bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP252: MARS: Migraine and Retinal Stroke - A Population-Based Cohort Study of 39 Million Patients
Authors: Lusk Jay B , Song Ailin , Unnithan Shakthi , Al-Khalidi Hussein , de Havenon Adam H , Biousse Valerie , Schrag Matthew , Poli Sven , Osazuwa-Peters Nosayaba , Xian Ying , Obrien Emily C , Mac Grory Brian C
Published: February 2024

Introduction:
Migraine is a risk factor for cerebral ischemic stroke. However, it is not known if migraine is a risk factor for retinal stroke (central retinal artery occlusion, CRAO).

Methods:
We performed a retrospective cohort study using population-based data from the State Inpatient Databases and State Emergency Department Databases from New York (2006-2015), California (2003-2011), and Florida (2005-2015) to determine the association between hospital-documented migraine and retinal stroke. The primary exposure was hospital-documented migraine. The primary endpoint was hospital-documented CRAO (ICD-9-CM code 362.31 in the primary diagnosis position) and secondary endpoints included BRAO and any retinal artery occlusion (RAO). Cause-specific hazard models were used to model the association between migraine and CRAO.

Results:
Of 39,835,024 patients included in the study, 1,109,140 had migraine documented during the exposure window. Patients with migraine were younger (40.2±15.2 vs. 46.9±19.8, standardized difference (SD) 0.38), more likely to be female (81.4% vs. 54.7%, SD 0.6), and had a lower burden of atrial fibrillation (4.5% vs. 6.9%, SD 0.1), chronic kidney disease (1.9% vs. 3.6%, SD 0.2), and congestive cardiac failure (2.7% vs. 5.1%, SD 0.12). Migraine was not associated with CRAO in the primary diagnostic position (adjusted hazard rate (aHR) 1.15 (95% CI: 0.79-1.67). However, it was associated with CRAO in any diagnostic position (aHR 1.39 (95% CI: 1.08-1.78). As positive controls, we replicated previously established associations of migraine with cerebral ischemic stroke (aHR 1.35 (95% CI: 1.32-1.38) and embolic ischemic stroke (aHR 1.15 (95% CI: 1.08-1.22).

Conclusions:
In a large, claims-based study, we found a risk-adjusted association between migraine and CRAO considered in any diagnostic position. This finding sets the stage for future work leveraging both outpatient and pharmacy-based claims to further explore this finding.
Abstract WP258: Younger Patients Have a Higher Likelihood of Recurrent Vessel Small Subcortical Infarct: A Post-Hoc Analysis of the SPS3 Trial
Authors: Goldstein Eric D , Liew Sabrina , Shu Liqi , Ikemenogo Princess , Grilli Anais , Furie Karen , Yaghi Shadi
Published: February 2024

Introduction:
Recurrent ischemic stroke due to intracranial large artery disease occurs in up to 20% of patients and is associated with uncontrolled cardiovascular risk factors. However less is known of recurrent vessel small subcortical infarcts (rvSSI), which may be related to branch atherosclerotic disease. The aim of this study was to describe the clinical risk factors associated with rvSSI.

Methods:
We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled participants between 2003 and 2007. All participants were ≥ 30 years old and had a SSI index event within the preceding 6 months of randomization, confirmed by MRI with a maximal diameter on diffusion weighted imaging (DWI) of ≤ 20 mm, and were without competing stroke mechanism (e.g. ipsilateral carotid stenosis ≥ 50%). Participants were followed over a mean duration of 4 years post-enrollment during which stroke recurrence was noted and characterized. rvSSI was defined as recurrent SSI within the same vascular distribution as an index enrolling infarct confirmed by brain MRI. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Adjusted logistic regression models were formed to calculate odds ratio. Statistical significance was ≤ 0.05.

Results:
Of the 3020 participants enrolled in SPS3, 1245 participants met inclusion criteria with 15 having a rvSSI (mean time post-enrollment: 427 days). Participants with rvSSI were younger (54.5 ± 10.2 years vs 61.2 ± 10.6 years, p = 0.008) and had enrollment diagnoses of obesity [BMI ≥ 30 kg/m2; 80% (12/15) vs 49% (598/1230), p = 0.016] and hyperlipidemia [87% (13/15) vs 58% (713/1230), p = 0.025]. Sex, former/current tobacco use, and known diagnoses of hypertension and diabetes mellitus did not differ. For every advancing decade of life, the likelihood of developing a rvSSI was 0.46 (95%CI 0.26 - 0.82, p = 0.008).

Conclusions:
Participants of the SPS3 trial who were younger in age had rvSSI more frequently with the likelihood decreasing by roughly half with advancing decade of life.
Abstract WP261: Healthcare Utilization Patterns and Disparities in High Intensity Statin Use in Stroke Patients
Authors: Laurido-Soto Osvaldo J , Faust Irene M , Racette Brad A , Searles Nielsen Susan
Published: February 2024

Objective:
Physician adherence to evidence-based clinical guidelines improves outcomes in acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients. We investigated compliance with the AHA 2008 high intensity statin recommendation for secondary prevention of AIS/TIA, and factors associated with adherence.

Methods:
In this population-based, cohort study of incident AIS/TIA patients, we included a random sample of U.S. Medicare beneficiaries age≥67 with Part A/B/D coverage, ≥1 ICD code for AIS/TIA in 2015-2018, and no prior AIS/TIA or high intensity statin use (N=76,707). We followed the cohort forward until end of 2019 for high intensity statin use (atorvastatin ≥40mg or rosuvastatin ≥20mg). We used logistic regression to examine factors associated with high intensity statin use within 3 months: demographics, urban residence, Area Deprivation Index (ADI), and provider specialty (neurologist vs. other).

Results:
Overall, during follow up, only 62.5% of beneficiaries with incident AIS/TIA received neurologist care. In this period only 19.4% incident AIS/TIA patients received a high intensity statin and 27.8% did not receive any statin. Female patients (OR 0.88, 95%CI 0.84-0.92), older beneficiaries (OR 0.984, 95%CI 0.981-0.987 per year), and urban residents (OR 0.84, 95%CI 0.80-0.88) were less likely to receive a high intensity statin within 3 months of their stroke. Race/ethnicity but not ADI was associated with high intensity statin use. Neurologist-treated patients were markedly more likely to receive a high intensity statin than other AIS/TIA patients (OR 3.42, 95%CI 3.22-3.63), even after adjusting for all sociodemographic variables.

Conclusions:
AIS/TIA patients treated by neurologists received care consistent with the clinical guidelines more often than those not treated by a neurologist. Female, older, and urban beneficiaries were less likely to receive care consistent with the guidelines.
Abstract WP285: Stroke Recurrence and Poststroke Mortality: Sex Differences and Contributors in a Population-Based Study
Authors: Chen Chen , Reeves Mathew J , Morgenstern Lewis B , He Kevin , Lisabeth Lynda D
Published: February 2024

Few population-based studies have assessed whether stroke recurrence differs by sex. Additionally, contributors, particularly social factors, to sex differences in recurrence and poststroke mortality are unclear.

Methods:
First-ever ischemic stroke cases (2008-2019) identified from the population-based Brain Attack Surveillance in Corpus Christi Project were included. Recurrence and all-cause mortality were ascertained through 2020. Sex differences in outcomes with and without adjustment for 21 potential contributors (Figure) were examined by Cox proportional hazard models. Contributions of each factor to sex differences were assessed by change in the β estimate for sex before and after adjustment. Final models including all identified contributors (≥ 10% contribution) were conducted.

Results:
Of 2,326 participants (mean age 68 years; 48% women; 57% Mexican American), 274 had a recurrence and 965 died (median follow-up 5.4 and 3.7 years, respectively). No significant sex difference in recurrence was noted before (HR 0.89, 95% CI 0.70-1.13) or after adjustment in the final model (HR 0.86, 95% CI 0.66-1.13). While women had a higher crude mortality rate than men (HR 1.23, 95% CI 1.08-1.39), after adjusting for identified contributors (Figure), women had lower mortality (HR 0.79, 95% CI 0.67-0.92). Age and marital status were the two most important contributors to the sex difference. Other contributors included social support, physician access, insurance, stroke severity, coronary artery disease, prestroke disability, and alcohol consumption (Figure).

Conclusion:
Crudely, women had a nonsignificantly lower recurrence rate but higher poststroke mortality rate than men. After adjustment, women had a similar recurrence rate but lower mortality rate. Findings suggest that in addition to clinical factors, social factors including physician access, private insurance, having a partner, and higher social support, impact sex differences in stroke outcomes.
Abstract WP286: Cerebral Amyloid Angiopathy and Risk of Seizures
Authors: Bruce Samuel S , Zhang Cenai , Kamel Hooman
Published: February 2024

Introduction:
Cerebral amyloid angiopathy (CAA) is associated with multiple conditions that are known to have an elevated risk of seizures, including intracerebral hemorrhage, CAA-related inflammation, and Alzheimer’s disease. However, there are limited population-based data regarding the risk of seizures associated with clinically diagnosed CAA.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims from 2016 to 2018 from a nationally representative 5% sample of Medicare beneficiaries. The study exposure was a diagnosis of CAA identified using ICD-10-CM code I68.0. The primary outcome was seizure, defined using previously validated ICD-10-CM code G40.x, but excluding diagnosis codes for epileptic conditions that are unlikely to be a result of CAA. Participants with prevalent seizures were excluded. Cox proportional hazards regression was used to determine the association between CAA and seizure after adjustment for age, sex, race, and vascular risk factors.

Results:
Of 1,403,686 patients included during the study period, 425 (0.03%) were diagnosed with CAA. Median follow-time was 3 years (IQR, 2.4-3). The cumulative incidence rate of seizures was 6.9 (95% CI, 4.8-9.9) per 100 person-years in patients with CAA and 0.30 (95% CI, 0.29-0.30) per 100 person-years in patients without CAA. In Cox proportional hazards analysis, CAA was associated with an increased risk of seizures (HR, 12.6; 95% CI, 8.8-18.0).

Conclusions:
In a nationally representative cohort of Medicare beneficiaries, CAA was associated with an increased risk of seizures.
Abstract WP29: Early Adopter of Intravenous Tenecteplase: Two Year Clinical Experience in a Non-Academic Suburban Comprehensive Stroke Center for Acute Ischemic Stroke Treatment
Authors: Jocson Michelle T , Grigoryan Mikayel , Siddiqi Fatima , Ayala Angela , Yepez Palmero Sandra , Arzoumanian Margarita , Pogosyan Jacquelyn , Lee Lance J
Published: February 2024

Background:
The most recent American Heart Association/American Stroke Association acute ischemic stroke guidelines recognize tenecteplase (TNK) as an alternative to alteplase (ALT) for acute ischemic stroke (AIS) treatment. TNK has a longer half-life, and is given as a single intravenous bolus compared to the complex and cumbersome ALT administration. A switch to TNK was implemented at our Comprehensive Stroke center (CSC) after a rigorous training of nurses and providers on May 1, 2021. We sought to evaluate the comparative performance of two thrombolytics over the period of last two years of ALT and first two years on TNK use.

Methods:
This was a retrospective review of prospectively collected database of consecutive AIS patients treated with ALT between May 2019 to April 2021 and those who received TNK from May 2021 to April 2023 at our CSC. Data samples were analyzed with respect to baseline patient characteristics, stroke severity, Door to Needle (DTN) time, 90 day Modified Rankin Scores (MRS), complications, and cost savings. Statistical analyzes were used for between group comparisons (SPSS).

Results:
A total of 115 patients were treated with ALT and 134 - with TNK. There were no significant differences in baseline characteristics or stroke severity between the groups (mean NIHSS of 10 for both). The mean DTN was 53.0 minutes for ALT and 41.5 minutes for TNK (p<0.001). There was a strong trend towards improved 90-day clinical outcomes for TNK-treated patients (mRS 2.5 vs 3.1, p=0.06). No significant differences in rates of symptomatic Intracerebral Hemorrhage (SICH) were observed between two groups (2.6% ALT vs 2.9% TNK). Estimated cost savings of TNK use over two year period were $75,102.

Conclusion:
Our real-world data suggests that intravenous TNK for AIS appears to be safe and may result in improved clinical outcomes and substantial cost savings compared to ALT.
Abstract WP295: Blocking the VCAM1-VLA4 Axis Prevents Cognitive Decline in a Mouse Model of Infarct-Induced Neurodegeneration
Authors: Zera Kristy A , Bradshaw Karen , Hahn Oliver , Foltz Aulden , Zhu Li , Peterson Todd , Yousef Hanadie , Lee Davis , Aghaeepour Nima , Wyss-Coray Tony , Buckwalter Marion S
Published: February 2024

Introduction:
Infarct-induced neurodegeneration occurs chronically after stroke and can be prevented by inhibiting B cell influx. Vascular cell adhesion molecule 1 (VCAM1) facilitates immune cell diapedesis by binding very late antigen 4 (VLA4), and plasma levels are elevated after stroke in humans and mice. We hypothesized that chronic treatment with antibodies anti-VCAM1 or anti-VLA4 would reduce lymphocyte infiltration and prevent cognitive decline.

Methods:
Aged (10 month old) C57BL/6 male & female mice (N=9-10/group) underwent permanent middle cerebral artery occlusion and were dosed with anti-VCAM1, anti-VLA4, or control IgG every 3 days beginning 4 days after stroke for 10 weeks. Sham mice were also dosed with IgG. Barnes maze and Novel object were performed at -1, 1 and 6 weeks and single-cell RNA sequencing was performed on immune and endothelial cells at 10 weeks.

Results:
Blocking either VCAM1 or VLA4 reduced B cells 67% or 55%, respectively, compared to IgG treated stroked mice. Stroked mice treated with IgG developed a cognitive deficit in both Barnes maze and novel object by 6 weeks, while both anti-VCAM1 and anti-VLA4 treated mice performed comparably to sham animals in the Barnes maze (p=0.398; p=0.972, respectively). Similarly, sham IgG (p<0.0001), stroke anti-VCAM1 (p<0.0001) and VLA4 (p=0.0059) could all perform the novel object task. Single-cell sequencing of immune and brain endothelial cells demonstrated that most transcriptional changes occur in endothelial cells and not immune cells, and that anti-VCAM1 and anti-VLA4 induce similar transcriptional changes compared to control IgG after stroke. Specifically, both therapeutic antibodies restore heat shock protein expression (
Dnaja1, Hsp90ab1, Hspa8
) and decrease inflammatory genes
CD74
and
IL1r1
. Transcriptional changes also reflect increased translation and
Sox18
upregulation, consistent with angiogenesis.

Conclusion:
Blocking either VCAM1 or VLA4 prevents infarct-induced neurodegeneration in aged mice. Changes in endothelial cell transcription and decreased immune cells in the brain may both contribute to therapeutic effects. Together, these findings establish the VCAM1-VLA4 axis as a promising target to prevent infarct-induced neurodegeneration.
Abstract WP302: Different Clot Characteristics According to the Clot Volume: A Microscopic Analysis of Clot Composition
Authors: Yun Jaeseob , Kim Kwanghyun , Jung Jae Wook , Heo Ji H , Nam Hyo Suk , Kim Young Dae D
Published: February 2024

Background and Objectives:
Understanding the mechanisms of thrombosis is crucial for the future advancement in treating ischemic stroke. While many researches on thrombogenesis have been conducted, there was a limited data on thrombus growth. In this study, we investigated whether the clot composition or clot characteristics differed by the clot size using microscopic analysis of ischemic clot.

Methods:
We obtained the clots from 238 ischemic stroke patients who received endovascular treatment between July 2017 and July 2023 at Severance Stroke Center. We quantitatively analysed the clot components identified using immunohistochemistry. The fractions of each component such as fibrin, red blood cells (RBC), and platelets were calculated as the percentage pixel density of the total clot area. Clot volume was semiautomatically measured on thin-section computed tomography performed at stroke presentation using software. We determined the association between clot volume and histopathologic composition, arrangement patterns, and clinical or radiological features.

Results:
Among the 238 patients, the median (interquartile) of clot volume was 47.0 mm
3
(range 23.8-79.8). As the clot volume increased, the proportion of RBC became larger (r = 0.307. P <0.001) and the proportion of platelet became smaller (r = -0.150, p=0.029). In terms of RBC patterns, purely aggregated RBC patterns, rather than RBC-fibrin mixture patterns, was positively associated with the clot volume. After adjusting for potential confounders including posterior circulation occlusion, serum hemoglobin levels, serum albumin levels, and the presence of active cancer (all p<0.05 in univariable analysis), clot volume was independently related with the proportion of RBC (ß 0.726, SE 0.302, p =0.017) or the presence of purely aggregated RBC pattern (ß 59.182, SE 11.684, p <0.001).

Conclusions:
As the clot volume increased, the proportion of RBCs increases, and areas of purely packed with RBCs become larger. These findings suggest that as the clot grows, RBC mainly involved the clot volume growth.
Abstract WP304: Investigating Thrombus Architecture Using Spatial Transcriptomics
Authors: Walker Melanie , Espinoza Josh L. , Federico Emma , Gonzalez Alexandra , Dupont Christopher
Published: February 2024

Introduction:
Spatial transcriptomic (ST) platforms provide high-resolution localization of gene expression profiles within intact tissue, offering insight to cellular phenotype and ultimately tissue function. While cerebral thrombus morphology has been well-characterized, their functional architecture has not. Although this study is insufficiently powered to infer specific pathophysiologic conclusions, our findings offer preliminary insight into the functional segmentation of cerebral thrombi using ST.

Methods:
Four thrombi retrieved from cerebral arteries of ischemic stroke patients during standard of care thrombectomy were formalin-fixed and paraffin-embedded. Morphology marker antibodies (vimentin, CD45) and RNA probes coupled to photocleavable oligonucleotide tags were applied to thrombus specimens. Regions of interest (ROI) were randomly selected based on visualized cellular clustering within each specimen. ST analysis was performed using NanoString's GeoMx Digital Spatial Profiling platform.

Results:
Of the 24 ROIs, 0 samples were below the 50% warning, and 18,676 targets were analyzed. 1,127 genes were expressed in 50% of ROIs. 8,793 genes normalized by 3rd quartile, expressed above the Limit of Quantitation in at least 1% of ROIs. Differential expression analysis using a false discovery rate of < 0.05 revealed 54 differentially expressed genes (DEG), all of which were protein-coding using edgeR’s exact test.

Conclusions:
Although ST does not offer visibility into the presence of fully formed ribosomes, the identification of intact cytoplasmic RNA suggests there is significant transcriptional activity within thrombi. We cautiously present pilot data to support feasibility for spatially-resolved transcriptomic analysis of cerebral thrombi which, upon further technical refinement, may facilitate discovery of new targets for stroke prevention or treatment.
Abstract WP306: Endothelial CD200 Signaling Protects Brain Against Ischemic Damage
Authors: Misrani Afzal , Ngwa Conelius , Mamun Abdullah , Ritzel Rodney , McCullough Louise , Liu Fudong
Published: February 2024

Background:
Stroke is currently the leading cause of death and long-term disability in the US. Ischemic stroke induced inflammatory responses contribute to neuronal damage and stroke outcomes. CD200 and its receptor, CD200R, constitute an endogenous inhibitory signaling that is being increasingly recognized in studies of neuroinflammation in various central nervous system disorders. CD200 is a type 1 membrane glycoprotein that is broadly expressed by endothelia and neurons in the brain. We have previously reported the role of neuronal CD200 in stroke; in the present study, we examined the role of endothelial CD200 signaling in acute ischemic stroke.

Hypothesis:
Endothelial CD200 signaling is neuroprotective in acute ischemic stroke.

Methods:
Endothelial CD200 conditional knock out (CKO) mice were generated by breeding CD200 gene floxed mice with Cdh5
Cre
mice. The mice were subjected to a 60-min transient middle cerebral artery occlusion (MCAO). Flow cytometry, Immunohistochemical staining, and western blotting were performed to assess the post-stroke inflammation; stroke outcomes (infarct volume and neurobehavioral deficits) were evaluated at 24 h or 72 h days after MCAO.

Results:
Flow cytometry results found CD200R was near null expressed on microglia at 24h and 72h after stoke and endothelial CKO of CD200 had no impact on peripheral immune cell development. Immunohistochemical staining confirmed CD200 was expressed on CD200 floxed but not on CD200 CKO endothelia. Western blot results showed CKO of CD200 from endothelia did not change BBB protein expression. CD200 CKO mice exhibited larger infarct size, worse neurological deficit scores (NDS), and more deficits in the tape adhesive/removal test than control mice 72h after MCAO (Fig. 1).

Conclusions:
Endothelial CD200 signaling protects brains against ischemic injury through a mechanism not directly related to microglial activation; instead, CD200R
+
circulating immune cells may be involved.
Abstract WP31: Real World Comparison of Outcomes of IV Tenecteplase versus IV Alteplase for Acute Ischemic Stroke
Authors: Sahito Sindhu , Gadallah Nancy E , Singh Zamir , Abbasi Hamidreza , Bozkurt Subutay , Ghori Arifa , Dubinsky Ilya , Panezai Spozhmy , Strauss Sara , Zacharatos Haralabos , Tabibzadeh Navid , Mehta Siddhart , Kirmani Jawad
Published: February 2024

Background:
Tenecteplase (TNK) has been reported to be non-inferior to alteplase from a clinical outcome and safety standpoint according to recent studies. In our study, we compare the outcomes of IV TNK & IV alteplase for acute ischemic stroke patients.

Materials and Methods:
We evaluated acute AIS patients treated with IVT between10/2020-03/2023 at theDepartment of Neurology, Hackensack MeridianHealth, JFKMedical Center. All analyses was done using SPSS version 29 software.

Results:
Among the total 270 patients, 150(55.6%) received IV alteplase and 120(44.4%) received IV TNK. Major neurological improvement (defined as improvement in NIHSS score by 8 or more points at 24hours) was observed with TNK. Any intracranial hemorrhage was higher among patients treated with IV TNK compared to alteplase (25% versus 14.7%, p=0.024). Symptomatic intracranial hemorrhage(sICH) was higher inTNK group (8.3% versus3.3%, p=0.075). The proportion of routine discharge was higher among alteplase patients, while non-routine discharge was higher among TNK patients (51.7% vs. 28%, p<0.001). In the logistic regression analysis, patients treated with IV TNK were at a significantly higher risk of any intracranial hemorrhage(odds ratio[OR], 1.93, 95% confidence interval [CI]1.051-3.57, p=0.034). After adjusting for age, gender, NIHSS, thrombectomy, hypertension, diabetes, hyperlipidemia, CHF, previous TIA and previous stroke, there was anon-significant higher rate of intracranial hemorrhage. A nonsignificant decrease in the odds of symptomatic intracranial hemorrhage (sICH) was seen with TNK. There were significantly higher rates of non-routine discharge (OR, 3.078, 95% CI 1.8-5.19, p<0.001) and death (OR, 4.84, 95% CI1.20-19.66, p=0.002) inpatients treated with IV TNK. After adjusting for the above-mentioned factors, there was a significantly higher rate of non-routine discharge in the TNK group and a higher trend of death in the TNK group.

Conclusions:
We found that IV TNK was associated with higher rates of intracranial hemorrhage compared to IV alteplase in patients with acute ischemic stroke.
Abstract WP315: Pharmacological Validation of Advanced Gamma Peptide Nucleic Acid (PNA) Based miR Inhibitors for Ischemic Stroke Treatment
Authors: Yadav Sanjeev K , Gamiotea Turro Daylin , Patel Vraj , Dhuri Karishma , Bahal Raman , Verma Rajkumar
Published: February 2024

Backgrounds:
Our prior work demonstrated the potential of targeting miR-141-3p to mitigate ischemic stroke damage. In this study, we aimed to synthesize and validate more advanced and efficacious gamma peptide nucleic acid (PNA) based anti-miR 141-3p inhibitors, comparing them with regular PNA and phosphothiorate (PS) based counterparts. These inhibitors were subsequently encapsulated in poly(lactide-co-glycolide) (PLGA)-based nanoparticles (NPs) for treatment in a mouse model of ischemic stroke.

Methods:
In-house synthesis yielded PS, PNA, and gamma-PNA anti-miR 141-3p, encapsulated in PLGA NPs via double emulsion solvent evaporation. After physiochemical characterization, in vitro safety and efficacy were evaluated in HEK293 cells via MTT, LDH cytotoxicity assays, and qPCR for gene expression. In vivo efficacy studies employed the most potent gamma-PNA based anti-miR 141-3p, administered intraperitoneally 4 hours after 60-minute of transient middle cerebral artery occlusion (MCAO). Mice were sacrificed at 3 (acute) or 30 (chronic) days post-stroke. Acute cohort brain tissues were analysed for miRNA and target mRNA levels, along with infarct volume. Chronic cohort mice were subjected to weekly behavioral task to major sensorimotor deficit or recovery.

Results:
twenty-four-hour exposed HEK-293 cells were no sign of mortality and toxicity at concentration range of 0.015-1.5ug/mL of various anti-miR 141-3p. Gamma-PNA based anti-miR exhibited notably higher efficacy in inhibiting miR-141-3p (IC50=0.05ug/mL) compared to PS (IC50>1.5ug/mL) or regular PNA (IC50>1.5ug/mL). A single dose of gamma-PNA-based anti-miR significantly reduced (P<0.05 vs. Scramble control) infarct injury and brain tissue miR-141-3p levels (>2-fold vs. scramble control). Gamma-PNA treatment also led to swift improvement in sensorimotor deficits in the rotarod task.

Conclusion:
NPs of gamma-PNA-based anti-miR 141-3p were both safe and potent in vitro and in vivo. They effectively mitigated infarct injury, improved neurobehavioral deficits, demonstrating promising translational potential for ischemic stroke treatment. In future we aim to explore more mechanistic studies to explore it mode of action.
Abstract WP319: Calvaria Hematopoiesis and Neuroinflammation: Insights From a Murine Stroke Model
Authors: West Bryce E , Korf Janelle , Do Trang , Devlin Patrick , Khan Romeesa , Guzman Gary , Maniskas Michael E , Venna Venugopal R , McCullough Louise D , Ritzel Rodney
Published: February 2024

Introduction:
The human skull has traditionally been perceived as a static protective structure guarding the brain and meninges. However, emerging data suggest there is a dynamic hematopoietic stem cell niche within the upper portion of the skull, or calvaria. This niche is important for sensing and contributing to central nervous system (CNS) inflammation. Murine models reveal dynamic neutrophil migration from the skull that infiltrates the ischemic brain, via the meninges, following stroke.

Methods:
To better understand the acute dynamics of the calvaria immune cell response to ischemic stroke, we investigated changes in hematopoiesis following a 60-minute transient middle cerebral artery occlusion (tMCAO) in young adult male C57Bl/6J mice. Bone marrow stem/progenitor cell proliferation and differentiation in the calvaria were measured at several time points during the first week of stroke utilizing flow cytometry.

Results:
We observed significant stress-induced myelopoiesis in the calvaria at 24-hours post-tMCAO, consistent with recent literature. An increasing trend for myeloid skewing in the ipsilateral (versus contralateral) calvaria was noted, suggesting unilateral activation. We also found a significant increase in Ly6C
hi
monocytes and Ly6G
+
neutrophils in the calvaria and ventral skull bone at 72-hours post-tMCAO.

Conclusions:
Our findings collectively suggest the calvaria plays an integral role in the acute inflammatory response to stroke. As the skull bone marrow contributes innate immune cells that both amplify inflammation and participate in debris clearance, future studies may help identify novel targets for interventions aimed at mitigating stroke-induced neuroinflammation.
Abstract WP327: Altered Bone Marrow Microenvironment Impacts Endothelial Precursor Cell Development and Egress in Mice With Type 2 Diabetes
Authors: Zhang Hongxia , Yu Kailin , Kato Yuya , Falcone-Juengert Jaime , Liu Jialing
Published: February 2024

Endothelial precursor cells (EPCs) are vital contributors to angiogenesis, a crucial process in tissue repair and functional recovery after ischemic stroke. However, in the context of Type 2 Diabetes Mellitus (T2DM), angiogenesis is compromised, particularly after ischemic stroke. The mechanisms underlying the impacts of T2DM on EPC dynamics in the bone marrow (BM), as well as its repercussions on functional recovery post-stroke, remain incompletely understood. We found that the EPC populations were significantly diminished in the BM of diabetic mice compared to control mice prior to stroke by immunofluorescence staining (IF). Interestingly, the number of EPC was not significantly changed in the BM of diabetic mice after stroke, in contrast to the reduction seen in the control mice, suggesting an inherent impairment of EPC production and migration in the diabetic BM milieu. Consistent with this finding, VEGF, a critical factor for EPC proliferation and migration, was found to be increased in the BM in the control mice but reduced in the diabetic mice after ischemic stroke. There was also an overall reduction of CD115 and Ly6G expression in the BM of diabetic mice, indicative of an altered microenvironment for hematopoiesis that could further affect EPC dynamics. Single-cell RNA sequencing of cells revealed the presence of hematopoietic precursor cells (HPC), monocytes, granulocytes, and macrophages among the clustered cell populations. Enrichment analysis unveiled pathways associated with mitotic DNA replication, myeloid cell differentiation, and leukocyte migration among the differentially expressed genes in HPC between diabetic and control BM. Strikingly, genes linked to the angiogenesis and endothelial cell migration were also down regulated in T2DM BM, potentially contributing to the impaired angiogenic response observed in T2DM after stroke. These findings underscore the intricate interplay among T2DM, EPC function, angiogenesis, and post-stroke recovery. The identification of disrupted pathways in the BM environment provides valuable insights into the compromised angiogenic response observed in diabetes and novel targets for therapeutic interventions in improving stroke outcomes in patients with T2DM.
Abstract WP36: Proven Strategies for Educating Staff and Reducing Hospital-Acquired Pressure Injuries in Stroke Hospital Units
Authors: Fazzino Kirsten , Hong Sarah , Thresher Catherine , Hewitt Jocelyn , Sher Karen
Published: February 2024

Introduction:
Hospital-Acquired Pressure Injuries (HAPI) are preventable complications that stroke patients are at risk for developing during hospitalization due to changes in mobility, nutrition, and continence as complications of stroke. The stroke units at a large teaching hospital saw an increase in HAPI’s during fiscal years (FY) 21 and 22 with 16 collective HAPIs in FY21 and 25 in FY22. Additionally, 12.5% of their unit-acquired HAPIs were reportable to the state’s Department of Public Health (DPH) in FY21 and 20% were reportable to the DPH in FY22. Nursing leadership hypothesized that a multi-year and multi-faceted plan would reduce unit-acquired HAPIs.

Methods:
In the first year of the plan, all RNs and Patient Care Assistants (PCAs) participated in a “Room of Wounds” education intervention in which they identified HAPI prevention errors in a simulation, matched appropriate dressings to wound images according to hospital policy, identified documentation gaps in a mock medical record, and completed a case study in which they applied the hospital’s Skin Injury Prevention Protocol (SIPP) to a patient scenario. The following year, the RNs all reviewed a handout on the hospital’s SIPP which included “Do’s and Don’ts” of documentation and participated in a Skills Day where an educational game was utilized identify wounds and appropriate dressing types. Additionally, unit leadership completed daily audits and provided timely feedback to RNs about patient care and documentation gaps.

Results:
Together, the neuroscience units saw a 48% reduction in HAPIs from FY22 to FY23 thus far with one of the units seeing a 71% reduction. In addition, none of the neuroscience units had a DPH reportable HAPI in FY23 thus far.

Conclusion:
Multi-faceted education approaches are critical when implementing education to counteract gaps in nursing care because they ensure that all learner types receive meaningful education. Consistent Auditing and feedback also improves patient care and staff accountability. A multi-faceted approach is a successful strategy that can be utilized when providing education about HAPI prevention, a major risk to patients after stroke, to staff members of multiple roles within the hospital’s stroke units.
Abstract WP38: Nurse-Driven Emergency Evaluation Improves Timely Acute Stroke Response
Authors: Fowler Madison , Hafen Heidi , Aucoin Michelle D , Chatwin Stephen , Johnson Paul
Published: February 2024

Background:
Stroke is associated with high rates of death and disability; prompt and effective interventions are imperative. Depending on emergency department (ED) physicians to initiate stroke codes may delay critical time targets, especially for patients arriving by private vehicle (POV). This study examines existing stroke care protocols in the ED of a Comprehensive Stroke Center and evaluates a new nurse-driven acute stroke response protocol.

Purpose:
The primary goal of this initiative was to improve outcomes for patients arriving by POV, by reducing triage delays and accelerating time-sensitive acute stroke interventions.

Methods:
This retrospective study implemented a nurse-led stroke activation process, in lieu of the conventional physician-led method. Nurses received comprehensive training in intervention goals and identification of stroke symptoms and last known-well times. The nurse-led model targeted patients presenting to the ED with a minimum of 2 stroke symptoms within 6 hours of symptom onset—an assessment tool, incorporating the FAST algorithm (Face, Arm, Speech, Time) and key National Institutes of Health Stroke Scale (NIHSS) exam components, enhanced symptom specificity. Critical intervention times were evaluated for improvement.

Results:
ED POV arrival patients with acute stroke symptoms were studied from 11/7/21-7/31/23; the nurse-driven process was implemented on 11/7/22. Pre-intervention review included 247 patients with 216 patients in the post-intervention review. Median door-to-activation times fell from 17 to 10 minutes, door-to-CT from 24 to 19 minutes, and door-to-needle times from 49 to 43.5 minutes. Median NIHSS scores in tPA-treated patients were compared pre- and post-intervention. In the physician-led group, initial median NIHSS scores were 6, reducing to 1 at discharge. The nurse-led group showed an initial median NIHSS score of 5, also reducing to 1 at discharge.

Conclusions:
The nurse-driven method effectively shortened critical time metrics in the stroke code process, while maintaining optimal patient outcomes. A paradigm shift towards ED triage nurse-led stroke code activation for acute stroke may lead to higher quality acute stroke care.
Abstract WP42: Transition to Tenecteplase: A Regional Experience
Authors: Macko Lauren , Karamchandani Rahul , Guzik Amy K , Asimos Andrew W , Goings Denise , Lycan Sarah L , Michael Catherine , Retelski Julia , Bear Susan , Hollinger Meredith
Published: February 2024

Background:
Timely recognition and treatment of acute ischemic stroke is well-supported to promote better outcomes. Historically, alteplase has been the drug of choice for thrombolytic treatment, and while it is an excellent drug, there were barriers that would routinely come up during administration. Following the results of several studies that compared alteplase to tenecteplase, our leadership team decided to initiate the transition to tenecteplase within our region, spanning several states with approximately 40 hospitals.

Purpose:
The purpose of this clinical initiative was to implement tenecteplase as the primary thrombolytic in acute ischemic stroke and evaluate time to treatment (door in door out [DIDO] and door to needle [DTN]).

Methods:
Following the approval by leadership, the first step was identification of stakeholders at facility, market, service-line, and regional levels and initiation of bi-weekly meetings. The project relied heavily on facility-level structure that facilitates stroke quality improvement. We were able to utilize market specific stroke databases to understand historical data and to monitor ongoing success and complications.

Results:
Post-implementation, several positive changes were noted, which are visualized in the graphs.

Conclusions:
Through reduction of DIDO, treatment is initiated sooner to reperfuse at-risk brain tissue. Further evaluation is needed on the correlation between the transition and decreased length of stay, but we recognize tenecteplase has been shown to have a better rate of recanalizing large vessel occlusions, potentially resulting in less disability and shorter hospitalizations.
Abstract WP46: Using a Nursing Focused Approach to Decrease Thrombolytic Administration Times
Authors: Schaefer Karen , Lima-Tessier Elizabeth , Coyne Kathleen , Lawler Rachel , Brooks Kate
Published: February 2024

Care of a stroke patient is time dependent as well as the benefits of thrombolytic administration. An interdisciplinary subgroup was created to evaluate the Emergency Department process for code strokes and administration of thrombolytics. This groups initiative was to improve door to needle time for eligible stroke patients. An opportunity was identified to improve thrombolytic administration times by identifying and creating a timer keeper role as well as having a nursing code stroke checklist. A form was developed for nursing staff which included stroke metrics as well as time goals for each metric. Face to face education was completed with all Emergency Department Nurses in April 2023 on code stroke metrics, timekeeper role, and use of nursing code stroke checklist. Outcome of this project was a significant decrease in thrombolytic administration times in the Emergency Department. Data was collected on all alteplase cases 12 months prior to implementation and four months post implementation. Results showed immediate improvement with a 42% reduction in door to thrombolytic times after implementation of the new timekeeper role and checklist. This improvement included achieving the hospitals first door to thrombolytic time under 30 minutes. Use of the nursing code stroke checklist and use of timekeeper has increased awareness to minutes passed since arrival, resulting in reduced door to thrombolytic times for stroke patients. Education continues with new staff, and staff continue to strive for even quicker times. Improvement in treatment times was possible due to staff understanding the importance of quick recognition and treatment for our stroke patients as well as having a designated timekeeper during the code stroke process.
Abstract WP53: Bringing Comprehensive Stroke Care Home: Supporting Early Supported Discharge
Authors: Nobles Kristen
Published: February 2024

Background and Issues:
Despite holding the highest certification as a Comprehensive Stroke Center, the project site's 'Discharge-to-Home' performance for ischemic stroke survivors ranked below the median compared to similar academic medical centers. Although an innovative Early Supported Discharge (ESD) program was available for patients who met geographical criteria, the utilization of these services was not optimal.

Purpose:
This Quality Improvement initiative aimed to investigate the impact of an early collaborative discharge planning process led by a multidisciplinary healthcare team on 'Discharge-to-Home' rates of ischemic stroke patients eligible for the site's ESD program, Homeward Stroke Recovery.

Methods:
Meleis' Transition Theory was used to shape the development of streamlined workflows, simplifying the identification of eligible patients and reducing the time taken to refer them to Homeward Stroke Recovery through enhancements to the electronic medical record system. Additionally, robust team education was provided to improve discharge coordination and improve the utilization of available ESD services. Existing system data was leveraged, and new data flows were created to monitor program-specific metrics. Descriptive statistics were used to examine the effect of an early collaborative discharge planning process on ‘Homeward Stroke Recovery Discharge Rates’ for ischemic stroke survivors.

Results:
There was a notable increase of 5.6% in the 'Homeward Stroke Recovery Discharge Rate' from Fiscal Year 2022 to Fiscal Year 2023 (rising from 43.9% to 49.5%).

Conclusions:
In conclusion, this Quality Improvement project successfully addressed the challenge of suboptimal 'Discharge-to-Home' rates for ischemic stroke patients eligible for the site’s ESD program. The observed 5.6% increase in the 'Homeward Stroke Recovery Discharge Rate' between Fiscal Year 2022 and Fiscal Year 2023 reflects the positive impact of the interventions performed, highlighting the importance of multidisciplinary teamwork and systematic improvements in healthcare delivery.
Abstract WP7: Utilization and Outcomes Associated With DAPT and ASA Monotherapy Amongst Hospitalizations With Large Vessel Occlusion: A Nationwide Cross-Sectional Analysis
Authors: Patel Hemal , Patel Urvish K , Shah Dhaivat , Khan Sumaiya , Priya Peram Raga , Nandigam Mani Deep , Matteda Tanmayi , Jayan Gopika , Gowdru Kiran , Kelangi Sarah Susan , Munnangi Jyothsna , Hariharan Vignesh Krishna , Khotele Chinmay , Sabapathy Pradeep Kumar , Arora Rohan
Published: February 2024

Background:
In clinical trials like SPS3, MATCH, CHANCE, and POINT, dual antiplatelet treatment (DAPT) has been compared to aspirin (ASA) alone for preventing symptomatic large vessel occlusion (LVO) and ischemic strokes. Based on the effect size in the aforementioned studies, nationwide research may provide a more complete assessment of outcomes and relationships and help fill knowledge gaps. We used a nationwide inpatient sample to evaluate the outcomes of symptomatic LVO among patients using DAPT versus ASA monotherapy.

Methods:
We performed a cross-sectional study of a nationwide inpatient sample (2003-2014) in adult LVO hospitalizations. The patients taking DAPT and ASA on admission were identified using ICD-9-CM code. The univariate analysis (chi-square test) and multivariable survey logistic regression analyses were performed to compare mortality, morbidity, discharge (home vs transfer to short-term hospital, skilled nursing facility, and home health care), and disability to calculate odds ratio with 95% CI using SAS 9.4.

Results:
Of 4,224,924 hospitalizations, 1.24% and 7.38% were on DAPT and ASA, respectively. In comparison to ASA monotherapy, DAPT users were associated with lower prevalence of mortality (2.2% vs 3.1%) and morbidity (3.8% vs 3.9%) with similar prevalence of discharge to the non-home (58.8% vs 58.8%), (p<0.0001). On weighted analysis, use of DAPT vs. ASA was associated with lower odds of mortality (DAPT: OR 0.45; 95%CI 0.39-0.51; ASA: 0.61, 0.58-0.64), morbidity (DAPT: 0.54, 0.49-0.61, ASA: 0.56, 0.54-0.59), discharge to non-home (DAPT: 0.78, 0.75-0.82, ASA: 0.80, 0.79-0.82), and disability (DAPT: 0.76, 0.73-0.80, ASA: 0.80, 0.78-0.82) compared to non-users.

Conclusion:
This comprehensive national investigation revealed that DAPT resulted in more favorable outcomes for individuals with symptomatic large vessel occlusion. There is a need for additional prospective studies to validate the findings and ascertain the most suitable population at risk for primary prevention of stroke.
Abstract WP79: Outcomes Of The Code Large Vessel Occlusion Process On Endovascular Intervention
Authors: Gilli Maria , Sanfillippo Geraldine , Rochestie Dustin , Patel Pratit , Sharp Gregg , Olkowski Brian , Oravsky Gary , Morris Kathleen
Published: February 2024

Introduction:
The code LVO alert was created to help decrease the time from arrival to MER for patients presenting with LVO stroke. The code LVO alerts the endovascular surgeon and team earlier in the stroke alert process with the goal of improving patient outcomes. The purpose of this study was to determine the impact of code LVO on stroke endovascular treatment times and patient outcomes.

Methods:
The code LVO is activated based on patient assessment. Criteria to call a code LVO includes a RACE score ≥ 5 or if a patient has disabling symptoms including aphasia, visual field cut or total limb weakness. The code LVO can be activated either as a prehospital alert or in the emergency department by either the provider or nurse. This notification makes the endovascular surgeon and team aware of a possible endovascular candidate prior to imaging to help reduce door to team activation, skin puncture, device, and reperfusion. We compared patients in 2022 that received MER with and without code LVO activation.

Results:
Eighteen patients with MER and code LVO activation were compared to 42 patients that received MER and no code LVO activation. Clinical and demographic characteristics were similar (p>.05). When comparing the two groups, the code LVO activation decreased the door to activation by 26.8 minutes (p=.003), door to puncture by 31.5 minutes (p=.005), door to device by 34.5 minutes (p=.026), and door to reperfusion by 41.3 minutes (p=.013). The 90-day mRS score and 90-day mortality rate were similar.

Conclusion:
In conclusion, the code LVO activation significantly decreased MER treatment times but these improvements did not translate to improved patient outcomes. We identified opportunities to improve our patient outcomes by increasing code LVO activation on all patients meeting criteria.