bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P210: Plasma Kallikrein Induces Ischemic Brain Damage Through Cleavage-Dependent Activation of NMDA Receptors
Authors: wu Gongxiong , Wu Long-Jun , Clapham David E. , Feener Edward P.
Published: July 2021

Background and Purpose:
Ischemic stroke ultimately leads to brain dysfunction and neurological deficits. However, the mechanisms that contribute to neuronal injury and dysfunction in ischemic stroke are not fully understood. Recent studies have shown that pharmacological inhibition of the serine protease plasma kallikrein (PK) reduced neuron death and neurological impairment in ischemic brain in mice. In this study, we examine the effects of PK on the neuronal cell death and brain damage in mice and investigate the molecular mechanism of PK-induced neuronal cell death in ischemic stroke.

Methods:
Ischemia was produced in wild-type (WT) and PK knockout mice by permanent middle cerebral artery occlusion (pMCAO). Infarct volume was quantified by TTC staining and brain function was evaluated by neurological scoring. The effect of PK on neuron cell death in cell culture was determined by lactate dehydrogenase (LDH) release. NMDA receptor function was measured by patch clamp and Ca2+ imaging. NR1 cleavage was detected by western blot. The effect of systemic PK inhibition on pMCAO-induced infarct volume was evaluated in mice treated with the PK inhibitor (BPCCB) or vehicle alone delivered using subcutaneously implanted osmotic pumps.

Results:
We show that PK deficiency in mice decreased MCAO-induced infarct volume by 39.8% (P<0.01) and improved neurological function compared responses in WT mice. Addition of PK to cell culture media enhanced NMDA-induced cell death of cortical neurons. We further show that PK induced cleavage of NR1 and identify the cleavage site in the extracellular N-terminal domain of NR1. The truncated form of NR1 displayed enhanced NMDA-stimulated current and calcium influx. Treatment of mice with a PK inhibitor reduced MCAO-induced brain damage and neuronal injury.

Conclusions:
PK enhances NMDA receptor-mediated excitotoxicity and ischemic neuronal death. These findings suggest that PK may serve as a potential therapeutic target for treatment of ischemic stroke.
Abstract W P239: Multiscale Entropy Analysis of Heart Rate Variability Predicts Functional Outcome in ICU-Admitted Acute Stroke Patients
Authors: Tang Sung-Chun , Jen Hsiao-I , Lin Yen-Hung , Hung ChiI-Sheng , Lai Dar-Ming , Wu An-Yeu , Jeng Jiann-Shing , Chen Ming-Fong
Published: July 2021

Objectives:
Heart rate variability (HRV) has been proposed as a predictor of acute stroke outcome. The present study aimed to apply a novel non-linear method, multiscale entropy (MSE) analysis to investigate the association between the complexity of HRV and outcome in intensive care unit (ICU) admitted acute stroke patients.

Methods:
Continuous EKG signals were recorded for one hour in non-atrial fibrillation (AF) stroke patients within 48 hours after admission and controls. The complexity index (CI) was defined as the area under the MSE curve from scale 1 to scale 20. The values of CI related to outcome of functional independence (modified Rankin Scale 0-2) and death at 3 months were analyzed.

Results:
From February, 2012 to February, 2013, a total of 109 non-AF acute stroke patients (mean age 61.7±15.0 years, female 45.9%) and 60 age-sex matched controls were recruited. The CI of the MSE was significantly lower in stroke patients than the controls (32.3 ±4.25 versus 25.2 ±6.84 p<0.001). After adjustment for age, gender, and known clinical predictors including NIH stroke scales and glucose levels at admission, the values of CI had significant associations with outcomes of both functional independence and death at 3 months (adjusted odds ratio=1.186, p=0.004 and 0.784, p=0.039, respectively).

Conclusions:
In ICU admitted non-AF acute stroke patients, early assessing the complexity of HRV via MSE can help in predicting long-term functional outcome.
Abstract W P242: Clinical Implications of Changes of Aspirin Reaction Unit in Acute Ischemic Stroke
Authors: Kim Joon-Tae , Choi Kang-Ho , Park Man-Seok , Cho Ki-Hyun
Published: July 2021

Background:
Some studies have shown that biological aspirin resistance (BAR) could be associated with an increased risk of early neurological deterioration (END). Considering the risk of END and recurrent stroke is greatest during the acute phase, it would be important to investigate the influences of acute BAR on early outcomes in acute ischemic stroke. However, it is still controversial if assays of aspirin resistance might accurate and consistent. Therefore, we sought to find whether the changes of aspirin responsiveness might be associated with END in patients with acute ischemic stroke.

Methods:
This study was a part 1 study of ongoing, single center, prospective observational study. Patients of part 1 study were consecutively recruited from our tertiary stroke center. These patients were those who (1) presented and were evaluated within the first 24 hours of symptom onset; (2) were no potential risks of cardioembolism; and (3) provided written informed consent. Aspirin reaction unit (ARU) was assessed using the VerifyNow. Acute ARU (aARU) was measured at 3 hours after aspirin loading in emergent department. Follow-up ARU (fuARU) was performed after 5 consecutive days of aspirin medication. An ARU value ≥ 550 was defined as BAR. Differences between fuARU and aARU were defined as “changes of ARU”. To evaluate the association between changes of ARU and END, ‘changes of ARU’ were classified according to 4 equal sized groups. END was defined as an increase in NIHSS scores by 1 or more points between hospital days 0 and 5.

Results:
Three-hundreds forty nine patients were performed both aARU and fuARU. END occurred in 72 (20.6%) patients. Patients with END had higher values of changes of ARU than those without (-7.1 vs -29.6, p=0.040, respectively). Furthermore, END more frequently occurred in patients in forth quartiles than those in other quatiles of changes of ARU (4
th
quartiles: OR, 3.188; 95% CI, 1.431-7.104; p=0.005).

Conclusions:
Our results showed that increase of fuARU was independently associated with END. The results of our study suggested that in acute stage of ischemic stroke, it may be helpful for serial assay of aspirin responsiveness to evaluate the association between early outcomes and aspirin resistance.
Abstract W P266: The Discharge Modified Rankin Score Correlates with Established Hemorrhagic Transformation Scores in Ischemic Stroke Patients Treated with Thrombolysis
Authors: Asuzu David T , Nystrom Karin V , Sheth Kevin N , Halliday Janet R , Wira Charles , Greer David M , Pritchard David , Schindler Joseph L
Published: July 2021

Introduction:
Several scores have been proposed to predict hemorrhagic transformation (HT) after IV r-tPA therapy. However, their utility in predicting adverse outcome has been limited to assessment of 30- or 90-day Modified Rankin Scale (mRS) scores, which are not readily available at many stroke centers. Studies evaluating discharge mRS scores as a predictor of long-term adverse patient outcome are lacking.

Hypothesis:
We tested the hypothesis that HT scores predicting long-term adverse outcome after r-tPA therapy correlate with readily available discharge mRS scores.

Methods:
Clinical data was analyzed from consecutive patients (n = 187) receiving IV r-tPA therapy from January 2009 until May 2013 at the Yale-New Haven Hospital. 8 HT scores were calculated for each patient: DRAGON, ASTRAL, Stroke-TPI, HAT Score, MSS, SITS-ICH, SEDAN and SPAN-100. Univariate logistic regression was performed using each HT score as an independent variable and discharge mRS≥5 or discharge mRS≥4 as the dependent variable. Receiver Operating Characteristic (ROC) analysis was used to test goodness of fit by the DeLong method.

Results:
All metrics except the HAT Score and SPAN-100 showed good agreement with discharge mRS≥5 (ROC area > 0.7). The 3 HT scores showing the best agreement with discharge mRS≥5 were Stroke-TPI (ROC 0.85 ± 0.07), ASTRAL (ROC 0.85 ± 0.06) and DRAGON (0.83 ± 0.07), with odds ratios: Stroke-TPI (1.09 ± 0.03), ASTRAL (1.17 ± 0.06) and DRAGON (2.23 ± 0.58). These 3 HT scores still performed best when the discharge mRS cutoff was relaxed to mRS ≥ 4, with similar odds ratios but modestly reduced ROC areas: ASTRAL (ROC 0.82 ± 0.06), DRAGON (ROC 0.79 ± 0.07) and Stroke-TPI (ROC 0.76 ± 0.07).

Conclusions:
Most established HT scores in our study showed good agreement with the discharge mRS score using two separate cutoff values. Therefore, readily available discharge mRS scores may be a useful predictor of adverse outcome following IV r-tPA therapy. These results warrant larger prospective studies to establish associations between discharge mRS scores and 90-day patient outcomes.
Abstract W P270: Impact of a Family Participation Program on Perceived Respect, Collaboration and Support
Authors: Milkosky Debra , Durand Deborah , Reehil Diane
Published: July 2021

Background/Issues:
Strokes are the leading cause of disability in the United States. Family centered care is a delivery model that can remove barriers to family participation in care.

Purpose:
To evaluate the impact of a family participation program on perceived respect, collaboration and support of family members of Intensive Care Unit (ICU) stroke patients.

Methodology:
This study was an experimental, post-test only design. The control group included 35 family members of stroke patients in the ICU who received usual care. The intervention group included 36 family members of ICU stroke patients who received an educational program on stroke care, instructions on providing safe care, and strategies to facilitate family participation. Study outcomes included family perception of respect, collaboration and support.

Results/Lessons learned:
The majority of family members were female (72.1%), children of patients (56.3%) and had previous experience with a family member in ICU (63.8%). Most patients had an ischemic stroke (62.0%) and were discharged to sub-acute/nursing home care (32.4%) and home (29.6%).

Characteristics of the study sample were similar for both groups except that there were more male family members in the control group (40.6% vs. 16.7%).

In a bivariate analysis, as one of the elements of collaboration, family members in the intervention group perceived that they were significantly less overwhelmed by the information given to them than those in the control group (24.2% vs. 63.6%; X
2
=10.40; p=.001). The perception of family members’ respect, collaboration and support experienced by each group was not statistically significantly different. Children caring for their parents had significantly lower perception of respect and collaboration than other types of family members.

Conclusions:
Families in both groups had similar levels of perceived respect, collaboration and support. Usual care in the ICU may already meet these family expectations. However, future studies are needed to examine the effectiveness of family participation among children of patients, who seem to have the lowest levels of perception of respect, collaboration and support.
Abstract W P275: Minimizing Door to Needle Times for Administration of rt-PA in Acute Ischemic Stroke
Authors: Videtto Catherine J , Finnegan Maryjane , Thomson Donna
Published: July 2021

Background:
A substantial opportunity exists to improve timeliness of IV rt-PA bolus administration within desired 60 minutes of Emergency Department triage presentation time in Ischemic Stroke patients. In 2010 only 21.4% (3/14) of eligible patients presenting to our 250 bed non-academic nonprofit community hospital received the IV rtPA bolus within time this time target.

Purpose:
The purpose of this study was to demonstrate that implementation of best practices shown to minimize door-to-needle (DTN) time for administration of rt-PA in eligible Ischemic Stroke patients will result in significant improvement in percentage of patients receiving rtPA within 60 minutes of Emergency Department arrival.

Methods:
A review of published data showing successful improvement methods to minimize DTN times was compiled to develop clinical practice guidelines which were implemented to increase staff commitment to implementation of best practices. Each thrombolytic stroke case was reviewed by members of Stroke Steering Committee throughout 2011, 2012 and 2013 to identify root causes contributing to delays, which allowed rapid performance data feedback to team members.

Results:
The baseline DTN time for 2010 of 89.4 minutes, decreased to 68.8 minutes in 2011, and achieved a mean of 61 minutes in 2012 with 17/26 patients, or 65% of patients receiving IV rtPA within 60 minutes of arrival time. During Q1 and Q2 2013, 100% of the six eligible ischemic stroke patients presenting at this hospital received IV rtPA in less that 60 minutes.

Conclusions:
Significant improvement in compliance for under 60 minutes DTN time for IV rtPA administration can be achieved with implementation of published best practices which encompasses collaboration with emergency medical system personnel to ensure rapid assessment for stroke signs and symptoms and pre-notification of our hospital to allow early activation of Laboratory and Imaging Department staff to ready for potential thrombolytic stroke patients, utilization of “thrombolytic stroke box” to facilitate prompt preparation of IV rtPA weight-based dose, and leveraging newly implemented electronic medical record to minimize documentation time.
Abstract W P277: Specialized Teams React on Key Examinations: The Impact of Triage in Acute Ischemic Stroke
Authors: Phillips Jennifer , Wright Leesa , Roberts James , Walther Ray , Wahba Mervat , Al Wafai Ameer , Lennon Joshua , Elijovich Lucas
Published: July 2021

Specialized Teams React On Key Examinations:
The Impact of Triage in Acute Ischemic Stroke

Category:
Emergency Care/Systems

Background and Purpose:
The Brain Attack Coalition recommends the initiation of thrombolytic therapy in ischemic strokes within 60 minutes of hospital arrival. Poor compliance in our Emergency Department with door to needle (DTN) challenged us to identify care strategies to rapidly identify, evaluate, and implement care in the acute stroke population. In 2012, we integrated resources caring for ST Elevation Myocardial Infarctions (STEMI) and acute strokes to form the Time is Tissue unit that would result in improved compliance.

Methods:
Specialized training was provided to Emergency Medical Services (EMS) and the STEMI unit staff in acute stroke recognition and care. Acute stroke patients identified by EMS bypassed standard triage and the Time is Tissue unit was responsible for care from arrival through disposition.

Results:
A retrospective and concurrent chart review was performed from January 2011 to June 2013 on 232 patients (100%) receiving rt-PA. The research confirmed that specialized teams increased compliance for DTN. An unexpected finding was rt-PA volume increased 117% when comparing 2011 to 2012 without a significant change in presenting ischemic stroke volume.

Conclusion:
Our strategy of aligning processes and utilizing specialized teams to meet time and quality goals resulted in exceptional gains in the volume of patients identified to receive rt-PA and improvement in DTN times.
Abstract W P284: Stroke CORE Measure Data Submission to CMS: Process Improvement Initiative
Authors: Richetts Renee , Clarkson-Afshar Katherine , Olson-Mack Lindsay , Berger Lynn , Bajkiewicz Christopher , Cantonis Matthew
Published: July 2021

Background:
As of January 2013, CMS required hospitals to submit Stroke CORE Measure data on all discharged patients in order to be eligible for full reimbursement in Federal Fiscal Year (FFY) 2014. Failure to do so results in a payment reduction to hospitals. Furthermore, rapid-change-cycle and continuous quality improvement programs suggest that a rapid communication feedback approach can improve compliance with evidence-based practice. To meet impending data-reporting and fiscal challenges, the 5 campus hospital organization implemented strategies in Aug-Dec 2012 to: reduce labor costs related to stroke core measure reporting without increasing risk to full CMS reimbursement; and decrease the FY 2012 lag time between patient discharge, and communication of core measure compliance to clinicians. The purpose of this study was to determine if: (1) savings in labor dollars were achieved; (2) risk of CMS payment reduction did not increase; and (3) reduction in time from discharge to internal reporting was achieved.

Methods:
Minutes/case abstraction of CORE Measures were directly measured for all inpatient stroke cases discharged in October, 2012/60 minutes. Number of hours was multiplied by the cost of labor/hour to establish a labor cost/case baseline. Time/case was reassessed in April, 2013. Successful submission of data to CMS Jan-March, 2013 was determiner of risk. Retrospective review of May -July, 2012 was used to establish a comparative baseline (equal to 65 days). Days from discharge until data resulted to clinician were audited from January-March, 2013 using quality control tool. Goal was set at 21 days or less.

Results:
In the time period analyzed, the labor cost related to time spent abstracting each case was reduced by 20%. Risk of failure to follow CMS public reporting rules was not increased, and the first quarter (Jan-March 2013) results were submitted/accepted by CMS with no quality control issues. During the time period reviewed, the days from patient discharge to internal reporting of compliance results was reduced from 65 to 21 or less.

Conclusion:
The process improvement strategies achieved all goals and clinical improvements during the period reviewed. The sustainability of these results is the subject of on-going, quarterly reassessment.
Abstract W P292: A Comparative Analysis of the Requirements for Certification of Stroke Programs, by Type and by Nationally Recognized Certifying Body
Authors: Lang Stacey
Published: July 2021

Background and Purpose:
There are currently three main, nationally recognized organizations that certify facilities as primary or comprehensive stroke centers. One of these organizations also offers a “Stroke Ready” designation. While each of these organizations share many of the same requirements, there are likewise many unique requirements between certifying bodies with respect to the certification requirements, process, performance, and on-going expectations. All should be considered when choosing a partner for certification by organizations that are committed to achieving an appropriate level of certification as determined by clinical capabilities. Differences in core measure requirements and definitions, data collection expectations and re-certification cycles among other factors are often overlooked when stroke program leaders are identifying the best certification partner for their particular organization. This poster will detail the similarities and differences among the various stroke program certifying organizations and present a detailed methodology to assist program leaders with the partner selection process.

Methods:
The three stroke program certifying organizations were examined for review cycles, levels of certification offered, requirements related to hospital certifications, and reportable core measures. Other factors such as cost, the actual certification process, and other considerations that may impact the successful achievement of certification within a particular organization were also reviewed.

Results/Conclusion:
While there are many similarities in the stroke center certification requirements and processes among the three certifying organizations, there are also significant differences. In order to ensure that the end product of a journey to certification will align with a hospital’s values, budget, and vision for the stroke program, an evaluation process in advance of certifying body selection is essential. Awareness of the similarities and differences among the stroke certification organizations can facilitate a hospital’s decision-making process for pursuit of certification as a stroke ready center, primary stroke center or comprehensive stroke center
Abstract W P296: Establishing a Stroke Protocol Based on the Trauma Model
Authors: Blosky Mary Ann , Raposo E. Andrew
Published: July 2021

Background and Purpose:
In the summer of 2012, the state of Pennsylvania adopted legislation mandating EMS providers to deliver all patients with clinical signs of stroke to a certified stroke center for evaluation. In response to this change, development of a new stroke program began at a tertiary medical center located in the northeastern region of the state. The facility was a certified trauma center and also held various other disease specific certifications through the Joint Commission. This project sought to examine the needs of a newly developing primary stroke center within the context of a healthcare organization with numerous other specialized medical and surgical programs. Specifically, the investigators hoped to illustrate the similarities between stroke and other specialized services to demonstrate that many of the requirements of these programs are shared.

Method:
The site stroke clinical coordinator and system stroke program coordinator kept detailed records of all phases of stroke program development. As resource needs were identified, notation was made indicating whether or not those resources were already available in the hospital. By examining these records, the coordinators were able to identify how many of the resources needed to develop an effective stroke program were already present within the system.

Results:
Information was collected beginning at the inception of program development in 2012 through the time of application for Joint Commission Primary Stroke Center certification in August of 2013. During these 9 months, many of the needed resources were found to already exist in the facility, with most having been created or added as a result of the hospital’s trauma program development several years earlier.

Conclusion:
The hospital was able to develop a high performing stroke center with comparative ease due to the preexisting resources from the institution’s trauma program. It is the belief of the stroke team that these results could be easily duplicated in other facilities with trauma services that wish to expand into stroke specialization as well.
Abstract W P304: Variation in Use of Carotid Revascularization Procedures and In-Hospital Mortality Among Large, Urban Teaching Hospitals in the United States
Authors: Lichtman Judith H , Leifheit-Limson Erica C , Wang Yun , Howard Virginia J , Goldstein Larry B
Published: July 2021

Background:
Guidelines and quality improvement efforts seek to minimize variation in care and outcomes across hospitals. We assessed hospital-level variation in procedure rates and in-hospital mortality for patients hospitalized with ischemic stroke at similar hospitals in the US. The use of procedures and in-hospital mortality were not expected to vary significantly among comparable, high-volume facilities after adjusting for patient case-mix.

Methods:
We selected urban teaching hospitals with ≥100 annual ischemic stroke discharges (ICD-9 433, 434, 436) from the Nationwide Inpatient Sample 2010-2011. Generalized linear mixed models were used to quantify between-hospital variation in the use of carotid artery stenting (CAS) and endarterectomy (CEA), as well as in-hospital mortality, adjusting for patient characteristics. Adjusted odds ratios were calculated to reflect the odds that patients would have the procedure/outcome when treated at hospitals 1 SD above relative to hospitals 1 SD below the overall rate for that procedure/outcome (an odds ratio of 1.0 would reflect no hospital variation in the procedure/outcome).

Results:
A total of 105 urban teaching hospitals were selected, with a median annual volume of 453 ischemic stroke discharges (IQR 351-600). Among a total of 52,090 ischemic stroke discharges (mean age 68±14.8 yrs), the overall rates were 3.7% (SD 3.1) for CAS and 15.6% (SD 8.0) for CEA; in-hospital mortality was 4.3% (SD 1.7). The odds of receiving CAS and CEA were almost 7 and 4 times as high, respectively, for a patient treated at a hospital 1 SD above versus 1 SD below the overall rate for that procedure (CAS: 6.68, 95% CI 4.97-8.98; CEA: 3.62, 95% CI 3.17-4.13). The odds of dying for those treated at a hospital 1 SD above relative to 1 SD below the overall mortality rate were 2.09 (95% CI 1.98-2.21).

Conclusions:
There was marked between-hospital heterogeneity in the use of carotid revascularization procedures and in-hospital mortality among large, urban US teaching hospitals. Future research needs to identify system-level factors contributing to these variations in care and outcomes.
Abstract W P306: Identifying Stroke Researcher Challenges to Minority Inclusion in Clinical Research
Authors: Carman Heather , Quarles Leigh , Southwick Lauren , Benn Emma K , Waddy Salina P , Farrar-Edwards Dorothy , Boden-Albala Bernadette
Published: July 2021

Background:
Race-ethnic disparities exist in stroke incidence, recurrence and mortality. Minority participation in stroke clinical trials is staggeringly low. A significant literature describes patient-reported barriers to recruitment, but researcher barriers are not well documented.

Aim:
To assess stroke researcher best practices and challenges to minority inclusion in stroke trials.

Methods:
The National Initiative for Minority Involvement in Neurological Clinical Trials (NIMICT) uses a mixed methods approach including surveys, focus groups and key informant interviews to expand on understanding of minority recruitment and retention in stroke clinical trials. We designed and tested a 40-item survey based on literature review and used the results to inform semi-structured focus groups and key informant interviews among stroke clinical trial investigators (N=110).

Results:
Key stroke investigators, identified through the Princeton Conference, were invited via email to participate in the survey. Over 70% (n=93) responded: 68% White. Less than half (N=43) reported actively setting recruitment goals for minority inclusion. Only 37% (N=29) required cultural sensitivity training for recruitment staff. Over 80% reported treating adults unable to consent and were concerned about acute stroke time constraints negatively impacting patient/family participation decisions. Key themes from focus groups (N=17) included: 1) Role of government in defining valid minority sub analyses and enforcing existing inclusion guidelines; 2) Challenges unique to acute setting including consent in conditions of prognostic uncertainty; 3) Lack of scientific/research literacy in the lay population; 4) Lack of community engagement including Primary Care Physicians; 5) Lack of cost data to adequately budget for inclusion efforts. Best practices included health literate consent forms, cultural competency, and motivational interview training for coordinators.

Conclusion:
NIMICT’s mixed methods approach contributes new perspectives on unique challenges in stroke clinical research. These findings will inform strategies to improve minority recruitment and retention among neurological clinical trials.
Abstract W P311: Demographic and Regional Characteristics Associated With Advanced Primary Stroke Center Designation
Authors: McDonald Catherine , Cen Steven , Ramirez Lucas , Mack William J , Sanossian Nerses
Published: July 2021

Background:
Nationwide less than a third of eligible hospitals have achieved advanced certification in stroke, and there may be disparities affecting less affluent areas serving a higher proportion of minorities. We aimed to characterize demographic and regional factors associated with achievement of stroke center certification while controlling for hospital characteristics.

Methods:
We linked the 2011 American Hospital Association survey of hospital characteristics to the 2010 national census for population and household data by region. Emergency medical services stroke routing data was obtained from communication with state and county contact. Only hospitals with ≥ 25 beds and 24-hour emergency departments were evaluated. The Joint Commission, Healthcare Facilities Accreditation Program and DNV Healthcare websites were used to determine certification status of each hospital. We controlled for hospital bed size, teaching affiliation (AMA, ACGME), emergency department volume, rural designation, hospital type (governmental/for-profit/nonprofit), and trauma center designation in analysis.

Results:
Of the 3696 hospitals to complete the survey, the 3069 fulfilling study criteria included 908 PSC (31%) and 2161 non-PSC. In univariate analysis PSC hospitals were located in areas with greater population in immediate vicinity (29, 316 vs. 20,901, p<0.0001), greater proportion of minorities (73% white, 16% black, 15% Hispanic vs. 80%/12%/11%, p<0.0001), greater number of households per zip code (11,540 vs. 8050, p<0.0001) and a higher regional mean income ($52,112 vs. $46,262, p<0.0001) and higher home value ($234,000 vs. $170,000, p<0.0001). More PSC hospitals were located in regions with preferential EMS routing of stroke (52% vs. 40%). While controlling for hospital-based factors, the demographic and regional factors independently associated with hospital PSC designation were number of households per zip code (per 1000 households OR 1.1, 95%CI 1.0-1.2), increasing Hispanic population (every 10% increase OR 1.1, 1.0-1.2), and income per household (per $10,000 OR 1.2, 1.1-1.3).

Conclusions:
Hospitals achieving PSC designation are located in more affluent and densely populated areas with higher population of Hispanic residents.
Abstract W P317: Pan-London Simulation Training for Hyperacute Stroke
Authors: Birns J , Jaye P , Roots A , Reedy G , Ross Alastair
Published: July 2021

Background:
City-wide re-organisation of stroke care in London, incorporating 8 hyperacute stroke units (HASUs), has improved thrombolysis rates and survival cost-effectively. Continued staffing of HASUs requires stroke-specialist training to develop competencies for managing neurological emergencies. Simulation training provides an education platform for health care professionals to become immersed in realistic scenarios where outcome is dependent upon technical and non-technical skills.

Methods:
A standardised, curriculum-mapped, high-fidelity, simulation-training programme was developed on 4 HASUs for city-wide staff to attend. Learning outcomes included technical (acute stroke assessment/management) and non-technical skills (including time management/decision-making/teamwork). A mixed-methods evaluation approach was used to evaluate data from participants before, during, and after training.

Results:
Over a 2 year period, 152 HASU staff (70 medical; 82 nursing) participated. Quantitative analysis showed a pre/post-course increase in candidates’ ability to manage emergency stroke situations (t=6.6, p<0.001), leadership skills (t=6.7, p<0.001) and communication skills (t=3.7, p<0.001), more so in junior compared with senior clinicians. Simulation training was enjoyable (mean (SD) rating 5.7(2) on 7 point Likert scale), with higher ratings from doctors compared with nurses (t=3; p<0.01). Enjoyment correlated positively (r=0.853; p<0.001) and previous experience of simulation correlated negatively (r=-0.228; p<0.05) with relevance to clinical practice. Thematic analysis of post-course semi-structured interviews demonstrated 5 important learning outcomes (assertiveness; calling for help; situational awareness; teamwork; verbalising thoughts) and 3 main responses for transference to practice (general enthusiasm with no particular practical change; immediate recognition of an emergency situation providing recall of the course; reflective change).

Conclusion:
Simulation training may be effective in helping achieve HASU-specific learning outcomes and may be delivered in a standardised manner across multiple sites.
Abstract W P328: Comparative Analysis of Two Methods to Score the modified Rankin Scale: Rankin Focused Assessment and Simple modified Rankin Scale Questionnaire
Authors: Patel Richa D , Starkman Sidney , Conwit Robin , Hamilton Scott , Chatfield Fiona , Saver Jeffrey
Published: July 2021

Background:
The modified Rankin Scale (mRS) of global disability is the most common primary endpoint in acute stroke clinical trials. Since intuitive scoring of the mRS yields only modest inter-rater reliability, more formal scoring methods, with improved reliability, have recently been developed, but little compared.

Methods:
The Rankin Focused Assessment (RFA) is a formally operationalized, rater-scoring method using all available data, including patient and caretaker reports, medical records, and direct patient exam. The simple modified Rankin Scale questionnaire is a formally operationalized, patient report-based scoring method. We obtained 3 month mRS scores using the RFA and smRSq in consecutive patients enrolled in the NIH FAST-MAG trial.

Results:
Among 143 patients assessed at 3 months, the mean age was 66.9 (range 40-89+), 48.2% were female, and stroke subtype was ischemic in 70.6%. Amongst living patients, 3-month assessments were performed in person in 95% and by phone in 5%. With the RFA, mean mRS score was 2.2 and with the smRSq 2.1. The two instruments showed high general rates of agreement amongst all patients: raw percent agreement was 117/143 (84.0%), weighted kappa 0.92 (95% CI 0.89-0.95) and unweighted kappa 0.82 (95% CI 0.75-0.88). Agreement was modestly higher for in person than for phone visits (weighted kappa 0.93 vs 0.77). Of the 26 discrepancies in scoring, 18 (69%) had higher and 8 (31%) lower disability scores with the RFA than with the smRSq. Content analysis of discrepant scores indicated the RFA had greater sensitivity to aspects of disability under-captured by patient self-report.

Conclusion:
The RFA and the smRSq show excellent convergent validity as tools to score the modified Rankin Scale. The findings of this study suggest that both are useful and have distinct advantages: the smRSq has greater ease of administration due to its brevity and the RFA has greater clinical validity with sensitivity to all sources of disability.
Abstract W P345: Increased Risk of Gastrointestinal Bleeding Associated With Antiplatelet Therapy in Patients With Cerebral Small Vessel Disease
Authors: Noh Sang-mi , Kim Jong S.
Published: July 2021

Background:
Gastrointestinal (GI) bleeding is a major complication of aniplatelets in patients with stroke. Although underlying gastrointestinal disease is an important factor for increased bleeding risk, the presence of cerebral small vessel disease (SVD) may also be a factor because it may indicate systemic small vessel pathologies. We assessed the association of cerebral SVD and GI bleeding in patients who are under treatment with antiplatelets for secondary stroke prevention.

Methods:
We compared stroke patients who visited our clinic between May 2007 and May 2013 who developed GI bleeding while receiving antiplatelets with age and sex matched patients who did not. Control subjects were randomly selected among those who were visited out-patients clinic on the same day as the study subjects. Patients who received anticoagulants were excluded. MRIs were evaluated for the presence of white matter changes (Fazeka scale) and microbleeds.

Results:
During the study period, 47 patients in the bleeding group and 94 patients in the control group were enrolled. No differences were found in baseline characteristics between the two groups including stroke subtypes and the number of antiplatelets (mono vs dual therapy). The prevalence of SVD (microbleeds or white matter hyperintensities) (p = 0.004), white matter hyperintensities (p = 0.008), but not microbleeds alone (p = 0.221), were significantly higher in the bleeding group. Multivariate analysis showed that the presence of SVD was independently associated with increased GI bleeding risk (OR 3.3, 95% confidence interval 1.5-7.3).

Conclusions:
Our data show the presence of cerebral SVD is a marker for increased GI bleeding risk in patients receiving antiplatelets in stroke patients, perhaps related with systemic small vessel pathology in this group of patients. Physicians may have to consider this association when antiplatelets are used for the secondary prevention of stroke.
Abstract W P360: A Hypertensive Reversible Encephalomyelitis Syndrome (HyRES)
Authors: de Havenon Adam , Joos Zachary , Longenecker Lauren , Shah Lubdha , Ansari Safdar , Digre Kathleen
Published: July 2021

Introduction:
Six patients have been described in the published literature with a clinical and radiographic presentation consistent with posterior reversible encephalopathy syndrome (PRES), but who also had extensive spinal cord lesions on MRI. We add two additional cases and after analyzing all eight cases have discovered characteristic patterns. In light of the already wide definition of PRES, we propose a new syndrome named hypertensive reversible encephalomyelitis syndrome or HyRES.

Methods:
We searched the Medline database using the terms “spinal PRES” and “spinal hypertensive encephalopathy,” which led to the identification of four case reports, that referenced another two cases. We analyzed these six cases in addition to our two cases.

Results:
Average age was 31 with five male and three female. All patients had severe acute hypertension and a longitudinally extensive myelitis with a confluent, expansive central cord T2 hyperintensity greater than 4 spinal segments in length, always involving the cervical spine. (see Figure 1) Almost all patients had hypertensive retinopathy (7/8), a favorable clinical course with only antihypertensive treatment (7/8), and resolution of the spinal cord lesions on follow-up imaging (7/8). Half of the patients had symptoms referable to the spinal cord lesions. Many of the features that are commonly seen in classic PRES were not present, such as seizure (0/8).

Conclusion:
HyRES shares clinical, radiographic, and, presumably, pathophysiologic attributes with PRES, but is a unique and consistent entity. Clinicians should suspect HyRES when patients with PRES have neurologic signs referable to the spinal cord or MRI lesions that extend to the cervicomedullary junction. It is important that clinicians and radiologists identify HyRES when they are considering, working up, or treating other causes of longitudinally extensive myelitis, which can have significant morbidity.
Abstract W P365: Critical Role of Smooth Muscle Cell Phenotypic Modulation in Cerebral Aneurysm Formation and Rupture
Authors: Starke Robert M , Ali Muhammad S , Chalouhi Nohra , Jabbour Pascal M , Tjoumakaris Stavropoula I , Gonzalez L. Fernando , Rosenwasser Robert H , Hasan David , Hashimoto Tomoki , Greig Nigel H , Owens Gary K , Dumont Aaron S
Published: July 2021

Objective:
Little is known about smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. TNF-α has been associated with aneurysms, but a direct role has not been established.

Methods:
Cultured cerebral SMC were treated with TNF-α for PCR, western blot, chromatin immune-precipitation (CHIP), and adenovirus promoter transfection.
In vivo
experiments were carried out in the following models: application of TNF-α to the surface of carotid arteries, cerebral model of hypertension and hemodynamic stress, and cerebral model of aneurysm formation and rupture. The TNF-α inhibitor 3,6’dithiothalidomide (DTH) was synthesized.

Results:
Cultured cerebral SMC over-expressing myocardin induced expression of key SMC contractile genes (SM-α-actin, SM-22α, SM-MHC), while dominant negative suppressed expression. TNF-α treatment inhibited this contractile phenotype and induced pro-inflammatory genes (MCP-1, MMPs, VCAM-1, IL-1β). TNF-α increased expression of KLF4 and KLF4 siRNA abrogated TNF-α induced phentotypic modulation. These mechanisms were confirmed
in vivo
following exposure of rat carotid arteries to TNF-α and early in a model of cerebral hypertension and hemodynamic stress prior to cerebral aneurysm formation. Treatment with DTH reversed these pathological vessel wall alterations. TNF-α knock-out mice and DTH pre-treatment decreased the incidence of aneurysm formation and rupture. As compared with sham mice, TNF-α expression was not significantly different in TNF-α knock-out mice or those pre-treated with DTH, but was elevated in unruptured and ruptured aneurysms. Initiation of DTH 7 days after aneurysm induction did not alter aneurysm incidence, but resulted in stabilization and decreased rupture. CHIP assays
in vivo
and
in vitro
demonstrated that TNF-α promotes epigenetic changes through KLF4 dependent alterations in promoter regions of myocardin, SMC’s, and inflammatory genes.

Conclusion:
TNF-α induces phenotypic modulation of cerebral SMC through myocardin and KLF4 regulated pathways. These results demonstrate a novel role for TNF-α in promoting a pro-inflammatory phenotype. These data suggests a critical role of TNF-α in the formation and rupture of aneurysms.
Abstract W P46: Permeability Surface Product as a Predictor of Hemorrhagic Transformation in Acute Ischemic Stroke Intervention
Authors: Parker Matt , Matthews Andrew , Rutledge Neal , Conrad Kirk , Luci Jeff
Published: July 2021

Introduction/purpose:
A significant complication in the intervention of acute ischemic stroke is hemorrhagic transformation (HT). It has been postulated that perfusion permeability imaging showing increased blood brain barrier permeability can be used to predict hemorrhagic transformation and possibly alter therapies.

Materials and Methods:
We retrospectively reviewed 1040 sequential CT perfusion scans with permeability surface area product maps calculated using the Patlak model for all patients that exhibited stroke like symptoms between October 2011 and November 2012. The size of the permeability surface product was ranked on a qualitative three-part scale of small, moderate and large permeability changes. A change smaller than 25% of the image was considered a small result. A moderate result is a permeability change that is approximately 25% of the image. A large permeability change exceeds 25% of the image. Follow up non-contrast CT images (>24 hours but <15 days after initial perfusion imaging) were used to determine if HT had occurred in the cases where an increase in permeability surface product was observed.

Results:
There was a positive increase in permeability maps in 142 of the 1040 cases. The size of the permeability change was moderate to large in 101 of the positive cases (71%). Hemorrhagic transformation was observed in 12 patients that showed an increase in permeability surface product (8.4%). Of the cases that resulted in HT, nine (75%) resulted in an HI1 and HI2 subtypes. There were three (25%) of the more severe parenchymal hemorrhages (PH1, PH2) observed. Out of the 12 positive hemorrhagic transformations four (33%) were treated with iv-TPA and two (17%) received endovascular thrombectomies, while six (50%) did not receive TPA or endovascular intervention. Of the major parenchymal hemorrhages (PH1/2) two occurred after iv-TPA treatment of the stroke, with the other arising after endovascular thrombectomy. No difference was found in the size or degree of the permeability changes and the incidence of HT.

Conclusions:
Elevated permeability on CT perfusion imaging had no relevant predictive value for hemorrhagic transformation in acute ischemic stroke at our institution.
Abstract W P47: Recanalization After IV TPA Alone Among Acute Ischemic Stroke Patients Treated With Combined IV-Endovascular Recanalization: Impact of Arterial Occlusion Site
Authors: Kim Seo Hyun , Liebeskind David , Jahan Reza , Starkman Sidney , Ali Latisha , Rao Neal , Hinman Jason , Vespa Paul , B. Blanco Manuel , Modir Royya , Tansy Aaron , Vinuela Fernando , Duckwiler Gary , Tateshima Satoshi , Gonzalez Nestor , Saver Jeffrey L.
Published: July 2021

Background:
Combined IV TPA and catheter-based reperfusion is an emerging treatment strategy for acute ischemic stroke. Both patient care and clinical trial design would be enhanced by delineation of which patients rapidly respond to IV TPA alone, before endovascular therapy can be initiated.

Methods:
In a prospectively maintained registry of patients treated under a general policy of combined IV TPA and endovascular therapy, we analyzed subjects with MRA/CTA-confirmed anterior circulation occlusions prior to IV TPA start.

Results:
Among 118 patients meeting study entry criteria, age was mean 71.5 (SD 14.5), 53.0% were female, and baseline NIHSS was 14.4 (SD 7.1). Confirmed sites of occlusion prior to IV TPA were internal cerebral artery (ICA) in 22.9%, M1 segment of middle cerebral artery (MCA) in 50.0%, and M2-3 in 27.1%. Among patients undergoing catheter cerebral angiography, median time from start of IV TPA to diagnostic catheter angiogram was 75 mins (IQR 50-113). A total of 48 (40.7%) patients achieved partial or complete recanalization (AOL 2-3) of the initial target artery with IV TPA alone (partial in 22 (18.6%) and complete in 26 (22.2%)); an additional 44 (37.3%) achieved partial or complete recanalization after endovascular therapy. Recanalization rates after IV TPA alone varied by target occlusion site: ICA - 22.2%, M1 - 40.7%, and M2-3 - 56.2%. In multivariate logistic regression analysis, independent predictors of recanalization with IV TPA alone were: M2-3 clot location, OR 3.04 (95% CI 1.20-7.73, p=0.019) and TOAST etiology large-artery atherosclerosis, OR 0.14 (CI 0.04-0.50, p = 0.003). Good outcome (mRS ≤ 3) rates at 3 months were 76.6% among recanalizers with IV TPA alone and 47.5% among recanalizers after both IV TPA and catheter therapy.

Conclusions:
When combined IV-endovascular treatment is pursued, recanalization with IV TPA alone occurs in 4 out of 10 patients before catheter therapy is started, is more common with more distal clot location, and is associated with a high rate of excellent clinical outcomes.
Abstract W P54: Renal Impairment in African American Stroke Patients and the Risk of Symptomatic ICH With Systemic tPA
Authors: Shiue Harn J , Sands Kara A , Bavarsad Shahripour Reza , Bitaraf Saeid , Alexandrov Andrei V
Published: July 2021

Background:
Uremia is a bleeding risk in chronic kidney disease (CKD) that has a higher prevalence among African Americans (AA). Recent studies in predominantly Caucasian populations showed that impaired renal function did not increase the risk of symptomatic intracranial hemorrhage (sICH) with intravenous tPA for acute ischemic stroke. We sought to determine if the risk of sICH is higher in AA patients with CKD at our institution.

Subjects & Methods:
Consecutive patients who received intravenous thrombolysis at our comprehensive stroke center were retrospectively analyzed. Demographics, stroke severity, and instances of sICH were recorded. Renal function was assessed by creatinine clearance (CrCl) and estimated with the Cockcroft and Gault equation. CKD was defined as CrCl < 60. CrCl was further stratified into the following groups: 59 - 30, 29 - 15, and < 15 ml/min.

Results:
We identified 236 patients with reported CrCl who received tPA at our institution (mean age 65+/-17 SD, 46% women, pre-treatment median NIHSS 5; IQR 8) and CKD was documented in 90/236 (38%) of all tPA-treated patients. AA patients comprised 36% (86/236) of the study population with 37 (43%) diagnosed with CKD, p=0.23 AA vs rest. Among all patients with CKD (n=90), 83% had CrCl between 59 - 30 ml/min, 9% had 29 - 15 ml/min and 8% had <15 ml/min CrCl range. sICH occurred in 2/90 (2.2%) of all patients with CKD (both in 30-59 ml/min group) compared to 4/146 (2.7%) without CKD (NS). sICH among AA patients with or without CKD was 2.7% and 2% respectively (NS).

Conclusions:
Our data are consistent with previous studies that severe renal impairment did not result in higher risk of sICH since the enzymatic activity of tPA may be limited by uremia. Although limited by relatively small numbers, our analysis did not show an increased sICH risk due to any renal impairment or AA race.