bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 27: Opioid Use Strongly Increases Incidence of Acute Kidney Injury in Patients With Acute Ischemic Stroke: An Analysis of 3.4 Million Admissions
Authors: Dasari Tejasvi K , Shah Rohan M , Spinner Joseph A , Walther Carl
Published: March 2021

Background:
The relationship of opioid use with the incidence of acute ischemic stroke (AIS) and subsequent complications remains poorly understood. However, both opioid use and AIS have been independently associated with increased risk of subsequent acute kidney injury (AKI). In patients with AIS patients, AKI is associated with increased in-hospital and 10-year mortality. We evaluate whether opioid use in patients with AIS is associated with increased risk of AKI, near-term complications, mortality, and increased healthcare utilization.

Methods:
All records of patients within the Nationwide Inpatient Sample carrying a primary discharge diagnosis of AIS and secondary diagnosis of AKI between 2012-2014 were stratified by opioid status. The effect of opioid use on outcomes following AIS was analyzed after adjusting for confounders using logistic regression analysis.

Results:
Of 3,396,664 patients with AIS, 17,575 were diagnosed with an opioid-use disorder. There were 4,786 (27.2%) patients with AIS with opioid use that experienced in-hospital AKI compared to 426,823 (12.6%, p<0.01) patients without opioid use, despite patients with opioid use being younger (53 vs. 70 years, p<0.01) with fewer comorbidities, including CHD, CKD, hypertension, and diabetes. Patients with opioid use had longer hospitalizations (10 vs. 6.5 days; p < 0.01) and higher costs ($26,022 vs. $16,419, p < 0.01). Adjusting for confounding factors, opioid use among AIS patients was associated with an increased odds of AKI (odds ratio [OR]=2.0; 95% confidence interval [CI]=1.8-2.2; p<0.01), major bleed (OR=1.2; 95% CI=1.0-1.3; p=0.04), and in-hospital mortality (OR=1.3; 95% CI=1.1-1.5; p<0.01).

Conclusions:
We demonstrate that opioid use in patients with acute ischemic stroke is independently associated with twofold increased risk of AKI (27% vs. 12%, p<0.01; [OR]=2.0; 95% CI=1.8-2.2; p<0.01). As AKI is strongly associated with increased in-hospital and long-term mortality in patients with stroke, opioid use carries particularly significant implications for prognosis and management of the AIS population. Strategic measures designed to reduce incidence of AKI in AIS patients with opioid use may reduce complications, healthcare utilization, and mortality following stroke.
Abstract 28: The Representation of Women in Randomized Clinical Trials of Acute Stroke (2010-2020)
Authors: Strong Brent W , Pudar Julia , Thrift Amanda G , de los Campos Gustavo , Howard Virginia J , Hussain Murtaza , Reeves Mathew J
Published: March 2021

Introduction:
The inadequate enrollment of women in RCTs represents a threat to trial generalizability and potential inequities in access to novel treatments. We sought to determine whether women were under-enrolled in contemporary acute stroke trials.

Methods:
We searched MEDLINE for completed RCTs published in one of nine major journals between 2010 and 2020. Eligible studies were phase 2 or 3 trials undertaken to test therapeutic interventions within one month of stroke onset. For each trial we calculated the proportion of trial participants that were women (PPW). We used Global Burden of Disease (GBD) data to estimate the expected proportion of strokes occurring in women in the underlying stroke populations (PSW). We matched individual estimates from the GBD data to each trial based on geographic location, year, and stroke type. To quantify disparities, we calculated the enrollment disparity difference (EDD), defined as EDD = PSW - PPW. A positive EDD indicates that women were under-represented in the trial. We used random effects meta-analysis to pool individual EDDs and conducted subgroup analyses.

Results:
We identified 115 trials that met eligibility criteria. The random effects summary EDD was 0.053 (95% CI = 0.040, 0.053), indicating that women were under-enrolled in acute stroke trials by 5% relative to their representation in the underlying stroke population. However, there was substantial between-trial variability in the EDD (I
2
=84.4%). In subgroup analyses, the EDD was similar across subgroups except for stroke type (figure); trials that only included subarachnoid hemorrhages enrolled women in excess of their representation in the underlying population (summary EDD = -0.117 [95% CI = -0.150, -0.084]).

Conclusions:
Overall, women were modestly under-represented in contemporary acute stroke trials compared to their representation among all strokes. Further study is needed to elucidate factors driving sex differences in enrollment between RCTs.
Abstract 30: Sex Differences in Faculty Rank Among Academic Vascular Neurologists in the United States
Authors: Bliss Lindsay A , Vitellas Carol A , Challa Nayanika , Lee Vivien H
Published: March 2021

Introduction:
The lower proportion of women at the rank of full professor compared to men has been documented in nearly all specialties. Women are under-represented in academic stroke neurology, but there is limited data.

Methods:
We reviewed all 160 U.S. medical schools and the associated medical centers for vascular neurologists. An internet search of stroke team websites and neurology department websites was performed from August 1, 2020 to August 25, 2020. We included 117 academic medical centers that had at least 1 vascular neurologist on faculty. We included vascular neurology ABPN certified or board eligible (fellowship-trained) neurologists. Data was collected on sex, academic rank, and American Board of Psychiatry and Neurology (ABPN) certification status. ABPN board certification status was verified on the ABPN verify CERT website. Social medical women’s neurology groups were also queried for names of women full professor to cross check.

Results:
Among 540 academic ABPN vascular neurologists, 182 (33.8%) were women and 358 (66.3%) were men. Among academic ranks, women made up 108/269 (40.1%) of Assistant professors, 49/137 (35.8%) of Associate professors, and 25/134 (18.8%) of full professors. Twenty two academic centers had vascular neurology female professors on faculty, compared to 70 academic centers with male full professors on faculty. Twenty nine academic centers had multiple male professors on faculty compared to only 3 centers with multiple female full professors. Among women, 108 (59.3%) were assistant professor, 49 (26.7%) were associate professor, 25 (13.7%) were full professor. Among men, 161 (45.0%) were assistant professor, 88 (24.6%) were associate professor, and 109 (30.5%) were professor. There was a significant difference between academic rank based upon sex (p <0.0001).

Conclusion:
Among academic medical centers in the United States, significant sex differences were observed in academic faculty rank for ABPN vascular neurologists, with women less likely than men to be full professors. Further study is warranted to address the gender gap in the field of stroke.
Abstract 32: Residual Perfusion Deficit is Common Post Successful EVT and is Associated With Worse Clinical Outcome
Authors: Luby Marie , Ansari Saeed , Davis Rachel , Fisher Marc , Latour Lawrence , Sukhdeo Singh Rena , Wright Clinton B , Lynch John K
Published: March 2021

Introduction:
A significant portion of patients despite achieving successful recanalization following endovascular therapy (EVT) still have some residual perfusion deficit. The objective of this study was to identify the association of residual perfusion deficit with recanalization status and clot presence post EVT.

Methods:
Patients were included if they were evaluated at one of two comprehensive stroke centers from January 2015 through February 2018, had LVO of the anterior circulation, had baseline MRI pre EVT, and treated with EVT. Independent image reads by two separate readers blinded to target vessel, TICI score, and clinical outcome, evaluated the pre EVT, 2 hours, and 24 hours post EVT MRI for perfusion deficit and clot presence. The MTT and TTP maps post EVT were read separately for residual perfusion deficit, compared to the pre EVT perfusion deficit. Clot presence was read as susceptibility sign on GRE consistent with the vascular territory identified on the pre EVT PWI. Successful recanalization was defined as TICI 2b\3 in the IR suite. Early neurological improvement (ENI) was defined as a reduction of the admit NIHSS by ≥4 points or a score of 0-1 at 24 hours.

Results:
Fifty-eight patients were included with median age of 58 years, 55% female, 47% Black\African-American, median admit NIHSS of 19, 72% with M1 LVO, 69% treated with IV tPA, 79% achieved TICI of 2b\3, and 52% with ENI at 24 hours. All patients had a perfusion deficit pre EVT with 73% having a corresponding clot on GRE. Following EVT, 76% and 52% of patients had residual perfusion deficit at 2 and 24 hours post EVT, but only 24% and 13%, respectively, still had evidence of clot. For the 46 patients with successful recanalization, 41% still had some residual perfusion deficit at 24 hours, but only 9% still had clot, suggesting inadequate perfusion without a mechanical obstruction. The frequency of ENI at 24 hours was associated with complete reperfusion, 88% versus 46% (p=0.039) at 2 hours post EVT, and 76% versus 33% (p=0.002) at 24 hours post EVT.

Conclusions:
Residual perfusion deficit on post EVT MRI is common, even with successful recanalization, and is associated with poor outcome. Patients with residual perfusion deficit may benefit from early adjunctive therapy following EVT to improve outcome.
Abstract 4: Glucose Control and Risk of Tpa-Related Symptomatic Intracerebral Hemorrhage in Patients With Hyperglycemic Acute Ischemic Stroke: Preplanned Analysis From the SHINE Trial
Authors: Southerland Andrew M , Chiota-McCollum Nicole A , Conaway Mark R , Bolte Ashley C , Pauls Qi , Mayer Stephan A , Pettigrew Creed , Bleck Thomas P , Johnston Karen C
Published: March 2021

Introduction:
In acute ischemic stroke (AIS), hyperglycemia promotes enhanced blood brain barrier permeability, tissue acidosis, and oxygen free radicals, and may increase risk of post-tPA symptomatic intracerebral hemorrhage (sICH). We performed a pre-planned analysis from the SHINE trial (NCT01369069) to examine the effects of blood glucose (BG) control on post-thrombolysis ICH.

Hypothesis:
In AIS, (1) post-tPA BG measures are associated with sICH, and (2) intensive insulin therapy can reduce the risk of sICH.

Methods:
Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard BG control (80-179 mg/dL) over a 72-hour period. Randomization was stratified by tPA treatment. Three independent vascular neurologists reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIHSS. Associations between BG control and sICH were analyzed using a logistic regression model accounting for NIHSS, age, systolic blood pressure, onset to tPA time, and endovascular therapy. Associations were reported as odds ratios (95% CI). Categorical variables and outcomes were compared using the chi-square test (p < 0.05).

Results:
Of the 1151 SHINE participants, 725 (63%) received IV tPA (median age 65, 46% women, 29% Black, 18% Hispanic). Median NIHSS was 7, baseline BG 187 (IQR 153-247) mg/dL, and onset to tPA was 2.2 hrs (1.6-2.9). Post-tPA sICH occurred in 3.6% (3% intensive vs. 4.3% standard, OR 1.10, 95% CI 0.60-2.01, p=0.697). There was a consistent association between post-tPA BG measures and sICH. In the first 12 hours, every 10 mg/dL increase in median BG increased odds of sICH by ~8% (OR 1.08, 95% CI 1.03-1.14, p=0.004), and a greater percentage of BG measures 80-130 mg/dL decreased odds of sICH by ~11% (0.89, 95% CI 0.80-0.99, p=0.030).

Conclusion:
In this pre-planned analysis, intensive insulin therapy was not associated with a reduced risk of post-tPA sICH. However, post-tPA hyperglycemia was associated with a higher risk of sICH overall, particularly in the early post-treatment period. These data provide class IIa, level B-R evidence that post-tPA glucose levels between 80-130 mg/dL are associated with decreased risk of sICH.
Acknowledgments:
NIH-NINDS U01 NS069498.
Abstract 42: Epidemiological Surveillance of the Impact of the Covid-19 Pandemic on Stroke Care Using Artificial Intelligence
Authors: Nogueira Raul , Davies Jason , Gupta Rishi , Hassan Ameer E , Devlin Thomas G , Haussen Diogo C , Mohammaden Mahmoud , Kellner Christopher P , Arthur Adam S , Elijovich Lucas , Owada Kumiko , Dina Dina , Narayan Mukund , Mordenfeld Nadia , TEKLE WONDWOSSEN , NAHAB Fadi B , Jovin Tudor G , Don Frei Don Frei , Siddiqui Adnan , Frankel Michael R , Mocco J D
Published: March 2021

Background:
The degree to which the COVID-19 pandemic has affected systems of care, in particular those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence (AI) platform.

Methods:
Data were derived from the Viz Platform, an AI application designed to optimize the workflow of acute stroke patients. Neuroimaging data on suspected stroke patients across 97 hospitals in 20 US states were collected in real-time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of CTA, CTP, Large vessel occlusions (LVOs) (defined according to the automated software detection), and severe strokes on CTP (defined as those with hypoperfusion volumes>70mL) normalized as number of patients per day per hospital. Data from the pre-pandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling.

Results:
A total of 23,223 patients were included. The incidence of LVO on CTA and severe strokes on CTP were 11.2%(n=2,602) and 14.7%(n=1,229/8,328), respectively. There were significant declines in the overall number of CTAs (-22.8%;1.39 to 1.07 patients/day/hospital,p<0.001) and CTPs (-26.1%;0.50 to 0.37 patients/day/hospital,p<0.001) as well as in the incidence of LVO (-17.1%;0.15 to 0.13 patients/day/hospital,p<0.001) and severe strokes on CTP (-16.7%;0.12 to 0.10 patients/day/hospital, p<0.005). The sampled cohort showed similar declines in the rates of LVOs versus thrombectomy (18.8%vs.19.5%, p=0.9) and CSC hospitalizations (18.8%vs.11.0%, p=0.4).

Conclusions:
A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This underscores the broader application of AI neuroimaging platforms for the real-time monitoring of stroke systems of care.
Abstract 43: Endovascular Delivery of Low Dose Compound 21 is Neuroprotective Independent of Reperfusion in Ischemic Stroke
Authors: Waters Michael F , Ahmad Saif , Yin Junxiang , Kindelin Adam , Ducruet Andrew F , Hoda Nasrul
Published: March 2021

Background:
Intracerebroventricular (ICV) injection of angiotensin type 2 receptor (AT2R) agonists is neuroprotective in stroke. However, ICV delivery of a blood brain barrier impermeable AT2R agonists has limited utility in clinical stroke treatment. We investigated whether low dose endovascular (EV) delivery of a selective AT2R agonist, Compound 21 (C21), after stroke confers neuroprotection under various states of reperfusion.

Methods:
Aged male mice (12 mos) underwent either permanent middle cerebral artery ligation (pMCAL)(n=12) or spontaneously reperfusing embolic clot MCA occlusion (eMCAo)(n=10). Mice were randomized to EV-delivery of either C21 (1 μg/kg) or 10μL saline at the site of occlusion 2h post-stroke. Statistical significance was determined at p<0.05.

Results:
C21 treatment following pMCAL prevented infarct progression and significantly reduced stroke injury by >30% at 48h post pMCAL (p<0.02). In eMCAo stroke, C21 was effective in reducing both infarction volume and edema by >25% (p<0.01).

Conclusions:
We demonstrate that EV-delivery of C21 is effective in both non-reperfused and spontaneously reperfusing stroke. This site-specific delivery may have potential benefits as an adjuvant neuroprotectant combined with endovascular thrombectomy, while averting possible blood-pressure lowering risks associated with AT2R agonism. Of additional translational interest, the current COVID19 pandemic and related ongoing recombinant huACE2-trial therapies will eventually affect ATRs physiology. Given the prominence of thrombotic strokes in COVID19 patients, C21 as an AT2R agonist may be a potential therapy to test in COVID19-related thrombotic stroke models.
Abstract 46: An Innovative Approach to the Bedside Nursing Swallow Screening Tool: Can Be Used as a Trigger for an Inpatient Cognitive Evaluation to Improve Timeliness of Post-Discharge Cognitive Therapy Referrals
Authors: Punsalang Lorina , Rojas Brenda , Manalo Chriselda , Gaffney Denise , Lapsys Katherine , Cuenca Regina , Mkrtumyan Alvina , Quezada Maria Edith , Veit Miho , Cheng Pamela , Le Duy , Sangha Navdeep S , Ajani Zahra
Published: March 2021

Background:
According to the American Heart Association, a formal assessment of cognitive dysfunction caused by stroke is a level I recommendation. However, cognitive evaluation is often missed or overlooked in the inpatient setting. When and who performs the assessment is not well-defined. Stroke nurses can corroborate with clinicians in completing the Montreal Cognitive Assessment (MoCA) 8.1, a validated tool for assessing cognitive function in stroke patients.

Purpose:
The purpose of this study was to evaluate the process of using the bedside nursing swallow screen (NSS) as a trigger for an inpatient cognitive evaluation by the Speech Therapist (ST). This study was also used to determine if post-discharge cognitive therapy referrals were placed based on the MoCA scores.

Methods:
All STs completed the required MoCA certification. The new process was implemented in October 2019. Data were analyzed from October 2019 through March 2020. NSS was performed on newly admitted stroke patients. If failed, an ST consult was ordered for a dysphagia evaluation. However, if passed, a cognitive evaluation consult was triggered by the RN. MoCA was completed within 24 hours. The total possible score is 30; a score of 26 or above is considered normal. A MoCA score of 25 or less, prompted a post-discharge cognitive therapy referral.

Results:
229 patients were assessed, all of whom had an NSS completed. 120 (52.4%) passed the NSS, of which 85 (71%) completed a MoCA evaluation. 42 (49.4%) scored 25 or less, of which 35 (83.3%) were referred for a post-discharge cognitive therapy. 7 (17%) had no referral, of which 4 (57%) were discharged home to self-care; 2 (29%) discharged to other healthcare facility; and 1 (14%) left against medical advice.

Conclusions:
Repurposing the NSS as a standardized tool to trigger an inpatient MoCA evaluation was innovative, practical and efficient. Timely post-discharge cognitive therapy referrals were also evident on MoCA scores of 25 or less.
Abstract 50: Virtual Care via Mobile Application Using a Patient Electronic Health Record Portal is Feasible and Increases Stroke Patient Engagement - A Pilot Study
Authors: Pope Leslie , Buchinsky Kelly , Noah Patty , Hackett Chris , Cerejo Russell , Tayal Ashis H
Published: March 2021

Introduction:
Improving patient engagement in post-acute stroke cohort is challenging. Additional tools are necessary to help patients take an active role their health. Care Companion is an interactive patient engagement tool embedded within a patient’s EHR portal that can provide disease-specific education, symptom monitoring, medication reminders and patient self-reported outcomes. The application was created for patients within the existing Stroke Care Model who are followed for 90 days post-acute. As the first organization to pilot EPIC Care Companion for acute stroke patients, we aimed to evaluate the feasibility of a mobile application and its impact on patient engagement.

Methods:
We developed stroke specific content for Care Companion including automated alert parameters. Patients were selected based on co-morbidities, willingness and ability to participate and access to a mobile device. Individualized content was electronically sent to the patient via mobile device notifications at predetermined intervals. Patients responded to questionnaires, and input individualized data including blood pressure readings, exercise logs, glucose levels, and nicotine consumption. Patients were able to contact all members of the care team and request assistance to manage risk factors. Participants completed a Likert scale impact survey at day 90. We compared total number of patient-nurse navigator interactions between Care Companion users versus non-users with a t-test.

Results:
Since January 2020, 406 patients were enrolled in the Stroke Care Model and completed 90 days of follow up. We enrolled 39 patients in the pilot. Patient reported impact surveys were returned in 25 out of 39 patients (64% response rate). Most patients reported that it was easy to enroll in Care Companion (100%) and complete assigned tasks (96%). Patients found the educational content useful (91%) and made lifestyle changes based on the information (90%). Patients enrolled in Care Companion had significantly more interactions with their care team compared to non-enrolled patients (6.6 ± 4.6 vs 3.1 ± 1.9), p<.0001.

Conclusion:
Implementation of Stroke Care Companion was feasible and increased patient engagement with the stroke care team.
Abstract 51: Disposition of Female Stroke Patients: The Interaction of Age and Race/Ethnicity
Authors: Gaillard Trudy R , Vaccaro Joan , Starosciak Amy K , Belnap Starlie , De Los Rios La Rosa Felipe
Published: March 2021

Background:
A previous study found racial/ethnic disparities in disposition post-acute rehabilitation care. The aim of this study was to examine disposition by type of stroke, stroke severity and comorbidities (diabetes, hypertension, obesity) among older female stroke patients by race/ethnicity and age group after inpatient hospitalization.

Methods:
Data were extracted from Get With The Guidelines-Stroke from Baptist Hospital of Miami, April 2014-March 2019. The sample included non-Hispanic Black (NHB), Hispanic (HIS), and non-Hispanic White (NHW) female stroke patients categorized by age group: 65-74 (Y), 75-84 (M) and ≥85 years (O) and disposition to home or other care facility (skilled nursing or rehabilitation) (OCF), N =1587. Characteristics were presented by race/ethnicity with the chi-squared test and partial correlations. Differences in discharge to home or OCF was determined by logistic regression.

Results:
There were 27.3% NHB, 37.5% HIS, and 35.2% NHW, however, there were significant differences in age group by race for ≥85 years: 18.4% NHB, 36.0% HIS, and 40.1% NHW. The majority of women had health insurance (98.8%) with 3.0% NHB, 1.2% HIS, and 0.3% NHW with no insurance/self-pay (p=0.017). There was a race/ethnicity by age group interaction. Stroke type, stroke severity, and obesity were statistically significantly associated with disposition. Controlling for age, stroke severity was higher in NHB and HIS than in NHW (r=-0.66, p=0.008). Adjusting for insurance, stroke severity, stroke type, and other comorbidities, NHB-Y (OR=4.24, 1.5-11.6), NHB-M (OR=2.40, 2.22-4.76), HIS-Y (OR=4.26, 1.6-11.4), and HIS-M (OR=2.57(1.40-4.72) had higher odds of being sent to OCF compared to NHW-O.

Conclusion:
Disposition was based on medical determinants, such as age, stroke severity, stroke type and other comorbidities. This study demonstrated a statistically significant race/ethnicity by age group interaction for rehabilitation care after inpatient hospitalization for women in our facility. Continued research is warranted to increase our understanding of these interactions in racial/ethnic minority women.
Abstract 58: Silent Myocardial Infarction and Subsequent Ischemic Stroke in the Cardiovascular Health Study
Authors: Merkler Alexander E , Bartz Traci , Kamel Hooman , Soliman Elsayed Z , Howard Virginia J , Psaty Bruce M , Okin Peter M , Safford Monica , Elkind Mitchell S , Longstreth W T
Published: March 2021

Background:
Whether silent myocardial infarction (MI) is a risk factor for ischemic stroke remains uncertain.

Hypothesis:
Silent MI is associated with incident ischemic stroke.

Methods:
The Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age with follow-up through June 30, 2015. For this study, we included participants from the first study cohort (enrolled in 1989-1990) without prevalent stroke or baseline electrocardiographic (ECG) evidence of MI. Our exposures were silent and clinically apparent MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989-1999. Clinically apparent (overt) MI was adjudicated on the basis of information about chest pain, ECG changes, and cardiac enzymes. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: non-lacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors. Due to a violation of the proportional hazards assumption, the association between overt MI and stroke was modeled separately for short-term (within 30 days) and long-term (beyond 30 days) risk.

Results:
Among 4,224 participants included in this analysis, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (HR, 1.47; 95% CI, 1.01-2.16). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53-119) and long term (HR, 1.60; 95% CI, 1.04-2.44). In secondary analyses, the association between silent MI and stroke was limited to non-lacunar ischemic stroke (HR 2.18; 95% CI, 1.24-3.83).

Conclusions:
In a community-based sample, we found an association between silent MI and ischemic stroke, specifically non-lacunar stroke. These findings suggest that silent MI may be a novel risk factor for ischemic stroke.
Abstract 59: Presence of Infarct Predicts Recurrence and Efficacy of Dual Antiplatelet Therapy: A Post-Hoc Analysis of the POINT Trial
Authors: Kvernland Alexandra , Rostanski Sara K , Mac Grory Brian , De Havenon Adam H , Liberman Ava , Kim Anthony S , Easton J Donald , Johnston S. Claiborne , Yaghi Shadi
Published: March 2021

Background:
The combination of aspirin and clopidogrel for 90 days after minor stroke or transient ischemic attack (TIA) reduced the risk of recurrent stroke in the POINT trial. The risk reduction was greater in patients with infarct on CT or MRI compared to those without infarct.

Objective:
To investigate the effect of DAPT on minor stroke and TIA in the POINT trial based on (1) the presence or absence of infarct attributed to the index event (“index infarct”) and (2) whether the index event was classified as stroke or TIA.

Design/Methods:
Patients were divided into two groups based on whether they had an “index infarct” or not. Baseline demographics and clinical variables were compared between groups using standard statistical tests. We used univariate and multivariable cox-regression models to determine associations between presence of infarct on imaging and primary and secondary outcomes, and interaction analyses to determine whether the presence of “index infarct” modifies the effect of DAPT on study outcomes. We also explored whether the association of “index-infarct” with primary and secondary outcomes varied by index diagnosis (TIA vs. minor stroke).

Results:
Amongst 4881 enrolled in POINT, 4876 patients had data on whether there was an “index-infarct”; 1793 (36.8%) had “index-infarct”. In adjusted cox-regression analyses, the presence of “index infarct” was associated with the primary efficacy outcome (HR 3.02 95% CI 2.34-3.89, p < 0.01) and subsequent ischemic stroke (HR 3.10 95% CI 2.39-4.02, p < 0.01). The effect of DAPT vs. aspirin on primary efficacy outcome was more pronounced in patients with “index infarct” (HR 0.58 95% CI 0.43-0.79, p <0.01) vs. those without (HR 1.16 95% CI 0.79-1.71, p=0.44) (p for interaction = 0.01). In a secondary analysis based on final diagnosis, the effect of “index infarct” on primary outcome was only significant in those with minor stroke at the time of randomization (p for interaction=0.01) but not TIA at the time of randomization (p for interaction=0.36).

Conclusions:
In the POINT trial, efficacy of DAPT was greater in patients with infarct on imaging attributed to the index event. Future work should focus on determining clinical factors associated with this group to help identify patients most likely to benefit from acute DAPT.
Abstract 62: Increased Monocyte/Macrophage Pro-Inflammatory Cytokines and Chemokines in Mice With Cerebral Amyloid Angiopathy
Authors: Finger Carson , Lee Juneyoung , Morales Diego , Manwani Bharti
Published: March 2021

Introduction:
Cerebral amyloid angiopathy (CAA) is one of the common causes of intracerebral hemorrhage in the elderly. It is caused by the deposition of amyloid-beta1-40 (Aβ1-40) deposition within cerebral blood vessels, especially the smooth muscle layer, that can cause cerebral microbleeds (CMBs) and cognitive impairment. We hypothesize Aβ deposition causes an innate inflammatory response characterized by an increase and activation of microglia and macrophages. This inflammation might cause CMBs, neuronal damage and cognitive decline CAA.

Methods:
C57BL6 Tg-SwDI male and female mice (18 months) were used as a mouse model for CAA. Age-matched wild-type (WT) mice were used as controls. Brain samples from these mice were fractionated and 23-plex cytokine multiplex was performed on the brain lysates. Data was analyzed using two sample t-test or GraphPad PRISM.

Results:
Our data showed that CAA increased levels of pro-inflammatory cytokines in the brain, as compared with WT mice. Multiplex analysis showed that Tg-SwDI mice had significantly higher levels of cytokines; tumor necrosis factor-α (TNF-α; 54.38 vs. 17.03 pg/ml, p=0.00207), IL-12 (70.81 vs. 53.95 pg/ml, p= 0.014), macrophage inflammatory protein-1α (MIP-1α, 113.92 vs. 16.81 pg/ml, p=3.85E-10), MIP-1β (86.15 vs. 53.43 pg/ml, p= 3.51E-09) and monocyte chemoattractant protein-1 (MCP-1, 109.46 vs. 118.53 pg/ml, p= 0.00033).

Conclusion:
This study highlights a monocyte/macrophage driven pro-inflammatory milieu in CAA. Recent studies using in vivo two-photon imaging and histology have found recruitment of microglia and monocytes/macrophages around induced 100 μm sized hemorrhage. The increase in these microglia is only found in Alzheimer’s patients who also had CAA and was not seen in patients with no CAA, suggesting the role of microglia in causing vascular frailty in CAA. Our study suggests that pro-inflammatory cytokines like TNF-a, IL-12, MIP-1α, MIP-1β and MCP-1 can be therapeutic targets for CAA.
Abstract 63: Mutation of Platelet-Derived Growth Factor Receptor B Causes Cerebrovascular Malformation and Enhances Brain Arteriovenous Malformation Severity in Mice
Authors: Prado Leandro , Tang Chaoliang , Shaligram Sonali , Liang Rich , Winkler Ethan , Su Hua
Published: March 2021

Background and Purpose:
Deletion of
Endoglin (Eng),
an arteriovenous malformation (AVM) causative gene causes AVM in the brain angiogenic region. Reduction of pericytes is correlate with brain AVM hemorrhage. The platelet-derived growth factor B and its receptor β (PDGF-B/PDGFRβ) play important roles in regulating pericyte recruitment during angiogenesis. We
hypothesize
that mutation of PDGFRβ causes cerebrovascular malformation and enhances bAVM severity in
Eng
mutant mice.

Methods:
Three mouse models were used: (1)
Pdgfrβ
F7 (F7) mice that have mutations disrupting Pdgfrβ signaling, (2)
Pdgfb
-icreER;
Eng
f
/f
mice that have
Pdgfb
promoter driving, tamoxifen (TM) inducible cre expression in ECs and an floxed
Eng
gene; and (3)
Pdgfb
-icreER;
Eng
f
/f
;F7
+/-
mice. Brain angiogenesis was induced by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF). Brain AVMs were induced in
Pdgfb
-icreER;
Eng
f
/f
and
Pdgfb
-icreER;
Eng
f
/f
;F7 mice by TM induced EC
Eng
deletion and intra-brain AAV-VEGF injection. Brain AVM phenotypes were analyzed 8-weeks after model induction by latex vascular cast to detect arteriovenous shunts and macroscopic level of AVMs, immunostaining and Prussian blue staining to quantify dysplasia vessels and hemorrhage.

Results:
Compared to WT mice, F7
+/-
and F7
+/+
mice have more dysplastic vessels and fewer vascular pericyte before and after AAV-VEGF injection. F7
+/-
and F7
+/+
mice showed hemorrhage on the AAV-VEGF injection sites and AVM like vessels (a few arteriovenous shunts) in 16% F7
+/-
and 66% of F7
+/+
mice.
Pdgfb
-icreER;
Eng
f
/f
mice showed dysplastic vessels and hemorrhage at AAV-VEGF injection sites. Compared to
Pdgfb
-icreER;
Eng
f
/f
mice,
Pdgfb
-icreER;
Eng
f
/f
;F7
+/-
had a higher penetrance of bAVM (71% vs 50%) and more dysplastic vessels.

Conclusion:
F7 mutation cause AVM like structure in mouse brain and exacerbates bAVM phenotype in
Eng
mutant mice.
Abstract MP10: Aneurysmal Subarachnoid Hemorrhage in Pregnancy: National Trends of Treatment and Outcomes
Authors: Khatibi Kasra , Saber Hamidreza , Ponce Mejia Lucido , Kaneko Naoki , Nour May , Colby Geoffrey , Szeder Viktor , Tateshima Satoshi , Jahan Reza , Duckwiler Gary , Afshar Yalda
Published: March 2021

Introduction:
Aneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. With advances in neurosurgical and neurocritical care, there have been significant improvement in survival and clinical outcome of patients with aSAH. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnancy.

Methods:
Retrospective analysis using the Nationwide Inpatient Sample identified women 18-45 years-old hospitalized between 2010-2015. We identified pregnancy state, subarachnoid hemorrhage, and aneurysm treatments in this cohort. The mode of aneurysm treatment, mortality, and discharge destination was compared in pregnant versus non-pregnant cohorts.

Results:
9,667 aSAH with treatment were identified, of which 341 were associated with pregnancy. Mortality in the pregnancy and non-pregnancy were not different (7.37% vs 7.39%, p=0.97). However, pregnancy-related admissions were more likely to be discharged to home or short-term facility (71.9% vs 63.8%, p=0.002). Endovascular treatment for aSAH was more prevalent in pregnancy vs non-pregnancy (73% vs 66.3%, p=0.004). During the study epoch, there was a significant increase in endovascular treatment in pregnancy related aSAH (p<0.001). Surgical clipping was associated with higher mortality in pregnancy compared to non-pregnancy (15.9% vs 6.8%, p<0.001). There was no difference in mortality following endovascular treatment in pregnancy vs non-pregnancy (6.1% vs 7.8%, p=0.26). Favorable discharge outcome was significantly higher for pregnancy vs non-pregnancy with endovascular treatment (75.8% vs 63.9%, p<0.001), whereas no significant difference was observed in rate of favorable outcome for pregnancy and non-pregnancy with surgical clipping (57.9% vs 61.2%, p=0.29).

Conclusions:
Pregnancy does not alter mortality from aSAH. Among interventions for aSAH, surgical clipping is associated with higher mortality in pregnancy compared to non-pregnancy. However, pregnancy is associated with more favorable discharge outcomes (vs controls) and no change in mortality in this cohort. Consideration for endovascular intervention with aSAH in this cohort should be considered.
Abstract MP12: Drivers of Rescue Therapy Efficacy for Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Score Matched Analysis With Machine Learning
Authors: Martini Michael L , Neifert Sean , Shuman William , Chapman Emily , Schupper Alexander , Oermann Eric , Mocco J D , MacDonald R Loch L
Published: March 2021

Introduction:
One of the foremost challenges in subarachnoid hemorrhage (SAH) management is understanding which patient characteristics and treatment decisions lead to good outcomes. This study uses novel game theory-based methods in explainable machine learning (ML) and propensity-score matching to elucidate the clinical factors driving outcomes following rescue therapy for post-SAH vasospasm.

Methods:
Data for patients with post-SAH angiographic or symptomatic vasospasm were obtained from six clinical trials and observational studies in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and 3-month Glasgow Outcome Scale (GOS) scores. Shapley Additive Explanation (SHAP) values were calculated to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores.

Results:
A total of 1,532 patients were included. SAH characteristics and neurological sequelae, but not admission neurological scores, heavily influenced the probability of receiving rescue therapy. Comparing feature importances showed cerebral ischemia/infarction was invariably linked to poor outcome, while other important predictors of outcome varied by rescue type. Higher blood pressures and fewer postoperative days until vasospasm treatment were more important for predicting worse outcome following interventional rescue, while high admission WFNS grade and pneumonia were important predictors of worse outcome for non-interventional rescue. Finally, in a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS of 4-5 (odds ratio: 1.63; 95%CI 1.22-2.17; p=0.001).

Conclusion:
Rescue therapy for vasospasm was associated with good functional outcomes. Future randomized trials focusing on preventative or therapeutic interventions may be able to demonstrate improvements in clinical outcomes. Insights from these models may help improve patient selection criteria and trial designs for rescue therapy.
Abstract MP13: Polygenic Susceptibility to Atrial Fibrillation is Associated With Silent Cerebrovascular Disease in Stroke-Free Persons Without Atrial Fibrillation
Authors: Both Cameron , Acosta Julian , Szejko Natalia , Vanent Kevin N , Leasure Audrey C , Payabvash Sam , Sharma Richa , Murthy Santosh , Sheth Kevin N , Kamel Hooman , Falcone Guido J
Published: March 2021

Introduction:
Clinically silent cerebrovascular disease is present in 40% of persons over the age of 60. We hypothesize that polygenic susceptibility to atrial fibrillation is associated with the burden of white matter disease in persons without atrial fibrillation or history of ischemic stroke.

Methods:
We conducted a nested genetic and neuroimaging study within the UK Biobank, a large cohort study that enrolled community dwelling Britons aged 40 to 65 at recruitment. We used data on a subcohort of patients evaluated with brain MRIs. The volume of white matter hyperintensities (WMH) was estimated using the BIANCA lesion segmentation tool. Genomic data was ascertained via genotyping with the Affymetrix UK Biobank Axiom array followed by imputation with 1000 Genomes reference panels. To model the polygenic susceptibility to atrial fibrillation (AFIB), we constructed a polygenic risk score (PRS) using 957 independent genetic risk variants known to significantly associate with atrial fibrillation. We used logistic and linear regression to test for association between the PRS and WMH.

Results:
A total of 38,914 study participants underwent brain MRI imaging in the UK Biobank. Of these, we excluded 124 (0.3%) with a history of stroke and 926 (2.4%) with AFIB. 37,864 study participants were included in this study, of which 19,059 (50.3%) had WMH. High genetic risk of AFIB was not associated with no-versus-any WMH (p=0.51). When evaluating persons with WMH lesions, high genetic risk of AFIB was associated with higher WMH volume (per 1 SD increase of the PRS, beta 0.019, SE 0.006; p=0.01). Gender was an important effect modifier of this association (interaction p=0.03): while high genetic risk of AFIB was associated with a significant increase in WMH volume in females (per 1 SD increase of the PRS, beta 0.03, SE 0.008; p<0.001), no association was found for males (p=0.99).

Conclusions:
Polygenic susceptibility to atrial fibrillation is associated with more severe silent cerebrovascular disease in persons without atrial fibrillation. Further research should evaluate whether this genetic information can be used to identify persons for tailored diagnostic or therapeutic interventions.
Abstract MP20: The Effect of the Covid-19 Pandemic on Stroke Code Time Metrics at an Academic, Comprehensive Stroke Center
Authors: Meyer Dawn M , Shifflett Benjamin , Bavarsad Shahripour Reza , Ranasinghe Tamra , Torres Dolores , Barminova Anna , Figurelle Morgan , Labin Edward , Meyer Brett C
Published: March 2021

Introduction:
The COVID-19 pandemic forced immediate changes to stroke code protocols to maintain safety of patients and providers. We hypothesize that stroke code time metrics were significantly longer in the peri-COVID stroke code activations compared to pre-COVID activations.

Methods:
We analyzed data from an IRB-approved, prospectively collected stroke registry at a large academic, comprehensive stroke center (CSC). We included all patients that presented as stroke code activations from June 2009-August 2020, excluding spoke telestroke and in-house codes. Pre-COVID was defined as June 1, 2009-March 11, 2020 and peri-COVID March 12, 2020 to August 11, 2020. The pre-pandemic stroke code protocol began June 2009. We assessed The Joint Commission stroke code time metrics between groups. Demographic variables of baseline NIHSS, sex, race/ethnicity, age, smoking, pertinent past medical history, arrival mode, and baseline glucose were assessed. A t-test was used to compare stroke code time metrics in minutes. All analyses were done unadjusted.

Results:
We assessed 813 pre and 328 peri-COVID stroke code activations. Baseline demographics were significant only for an increased number of Hispanics in the pre-COVID group (22.9% vs 11.1%, p<0.001). Onset to hospital arrival time was significantly longer in the peri-COVID compared to pre-COVID group (244 vs 110 min, p<0.001). Onset to stroke code activation was significantly longer in the peri-COVID compared to pre-COVID group (243.8 vs 116.8 min, p<0.009). Time from arrival to treatment decision was significantly decreased in the peri-COVID group (29.9 vs 39.6 min, p=0.04). Time from arrival to CT scan completed (p=0.37), arrival to treatment administration (p=0.06), and onset to treatment administration (p=0.48) were not significantly different between groups.

Conclusion:
The COVID-19 pandemic significantly impacted the volume and demographic of stroke patients seeking emergency care. This data supports the trend of patients delaying emergent stroke care. This academic, CSC developed and implemented a COVID-19 stroke code protocol within days of a statewide lockdown. The use of telestroke in this peri-pandemic protocol may have accounted for the significant decrease in time to treatment decision.
Abstract MP23: Clinical and Demographic Factors Influence Clinical Trial Enrollment
Authors: Suto Daniel , Perrinez Emily , Rapp Karen , Nabulsi Mohammed , Hemmen Thomas M
Published: March 2021

Introduction:
Inclusion of diverse patients in clinical trials is essential to represent patient populations and to ensure that results are generalizable. Analysis of this topic is motivated by prior reports of clinical trials underrepresenting historically disadvantaged groups. We aimed to understand if the clinical trial population is representative of the overall stroke population in our community.

Methods:
We obtained clinical and demographic data from hospital administrative records including all acute ischemic stroke patients between March 2019 and February 2020. Consent was counted when a signed consent for study participation was documented in the inpatient record. Enrollment in studies with a primary inpatient population at the time of consent (MOST, TIMELESS, ARCADIA, SleepSMART, and STRONG) were included. Patients with consent (CP) and without consent (NCP) were compared using chi-square analysis and t-test probability with SPSS.

Results:
During the study period, 504 patients met the above criteria; 55 were consented to participate in clinical trials. Overall CP did not differ from NCP in % women (45.5% vs 41.2%, not significant), Hispanic ethnicity, discharge medications, hypertension, diabetes, heart failure, drug and alcohol abuse, atrial fibrillation, and payer (Medicare versus non-Medicare). Median age was lower in CP compared to NCP (63 ± 12.8 vs. 67 ± 13.9, p=.046). The mean NIHSS was lower in CP (6.37 ± 5.95 vs. 8.21 ± 8.91, p=.048). The CP group had lower incidence of prior stroke (9.1% vs. 20.9%, p=.037), less dyslipidemia (12.7% vs. 30.1%, p=.007), fewer comorbidities on average (1.9 ± 1.1 vs. 2.2 ± 1.5, p=.044), was less likely to identify as Asian (0% vs. 8.4%, p=.015) and more likely to identify as white (59.3% vs. 45.7%, p=.045). The CP group was more likely to have migraine (12.7% vs. 1.8% p<.001) and were discharged on more stroke risk-factor modifying medications (2.2 ± .558 vs. 1.9 ± .902, p=.001).

Conclusions:
While the study population is largely representative, they are more likely to be White, with lower stroke severity, fewer medical comorbidities and less likely to be Asian. We plan to expand this analysis to include more study centers and to guide future clinical trial design.