bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP207: Clinically Important Effect Sizes for Clinical Trials Using Infarct Growth Reduction as the Primary Outcome
Authors: Liao Nien-chen , Bahr-Hosseini Mersedeh , Saver Jeffrey L
Published: February 2024

Background:
Infarct growth on multimodal imaging is a common lead outcome in phase 2 proof-of-concept and dose-optimization neuroprotective agent stroke trials. However, the effect size in infarct growth reduction that correlates with clinically meaningful differences in clinical global disability outcomes has not been well delineated.

Methods:
Systematic literature search identified all endovascular thrombectomy randomized trials reporting magnitude of treatment effect on both infarct growth reduction and increase in functional independence (modified Rankin Scale, mRS, 0-2). Data aggregation determined the size of infarct growth reduction correlating with 3 types of clinically meaningful effect sizes of increase in functional independence: 1) the minimal clinically import difference (MCID), the 2) the realistic effect size, and 3) the reasonable comparability effect size.

Results:
Systematic search identified 4 trials enrolling 612 imaged participants. Across trials, the amount of functional independence (mRS 0-2) increase associated with each 1 ml reduction in infarct growth was median 1.7% (range 1.3% to 3.0%). An infarct growth reduction of 0.57 ml correlated with the mRS 0-2 increase MCID of 1.3%. Infarct growth reductions of 2.27 ml, 4.35 ml, and 6.53 ml correlated with realistic effect and reasonable comparability effects sizes of mRS 0-2 increases of 5%, 10%, and 15%, respectively.

Conclusion:
In formal meta-analysis of randomized trials, every 1 ml reduction in infarct growth by endovascular thrombectomy was associated with a 2.3% increase in functional independence (mRS 0-2) at 3 months. This conversion factor can inform selection of infarct growth effect size targets for phase 2 trials of neuroprotective agents.
Abstract WP209: Functional Outcomes After Craniotomy or Endoscopic Procedure for Hematoma Evacuation in Patients of Intracerebral Hemorrhage Associated With Oral Anticoagulants
Authors: Gillani Syed A , Ahmed Rehan , Maqsood Hamza , Ma Xiaoyu , Fakih Rami , Bains Navpreet , Siddiq Farhan , French Brandi R , Gomez Camilo R , Qureshi Adnan I
Published: February 2024

Background and Purpose:
The role of surgical evacuation using craniotomy or endoscopic procedure in patients with intracerebral hemorrhage (ICH) associated with oral anticoagulants is not well described. We investigated the 6-month functional outcomes of patients with ICH associated with oral anticoagulants after hematoma evacuation using either craniotomy or endoscopic procedures.

Methods:
We analyzed data of consecutive ICH patients who underwent hematoma evacuation using either craniotomy or endoscopic procedures. We compared the outcomes between patients with ICH associated with oral anticoagulants to those with spontaneous ICH. We also compared the results between patients treated with craniotomy and those treated with endoscopic procedures. We performed multivariate analyses to assess the effect of ICH associated with oral anticoagulants on modified Rankin Scale (mRS) at 6 months, which was analyzed both as dichotomous and ordinal endpoints after adjusting for age, gender, initial GCS score, initial hematoma volume, and presence or absence of intraventricular hemorrhage.

Results:
Of the 148 ICH patients undergoing hematoma evacuation, 25 (17%) had ICH associated with oral anticoagulants. There were no statistically significant differences between the two groups in terms of age, gender, admission Glasgow Coma scale (GCS) score, admission National Institutes of Health Stroke Scale (NIHSS) score, peri and post-operative hematoma volume, presence of cardiovascular disease, hypertension, or dyslipidemia. There was no difference in the proportion of patients with mRS 0-2 at 6 months among patients with and without ICH related to oral anticoagulants (4/25 (16%) versus 27/123 (22%), p-value = 0.5). In the ordinal analysis, there was no significant association between ICH associated with oral anticoagulants and mRS grades (OR 1.62 (0.25, 9.65), p-value 0.598.

Conclusion:
Prior anticoagulation use is not associated with poor functional outcome (mRS 3-6) in patients with intracerebral hemorrhage, procedure use for hematoma evacuation (craniotomy or endoscopic) does not predict good functional outcome at 6 months.
Abstract WP211: Mechanical Thrombectomy in Patients With Mild Thrombocytopenia is Safe and Effective; a Systematic Review and Meta-Analysis
Authors: Ahmed Muhammad K , Chaychi Muhammad Tayyab Muzaffar , Bosan Danial , Mumtaz Mishal , Shafiq Mudassir , Maaz Hafiz Muhammad , Zahid Atrooba , Rashid Rahimeen , Khan Muhammad Shahzaib , Kamal Haris
Published: February 2024

Background:
MT is a effective treatment for AIS patients with LVO, but MT on TP patients is risky due to lack of data and potential hemorrhage.

Methods:
Our review followed the PRISMA guidelines for systematic review and meta-analysis. We defined thrombocytopenia as platelet count ≤150х109/L, with further sub-classification into two groups: 1) Mild TP (Platelet count 100,000 - 149,000x109/L); 2) Moderate/severe TP (platelet count <100х109/L). A favorable outcome was 90-day functional independence (mRS) ≤ 2). Unfavorable outcomes were mortality at 90 days and (sICH).

Results:
Compared to patients with normal platelets, patients with TP had no significant difference in outcomes (mRS >2) at 90 days (RR 0.80 [95% CI: 0.69 - 0.94] p = 0.006). Further analysis based on sub-groups, the difference in mRS score was not statistically significant in patients with mild TP group (RR 0.84 [95% CI: 0.70 - 1.00] p = 0.05) and moderate/severe TP group (RR 0.71 [95% CI: 0.48 - 1.06] p = 0.09) when compared to patients with normal platelets. However Mortality was found to be higher in the TP group (RR 1.95 [95% CI: 1.62 - 2.36] p < 0.00001), with similar trends of increased mortality in the mild and severe TP group (RR 1.88 [ 95% CI: 1.34 - 2.63] p = 0.0002 and RR 2.07 [95% CI: 1.46 - 2.92] p < 0.0001). There was an overall slight increase in the incidence of sICH in the TP group (Relative Risk [RR] 2.47 [95% CI: 1.51 - 4.05], p = 0.0003) compared to patients with normal platelet counts, however subgroup demonstrated no significant higher risk in the mild thrombocytopenia group (RR 2.34 [95% CI: 1.24 - 4.40], p = 0.008)

Conclusions:
Mechanical thrombectomy for LVO in patients with mild thrombocytopenia is safe and does not increase the risk of sICH or worse outcomes. However, caution is advised in cases of moderate to severe thrombocytopenia, as there is a slightly higher risk of sICH and mortality. Nonetheless, we recommend thrombectomy for LVO patients with thrombocytopenia.
Abstract WP212: Site vs. Core Lab Adjudicated eTICI Scores Compared During Off and Normal Hours - Insights From the ASSIST Registry
Authors: Gupta Rishi , Miralbes Salvador , Naravetla Bharath R , Spiotta Alejandro M , Loehr Christian , Martínez-Galdámez Mario , McTaggart Ryan , Defreyne Luc , VEGA PEDRO , Zaidat Osama O , Price Lori Lyn , Liebeskind David S , Moehlenbruch Markus
Published: February 2024

Introduction:
The ASSIST registry is a prospective, global registry whose primary aim was to identify which endovascular technique yields the highest rate of first pass TICI 2C reperfusion. Data from this registry was analyzed for this secondary analysis to assess if site adjudicated eTICI scores differ from the core lab during off hours [7 PM to 6:59 AM plus weekends (7 PM Friday - 6:59 AM Monday)] compared to normal hours (7 AM - 6:59 PM on weekdays). An additional objective is to assess if outcomes are worse with regards to core-lab adjudicated reperfusion grades and mRS 0-2 in procedures performed during off hours.

Methods:
Details from the ASSIST registry have been previously presented. Descriptive statistics for outcomes and percent agreement between core-lab and site-reported eTICI were calculated. Regression models were performed for first pass treatment of target occlusion resulting in ≥ 2c by core-lab, mRS 0-2 at 90 days, and whether first pass eTICI agreed for both core-lab and site-reported.

Results:
A total of 1318 patients were included in the analysis with 652 patients presenting during normal hours and 666 patients presenting during off hours. Overall, agreement between core-lab and site-reported eTICI at first pass occurred in 86.7% and 78.5% for final eTICI ≥2c. Agreement occurred for first pass eTICI ≥2c 87.2% during normal hours and 86.1% during off hours. Agreement occurred less often on final pass eTICI ≥2c during both normal and off hours (77.7% and 79.3%, respectively). Good functional outcomes based on 90-day mRS 0-2 occurred in 55.5% in patients presenting during normal hours and 53.8% in patients presenting during off hours. Off-hour vs. normal hour procedures was not significantly associated with first pass efficacy, mRS 0-2 at 90 days, or whether first pass eTICI agreed for both core-lab and site-reported in adjusted regression analyses.

Conclusions:
There was a higher level of agreement between core-lab and site-reported first pass eTICI scores during all hours while agreement occurred less often for final reperfusion. These results suggest a high level of correlation with site adjudicated and core lab adjudicated successful reperfusion grading. ClinicalTrials.gov ID: NCT03845491
Abstract WP217: 4D Flow MRI Monitoring of Pediatric Brain Arteriovenous Malformations: A Feasibility Study
Authors: Schollenberger Jonas , Mahuvakar Shivani , Fox Christine K , Mukherjee Pratik , Fullerton Heather J , Kim Helen , Saloner David ,   UCSF AHA Bugher Hemorrhagic Stroke Rsch Group
Published: February 2024

Introduction:
While some brain arteriovenous malformations (bAVM) demonstrate long-term stability, others demonstrate dynamic changes (new aneurysms or venous outflow stenosis) that confer higher rupture risk even after apparent cure. The objective of this study is to evaluate the feasibility and efficacy of 4D Flow MRI to quantitatively assess the hemodynamic changes in pediatric bAVMs following treatment and its use for early detection of high-risk changes.

Methods:
We have prospectively enrolled 20 children (mean age 11.8 ± 3.8 years) with bAVM into a single center cohort study. 4D Flow MRI was acquired in a transverse slab covering the circle of Willis using prospective gating, compressed sensing, and a resolution of 0.7 x 0.7 x 1.0 mm
3
on a 3T GE Discovery MR750 scanner. MRI at baseline and post-intervention (6-month and 1-year follow up) has been acquired for 5 patients thus far. 4D Flow data was post-processed by segmenting the main cerebral arteries and calculating cardiac-averaged flow rates in cross-sections orthogonal to the centerline of each vessel segment.

Results:
The flow rate accuracy was evaluated by calculating the flow conservation at the right/left internal carotid and basilar junctions, yielding average errors of 10.7% ± 12.7, 14.0% ± 9.5, and 19.3% ± 13.8 respectively. The hemisphere containing the bAVM received an average of 57.2% ± 2.8 of total brain flow at baseline, which decreased to an average of 51.2% ± 2.9 1-year follow-up. In 2 of 5 patients, the flow laterality between hemispheres flipped post-intervention with increased flow to the contralateral hemisphere. In all the post-intervention studies, we observed a decrease in flow and maximum velocities, as well as an increase in pulsatility index, in the primary feeding arteries to the bAVM (Figure).

Conclusion:
These preliminary results indicate that 4D Flow MRI may be a robust and useful tool for monitoring changes in intracranial flow patterns after bAVM treatment in children.
Abstract WP22: “Chopperlysis:” Improved Functional Outcomes Associated With Helicopter Transport in Large Vessel Occlusion Stroke Patients Treated With Tenecteplase
Authors: Koneru Manisha , Penckofer Mary , Thon Jesse , Tonetti Daniel , Wolfe Jared , Patel Karan , Vigilante Nicholas , Zhang Linda , Elgendy Omnea , Sprankle Kenyon , Ackerman Jiyoun , Kalladanthyil Abyson , Yi Zixin , Shi Rosa , Jefferson Abbie , Kumar Arjun , Siegler James E , Schumacher Hermann , Khalife Jane , Shaikh Hamza
Published: February 2024

Introduction:
Tenecteplase (TNK) is increasingly being utilized for IV thrombolysis in acute ischemic stroke, including for patients with large vessel occlusion (LVO) prior to transfer to an endovascular thrombectomy (EVT) capable center (TCC). However, there is limited data regarding factors that influence functional outcome between the time of TNK administration and TCC arrival. The purpose of this analysis is to characterize the effect of the arrival method on the effectiveness of TNK to improve patient outcomes.

Methods:
A retrospective registry of stroke patients between 2019-2023 at a single comprehensive stroke center was queried. Patients with LVO stroke who had complete data for method of arrival (i.e. ground transportation versus helicopter), TNK treatment, and available 90-day modified Rankin score (mRS) were included. The primary outcome was a favorable 90-day mRS of 0-2. Categorical variables were reported as frequencies, and associations across variables were analyzed using Chi-square test or Fisher's exact test. Odds ratios were calculated with univariate logistic regressions.

Results:
Of 2675 patients meeting inclusion criteria, 14.4% arrived by helicopter and 85.6% arrived by ground transportation. 174 (6.5%) were treated with TNK, including 5.1% of ground transported patients and 14.1% of air transported patients. Irrespective of EVT, patients arriving by ground did not differ in likelihood of achieving the primary outcome whether they did or did not receive TNK (53.9% TNK vs. 48.4% no TNK, p=0.35). However, patients arriving by helicopter had a significantly higher likelihood of achieving the primary outcome with TNK, regardless of EVT (60% TNK vs. 41.2% no TNK, p=0.04), and in patients transported by helicopter who did not undergo EVT, there was an even higher likelihood of good functional outcome associated with TNK treatment (69.2% TNK vs. 40.1% no TNK, p=0.049).

Conclusion:
In our cohort, treatment with TNK was associated with improved functional outcomes in helicopter transported patients but not in those transported by ground, and this benefit was found to be even more robust in patients who did not undergo EVT. Future studies are needed to validate these findings and investigate the underlying pathophysiological mechanism.
Abstract WP229: Comparing the Real-World Effects of Once-Weekly Semaglutide and Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcomes, Health Care Resource Utilization, and Medical Costs in Individuals With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease
Authors: de Havenon Adam H , Tan Xi , Liang Yuanjie , Yedigarova Larisa , Noone Josh , Xie Lin , Inzucchi Silvio E
Published: February 2024

When compared with placebo, glucagon-like peptide-1 receptor agonists such as once-weekly semaglutide (semaglutide OW T2D) improve cardiovascular outcomes in people with type 2 diabetes (T2D), whereas dipeptidyl peptidase-4 inhibitors (DPP-4is) do not. However, no head-to-head trials of these 2 incretin-based drug classes have been conducted. This retrospective cohort study used 2018-2022 data from the Optum
®
Clinformatics
®
Data Mart to compare on-treatment time with incidence of ischemic stroke, myocardial infarction (MI), and 2-point major adverse cardiovascular events (MACE; composite of ischemic stroke and MI); health care resource utilization; and medical costs in new adult users of semaglutide OW T2D and DPP-4is with T2D and atherosclerotic cardiovascular disease (ASCVD). Patients were followed until drug discontinuation, enrollment end, or an event. Baseline characteristics (
Table
) were balanced using inverse probability of treatment weighting. On average, patients were aged 70 years, with 5.6- and 4.3-year history of T2D and ASCVD, respectively. Survival analyses were conducted to compare risks during exposure. Users of semaglutide OW T2D (weighted n=14,461) had 46%, 36%, and 40% lower relative risk of ischemic stroke, MI, and 2-point MACE, respectively, compared with users of DPP-4is (weighted n=38,630; all
P
≤0.001;
Figure
). Users of semaglutide OW T2D also had decreased ASCVD-related and all-cause hospitalizations, outpatient visits, hospitalization costs, and total medical costs (all
P
<0.05). This study suggests that semaglutide OW T2D reduces the risk of stroke and MI while reducing medical costs relative to DPP-4is in adults with T2D and ASCVD.
Abstract WP23: Hemorrhagic Transformation Following Anticoagulation in Victims of Acute Ischemic Stroke Secondary to Intra-Cardiac Thrombi
Authors: Hakoun Abdullah M , Cardoza Krislyn , Abeer Aysha , Awad Adam , Ali Ahsan , Miremadi Brian B
Published: February 2024

Introduction:
Hemorrhagic transformation (HT) following acute ischemic stroke (AIS) is a common consideration especially when therapeutic anticoagulation is indicated in cases such as left ventricular or left atrial appendage thrombi. Although there have been multiple studies investigating the safe timing of anticoagulation initiation following AIS in patients with atrial fibrillation, the results varied. Evaluating the infarct volume and correlating it to time of anticoagulation initiation and HT can be detrimental to patient safety.

Methods:
We performed a retrospective review of all patients who were diagnosed with AIS secondary to cardio-embolic mechanisms and were admitted to our hospital between January 1, 2018, and December 31, 2022. The inclusion criteria consisted of patients aged 18 to 100 years who were found to have intra-cardiac thrombi and were initiated on anticoagulation within 80 hours of symptom onset. Infarct volume was measured using the ABC/2 formula. Statistical analysis was conducted using the R statistical program. For variables with a normal distribution, we used the mean and standard deviation (SD), and for variables with skewed distribution, we reported the median with interquartile range (IQR).

Results:
A total of 597 patient charts were reviewed for this study. After applying the inclusion criteria, 36 patients were deemed eligible for inclusion in the analysis. Among the included patients, a majority were male, constituting 80.6% (n=29) of the sample. The infarct volume among the included patients ranged from 0 ml to 100 ml. A breakdown of infarct volumes is as follows: Twenty-three patients (63.9%) had infarct volumes of 10 ml or less. Seven patients (19.4%) had infarct volumes ranging between 11 - 20 ml. Six patients (16.7%) had infarct volumes that exceeded 21 ml, with the largest infarct measuring 100 ml. There was no clinically significant HT. There were no surgical interventions required for any of our study subjects.

Conclusion:
The initiation of anticoagulation within 80 hours following AIS secondary to intra-cardiac thrombi may be safe, especially in patients with infarct volumes of 20 ml or less when using the ABC/2 formula.
Abstract WP232: The Association Between Migraine and Postpartum Adverse Vascular Events
Authors: Prince Taya , Potter Thomas B , Pan Alan P , Borei Karim , Britz Gavin W , Vahidy Farhaan , Bako Abdulaziz T
Published: February 2024

Background:
We evaluate the association of migraine before and during pregnancy with the development of major adverse vascular events (MAVE) during an extended postpartum period of 24 weeks.

Methods:
We identified pregnant women aged between 12 and 44 years from the state inpatient databases of New York, Florida, Georgia, Maryland, and Washington (2016 - 2019). Patients were followed up for up to 24 weeks postpartum. Patients with migraine (ICD-10 code: G43) before or during pregnancy were considered to have a history of migraine. We fit multivariable logistic regression models to evaluate the association between the history of migraine and the development of MAVE (stroke, acute coronary syndrome, systemic thromboembolism, hypertensive encephalopathy, pulmonary heart disease, or death) up to 24 weeks after delivery. Patients with a history of MAVE before or during pregnancy were excluded. Adjusted odds ratios (aOR) and 95% confidence interval (CI) are reported.

Results:
Among 1,568,646 eligible participants (mean age [SD]: 29 [5.7] years), 43,840 (2.79%) had a documented history of migraine. Women with a history of migraine (vs. those without a history of migraine) had higher odds of experiencing MAVE (268/43840 [0.61%] vs. 4556/1524806 [0.3%], aOR, 95% CI: 1.47, 1.30 - 1.67). Also, older age (aOR, CI: 1.02, 1.02 - 1.03), smoking during pregnancy (2.14, 1.97 - 2.32), and pre-eclampsia (1.87, 1.72 - 2.03) were independently associated with a higher likelihood of developing postpartum MAVE. Additionally, those with a history of kidney failure (2, 1.76 - 2.27), liver disease (1.32, 1.11 - 1.56), and heart failure (1.59, 1.35 - 1.86) had higher odds of experiencing MAVE. Furthermore, those with a history of hypertension (1.23, 1.13 - 1.33), diabetes (1.30, 1.17 - 1.45), obesity (1.31, 1.22 - 1.41), and coagulopathy (2.36, 2.17 - 2.57) were more likely to experience MAVE.

Conclusions:
Migraine seems to be independently associated with a higher risk of post-partum MAVE. Further studies are needed to assess the utility of extended workup for evaluating the risk of MAVE among pregnant females with migraines.
Abstract WP248: Developing and Validating Post-Treatment HERMES Score to Predict Outcome From Anterior Circulation Large Vessel Occlusion Stroke: A Meta-Analysis of Individual Data From 7 Randomized Clinical Trials
Authors: Tanaka Koji , Brown Scott , Goyal Mayank , Menon Bijoy K , Campbell Bruce C , Mitchell Peter J , Jovin Tudor G , Saver Jeffrey L , Muir Keith W , White Philip M , Bracard Serge , Guillemin Francis , Dippel Diederik W , Majoie Charles B , Hill Michael D , Demchuk Andrew M
Published: February 2024

Introduction:
Clinicians need simple and highly predictive prognostic scores to assist practical decision-making and family discussion. We aimed to develop and validate a simple prediction score applied at 24 hours to assist prognostication in patients with anterior circulation ischemic stroke due to large vessel occlusion.

Methods:
Using the HERMES collaboration dataset (n = 1764), patients in the endovascular therapy (EVT) arm were divided randomly into a derivation cohort (n = 430) and a validation cohort (n = 441). From a set of candidate predictors, forward selection using c-statistics was employed to select a model which was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in both the EVT validation cohort and in the control arm (n = 893) for mRS ≤2 and ≤3.

Results:
In the derivation cohort, two significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale [NIHSS] score at 24 h and age [β-coefficient 0.34 and 0.06]) were selected. Incorporating other variables did not much improve model performance. Among models with different weights, we derived the HERMES score: age (years)/10 + NIHSS score at 24 h, based on model performance and simplicity. The HERMES score was highly predictive for mRS ≤2 in the derivation cohort, validation cohort-EVT, and control arm (c-statistics 0.907, 0.914, and 0.909, respectively). Evaluation of the score against mRS ≤3 as an alternative outcome yielded similar results (c-statistics 0.911, 0.903, and 0.885). Among 435 subjects (24.7%) with HERMES score ≥25, the observed probability was 3.1-3.4% for mRS ≤2 and 9.4-16.7% for mRS ≤3 in the derivation cohort, validation cohort-EVT, and control arm (Figure).

Conclusions:
The HERMES score is a simple validated score to predict outcomes in patients with anterior circulation large vessel occlusion ischemic stroke regardless of intervention. HERMES score should be helpful in prognostic discussion with families on day two.
Abstract WP253: Prevalence of Undiagnosed and Uncontrolled Hypertension Among Low-Wage Workers in North Carolina With Elevated Stroke Risk
Authors: Burch Ashley , Bolin Paul
Published: February 2024

Introduction:
Compared to the rest of the United States, North Carolina has an elevated stroke mortality rate. Risk factors, including uncontrolled hypertension (HTN), associated with disparities in stroke outcomes are also prevalent in North Carolina. We sought to determine the prevalence of undiagnosed and uncontrolled HTN among a sample of low-wage workers with elevated stroke risk.

Methods:
Between February 2021 and June 2023, we partnered with 35 business to provide worksite-based health screenings to rural, low-wage workers. Demographic information and a brief medical history were collected. A physical assessment included automated blood pressure measurement. Risk of stroke was assessed using the CHA
2
DS
2
-VASc.

Results:
A total of 930 screened individuals (52.5% Black) are included in this report. Among the 488 Black participants screened, 29.1 percent (n=142) had a CHA
2
DS
2
-VASc score ≥2. In comparison, less than 20 percent (n=79, 17.9%) of the 442 White participants had an elevated stroke risk (Figure 1). Of the 221 participants with a CHA
2
DS
2
-VASc score ≥2, stage 1 HTN (systolic blood pressure (SBP) = 130-139) and stage 2 HTN (SBP ≥ 140) was found among 19.5 and 52 percent of participants, respectively. We identified previously undiagnosed HTN among 6.3 percent of Black participants and 15.2 percent of White participants. In addition, over 60 percent of participants (Black = 62.7%, White = 60.8%) had been previously diagnosed with HTN, but screening results indicated their HTN was not well controlled.

Conclusions:
The prevalence of elevated stroke risk was 11.2 percent greater among Black participants compared to White participants. Using a worksite-based approach to health screening, we found high rates of undiagnosed and uncontrolled HTN among both Black and White participants with elevated stroke risk. This novel approach to care delivery facilitates screening among individuals who may otherwise underutilize or avoid engagement with the healthcare system.
Abstract WP257: Prevalence of Co-Morbid Ischemic Stroke and Antiphospholipid Syndrome and Characteristics of Patients: Analysis of the National Inpatient Sample
Authors: Gordon-Kundu Barbara , Mariscal Melissa , Sharma Richa , Narula Reshma , de Havenon Adam H
Published: February 2024

Background:
Antiphospholipid syndrome (APLS) is an acquired thrombophilia that is a known cause of ischemic stroke (IS). However, there is a paucity of population-based studies of the prevalence and effects of APLS diagnosis on patients hospitalized with IS. Here we use the National Inpatient Sample (NIS) to evaluate the characteristics of patients admitted to the hospital for IS with a diagnosis of APLS.

Methods:
Adult patients in the NIS from 2016-20 with non-elective admissions and a primary discharge diagnosis of IS (ICD-10 I63*) were included. The study exposure was APLS, defined in ICD-10 codes D68.61-62. We excluded individuals with ICD codes for other thrombophilia conditions (D6*). The primary outcomes were in-hospital death vs good outcome (discharge home/self care). We fit logistic regression models adjusted for age, race/ethnicity, Charlson index, household income by ZIP code, administration of IV thrombolysis or thrombectomy (EVT), hospital teaching status, census region, and bedsize.

Results:
We included 434,463 IS discharges, of which 1,407 had APLS. Discharges with APLS were younger, more likely to be female, non-white, lower income, less vascular comorbidities, and less likely to receive IV thrombolysis but more likely to receive EVT (Table 1). In the multivariable logistic regression model, those with APLS were more likely to have in-hospital death (OR 1.49, 95% CI 1.12-1.98, p=0.006) and less likely to have discharge home (OR 0.70, 955 CI 0.62-0.78, p<0.001). In a subset of this cohort (n=175,428), the NIH Stroke Scale (NIHSS) was available and not significantly different (p=0.768) between patients with and without APLS.

Conclusion:
IS with APLS happens in younger individuals with fewer vascular risk factors but worse outcomes and higher odds of in-hospital death. The NIHSS findings suggested that stroke severity alone does not account for the observed differences in outcome. Further research is needed to understand these findings and their causes. .
Abstract WP263: Associations of Equol-Producing Status With Cardioembolic Stroke in Japanese Patients With Stroke
Authors: Noda Kotaro , Hattori Yorito , Higashiyama Aya , Murata Hiroaki , Kokubo Yoshihiro , Miyamoto Yoshihiro , Ihara Masafumi
Published: February 2024

Introduction:
Equol, a metabolite of a soy isoflavone daidzein transformed by the gut microbiota, is associated with the amelioration of cardiovascular diseases and cognitive impairment. Approximately 50% of Asians and 30% of Westerners may be equol producers depending on the presence of equol-producing gut microbiota. It is still unknown whether equol-producing status is associated with development of stroke and its prognosis.

Methods:
In this single-center, retrospective study, we investigated the serum concentration of equol in 200 patients with stroke hospitalized in the National Cerebral and Cardiovascular Center (NCVC) from September 2019 to October 2021, and 103 healthy subjects registered in the Suita Study, a population-based cohort study at NCVC from November 2016 to September 2018. The concentration of equol was measured using liquid chromatography-mass spectrometry.

Results:
Eighty-five patients with stroke (43.5%) and 50 healthy subjects (48.5%) were equol producers (
p
=0.32). However, patients with cardioembolic stroke (CES) had a significantly lower frequency of the equol producers (28.9%) compared to healthy subjects (
p
=0.04), as well as patients with other stroke subtypes (48.0%) (
p
=0.04). The prevalence of atrial fibrillation was significantly lower in equol producers than that in non-producers (26.3% vs. 47.3%,
p
=0.04) among patients with ischemic stroke. Additionally, equol-producing status was an independent predictor for a favorable outcome (modified Rankin scale 0-2) at discharge for ischemic stroke in a multivariable logistic regression analysis (odds ratio 2.75, 95% confidential interval 1.05-7.27,
p
=0.04).

Discussion:
CES, atrial fibrillation, and clinical outcome may be influenced by equol-producing status. These findings could provide new insights into the racial difference in the prevalence of CES between Asians and Westerners.
Abstract WP266: Prediction of Stroke Incidence Using Machine Learning: The Suita Study
Authors: Vu Thien , Inoue Mai , Yamamoto Masaki , Mohsen Attayeb , Martin-Morales Agustin , Inoue Takao , Dawadi Rsch , Kokubo Yoshihiro , Araki Michihiro
Published: February 2024

Background:
This population-based study investigated the potential of machine learning algorithms to predict stroke incidence and identify important risk factors. This study aimed to evaluate the accuracy of these algorithms in constructing a stroke prediction model.

Methods:
Participants from the Suita study were included, and baseline measurements were used to predict stroke outcomes over a 15-year follow-up period. In total, 7,389 participants and 51 variables were investigated, including demographics, medical history, medical imaging, laboratory data, and lifestyle habits. Initially, unsupervised K-prototype clustering was used to group participants based on their stroke risk. Subsequently, five supervised models (logistic regression, random forest, support vector machine, extreme gradient boosting, and light gradient boosted machine) were applied to predict the stroke outcomes. The Shapley Additive Explanations (SHAP) method determined the most critical variables.

Results:
Unsupervised clustering revealed significant differences in stroke incidence among the three identified risk clusters (9.1%, 6.6%, and 3.2%). These clusters were categorized into high-, medium-, and low-risk groups. Among the supervised models, the random forest algorithm demonstrated the best performance. The top ten most important variables for predicting stroke incidence were identified using the SHAP, with age being the most influential variable. Other significant risk markers included systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood sugar level. Additionally, elbow joint thickness and fructosamine, hemoglobin, and calcium levels were found to be potential predictors of stroke risk. Notably, the variables identified by the SHAP were consistent with those obtained from the unsupervised clustering approach in the high-risk group.

Conclusion:
Machine learning algorithms provide accurate predictions of stroke incidence and offer valuable insights into subclinical markers without the need for prior assumptions of causality. This study presents a data-driven machine-learning framework for stroke risk prediction and biomarker identification.
Abstract WP269: Food Desert Residence as a Contributing Risk Factor for Acute Ischemic Stroke Patients
Authors: Rahman Line A , Grewal Parneet , Emetu Sophia , Turan Tanya N , Boan Andrea D
Published: February 2024

Background:
Research suggests that residing in a food desert (FD) area may negatively impact health by increasing cardiovascular risk factors. The USDA defines FD as an area of low income in addition to low access to grocery stores at a 1 (urban) or 10-mile (rural) radius and/or low vehicle access. This study aims to assess sociodemographic profile and stroke risk factors among individuals residing in FDs within the predominantly rural state of South Carolina (SC).

Methods:
Deidentified administrative discharge data included all individuals admitted to SC hospitals between 2010 and 2019 with ICD-9/10 codes for ischemic stroke. Public USDA census tract data were used to define FDs based on patients’ residential addresses at time of admission, with encrypted linkages provided by SC’s clinical data warehouse. Stroke risk factors were compared between those residing in a FD vs. not via chi-square analyses.

Results:
Out of the identified 63,330 patients with an index ischemic stroke event, 36.8% were classified as residing within a USDA defined FD. Acute stroke patients residing within a FD were significantly more likely to be younger (age <65), of black race, and without health insurance (all p<.0001). FD residents were significantly more likely to have comorbid hypertension (OR 1.14, 95%CI 1.09, 1.19), type 2 diabetes (OR 1.21, 95%CI 1.17, 1.25), heart failure (OR 1.14, 95%CI 1.09, 1.19), and chronic kidney disease (OR 1.24, 95%CI 1.18, 1.30) associated with acute stroke hospital admission. Also, those residing in FDs were significantly more likely to have a history of obesity (OR 1.17, 95%CI 1.11, 1.23), mental health (OR 1.14, 95%CI 1.10, 1.18), tobacco use (OR 1.28, 95%CI 1.23, 1.33), and substance abuse (OR 1.40, 95%CI 1.35, 1.45). There were no significant differences noted in terms of sex/gender, dyslipidemia, discharge disposition, or case fatality.

Conclusion:
Stroke patients living within FDs are at heightened risks of comorbidities associated with ischemic stroke. Limitations in access to high quality food and suboptimal nutrition may be a contributing risk factor. Future studies focusing on shopping and eating behaviors among those living within FDs are needed to further reduce health disparities within rural and urban geographic locations nationwide.
Abstract WP279: Stroke in Young Adults With Congenital Heart Disease a Single Center Case Control Study
Authors: Mammadli Gular , Kochav Jonathan , Sariyeva Mehriban , Argenio Melissa , Bilski Amanda , Ibeh Chinwe , Willey Joshua Z , Rosenbaum Marlon , Lewis Matthew , Miller Eliza C
Published: February 2024

Introduction:
Adults with congenital heart disease (ACHD) are at risk for stroke, but risk factors within this population are not well characterized.

Methods:
We reviewed medical records of patients evaluated in an ACHD clinic from 8/1/1995- 3/1/2022 who underwent brain imaging for any reason. We categorized patients by anatomical complexity based on American Heart Association guidelines (simple, moderate or high complexity). The primary outcome was ischemic or hemorrhagic stroke. TIA and silent infarcts were excluded. We created logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between anatomic complexity and stroke.

Results:
Out of 184 patients, 48 (26.1%) had any stroke (62% ischemic, 38% hemorrhagic). Median age at first stroke was 26.2 years (IQR 19.2-38.5) (Figure). Those with stroke had higher proportion of Black race, more major cardiac surgeries, and more use of antithrombotic medications prior to stroke (see Table). Adjusting for age, sex, race, number of cardiac surgeries, and use of antithrombotic medications, those with highly complex lesions had a trend towards higher odds of any stroke (adjusted OR 2.0, 95% CI 0.89 - 4.4). Effect size was higher for ischemic stroke (adjusted OR 2.6, 95% CI 0.99-6.7).

Conclusion:
In our sample of 184 ACHD patients who underwent brain imaging, stroke was common with half of strokes occurring before the age of 26 years. High complexity cardiac lesions were associated with more than double the odds of ischemic stroke. Larger studies are needed to develop effective stroke prevention strategies in this growing young adult population.
Abstract WP28: A Multiscale, Anatomically, and Neurochemically Realistic In Silico Toolbox for the Simulation of Cerebrovascular Ischemia
Authors: Collins Christopher M , Kancherla Jeevika , Carluccio Giuseppe , Liang Jiazhao , Dehkharghani Seena
Published: February 2024

Introduction:
Despite therapeutic advances, roughly half of acute ischemic stroke (AIS) patients fail to achieve independence. Multiscale tools permitting nano- to macroscalar representations of the hemodynamic, electrical, and neurochemical disturbance in AIS are thus demanded. The vastness of potential scenarios evolving in individual patients renders full investigation into all possible courses of disease unattainable in human or animal subjects. Digital phantoms have proliferated in the precision medicine era, yet such frameworks remain immature in neuroscience. Here, we introduce a realistic simulation toolbox governed by a vast parameter space to model AIS.

Methods:
A numerical implementation of a 4-compartment (neuronal, astrocytic, extracellular, and capillary) model (www.cellml.org) was modified to simulate evolution of AIS, including the dynamic interplay of >80 neurochemical processes related to cellular energetics and tuned with hemodynamic (e.g. CBF) aberrations relevant to the neurovascular unit. Two different ischemic conditions are simulated to illustrate use of the framework: i. ~50% CBF reduction; ii. ~80% CBF reduction.

Results:
As seen in Fig. 1, while a 50% reduction in CBF reduces glucose concentration ([GLC]) in extracellular, glial, and neuronal spaces, ATP concentrations are maintained (with glial levels dropping slightly in order that glial cells can offer support to neuronal function), and sodium concentrations ([Na+]) in both cell spaces remain constant. By comparison, an 80% CBF reduction yields falling [ATP], such that Na homeostasis is disturbed and dynamic alterations in [Na+] in the cellular compartments can be observed, leading to time-dependent cytotoxicity.

Conclusion:
We present a digital model and generalized framework for modeling the evolution of hemodynamic, thermal, ionic, and other disturbances in AIS, conceived as a multifaceted tool for hypothesis building and testing pathologic scenarios
Abstract WP291: Cerebral Amyloid Angiopathy Induces Liver Inflammation in Aged Mice
Authors: Zhang Euan Y , Banerjee Anik , Maniskas Michael E , McCullough Louise D , Lee Juneyoung
Published: February 2024

Introduction:
Cerebral amyloid angiopathy (CAA) is a chronic age-related neurodegenerative disease, identified by the presence of amyloid-beta (Aβ) deposition within the vasculature of the brain, leading to stroke and progressive cognitive decline. The liver is a key peripheral organ involved in the clearance of excess Aβ in the circulation. However, the role of the brain-liver axis in CAA is unknown. Here, we investigate inflammatory changes in the liver in a murine model of CAA.

Methods:
Aged (>23 months) male and female Tg-SwDI (CAA) mice harboring Swedish, Dutch, and Iowa mutations of the human amyloid precursor protein were used as a mouse model of CAA along with age-matched wild-type (WT) controls (n=3-7/grp). Hepatic inflammation was analyzed with histological and immunofluorescence imaging. Single cells from liver tissue were isolated and analyzed using flow cytometry. Total RNA was isolated to examine gene expression in the liver using real-time quantitative PCR.

Results:
Our data showed that CAA increases infiltration of immune cells proximal to liver sinusoids across both sexes compared to WT mice. We found increased macrophages (i.e., F4/80
+
cells) in the liver of CAA mice compared to WT controls. Flow cytometry on the liver revealed that female CAA mice had a significant increase in dendritic cells (i.e., CD80
+
CD45
+
CD11c
+
cells, ***
P
<0.001) compared to WT females. Further, we found that
Oatp2
, a membrane transporter which mediates hepatocytic uptake of toxic molecules (e.g., Aβ), is associated with sex-specific CAA pathophysiology in the liver.

Conclusions:
In this study, we found that sex differences may exist in CAA-induced liver inflammation. Further investigations are needed to study how vascular amyloidosis shapes the immune responses and peripheral Aβ clearance in the context of aging and CAA.
Abstract WP293: Elucidating the Neuronal Basis of Diaschisis in Stroke Recovery
Authors: Brown Craig E , Butterworth Jenna , Van Sprengel Myrthe , Reeson Patrick
Published: February 2024

Numerous studies have shown that focal ischemic stroke changes cortical activity patterns, metabolism and blood flow not only in peri-infarct regions, but also in remote regions connected to the ischemic core. This phenomenon known as “diaschesis”, was predicted over 100 years ago and is presumed to play an important role in dictating the extent of stroke recovery. Although regional brain imaging studies provide some support to this idea (with caveats), direct examination of the structure and function of neurons connected to neurons lost in the infarct core, has not been adequately addressed. One reason for our lack of a detailed understanding is the methodologies to trace connected neurons and track their function/activity patterns over weeks and months time after stroke, did not exist until recently. To address this issue, we injected adeno-associated virus (AAV) into the adult mouse primary forelimb somatosensory cortex (FLS1) 2-3 weeks before induction of photothrombotic stroke. These AAVs could either be transported in a retrograde fashion to label neural inputs to the FLS1 (retro pAAV.CAG.GFP), or conversely move in an anterograde, trans-synaptic manner (AAV.Syn.Cre) to label neurons downstream of FLS1 neurons, such as in motor cortex. In the latter case, we utilized a transgenic mouse that co-expressed a cre-recombinase dependent fluorescent reporter (tdTomato), as well as a genetically encoded calcium sensor (GCaMP6s) in neurons. These dual reporters (tdTomato and GCaMP6s) allowed us to examine changes in dendritic structure as well as functional activity patterns in downstream motor neurons. Our initial findings using confocal microscopy to assess dendritic structure, indicate subtle changes in spine density in neuronal inputs and outputs of the FLS1, within the first week after stroke. Repeated
in vivo
imaging of calcium transients in downstream motor cortex neurons in awake mice before and after FLS1 cortex stroke, suggested a long lasting disruption in neuronal and ensemble activity patterns. These preliminary findings provide direct evidence that neurons in remotely connected brain regions suffer long-lasting impairments after stroke, thereby providing another potential target or substrate for future therapeutics to consider.
Abstract WP294: Endothelial Deletion of Complement C3a Receptor is Neuroprotective in Murine Stroke
Authors: Ahmad Saif , Contreras Jessica , Raikwar Sudhanshu , Akhter Naseem , Bhatia Kanchan , Jha Ruchira , Waters Michael F , Ducruet Andrew F
Published: February 2024

Background:
Stroke is among the leading causes of death and disability worldwide. We and others have shown that endothelial C3a receptor (C3aR) expression is enhanced in murine stroke models as well as in OGD induced brain endothelial cells. Therefore, it is critical to investigate the role of endothelial C3aR in post-stroke neurovascular dysfunction.

Hypothesis:
Genetic ablation of endothelial C3aR will afford neuroprotection in stroke.

Methods:
We used a
loxP-cre
approach (C3aR

Flox/Flox

x Cdh5
Cre
) to generate conditional C3aR endothelial deficient or sufficient mice (C3aR

Endo+/+

or C3aR

Endo-/-
)

of both sexes (3-4 months old) which were subjected to photothrombotic stroke. WT littermates were used as controls. We assessed cerebral blood flow (CBF), Infarct volume, BBB integrity, and myeloid cell infiltration. Neurobehavioral functions were tested at 3 and 21 days. P<0.05 was considered statistically significant.

Results:
Photothrombotic (PT) stroke resulted in decreased CBF in C3aR

Endo

+/+
mice compared with sham animals. However, infarct volume and CBF were improved after 72 h post PT in C3aR

Endo-/-

vs C3aR

Endo

+/+
. C3aR

Endo-/-

mice showed improved motor and cognitive function when compared with C3aR

Endo+/+

. Furthermore, reduced myeloid cell/neutrophil infiltration and improved BBB integrity in C3aR

Endo

-/-
vs C3aR

Endo+/+

were observed.

Conclusion:
Genetic deletion of C3aR expression from endothelial cells is neuroprotective in a PT murine stroke model through suppression of inflammation. Further work is warranted to explore underlying mechanisms of C3aR mediated brain injury in stroke.
Abstract WP300: Ifi27l2a is a Novel Target for Dampening Microglial Inflammation Following Stroke
Authors: Wise Zachary , Vance Lauren , Doan Andrea , Ahn John , Andersohn Alexander , Bautista-Garrido Jesus , Wu Ting , Jung Joo Eun , Marrelli Sean P , Kim Gab Seok
Published: February 2024

Microglia play a critical role in initiating and spreading inflammation and are involved in the chronic recovery phase following stroke. Microglia express multiple interferon-stimulated genes (ISGs) in response to inflammatory cues, including
Ifi27l2a
. However, the specific roles of individual ISGs, such as
Ifi27l2a
, have not been well-studied in the context of stroke. We tested the hypothesis that induction of
Ifi27l2a
in microglia contributes to the pro-inflammatory response following stroke.

We used
Ifi27l2a
heterozygote (Het) mice to determine the effect of partial reduction of Ifi27l2a in primary microglia and in an experimental stroke model. Primary microglia isolated from WT and Het brains were stimulated with LPS to investigate the role of Ifi27l2a in microglial activation
in vitro
. Permanent distal middle cerebral artery occlusion (pdMCAO) was performed in young mice (WT vs Het, male, 3 months old) to determine whether deletion of
Ifi27l2a
reduces microglial activation and improves functional outcome following stroke.

We found that LPS-induced expression of
Il1b
was markedly reduced in Het microglia compared to WT microglia (n=6, p<0.01). Moreover, other inflammation marker genes (
Il1a
and
Tnfa
) were significantly reduced in Het microglia compared to WT microglia in LPS-stimulated conditions (n=6, p<0.05). The levels of inducible forms of
Mmp3
and
Mmp9
, which are responsible for blood-brain barrier (BBB) dysfunction, were significantly reduced in Het microglia (n=3, p<0.01). However,
Mmp2
expression was not altered by deletion of Ifi27l2a. These findings suggest that Ifi27l2a is involved in the process of BBB dysfunction and microglial inflammation. Lastly, gliosis (microgliosis and astrogliosis) was significantly reduced at 14 days post-stroke in the thalamus of Het brains, a known site of secondary injury in pdMCAO model (n=6, p<0.05). Foot fault tests showed improved functional outcome in Het mice (n=4-6, p<0.05).

Ifi27l2a appears to be a critical molecular switch for inflammatory mechanisms in the post-stroke brain. These findings suggest that interventions targeting Ifi27l2a regulation (even partial inhibition) could reduce harmful inflammation and promote improved functional outcome following stroke.