bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary Data Usage in Direct-to-Consumer Genetic Testing: To What Extent Are Customers Aware and Concerned?
Authors: Mladucky Janessa , Baty Bonnie , Botkin Jeffrey , Anderson Rebecca
Published: March 2021

Introduction: Customer data from direct-to-consumer genetic testing (DTC GT) are often used for secondary purposes beyond providing the customer with test results. Objective: The goals of this study were to determine customer knowledge of secondary uses of data, to understand their perception of risks associated with these uses, and to determine the extent of customer concerns about privacy. Methods: Twenty DTC GT customers were interviewed about their experiences. The semi-structured interviews were transcribed, coded, and analyzed for common themes. Results: Most participants were aware of some secondary uses of data. All participants felt that data usage for research was acceptable, but acceptability for non-research purposes varied across participants. The majority of participants were aware of the existence of a privacy policy, but few read the majority of the privacy statement. When previously unconsidered uses of data were discussed, some participants expressed concern over privacy protections for their data. Conclusion: When exposed to new information on secondary uses of data, customers express concerns and a desire to improve consent with transparency, more opt-out options, improved readability, and more information on future uses and potential risks from direct-to-consumer companies. Effective ways to improve readership about the secondary use, risk of use, and protection of customer data should be investigated and the findings implemented by DTC companies to protect public trust in these practices.
ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia—Brief Report
Authors: Reeskamp Laurens F. , Millar John S. , Wu Liya , Jansen Hans , van Harskamp Dewi , Schierbeek Henk , Gipe Daniel A. , Rader Daniel J. , Dallinga-Thie Geesje M. , Hovingh G. Kees , Cuchel Marina
Published: March 2021

Objective:

The mechanism by which evinacumab, a fully human monoclonal antibody directed against ANGPTL3 (angiopoietin-like 3 protein) lowers plasma LDL (low-density lipoprotein) cholesterol levels in patients with homozygous familial hypercholesterolemia is unknown. We investigated apoB (apolipoprotein B) containing lipoprotein kinetic parameters in patients with homozygous familial hypercholesterolemia, before and after treatment with evinacumab.

Approach and Results:

Four patients with homozygous familial hypercholesterolemia underwent apoB kinetic analyses in 2 centers as part of a substudy of a trial evaluating the efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia. The enrichment of apoB with the stable isotope (5,5,5-
2
H
3
)-Leucine was measured in VLDL (very LDL), IDL (intermediate-density lipoprotein), and LDL at different time points before and after intravenous administration of 15 mg/kg evinacumab. Evinacumab lowered LDL-cholesterol by 59±2% and increased IDL apoB and LDL apoB fractional catabolic rate in all 4 homozygous familial hypercholesterolemia subjects, by 616±504% and 113±14%, respectively. VLDL-apoB production rate decreased in 2 of the 4 subjects.

Conclusions:

In this small study, ANGPTL3 inhibition with evinacumab is associated with an increase in the fractional catabolic rate of IDL apoB and LDL apoB, suggesting that evinacumab lowers LDL-cholesterol predominantly by increasing apoB-containing lipoprotein clearance from the circulation. Additional studies are needed to unravel which factors are determinants in this biological pathway.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04722068.
Calciprotein Particles
Authors: Kutikhin Anton G. , Feenstra Lian , Kostyunin Alexander E. , Yuzhalin Arseniy E. , Hillebrands Jan-Luuk , Krenning Guido
Published: March 2021

Hypercalcemia and hyperphosphatemia associate with an elevated risk of cardiovascular events, yet the pathophysiological basis of this association is unclear. Disturbed mineral homeostasis and the associated hypercalcemia and hyperphosphatemia may result in the formation of circulating calciprotein particles (CPPs) that aggregate the excessive calcium and phosphate ions. If not counteracted, the initially formed harmless amorphous spherical complexes (primary CPPs) may mature into damaging crystalline complexes (secondary CPPs). Secondary CPPs are internalized by vascular cells, causing a massive influx of calcium ions into the cytosol, leading to a proinflammatory response, cellular dysfunction, and cell death. Although the pathophysiological effects induced by CPPs in vascular cells receive increasing attention, a complete picture of how these particles contribute to the development of atherosclerosis and vascular calcification remains elusive. We here discuss existing knowledge on CPP formation and function in atherosclerosis and vascular calcification, techniques for investigating CPPs, and models currently applied to assess CPP-induced cardiovascular pathogenesis. Lastly, we evaluate the potential diagnostic value of serum CPP measurements and the therapeutic potential of anti-CPP therapies currently under development.
Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation
Authors: Xu Zheng , Liang Ying , Delaney M. Keegan , Zhang Yaping , Kim Kyungho , Li Jing , Bai Yanyan , Cho Jaehyung , Ushio-Fukai Masuko , Cheng Ni , Du Xiaoping
Published: March 2021

Objective:

Despite the importance of reactive oxygen species (ROS) and NOX (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) 2 in platelet activation and in vivo thrombosis, it is unclear how ROS and NOX2 play a role in platelet activation and why NOX2 deficiencies in humans and mice do not affect hemostasis. Outside-in signaling of integrin α
IIb
β
3
mediates platelet response to shear stress, secondary platelet activation, and thrombus expansion and is critical to thrombosis but dispensable for hemostasis. We studied the mechanisms of platelet ROS generation, ROS-mediated platelet response, and the role of ROS in integrin α
IIb
β
3
outside-in signaling.

Approach and Results:

ROS generation in activated platelets was low and slow without shear but was robust under shear. Shear-enhanced ROS generation and activation of p47phox, an important regulatory subunit of NOX2, were diminished by the integrin antagonist integrilin or β
3
knockout, and by Gα
13
knockout or blocking the Gα
13
-β
3
interaction. Resting platelets spreading on integrin ligand fibrinogen also Gα
13
-dependently stimulated ROS generation and p47phox activation. Hence, Gα
13
-mediated outside-in signaling induces NOX2 activation and ROS generation which is greatly enhanced by shear. Outside-in NOX2 activation requires Src, phosphoinositide 3-kinase and Akt downstream of Gα
13
. Importantly, NOX2-knockout platelets showed defective ROS generation, reduced platelet spreading without shear, and reduced platelet adhesion and thrombus volume on collagen and VWF (von Willibrand factor) under shear, whereas ROS inhibition diminished activation of tyrosine kinase Syk.

Conclusions:

Outside-in signaling activates the mainly NOX2-mediated ROS generation, which mediates Syk-dependent secondary platelet activation, adhesion, and thrombosis with minimal effect on hemostasis.
Abstract 1: Thrombolytic Therapy for ‘Wake-Up Stroke’ - A Systematic Review and Meta-Analysis
Authors: Mac Grory Brian C , Saldanha Ian J , Mistry Eva , Poli Sven , Sykora Marek , Kellert Lars , Feil Katharina , Shah Shreyansh , McTaggart Ryan , Riebau Derek , Yaghi Shadi , Gaines Kenneth , Feng Wayne , Schrag Matthew
Published: March 2021

Introduction:
Twenty-five percent of strokes are detected upon awakening (‘wake-up strokes’; WUS) and are not amenable to thrombolytic therapy via existing time-based treatment approaches. We performed a systematic review and meta-analysis of the efficacy and safety of thrombolysis in patients with WUS using imaging-based selection algorithms.

Methods:
This systematic review was registered through PROSPERO (CRD42020151552). We searched PubMed, Web of Science, and Scopus between January 1, 2006 and April 30, 2020 for controlled trials and observational cohort studies (prospective or retrospective), in which adults with WUS were administered thrombolysis after MR- or CT-based imaging. Our primary outcome was recovery (mRS 0-2) at 90 days and our secondary outcome was symptomatic intracranial hemorrhage (sICH). We assessed risk of bias using the Cochrane Risk of Bias 2.0 and ROBINS-I tools.

Results:
We included 16 studies that enrolled a total of 14,017 patients. Sixty-one percent of patients receiving tPA achieved a functional recovery at 90 days (95% CI: 51% to 70%; 12 studies), with a relative risk (RR) of recovery of 1.21 compared with patients not receiving tPA (95% CI 1.01 to 1.46; 4 comparative studies). As shown in
Figure 1,
3% of patients receiving tPA in the treated WUS stroke group experienced sICH, an RR of 4.0 (95% CI 2.85-5.61) compared with patients not receiving tPA. On meta-regression, advancing age was negatively associated with the RR of recovery (p<0.001) and there was a trend that increased NIHSS was associated with the RR of sICH (p=0.083).

Conclusions:
In patients with WUS, thrombolysis is associated with functional recovery and with a low risk of sICH. This risk is comparable to the sICH rate from tPA-treatment of stroke utilizing the standard protocol timeframe (2.4% in ECASS III). Thrombolysis should be considered in the treatment of WUS in patients with favorable neuroimaging.
Abstract 12: Feasibility of Monitoring Covid-19 Related Stroke Patients Across a 14 Hospital Stroke System of Care
Authors: Rho Howard J , Sangha Navdeep S
Published: March 2021

Background:
Identifying and tracking COVID-19 related data has been crucial to the pandemic response. Most hospital systems have created internal tracking databases specific to COVID-19 but separated from other disease specific data pools. Traditional methods for tracking and trending novel and specific data such as COVID-19 related strokes may require personnel with highly technical skills to abstract the data. We aimed to create a COVID-19 stroke dashboard which would easily auto-abstract and update data.

Methods:
A simple monitoring system was designed using PowerBI™ and Microsoft Suite™ products that model existing data sources without using other IT resources. Existing data queries from various sources were modeled into one report and the resulting data model was used to track and trend incidence of COVID-19 and its relationship to stroke care throughout a 14- hospital stroke system.

Results:
The report allowed region-wide identification and evaluation of several metrics, including: volume of code strokes, the volume of patients who had a stroke within two weeks before or after testing positive for COVID-19, the initial NIHSS, if alteplase was administered, reason for no alteplase administration, delay in alteplase administration and if related to COVID-19 and the relationship of COVID-19 cases to the volume of code strokes. It was found that the volume of code strokes significantly decreased during the time of the pandemic and was inversely related to the volume of COVID-19 positive cases being reported in a county. The tool also found that COVID-19 positive stroke patients increased as the overall COVID-19 hospital volume increased.

Conclusion:
Assessing the relationships between a novel disease and other disease states may lead to changes in hospital workflows and practices resulting into improved patient outcomes.
Abstract 13: Sex Differences in Mortality Among Patients With Covid-19 Related Stroke
Authors: Vahidy Farhaan S , Meeks Jennifer , Pan Alan , Potter Thomas , Khan Osman , Gomez Juliana , Misra Vivek , McCullough Louise D
Published: March 2021

Introduction:
Overall poor COVID-19 outcomes have been reported among males. We evaluated sex differences in mortality among patients with stroke related to COVID-19.

Methods:
Utilizing pooled deidentified data from 30 healthcare organizations, we identified COVID-19 patients via ICD-10 diagnosis or documented laboratory confirmation of SARS-CoV-2 RNA or antibodies. Patients with ICD-10 diagnoses of ischemic stroke or intracerebral hemorrhage within 30 days before or after the COVID-19 event were flagged. Male and female patients were propensity score (PS) matched on other demographic and comorbidity variables. Risk Ratio (RR) and 95% Confidence Interval (CI) for association between sex and 90-day mortality is reported. Kaplan-Meier analyses with log rank test (LRT) were conducted for time-to-death. As a sensitivity analysis, we only included a smaller sub-set with first instance of IS or ICH ± 30-days of COVID-19 diagnosis.

Results:
Among 149,410 COVID-19 patients, 1,618 (1.1%) had a stroke diagnosis ± 30-days of confirmed COVID-19. Of whom, 1,609 patients (847 males and 762 females) were included in primary analyses. Females were older (67.7 vs. 65.7 years) and were more likely to be of black race (34.1% vs. 27.6%). Females had a significantly higher proportion of chronic pulmonary disease (38.8% vs. 28.8%) and obesity (34.2% vs. 24.8%); whereas males had higher proportion of alcohol abuse (8.5% vs. 3.8%). A 1:1 PS algorithm yielded an optimally matched sample of 634 males and females each, balanced on all covariates. In the matched sample, 11.7% of females and 15.8% of males experienced 90-day mortality; RR (CI): 1.35 (1.02 - 1.78), LRT p value 0.04. Higher risk of 90-day mortality among males with COVID-19 and stroke was maintained in the sensitivity analyses, RR (CI): 1.47 (1.06 - 2.00), LRT p value = 0.03 (graphic).

Conclusion:
Future studies examining the socio-demographic and biological mechanisms for poor stroke outcomes among males with COVID-19 are needed.
Abstract 18: The Role of Vascular Imaging at Primary Stroke Centers in the Drip and Ship Paradigm
Authors: Flores Alan , Seró Laia , Ustrell Xavier , Pellisé Anna , Gomez Choco Manuel , Viñas Jaume , Palomeras Ernest , Krupinski Jurek , Más Natalia , Cocho Dolores , Purroy Francisco , Zaragoza-brunet Jose , Cardona Pedro , Serena Joaquin , Ribó Marc , Obach Victor , Rubiera Marta , Perez de la Ossa Natalia
Published: March 2021

Background:
In drip-and-ship protocols, vascular imaging at Primary Stroke Centers (PSC), although recommended, is not usually performed in many PSC, and its value is uncertain. Our aim was to evaluate the role of performing vascular imaging at PSC, comparing patients with vascular imaging at PSC (VI+) Vs. those without vascular imaging (VI-) in several outcomes.

Methods:
Observational, multicenter study from a prospective, government-mandated, population-based registry of ischemic stroke code patients firstly evaluated at a PSC from January-2016 to June-2020. We determined and compared rates of Mechanical Thrombectomy (MT) candidates transferred to CSC from all ischemic stroke codes at PSC, MT treated at CSC patients from all MT candidates transferred, and metrics related to drip-and-ship paradigm between VI + and VI- groups. A multivariate analysis to determine PSC related factors associated with receiving EVT at CSC was performed.

Results:
From 5792 ischemic stroke code patients at PSC, 3384 (58.4%) received a vascular imaging at PSC (VI+). Among all, 32.6% were transferred to CSC as MT candidates, and finally, 10.6% were treated with MT at CSC. The rate of transferred MT candidates was lower in the VI+ than VI- group (n: 783, 23.1% Vs. n: 1109, 46 %, p< 0.001). Among the transferred MT candidates, MT treatment at CSC was more common in the VI+ than VI- (n: 377, 48.1% Vs: n: 239, 21.5%, p<0.001). In patients transferred with baseline mild strokes (NIHSS <6), the rate of MT treated patients was higher in VI+ than VI- (n: 31, 29% Vs. n: 20, 7% p<0.001). Interval times as DIDO (median minutes 84 Vs. 81) and DTP time (188 Vs. 182) did not show differences between VI+ and VI-. In multivariate analysis adjusted by age, the independent factors associated to receiving MT at CSC were VI+ (OR: 2,128, CI95%:1,549-2,922, p<0.001), baseline NIHSS, and RACE scale.

Conclusion:
In the present study, performing vascular imaging at PSC diminishes unnecessary transfers to CSC and is associated with a higher probability of receiving MT at CSC in transferred patients. In mild strokes, performing a vascular imaging at PSC increases the probability of receiving MT at CSC. Metrics related to drip-and-ship model were not affected by performing a vascular imaging at PSC.
Abstract 19: Prehospital Identification of Acute Ischemic Stroke is Associated With Faster and More Frequent Thrombolysis
Authors: Richards Christopher T , Sucharew Heidi , Kissela Brett M , Kleindorfer Dawn , Alwell Kathleen S , Woo Daniel , Khoury Jane C , De Los Rios La Rosa Felipe , Mackey Jason , Ferioli Simona , Mistry Eva , Demel Stacie L , Coleman Elisheva R , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , Haverbusch Mary , McMullan Jason , Khatri Pooja , Adeoye Opeolu M
Published: March 2021

Background:
Functional outcomes are improved when AIS patients receive faster treatment. The first medical contact for many AIS patients is with emergency medical services (EMS) providers. We hypothesize that AIS treatment is faster when EMS providers suspect stroke.

Methods:
We performed a retrospective analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a comprehensive study of stroke patients in a large geographical area with 1.3 million inhabitants whose demographics are representative of the United States. We compared AIS patients age ≥18 years transported by EMS in 2015 with an EMS impression of “stroke” or “weakness/numbness” to those with other EMS impressions. Primary outcome was thrombolysis rate, and secondary outcomes were times from EMS scene arrival to ED arrival, CT, and treatment and times from ED arrival to CT and treatment. Chi-square and Mann-Whitney U-tests were used to compare treatment rates and times, respectively. Logistic regression (for rates) and median regression (for times) adjusted for NIHSS, GCS, age, sex, race, and prior stroke history.

Results:
Among 2,486 confirmed AIS patients from 1/1/2015-12/31/2015, 868 were transported by EMS, including 595 (69%) with EMS suspected stroke. Compared to EMS non-suspected strokes, patients with EMS suspected stroke patients were more likely to receive thrombolysis (18% vs 8%; OR 2.67, 95% CI 1.63-4.47) and had faster prehospital transport (30 vs 32 min, p=0.02), ED arrival to CT (27 vs 46 min, p<0.01) and thrombolysis (64 vs 83 min, p=0.03), and EMS scene arrival to thrombolysis (91 vs 118 min, p=0.03) and EVT (164 vs 250 min, p=0.03). Findings were maintained in the adjusted models except for EMS arrival to EVT (Table).

Conclusions:
In a large population-based study, EMS stroke identification is associated with a higher rate of and faster thrombolysis. Efforts to increase accuracy of EMS stroke identification is likely to have significant clinical impact by shortening treatment times.
Abstract 20: Patterns of Stroke Center Certification and the Impact on Stroke Mortality in Counties of New York State
Authors: Chapman Emily , Yaeger Kurt A , Mocco J D
Published: March 2021

Introduction:
To establish a statewide stroke system in March 2019, New York State (NYS) created the Stroke Designation Program. Stroke centers (SCs) must be certified by a state-approved certifying organization (CO), which is tasked with initial designation and ongoing re-certification. Previous research has found an association at the national level between socioeconomic status and access to higher levels of acute stroke care.

Objective:
This study characterizes the relationship between socioeconomic status of NYS populations and stroke care level access by comparing median household income and wealth in counties with and without certified SCs.

Methods:
Population and median household income from the U.S. Census (2010), stroke epidemiological data from the Center for Disease Control, and Area Deprivation Index (ADI) data (ranked within NYS) from the Neighborhood Atlas, a project that quantifies disadvantage by census tract, were collected and averaged for each county. Income has been used to assess local wealth and ADI to analyze community health risks. Certification data were mined from quality check databases for The Joint Commission and Det Norske Veritas, the most commonly used COs. Student’s t-tests compared income and ADI in counties with at least one certified SC to those without. Linear regression characterized the relationship between income and ADI with number of certified SCs, stroke incidence and stroke mortality.

Results:
All 62 counties in NYS were investigated to yield 40 certified SCs. Counties with at least one certified SC had a significantly higher income ($68,183.63 vs. $57,155.12; p=0.03) and lower ADI (5.90 vs. 7.37; p=0.004) compared to counties with no certified SC. Higher income (p<0.001) and lower ADI (p<0.001) were also associated with more certified SCs. Counties with fewer certified SCs had significantly higher stroke mortality (p<0.001) despite having similar stroke incidence.

Conclusion:
Socioeconomic heterogeneity in NYS counties is correlated to differential access to certified SCs and quality stroke care, as fewer centers are found in lower-income and disadvantaged communities. Although populations with less access experience stroke at similar rates, this study finds higher death rates in these counties.
Abstract 21: Sex Differences in Post-Stroke Depression in the Elderly
Authors: Mayman Naomi , Tuhrim Stanley , Jette Nathalie , Dhamoon Mandip S , Stein Laura K
Published: March 2021

Introduction:
Post-stroke depression (PSD) occurs in approximately one-third of ischemic stroke patients. However, there is conflicting evidence on sex differences in PSD.

Objective:
We sought to assess sex differences in risk and time course of PSD in US ischemic stroke (IS) patients. We hypothesized that women are at greater risk of PSD than men, and that a greater proportion of women experience PSD in the acute post-stroke phase.

Methods:
Retrospective cohort study of 100% de-identified data for US Medicare beneficiaries ≥65 years admitted for ischemic stroke from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression, stratified by sex, up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio (HR) for diagnosis of depression up to 1.5 years post-stroke in males vs. females, adjusting for patient demographics, comorbidities, length of stay, and acute stroke interventions.

Results:
Female stroke patients (n=90,474) were 20% more likely to develop PSD than males (n=84,427) in adjusted models. Cumulative risk of depression was consistently elevated for females throughout 1.5 years of follow-up (0.2055 [95% CI 0.2013-0.2097] vs. 0.1690 [95% CI 0.1639-0.1741] (log-rank p<0.0001). HR for PSD in females vs. males remained significant in fully adjusted analysis at 1.20 (95% CI 1.17-1.23, p<0.0001).

Conclusions:
Over 1.5 years of follow-up, female stroke patients had significantly greater hazard of developing PSD, highlighting the need for long-term depression screening in this population and further investigation of underlying reasons for sex differences.
Abstract 31: Penumbra Consumption Rates Based on T Max Delay and Reperfusion Status: A Post-Hoc Analysis of the Defuse-3 Trial
Authors: Yaghi Shadi , Raz Eytan , Dehkharghani Seena , Riina Howard , McTaggart Ryan , Jayaraman Mahesh V , Prabhakaran Shyam , Liebeskind David S , Khatri Pooja , Mac Grory Brian C , Lansberg Maarten G , Albers Greg W , De Havenon Adam H
Published: March 2021

Introduction:
In patients with acute large vessel occlusion, the definition of penumbral tissue based on T max delay perfusion imaging is not well established in relation to late-window endovascular thrombectomy (EVT). In this study, we sought to evaluate penumbra consumption rates for T max delays in patients treated between 6 and 16 hours from last known normal.

Methods:
This is a secondary analysis of the DEFUSE-3 trial, which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6-16 hours of last known normal. The primary outcome is percentage penumbra consumption defined as (24 hour infarct volume-core infarct volume)/(Tmax volume-baseline core volume). We stratified the cohort into 4 categories (untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates.

Results:
We included 143 patients, of which 66 were untreated, 16 had TICI 0-2a, 46 had TICI 2b, and 15 had TICI 3. In untreated patients, a median (IQR) of 48% (21% - 85%) of penumbral tissue was consumed based on Tmax6 as opposed to 160.6% (51% - 455.2%) of penumbral tissue based on Tmax10. On the contrary, in patients achieving TICI 3 reperfusion, a median (IQR) of 5.3% (1.1% - 14.6%) of penumbral tissue was consumed based on Tmax6 and 25.7% (3.2% - 72.1%) of penumbral tissue based on Tmax10.

Conclusion:
Contrary to prior studies, we show that at least 75% of penumbral tissue with Tmax > 10 sec delay can be salvaged with successful reperfusion and new generation devices. In untreated patients, since infarct expansion can occur beyond 24 hours, future studies with delayed brain imaging are needed to determine the optimal T max delay threshold that defines penumbral tissue in patients with proximal anterior circulation large vessel occlusion.
Abstract 37: Outcomes Associated With Intraventricular Thrombolysis Among Patients With Intracerebral Hemorrhage: Propensity Score Analysis of 10-Year Contemporary Real-World Data
Authors: Vahidy Farhaan S , Meeks Jennifer , Potter Thomas , Khan Osman , Pan Alan , Misra Vivek , Hanley Daniel F , Ziai Wendy C , Britz Gavin W
Published: March 2021

Introduction:
Intraventricular thrombolysis (IVT) for hematoma evacuation among eligible intracerebral hemorrhage (ICH) patients is a promising modality to improve outcomes.

Methods:
We analyzed deidentified pooled data from a network of 40 healthcare organizations (Aug 2010 - Jul 2020). Using ICD-10 diagnosis / procedure, current procedural terminology codes, and medications; we identified index ICH events for extra ventricular drain (EVD) placement with or without IVT. Non adult (< 18 years) patients with thrombolysis use or conditions requiring thrombolysis (cerebral / myocardial infarction, pulmonary embolism, hemodialysis) within 3-days prior to the index event were excluded. IVT and non-IVT patients were propensity score (PS) matched for demographic, comorbidity and clinical variables. Match adequacy was assessed by standardized mean difference (SMD). Risk Ratios (RR), 95% Confidence Intervals (CI) were calculated for mortality at 7,30, and 90-days. Kaplan-Meier (KM) analysis with log rank test (LRT) was performed.

Results:
Among 109,754 patients with an index ICH event 76,608 met the inclusion criteria. Of whom, 7,539 (9.8%) were coded for EVD presence, and 1,688 (22.4%) received IVT. Significant differences in demographic and clinical parameters were observed between IVT and non-IVT groups (graphic). At 90-days 28.4% of non-IVT and 23.2% of IVT ICH patients had died. PS algorithm yielded a 1:1 optimally matched sample (94% SMD reduction) of 1,163 IVT and non-IVT ICH patients each, without significant differences across any co-variates. In the matched sample, the mortality risk was significantly lower for the IVT group at all three timepoints. RR (CI) for 7-day: 0.62(0.50 - 0.77), for 30-day: 0.76(0.65 - 0.88), and for 90-day 0.85(0.74 - 0.97). LRT p < 0.001 for all timepoints, KM curve for 30-day outcome shown in the graphic.

Conclusion:
Real world utilization of IVT for eligible ICH patients demonstrates significant reduction in early mortality.
Abstract 44: DEVT: Endovascular Treatment Alone versus Intravenous Alteplase Plus Endovascular Treatment in Stroke
Authors: Zi Wenjie , Qiu Zhongming , Li Fengli , Sang Hongfei , Luo Weidong , Liu Shuai , Yuan Junjie , Song Jiaxing , Nogueira Raul G , Yang Qingwu
Published: March 2021

Background:
In large vessel occlusion strokes, it is unknown whether the potential risks and added costs associated with intravenous alteplase before mechanical thrombectomy remain justifiable.

Methods:
In 33 stroke centers in China, patients presenting with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from onset and eligible for intravenous thrombolysis underwent 1:1 randomization mechanical thrombectomy alone (primary-thrombectomy group) or standard dose of intravenous alteplase followed by mechanical thrombectomy (bridging-therapy group). The primary endpoint was non-inferiority of functional independence at 90 days (defined as score 0-2 on the modified Rankin scale). Non-inferiority was established with a margin of -0.1. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality.

Results:
The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization (116 to the primary-thrombectomy and 118 to the bridging-therapy group). The primary endpoint of functional independence at 90 days was achieved by 63(54.3%) patients in the primary-thrombectomy versus 55(46.6%) in the bridging-therapy group (incidence difference, 7.7%; 95% confidence interval, -5.1% to 20.5%), indicating that primary-thrombectomy was non-inferior to bridging-therapy (Z=2.7157, P
non-inferiority
=0.00330). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% versus 6.8%) and 90-day mortality (17.2% versus 17.8%).

Conclusions:
In stroke patients with proximal anterior circulation occlusions within 4.5 hours from onset, mechanical thrombectomy alone was non-inferior to intravenous alteplase followed by mechanical thrombectomy in terms of 90-day functional independence. (Funded by the Natural Science Foundation of China and others; DEVT chictr.org.cn number, ChiCTR-IOR-17013568.)
Abstract 49: Building a Bridge From Hospital to Home Reduces Readmissions After Ischemic Stroke
Authors: Leonhardt-Caprio Ann M , Sellers Craig R
Published: March 2021

Background:
Readmission within 30 days after hospitalization due to ischemic stroke (IS) is associated with increased healthcare costs and higher risk of death and disability. Efforts to decrease hospital readmissions following IS may improve quality and cost of care.

Methods:
A multi-component improvement intervention to bridge the transition from hospital to home through increased certified home health agency (CHHA) referrals, post-discharge telephone calls, and enhanced communication with outpatient providers was developed. The project was implemented in July, 2019, and evaluated for six months following initiation. The primary outcome measure was same-hospital, 30-day readmission rate in the project-specific population of IS patients discharged to home from a stroke unit, and the overall IS population during the six-month baseline period compared to the six-month intervention period. Statistical significance was determined using chi square analysis (
p<.05
) and clinical significance with Cohen’s alpha (
d
>1.0).

Results:
Following implementation, a decrease in month to month variation in readmission rates (Figure 1) and a statistically and clinically significant decrease in 30-day, all-cause, same-hospital readmission rates from 7.389% to 2.791% (62.23% decrease,
p
= .010,
d
= 1.43) in the project population and from 6.557% to 2.995% (54.32% decrease,
p
= .031,
d
= 1.61) in the overall IS population, was seen. Improvement was seen in all process measures, with a statistically significant increase in CHHA referrals from 44% to 56% (28% increase,
p
=.04).

Conclusions:
Implementation of an evidence-based, bundled improvement intervention, which contributed to a significant increase in CHHA referrals for IS patients discharged to home, was associated with a meaningful decrease in readmission rates.
Abstract 64: Scar-Forming Glial Cells Engulf Synapse and Worsen Stroke Outcome Through Megf10 and Mertk
Authors: Shi Xiaojing , Luo Longlong , zhang zhijun , Tang Yaohui , yang guo-yuan
Published: March 2021

Objective:
Previous studies showed that microglia and astrocytes actively engulf synapse through MEGF10 and MERTK in the developing brain. But whether microglia and astrocytes in ischemic stroke (IS) or hemorrhagic stroke (HS) mice are still phagocytotic and how they affect the outcome of stroke remain unclear.

Methods:
Microglia or astrocyte-specific MEGF10 or MERTK knockout mice were generated, and subjected to transient middle cerebral artery occlusion (tMCAO), or collagenase-induced intracerebral hemorrhage. Immunostaining, Transmission electron microscope and Western blot were used to evaluate synapse engulfment, and dendritic spines were quantified using Golgi staining. Cresyl violet staining was used to evaluate atrophy volume and lateral ventricle enlargement of stroke mice. Neurobehavioral test including
mNSS
, rotarod, grid-walking and smart cage were performed to assess neurofunctional recovery. Single-cell RNA sequencing was further conducted to compare gene expression between IS and HS mice.

Results:
We showed that 14 days after IS, 25% of microglia and 50% of astrocytes were phagocytotic and engulfed synapses in the glial scar. However, in HS, 25% of microglia and 5% of astrocytes were phagocytotic, and only microglia were found to engulf synapses. We further demonstrated that MEGF10 and MERTK were upregulated in both astrocytes and microglia of mice subjected to IS and HS, and knockout of MEGF10 or MERTK in astrocytes or microglia inhibited synapse engulfment, which further increased synaptic density, reduced brain atrophy volume and improved neurobehavioral recovery after IS. However, knockout of MEGF10 or MERTK in microglia but not astrocytes in HS mice resulted in increased synaptic density and neurobehavioral recovery improvement. Single-cell RNA sequencing revealed that phagocytosis-related processes were downregulated in a subtype of astrocytes in HS brain than that in IS brain.

Conclusion:
Our study revealed a previously unknown role for astrocytes and microglia in engulfing synapse in the glial scar in stroke brain, and showed phagocytic astrocytes and microglia contribute differently to brain function recovery of mice that subjected to IS and HS, opening a new avenue to develop effective strategy for stroke treatment.
Abstract MP21: Mobile Interventional Stroke Teams Lead to Improved Outcomes in the Early Time Window for LVO Stroke
Authors: Morey Jacob , Zhang Xiangnan , Marayati Naoum Fares , Matsoukas Stavros , Fiano Emily , Oxley Thomas , Dangayach Neha S , Stein Laura K , Fara Michael , Skliut Maryna , Fifi Johanna T
Published: March 2021

Introduction:
Endovascular therapy (EVT) for large vessel occlusion (LVO) stroke is time-sensitive. At Mount Sinai Health System, we developed a novel Mobile Interventional Stroke Team (MIST) that travels to Thrombectomy Capable Stroke Centers to perform EVT, as opposed to transferring patients in the Drip-and-Ship (DS) model. We have shown significantly faster initial door-to-recanalization times and improved discharge outcomes. The effect of the MIST stratified by time of presentation has yet to be studied.

Hypothesis:
In patients presenting with a last known well [LKW] of <6 hours, the MIST model leads to better clinical outcomes as compared to the DS model.

Methods:
In a prospectively collected stroke database at a multicenter health system, patients undergoing EVT performed by a MIST or after transfer in a DS model from January 2017 to March 2020 with baseline mRS 0-2 were selected. Patients presenting in the early time window and late time window (LKW >6 hours) were analyzed separately. The primary endpoint was the proportion with a good outcome (mRS of 0-2) at 90 days. Secondary endpoints included discharge NIHSS and mRS.

Results:
In the 242 selected patients, the MIST and DS cohorts were similar in age, gender, initial NIHSS, pre-stroke mRS, and procedural details. In the early window, 54% (39/72) had a good 90-day outcome in the MIST model, as compared to 28% (25/88) in the DS model (p<0.01). In the late window, good 90-day outcomes were similar (29% vs 43%; p=0.40). The median NIHSS at discharge was 4.0 and 12.0 in the early window (p<0.01) and 5.0 and 11.0 in the late window (p=0.16) in the MIST and DS models, respectively. The early window discharge mRS was significantly better in the MIST model (p<0.01) and similar in the late window (p=0.74).

Conclusions:
The MIST model used in the early time window produces better 90-day outcomes compared to the DS model. This is likely due to the MIST’s ability to capture fast progressors in the early window.
Abstract MP39: Modeling the Clinical Implications of Andexanet Alfa in Factor Xa Inhibitor-Associated Intracerebral Hemorrhage
Authors: Chuck Carlin , Kim Daniel , Kalagara Roshini , Rex Nathaniel , Madsen Tracy , Mahmoud Leana , Thompson Bradford B , Jones Richard N , Furie Karen L , Reznik Michael
Published: March 2021

Background:
Andexanet alfa was recently approved as a reversal agent for the Factor Xa inhibitors (FXai) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown.

Methods:
We performed a simulation study to determine the potential clinical implications of andexanet alfa across a range of possible hemostatic effects using data from a single-center cohort of ICH patients who did not receive the drug. We used this data to determine the baseline probability of insufficient hemostatic efficacy (IHE) across patients with and without FXai use via k-fold cross-validated multivariable regression models, which we aggregated into an IHE propensity score. We then determined the probability of unfavorable 3-month outcome (modified Rankin Scale 4-6) using a model comprised of established clinical predictors and IHE propensity. We applied model parameters from this derivation cohort to simulate a range of IHE reductions and corresponding outcomes, which we used to calculate absolute risk reduction (ARR) and projected number needed to treat (NNT) to prevent one unfavorable outcome.

Results:
Training models using a real-world ICH cohort (n=604 total; 55 FXai patients) had good accuracy in predicting IHE (AUC 0.78) and unfavorable outcome (AUC 0.82). IHE was strongly associated with unfavorable outcome (OR 6.7, 95% CI 3.8-11.8) and occurred in 11.4% of FXai patients. Predicted ARR of unfavorable outcome was 5% (95% CI 3-8%) at one-third reduction of IHE and 8% (95% CI = 4-13%) at 50% IHE reduction, translating to a projected NNT of 20 (cumulative treatment cost $495,000) and 13 ($321,750), respectively.

Conclusion:
Even optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered, and placebo-controlled randomized trials are needed before its use can definitively be recommended.
Abstract MP4: Ticagrelor Plus Aspirin Versus Aspirin Alone in Acute Ischemic Stroke or TIA - Analysis of Bleeding Events in the THALES Trial
Authors: Molina Carlos , Amarenco Pierre , Ladenvall Per , Aunes Maria , Denison Hans , Evans Scott , Himmelmann Anders , Jahreskog Marianne , James Stefan , Knutsson Mikael , Nylander Sven , Röther Joachim , Wang Yongjun , Johnston S. Claiborne
Published: March 2021

Introduction:
In the THALES trial, ticagrelor and aspirin was superior to aspirin alone in reducing the primary endpoint of stroke or death, and subsequent disabling strokes, but increased risk of bleeding, as expected for dual antiplatelet therapy.

Aim:
Present the bleeding profile of ticagrelor in combination with aspirin in patients with acute cerebrovascular events.

Methods:
The THALES trial randomized patients with non-cardioembolic, non-severe ischemic stroke (NIHSS≤5) or high-risk TIA to ticagrelor (180mg loading dose on day 1 followed by 90mg twice daily until day 30) or placebo within 24h of symptom onset in 28 countries. All patients received aspirin 300-325mg on day 1 followed by 75-100mg daily until day 30. Primary safety endpoint was time to severe bleeding, defined by GUSTO criteria, within 30 days. Analyses were by intention to treat. (ClinicalTrials.gov number, NCT03354429).

Results:
Among 11016 patients randomized, 28 (0.5%) in the ticagrelor+aspirin group (T+A) and 7 (0.1%) in the aspirin group (A) had a severe bleeding event; HR 3.99 (1.74-9.14); p=0.001. Among these, 22 (0.4%) (T+A) vs 6 (0.1%) (A) were fatal or intracranial hemorrhages (ICHs) and 6 (0.1%) (T+A) vs 1 (<0.1%) (A) non-fatal events with hemodynamic compromise. ICHs included 10 (0.2%) (T+A) vs 2 (<0.1%) (A) hemorrhagic strokes and 4 (0.1%) (T+A) vs 2 (<0.1%) (A) symptomatic haemorrhagic transformations of ischemic stroke and other ICHs. Most severe bleeding events were spontaneous; 1 (T+A) and 2 (A) were traumatic and 1 in each treatment group were procedural. No predefined subgroup was associated with severe bleeding risk though analyses were limited by a small number of events. Moderate/severe bleeding events occurred in 36 (0.7%) (T+A) vs 11 (0.2%) (A) patients. Bleeding leading to discontinuation occurred in 152 (2.8%) (T+A) vs 32 (0.6%) (A) patients.

Conclusion:
While the rate of severe bleeding in the patients with acute ischemic stroke or TIA was low, patients randomized to receive ticagrelor more often experienced severe bleeding events. No subgroup with different bleeding risk could be identified. Given the high risk of disability following a subsequent stroke, the benefit of adding ticagrelor to aspirin in reducing subsequent stroke appears to outweigh the risk of bleeding.
Abstract MP44: Sex and Outcomes After Carotid Stenting and Endarterectomy for Asymptomatic Patients: A Pooled Analysis of the Crest and Act I Trials
Authors: Hanlon Bret , Voeks Jenifer H , Panthofer Annalise , Howard Virginia J , Howard George , Roubin Gary S , Brott Thomas , Rosenfield Kenneth , Matsumura Jon
Published: March 2021

Introduction:
Previous analyses of randomized trials comparing carotid artery stenting (CAS) versus carotid endarterectomy (CEA) have revealed varying sex-associated risk. To better understand sex as an effect modifier in the asymptomatic population, we combined the asymptomatic patients from CREST with the asymptomatic patients from ACT I.

Methods:
We analyzed data from 2544 subjects with ≥ 70% carotid stenosis randomized to CAS or CEA in addition to standard management of cardiovascular risk factors. CREST enrolled 1091 (548 CAS, 543 CEA) and ACT I enrolled 1453 (1089 CAS, 364 CEA) asymptomatic patients less than 80 years old (upper age eligibility in ACT I). We examined the impact of sex on risk within CAS-treated and CEA-treated patients using Kaplan-Meier methods. The pre-specified, primary composite endpoint was stroke, myocardial infarction, or death during the periprocedural period (within 30 days of randomization) or any ipsilateral stroke within 4 years after randomization.

Results:
For patients assigned to CAS, there was no difference in risk between the sexes (female-to-male HR = 1.04, 95% CI 0.65 -- 1.66, P = 0.87). For patients assigned to CEA, the difference in risk detected was not significant (female-to-male HR = 1.43, 95% CI 0.77 - 2.67, P = 0.26).

Conclusions:
Sex-differences in risk were not significant for those assigned CAS nor those assigned CEA in this largest pooled analysis of asymptomatic patients comparing CAS to CEA.
Abstract MP53: Intensive Blood Pressure Reduction and Secondary Stroke Risk: A Posthoc Analysis of the Sps3 Trial
Authors: de Havenon Adam H , Lansberg Maarten G , Falcone Guido J , Noche Rommell , Yaghi Shadi , Sheth Kevin N
Published: March 2021

Introduction:
The SPRINT trial demonstrated cardiovascular benefit for a target systolic blood pressure (SBP) <120 mm Hg, but the effect on primary stroke was neutral. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial did not reduce secondary stroke with a target SBP <130 mm Hg. No trial has investigated the effect of the more intensive SPRINT target of <120 mm Hg on secondary stroke risk.

Methods:
We performed a secondary analysis of SPS3 and included patients with at least 10 SBP readings. The primary predictor is mean SBP from day 30 (to avoid confounding from the initial study intervention) to 2 years. The primary outcome is recurrent ischemic stroke from day 30 to 2 years. We fit Cox models to our outcomes to derive hazard ratios for recurrent stroke events.

Results:
We included 2,859 patients, of which 121 (4.2%) had ischemic stroke during follow-up. There were 321 patients with SBP <120 (mean=115.5 mm Hg) and 2,538 with SBP ≥120 (mean=134.6 mm Hg), with a respective recurrent stroke rate of 1.9% versus 4.5% (p=0.026). In the Cox model, the hazard ratio for stroke with mean SBP <120 mm Hg was 0.40 (95% CI, 0.18-0.92) (Figure 1) and after adjustment for potential confounders (age, sex, race, education, smoking, prior stroke, prior myocardial infarction) the hazard ratio was 0.39 (95% CI, 0.16-0.96).

Conclusion:
In patients with lacunar stroke, achieving the SPRINT intensive blood pressure goal of <120 mm Hg was associated with a lower risk of recurrent stroke. While the current study is underpowered and has bias, these preliminary results suggest that the SPRINT definition of intensive blood pressure reduction could be beneficial for secondary stroke prevention.
Abstract MP54: Increase in the
Urban-Rural Divide
in Cerebrovascular Mortality Among Middle-Aged Adults From 2013 to 2018
Authors: Cierny Marek , Man Shumei , Uchino Ken
Published: March 2021

Introduction:
Despite observed overall decline cerebrovascular mortality in the United States over the past 2 decades, geographic pockets of increasing cerebrovascular mortality among middle aged adults have been reported on county-level data; and factors driving this regional increase are poorly understood.

Methods:
We extracted cerebrovascular mortality rates (ICD tenth revision codes I60-I69) in middle aged adults (age 35-64) from Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research database from 1999 to 2018. Variations in annual age-adjusted mortality rates, assessed with Joinpoint regression modeling, are expressed as estimated Annual Percentage Change [APC (95% confidence interval)], stratified by urbanization. In regions with increasing stroke mortality, race-ethnicity and gender subgroups were compared.

Results:
Mid-age cerebrovascular mortality decreased across urbanization strata between 1999 and 2012. Since 2013, stroke mortality has been increasing in Rural counties [APC +1.8% (+1.0% to +2.6%)] and stagnating in Small-to-Medium Metro counties [APC +0.7% (-0.1% to +1.5%)] and Large Metro counties [APC +0.1% (-0.8% to +0.9%)]. Focusing on rural counties, the profound rate difference between non-Hispanic African Americans and non-Hispanic whites decreased between 1999-2012 at Average APC -1.7% (-2.3% to -1.2%) and since then persisted [Average APC -0.2% (-2.1% to 1.8%)]. Both genders were affected.

Conclusion:
Since 2013, increase in cerebrovascular mortality in middle-aged adults in rural counties contributes to growing urban-rural divide; while the high stroke mortality rate in non-Hispanic African Americans have ceased to converge with non-Hispanic whites. Upstream drivers of stroke mortality in young and middle-aged rural residents and non-Hispanic African Americans should be further elucidated and vigorously targeted by public health initiatives.