bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 48: Outcomes And Risk Of Hemorrhagic Transformation Following Mechanical Thrombectomy In Primary Distal Posterior Cerebral Artery Occlusions-subgroup Analysis From STAR
Authors: Almallouhi Eyad , Al Kasab Sami , Maier Ilko , Jabbour Pascal M , Kim Joon-Tae , Quintero Wolfe Stacey C , rai ansaar , Starke Robert , Psychogios Marios , Samaniego Edgar A , Arthur Adam S , Yoshimura Shinichi , Grossberg Jonathan A , Alawieh Ali , Fragata Isabel , Cuellar Hugo , Polifka Adam , Mascitelli Justin , Osbun Joshua , Matouk Charles , Park Min S , Levitt Michael , Dumont Travis , Williamson Richard , Spiotta Alejandro M , Grandhi Ramesh
Published: February 2023

Background:
While mechanical thrombectomy (MT) has become the standard of care for acute stroke patients presenting with large vessel occlusion (LVO) and salvageable brain tissue, limited data is currently available regarding the benefits of MT in patents with medium vessel occlusions (MeVO) especially in the posterior circulation (P2 occlusions).

Methods:
We used the Stroke Thrombectomy and Aneurysm registry (STAR) which included data from 35 stroke centers in North America, Europe, Asia, and South America. We included patients who presented with MeVO in the M2, M3 or P2 segments and underwent MT. We used a Generalized Linear Model to assess the relationship between location of occlusion and outcomes.

Results:
9812 patients were included in STAR at the time of this analysis; 43 underwent MT for P2 occlusion, 130 underwent MT for M3 occlusion; and 1273 underwent MT for M2 occlusion. There was no difference in age, sex, race, rate of IV-tPA and stroke severity between patients in all 3 groups (Table 1). There was a trend toward lower rate of atrial fibrillation in patients with P2 and M3 occlusions. Patients with P2 occlusions were less likely to achieve successful recanalization (modified treatment in cerebral infarction score≥2b); intraarterial thrombolysis was used less in P2 occlusions (4.7% compared to 16.2% in M3 occlusions and 10.1% in M2 occlusions). However, there was no difference in the rate of successful first pass. On multivariable analysis, P2 occlusions were not associated with hemorrhagic transformation (OR 2.0, 95% CI 0.7-5.7, P 0.186), 90-day mortality (OR 0.5, 95% CI 0.2-1.4, P 0.183), or 90-day favorable outcome (OR 2.0, 95% CI 0.9-4.4, P 0.084).

Conclusions:
In this multicenter study, there was no significant difference in safety and efficacy of MT in patients with MeVOs in posterior circulation (P2 occlusions) compared to M2 and M3 occlusions. Improved techniques for successful recanalization are needed for posterior circulation MeVOs.
Abstract 51:
Apoe
Epsilon 4 And Risk Of Bleeding Patients With Brain Arteriovenous Malformations. A Combined Genetic Study In The Uk Biobank And All Of Us
Authors: Renedo Daniela , Rivier Cyprien , Acosta Julian , Clocchiatti Santiago , Wu Kane H , Torres-Lopez Victor M , Sheth Kevin N , Gunel Murat , Matouk Charles , Falcone Guido J
Published: February 2023

Background:
Patients with brain arteriovenous malformation (AVM) are at risk of intracranial hemorrhage (ICH). The epsilon 2 and 4 alleles within the
APOE
gene are well-described genetic risk factors for spontaneous, non-traumatic intraparenchymal hemorrhages. We tested the hypothesis that the
APOE
epsilon variants lead to higher risk of ICH in patients with AVMs.

Methods:
We conducted a two-stage (discovery and replication) genetic association study using individual-level data from the UK Biobank and the All of Us Research Program. We ascertained AVMs and ICH using validated ICD-9/10 codes. Genome-wide array genotyping was completed using the UK Biobank Axiom Array in the UK Biobank, and Illumina’s Global Diversity Array in All of Us. We used genotypic data on the
APOE
variants rs429358 and rs7412 to ascertain the epsilon 2 and 4 status. Within each study, we tested for association between
APOE
epsilon variants and ICH risk using multivariable logistic regression.

Results:
The discovery phase included 189 UK Biobank participants with an AVM (mean age 57 years, female sex 49%), including 37 (19.6%) that sustained an ICH. After adjusting by age, sex, and race/ethnicity,
APOE
epsilon 4 was associated with a higher risk of ICH (OR 4.20; 95%CI 1.99-9.25; p<0.001) whereas epsilon 2 was not (p>0.05). These results were replicated in 228 participants with AVMs enrolled in All of Us (mean age 56 years, female sex 66%), including 31 (13.6%) who sustained an ICH, where
APOE
epsilon 4 was associated with a higher risk of ICH (OR 2.73; 95%CI 1.05-7.22; p=0.038) whereas epsilon 2 was not (p>0.05).

Conclusion:
Among study participants with AVMs enrolled in two large population studies, the
APOE
epsilon 4 variants were associated higher risk of sustaining a brain bleed. These results point to shared pathophysiology with spontaneous intraparenchymal hemorrhages and provide support for further research focused on evaluating the role of
APOE
in risk stratification strategies.
Abstract 52: Prevalence Of Somatic Activating Kras Mutations In Pediatric And Adult Sporadic Brain Arteriovenous Malformations
Authors: Winkler Ethan A , Garcia Joseph , Tsang Cynthia , Nelson Jeffrey , McCulloch Charles , Weinsheimer Shantel , Fox Christine K , Fullerton Heather , Ko Nerissa , Su Hua , Nowakowski Tomasz , Cooke Daniel L , Hetts Steven , Guney Ekin , PEKMEZCI MELIKE , Tihan Tarik , Lawton Michael , Abla Adib , Gupta Nalin , Kim Helen
Published: February 2023

Introduction:
Sporadic brain arteriovenous malformations (bAVMs) are a potentially treatable cause of stroke disproportionately affecting young people. Non-inherited somatic activating mutations in
KRAS
have been reported in ~50% of bAVM specimens primarily from adults. We hypothesized that
KRAS
mutations would be associated with an earlier age at diagnosis, larger bAVM size, or earlier time to hemorrhage.

Methods:
Sporadic bAVM tissue and clinical data were collected from patients seen at our institution. Genotyping was performed by digital droplet polymerase chain reaction to detect
KRAS
mutations (p.G12D, p.G12V or p.Q61H) in three batches and coded as presence/absence of any
KRAS
mutation (primary predictor). Age at diagnosis was dichotomized into adults (18 years) or children (<18 years). Regression analyses adjusting for genotyping batch were performed to test association of
KRAS
mutations between children and adults (logistic), with bAVM size (linear), or with time from diagnosis to hemorrhage (survival), censoring at treatment or last follow-up.

Results:
We analyzed data from 221 patients: median age at bAVM diagnosis was 20 years; 44% were diagnosed as children; 53% were female; and 56% were ruptured on presentation. Median bAVM diameter was 2.1 cm (IQR: 1.4 - 3.0).
KRAS
mutations were detected in 53% of samples. Childhood bAVMs were significantly more likely to harbor
KRAS
mutations than those diagnosed in adulthood (OR=2.20, 95% CI: 1.24 - 3.91, p=0.007).
KRAS
-mutant bAVMs tended to be larger than
KRAS
-wildtype bAVMs, but this did not reach significance (+0.29 cm, 95% CI: -0.03 - 0.62, p=0.08). No association was observed for time to hemorrhage (HR=1.31, 95% CI: 0.91 - 1.88, p=0.15).

Conclusions:
Somatic activating
KRAS
mutations are more prevalent in bAVMs diagnosed in childhood than adulthood. Further work is required to elucidate mechanisms of mutagenesis and bAVM progression, which may differ in children and adults.
Abstract 54: Incidence And Predictors Of Dural Arteriovenous Fistulae After Cerebral Venous Sinus Thrombosis: Analysis Of ACTION-CVT
Authors: Shoskes Aaron , Shu Liqi , Nguyen Thanh N , Giles James , Siegler James E , Henninger Nils , Al Kasab Sami , Klein Piers , Heldner Mirjam R , Psychogios Marios , Liebeskind David S , Abdalkader Mohamad , Starke Robert M , Morcos Jacques J , Romano Jose G , Yaghi Shadi , Asdaghi Negar
Published: February 2023

Background:
Intracranial dural arteriovenous fistulae (DAVF) are uncommon vascular anomalies with a reported incidence of 0.2 per 100,000 person years. An association between cerebral venous thrombosis (CVT) and DAVF has been reported; however, the direction of causality between the two remains uncertain. We aimed to identify the incidence and predictors of development of DAVF among patients with CVT.

Methods:
This is a post-hoc analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT), a multicenter retrospective study comparing outcomes of CVT patients treated with warfarin versus direct oral anticoagulants (DOACs) from 2015 to 2020. Patients were included in this analysis if they did not have DAVF on initial imaging and had follow-up vascular imaging during the study. Clinical, imaging, and anticoagulation characteristics of patients who developed DAVF were compared to those who did not. Stepwise binary logistic regression including important variables (achieving p<0.1 on univariate analyses) was used to determine predictors of DAVF development.

Results:
A total of 751 patients (median age 43, 66% female) met inclusion criteria of whom 13 (1.7%) developed DAVF with an estimated rate of 2.40 per 100 patient years. Patients with DAVF were less likely to have headache at presentation (53.8% vs 79.3%, p=0.037), but more likely to have no venous recanalization on follow-up imaging (46.2% vs 14.8%, p=0.008), baseline cortical vein thrombosis (15.4% vs 2.7%, p=0.053), and received warfarin (vs. DOACs) as initial oral anticoagulant (84.6% vs 58.7%, p=0.085) but the latter two missed the statistical significance threshold. In stepwise binary logistic regression analysis, cortical vein thrombosis (OR 7.98, 95% CI 1.40-45.35, p=0.02) and lack of venous recanalization (OR 4.93, 95% CI 1.48-16.39, p=0.01) were associated with development of DAVF.

Conclusion:
In this large multicenter study of CVT, the incidence of DAVF development was higher than the previously reported rate in the general population. The presence of cortical vein thrombosis and lack of venous recanalization were associated with increased risk of development of DAVF.
Abstract 57: Sleep Duration Is Associated With Clinically Silent Brain Injury In Middle-aged Persons Without Stroke
Authors: Clocchiatti-Tuozzo Santiago , Rivier Cyprien , Renedo Daniela , Torres Lopez Victor M , Payabvash Sam , Sheth Kevin N , Gill Thomas M , Falcone Guido J
Published: February 2023

Background:
Evidence indicates that optimization of cardiovascular health during middle age leads to brain health benefits later in life. The AHA Life’s Simple 7, a research and public health construct capturing determinants of cardiovascular health, recently added sleep as a risk factor, becoming the Life’s Essential 8 (LE8). We hypothesize that suboptimal sleep duration worsens neuroimaging brain health profiles in middle-aged persons without stroke.

Methods:
We conducted a nested, cross-sectional neuroimaging analysis within the UK Biobank, a large population study conducted in the United Kingdom. We included participants without stroke/dementia who underwent a research brain MRI. We created a 6-category sleep score according to hours of sleep (best to worse): 7 to <9h; 9 to <10h; 6 to <7h; 5 to <6 or >=10h; 4 to <5h; and <4h. We evaluated 3 neuroimaging traits: white matter hyperintensity volume (natural log-transformed), fractional anisotropy (FA) and mean diffusivity (MD). For the last two traits, we evaluated the first principal component of measurements obtained across 48 neuroanatomical regions.

Results:
Of 502,408 participants enrolled in the UKB, 39,937 (7.9%) stroke/dementia-free enrollees participated in the brain MRI study (mean age 55, 53% female). The distribution of sleep categories was: 1 (n=28,958, 72.51%), 2 (n=2060, 5.16%), 3 (n=7165, 17.94%), 4 (n=1,562, 3.91%), 5 (n=163, 0.41%) and 6 (n=29, 0.07%). In multivariable linear regression analyses, a higher (worse) sleep score was associated with larger WMH volume (beta 0.026, SE=0.0046; p<0.001) and worse FA profile (beta 0.003, SE=0.0008; p<0.001), with no association observed for MD (p=0.77). For FA, when evaluating the 48 neuroanatomical regions separately, the most compromised areas were the right cerebral peduncle (p<0.001) and left and right cerebellar peduncles (p<0.001).

Conclusion:
Among middle-aged participants enrolled in the UKB, suboptimal sleep duration was significantly associated with adverse neuroimaging brain health profiles. These results emphasize the importance of sleep duration, the new component of the LE8, in determining brain health in middle-aged persons who have not developed clinically evident manifestations of poor brain health (stroke).
Abstract 58: ASCVD Risk Score Trajectories During 25 Years Of Follow-up And Risk Of Ischemic Stroke And Cognitive Impairment
Authors: de Havenon Adam , Bangad Aaron , Yaghi Shadi , Abbasi Mehdi , Sharma Richa , Sheth Kevin N
Published: February 2023

Background:
An individual’s atherosclerotic burden is associated with the cumulative exposure to vascular risk factors across the lifespan. We used the ARIC study to identify trajectories of atherosclerotic cardiovascular disease (ASCVD) risk over time and to evaluate their association with risk of stroke and cognitive impairment.

Methods:
We included cardiovascular disease-free ARIC participants with low or borderline ASCVD risk at the baseline study visit (10-year ASCVD Risk Score <7.5%) and those who attended all 5 ARIC study visits (~25 years of follow-up). We used group-based trajectory modelling to define ASCVD trajectories. We report baseline characteristics of individuals in the four trajectories and the incidence of stroke (ischemic and hemorrhagic) and cognitive impairment (either MCI or dementia) during follow-up.

Results:
We included 3,470 ARIC participants. The four trajectories of ASCVD risk during follow-up are in Figure 1. The low and high increase trajectories comprised 46.5% and 7.0% of participants. Vascular risk factors such as hypertension, diabetes, hyperlipidemia, and obesity were more common in trajectories with higher ASCVD risk (Table 1). The rate of ARIC-adjudicated stroke during follow-up increased from 1.6% in the low trajectory to 4.6% in the high trajectory (p<0.001), of self-reported stroke from 8.6% to 16.6% (p<0.001), and of ARIC-adjudicated cognitive impairment from 16.0% to 35.0% (p<0.001).

Conclusions:
We found four main trajectories of ASCVD risk over 25 years of follow-up in individuals with baseline low or borderline ASCVD risk, which are associated with the risk of incident stroke and cognitive impairment.

assessment.
Abstract 59: Reduced Readmissions And Improved Outcomes In Hemorrhagic Stroke Patients Actively Involved In Post-acute Care With Nurse Navigators
Authors: Dellostretto Nicole , Hackett Chris , Pope Leslie , Noah Patty , Cerejo Russell
Published: February 2023

Objective:
To evaluate whether the level of engagement of hemorrhagic patients with nurse navigators affected readmissions and outcomes.

Methods:
Retrospective multicenter study of hemorrhagic stroke patients from seven hospitals between January 2021 and April 2022. Patients who died or discharged to hospice were excluded. Navigators contacted patients at scheduled intervals to review care, medications, confirm appointments and provide education. Engagement was defined as a phone or virtual encounter with patient: low (< 5 encounters) or high (≥ 5 encounters) during 90-day epoch. The primary outcome examined readmission within 90 days using a binomial logistic regression. Secondary outcomes included: attendance of neurology visit; new or worsening symptoms and 90 day modified Rankin Scale (mRS) analyzed with binomial logistic and ordinal regressions. Sensitivity analysis examined outcomes in patients discharged to inpatient rehabilitation or skilled nursing. Multivariable analyses were adjusted for potential confounding variables.

Results:
We enrolled 368 hemorrhagic stroke patients, of which, 281 were included; 217 (77.2%) intracerebral hemorrhage and 64 (22.8%) subarachnoid hemorrhage. There were 144 (51.2%) less engaged and 137 (48.8%) highly engaged patients. Highly engaged patients were less likely to be readmitted compared to less engaged patients (23% vs. 42%), adjusted odds ratio (aOR) = 0.49 [95%CI, 0.28 - 0.87], p= 0.02. There was no difference in engagement and attendance of appointments, aOR = 1.73 [95%CI, 0.96 - 3.11], p = 0.07 or new neurologic events, aOR = 0.52 [95%CI, 0.25 - 1.08], p = 0.08. Highly engaged patients had less disability at 90 days compared to less engaged patients, median mRS = 2 (IQR, 1 - 3) versus 3 (IQR, 2 - 5), aOR = 0.49 [95% CI, 0.30 - 0.81], p = 0.006. Highly engaged patients discharged to a health care facility were also less likely to be readmitted and had less disability at 90 days compared to less engaged patients, all p< 0.05.

Conclusions:
Patients were found to have lower readmission rates and less disability at 90 days if they had a high level of engagement with the nurse navigators.
Abstract 68: Socioeconomic Factors Associated With Ems-documented Stroke Chief Complaints In The Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS)
Authors: Madsen Tracy E , Sucharew Heidi , Haverbusch Mary , Adeoye Opeolu M , Coleman Elisheva R , Demel Stacie L , De Los Rios La Rosa Felipe , Ferioli Simona , Jasne Adam , Li James , Mackey Jason , Mistry Eva , Slavin Sabreena , Star Michael , Walsh Kyle B , Woo Daniel , Kissela Brett M , Kleindorfer Dawn O
Published: February 2023

Background:
Accurate identification of stroke by EMS is necessary for triage and pre-notification within stroke systems of care. Our objective was to describe disparities in the documentation of stroke as the patient’s chief complaint (CC) by EMS in a large population-based stroke study.

Methods:
We included physician-adjudicated strokes and TIAs occurring among adults ≥18 years old in 2015 in the GCNKSS study population, based in a 5-county area of Southern Ohio/Northern Kentucky. Strokes in which EMS was not used and events occurring in the hospital, during EMS transport, at an unknown location, or outside the study region were excluded. The documented CC by EMS (stroke/CVA, MI, seizure, fall, weakness/numbness, headache, or other) were compared between race/sex subgroups. Sequential multivariable logistic regression was performed to identify associations between race, sex, and social determinants of health with an EMS-documented stroke CC. Social determinants included living arrangement and census tract social deprivation index (SDI).

Results:
A total of 1451 stroke/TIA events were included. White women had the highest proportion of EMS-documented stroke CCs (56%), more than Black women (48%), White men (45%), and Black men (42%), (p=0.02). Black race was inversely associated with an EMS-documented stroke CC in initial models but was collinear with SDI and no longer significant when SDI was included. In the full model, age, previous stroke, and living with others were associated with an EMS-documented stroke CC, while SDI and CAD were inversely associated with EMS-documented stroke CCs. (Table)

Conclusion:
Patients living in census tracts characterized by social deprivation were less likely to have EMS-documented stroke CCs, suggesting differences in either patient or EMS recognition of stroke. Further work is needed to explore potential confounders including EMS protocols and to improve identification of stroke by patients and EMS providers.
Abstract 69: Blood-brain Barrier Profile Influences Outcome After Mechanical Thrombectomy In The Frame Study.
Authors: Leigh Richard , Rousseau Vanessa , Christensen Soren , Albucher Jean-Francois , drif amel , Cognard Christophe , Guenego Adrien , Calviere Lionel , Viguier Alain , Sommet Agnes , BONNEVILLE FABRICE , raposo nicolas , JANUEL ANNE CHRISTINE , Mlynash Michael , Gaudilliere Brice , Thalamas Claire , Tourdias Thomas , Sibon Igor , Mazighi Mikael , Albers Greg , Olivot Jean M ,   FRAME Investigators
Published: February 2023

Background and Purpose:
The FRAME study demonstrated that even in the early time window (<6hrs) perfusion imaging profiles can influence response to mechanical thrombectomy. Perfusion imaging (PWI) can also be used to measure damage to the blood-brain barrier (BBB) which has been shown to be associated with increased risk of hemorrhagic complications (HC) with treatment. We aimed to determine if BBB profiles in the FRAME study would influence outcome after mechanical thrombectomy (MT).

Methods:
This was a post-hoc analysis of the FRAME study which enrolled stroke patients with large vessel occlusion who received MT within 6 hours of stroke onset. Patients with successful pre-treatment MRI PWI were included. We tested the hypothesis that more severe pre-treatment BBB disruption is associated with higher frequency of HC after MT. BBB disruption was measured as the percent of signal change due to gadolinium leakage on the PWI source images. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The outcome of HC was defined as any type of parenchymal hematoma (PH1 or PH2); poor functional outcome was defined as mRS >2 at 90 days. MPD was compared with HC and functional outcome using the Wilcoxon signed-rank test and logistic regression. A prespecified MPD threshold of 20% was tested as a predictor of HC based on prior studies.

Results:
There were 164 patients included in the analysis, median age 74 and 48% female. HC occurred in 57 patients. The average MPD was 15.1% for patients with HC and 8.7% for patients without HC. Elevated MPD was significantly associated with HC (p<0.0001) with a 25% increased risk of HC for each 5% increase in MPD (OR 1.25; CI 1.09:1.45; p=0.0018). Increased MPD was also associated with poor functional outcome (p=0.0002). ROC analysis confirmed the prespecified MPD threshold, identifying 19.7% as the optimal cut point for classification. MPD greater than 20% more than tripled the risk of HC (OR 3.37; CI 1.49:7.85; p=0.004).

Conclusions:
Increased pre-treatment BBB disruption has a substantial influence on the risk of HC after MT. Integration of BBB imaging into patient selection algorithms to improve MT outcomes should be tested further.
Abstract 70: Reducing Onset-to-reperfusion Times Through The Implementation Of A Prehospital Large-vessel Occlusion Bypass Protocol: A Real-world Experience
Authors: Chun Ian , Nakagawa Kazuma , Koenig Matthew , Brown Stacy , Tsappidi Samuel , Hui Ferdinand , Panczykowski David , SALEM Rony N , Chojecka M D Pola A , Kipta Joseph , Zhang Guangxiang , Sun Chung-Huan
Published: February 2023

Introduction:
Time to endovascular treatment (EVT) is a major determinant of patient outcomes for large vessel occlusion (LVO) strokes. Delays in interfacility transfers, however, can limit treatment efficacy. The Cincinnati Stroke Triage Assessment Tool (C-STAT) is a pre-hospital screen used to identify patients suspected of having LVOs. In October 2019, the “Oahu LVO Bypass Protocol” was adopted island-wide for all EMS evaluations. In this protocol, patients with C-STAT+ scores bypassed the nearest local hospital and were diverted to a Comprehensive Stroke Center (CSC). Our study aims to identify how this protocol has impacted onset-to-reperfusion times for patients with LVOs.

Methods:
A retrospective chart review was performed on all patients receiving EVT from January 1
st
, 2017 to February 1
st
, 2022. Patients were dichotomized into pre and post bypass groups using October 1
st
, 2019 as the implementation date. All non-EMS transfers, posterior circulation strokes, and patients >8 hours from symptom onset were excluded from analysis. We compared the two time epochs using descriptive statistics and an interrupted time-series analysis (ITS).

Results:
During the 5-year study period, 520 patients received EVT at our institution with an average age of 70.6 and median NIHSS of 19. A total of 115 patients met inclusion for the pre-bypass cohort and 172 patients for the post-bypass cohort. Significant reductions were observed in the median times (pre-bypass(min) [IQR] vs. post-bypass(min) [IQR]) from onset-to-CSC arrival (140[65-214] vs. 68[46-157], p<.001) and onset-to-reperfusion (233[167-310] vs. 189[151-250], p=.005) without significant delay in onset-to-tPA time (100[70-169] vs. 88[67-119], p=.121). The proportion of interfacility EVT transfers also declined from 51% to 17% between the pre and post bypass eras (p<0.001). On ITS analysis, the mean and median level of onset-to-CSC arrival times were significantly reduced by 30% and 51%, respectively. This reduction in treatment time was maintained for a 28-month post-bypass period.

Conclusion:
Implementation of the Oahu LVO bypass protocol shows significant reduction in onset-to-reperfusion times without delays to tPA administration, while also reducing rates of interfacility transfers.
Abstract 71: Temporal Trends In 30-day And 5-year Stroke Case Fatality Rates
Authors: Robinson David , Ding Lili , Khoury Jane C , Stanton Robert J , Alwell Kathleen , Khatri Pooja , Adeoye Opeolu M , Broderick Joseph P , Mackey Jason , Mistry Eva , Star Michael , Martini Sharyl R , Haverbusch Mary , Ferioli Simona , Woo Daniel , De Los Rios La Rosa Felipe , Demel Stacie L , Flaherty Matthew L , Slavin Sabreena , Walsh Kyle B , Coleman Elisheva R , Jasne Adam , Kleindorfer Dawn O , Kissela Brett M
Published: February 2023

Background:
Previous studies spanning the 1990s-2010s have inconsistently identified a decline in 30-day stroke case-fatality rate (CFR), and little is known about trends in longer term stroke CFR over that period. We studied temporal trends in 30-day and 5-year CFRs in the well-defined Greater Cincinnati/Norther Kentucky (GCNK) stroke population.

Methods:
The NIH-funded GCNK Stroke Study is a population-based study conducted in a 5-county region that is representative of the USA in terms of Black race, income, and education. The study ascertained all strokes in 1993/4, 1999, 2005, 2010, and 2015 using well-validated methods. All stroke subtypes were included: ischemic strokes (IS), intracerebral hemorrhages (ICH), and subarachnoid hemorrhages (SAHs). Deaths were identified via the National Death Index. Cox proportional hazards models were used to assess all-cause fatality, by subtype, to examine temporal trends adjusting for age, sex, and race.

Results:
A total of 10372 stroke cases were ascertained over the five study periods (8428 IS, 443 SAH, and 1501 ICH). IS patients did not demonstrate a decline in 30-day CFRs over time, but did show a nonsignificant decrease in 5-year CFR. Among IS patients, female sex was associated with a lower 5-year CFR, whereas Black individuals had a lower 30-day CFR but a higher 5-year CFR. For ICH, there was a small increase in both 30-day and 5-year CFR in later study periods, although this did not reach significance in all years. SAH showed a lower 30-day CFR over time but no change in 5-year CFR. Older age was associated with a higher 30-day and 5-year CFR in all subtypes.

Discussion:
Despite widespread advances in post-stroke care, adjusted 5-year CFR has not clearly improved for any stroke subtype and may have slightly worsened for ICH. 30-day CFR has shown a modest improvement among SAH patients. Future studies should investigate why Black individuals with IS experience lower early CFR but a higher late CFR.
Abstract 72: Association Between Patient And Hospital-level Factors With Door-in-door-out Times In Stroke Transfers: Findings From Get With The Guidelines®
Authors: Stamm Brian , Royan Regina , Giurcanu Mihai , Messe Steven , Jauch Edward C , Prabhakaran Shyam
Published: February 2023

Introduction:
Advanced acute stroke treatments (endovascular therapy (EVT), neurosurgery) are time sensitive and often require emergent interfacility transfer. Thus, Door-in-door-out (DIDO) times at transferring hospitals are an important quality improvement metric. We sought to characterize DIDO times for acute stroke transfers in the Get With The Guidelines® (GWTG)-Stroke registry and identify patient and hospital factors associated with DIDO time.

Methods:
Patients with stroke presenting between January 2019 and December 2021 transferred from the emergency department (ED) at the presenting hospital to another acute care hospital were included. Primary outcome was DIDO time (time of transfer out minus time of arrival to presenting ED). Generalized estimating equation (GEE) regression models were used to identify patient and hospital characteristics associated with DIDO time. Subgroup analyses were performed for hemorrhagic and ischemic stroke patients transferred for EVT.

Results:
Among 153,434 patients (age 67.3+15.0 years, 72.9% White, 51.2% male), 107,897 were ischemic and 41,736 hemorrhagic strokes. Overall, median DIDO time was 216 (25th-75th percentile 131 - 457) minutes. The following were associated with increased DIDO time: age >80 years (+36.18 minute increase in median DIDO time), Black race (+11.23 min), Hispanic ethnicity (+9.65 min), ischemic stroke type (+156.51 min), and urban location (+44.54 min) while the following were associated with decreased DIDO time: EMS prenotification (-49.19 min) and NIHSS >12 (-139.81 min). In the EVT ischemic stroke subgroup, age, sex, race, EMS prenotification, stroke severity, and after-hours timing were strongly associated with median DIDO time.

Conclusions:
Opportunities to reduce DIDO times for acute stroke interhospital transfers require focus on modifiable health system factors such as EMS pre-notification but also persistent race-ethnic and urban-rural disparities.
Abstract 74: Transition To Tenecteplase From Alteplase Improves Ambulance And Interfacility Transfer Time Metrics In A Large Regional Healthcare System
Authors: Cline Trevor E , Sangha Navdeep S , Rho Howard J , Yang Su-Jau , Cheng Pamela , Le Duy , Ajani Zahra , Taleb Shayandokht
Published: February 2023

Introduction:
The effect of tenecteplase (TNK) use on reducing interfacility transfer times and ambulance-based metrics for patients with a large vessel occlusion (LVO) eligible for endovascular thrombectomy (EVT) is not well studied. We analyzed how the administration of IV-TNK vs IV-tPA affected the Door In Door Out time (DIDO) as well as two novel ambulance-based metrics in patients arriving to the emergency department (ED) with an LVO who were transferred from 13 primary stroke centers to undergo EVT.

Methods:
Data were retrospectively abstracted for patients with an LVO from 09/2020 to 04/2022. Median DIDO times were calculated for patients who received no thrombolysis, tPA, and TNK. Subgroup analyses were performed for two novel time metrics, Door to Ambulance Arrival (DAA) and Ambulance Arrival to Ambulance Departure (AAAD), for patients that received IV thrombolysis. Statistical analysis was performed using the Wilcoxan rank sum and chi square tests.

Results:
There were 191 patients with AIS and an LVO. 130 received no IV thrombolysis and 62 received IV thrombolysis (32 tPA vs 29 TNK). There were no significant differences in baseline demographics between the thrombolysis and non-thrombolysis groups. Our sample was diverse in ethnicity with 60.7% being non-white. DIDO (TNK: 73 min {IQR 59-107} vs tPA: 106 min {IQR 88-137}, p = 0.01), DAA (TNK: 52.5 min {IQR 38-84} vs tPA: 77 min {IQR 61-105}, p = 0.03), and AAAD (TNK: 16.5 mins {IQR 10-22} vs tPA: 22 mins {IQR 18-40}, p = 0.01) were all faster for TNK cases compared to tPA cases. 58.5% of the TNK cases had a DIDO of ≤ 90 minutes vs 34.4% of tPA cases.

Conclusions:
Switching from IV-tPA to IV-TNK improved the DIDO by 33 minutes. This improvement was driven by two novel DIDO metrics: Door to Ambulance Arrival Time (DAA) and Ambulance Arrival to Ambulance Departure Time (AAAD) likely because the absence of a tPA infusion (drip & ship) allowed the use of non-critical care ambulances, which are more widely available, to transport patients.
Abstract 76: Estimating The Impact Of Hospital-level Variation In The Use Of Inpatient Rehabilitation Facilities Versus Skilled Nursing Facilities On Individual Stroke Patients
Authors: Simmonds Kent P , Burke James , Kozlowski Allan , Andary Michael , Luo Zhehui , Reeves Mathew J
Published: February 2023

Introduction:
Observational studies indicate that stroke rehabilitation at Inpatient Rehabilitation Facilities (IRFs) is superior to Skilled Nursing Facilities (SNFs). Nationally, IRF vs. SNF use varies widely at the hospital level, but the impact on individual patients is unclear. Our objective was to quantify the effect of the admitting hospital on the probability of receiving IRF or SNF care for individual stroke patients.

Methods:
Medicare claims data (2011-2014) was used to generate a cohort of acute ischemic and hemorrhagic stroke patients who were discharged to IRFs or SNFs. We generated 2 multivariable effects logistic regression models. Model 1 predicted IRF admission (vs. SNF) using only patient-level factors as fixed effects, whereas Model 2 added a hospital random effect. The impact of the admitting hospital on an individual patients’ probability of IRF care was estimated by taking the difference in predicted probabilities (p^) between the 2 models. Hospital effects were categorized as moderate (10-19%) or large (>20%) based on the change in size of p^. The magnitude and direction of the random effect terms in Model 2 was used to categorize individual hospitals as being either neutral, SNF-, or IRF- favoring.

Results:
The cohort included 1,816 acute care hospitals which discharged 135,415 patients to IRFs (n=66,548) or SNFs (n= 68,867). Half of the hospitals were categorized as neutral (n=870, 47.9%) with the remaining being SNF- favoring (n=485, 26.7%) or IRF- favoring (n=461, 25.4%). For half of all patients, acute care hospital had a moderate influence on the type of rehabilitation that they received. For SNF and IRF-favoring hospitals, there were large (55% and 37% of patients) or moderate (30% and 42% of patients) hospital effects on discharge setting for the majority of patients.

Conclusion:
For the majority of stroke patients, which acute care hospital they happen to be admitted to meaningfully impacts the type of rehabilitation care they receive
Abstract 79: Long-term Patterns Of Patient Transfer In A Regional Telestroke Network
Authors: Estrada Juan , Yan Zhiyu , Zachrison Kori S , Viswanathan Anand , Turner Ashby , Matiello Marcelo , Schwamm Lee H
Published: February 2023

Background:
Telestroke has been increasingly adopted by hospitals with limited access to neurological expertise and is often followed by transfer for a higher level of care. We sought to characterize factors independently associated with patient transfers after telestroke consultation in our regional telestroke network.

Methods:
We studied all telestroke consults from our urban comprehensive stroke center from 1/1/2005 to 06/30/2022 using the records in our telehealth portal. We examined the annual proportion of transfers among all consults overall and stratified by 6 levels of NIHSS severity and 4 levels of spoke hospital rurality. We used generalized linear mixed models to evaluate the association between transfer and patient demographics, hospital characteristics, use of video and care quality metrics (timeliness and tPA use), accounting for clustering by spoke hospital.

Results:
We identified 20,618 consecutive telestroke consults, of which 5,276 (25.6%) were transferred (602 cases excluded with unknown transfer status). The proportion of transfers decreased significantly over the study period (Figure). Decreases were observed for all rurality strata and all but the most severe strokes. After adjusting for temporal trends, factors independently associated with transfer included younger age, male gender, more severe stroke, and tPA use (Table).

Conclusion:
In our regional telestroke network, the proportion of transfers decreased substantially from 2005 to 2022 overall and across almost all patient and hospital groups. Telestroke may facilitate capacity management and retaining care in lower cost community settings, which may increase healthcare value.
Abstract 8: Outcomes And Recurrence Rates Among Patients With Provoked And Cryptogenic Cerebral Venous Thrombosis: Analysis Of The ACTION CVT Study
Authors: Almallouhi Eyad , Shu Liqi , Salehi Omran Setareh , Henninger Nils , Zubair Adeel , Vedovati Maria Cristina , Antonenko Kateryna , Heldner Mirjam , Liebeskind David S , Yaghi Shadi , Al Kasab Sami ,   ACTION CVT
Published: February 2023

Introduction:
Cerebral venous thrombosis (CVT) is a rare cause of stroke. While the standard treatment is anticoagulation, the type and duration of anticoagulation depend on the underlying etiology. This study aims to identify the characteristics and risk of recurrent venous thromboembolism (VTE) in patients with unprovoked CVT (cryptogenic), transient provoked CVT (peripartum, contraception, infection, trauma) and persistent provoked CVT (cancer, hereditary thrombophilias).

Methods:
We used the ACTION CVT retrospective database which included consecutive CVT patients in 27 stroke centers in the United States, Europe, and New Zealand from January 2015 to December 2020. Baseline characteristics were compared between the groups using Chi square test, T test or Mann-Whitney-U test, followed by multivariable logistic regression. We used interaction analysis to assess the risk of recurrent venous thromboembolism (VTE).

Results:
A total of 1025 CVT patients were included in this study; 363 (35.4%) had transient provoking factors, 152 (14.8%) had persistent provoking factors, and 510 (49.8%) had cryptogenic CVT. Patients with transiently provoked CVT were younger (P=0.003) and more likely to be women (P<0.001), and patients with cryptogenic CVT were less likely to have a prior VTE (P<0.001). Compared to patients with transient provoked, there was higher risk of recurrent VTE in patients with persistent provoking factors (HR 2.59, 95% CI 1.29-5.22, P=0.008) and numerically higher recurrent VTE risk in cryptogenic CVT (HR 1.85, 95% CI 0.98-3.51, P=0.059). These associations did not vary by age, sex, or history of VTE status (p-interaction > 0.1 for all). Results were similar in sensitivity analyses excluding those with positive Factor V Leiden or Prothrombin gene mutation as well as in analyses excluding patients with positive antiphospholipid antibody test.

Conclusions:
In this multicenter study, we found that the risk of recurrent VTE after CVT may vary depending on the underlying etiology with higher rates in patients with cryptogenic CVT and those with persistent provoking factors. Longer anticoagulation duration may be needed in such groups compared to CVT with transient provoking factors.
Abstract 81: Quality Of Life Trajectory In Stroke Survivors And Their Effect On Caregivers, One Year After Discharged From Rehabilitation Hospitals: A Longitudinal Study
Authors: Bartoli Davide , Vellone Ercole , Pucciarelli Gianluca , Brugnera Agostino , Alvaro Rosaria , Greco Andrea
Published: February 2023

Introduction:
A stroke survivor’s Quality of life (QOL) could be associated with the caregiver’s anxiety, depression and burden. The identification of specific trajectories in stroke survivors and their associations with caregivers’ outcomes, would be helpful for developing more tailored interventions for survivors and caregivers within the first year after the stroke onset. The aims of this study were to: identify the distinct trajectories of the stroke specific QOLs of stroke survivors discharged from rehabilitation hospitals; examine the associations between the stroke survivors’ QOL trajectories and the caregivers’ anxiety, depression and burden over time; and identify the predictors of the survivors’ QOL trajectories.

Methods:
This is a longitudinal, multicentre prospective study. Were recruited 415 stroke survivors and their caregivers, after the patients’ discharge from one of 20 rehabilitation hospitals located in central and southern Italy and were followed up every 3 months for 1 year.

Results:
Stroke survivors had similar trajectories in the physical dimensions of QOL, unlike psychological dimensions, where emerge two distinct trajectories of change in the QOL stroke survivor. The first trajectory (86%) included those who started with greater levels of QOL and improved slightly to markedly in all psychological domains, with this improvement decelerating over time. The second trajectory (14%) comprised those who started with lower overall levels of psychological QOL and experienced a linear worsening in Memory and Communication and no changes in Emotion and Participation. The impact of the distinct stroke survivors’ QOL trajectories on caregiver variables, such as burden, anxiety, and depression were examined. Caregivers experienced linear decreases in anxiety (
p
< .001)during the first year post-stroke, while burden (
p
= .086)and depression (
p
= .057)did not significantly change over time.

Conclusion:
Preventing the risk factors of a stroke survivor from causing a deterioration in QOL is a fundamental role in public health. Adopting precautionary strategies, for those who present certain risk factors for survivors’ discharged from rehabilitation hospitals, could lead to an improvement in the burden and depression of the caregiver.
Abstract 84: Impact Of Gastrointestinal Surgery On Efficacy Of Oral Anticoagulants In Patients With Nonvalvular Atrial Fibrillation: A Nationwide Population-based Study
Authors: Kang Dong-Wan , Kim Mi-Sook , Yang Wookjin , Kim Youngjoon , Chung Matthew , Ha Jiyeon , Lee Eung-Joon , Jeong Han-Yeong , Kim Jeong-Min , Jung Keun-Hwa , Ko Sang-Bae , Lee Seung-Hoon
Published: February 2023

Introduction:
Alteration of the gastrointestinal (GI) tract by resection or bypass surgery might affect the absorption of both warfarin and direct oral anticoagulants (DOACs). The clinical trials of DOACs excluded individuals with altered GI tract, hence there are limited pharmacokinetic data for them. Only several cases have been reported suggesting atrial fibrillation-related stroke due to reduced absorption of DOACs after GI surgery. We aimed to investigate the efficacy of warfarin and DOACs who underwent GI surgery using nationwide population-based data.

Methods:
This was a retrospective cohort study using claim-based national data from 2013 to 2020 from Korean Health Insurance Review and Assessment Service (HIRA). Patients with nonvalvular AF (NVAF) taking oral anticoagulants (OACs) were included. The patients taking OACs due to other indications than NVAF were excluded. Cox proportional hazard models with time-varying covariates were used to investigate the impact of GI surgery in patients taking warfarin and DOACs.

Results:
Of the 311,782 patients (mean age 72, male 56.7%) with NVAF, 3,807 underwent GI surgery. Warfarin and DOACs were prescribed in 14.3% and 85.7% of the patients, respectively. Overall, warfarin was associated with a higher risk of ischemic stroke compared with DOACs (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.44-1.59). In the GI surgery group, the hazard ratio for ischemic stroke for warfarin compared with DOACs was 2.70 (95% CI, 1.63-4.45, Figure). In the no GI surgery group, warfarin also had a higher risk of ischemic stroke compared with DOACs (HR 1.51, 95% CI 1.44-1.59). Among DOAC-treated patients, GI surgery was not associated with a risk of ischemic stroke (HR 0.87, 95% CI 0.67-1.12).

Conclusions:
DOACs were more effective for stroke prevention than warfarin in patients with NVAF whose GI tracts were altered due to previous surgery. GI surgery did not affect the risk of stroke in patients with NVAF taking DOAC.
Abstract 85: Food Swamps Are Associated With Incident Stroke In The Health And Retirement Study
Authors: Yang Dixon , Naqvi Imama A , Gutierrez Jose , Tom Sarah
Published: February 2023

Introduction:
The role of “food swamps”, an area characterized by a high-density of establishments selling fast-food and junk food relative to healthier options, on incident stroke is not well studied.

Hypothesis
We hypothesized that a higher retail food environment index (RFEI), indicative of food swamps, would be associated with greater odds of incident stroke.

Methods:
The sample comprised of community-dwelling stroke-free participants aged ≥50 years who enrolled in the 2010 epoch of the Health and Retirement Study (HRS), which is representative of the US population. If a participant moved to a new area during follow-up through 2016, we only considered incident strokes reported before relocation. The traditional RFEI is a county’s ratio of the number of fast-food restaurants and convenience stores to the number of grocers. The expanded RFEI additionally includes full-service restaurants as unhealthy food options, and farmers’ markets and specialized food stores as healthy food retailers. We averaged RFEI across all included follow-up years and dichotomized RFEI using a threshold of 5, previously shown to discriminate obesity rates. We used logistic regression models to assess the association between RFEI groups and incident stroke, adjusting for key covariates and weighting to account for survey design.

Results:
Among 84,023,542 participants (mean age 64±10 years, 54% female, 84% white) in weighted analysis, 3,224,378 (3.8%) reported an incident stroke during follow-up. The average traditional and expanded RFEI were 6.5±2.7 (72% in ≥5 group) and 6.9±2.3 (84% in ≥5 group), respectively. In fully adjusted weighted analyses, the higher traditional RFEI group had greater odds of incident stroke compared to the lower group (OR [95% CI]: 1.135 [1.132-1.138]). We found a similar association with expanded RFEI groups and incident stroke (OR [95% CI]: 1.095 [1.092-1.098]).

Conclusions:
Among community-dwelling adults in HRS, RFEI was associated with incident stroke, independent of demographics and health characteristics. Results highlight the potential importance of an area’s food options as a structural determinant in stroke, especially given most participants resided in areas with 6 times the amount of relative unhealthy to healthy food choices.
Abstract 86: Understanding Patterns Of Missingness In Acute Ischemic Stroke Trials: A Secondary Analysis Of Pooled Patient-level Follow-up Data.
Authors: de Havenon Adam , Skolarus Lesli , Aldridge Chad , Braun Robynne , Cole John W , Cramer Steven C , Lindgren Arne , Sunmonu N A , Worrall Bradford B , Lohse Keith
Published: February 2023

Background:
Understanding the magnitude and causes of missing data is crucial to ensuring scientific integrity of clinical trials. Missing data threaten statistical and ecological validity, as results will only generalize to those who remain represented in the sample.

Goal:
Identify factors associated with loss at follow-up in acute ischemic stroke trials.

Methods:
We harmonized patient-level data from multiple NIH-funded acute ischemic stroke trials including NINDS IV-tPA, ALIAS part 2, SHINE, FAST-MAG, IMS-III, POINT, and DEFUSE 3, all of which had a 90-day study outcome. The primary outcome was the proportion of missing modified Rankin Scale (mRS) scores at 90 days. We compared patients with and without a 90-day mRS score among a variety of baseline patient characteristics.

Results:
Among 9580 subjects, 459 (4.8%) were missing their 90-day mRS. Age and race were associated with missingness. Compared to those with complete data, participants with missing data were younger (62 vs 66 years, p<0.001). Non-Hispanic Black participants represented 18.8% of those with complete data, but 25.3% of those with missing data (p=0.001). History of cardiac disease —atrial fibrillation, coronary artery disease, myocardial infarction—and better baseline NIHSS score were associated less missingness (p’s≤.002 and p<.001, respectively). History of stroke/TIA, however, was positively associated with missingness (50.3% vs. 35.4%, p<.001).

Conclusion:
Bias due to missingness is an important consideration for all clinical trials, including genetic studies. Disparities in the availability of genetic data compounded by missing phenotypic data creates a twofold disadvantage for underrepresented groups. Long term, we need to understand the biomedical and sociological causes of these associations and develop recruitment and retention strategies to ensure the generalizability of trial results.