bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP302: Low Volume Non-PSC Hospitals Are More Likely to Transfer Whites but Not Blacks for a Higher Level of Stroke Care
Authors: Lyerly Michael J , Albright Karen C , Vahidy Farhaan S , Howard George , Donnelly John
Published: January 2019

Introduction:
We previously reported that “drip and ship” patients received at our tertiary center were younger and less often black when compared to those presenting directly. Given that disparities exist at many levels of acute ischemic stroke (AIS) care, the objective of this analysis was to determine if age and race disparities exist in inter-hospital transfer to a higher level of care (HLOC).

Methods:
In this cross-sectional analysis, we extracted patient characteristics and transfer status of AIS patients from the State Emergency Department Databases (SEDD) and Inpatient Databases (SID) of 5 states between 1/1/2010 and 12/29/2010. Hospital characteristics were determined using the American Hospital Association Database and The Joint Commission. We used Poisson regression with robust variance estimation adjusted for age, gender, payer type, Elixhauser comorbidities, and state to estimate prevalence ratios (PRs) and the proportion of whites and blacks, aged 18-64 or ≥65 years transferred by PSC status and hospital AIS volume.

Results:
We identified 58,321 AIS discharges (29% age 18-64 years) of whom 4.8% were transferred to a HLOC. Blacks were less likely to be transferred compared with whites (3.9% vs. 5.0%, PR 0.76; 95% CI 0.68-0.84). Among those age 18-64 years presenting to very low volume non-PSC hospitals (2 AIS discharges/month), blacks had a lower predicted percent transferred when compared with whites (16.2% vs 29.9%: 13.6% difference; 95% CI 6.6-20.6[Figure 1]). Differences by race were present for non-PSC hospitals with volumes as large as 8 AIS discharges/month (9.8% vs. 12.7%: 2.9% difference; 95% CI 0.9-4.9). Similar, although smaller, differences were observed in older patients (data on minority serving hospitals to be presented also).

Conclusions:
These findings suggest that age and race disparities exist in inter-hospital transfer for AIS. Specifically, black AIS patients aged <65 years have a lower probability of being transferred to a HLOC.
Abstract WP303: Improving Treatment Within the Golden Hour in and Out of Hours With a Multi-Disciplinary Pre-Hospital, Within-Hospital Communication System
Authors: Bagot Kathleen L , Cadilhac Dominique A , Smith Karen , Bernard Stephen , Kim Joosup , Coupland Tessa , Pearce Wayne , Putland Mark , Budge Marc , Nadurata Voltaire , Pearce Debra , Hall Howard , Hocking Grant , Kelly Ben , Spencer Angie , Chapman Pauline , Oqueli Ernesto , Sahathevan Ramesh , Kraemer Thomas , Stub Dion , Bladin Chris F
Published: January 2019

Delivery of time-critical stroke care requires rapid assessment, diagnosis and treatment, involving multiple clinicians. However, disparate communication systems exist between in-field paramedics and hospital clinicians, with variation for in and out of hours presentations. Repetition of patient information and fragmented systems may contribute to delayed processes.

Aim:
To determine if smartphone communication technology can improve clinical care timelines for patients with suspected acute stroke in and out of hours.

Methods:
A 12 month pre-post historical-control design was used. The Pulsara
TM
Stop Stroke/STEMI smartphone and tablet app (Pulsara) was implemented in 25 Ambulance Victoria branches and 2 hospitals in rural Victoria, Australia, during 2016/2017. Pulsara provides secure, simultaneous, two-way, real-time communication. Eligible patients had suspected acute stroke as assessed by paramedics or hospital clinicians. Analyses compare timelines (median minutes) for when Pulsara is (Pulsara+), or is not (Pulsara-), used by clinicians in hours (08:00-17:00; IH) and out of hours (17:01-07:59; OH).

Results:
Pulsara was used in 80% (210/265) of cases. Using Pulsara, patients are off-ambulance stretcher 5 minutes faster (10 minutes Pulsara+ vs 15 minutes Pulsara- ; p=0.23), and depart hospital 4 minutes faster (11 minutes Pulsara+ vs 15 minutes Pulsara- ; p=0.02). The time to first medical review is similar IH (7 minutes), but 7 minutes faster OH (7 minutes Pulsara+ vs 14 minutes Pulsara-; p=.03). Time to CT scan is 40 minutes faster IH (27 minutes Pulsara+ vs 67 minutes Pulsara- ; p=.02), and 29 minutes faster OH (29 minutes Pulsara+ vs 58 minutes Pulsara- ; p=.0001). Pulsara was used on all cases receiving thrombolysis. Compared to the pre-Pulsara period, when Pulsara was used the proportion treated within 60 minutes increased from 9% (1/11) to 23% (3/13) during in hours, and from 13% (2/15) to 26% (7/27) out of hours.

Conclusion:
The use of Pulsara improved hospital metrics and care timelines for treatment of patients with suspected stroke. There is a two-fold increase of patients treated within 60 minutes in hours, and also out of hours (when staffing levels are less). Pulsara has significantly improved stroke care in these two rural hospitals.
Abstract WP305: Field Assessment of Potential Large Vessel Occlusions in Patients With Suspected Acute Ischemic Stroke: Results From a Clinician Survey
Authors: Warach Steven , Korner Eli , Harbour Kathy , Salem Cindy , Jacobs Joan , Lu Xiao-Yu , Purdon Barbara , Jovin Tudor G
Published: January 2019

Introduction:
Acute ischemic stroke (AIS) caused by large vessel occlusions (LVOs) has high morbidity and mortality. Reliable prehospital identification of LVOs may improve patient care, hospital routing and ultimately outcomes. This analysis characterizes current expert opinion on preferred stroke scales for field assessment of LVOs, factors driving scale preferences and associated research data gaps in a sample of multidisciplinary key stakeholders who care for patients with AIS.

Methods:
In total, 248 HCPs from 4 specific disciplines responsible for AIS patient care were asked to participate in an in-person survey. The survey was administered by trained interviewers using structured interviews between Sep 2017 and Jan 2018. Responses were analyzed overall and stratified by HCP type with descriptive statistics.

Results:
Of 169 participating HCPs, 22% were general neurologists, 25% neuro-interventionalists, 24% emergency department physicians (38% emergency medical system [EMS] directors), 26% stroke coordinators and 2% other. Most respondents were from comprehensive stroke centers (64%) and represented a broad US geography. Among the respondents, 86% agreed or strongly agreed that prehospital stroke scales are effective in identifying LVOs, and 63% (n=107) had a preferred prehospital LVO scale (
Table
). Among those who stated a preference (n=107), 65% cited practical considerations for their choice (eg, ease of use, already in use by local EMS) and 46% cited the scale’s properties (psychometric or clinical). Regarding the greatest need in the prehospital assessment of stroke (n=169), 56% of respondents called for more research on LVO scales, 24% for other prehospital assessment tools and 26% for EMS training and standardization.

Conclusions:
The majority of HCPs surveyed support the use of prehospital LVO scales but request further research. No one scale was preferred over another.
Abstract WP306: IV tPA Treatment Facilitated by Advanced Practice Providers in an Academic Program
Authors: Shawver Julie , Zaidi Syed , Jumaa Mouhammad
Published: January 2019

Background:
There is a nationwide shortage of stroke physicians to manage the ever increasing patient population. Many stroke centers rely on advanced practices providers (APP) to bridge this coverage gap. We sought to compare the IV tPA treatment time efficiencies when care is mediated by stroke APPs as compared to neurology residents (NR).

Methods:
Case records of all IV tPA treatments between Jan 1, 2017- July 15, 2018 at our comprehensive stroke center were reviewed. Basic demographics, risk factors, door to needle time (DTN), stroke alert activation to treatment time (ATN), and outcomes were compared.

Results:
Between Jan 1, 2017 - July 15, 2018, 66 patients were treated with IV tPA at our center. Of these, the NRs managed 37 (56.1%) whereas the APPs were primarily involved in 29 (43.9%) treatments. Most of the treatments were in ER 59 (89.4%), while 7 were inpatients (10.6%). Patients in the APP cohort were older (median age 74 vs 67, p0.01) and underwent MT at a higher rate (41.3% vs 13.5%, p 0.01). The DTN time was significantly shorter with APPs responding to stroke alert (31.6 vs 52.5 mins, p<0.01). However, clinical outcomes were comparable (see table).

Conclusion:
In our experience, IV tPA treatment facilitated by APPs is more time efficient when compared to NRs. However, given small sample size and cohort mismatch, future larger prospective studies are warranted.
Abstract WP308: BEMI (Brain Emergency Management Initiative) for Optimizing Hub-EMS-Spoke Transfer Networks
Authors: Modir Royya F , Meyer Dawn , Hamidy Morcel , Delima Teneille , Steinberg Jeffrey , Mukau Leslie , Walls Dannielle , Walls Brandon , Sloane Christian , Meyer Brett
Published: January 2019

Objective:
To evaluate an expedited “Brain Emergency Management Initiative (BEMI)” transfer process within a telestroke network with the goal of decreasing transfer delays and time to stroke embolectomy intervention.

Methods:
We conducted an exploratory, retrospective assessment of consecutive acute telestroke patients transferred for potential intervention to compare outcomes in pre-BEMI vs. BEMI periods. Baseline characteristics included age, sex, ethnicity, stroke risk factors, and NIHSS. Times included Spoke In, Spoke Out, Hub In, and groin puncture. Outcomes included discharge destination home, and Symptomatic Intracranial Hemorrhage (SxICH).

Results:
Overall, 68 transfers were assessed. There were no differences for age, sex, diabetes, hypertension, or atrial fibrillation. There was a higher NIHSS in BEMI (11 pre-BEMI vs. 20 BEMI;p=0.01). There was a shorter spoke door in to door out (143 vs 118 minutes; p=0.01) and spoke door out to hub door in (23min pre-BEMI vs. 21min BEMI;p=0.001). For embolectomy patients, there was a shorter hub door in to reperfusion (83min Pre-BEMI vs. 74min BEMI;p=.04), and rt-PA decision to groin puncture (155min Pre-BEMI vs.130min BEMI;p=.01). There were no sxICH or discharge home differences. Though NIHSS was correlated with home discharge destination (r=-0.26;p=0.04), Hispanic ethnicity (r=0.33;p=0.01), hub door in to reperfusion (r=0.11;p=0.04) and spoke out to reperfusion (r=0.28;p=0.04), no relationship was strong.

Conclusions:
In our Hub-EMS-Spoke telestroke network, BEMI led to improved evaluation times. Rapid transfer protocols are critical for improving outcomes. BEMI can serve as a model for future rapid stroke transfer pathways. Further work assessing generalizability and outcomes is underway.
Abstract WP31: A Comparison of Outcomes Associated With Mechanical Thrombectomy in Acute Ischemic Stroke Patients Performed Within and Outside Clinical Trials in the United States
Authors: Qureshi Adnan I , Singh Baljinder , Huang Wei , Malik Ahmed A
Published: January 2019

Background:
A discrepancy between characteristics of patients treated with mechanical thrombectomy in acute ischemic stroke patients within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may limit generalization of clinical trial results. The objective of this study was to identify differences in demographic and clinical characteristics and outcomes related to mechanical thrombectomy in patients treated in clinical trials and those treated outside clinical trials in a large national cohort.

Methods:
We determined the frequency of mechanical thrombectomy in acute ischemic stroke patients performed within and outside clinical trials and associated in-hospital outcomes using nationally representative data from the Nationwide Inpatient Survey data files from 2013 to 2015. We compared in-hospital mortality and discharge to home in patients who were treated within and outside the clinical trials.

Results:
Of the 23,375 patients who underwent mechanical thrombectomy, 430 (1.8%) underwent the procedure as part of a clinical trial. There was no difference in mean age of the patients treated with mechanical thrombectomy as part of a clinical trial than those treated with thrombectomy outside a clinical trial. The proportion of women was lower among patients treated with thrombectomy as part of a clinical trial. After adjusting for age, mechanical thrombectomy performed as part of a clinical trial was associated with lower rates of in-hospital mortality (odds ratio [OR]: 0.13; 95% confidence interval [CI]: 0.03-0.55; P = .002) and higher rates of discharge to home (OR, 2.5; 95% CI, 1.6-3.9; P = .003).

Conclusions:
Our results suggest that mechanical thrombectomy procedures performed as part of clinical trials were associated with lower rates of in-hospital mortality and higher rates of discharge home in the United States. These findings highlight the need for strategies that ensure appropriate adoption of mechanical thrombectomy to ensure that the benefits observed in clinical trials can be replicated in general practice.
Abstract WP315: Nationwide Channel Routing for Endovascular Treatment in Patient With Acute Ischemic Stroke
Authors: Kang Jihoon , Kim Seong-Eun , Bae Hee-Joon
Published: January 2019

Purpose:
This study aimed to investigate the initial and subsequent interhospital transfer routes for endovascular treatment in patients with ischemic stroke and to estimate their effects on recanalization therapy and outcome.

Methods:
From the nationwide acute stroke quality assessment program database, patients diagnosed with ischemic stroke were identified through all kinds of acute stroke care hospitals in South Korea for 6 months survey period. Among them, we defined thrombectomy-eligible patients who had NIHSS score of 7 or more and arrived at the hospital within 6 hours from last well-being time. After determining the in- and outflow routes per person, patients were dichotomized into initially anchored in thrombectomy capable hospital (TCH) and initially anchored in non-TCH according to the initial visiting hospital. In each group, they were subclassified into stay-on and transfer-out according to outflow routes. Implementation of intravenous thrombolysis (IVT) and endovascular treatment (EVT), and clinical outcomes were compared by initial visiting hospitals and sub-groups.

Results:
Of 14902 patients with ischemic stroke, thrombectomy-eligible patients were 2180 (male, 51.9% and age, 72.9 ± 12.5 years old). Initial routes were TCH (35.5%) and non-TCH (64.5%), which were associated with IVT (53.8% for patients anchored in TCH versus 35.5% for patients initially anchored in non-TCH, P < 0.001) and EVT (33.3% versus 8.1%, P < 0.001). Initial visiting hospital showed a significant difference in 1 y mortality (29.3% versus 36.0%, P = 0.002). Transfer-out to TCH in patients initially anchored in non-TCH (n = 1406) was rated 17.4%, which was significantly associated with higher EVT (34.8% versus 7.5%) compare to stay-on, not with IVT (35.7% versus 34.9%).

Conclusion:
In acute stroke, the initial route and interhospital transfer affected the implementation of recanalization therapy and would be the key step toward renovating the stroke care system.
Abstract WP321: Enhancing Stroke Systems of Care in the United States through Evidence-Informed State Policy Interventions
Authors: Shantharam Sharada , Bhuiya Aunima , Chowdhury Farah M , Barbero Colleen , Taylor Lauren , Fulmer Erika , Graff Kaitlin , Gilchrist Siobhan , Bernard Stephanie
Published: January 2019

In the United States (US), a stroke occurs every 40 seconds. Stroke care policies vary across federal, state, and local levels. Differences in health outcomes could be addressed through adoption of evidence-informed stroke policies. We examined early evidence to identify state policy interventions that may improve quality of stroke care. The US Centers for Disease Control and Prevention (CDC) examined the evidence base for stroke systems of care policy interventions enacted by the US state governments. We assessed 16 policy interventions impacting the entire continuum of stroke care, including those in the pre-, in-, and post-hospital settings. An expert group representing CDC, state stroke programs, and the American Heart Association informed the assessment. Over 460 items were assessed using the Quality and Impact of Component Evidence Assessment methodology for effectiveness, equity, reach, efficiency, and transferability. Each policy intervention’s evidence base was assigned to one of four levels: “best,” “promising potential public health impact,” “promising quality,” or “emerging.” Of the policy interventions assessed thus far, eight had “best” evidence, one had “promising potential public health impact” evidence, one had “promising quality” evidence, and six had “emerging” evidence (see Table). State laws addressing policy interventions with “best” evidence, such as pre-notification of receiving facilities by emergency medical service providers or telestroke to initiate treatment on-site, are expected to have the greatest potential for positive impact. A greater focus on policy evaluation research could help policymakers understand their options for implementing and scaling up stroke policies with emerging and promising evidence bases in their state. States may improve population health and economic outcomes by strengthening health care delivery using policy interventions with “best” available evidence.
Abstract WP322: Transfer Guidelines for IV Alteplase (tPA) Patients Improves Outcomes
Authors: Patterson Michele , Moore Tracy , Cline Beth , Birnbaum Lee , Behrouz Reza
Published: January 2019

Background:
Comprehensive Stroke Center (CSC) identified tPA transfers were missing documentation of treatments and vital signs from transferring facilities (TFs) and during transfer by Emergency Medical Services (EMS). A patient who became hypertensive and had hemorrhagic transformation (HT) arrived without documentation.

Purpose:
Implement transfer guidelines to ensure documentation is received and blood pressures (BP) are monitored and treated during transfer to avoid HT.

Method:
Guidelines developed included required documentation from TFs to be sent with patients; parameters for BP monitoring and treatment during EMS transfer; and receiving nurse checklist to verify receipt of documented care prior to arrival. Guidelines were communicated to TFs, EMS, and CSC nurses.

Results:
Review of 293 tPA records, excluding endovascular interventions, were compared pre-guidelines 2016 (Pre-G) and post-guidelines January 2017-June 2018 (Post-G). Transfer volumes Pre-G were 37 of 129 and Post-G 54 of 164. Rate of hemorrhage on brain imaging within 36 hours after tPA was higher on transfers for both review periods 19%(7/37) and 15%(8/54) compared to non-transfers 8%(7/92) and 8%(9/110). Of the Pre-G HTs that were symptomatic, transfers had a higher rate 71%(5/7) than non-transfers 29%(2/7) and decreased to a rate of 50%(4/8) Post-G. Blood pressures were controlled on 60% of 2016 cases versus 75% in 2017. There were zero transfer symptomatic HTs in 2018. Pre-G and Post-G transfers with symptomatic HT had dispositions of Hospice 60%(3/5) and 25%(1/4), Rehab 40%(2/5) and 25%(1/4), Home 0%(0/5) and 50%(2/4), respectively. Pre-G and Post-G modified Rankin Score (mRS) at discharge for symptomatic HT transfers were mRS 4-5 = 100%(5/5) and 50%(2/4) and mRS 2-3 = 0%(0/5) and 50%(2/4), respectively. mRS at 90 days hospice or expired was Pre-G 60%(3/5) and Post-G 25%(1/4).

Conclusion:
Prior to implementing transfer guidelines for tPA patients, this population had higher rates of HT, symptomatic HT, and mRS at discharge. Transfer guidelines improved acquisition of documentation for continuum of care and BP management with decreased rates of symptomatic HT and improved outcomes.
Abstract WP324: Factors Associated With Clinicians’ Intention to Use Acute Stroke Telemedicine Service: Perceived Usefulness Critical to Uptake
Authors: Cadilhac Dominique A , Bagot Kathleen L , McGuinness Connor , Moloczij Natasha , Donnan Geoffrey A , Bladin Chris F
Published: January 2019

Introduction:
Benefits of acute telestroke services include improving equity of access to acute therapies. However, these benefits require a change in clinicians’ usual practice and there may be resistance to use of technology. We aimed to examine factors associated with clinicians’ intentions to use a new acute telestroke service within rural hospital settings.

Methods:
A pre-post 6 month design was used during the implementation of the Victorian Stroke Telemedicine (VST) Program in 16 rural hospitals in a south-eastern state of Australia. A survey based on an extended Technology Acceptance Model (TAM) was administered to clinicians involved in the VST program. Five factors comprised between 4-6 items, with responses on a 7 point Likert scale (1=strongly disagree, 7=strongly agree). Surveys were completed between February 2014 and May 2017. Analyses included t-tests and linear regressions.

Results:
Participants were 303 clinicians (pre-implementation n=167, 66% female, 46% nurses; post-implementation n=136, 74% female, 68% nurses). Mean scores were significantly higher post-implementation than pre-implementation: Perceived Usefulness (pre 5.91, post 6.27; p<.001), Perceived Ease of Use (pre 5.12, post 5.92; p<.001), Social Influence (pre 5.03, post 5.84; p<.001), Facilitating Conditions (pre 5.17, post 6.16; p<.001) and Intention to Use (pre 5.83, post 6.36; p<.001). Intention to Use Telemedicine pre-implementation [Adj R
2
=.41, F(4, 132)=24.26, p<.001] was predicted by Perceived Usefulness (
β
=.29, p<.001), Perceived Ease of Use (
β
=.22, p=.02), Social Influence (
β
=.20, p=.02) but not Facilitating Conditions (
β
=.13, p=.16). Post-implementation [Adj R
2
=.69, F(4, 117)=67.07, p<.001], only Perceived Usefulness (
β
=.59, p<.001) predicted intentions to use telemedicine.

Conclusion:
Factors driving intentions to use acute telestroke vary pre- and post-implementation of a new service. Influential colleagues and managers should emphasise the usefulness and ease of use to facilitate uptake by clinicians.
Abstract WP325: A Travel Time and Efficiency Simulation for Patient Transport to Primary and Comprehensive Stroke Centers
Authors: Hussein Haitham M , Brown Morgan M , Herrmann Amanda A
Published: January 2019

Introduction:
The purpose of this study was to identify the conditions in which bypassing a near Primary Stroke Centers (PSC) to go straight to a further Comprehensive Stroke Centers (CSC) leads to shorter time to treatment (IV Alteplase and mechanical thrombectomy).

Methods:
For this study, two simulations were performed. The first simulation evaluated time to IV Alteplase, taking in account travel and door-to-needle (DTN) times. The second simulation evaluated time to thrombectomy and accounted for travel time, door-in-door-out time if patient goes to PSC first, presence of absence of CTA at PSC, and door-to-groin (DTG) time at the CSC. In both simulations, we assumed that thrombectomy can only happen at the CSC. Regarding travel time, we implemented a rule that the longest distance between the three points of interest must be within three times the sum of the two smaller distances to be considered feasible. For example, if the patient was 5 minutes from the PSC and 5 minutes from the CSC, it would not be logical to consider a case where it takes over 30 minutes to travel from the PSC to the CSC.

Results:
For the first simulation, in 46.6% of cases DTN was faster going to the PSC. This occurred when the combination of travel time and PSC efficiency outweighed those elements at the CSC. In 6.8% of cases, the hospitals provided treatment within an equal amount of time.

For the second simulation, DTG was better going straight to CSC in the vast majority (86.7%) of cases, assuming CTA must be done at the CSC. If CTA can be done at either hospital, going to PSC first was favored in a small number of cases (10.5%). In 2.8% of cases, the hospitals provided treatment within an equal amount of time.

Conclusion:
This study illustrates that an efficient PSC with CTA capability would lead to faster DTN and DTG times. A universal prehospital triaging model would not benefit all patients in all scenarios if it is only based on time to reach destination hospital. Such a model should take in account the quality of care and the available resources in the community.
Abstract WP329: Time Dependent Recanalization and Outcomes in Transferred Stroke Patients With Large Vessel Occlusion (LVO) After IV rt-PA
Authors: Swamy Nikil , Barazangi Nobl , Kim Warren , Chen Charlene , Ke Michael , Wong Christine , Gao Billy , Choe Jessica , Yee Alan , Spokoyny Ilana , Bedenk Ann , Fernandez Julia , Patel Susila , Grovsenor David , Telischak Nick , English Joey , Tong David
Published: January 2019

Background:
The time dependent benefit of rt-PA in acute stroke patients is established. However, only limited data exist on LVO outcomes post remote telemedicine administered rt-PA. We report the outcomes of such patients.

Methods:
A retrospective study of the CPMC stroke database was performed. Primary outcome measures were neurologic outcome at discharge, mortality, and TICI reperfusion scores of mechanical thrombectomy (MT) treated patients. The safety outcome measure was symptomatic hemorrhage rate (SICH; NIHSS > 1 at ≤ 36hr).

Results:
From 1/2014-2/2018, 233 transferred rt-PA patients were identified. Median age was 73, and median NIHSS 6. Risk factors included hypertension (69%), dyslipidemia (43%), AF (27%), prior stroke/TIA (26%), CAD (26%), DM (24%), smoking (16%), and CHF (13%). The post rt-PA SICH rate was 4% and discharge mRS≤2 rate was 43%. Mortality rate was 11%, 43% required help at discharge, and 40% were discharged home. For the 61 patients who received rt-PA + MT, the SICH rate was 2% and mortality rate 12%. Median discharge NIHSS was 2 and mRS ≤2 rate was 19%. Of the 233 transferred patients, 40 had a pre rt-PA CTA with LVO available for review. For these patients, median time to scan was 76 min. Median time to repeat CTA at CPMC was 180 min. LVO was 80% anterior circulation, clot migration was seen in 5%, and >90% of MT patients had AF. Post rt-PA recanalization rate was 12% (0% posterior circulation). MT after rt-PA was performed in 62% (TICI ≥ 2b 88%). Longer time to treatment trended towards poorer result and longer MT time. Average NIHSS dropped from 12 to 5 and average discharge mRS was 3.

Conclusions:
These data confirm that remote IV rt-PA followed by MT is safe and effective. Of LVO rt-PA patients 17% experienced full or partial recanalization suggesting repeat imaging is appropriate before initiating MT, possibly with the exception of posterior circulation strokes because of poor response to rt-PA. AF is common and may predict need for MT after rt-PA. A trend was observed towards improved TICI score and shorter recanalization time with a shorter latency between rt-PA and MT. These data support the use of stroke systems of care to ensure rapid triage and treatment of LVO patients.
Abstract WP332: Social Determinants of Access to Stroke Care in Women
Authors: LaHue Sara C , Gautami Richa , Singh Vineeta , Singh Vineeta
Published: January 2019

Objective:
To identify differences in access to stroke care in a multiethnic population of women.

Methods:
In this retrospective cohort study, all women hospitalized at an urban, public safety net hospital from January 1, 2012, through December 31, 2015, with possible stroke were ascertained. Male and transgender patients, as well as patients without an estimated time of stroke symptom onset, were excluded. Patient charts were reviewed by the study coauthors for demographics, pre-hospital characteristics, and details of acute care. Differences between groups were calculated using t-test, chi-square, one-way ANOVA or Kruskal-Wallis tests.

Results:
A total of 287 women were included in this study. The average age was 71±15 (range 28-100) years. Distribution of race/ethnicity was 36% Asian/Pacific Islander (n=103), 24% Hispanic (n=69), 21% Black (n=60), and 19% Caucasian (n=55). Forty-nine percent of patients spoke a primary language other than English: 22% Spanish, 17% Cantonese, and less than 3% Mandarin, Tagalog, Toisonese, Vietnamese, Russian, and other. Average latency between stroke symptom onset and hospital presentation was 10.9±21.3 hours; this did not differ by race/ethnicity [H(3)=2.683, p=0.443] or use of English as primary language (p=0.556). The number of patients who presented within 4.5 hours of symptom onset did not differ by race/ethnicity [χ
2
(3, n= 287) = 3.902, p=0.272] or use of English as primary language (p=0.5). However presentation to the emergency department by ambulance, as opposed to an alternate means of travel, trended toward significance when differentiated by race/ethnicity: 81% of Caucasians, 78% of Blacks, 68% of Asians/Pacific Islanders and 62% of Hispanics presented by ambulance [χ
2
(3, n= 287) = 7.723, p=0.052]. Ambulance use did not differ by use of English as the primary language [χ
2
(3, n=287) = 0.942, p=0.332). Administration of tPA, and door-to-needle time for tPA, were similar across races/ethnicities and primary language (p > 0.1).

Conclusions:
While time to presentation and eligibility for stroke treatment did not differ by race/ethnicity or use of a non-English primary language, there may be a difference between races/ethnicities in the means of transport to the hospital for stroke care.
Abstract WP333: Endothelium-Specific Sox17 Deletion Ameliorates ALK1-mediated Arteriovenous Malformation (AVM)
Authors: Kim Moinay , Park Wonhyoung , Ahn Jae Sung , Lee Seungjoo
Published: January 2019

Introduction:
Sox17 promotes endothelial migration by destabilizing endothelial adherens junctions, rearranging cytoskeletal structure and upregulates expression of a number of genes preferentially expressed in angiogenic tip cells. However, the deletion of Sox17 stabilizes endothelial junctions and decreased proliferation, vice versa. The AVM after endothelial Alk1 deletion shows uncontrolled endothelial proliferation and cytoskeletal misarrangement. Therefore, we hypothesized that deletion of Sox17 in endothelial cells are sufficient to ameliorate brain AVM via Notch pathway modulation.

Methods:
Alk1
2f/2f
Sox17
2f/2f
double transgenic mice (Alk1 exons 4-6 flanked by loxP sites) were bred with VEcad-iCreER
T2
mice that express tamoxifen-inducible cre re-combinase (iCreER) in EC. EC-Alk1 and Sox17 deletion was induced by intraperitoneal injection of tamoxifen (25mg/kg, Sigma-Aldrich) with interval of 3 days. The spatiotemporal changes of blood vessel were investigated in Alk1 deletion alone and Alk1-Sox17 co-deletion mice. Vascular morphology was analyzed 9 days after tamoxifen administration. The transcripts (mRNA) and protein expression of target molecules of Notch pathway (Dll4, Hey1, Hey2, NIICD) were also evaluated.

Results:
The dysplastic blood vessel index of solitary Alk1
2f/2f
deletion mice was higher than Alk1
2f/2f
-Sox17
2f/2f
double transgenic mice (P<0.001) and was similar to human AVM. Dysplasia in Alk1
2f/2f
mice was partially rescued by Sox17 co-deletion in morphologically. In addition, target molecules of Notch pathway, Dll4, Hey1, Hey2, Jag1 was increased in Alk1-Sox17 co-deletion mice rather than solitary Alk1 deletion mice.

Conclusions:
Collectively, our findings demonstrate that the modulation of Sox17 could restrict the Alk1-induced AVM by upregulation of Notch pathway. This work establishes the Notch-Sox17 axis as a novel regulatory mechanism underlying Notch-mediated vascular stabilization in brain AVM.
Abstract WP334: Brain Permeable Iron Chelator HBED Improves White Matter Integrity After Traumatic Brain Injury
Authors: Golovachev Nikita , Khalaf Saher , Ahmad Abdullah S , Dore Sylvain
Published: January 2019

Introduction:
Traumatic brain injury (TBI) contributes significantly to the overall disabilities and mortality in the United States and worldwide. Many distinct pathophysiological processes follow brain trauma. Iron is postulated to contribute majorly to the secondary cascades after TBI. Therefore, the use of a potent iron chelator like N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid monohydrochloride (HBED) which has higher affinity, better permeability to BBB and longer half-life than most of the commonly used chelators is expected to improve outcomes after TBI.

Methods:
a controlled-cortical impact model of traumatic brain injury (TBI) was induced in two groups of WT male mice at 4.0±0.5mo of age (n=12/group). Mice were subcutaneously injected with HBED immediately after TBI, then at 12h after, followed by a twice-a-day regimen until the 3d end-point.

Results:
In addition to the overall anatomical and functional benefits, HBED-treated mice show a significantly thicker, more intact corpus callosum when compared with vehicle control mice (p<0.05). HBED mice also demonstrate a significant decrease in Iba1 expression in the body of the corpus callosum when compared to controls (p<0.05). More testing for the effect of HBED on iron susceptible oligodendrocyte and white matter affected proteins is under currently under investigation.

Conclusion:
HBED uniquely protects and maintains the integrity of the corpus callosum. This beneficial effect appears to be mediated through decreasing microglial activation and preserving the anatomical structure of corpus callosum. Such effects are being added to the previously published work on HBED role in mitigating oxidative stress injury and inflammation after TBI. HBED is clinically tested and proven to be safe in humans; thus, further strengthening its possible clinical use after acute brain trauma. [This work was supported in part by grants from the McKnight Brain Research Foundation, Brain and Spinal Cord Injury Research Trust Fund, AHA33450010, and NIH R21NS095166 (SD).]
Abstract WP335: Role of
Sorbs2
Gene in the Development of Atrial Cardiomyopathy and Atrial Fibrillation in Mice
Authors: Lu Tong , Xu Xiaolei , Lee Hon-Chi
Published: January 2019

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is a major cause of thromboembolic stroke in the United States. The risk of stroke is a 5-fold increase in patients with AF. The Sorbin and SH3 domain-containing protein 2 (Sorbs2) is a scaffolding protein known to interact with actin and several other cytoskeletal proteins in the intercalated discs and Z band of cardiomyocytes. However, the role of
Sorbs2
gene in cardiovascular diseases is largely unknown. Using the loss-of-function of Sorbs2 (

Sorbs2
e8/e8
)

mice, we found that

Sorbs2
e8/e8

mice had an abnormal lifespan and die at 4 to 7 months of age. Echocardiogram examine revealed that there was a significant decrease in right ventricle (RV) and left ventricular (LV) ejection fraction (EF), increase in RV end-diastolic volume (EDV) and end-systolic volume (ESV), and progressive chamber enlargement in left atria (LA) and RV, particularly in LA with severe fibrosis and intramural thrombus formation, in

Sorbs2
e8/e8

mice after 3 months of age. Surface electrocardiograph also showed a significant conduction delay and spontaneous arrhythmias including those of bifid P wave configuration, right bundle branch block (RBBB), spontaneous AF and non-sustained ventricular tachycardia (VT) in

Sorbs2
e8/e8

mice. Intracellular recordings in the freshly isolated LA demonstrated that

Sorbs2
e8/e8

myocardium had a delayed action potential activation in response to electrical impulse excitation, reduced amplitude and upstroke velocity (dV/dt) at phase 0, slowed repolarization at phase 1 and phase 2, prolonged atrial effective refractory period (aERP), action potential durations at 50% (APD
50
) and 90% (APD
90
) repolarization, and decreased resting potentials. Moreover, the mRNA and protein expressions of voltage-gated Na
+
channels, L-type Ca
2+
channels, transient outward K
+
channels and inward rectifier K
+
channels were significantly downregulated in the LA of

Sorbs2
e8/e8

mice, compared wo those of wild type mice. Our results indicate that Sorbs2 gene plays an important role in atrial myocardium architecture and electrophysiology. Sorbs2 dysfunction leads to atrial cardiomyopathy, spontaneous AF and cardiac embolism in mice. Hence,
Sorbs2
is a new genetic association with cardioembolic stroke.
Abstract WP336: Effects of ONO-8610539, an Injectable Small-Molecule Inhibitor of Blood Coagulation Factor XIa, on Rabbit Photothrombotic Stroke Model: Comparison With Tissue Plasminogen Activator
Authors: Sakimoto Shinya , Hagio Tetsuya , Yonetomi Yasuo , Ono Takehiro , Kouyama Sho , Miyata Hidenori , Yasuhiro Tetsuya , Sakai Masaru , Sasamura Takashi , Katsumata Seishi
Published: January 2019

Introduction:
Factor XI (FXI) is an important component in the intrinsic pathway of the coagulation system. FXI antisense oligonucleotide achieves antithrombotic efficacy with a low risk of bleeding in preclinical and early clinical studies. ONO-8610539 is a potent, injectable small-molecule inhibitor of activated FXI. We previously reported ONO-8610539 attenuated cerebral ischemic injury without increasing cerebral hemorrhage in a rabbit photothrombosis model. In this study, we aimed to compare the efficacy of ONO-8610539 and tissue plasminogen activator (t-PA) in the stroke model.

Methods:
Animal experiments were performed in accordance with Regulations for Animal Experiments of ONO Pharmaceutical Co., Ltd. Using a rabbit photothrombosis model, t-PA was intravenously infused at 1 mg/kg/h for 1 hour from immediately or 1 hour after thrombosis induction. ONO-8610539 at 0.3 mg/kg/h was intravenously infused for 24 hours from 1 or 2 hours after thrombosis induction. Moreover, ONO-8610539 was intravenously infused at 0.3 mg/kg/h for 24 hours from 3, 4.5 or 6 hours after thrombosis induction to examine the therapeutic time window (TTW) of ONO-8610539. The neurological function, infarct volume and cerebral hemorrhage volume were evaluated at 24 hours after thrombosis induction. Blood was collected to measure activated partial thromboplastin time (APTT) and prothrombin time (PT) before and 24 hours after thrombosis induction.

Results:
Administration of t-PA immediately after thrombosis induction tended to attenuate neurological deficits and infarct volume without increasing cerebral hemorrhage. Administration of t-PA at 1 hour after thrombosis induction did not attenuate neurological deficits and infarct volume and tended to exacerbate cerebral hemorrhage. ONO-8610539 significantly attenuated neurological deficits and infarct volume without increasing cerebral hemorrhage, with a TTW of 4.5 hours. The APTT ratios of ONO-8610539 increased by 2.0-fold from baseline, while changes in PT were not observed.

Conclusion:
ONO-8610539 has a potent effect comparable to t-PA with a wide TTW in rabbit photothrombosis model and is expected to be a useful anticoagulant for ischemic stroke without increasing the risk of bleeding.
Abstract WP337: The Ischemic Neuroprotectant Protein Kinase C Epsilon, Phosphorylates Enzymes in Neuronal NADH Shuttle and Regulates Mitochondrial Respiration and Glycolysis
Authors: Xu Jing , Khoury Nathalie , Stegelmann Samuel D , Dave Kunjan , Perez-Pinzon Miguel A
Published: January 2019

Background:
Among PKCε-mediated potential protective mechanisms in ischemic preconditioning, one target that we surmise is crucial for neuroprotection is the malate-aspartate shuttle (MAS). MAS is the most important NAD
+
/NADH shuttle importing reducing equivalents (NADH) generated by glycolysis from the cytosol into the mitochondria, and thus, tightly controls neuronal respiration. We hypothesized that PKCε regulates MAS in the brain and mediates neuronal mitochondrial respiration.

Method:
Phosphoproteomics analysis and immunoprecipitation (IP) were used to determine PKCε-induced phosphorylation of MAS components. Synaptosomes from cortices of naïve SD rats were treated with Tat-conjugated ΨεRACK (selective PKCε activator) or control Tat peptide and sent for phosphoproteomics analysis. To confirm the predicted phosphorylation, IP was performed. SD rats were treated with ΨεRACK (i.p.) or Tat and sacrificed 48hrs later. Proteins from rat cortical synaptosomes were immunoprecipitated with phosphoserine/threonine/tyrosine and immunoblotted for predicted phosphorylated proteins. Once phosphorylation was determined, we evaluated energy metabolism in primary neurons. Neuronal cultures were obtained from embryonic pups cortices and treated with ΨεRACK or Tat on DIV 7-10. Cellular respiration and glycolytic function were evaluated 48hrs after treatment using Seahorse XF Analyzer.

Result:
Phosphoproteomics analysis and IP results revealed increased phosphorylation of key MAS components: the mitochondrial aspartate aminotransferase (GOT2) and the oxoglutarate carrier (OGC). After PKCε activation, GOT2 and OGC exhibited serine phosphorylation increased by 2.14 fold (P < 0.05, n=4-5), and 1.74 fold (P < 0.01, n=4-5), respectively. In addition, in primary neurons, ΨεRACK treatment increased the basal and maximum cellular respiration by 0.13 (P < 0.05, n=4), and 0.22 fold (P < 0.01, n=4), respectively. The basal and maximum glycolysis were increased by 0.14, and 0.21 fold (P<0.05, n=4), respectively.

Conclusion:
Our data strongly suggest that PKCε regulates MAS, and increases neuronal metabolism by promoting cellular respiration and glycolysis. These changes may be linked to our observed PKCε-induced ischemic tolerance in the brain.
Abstract WP338: Penetrating Arteriole Flow Dynamics and Capillary Transient Time Heterogeneity Following Experimental Stroke in Two Mouse Strains With Distinct Pial Collateral Circulation
Authors: Kanoke Atsushi , Omodaka Shunsuke , Akamatsu Yosuke , Nishijima Yasuo , Sugawara Takayuki , Tominaga Teiji , Wang Ruikang K , Liu Jialing
Published: January 2019

Introduction:
In the pathophysiology of ischemic stroke, Leptomeningeal collateral circulation plays a key role on the severity of infarction. Balb/C mice have impaired leptomeningeal collateral due to variants of
Rabep2
on chromosome 7 (
Candq1
), causing sever stroke compared to C57BL/6 mice with rich collateral anastomosis. However, it still remains unclear whether and how poor collateral circulation specifically affects hemodynamic adaptation of microvessels during cerebral ischemia.

Method:
Male C57BL/6 and Balb/C mice were subjected to distal middle cerebral artery occlusion (dMCAO) combined with 90 minutes-occlusion of the ipsilateral common carotid artery. A 4x4 mm
2
cranial window was created on the parietal cortex 2 mm lateral and 1 mm posterior from the bregma 3 weeks prior to imaging. Spatial and temporal changes of the total flow and axial velocity of the penetrating arterioles (PA), as well as mean transit time (MTT) and capillary transit time heterogeneity (CTTH) in the capillaries bordering the distal MCA and ACA branches were determined by optical coherent tomography-based microangiography and capillary velocimetry at baseline, during dMCAO, 1 hour, 1 day and 7 days after reperfusion in each strain.

Results:
Stroke-induced increase in CTTH in the region of middle cerebral artery was significantly greater in Balb/C compared to C57BL/6 mice, leading to significantly increased microvascular resistance and reduced oxygen extraction during MCAO and 1 hour after reperfusion in the former (P<0.05). The total blood flow in PA reduced immediately after dMCAO in both strains of mice but it remained reduced in Balb/C mice after reperfusion in contrast to a sustainable recovery at 50% of prestroke level 7 days after stroke.

Conclusion:
Poor collateral anastomosis and impaired flow of penetrating arterioles is an additional risk factor for hemodynamic compromise during cerebral ischemia caused by reduced oxygen extraction, which may increase the severity of stroke.
Abstract WP340: Dimethyl Fumarate Controls Inflammation-Associated Brain Damage under Hypoxia through Nrf2 Mechanism
Authors: Fernandez Tyler G. , Liu Lei , Vollmer Mary K. , Fernandez Victoria M. , Kim Hocheol , Dore Sylvain
Published: January 2019

Introduction:
Cerebral ischemia triggers a complex cascade of pathophysiological changes including the activation of resident cells, production of inflammatory mediators and infiltration of inflammatory cells. Clinical and experimental studies have revealed that inflammatory interaction following cerebral ischemia is closely related to the pathogenesis and the extent of ischemic brain injury. Therefore, targeting inflammation modulation has emerged as a promising therapeutic strategy. Dimethyl fumarate (DMF) is a typical transcriptional factor Nrf2 activator that exhibits an encouraging anti-inflammatory property. However, the effect of DMF on inflammation-associated ischemic brain injury is still inconclusive.

Hypothesis:
Here, we present that Nrf2 can serve as a modulator that links inflammation and subsequent brain injury following ischemia.

Methods:
Adult Nrf2 knockout and WT mice were pretreated with DMF for 7 days and were subjected to cerebral hypoxia-ischemia (HI) surgery. The infarct volume, neurobiological deficits, reactive gliosis, inflammatory mediators, and Nrf2 target protein were examined after HI.

Results:
DMF significantly reduced the ischemia-induced infarct volume, brain edema (P≤0.05, n=4-6) and neurological deficits (P≤0.05, n=7-11) in WT, but not Nrf2
-/-
, mice at both 6h and 24h after HI. In both ischemic striatum and cortex, the inflammation associated reactive gliosis in astrocyte and microglia at a spatiotemporal pattern was significantly attenuated by DMF in ischemic-WT mice (P≤0.05, n=4-6), correlating well with the Nrf2-dependent neuroprotection by DMF. Meanwhile, DMF dramatically suppressed the expression levels of pro-inflammatory mediators and enhanced the expression levels of Nrf2 downstream cytoprotective proteins (P≤0.05, n=4-5), thereby supporting the Nrf2-mediated neuroprotection by DMF in this process.

Conclusion:
Overall, this proof-of-principle study provided the direct
in vivo
evidence that Nrf2 activation by DMF suppresses the neuro-inflammation and leads to long-last neuroprotection against ischemic brain damage.