bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP58: The Effects of IV Thrombolytics for Stroke on Length of Stay and Time of ICU Admission in the Emergency Department - A Retrospective Comparative Review
Authors: Ly Doanh
Published: January 2025

Background:
Stroke is a leading cause of disability and death. The use of intravenous (IV) thrombolytics, such as alteplase and tenecteplase (TNKase), for acute ischemic stroke (AIS) is a standard of care. Tenecteplase has been recommended as an alternative agent to alteplase. In November 2020, the use of IV TNKase for AIS at a standard 0.25mg/kg dose was implemented at a small community hospital within a large integrated healthcare system. The use of TNKase without the required infusion may expedite admission to the intensive care unit (ICU).

Purpose:
The aim of this retrospective comparative review was to ascertain the effects of IV TNKase, compared to IV alteplase, on average length of stay (LOS) in the emergency department (ED) and time of ED to admission to the ICU (ED to floor).

Methods:
A total of 155 electronic patient charts were reviewed from January 2018 to June 2024. An unpaired t-test was used to determine the
p
value. The
p
value of < 0.05 was considered statistically significant.

Results:
There were no significant differences in the age and sex between the alteplase and TNKase patients. The average LOS and ED to floor measure were also not significant between the two groups (3.24 versus 2.87 hours,
p
= 0.11; 79.7 versus 63.4 minutes,
p
= 0.20, respectively). When examining the ED to floor measure from a different perspective, there was a significant improvement in the percentage of patients admitted to the ICU within 60 minutes – 54.3% (2018 – 2020) to 72.7% (2021 – 2023) to 85.7% in 2024.

Conclusion:
There have been numerous trials and studies published on the use of IV TNKase for AIS with promising results. The single bolus IV TNKase dose given over 5 seconds is an attractive nursing workflow. Without the use an infusion, post-TNKase patients may be admitted sooner to ICU. Reducing ED LOS improved throughput in a small often overcrowded ED. Additional in-depth reviews and data analysis would be needed to examine patient characteristics and clinical conditions, variations in workflow, operational needs, staffing, and documentation accuracy contributing to ED LOS and ED to floor measure.
Abstract TP59: Dysphagia Screening: Achieving and Maintaining High Compliance
Authors: Patterson Michele , MOORE TRACY
Published: January 2025

Background:
Baptist Health System [BHS] is a five-hospital system operating under one Provider Number with one combined Medical Staff. During a recent stroke certification survey, the BHS Comprehensive Stroke Center was recognized for consistent compliance with Dysphagia Screening [DS] that was well above the national benchmark. This was also true of all the hospitals within the BHS.

Purpose:
Share best practices for achieving and maintaining high compliance with DS within a system of hospitals.

Method:
Customized physician stroke orders [CSO] were developed for the Emergency Department [ED] and Inpatient [IP] units and utilization mandated across BHS to ensure completion of DS prior to first oral intake [FOI]. Both the ED and IP Registered Nurse [RN] were required to complete DS. ED CSO included 1] NPO until DS by RN passed; 2] Stat DS by RN prior to FOI, including medication and ice chips [Meds/Ice]. A “Reasons for Dysphagia Screening” job aid was developed and posted in the ED to prompt DS by RN for all stroke alert patients, all ED patients with brain imaging ordered and all patients with conditions/symptoms that may be associated with a high suspicion of aspiration risk. A “Dysphagia Screening Pathway” job aid was developed to ensure appropriate actions taken if passed or failed. IP CSO included 1] DS upon admission by RN prior to FOI, including Meds/Ice; 2] NPO until DS by RN passed, or if failed, then Speech Language Pathologist [SLP] swallow assessment completed; 3] SLP consultation for Evaluation&Treatment Dysphagia/Bedside swallow evaluation within 24 hours of admission. For NPO patients the route for medication administration was updated appropriately. DS metric compliance is shared with ED and IP RNs monthly. A written performance improvement plan using the Plan-Do-Study-Act model is implemented when the goal is not met for 3 consecutive months.

Results:
BHS DS compliance has remained between 91% - 95% for 10 consecutive years 2014-2023. National benchmarks range between 83-85% annually for the same period.

Conclusion:
Standardized processes, monthly data review, staff feedback, and written performance improvement plans led to a higher level of DS compliance within BHS.
Abstract TP69: Stroke Coordinator Academies: Providing Mentored Experiences for Novice Presenters
Authors: Hundt Beth , Funk Kathryn
Published: January 2025

Background:
According to AHA’s Scientific Statement,
Ideal Foundational Requirements for Stroke Program Development and Growth
, an essential role responsibility for stroke coordinators (SC) is to optimize stroke care within their facility and the community. SCs accomplish this by designing and implementing quality improvement (QI) projects close gaps in care identified through analysis of performance data. External sharing of QI work is essential to improve stroke care regionally and nationally.

Our statewide stroke coordinator consortium (SCC) has over 50 members, primarily nurses with stroke programs at varying certification levels. The SCC has quarterly stroke coordinators’ academies (SCA) with the goal to optimize stroke care across the state. During one academy, a poll revealed that few members had presented QI project externally, due to lack of knowledge and/or confidence.

Purpose:
To provide SCs with a mentored opportunity to present locally and submit abstracts to external conferences.

Methods:
Experienced presenters conducted two sessions at the SCA on conference abstracts and presentations, followed by an interactive abstract writing session, ending with a call for abstracts for an SCA conference. Presenters submitted a structured abstract for review. Accepted presenters met with mentors to refine abstracts, develop slides, and practice presentation. Presenters were allotted ten minutes for presentation and two minutes for questions. Audience members completed speaker feedback on delivery, content and organization, enthusiasm, and engagement. Organizers of the conference also asked for feedback from the presenters.

Results:
The SCA conference was well attended, and attendees indicated that this was a meaningful addition to the academy. Each presentation included robust discussion, supportive statements from the audience, and recommendations for further presentation. Presenters indicated that they received a high level of pre-presentation and audience support. Two thirds of the presenters indicated a high likelihood of presenting their work at an external conference within the year.

Conclusion:
For SCs who are novice presenters, participating in a mentored local stroke conference was a positive experience. Presenters indicated a high likelihood of sharing their work at a regional or national conference. The SCA conference was well received and the SCC plans to offer this opportunity at regular intervals going forward.
Abstract TP72: Large Core Trials – Game Changing for Stroke Care or falling on deaf ears?
Authors: Nguyen Dan , Ezzeldin Mohamad , Ezzeldin Rime , Mealer LeighAnn , Mir Osman
Published: January 2025

Introduction:
After publication of Large core trials that offered evidence that endovascular therapies (EVT) was more beneficial versus medical management for acute ischemic strokes with large vessel occlusion (LVO) in carefully selected patients. We aimed to see how the treatment paradigm has evolved following the publications of the large core trials at different institutions.

Hypothesis:
After Large Core Trials, we suspect moderate increase in EVT/MT for large core ischemic infarcts with LVO based on prior reported data of 20% more increment.

Methods:
This study was done as a retrospective review with IRB approval for chart review. Included population was defined those with ASPECTS 5 or less with LVO within 24 hours of presentation presenting to one of the 4 included Comprehensive stroke centers (CSC’s). Using Viz.ai automated software data, 3-month sampling of LVO alerted scans between the time period of 11/1/2021 to 1/31/2022 (before trials) and 11/1/2023 to 1/31/2024 (post Trials) at 5 CSC’s. Non contrast head CT was reviewed to select large core strokes defined as ASPECTS 5 or less, and evaluated whether or not these patients were taken for EVT/MT, and the primary reason for exclusion from EVT. Primary outcome was defined as percentage of patients taken for EVT in above population.

Results:
3-month sample of pre-large core data showed that 4/17 (23.5%) of patients with large ischemic core (ASPECTS 5 or less) had EVT. Of these 4, one was taken as a TESLA enrollment as we were a participating site for TESLA. Post large-core 3-month sampling revealed an improvement of 5/11 (45.4%) EVT rate for large core patients. Overall average discharge MRS (DC MRS) for large-core patients who received EVT with TICI 2B or greater revascularization was 3. Large core patients who did not receive EVT had average DC MRS of 5.1. The primary stated reason for not taking patients with large ischemic core for EVT pre and post large core trials was ‘large-core’ in every reviewed case.

Conclusion:
Given the favorable data seen in the recent Large-Core trials, the patients will probably benefit from EVT, however even in clinical trial enrolling site majority of Large core patients are still being taken for EVT. Some barriers to changing the treatment paradigm may include: slow adaptation of new data/trials, concern for symptomatic ICH, concern for futility, and recognition of the more favorable patient selection in terms of age/MRS in the Large-Core trials.
Abstract TP78: TIEMPPO: Telestroke Influence of Educating Minority Patients and Providers to Optimize treatment times and stroke awareness
Authors: Carrion Penagos Julian , Meyer Dawn , Torres Dolores , Baniqued Matthew , Ravi Vikas , Bowers Jeffrey , Pirahanchi Yasaman , Rapp Karen , Agrawal Kunal , Bavarsad Shahripour Reza , Modir Royya , Hemmen Thomas , Boden Bernadette , LaFree Andrew , Meyer Brett
Published: January 2025

Introduction:
Stroke education is critical for patients and healthcare providers managing acute ischemic stroke (AIS). In our hyperacute telestroke network, most spoke centers have shown improved key performance indicators (KPIs) for IV thrombolytics. However, some spoke centers with predominantly Spanish-speaking population and staff continue to face operational hurdles hindering KPI optimization. Previous bilingual education efforts in English and Spanish have shown limited success. We hypothesize that the cultural background of staff and patients at these sites may impact these efforts. Our goal was to explore the cultural factors influencing telestroke care to design an educational initiative that addresses the cultural context of our local community, with a focus on both cultural humility and competency, to improve AIS KPIs in telestroke networks.

Methods:
We conducted a descriptive, exploratory survey to identify key factors contributing to AIS KPIs, with a focus on cultural and language challenges. First, a survey was distributed online via RedCap to Emergency Department (ED) physicians, nurses, technicians, patients, and families. Survey data was analyzed to identify key themes. Based on these findings and future focus groups, culturally tailored educational lectures will be developed and presented. Time-sensitive KPIs will be tracked pre- and post-intervention using data from the Hub center’s clinical database.

Results:
From January 1st to September 12th, 2024, these spoke sites recorded overall KPI times slightly longer than the network median: Door-to-CT 21 minutes, Door-to-CT read 40 minutes, Door-to-stroke-code page activation 26 minutes, Door-to-decision 50 minutes, and Door-to-thrombolytic 68 minutes. To date, 25 ED staff members have completed the survey. Key findings include: 68% of staff are involved in Telestroke cases at least weekly, 80% feel prepared for Telestroke cases, and 68% expressed a need for post-stroke debriefings. Barriers to care included CT delays (44%) and difficulties with the Telestroke machine (44%). Additionally, 64% of staff indicated an immediate need for translation support. Further qualitative themes and updated KPI metrics will be reported.

Conclusion:
In a culturally diverse country like the U.S., medical conditions must consider the cultural backgrounds of both patients and care providers. Integrating cultural humility and competency into stroke care can enhance understanding and improve stroke outcomes.
Abstract TP8: Prolonged Low-Dose Intravenous Thrombolysis in early recurrent Stroke: ESR-PROLONG Study
Authors: Cernik David , Neumann Jiri , Vondrackova Simona , Vachova Marta , Macko Jan
Published: January 2025

Introduction:
Treatment of acute stroke has its clear rules and established standards. However, in the case of a very early recurrence, the situation is unclear, there is no clear recommendation and the options are limited. We present the results of a multicenter retrospective study using prolonged low-dose intravenous thrombolysis.

Methods:
The multicenter retrospective study ESR_PROLONG (2020-2024) included consecutive patients who were given intravenous thrombolysis (20 mg alteplase continuously for 10 hours) during an early (within hours after standard recanalization therapy) recurrence of ischemic stroke. The clinical status was evaluated according to the NIHSS (National Institutes of Health Stroke Scale) at the time of recurrence and the day after the application of rescue therapy, and further according to the mRS (modified Rankin Scale) at an interval of 90 days. The safety of the treatment was evaluated based on the occurrence of any complications, the occurrence of intracerebral hemorrhage, and the occurrence of symptomatic intracerebral hemorrhage (assessed according to SITS-MOST criteria).

Results:
44 patients were enrolled in 4 centers (45.5% men, average age 71.5±12.2 years). The neurological deficit corresponded to 5 points in the median NIHSS after a previous stroke, 11 points at the time of recurrence, and 7 points after rescue therapy. Improvement occurred in 70.5% of patients. A good clinical outcome (mRS 90day ≤2) was achieved by 61.4%. Mortality was 15.9%. The incidence of intracerebral hemorrhage was 9.1% and we did not observe symptomatic intracerebral hemorrhage. There were also no other complications.

Conclusion:
Rescue therapy in the form of prolonged low-dose thrombolysis seems to be an effective and safe alternative to therapeutic nihilism in ultra-early stroke recurrence. Data from a randomized trial would significantly contribute to confirming the results.
Abstract WMP10: Evaluating Tenecteplase Versus Alteplase in Acute Ischemic Stroke Management: Real-World Insights for Clinical Decision-Making
Authors: Hong Lucia , Bannoud Makhlouf , Ibelaidene Maya , Woo Daniel , Novak Daniel
Published: January 2025

Introduction:
Tenecteplase (TNK) has 14-times greater specificity for fibrin and a longer half-life compared to alteplase (ALT), offering practical advantages for ease of administration and cost effectiveness in managing acute ischemic stroke (AIS). Studies regarding safety and efficacy have shown TNK to be non-inferior to ALT, with some analyses showing greater improvements in AIS recovery with TNK compared to ALT. Our study investigated outcomes following TNK or ALT for AIS by stroke severity.

Methods:
Data was collected from the TriNetX US Collaborative Network, which allowed access to de-identified retrospective electronic medical records. Patients treated with TNK or ALT for AIS after January 1, 2019 were divided into subgroups by stroke severity using the National Institutes of Health Stroke Scale (NIHSS). Patients who underwent acute mechanical thrombectomy were excluded. Propensity score matching for baseline characteristics was performed (Figure 1). Outcomes including any (asymptomatic or symptomatic) nontraumatic intracerebral hemorrhage (ICH), mortality, non-intracerebral hemorrhage, and changes in NIHSS score were assessed over 7 days from the index event. Statistical analysis was completed on the TriNetX platform.

Results:
Patients with mild AIS (NIHSS 1-4) who received TNK (n=1,639) versus ALT (n=1,639) had greater risk for developing ICH (10.3% vs 7.4%, p=0.004) and worsened NIHSS score (15.8% vs 9%, p<0.0001). For moderate (NIHSS 5-15, n=1,908), moderate severe (NIHSS 16-20, n=329), or severe (NIHSS 21-42, n=372) AIS, TNK had greater likelihood for improved NIHSS score compared to ALT (moderate 14.3% vs 8.3%, p<0.0001; moderate severe 21.9% vs 14.3%, p=0.011; severe 20.2% vs 13.4%, p=0.014). For moderate to severe AIS, there was similar risk for ICH with TNK versus ALT (moderate 12.5% vs 11.2%, p=0.21; moderate severe 23.4% vs 21.6%, p=0.575; severe 26.9% vs 22.8%, p=0.203). There were no statistically significant differences in risk for mortality and non-intracerebral hemorrhage for TNK versus ALT across all NIHSS categories (Figure 2, Table 1).

Conclusion:
For NIHSS ≤4, TNK was associated with higher risk of ICH and worsened stroke severity compared to ALT, suggesting ALT may be safer for mild AIS. However, TNK may be preferrable for moderate to severe AIS with NIHSS ≥5 as TNK was associated with greater likelihood for improved stroke severity with similar risks for ICH, mortality, and other non-intracerebral hemorrhages compared to ALT.
Abstract WMP101: Atrial Cardiopathy Biomarkers and Brain Infarction in Multiple Territories in ARCADIA
Authors: Gologorsky Rachel , Karunamuni Nilushi , Longstreth W , Tirschwell David , Elkind Mitchell , Kamel Hooman
Published: January 2025

Introduction:
The ARCADIA trial (Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy) found no benefit of anticoagulation for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. It remains unclear if the biomarkers used in the trial reliably identified atrial cardiopathy. We examined the association between biomarkers of atrial cardiopathy and acute brain infarction in multiple arterial territories, an imaging signature of cardioembolic stroke.

Hypothesis:
Biomarkers of atrial cardiomyopathy are associated with acute brain infarction in multiple arterial territories.

Methods:
The ARCADIA trial screened patients with cryptogenic stroke for atrial cardiopathy at 185 centers in the U.S. and Canada. Investigators were asked to record the presence and topography of acute brain infarction on baseline imaging. Multi-territorial infarction was defined as acute infarction in at least two of the left middle cerebral artery (MCA), right MCA, and posterior circulation. P-wave terminal force in ECG lead V1 (PTFV1) and left atrial dimension index (LADI) were modeled as continuous variables, whereas N-terminal pro-B-type natriuretic peptide (NT-proBNP) was log-transformed. Relative risk regression was used to examine the association between atrial cardiopathy biomarkers and multi-territorial infarction.

Results:
Of 3,745 patients enrolled in ARCADIA, 3,301 had available data on atrial cardiomyopathy biomarkers and the topography of acute infarctions seen on baseline imaging. Of these 3,301 patients, 452 (13.7%) had multi-territory brain infarction. We found no association with multi-territory brain infarction for ln(NT-proBNP) (OR per SD, 1.06; 95% CI, 0.97-1.16), PTFV1 (OR per SD, 1.06; 95% CI, 0.98-1.15), or LADI (OR per SD, 0.95; 95% CI, 0.86-1.05). Patients who met criteria for atrial cardiopathy and were randomized into the treatment phase of the study had a similar likelihood of multi-territorial infarction (13.4%) compared with those who were not eligible for randomization (13.8%) (P = 0.77).

Conclusions:
The atrial cardiopathy biomarkers used in the ARCADIA trial were not associated with patterns of brain infarction suggestive of a cardioembolic source.
Abstract WMP103: Transportation and biomass combustion (including from wildfires) are air pollution sources associated with stroke incidence among women in the California Teachers Study cohort (2000-2018)
Authors: Wang Sophia , Franklin Meredith , Cauble Emily , Epeldegui Marta , Spielfogel Emma , Lacey James , Benmarhnia Tarik , Yao Mandy , Wu Jingyuan , Zhao Juan , Anderson Cheryl , Elkind Mitchell , Kleeman Mike
Published: January 2025

Introduction:
Ambient air pollution (particulate matter (PM) 2.5, defined as particles
<
2.5 microns in diameter) has long been linked to increased stroke risk. However, few studies have described the specific sources or estimated the effects of the PM2.5 constituents responsible for stroke and stroke subtype risk.

Hypothesis:
We hypothesize that chronic long-term exposure to a major source of air pollution, transportation and its related constituents, will be associated with elevated stroke risk.

Methods:
In a prospective cohort study of 133,477 women enrolled in the California Teachers Study in 1995-96, we evaluated 110,120 women who resided in California from 2000-2018 (median follow-up=19 years) for residential exposure to primary aerosol concentrations of 8 PM2.5 sources (on- and off-road gasoline vehicles, on- and off-road diesel, biomass combustion, food cooking, aircraft, natural gas combustion), and 11 constituents (including copper, iron, manganese, nitrate, elemental carbon, organic compounds) generated from a 4-km grid chemical transport model. Stroke and stroke subtypes were identified during cohort follow-up with ICD-9 and ICD-10 codes from state hospitalization records (all stroke n=4,348; ischemic stroke n=3,596; hemorrhagic stroke n=752). Cox proportional hazards models were used to estimate hazard ratios (HRs) for associations between the pollutants (average exposure across follow-up) ) with overall stroke and stroke subtypes, adjusted for stroke risk factors.

Results:
We observed positive associations between PM2.5 exposure from on-road gasoline vehicles with all stroke (HR=1.18, 95% CI=1.11-1.26), ischemic stroke (HR=1.16, 95% CI=1.09-1.26), and hemorrhagic stroke (HR=1.28, 95% CI=1.09-1.49). PM2.5 from off-road diesel was also associated with all stroke (HR=1.21, 95%CI=1.11-1.31), ischemic stroke (HR=1.19, 95% CI=1.09-1.30), and hemorrhagic stroke (HR=1.29, 95% CI=1.06=1.57). PM2.5 from biomass combustion was positively associated with ischemic stroke (HR=1.10, 95% CI=1.02-1.19), but not hemorrhagic stroke. Of PM2.5 constituents evaluated, organic compounds were associated with ischemic stroke (HR=1.14, 95% CI=1.00-1.31).

Conclusions:
Two major PM2.5 sources, on-road gasoline transportation and off-road diesel, are associated with increased risk of all stroke and stroke subtypes among our female cohort. Long-term exposure to biomass combustion, which includes wildfires, and organic compounds from PM2.5 were linked to ischemic stroke only.
Abstract WMP105: Multimodal Deep Learning for Ischemic Stroke Prediction by Integrating Demographic, Clinical, and Atrial Phenotypic and Genotypic Data
Authors: Leifer Dana , Bai Zilong , Perry James , Cole John , Nguyen Kevin , Gaynor Brady , Xu Huichun , Wang Fei
Published: January 2025

Introduction:
Accurate prediction of the risk of ischemic stroke (IS) is vital for prevention and would be aided by multimodal biomarkers integrating genetic, clinical, and functional data. The role of imaging and EKG based atrial measurements, other than atrial fibrillation (AF), in IS prediction is uncertain and many strokes remain cryptogenic despite extensive work-up. As an exploratory step to improve stroke evaluation by including atrial traits, we developed a novel multimodal deep learning model integrating demographic and clinical variables with atrial phenotypic and genotypic data.

Methods:
We collected individuals from UK Biobank (UKBB) and defined ischemic stroke (IS) by the UKBB Algorithmically Defined Outcome (ADO). We developed a multimodal multi-layer perceptron with late fusion (MMLP-LF) model to predict whether a subject has IS by integrating five data modalities from UKBB: 1) MRI and EKG derived atrial traits, 2) lead genetic variants (P<5e-8) from GWAS of atrial traits, 3) patient demographics, 4) ICD codes including AF but excluding IS codes and 5) procedure codes related to cardiac valve surgery. We split the samples into 64%-16%-20% train-validation-test sets via stratified random sampling. Models were trained on the training set with 20 rounds of random initialization. The validation set was used for model selection. We used Area Under the Receiver Operating Characteristic Curve (AUROC) for performance evaluation. Shapley additive explanation (SHAP) analysis was conducted for feature importance attribution.

Results:
Our dataset included 24,582 individuals from the UKBB, among which 100 (0.41 %) had IS. Our full MMLP-LF model including 5 modalities achieved the highest AUROC of 0.85 for predicting IS on the hold-out test set, substantially outperforming the best unimodal branch (AUROC 0.79 with ICD codes, 0.71 with demographic variables). If we excluded atrial phenotypes, the AUROC was still 0.85. If genetic traits were also removed, the AUROC declined to 0.82. SHAP analysis revealed that ICD codes for hypertension and hyperlipidemia are the most influential contributors to the full model followed by GWAS-identified lead genetic variants associated with atrial traits (Figure).

Conclusion:
Our MMLP-LF model improved IS prediction over unimodal models by integrating multimodal data and identified genetic and clinical drivers predicting IS. This model establishes a new paradigm for integrating multiple modalities to predict IS outcomes.
Abstract WMP110: The activation of β-catenin in cerebral endothelial cells alleviates neurovascular damage after ischemic stroke
Authors: Zhang Li , Teng Hua , Luo Hao , Powell Brianna , Taketo Makoto , Chopp Michael , Zhang Zheng Gang
Published: January 2025

Background:
Stroke induced disruption of the blood-brain barrier (BBB) exacerbates neurovascular damage. Emerging data show that deficiency of endothelial β-catenin contributes to stroke-induced BBB disruption and hemorrhagic brain injury. However, whether activation of β-catenin in cerebral endothelial cells (CECs) alleviates stroke induced neurovascular damage is unknown. Using transgenic mice with CEC specific activation of β-catenin, the present study investigated whether enhancement of CEC β-catenin activity reduces neurovascular damage after stroke.

Methods:
A transgenic mouse line with inducible CEC specific expression of a stable β-catenin mutant (CEC-Ctnnb1 mice) was generated by crossing Slco1c1-Cre
ERT2
mouse with Ctnnb1
flex3
mouse. Tamoxifen (TAM) was injected for 5 days to active Cre recombinase. Western blot was performed to verify β-catenin activation in the adult CEC-Ctnnb1 and their wild-type (WT) littermates (n=6/group) after termination of TAM. Male CEC-Ctnnb1 and WT mice treated with TAM were subjected to permanent middle cerebral artery occlusion (MCAO, n=10/group). Neurological function was evaluated with modified neurological severity score and foot-fault test at 1 and 7 days after MCAO. Brain tissues were processed for evaluations on infarct volume, gross hemorrhage, vascular leakage, and tight junction protein expression.

Results:
Immunohistochemistry and Western blot analyses revealed nuclear β-catenin expression specifically in the CECs of CEC-Ctnnb1 mice, but not in the WT mice, which was associated with significant elevation of β-catenin regulated the tight junction proteins, claudin 5 and ZO-1 by ~2 fold, compared to the WT mice. The ischemic CEC-Ctnnb1 mice exhibited significantly reduced infarct volume (16±5% vs 25±6% in WT), which was associated with a robust reduction of neurological deficits by 35% and 53% at 1 and 7 days after MCAO, respectively. Compared to the WT ischemic mice, ischemic CEC-Ctnnb1 mice exhibited significant increases of vascular claudin-5 by 45% and ZO-1 by 31%, which were associated with a significant reduction of extravascular fibrin deposition (5±1/mm
2
vs 8±1/mm
2
in WT). However, the incidence of gross hemorrhage was not different between the groups.

Conclusions:
The activation of β-catenin in CECs attenuates ischemic brain damage by alleviating stroke induced cerebrovascular disruption. Thus, targeting endothelial β-catenin signal may be a promising strategy for treatment of acute ischemic stroke.
Abstract WMP114: Clonal hematopoiesis of indeterminate potential promotes the development of intracranial aneurysm rupture
Authors: Uchikawa Hiroki , Maeda Takuma , Cisneros Oscar , Nisson Peyton , Fraser Claire , Bowen Sara , Ai Jinglu , Lawton Michael , Hashimoto Tomoki
Published: January 2025

Introduction:
Clonal Hematopoiesis of Indeterminate Potential (CHIP) is characterized by the expansion of a blood-cell clone due to somatic mutation in hematopoietic stem cells, in the absence of other hematologic abnormalities. Initially, CHIP was identified as a risk factor for hematologic cancer, but recently, many studies have implicated it as a risk factor for cardiovascular disease. CHIP is also considered a risk factor for subarachnoid hemorrhage. However, the causality between CHIP and aneurysm rupture, as well as the mechanism by which CHIP promotes aneurysm rupture, remains unclear. Our study aimed to assess whether CHIP promotes the development of intracranial aneurysm rupture and investigate its mechanisms in mice. We induced intracranial aneurysms on chimeric mice with partial bone marrow transplantation of TET2-knockout hematopoietic stem cells, widely used to recapitulate human CHIP to test our hypothesis.

Methods:
We used competitive bone marrow transplantation as a model of CHIP. We used the C57BL/6 congenic mice that express the CD45.1 allele as a recipient and TET2-knockout mice that carry CD45.2 alleles as a donor. C57BL/6 CD45.1+/CD45.2- congenic mice were transplanted with suspensions of bone marrow cells containing 10% CD45.1-/CD45.2+ TET2-/- cells and 90% CD45.1+/CD45.2- TET2+/+ cells as a TET2-derived CHIP model. We induced intracranial aneurysms by a combination of elastase injection and DOCA-salt hypertension at 8 weeks later. We evaluated the formation and rupture rates of intracranial aneurysms and the survival curve. The qPCR was used to reveal molecular change in the intracranial artery. From the result of qPCR, we utilized IL-6 monoclonal antibody and NLRP3 inhibitor as a treatment for CHIP-related intracranial aneurysm rupture.

Results:
First, CHIP mice show clonal expansion of TET2-knockout cells in flow cytometry (Fig.1). Our studies demonstrated increased aneurysmal rupture rates in CHIP mice of both sexes (Fig.2). Second, Inflammatory cytokines including IL-6, IL-1β, and NLRP3 were elevated in qPCR (Fig.3). Lastly, both IL-6 monoclonal antibody and NLRP3 inflammasome inhibitor significantly decreased aneurysm rupture rate in CHIP mice.

Conclusions:
Our study showed that CHIP promotes the development of intracranial aneurysm rupture. Its mechanism is through the upregulation of inflammatory cytokines. Our findings suggest that IL-6 and NLRP3 are promising therapeutic targets for CHIP-related intracranial aneurysm rupture.
Abstract WMP13: Cardiac Injury Potentially Contributes to Neuroinflammation via Extracellular Vesicles
Authors: Li Qingxuan , Dhyani Neha , Gao Lie , Rudebush Tara , Zucker Irving , Tian Changhai
Published: January 2025

Cognitive impairment (CGI) is common in patients with cardiovascular diseases, contributing to morbidity and mortality, especially among people over the age of 64. Cardiogenic dementia has been suggested to characterize patients suffering from cognitive decline after heart disease. Clinical and experimental evidence further suggest that 35%-65% of patients with myocardial ischemia are affected by CGI which include memory and global cognitive deficits. Although increasing evidence suggests that neurological disorders, such as stroke underlying a brain-heart axis can lead to myocardial injury and cardiac dysfunction, the heart-brain axis remains to be completely understood.

To elucidate the potential effects of myocardial injury on the CGI and the underlying mechanism by which cardiac damage regulates brain dysfunction, we employed a rodent model of myocardial infarction (MI) generated by left coronary artery ligation and a cardiac-specific GFP
+
Tg reporter mouse model to track the brain distribution of cardiac extracellular vesicles (EVs), combining
in vitro
imaging, cellular and molecular techniques. Here we demonstrate crosstalk between heart and brain via EVs, and glial cell uptake of GFP
+
cardiac EVs (See Figure). Importantly, myocardial injury not only promotes the brain distribution of cardiac EVs, but also elicits a neuroinflammatory response
in vitro
and
in vivo
. Further molecular studies suggests that cardiac EVs are abundant with miR-21-5p, which was selectively upregulated in cardiac cells in the post-MI model and transported by EVs. We also confirmed that miR-21-5p overexpression
in vitro
caused a pro-inflammatory response in brain microglia.

Taken together these observations indicate that weeks following MI, cardiac-secreted EVs abundant with miRNAs communicate with the brain and are associated with microglial activation, which may be responsible for neuroinflammation and neurotoxicity leading to cognitive impairment.

Keywords:
Myocardial injury; Cardiogenic dementia; Neuroinflammation; Extracellular vesicles; microRNAs

Funding source:
This work was supported by the National Institution of Health R01HL153176 (IZ/CT); American Heart Association (AHA) Career Development Award (19CDA34520004) and AHA Transformational Program Award (https://doi.org/10.58275/AHA.24TPA1300008.pc.gr.198448) to CT.
Abstract WMP2: A Trial of Patients Receiving Remote Ischemic Conditioning in Early Stroke (PRICES) in a Tertiary Hospital in the Philippines: An Open Label Study
Authors: Ang Kevin Royce , Juangco Dan , Hernandez Maria Kim
Published: January 2025

The treatment strategy for acute ischemic stroke (AIS) is reperfusion. In addition, neuroprotective measures have influenced outcomes in mortality, morbidity, and disability. Remote ischemic conditioning (RIC) is a neuroprotective measure that minimizes ischemic reperfusion injury to the target organ. Previous trials have showed its safety and efficacy, but its impact to vascular cognitive impairment and quality of life is undermined. This study aimed to demonstrate its efficacy and impact in terms of disability, cognitive impairment, and quality of life.

This is a single center, open-label trial conducted in a tertiary center in the Philippines which included 104 patients randomized to RIC (n=52) and control (n=52) groups. One dose of RIC comprised of 4 cycles of BP cuff inflation 20mmHg above baseline systolic blood pressure (ceiling of 180mmHg) for 5 minutes followed by 5 minutes of cuff deflation; a total of 8 doses of RIC were given over four days with 12 hour intervals. The control arm did not receive cuff inflations; both groups received guideline-based standard stroke care.

Out of 104 patients, 10 (9.6%) were excluded from full analysis; 6 patients were excluded due to mortality, while 4 patients failed to undergo MOCA-P and HRQoL testing due to severe aphasia. RIC procedure was completed according to the study protocol in all enrolled 52 patients.

Both groups had similar baseline clinical and radiologic findings. NIHSS scores across admission, 24 hours, and discharge timepoints show significant change in the RIC group, while the control group only showed significant NIHSS change between the admission and 24 hour timepoints. The mean MOCA-P scores are 26.5 for RIC group vs control group (25.9). Subgroup analysis for MOCA-P classification showed that RIC group had more normal scores (70.8%) vs control group (65.2%). The control group also had more patients under moderate/severe scores (6.4%). The mean HRQoL score at 90 days for RIC group was 90.6 vs 84.7 for control group. Subgroup analysis showed that the RIC group had a mean pain score of 92.5 vs control group 78.7, which was statistically significant (p<0.01).

Remote ischemic conditioning in acute ischemic stroke reduced stroke severity during admission, and increased the likelihood of better quality of life at 90 days. The prevalence of cognitive impairment was more evident in patients who did not receive RIC, but these findings require replication in a larger trial to prove its statistical power.
Abstract WMP25: Predictors of Certified Stroke Center Presence in the Northeastern United States
Authors: Teshome Abigail , Taman Mazen , Perelstein Elizabeth , Proulx Jeffrey , Feler Joshua
Published: January 2025

Introduction:
Timely intervention is essential for reducing stroke mortality, yet the distribution of AHA-certified stroke centers (SCs) is not always in line with community needs, particularly in areas with high stroke prevalence. This study examines the relationship between the presence of certified stroke centers and county-level characteristics such as demographics, stroke prevalence and mortality, risk factors, and urbanization in the northeastern United States.

Methods:
Publicly available data from the U.S. Census Bureau and CDC Interactive Atlas of Heart Disease and Stroke were analyzed using a generalized linear model to examine the relationship between SC distribution and county demographics, stroke prevalence and mortality, and prevalence of stroke risk factors. Northeastern states were identified as Connecticut, Maine, Massachusetts, New Hampshire, New Jersey.

Results:
Comprehensive (CSC) (adjusted odds ratio, 0.87 [95% CI, 0.83–0.91];
P
<0.001), Primary (PSC) (adjusted odds ratio, 0.84 [95% CI, 0.79–0.89];
P
<0.001), and Thrombectomy-Capable (TSC) (adjusted odds ratio, 0.97 [95% CI, 0.95–0.99];
P
=0.003) center presence demonstrated a negative relationship with rurality. Lower overall SC density was observed in counties with high prevalence of hypercholesterolemia (adjusted odds ratio, 0.96 [95% CI, 0.93–0.99];
P
=0.003). The absence of a CSC or PSC in a county was associated with a mean household income decrease of over $9,000 (
P
=0.005;
P
<0.001, respectively). Additionally, higher prevalence of stroke was associated with lower odds of PSC presence (adjusted odds ratio, 0.78 [95% CI, 0.67–0.90];
P
<0.001).

Conclusion:
This study reveals significant disparities in certified stroke center distribution in the northeastern U.S. While these centers reduce stroke mortality, their distribution does not uniformly reflect community needs. Of particular note was the negative association between stroke prevalence and the presence of PSCs, as PSCs often serve as the care access point for stroke patients in a hub-and-spoke system. These data point to a gap in access to specialized stroke care where it is most needed. Addressing the gap requires policymakers to consider both geographic and social factors, potentially expanding stroke centers in underserved regions to improve outcomes. Future research should focus on strategies to reduce these inequities and enhance access to stroke care.
Abstract WMP31: Comparison of FAST and BE-FAST Performance Among the General Public
Authors: Ancheta Selina , Denny Mary Carter , Dunn Mary , Elkind Mitchell , Kleindorfer Dawn , Lane Patricia , Madhok Debbie , Miller-Smith Katie , Mohl Stephanie , Philpot Debra , Reeves Mathew , Witt John , Zachrison Kori , Adeoye Opeolu
Published: January 2025

Introduction:
Retrospective studies have compared the sensitivity of FAST (Face drooping, Arm weakness, Speech difficulty, and Time to call 911) to BE-FAST (adds Balance loss, Eye changes to FAST), but rigorous studies comparing these mnemonics’ effectiveness in motivation to call 911 and testing recall of key stroke symptoms are lacking. Our objectives were to determine if FAST or BE-FAST was associated with better recall of the mnemonic at 30-days, and whether either mnemonic was more likely to prompt calling 911.

Methods:
A nationally representative online survey of English-speaking members of the US general public was conducted. A randomized parallel 2-group design was used to compare the efficacy of FAST and BE-FAST presented as 1-minute educational videos. Assessments were made immediately (n=1,900) and 30-days later (n=1,393). T-Tests and ANOVA were used to estimate differences between groups on intent to call 911 and stroke symptom knowledge at baseline, immediately after the education, and at 30-days. Analyses were adjusted for age, stroke knowledge/experience, education level and baseline familiarity with the mnemonic.

Results:
Immediately after the educational video, the likelihood of calling 911 if a stroke was suspected increased in both groups (72% to 90% in FAST and 71% to 90% in BE-FAST, p<0.001), with no difference between the groups (Figure 1). Participants’ ability to identify what the common letters F, A, and S represent was significantly higher immediately after the video than at baseline for both mnemonics (34% to 70% in FAST and 29% to 50% in BE-FAST, p<0.001). FAST had significantly higher common letter performance than BE-FAST immediately after education (70% versus 50%, p<0.001) (Figure 2).

At 30-days, the likelihood of calling 911 had declined slightly in both groups but remained increased compared to baseline with no difference between groups (Figure 1). Participants’ ability to recall what the common letters meant declined for both groups but remained higher than at baseline. Again, FAST had significantly higher common letter performance than BE-FAST after 30-days (50% versus 40%, p<0.001) (Figure 2).

Conclusions:
Amongst the general public, FAST and BE-FAST were equally effective in increasing participants’ likelihood of calling 911 immediately if they suspected a stroke, and this effect persisted at 30-days. FAST performed significantly better than the BE-FAST in recalling face, arm and speech symptoms at all time points.
Abstract WMP32: Cross-Platform Proteomics and Machine Learning Algorithms Nominate Biomarkers of Stroke Diagnosis: An Exploratory Study
Authors: Misra Shubham , Natu Aditya , Kumar Prateek , Watson Caroline , Frankel Michael , RANGARAJU Srikant
Published: January 2025

Introduction:
Rapid stroke diagnosis is critical in the early stages to initiate stroke subtype-specific treatment soon after symptom onset.

Objectives:
We undertook a cross-platform proteomics study to discover plasma biomarkers of stroke diagnosis in emergency room (ER) settings.

Methods:
We analyzed clinical and proteomics data from stroke patients aged ≥18 years using a prospective plasma repository from 2010 to 2014. Blood samples were collected at admission to the ER before any therapeutic intervention. Our outcomes were differentially expressed protein (DEP) levels between patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimics (MIM). We performed aptamer-based proteomics using the plasma 7K SomaScan assay. For pairwise comparisons, we identified the DEPs using ±1.5-fold change and unadjusted p-value <0.05 cut-offs, Boruta random forest feature selection, and variance partitioning analyses. We identified the top proteins and conducted multivariable logistic regression analyses. For multigroup comparisons, we performed feature selection by sparse partial least squares discriminant analysis (sPLS-DA) using the mixOmics R package. We conducted internal validation on the same samples using the PeptiQuant Plus biomarker assessment kits (BAK-270) for targeted protein quantitation (Figure 1).

Results:
We included 100 patients (mean age 58.6 years, 43% males) classified into four subgroups: 40 AIS, 20 ICH, 20 TIA, and 20 MIM (Figure 2). SomaScan quantified 7307 somamers targeting 6373 unique proteins. Using pairwise and multigroup comparisons, we nominated the top 58 proteins that differentiated the stroke subtypes. We identified a panel of 7 proteins as top AIS classifiers (area under the curve (AUC): 0.82, negative predictive value (NPV): 74%), 5 proteins as top ICH classifiers (AUC 0.88, NPV: 90%), 8 proteins as top MIM classifiers (AUC 0.94, NPV: 94%), and 6 proteins as top TIA classifiers (AUC 0.94, NPV: 91%) (Figure 3). In the validation phase, targeted proteomics validated VTN and PLG as top MIM classifiers against AIS, ICH, and TIA.

Conclusions:
Our exploratory study highlights plasma proteomics as a valuable tool for discovering protein biomarkers for stroke diagnosis. Further research is warranted to validate these findings in larger multi-center cohorts and to elucidate their clinical utility in ER settings for guiding therapeutic decision-making and improving patient outcomes.
Abstract WMP51: Addressing Sleep Apnea Post-Stroke and Transient Ischemic Attack (ASAP) Stepped-Wedge Cluster-Randomized Trial: Effectiveness of a Quality Improvement Intervention to Increase Sleep Apnea Diagnostic Testing
Authors: Bravata Dawn , Perkins Anthony , Myers Laura , Daggy Joanne , Sexson Ali , Taylor Stanley , Burrone Laura , KOO BRIAN , Miech Edward , Rattray Nicholas , Story Kristin , Waddell Kimberly , Ding Qinglan , Jason Sico
Published: January 2025

Background:
Obstructive sleep apnea (OSA) is common among patients with ischemic stroke and transient ischemic attack (TIA) and has been associated with poor outcomes. Guidelines recommend evaluating eligible patients with cerebrovascular events for OSA.

Objective:
to examine whether a quality improvement (QI) intervention could increase OSA testing post-stroke/TIA.

Methods:
ASAP (NCT04322162) was a stepped-wedge cluster-randomized trial evaluating the effectiveness of a QI intervention to increase OSA testing among ischemic stroke or TIA patients at intervention (N=6) vs. control sites (N=30). Recruitment was at the facility level. The study involved 3 phases: baseline, implementation, and sustainability. The primary outcome was: 30-day OSA diagnostic testing rate. Secondary outcomes were: 30-day continuous positive airway pressure treatment rate, and 90-day recurrent vascular event and readmission rates. ASAP was powered to detect a difference in the primary outcome: baseline vs. implementation. Generalized linear mixed-effects models with binomial distribution and log link fit to patient-level data with site-level random effects were used. The QI intervention included: a virtual kickoff (teams reviewed data, identified improvement opportunities, considered barriers and solutions to diagnosing OSA post-stroke/TIA, and action plan development); monthly collaborative conferences; web-based platform displaying quality data and resource library; and external facilitation.

Results:
Among 1747 patients at 6 intervention sites the diagnostic rate increased from 2.1% (baseline, 20/952) to 29.1% (implementation, 189/650); among 7454 patients at 30 control sites the 30-day diagnostic rate varied (0.6%-2.2%; adjusted odds ratio (aOR) 16.90 (95%CI, 9.49-30.10). The diagnostic rate during sustainability was 11.7% (17/145); aOR 3.58 (1.59-8.04). The 30-day treatment rate varied (0.0%-0.4%) at control sites and increased at intervention sites: 0.3% (baseline, 3/952) to 2.8% (implementation, 18/650; OR 14.22 (2.40-84.40). The treatment rate during sustainability was 0.7% (1/145); aOR 2.66 (0.13-56.21). 90-day readmission and recurrent event rates were lower during implementation and sustainability (vs. baseline); these changes were not statistically significant.

Conclusions:
QI approaches can markedly increase OSA testing among patients with acute cerebrovascular events. Additional work should identify strategies to increase treatment rates among stroke/TIA patients with OSA.