS) score at discharge, and poor outcome was defined as a mRS score of 3-6.

Results:
The patient proportion in groups M, IVT, and ET changed from 94.3%, 3.2%, and 1.6% in 2010 to 90.9%, 4.3%, and 3.7% in 2014, respectively (P<0.0001). In all AIS patients, in-hospital mortality significantly decreased from 6.5% in 2010 to 5.3% in 2014 (p<0.0001) and poor outcome at discharge also decreased from 42.7% in 2010 to 41.6% in 2014 (p<0.0001). In groups M and IVT, in-hospital mortality significantly decreased from 6.3% and 12.0% in 2010 to 5.0% and 9.1% in 2014, respectively (p<0.0001), and poor outcome at discharge also decreased from 42.1% and 60.7% in 2010 to 40.7% (P<0.0001) and 55.4% (p<0.005) in 2014, respectively. In contrast, in group ET, both in-hospital mortality (from 11% in 2010 to 9.5% in 2014) and poor outcome at discharge (from 53.4% in 2010 to 54.0% in 2014) were not significantly different between the two time points.

Conclusion:
In Japan, during the 5-year period before the guidelines concerning proper use of ET for AIS were revised in 2015, a significant improvement in in-hospital mortality and functional outcomes of AIS patients undergoing medical treatment and intravenous rt-PA infusion was observed. This was probably due to a gradual increase in the proportion of patients undergoing IVT; the outcomes of ET, however, remained the same.
Abstract WP292: Insulin Resistance is Associated with a Reduction of Leukocyte Surface CD36 Expression and an Increase of Soluble CD36
Authors: Kanoke Atsushi , Nishijima Yasuo , Hsieh Christine L , Liu Jialing
Published: June 2021

Introduction:
Diabetes is a major risk factor for ischemic stroke. Evidence suggests that the deficiency in CD36 is linked to insulin resistance in humans, yet patients with type 2 diabetes often display elevated plasma level of soluble CD36 (sCD36). However, cell type specific expression of CD36 is not well understood in the context of type 2 diabetes.

Hypothesis:
We hypothesize that insulin resistance is correlated with a reduction in the surface expression of CD36 among inflammatory cells, coincident with an increase in sCD36.

Methods:
Middle-aged db/db and db/+ mice (30-50 weeks-old) were subjected to left distal middle cerebral artery occlusion (dMCAO) or sham surgery. One, 3, or 7 days after stroke, leukocytes from blood and left hemisphere of the brain were analyzed by flow cytometry for cell type specific expression of CD36. The level of sCD36 in platelet free plasma was determined by ELISA. PPAR-γ agonist pioglitazone was administered at 2.5 mg/kg/day by oral gavage. Oral glucose tolerance test was performed at baseline and following two weeks of drug treatment. Both form of CD36 was also measured in 3-week-old mice without stroke.

Results:
Infiltrating neutrophils in brain peaked at 1 day after dMCAO, in contrast to a delayed but sustained increase of macrophages from 3 to 7 days post stroke. The adult db/db mice had a lower leukocyte surface expression of CD36 in both blood and brain, but had a higher level of sCD36 compared to age-matched db/+ mice whether at baseline or after stroke. The sCD36 is unlikely to exist in the form of extracellular vesicles (EV) since there were very few CD36(+) EVs detected in either type of mice. Prior to the development of obesity, 3-week-old db/db mice had similar leukocyte CD36 surface expression and plasma level of sCD36 compared to juvenile db/+ mice. Pioglitazone improved glucose sensitivity and enhanced macrophage CD36 surface expression in db/db mice after stroke.

Conclusions:
The reduced surface expression of CD36 on leukocytes and increased sCD36 was directly correlated with insulin resistance. Ongoing studies will determine the molecular event induced by obesity that triggers the cleavage of CD36 and how it affects macrophage function in the setting of diabetes.
Abstract WP293: Necroptosis Cell Death Signaling Amplifies Acute Hyperglycemic Stroke Injury
Authors: Yi Liye , Zhang Jian , Yang Zeng-Jin , Koehler Raymond C
Published: June 2021

Introduction:
Acidic pH is an important feature of the microenvironment of cerebral ischemic injury. Acute hyperglycemia has been used as a tool to augment intraischemic acidosis, oxidative stress, edema, and cell necrosis. In addition to classical unregulated necrosis, neurons can undergo regulated necrosis. One form of regulated cell death is RIP1-regulated necroptosis. However, the effect of acidosis on the RIP1 signaling pathway has not been well studied.

Hypothesis:
The acidic microenvironment associated with hyperglycemic middle cerebral artery occlusion (MCAO) amplifies oxidative stress, which then augments RIP1-regulated necroptosis.

Methods:
MCAO was produced for 1 h in male Sv/Ev129 mice by the filament technique. To produce acute hyperglycemia, mice received an ip infusion of 25% dextrose before and during MCAO to increase blood glucose into the 350-400 mg/dL range and further decrease ischemic tissue pH from 6.8 to 6.4.

Results:
As expected, hyperglycemic mice had a greater infarct volume (41.4±4.9% of hemisphere) than did normoglycemic mice (28.4±5.3%). With intraventricular injection of the RIP-1 kinase inhibitor necrostatin-1, infarct volume decreased significantly in hyperglycemic mice (14.9±3.1%). Hyperglycemic MCAO increased protein carbonyls and 3-nitrotyrosine to a greater extent than normoglycemic MCAO, whereas necrostatin-1 attenuated their formation in hyperglycemic mice. Using immunoprecipitation, we found that hyperglycemic MCAO augmented the association of RIP3 with RIP1, MLKL, and PGAM5 and that these associations were blocked by necrostatin-1.

Conclusions:
These results indicate that RIP1-regulated necroptosis can make a major contribution to the ischemic neuronal injury that is augmented by acute hyperglycemia. The mechanism of augmentation of oxidative stress by intraischemic acidosis appears to require RIP1 kinase activity because necrostatin-1 attenuated protein carbonyl and 3-nitrotyrosine formation. Because much of the cell death appears to result from regulated necrosis rather than classical unregulated necrosis, RIP1-regulated necroptosis may serve as a therapeutic target for cerebral ischemia associated with severe acidosis.