bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 94: Randomized, Double-blind, Placebo-controlled Phase 1 Study Of Vwf-binding Aptamer, Bb-031: Safety, Tolerability, Pharmacokinetic And Pharmacodynamic Activity In Healthy Volunteers
Authors: Nimjee Shahid M , Wheeler Debra , Nelson Stacy , Shea Richard J , Sullivan Taegen , Mayer Christina , Pavliv Leo , Layzer Juliana M , Lickliter Jason , Sullenger Bruce , Campbell Bruce , Becker Richard C
Published: February 2023

Introduction:
Von Willebrand Factor (VWF) is a ubiquitous component of thrombi extracted by endovascular thrombectomy from patients with large vessel occlusion (LVO) stroke. BB-031 is a modified RNA aptamer that targets von Willebrand Factor (VWF) that lyses occlusive thrombi and improves outcomes in pre-clinical models of acute ischemic stroke (AIS).

Hypothesis:
BB-031 is safe, tolerable, and inhibits both VWF binding and activity in a dose-dependent manner.

Methods:
Healthy participants were randomized to receive BB-031 or placebo (6:2) by intravenous bolus injection at single ascending doses (SAD) of 0.1, 0.3, 1.0, 2.0 and 4.0 mg/kg (total n=40). Serial Clinical assessment, and blood sample collection for pharmacokinetic (PK) and pharmacodynamic (PD) analysis were performed. Non-compartmental PK analysis was conducted using Phoenix WinNonlin. PD evaluation included measurement of VWF inhibition and whole blood thrombosis (Platelet Function Analyzer [PFA-200]).

Results:
BB-031 was safe and well-tolerated for 28 days following single IV doses up to 4.0 mg/kg. There were no significant adverse events (SAEs), or treatment-emergent adverse events (TEAEs) leading to dose discontinuation. Minor events included bleeding at an IV site in 1 participant, and minor bleeding of an ulcer on the tongue in 1 participant. None of the minor TEAEs were dose-dependent. BB-031 demonstrated nonlinear, dose-dependent plasma PK across the dose range tested, with an apparent mean terminal half-life (t
1/2
) of 18 min at 0.1 mg/kg to 67 min at 4.0 mg/kg. Dose-dependent changes in VWF binding were observed; >95% maximal mean change from baseline was reached following a single IV dose of 4.0 mg/kg. Finally, PFA-200 results showed complete inhibition of clot formation (closing time ≥300 seconds) at all doses tested with a dose-dependent duration of inhibition and return to normal range.

Conclusion:
This first-in-human SAD study of BB-031 demonstrated safety following a single IV dose of 0.1 to 4 mg/kg, and dose-dependent patterns of VWF binding and platelet function changes. These results lay the foundation for future studies in patients suffering from thrombotic conditions including AIS.
Abstract 99: Clot Composition And Reperfusion Outcomes In 1430 Mechanical Thrombectomy Patients: Analysis Of The Stroke Thromboembolism Registry Of Imaging And Pathology
Authors: Nogueira Raul G , Pinheiro Agostinho , Brinjikji Waleed , Abbasi Mehdi , Al-Bayati Alhamza R , Mohammaden Mahmoud , Viana Lorena S , Ferreira Felipe , Abdelhamid Hend M , Bhatt Nirav , Kvamme Peter , Layton Kennith , Delgado Almandoz Josser , Hanel Ricardo , Mendes Pereira Vitor , Almekhlafi Mohammed , Yoo Albert J , Jahromi Babak S , Gounis Matthew J , Patel Biraj M , Arturo Larco Jorge , Fitzgerald Sean , Mereuta Oana M , Doyle Karen , Savastano Luis , Cloft Harry J , Thacker Ike , Kayan Yasha , Copelan Alexander , Aghaebrahim Amin , Sauvageau Eric , Demchuk Andrew M , Bhuva Parita , Soomro Jazba , Nazari Pouya , Cantrell Donald , Puri Ajit S , Entwistle John , Polley Eric C , Frankel Michael R , Kallmes David F , Haussen Diogo C
Published: February 2023

Background:
Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT.

Methods:
Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes.

Results:
A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,17.2 [10.5-23]; IV-tPA use, 36%; Stent-Retrievers [SR], 27%; Contact Aspiration [CA], 27%; Combined SR + CA, 43%) were included. The median [IQR] number of passes was 1 [1-2]. FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for RBC-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes compared to RBC-rich and mixed clots (median, 2 and 1.5 vs.1, respectively, P=0.02). CA displayed a trend towards a higher number of passes with fibrin-rich clots (2 vs.1, P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots.

Conclusion:
Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.
Abstract HUP1: Neighborhood Deprivation And Polygenic Contribution To Acute Ischemic Stroke: Results From The
All Of Us
Research Program
Authors: Rivier Cyprien , Acosta Julian , Renedo Daniela , Sheth Kevin N , Falcone Guido J
Published: February 2023

Background:
The interaction between social determinants of health and genetic risk factors in causing acute ischemic stroke (AIS) is poorly understood. We hypothesize that community deprivation, a geographic metric that captures several social determinants of health, modifies the effect of genetic variation on risk of AIS.

Methods:
We analyzed data from
All of Us
, a large population study that aims to enroll one million Americans. We ascertained AIS cases using Observational Medical Outcomes Partnership codes. We evaluated community deprivation using the deprivation index, an aggregate variable derived from six metrics of the American Community Survey that was divided into tertiles. We modeled the polygenic contribution to AIS through a polygenic risk score that included 530 known genetic risk variants for cardiometabolic risk factors. We used multivariable logistic regression to model AIS risk as a function of community deprivation and polygenic risk, using product terms to test for interaction.

Results:
Out of 372,397 participants currently enrolled in
All of Us
, 147,492 had available genetic and deprivation index data, including 3,201 (2.2%) strokes. Both community deprivation and the polygenic risk score were independently associated with AIS risk (both p<0.05). We found a significant interaction between community deprivation and polygenic risk (interaction p=0.02, Figure): the polygenic risk score was significantly associated with AIS risk in areas with low community deprivation (OR 1.08, 95%CI 1.02-1.15; p=0.01) but was not associated with this risk in areas of intermediate and high deprivation (both p>0.05).

Conclusion:
Among study participants enrolled in All of Us, those living in areas of low community deprivation were more susceptible to the effects of polygenic variation. We speculate that in areas with high deprivation, several social determinants of health known to lead to higher risk of AIS dilute the contribution of genetic risk factors.
Abstract HUP10: Stroke Codes In Limited English Proficiency Patients - Current State And Scope For Improvement With Interpreter Education And Need For NIHSS Revision
Authors: Pankaj Preethy , Sharma Malveeka , Tirschwell David L
Published: February 2023

Objective:
Improve the institution of NIH Stroke scale (NIHSS) and outcomes of Stroke codes in low English proficiency population (LEP) at a comprehensive stroke center.

Background:
LEP individuals are those with limited ability to read, write, speak, or understand English. The 2000 national census showed 47 million U.S. citizens/residents aged 5 years and older spoke a language other than English at home. This is projected to grow by 67 million by 2050. For patients from culturally and linguistically diverse backgrounds, language barriers contribute to poorer quality of care. Stroke is a leading cause of serious long-term disability and death and our aim is to ensure that time-sensitive interventions during a Stroke code are available to our LEP patients in the most efficient and fastest manner.

Design/Methods:
1) Pre-intervention survey of providers 2) Creating a set of English words that are more internationally used to assess dysarthria 3) Interpreter Education (for select languages) regarding stroke, acuity of Stroke codes, NIHSS content, tPA and thrombectomy 4) Easy access for providers to the trained interpreters and use of the new Dysarthria words 5) Post-intervention survey of providers running Stroke code 6) Compare post-intervention door-to-needle and door-to-thrombectomy times in languages intervened to other languages in the same period of time.

Results:
Pre-intervention survey shows that 84.6% of the providers (n=26) deemed running LEP stroke codes in a time-efficient manner as difficult or very difficult. 50% found getting a telephonic interpreter to start the communication to be slow/very slow. 88.5% found the telephonic providers to be either somewhat helpful or not so helpful during the code. 92% of the providers found the words to test dysarthria on the NIHSS to be not helpful in LEP stroke patients.

ConclusionS:
It is apparent that LEP Stroke codes can be improved based on the above provider opinions. Therefore, we have set into motion a multi-pronged strategy by rethinking the contents of NIHSS, interpreter education and finally instituting an intervention based on the same. The study has started the final phase of having providers access the trained interpreters. The data of the latter will be collected in about 2 years’ time.
Abstract HUP13: Assessing Patient Perceptions Of Strokes Reveals Limited Coherence And Perceived Barriers To Treatment Compliance In Hospitalized Stroke Patients Independent Of Race/ethnic And Socioeconomic Factors
Authors: Dickens Rondalyn R , Gyang Tirisham , Sanders Sadie B , Simpkins Alexis N
Published: February 2023

Introduction:
A large factor contributing to stroke prevention is medication adherence and lifestyle adjustments. Patients' attitudes and perceptions towards health may contribute to a patient's likelihood of optimal stroke prevention.

Methods:
We surveyed hospitalized stroke patients and their caregivers using the Cerebrovascular Attitudes and Beliefs Scale-Revised and the Illness Perception Questionnaire-Revised survey before hospital discharge. Parametric and nonparametric tests were used to assess statistical significance, and Cronbach's was used for inter-rater variance using SPSS Statistics 27.

Results:
Our study included 39 patients & 6 caregivers, median age 66 (interquartile range 56-78), 60% woman, 69% Non-Hispanic White, 71% ischemic, 58% non-LVO, 4% tPA, 67% Medicare, 36% rural, and the median time since stroke onset was 3-5 days. Cronbach's alphas indicated that all sub-scales were reliable with a high level of internal consistency (α=0.829). More patients identified as having difficulty understanding their medical condition smoked (p=0.024), did not have atrial fibrillation (p=0.009), and did not have hyperlipidemia (p=0.036). Also, patients with diabetes were more likely to perceive obstacles to treatment compliance (p=0.039), prolonged recovery (p=0.042), and more severe consequences (p=0.046). Patients who had experienced a non-LVO were more likely to perceive the ineffectiveness of their treatments (p=0.034). More patients who had experienced a TIA perceived barriers to treatment compliance (p=0.049). Though there were no readmissions within 30 days and only one fatality related to GI bleed, of the 38% of patients that did not keep their post-hospital discharge follow-up neurology appointment, more had difficulty understanding their medical condition (p=0.036). There was no association with race, gender, insurance, rural vs. urban, or ethnicity.

Conclusions:
Interestingly, our findings identified modifiable stroke risk factors. We also saw a link between health care perceptions and no-show neurology clinic visits post-stroke hospitalization. Effective personalized patient education before hospital discharge is needed to help improve secondary stroke prevention management.
Abstract HUP19: Sex Differences In Incidence Of Intraventricular Hemorrhage And Hydrocephalus In Patients With Non-traumatic Intracerebral Hemorrhage
Authors: Iyer Ankitha , Horn Alexander , Kolahi Sohrabi Arian , Kawas Mohammad Iyas , Spicer Alan , Kittel Carol , Quintero Wolfe Stacey
Published: February 2023

Introduction:
Non-traumatic Intracerebral Hemorrhage (ICH) accounts for 2 million strokes annually worldwide. This stroke burden disproportionately impacts minorities, and results in severe neurological deficits. Sex differences in brain structure and function, such as a larger mean length of frontal horn in males and increased global cerebral blood flow in women, can contribute to hematoma volume and expansion of ICH into nearby structures. No studies have yet to investigate sex differences in the incidence of Intraventricular Hemorrhage (IVH) and hydrocephalus as sequelae of ICH, both or which correlate with poor long-term outcomes.

Methods:
A retrospective review of a comprehensive stroke center spontaneous ICH database from 2019-2022 was performed, including patient characteristics such as history of diabetes mellitus, hypertension, coronary artery disease, tobacco use, and anticoagulant use in addition to ICH characteristics such as hematoma location volume, expansion, incidence of IVH and hydrocephalus. A logistic regression model controlling for these covariates was built to investigate sex differences in incidence of IVH and hydrocephalus.

Results:
This cohort had 100 patients with spontaneous, non-traumatic ICH, of which 39% were female. Overall, 52/100 (52%) patients had IVH and 21/100 (21%) patients developed hydrocephalus. Among males, 29/61(48%) had IVH as opposed to 23/39 (59%) in females, p = 0.264. There was similar development of hydrocephalus in both males 13/61(21%) and females 8/39 (21%). Logistic regression showed females had higher odds of IVH. Higher diastolic blood pressure and anticoagulant use on admission also had higher odds of IVH.

Conclusion:
This pilot study demonstrates a trend towards higher incidence of IVH among females when controlling for history of diabetes mellitus, hypertension, coronary artery disease, tobacco use, and anticoagulant use. Higher odds of IVH in patients with higher diastolic blood pressure on admission adds to the previously investigated association between systolic blood pressure and ICH hematoma volume. Our sample validated the higher odds of IVH in patients with anticoagulant use on admission.
Abstract HUP5: Racial Disparities Of Post-acute Service Utilization In The United States After Ischemic Stroke
Authors: Man Shumei , Bruckman David , Schold Jesse , Uchino Ken
Published: February 2023

Objective:
This study aimed to examine the impact of race/ethnicity on discharge to one pathway versus others after ischemic stroke in the U.S.

Methods:
We included patients admitted for ischemic stroke in 2017-2018 using the National Inpatient Sample, a 20% stratified sample of all admissions from U.S. community hospitals. Discharge destinations were classified as: Home/Routine (home without home health care); Home Health Care (HHC); and Facility (inpatient rehabilitation or skilled nursing Facility). Survey-weighted binomial and multinomial logistic regressions were used to examine associations of race/ethnicity with discharge to one pathway versus others, adjusting for patient socioeconomic status, comorbidities, proxies of stroke severity, and hospital characteristics.

Results:
Among the 1,000,980 weighted admissions included, 2.6% died in the hospital, 42.7% were discharged to Home/Routine, 15.2% to HHC, and 35.7% to Facility. Hispanics had the highest Home/Routine discharge rate (49.1%) and lowest Facility discharge rate (29.1%). Compared to White patients, minorities had significantly lower odds of Facility over any home discharge (adjusted aOR 0.72 for Hispanics, 0.75 for Asian/Pacific Islanders, and 0.95 for Blacks). Hispanics and Asian/Pacific Islanders had significantly lower odds of Facility over HHC discharge (adjusted OR 0.81 and 0.85, respectively). Minorities had greater likelihood of HHC over Home/Routine discharge (adjusted OR 1.37 for Blacks, 1.35 Asians/Pacific Islanders, and 1.08 for Hispanics).

Conclusion:
This study using a nationally representative dataset demonstrated significant racial/ethnic disparities in post-acute service utilization after stroke. Hispanics had the lowest utilization of formal post-acute service. The low facility discharge among Blacks and Asians/Pacific Islanders might be, to some degree, compensated by HHC utilization while this compensatory phenomenon was minimum among Hispanics.
Abstract HUP6: Community Deprivation And Healthcare Access/Utilization In Patients With Carotid Stenosis: Results From The
All Of Us
Research Program
Authors: Clocchiatti-Tuozzo Santiago , Renedo Daniela , Rivier Cyprien , Torres Lopez Victor M , Matouk Charles , Sheth Kevin N , Gill Thomas M , Falcone Guido J
Published: February 2023

Background:
Social determinants of health are emerging as a key group of risk factors for cerebrovascular disease. Carotid artery stenosis (CAS) is an important risk factor for ischemic stroke. We hypothesize that community deprivation, an exposure that captures several social determinants for health, leads to significant disparities in healthcare access in patients with known CAS.

Methods:
We conducted a cross-sectional study within the All of Us Research Program, a prospective population study that aims to enroll 1 million Americans. We included study participants with CAS, as defined by validated ICD-9/10 codes. We evaluated access to healthcare using 5 metrics included in the Health Care Access and Utilization Survey (Table 1). We evaluated community deprivation using the Deprivation Index, a novel compound metric developed by the American Community Survey. We tested for association between tertiles of the Deprivation Index (labeled low, intermediate and high community deprivation) and health care access using multivariable models adjusting for potential confounders.

Results:
Of 333,845 participants enrolled in All of Us, we identified 2,465 (0.74%) participants with CAS (mean age 69, 53% female). Of these, 259 (10.5%) could not afford prescription medication, 132 (5.4%) could not afford specialist care, 144 (5.8) skipped medications, 109 (4.4%) could not afford to follow up care and 97 (3.9%) could not afford mental health care. In unadjusted analysis, higher community deprivation was associated with a higher prevalence of all 5 evaluated indicators of poor access to health. In multivariable analysis adjusted for potential confounder variables, difficulty affording prescription medication, specialist care and follow up care remained statistically significant (Table 1).

Conclusion:
Among persons with CAS enrolled in All of Us, community deprivation was associated with a lower likelihood of accessing and utilizing important healthcare services.
Abstract HUP8: Higher Prevalence Of Ischemic Stroke In Black Down Syndrome Patients
Authors: Ahmed Ibrahim
Published: February 2023

Introduction:
Ischemic cerebrovascular accidents (CVA) contribute to major morbidity in hospitalized patients. Little is known of its impact in Down Syndrome (DS) patients. Our aim was to characterize the patient demographic and to investigate the impact of CVA on hospitalized DS patients.

Method:
This was a retrospective cohort study utilizing 2019 National Inpatient Sample database. Adults with DS and CVA diagnoses were included. Regression models adjusted for demographic variables were used. Primary outcome was evaluating all-cause mortality, and secondary outcomes were evaluating length of stay (LOS) and total hospitalization charge.

Results:
Out of 44720 admissions with Down Syndrome, 355 had a ischemic cerebrovascular accident. Compared to Non-CVA-DS cohort, CVA-DS cohort were older (39.04 vs 24.71 years,p<0.001), more Black (19.72% vs 10.83%,p<0.05), Medicare (57.75% vs 35.03%,p<0.001), more hypertension (21.13% vs 6.16%,p<0.001), PVD (11.27% vs 1.75%,p<0.001), diabetes mellitus (18.31% vs 3.93%,p<0.001), but less Hispanic (9.86% vs 19.73%,p<0.05), private insurance (12.68% vs 23.96%,p<0.05), and West region hospital (11.27% vs 23.10%,p<0.05). There was no statistically significant difference in the prevalence of females, White, API, household income, hospital teaching status, dementia, chronic pulmonary disease, obesity, hypothyroidism. CVA-DS cohort had a similar all-cause mortality rate (3.19% vs 1.28%,p=0.1029), all-cause odds of mortality 1.48 (95%CI 0.39-5.63,p=0.563), mean LOS (9.79 vs 8.40 days,p=0.498), and mean total hospitalization charge ($172327.20 vs $99913.84,p=0.076).

Conclusion:
In patients admitted with DS, the presence of CVA was not associated with an increase in all-cause mortality, odds of mortality, mean LOS, or total charge, however it was associated with a higher prevalence in Black patients, older age, Medicare, hypertension, diabetes mellitus, and PVD, and a lower prevalence in Hispanic patients.
Abstract HUP9: Racial Disparities In Acute Ischemic Stroke At A Large Metropolitan Stroke Center
Authors: Inikori Eno , Ross Lindsey , Mirocha James , Lee Harlem , Ditman Elisa , Figueroa Sonia , Paletz Laurie B , Torbatti Sam , Song Shlee S , Harris Jennifer
Published: February 2023

Background:
Race and ethnicity can have a major impact on the quality of care patients with acute ischemic stroke (AIS) receive. We sought to assess the impact of race and ethnicity on quality benchmarks of AIS therapy and clinical outcomes at a comprehensive stroke center (CSC).

Methods:
A retrospective analysis of AIS patients presenting to a CSC between 2015 to 2020 was performed. Data included demographics, NIH Stroke Scale scores, time to thrombolysis, discharge diabetic and hypertensive medications, length of stay (LOS), discharge functional status, 30-day readmission, and 30-day mortality. Quality benchmarks and outcomes were analyzed by the five most prevalent racial-ethnic groups including Non-Hispanic White (NHW), Hispanic, Black, Asian, Other and Unknown.

Results:
3,735 AIS patients were identified. NHW represented 53.3% (n=1992),Black 21.3% (n=797), Hispanic 10.4% (n=390), Asian 7.2% (n=267), Other 4.6% (n=170) and Unknown 3.2% (n=119). There were no significant differences in door to needle (P=0.93), door to puncture time (P=0.98), intravenous thrombolysis (P=0.32) and mechanical thrombectomy utilization (P=0.19) by race-ethnicity. In univariable analysis, there was a higher rate of 30-day mortality in Unknown 23.5% vs NHW 7.3% (P< 0.0001). A significantly (P>0.05) higher rate of 30-day readmission was noted in NHW 20.3% vs Black 15.7%, Hispanics 15.6%, Others 11.8% and Unknown 8.4%. Black 67.6%, Hispanic 64.9% and Unknown 80.5% had a significantly (P<0.05) higher rate of post stroke disability (mrs>2) vs NHW 60.3%. A significant difference (P<0.05) in LOS with Black patients staying 8.4, Hispanic 10.8, Asians 11.9 and Unknown 11.2 days vs NHW 7.7.Adjusting for age, sex, NIHSS and comorbidities, multivariable logistic regression continued to show differences in post stroke disability for Black (OR=1.40, P=0.003), Hispanic (OR=1.49, P=0.008) and Unknown (OR=2.03, P=0.016) vs NHW. Median LOS was 0.85 and 0.77 days longer for Asian and Hispanic (P=0.006, P=0.014) respectively vs NHW.

Conclusions:
Our analysis reveals persistent disparities in stroke outcomes, with Black and Hispanic patients suffering greater disability post stroke. Further investigation is needed to uncover how race-ethnicity mediates stroke care and outcomes.
Abstract NS1: Depression Vs Psychiatry Appointments Post Stroke Discharge Phone Call
Authors: Mkrtumyan Alvina , Gaffney Denise , Punsalang Lorina , Sangha Navdeep S , Le Duy , Cheng Pamela , Ajani Zahra
Published: February 2023

Background:
Post-stroke depression (PSD) affects up to one-third of stroke survivors and remains under-recognized. The optimal time for PSD screening seems to be about 30-45 days post-stroke. However, screening and follow up remains insufficient.

Methods:
Our stroke certified registered nurse contacted stroke patients admitted to Kaiser Permanente Los Angeles in 2021 to assess depression within 30-45 days post discharge using the Patient Health Questionnaire Screening Tool (PHQ9). Two call attempts were made. Based on the PHQ9 scores, patients were referred to different clinical care pathways. Patients who scored10-19 were referred to depression care management (DCM), while 20 and above were referred to psychiatry directly. We collected the demographics, stroke types and discharge disposition inpatients who were lost to follow up and patients who completed the follow up. Data were analyzed using R-Statistics.

Results:
Among 92 patients, 41 (45%) had follow-up depression screening completed; 13 (32%)received psychiatry referral given severity of depression, and 28 (68%) received a depression care management referral. Of 51 patients who did not complete follow-up screening, 27 (53%)declined to participate in screening, while 22 (43%) could not be reached. Patients who did not receive follow-up screening were older (P=0.02). Race, gender, discharge mRS or length of acute hospital stay did not have a significant effect on patient’s depression screening follow-up status. Patients discharged home with home health showed a trend for better completed follow-ups despite not reaching statistical significance (P=0.07).

Conclusion:
Raising awareness about the necessity of depression screening and its treatment is of utmost importance for reaching optimal recovery and rehabilitation potential in stroke patients. Post-discharge follow-up and education can be implemented to narrow the PSD recognition gap.
Abstract NS6: Impact On Mechanical Thrombectomy Numbers: Advanced Imaging For All Versus Large Vessel Occlusion Screen Triage
Authors: Patterson Michele , Birnbaum Lee , Mascitelli Justin , Cline Paula , Moore Tracy , Tully John
Published: February 2023

Background:
Our five-hospital Comprehensive Stroke Program utilized the vision, aphasia, neglect [VAN] large vessel occlusion [LVO] screening tool to triage patients for Computed Tomography Angiography [CTA] with initial imaging. With the development of a Mechanical Thrombectomy [MT] Capable Center the decision was made to perform CTA on all stroke alerts [CTA-ALL] in an effort to increase the numbers treated with MT.

Purpose:
To evaluate the effectiveness of CTA-ALL in our emergency departments and the impact on numbers with MT.

Method:
A retrospective review of 426 acute ischemic stroke alert patients [AIS-SA] who arrived within 8 hours of last known well over an 18-month period was conducted with 206 identified as pre-change [PRE] and 220 as post-change [POST]. The NIHSS was evaluated for components of the VAN screening tool to determine if patients were VAN positive [VAN+]. Each group was divided into NIHSS 0-5, NIHSS ≥ 6 and VAN+. Groups were then compared by VAN+, CTA-ALL, LVO+ and MT to determine the impact on numbers treated.

Results:
The POST group showed a 12% increase of CTA-ALL, with the largest increase in NIHSS 0-5 [22%]. In addition, there was a 3% increase in LVO+ and a 5% increase in MT, with the largest increase in NIHSS ≥ 6, 5% and 11% respectively. There were no additional patients treated in POST NIHSS 0-5. AIS-SA patients with a VAN+ screen resulted in fewer CTAs, identified a higher percentage of LVO+ and treated the same number of MT.

Conclusion:
Performing CTA-ALL for NIHSS 0-5 did not increase our MT numbers; in fact, it remained zero. Although an increased number of LVO+ was noted POST CTA-ALL in the NIHSS≥ 6 compared to VAN+, the total number of MT was the same in both groups. Thus, compared to PRE triage with VAN+, POST CTA-ALL increased overall imaging use without increasing the sensitivity of our MT triage. Our results support stroke triage with stroke severity scales such as VAN rather than CTA-ALL to optimize sensitivity and neuroimaging utilization.
Abstract TMP103: Acute Ischemic Stroke Readmission In Patients With Periprocedural Atrial Fibrillation
Authors: Shu Liqi , Xiao Han , Yaghi Shadi
Published: February 2023

Introduction:
Anticoagulation therapy are commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, risk factors of subsequent stroke during the periprocedural period is uncertain. We performed a nationwide analysis to evaluate risk factors for acute ischemic stroke (AIS) readmission in patients with AF admitted for elective procedure.

Methods:
Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included electively admitted adult patients, who had AF diagnosis and procedural Diagnosis-related group code from 2016 to 2019. AF, AIS and other diagnosis were identified based on standard ICD-10 CM codes. Patients who had history of stroke or stroke during the index admission were excluded. We constructed a Cox regression model to determine hazard ratios (HR) of demographic, clinical factors and procedural type associated with AIS readmission.

Results:
Of the 1,048,422 patients with AF admitted for elective procedure, the mean age was 71.5 and 39.1% were female, and 1625 (0.15%) had AIS readmission within 30 days of discharge. In the adjusted Cox regression model, age (adjusted HR 1.05, 95% CI 1.04-1.06, P < 0.001), female sex (aHR 1.22, 95% CI 1.05-1.41, P = 0.009), cancer (aHR 1.45, 95% CI 1.89-1.76, P < 0.001), congestive heart failure (aHR 1.22, 95% CI 1.03-1.44, P = 0.021), diabetes (aHR 1.33, 95% CI 1.14-1.55, P < 0.001), neurological surgery (aHR 2.27, 95% CI 1.69-3.06, P < 0.001), cardiovascular surgery (aHR 1.59, 95% CI 1.32-1.91, P < 0.001). Furthermore, higher CHADS
2
VASC
2
score (aHR 1.29 by one point, 95% CI 1.22-1.37, P < 0.001) were associated with AIS readmission.

Conclusion:
AF patients with higher CHADS
2
VASC
2
score and those undergoing cardiac or neurological surgeries are at higher risk of perioperative stroke. Studies are needed to tailor anticoagulation management during the perioperative time to reduce perioperative AIS risk in such patients.
Abstract TMP104: Effect Of Statin Therapy In Stroke Patients With Low Baseline Low-density Lipoprotein Cholesterol
Authors: Kim Yong Soo , Jeong Han-gil , Park Chan-Young , Kim Museong , Lee Subin , Han Moon K
Published: February 2023

Introduction:
Post-stroke statin therapy is known to reduce subsequent major vascular events in patients with ischemic stroke. However, the efficacy of statin therapy in acute ischemic stroke patients with low low-density lipoprotein cholesterol (LDL-C) at baseline is not well defined. This study aimed to determine whether statin therapy would be beneficial in stroke patients with low or well-controlled LDL-C at baseline.

Methods:
We assessed ischemic stroke patients with baseline LDL-C <100mg/dL without prior statin therapy or <70mg/dL with prior statin therapy who were hospitalized between 2011 and 2020. The effect of post-stroke statin therapy on major vascular events, defined as a composite of recurrent stroke, myocardial infarction, and all-cause death within 1 year after stroke was assessed using multivariable Cox regression analyses.

Results:
A total of 3,350 patients (mean age 68.6 ± 13.9 years; 62.9% male; 21.5% with previous statin therapy; 37.0% with atherosclerotic stroke) were included. The mean baseline LDL-C of the patients was 73.6 ± 17.6mg/dL, which did not differ between patients with or without post-stroke statin therapy (74.0 ± 17.7mg/dL in statin users; 73.4 ± 17.6mg/dL in statin non-users). Statins were prescribed in 2,638 (78.8%) after stroke and LDL-C was significantly reduced in patients who received statin therapy (65.9 ± 21.7mg/dL in statin users; 80.2 ± 26.7mg/dL in statin non-users). Statin therapy was significantly associated with a lower risk of major vascular events (adjusted hazard ratios (aHR) 0.37 [95% confidence interval (CI) 0.31 - 0.46]). However, post-stroke LDL-C reduction (aHR 1.00 [95% CI 0.995 - 1.01]), percent LDL-C reduction (aHR 0.999 [95% CI 0.996 - 1.003]) and achieved LDL-C <55mg/dL after stroke (aHR 0.96 [95% CI 0.67 - 1.37]) were not associated with the occurrence of major vascular events within 1 year after stroke.

Conclusions:
Post-stroke statin therapy was associated with a reduction in major vascular events after acute ischemic stroke, even in patients with low or well-controlled LDL-C. However, achieved LDL-C levels were not associated with post-stroke major vascular events in this population.
Abstract TMP111: Electronic Cigarette Exposure Exacerbates Ischemic Stroke Outcome Via Altered Neurotransmitter Metabolism In Rats Of Both Sexes
Authors: Pradhyumnan Hari , Patel Shahil H , Furones-Alonso Ofelia , Bramlett Helen , Raval Ami P
Published: February 2023

Introduction:
Smoking is a preventable risk factor for stroke and battery-operated nicotine delivery systems known as electronic cigarettes (EC) are popular. EC vapes aerosolize a mix of nicotine and chemicals forming harmful toxicants such as formaldehyde hemiacetal. Our understanding about effects of EC vaping on stroke outcome is limited. This study investigated effects of EC on global metabolic signature and stroke outcome in animals of both sexes.

Methods:
Sprague-Dawley rats (2-3 months old; n=8) of both sexes were randomly assigned either to air or EC vapor (5% nicotine Juul pods) exposure using the EcigAero-TM Aerosol Exposure Apparatus. Rats were exposed to air/EC for 16 nights. Per night, rats were exposed to 16 episodes of EC vapor. Each episode consisted of 2 seconds of Juul puffs followed by 8 seconds of air over the period of 8 minutes. After 16 days, the rats were divided into two cohorts. The first cohort of rats exposed to EC/Air was tested for cognitive capacities using the Morris water maze (WM) followed by brain collection for unbiased metabolomic (Metabolon Inc.) or Western blot analysis. The second cohort of rats exposed to EC/Air was subjected to transient middle cerebral artery occlusion (tMCAO; 90 min) or sham surgery and survived for 15-21 days. During the post-tMCAO survival, rats were tested for cognition using WM followed by brain collection for histopathological analysis.

Results:
Metabolomic analysis indicated that EC exposure resulted in significant increases (p≤0.05) in phenylalanine and tryptophan metabolites, and both increases (p≤0.05) and decreases (p≤0.05) in histamine and tyrosine metabolites in the brains of female and male rats. Western blotting of rate-limiting enzymes in respective NT pathways corroborated the metabolomic data. Behavioral testing indicated worsened cognitive outcome in EC groups compared to air groups in rats of both sexes.

Conclusion:
EC vape exposure, even for as short as 2 weeks, impacts the metabolism of NT, induces cognitive deficits and worsens stroke outcomes in young male and female rats. Future studies investigating the impact of EC withdrawal on NT metabolism are needed to understand how long the deleterious effects of EC vaping persist in the brain.
Abstract TMP118: Brain Derived Neurotrophic Factor Secretion From Lungs Mediate The Post-stroke Functional Recovery After Systemic Administration Of MSCs
Authors: Davis Courtney , Goh Andrew , Flores Sylvia A , Wewior Natalia , Aronowski Jaroslaw A , Savitz Sean I , Satani Nikunj
Published: February 2023

Background:
Bone marrow derived mesenchymal stromal cells (MSCs) have been actively tested in clinical trials. After intravenous (IV) administration, vast majority of them are trapped in lung vasculature, with only few reaching brain. Even though MSCs are short-lived in the lungs, their beneficial effects on post-stroke recovery extends for weeks, suggesting a paracrine mechanism of action. Integrins expression on MSCs is known to mediate the lung entrapment by binding to ICAM1-expressing endothelial cells (ECs). Furthermore, ECs can perform paracrine functions by releasing neurotrophins, such as brain derived neurotrophic factor (BDNF). We explored EC-MSC interaction in lungs, and its effect on BDNF release from lung ECs, in an experimental stroke model.

Methods:
Human lung ECs (Cell Biologics) were cultured at P3. Human MSCs were isolated from bone marrow of healthy donor and P3 MSCs were used for experiments. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 10 was collected at 24 hours after stroke. Co-culture experiments were done in trans-well plates. BDNF mRNA was isolated using Qiagen RNeasy kit. Middle Cerebral Artery Occlusion model (filament model) was used in C57BL/6 mice. Modified Neurological Severity Score (mNSS) was used for functional assessment in mice stroke model.

Results:
Human primary lung ECs exposed to plasma from stroke patients as well as recombinant TNF-α showed robust increase in BDNF secretion, with MSCs enhancing the secretion furthermore. BDNF mRNA was robustly increased in whole mouse lungs as well as lung ECs. IV MSC administration robustly increased plasma BDNF and BDNF mRNA expression in mouse lung ECs. Furthermore, IV MSCs provided better functional recovery as compared to IV BDNF.

Conclusion:
BDNF is already known to be neuroprotective. Our results show that BDNF secretions increase from lung ECs after IV MSC administration, which could mediate functional recovery in mice after stroke.
Abstract TMP12: COVID-19 Increases The Risk Of In-Hospital Acute Stroke Mortality: A Cohort Study
Authors: Piva Mariana , Avezum Luisa , Santos Isabel , Dousseau Gabriella , Tolentino Mateus , Canedo Nalcer , Terehoff Igor , Domingues Pedro , Machado Michel , Rocha Maria Sheila G
Published: February 2023

Introduction:
Coronavirus disease (COVID-19) infection has an increased risk for neurological complications. Stroke has been associated with COVID-19 in 1-3% of hospitalized patients.

Methods:
This is a retrospective cohort study of stroke patients admitted in a health center in Brazil. We aimed to investigate whether the exposure to COVID-19 was associated with an increase in acute stroke mortality. The primary outcome was in-hospital mortality.

Results:
The cohort included 1191 stroke patients (54% male). All strokes were included: Ischemic stroke (81.2%), hemorrhagic stroke (14.9), cerebral venous thrombosis (2.1%) and subarachnoid hemorrhage (1.3%). Stroke associated with COVID-19 represented 5.4% of all patients. Mean age was 64.4 years (SD 0.5) and did not differ between groups. Sex distributions were equal in patients with or without covid-19. The prevalence of stroke type and the TOAST classification were similar in both groups. Mean NIHSS score was 8.7 (SD 6.3) being significantly higher in COVID-19 patients (p=0.036). COVID-19 patients disclosed a higher frequency of previous ischemic heart disease (OR: 3.5 - CI: 1.86-6.46). The frequency of arterial hypertension, diabetes mellitus, tobacco and alcohol use, and atrial fibrillation were similar for both groups. COVID-19 patients disclosed higher odds for in-hospital infection (OR: 4.5; CI: 2.67-7.48). Mortality rate was higher for COVID-19 patients (44.6% against 20.1% in non-Covid-19 group) in all subtypes of stroke. The mortality risk was twofold for COVID-19 stroke patients (CI: 1.62-2.92). Multivariate logistic regression considering mortality as the primary outcome and adjusted for multiple confounders disclosed an adjusted OR of 2.3 for COVID-19 infection (CI: 1.1-4.9) (Figure).

Conclusion:
In this cohort study, COVID-19 infection was an independent risk factor for mortality in stroke patients, regardless of comorbidities, age, sex and NIHSS.
Abstract TMP13: Thin Wall Regions Of Intracranial Aneurysms Are Associated With High Wall Shear Stress
Authors: Veeturi Sricharan , Patel Tatsat Rajendra , Chien Aichi , Baig Ammad , Monteiro Andre , Siddiqui Adnan H , Tutino Vincent
Published: February 2023

Background:
Intra-saccular hemodynamics play a key role in the pathobiological remodeling of the intracranial aneurysm (IA) wall. Evaluating the relationship between hemodynamic forces at the aneurysm wall and wall presentation can help us understand the complex processes of dysregulated vascular remodeling that occurs during IA natural history.

Hypothesis:
We hypothesized that greater hemodynamic insult, i.e., high wall shear stress (WSS) and high wall shear stress divergence (WSSD), results in endothelial damage and loss of internal elastic lamina, which presents as thin, translucent regions on interoperative imaging.

Methods:
From digital subtraction angiography images of 15 patients with IAs, aneurysm and surrounding vessels were segmented. Computational fluid dynamics (CFD) simulations were performed using generic boundary conditions for all the patients. Aneurysm walls were identified from 2D intraoperative images of IAs taken during clipping, and wall regions were classified as thick regions (white), normal (purple-crimson), and thin/translucent (red), using a semi-supervised machine learning algorithm. 2D wall classifications were mapped onto the 3D geometries for statistical analysis of differences between average hemodynamic properties across wall regions.

Results:
On an average, more than 30% of IA sac was visible on the 2D intra-operative image. Of the
n
=15 IAs,
n
=8,
n
=5 and
n
=2 showed pre-dominantly thick, thin, and normal wall types respectively. Average WSS and WSSD were significantly higher at thin regions of IAs as compared to both normal and thick regions. Thin wall regions also tended to co-locate with significantly lower RRT as compared to the thick and normal regions.

Conclusion:
Thin wall regions observed on intra-operative images of IAs are associated with greater hemodynamic insult (higher WSS and WSSD) and higher flow velocity (lower RRT).
Abstract TMP2: Intravenous Thrombolysis For Ischemic Stroke With Unknown Time Of Onset: Differences Between Wake-up Stroke And Non-wake-up Subtypes: EOS
Authors: Naruhiko Kamogawa , Miwa Kaori , Koga Masatoshi , Märit Jensen , Inoue Manabu , Yoshimura Sohei , Fukuda-Doi Mayumi , Ma Henry , Ringleb Peter , Wu Ona , Schwamm Lee H , Davis Stephen , Donnan Geoffrey A , Gerloff Christian P , Thomalla Götz , Toyoda Kazunori
Published: February 2023

Background:
The unknown onset stroke can be categorized into two groups; wake-up stroke (WUS) and non-wake-up unwitnessed stroke with a time of onset unavailable due to aphasia, impaired consciousness, or cognitive impairment (non-wake-up unknown onset stroke, non-WUS). We aimed to assess the differences in efficacy and safety of intravenous thrombolysis (IVT) for these subgroups.

Methods:
Patients with an unknown onset stroke from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo/standard treatment. A favorable outcome was defined as a modified Rankin Scale score 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22-36 hours and 90-day mortality. The effect of IVT was compared between the treatment groups in the WUS and non-WUS with mixed-effect logistic-regression analysis.

Results:
A total of 634 patients (233 women [36.8%], median age 70 years [IQR 61-76]) were analyzed. In patients with non-WUS (n=92 [14%]), advanced age, atrial fibrillation, vessel occlusion on MRA and high NIHSS score were more prevalent (P<0.01 for each) than those with WUS (n=542 [86%]). Overall, no significant interaction was noted between the mode of onset and treatment effect (Pinteraction=0.782). In patients with WUS, a favorable outcome was more common in the IVT group than the control (149 [54.8%] vs. 117 [45.5%], adjusted OR: 1.45, 95% CI 1.01-2.11), death occurred in 11 [4.0%] and 5 [1.9%] (p=0.099), and sICH occurred in 5 [1.8%] and 1 [0.3%] (p=0.142). In patients with non-WUS, no significant difference was observed for a favorable outcome (16 [37.2%] vs. 14 [29.2%], aOR 1.73 [0.60-4.98]). One death and one sICH were reported in the IVT group, but none in the controls.

Conclusions:
The benefit of IVT was significant in patients with WUS. Excellent outcome was also numerically more prevalent in non-WUS but this did not reach significance, probably due to the lack of statistical power.
Abstract TMP29: Elevated Levels Of Palmitic Acid Mediate Early Disruption Of Endothelial Barrier Integrity And Promote Behavioral Dysfunction Relevance To Vascular Cognitive Impairment And Dementia (VCID)
Authors: Karakaya Eda , Berber Burak , Tomberlin Jensen , Kurtz John , Courson Parker , Edwards Jazlyn , Albayram Onder , Ergul Adviye
Published: February 2023

Increased consumption of a high-fat diet (HFD) is believed to increase the risk for the development and progression of VCID, but the underlying mechanisms of how HFD leads to cognitive impairment are unclear, partly due to the use of different HFD models in preclinical studies. Palmitic acid (PA), the most common form of saturated fatty acid, found in the human cerebrospinal fluid in obesity, promotes disruption of BBB integrity. We hypothesized that a PA-rich diet mediates early disruption of blood brain barrier (BBB) integrity which leads to progressive neurovascular pathologies and cognitive impairment in VCID.

Methods:
Experimental design for
in vivo
studies is depicted in Fig 1.
In vitro
studies included assessment of endothelial integrity by trans-endothelial electrical resistance (TEER) and FITC measurements, cell viability, and expression levels of tight junction proteins and cell stress markers (Hsp70, Occludin1, Claudin 5, and Carnitine Palmitoyl transferase 1A -CTP1A) in male BMVECs cultured in normal and high PA conditions.

Results (Table):
Animals that were on the PA-rich diet exhibited risk-taking behavior. BMVECs showed significantly increased permeability of FITC-dextran and decreased TEER measurements. While Hsp70 and CTP1A increased with PA treatment, tight junction protein levels did not change.

Conclusion:
A special PA-rich diet mediates an anxiety-like behavior as early as 8 weeks without any metabolic effects. Assessments at 22 and 24W will determine whether behavioral dysfunction worsens and progresses to cognitive deficits. In vitro results suggest that initiation of the stress response may be the underlying mechanism of early BBB impairment. Modulation of the endothelial stress response may prevent/attenuate the development/progression of cognitive deficits induced by a PA-rich diet.