bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 58: Calcium/Calmodulin-dependent Protein Kinase Kinase (CaMKK) Promotes Post-stroke Brain Plasticity and Recovery in Aged Mice
Authors: Liu Lin , Yuan Hui , Li Xue-Jun , Sun Ping , Qi Li , Yi Yanhua , McCullough Louise , Li Jun
Published: June 2021

Reduced brain plasticity, including axonal regeneration and angiogenesis, is thought to contribute to poorer functional recovery in the aged brain after a stroke. CaMKK has been suggested to activate major molecular pathways that enhance brain plasticity. Here we evaluated the hypothesis that CaMKK promotes post- stroke recovery by stimulating axonal regeneration and angiogenesis in aged mice.

Ischemic stroke was induced by middle cerebral artery occlusion for 60 minutes in aged WT male mice followed by reperfusion. STO-609, a pan-CaMKK inhibitor, and lentiviral vectors carrying CaMKK β (LV-CaMKK β) were started 3 days after stroke onset. Pellet reaching test (success rate) was carried out to evaluate the integrity of sensorimotor function every week for a total of 5 weeks.

Pharmacological inhibition of CaMKK by STO-609 significantly worsened stroke recovery evaluated by pellet reaching test from day 14 to day 35 after stroke (Day 35:Vehicle 0.29±0.02 vs. STO 0.16±0.02, n=8 in vehicle/n=5 in STO, p<0.05). Meanwhile, it significantly reduced axonal density assessed by neurofilament light (NFL) staining (Vehicle 1.00±0.06 vs. STO 0.53± 0.14, n=4, p<0.05) and vascular density represented by CD31 (Vehicle 1.00±0.20 vs. STO 0.48±0.06, n=4, p<0.05) in the peri-infarct zone on 35 days post-stroke, without changing brain cavity size (Day 35: Vehicle 0.13±0.01 vs. STO 0.13±0.02, n=8 in Vehicle/n=5 in STO, p>0.05). Additionally, CaMKK β overexpression improved mouse performance on pellet reaching test after stroke (day 35: LV-GFP 0.26±0.02 vs. LV-CaMKK β 0.36±0.02, n=7 LV-GFP/n=9 in LV-CaMKK β, p<0.05).

Conclusions:
Pharmacological inhibition of CaMKK worsened post-stroke recovery while overexpression of this molecule improved outcome. We observed reduced axonal density and cerebral vascular density with CaMKK inhibition, indicating CaMKK is an endogenous activator of brain plasticity in stroke. Our data suggested that CaMKK signaling may reduce long-term disability in the population at the greatest risk of stroke, the elderly.
Abstract 59: Post-stroke Delivery of Microrna-363 to Middle-aged Female Rats is Internalized by Neurons and Suppresses the Cell Death Effector Pathway
Authors: Selvamani Amutha , Sohrabji Farida
Published: June 2021

Background:
MicroRNAs serve as translational inhibitors and offer a unique therapeutic target for acute diseases such as stroke. Profiling of circulating miRNA after stroke identified mir363, whose expression was inversely correlated with infarct volume. Middle aged female rats show worse stroke outcomes than younger females and have much lower levels of mir363. Our recent studies showed that iv injections of miR363 mimic to middle aged females, significantly improved stroke outcome. The present study is designed to determine the mechanisms by which miR-363 acts as a therapeutic miR.

Methods:
Middle aged (12 mo) females were subject to MCAo. At 4h post-stroke, animals received a tail-vein injection of miR-363-3p FAM or scrambled control. Animals were terminated at 48h or 5d post-MCAo and perfused transcardially or processed for protein, respectively. To determine which neural cell types localized exogenous mir363-3p, combined immunofluorescence was performed for cell specific markers (neuronal (NeuN), astrocytic (GFAP), microglial (CD11b) and endothelial (PECAM)) and mir363-3p-FAM mimic on coronal brain sections (25 mm thickness). Protein lysates from the ischemic tissue was analyzed for caspase-3 expression by Western blot analysis.

Results:
FAM-labeled mir363-3p was widely detected in the forebrain. The majority of NeuN+ cells in the cortex and striatum were also labeled with FAM-363-3p, indicating a robust internalization of the mimic in neurons. FAM-mir363-3p was also localized to a few microglia (CD11b +), virtually no double-label was seen in astrocytes and endothelial cells. Mir363 decreased the expression and functional activity of caspase3 in the ischemic hemisphere.

Conclusion:
Collectively, the data suggests that exogenous miR-363-3p is shuttled to the brain and is preferentially internalized by neurons. Together with the caspase-3 regulation, our data suggests that mir363 may improve stroke outcomes by suppressing a cell death effector.
Abstract 71: PFO Closure Reduces Long Term Recurrence of Ischemic Stroke: Final Primary and Secondary Population Results From the RESPECT Multicenter Trial
Authors: Thaler David , Carroll John , Saver Jeffrey , Smalling Richard , MacDonald Lee , Larkin Brian , Marks David , Tirschwell David
Published: June 2021

Introduction:
In the intention-to-treat (ITT) analysis of the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial, a trend favoring PFO closure in the primary analytic period (median follow-up 2.1y) was statistically significant with longer follow-up (median 5.9y).

Hypotheses:
Populations with less clinical trial noise [Per Protocol (PP), As Treated (AT), Device in Place (DIP)] will show > benefit, consistent with a genuine treatment effect of closure. Analysis of strokes without known mechanisms (per ASCOD) or occurring while patients are less subject to non-PFO stroke mechanisms (<60y) will show heightened treatment effect.

Methods:
RESPECT was a prospective, multicenter, RCT comparing patients assigned 1:1 to PFO closure (Amplatzer PFO Occluder) or to medical management (MM) alone. Data were collected through May 2016.

Results:
We enrolled 980 patients who were followed for a median of 5.9y (IQR 4.2-8.0, range 0-11). All primary endpoint events were nonfatal ischemic strokes. The efficacy outcome in the ITT population significantly favored device closure over MM alone (HR: 0.55, 95% CI: 0.305 to 0.999, log-rank p=0.046) and was equal (PP) or magnified in the other populations analyzed by treatment actually received. It was also greater if events were excluded when they occurred after patients reached 60y or had a known (non-PFO) mechanism (Table).

Conclusions:
The final data from RESPECT, after long-term follow-up, show that the benefit of PFO closure seen in the ITT population is magnified in populations that account for treatment crossover and that include the age range in which recurrent ischemic strokes are predominantly cryptogenic. These secondary analyses reinforce the main trial finding that PFO closure with the Amplatzer PFO Occluder is superior to medical therapy alone in preventing recurrent ischemic stroke.
Abstract 76: Long-term Regular Remote Ischemic Conditioning Promotes Arterial Collateral Opening and Reconstruction in Patients with Intracranial Atherosclerotic Stenosis
Authors: Meng Ran , Zhao Wenbo , Li Sijie , Sui Meng , Zhou Da , Wu Weijun , Guo Linlin , Duan Jiangang , Lang Ye , Geng Tingting , Huang Tao , Zhou Jialei , Ma Xuesheng , Yin Liang , Du Haoze , Ding Yuchuan , Feng Wuwei , Ovbiagele Bruce , Song Haiqing , Ji Xunming
Published: June 2021

Background and purpose:
A previous study (NCT01570231) showed that long-term remote ischemic preconditioning (RIPC) prevents cerebral ischemic events in patients with symptomatic intracranial atherosclerotic stenosis (SIAS). This study aims to further evaluate its beneficial impact on cerebral collateral flow and its underlying mechanisms.

Methods:
Patients with SIAS were randomized to RIPC group (n=30) or sham group (n=28, NCT01570231). RIPC was achieved by blocked bilateral arm arterial blood flow 5-min with double cuffs inflated to 200mmHg, followed by deflation for 5-min, and this was repeated 5 times automatically in every training cycle by the RIPC training device. Sham-RIPC was done in the same fashion with the exception of Inflating pressure at 60mmHg, which make the subjects feel a pressure but does not block the blood flow. RIPC and sham-RIPC were performed twice a day for 180 consecutive days. All subjects received standard background medical treatment. Status of cerebral collateral flow was evaluated with the regional leptomeningeal collateral (rLMC) score either by MRA and/or CTA. Plasma levels of VEGF were measured by ELISA, and circulating endothelial progenitor cells (EPCs) marked of CD45-CD133+CD34+VEGF-R2+ were quantified by flow cytometry from the mononuclear cells, which were isolated from venous blood samples at Day 0, Day 30 and 180.

Results:
23(76.7%) patients in RIPC and 19(67.9%) in sham group completed MRA evaluation, and 7(23.5%) in RIPC and 9(32.1%) sham group finished CTA evaluation. The average rLMC score were 0.233±0.37, 1.133±0.24, and 2.066±0.31 in RIPC versus 0.214±0.35, 0.535±0.49 and 0.964±0.34 in sham group at Day0, 30 and 180(p
0
>0.05, p
30
<0.01, and p
180
<0.01). Plasma VEGF levels were 33.03±7.41, 136.88±60.79, and 285.37±77.75 in RIPC group versus 34.31±8.41, 66.85±16.89, and 93.86±18.97 in sham group (p
0
>0.05, p
30
<0.01, and p
180
<0.001). The ratios of EPCs were 0.018±0.012%, 0.086±0,015%, and 0.115±0.013% in RIPC group versus 0.019±0,011%, 0.045±0,012%, and 0.067±0,012% in sham group.

Conclusions:
Long-term regular RIPC appears to accelerate cerebral collateral open and vascular remodeling. It is associated with the elevated level of plasma VEGF and an increased ratio of circulating EPCs.
Abstract 78: Incidence of Atrial Fibrillation Among Patients with an Embolic Stroke of Undetermined Source
Authors: Passman Rod S , Rymer Marilyn M , Liu Shufeng , Ziegler Paul D
Published: June 2021

Introduction:
Trials are underway to evaluate the prophylactic use of novel oral anticoagulants (NOAC) in patients with embolic strokes of undetermined source (ESUS). It is uncertain whether the bleeding risks associated with prophylactic NOAC use will outweigh any stroke prevention benefit in ESUS patients who lack underlying atrial fibrillation (AF).

Methods:
We determined the proportion of patients in the CRYSTAL AF study who met ESUS trial criteria and had AF (≥2 minutes) detected within 3 years via an insertable cardiac monitor (ICM). Cryptogenic stroke patients ≥50 years old with a modified Rankin score ≤3 and no evidence of lacunar infarcts after an extensive stroke work up were included. Age ≥60 years and CHA
2
DS
2
VASc score ≥3 were required for patients whose index stroke occurred 3-6 months before randomization. We also compared AF detection rates between the ICM and standard monitoring arms using Kaplan-Meier estimates and computed the percentage of patients with AF detected within the initial 30 days of ICM monitoring.

Results:
Among the 441 patients enrolled in CRYSTAL AF, 246 (55.8%) met inclusion criteria for the ongoing ESUS trials. AF detection rates at 3 years reached 38.5% in the ICM arm vs. 2.7% in the control arm (HR 12.1 [3.7-39.3], p<0.0001, Figure). In contrast, AF detection rates at 30 days were only 6.7% and 0.8% in the ICM and control arm, respectively.

Conclusions:
Among the subset of CRYSTAL AF patients who met the ESUS trial criteria, >60% did not have AF detected via ICMs within 3 years of their index stroke event. Prophylactic NOAC use in the absence of AF may therefore increase bleeding risks without providing protection against AF-related stroke in the majority of ESUS patients. Furthermore, ICMs were superior to standard monitoring for AF detection in this ESUS population. Monitoring continuously for only the initial 30 days would have failed to identify AF in >80% of patients ultimately found to have AF via an ICM.
Abstract 84: Ischemic and Hemorrhagic Stroke in Infective Endocarditis: Features, Predictors and Trends Over Three Decades
Authors: Topcuoglu Mehmet A , Kursun Oguzhan , Buonanno Ferdinando S , Isselbacher Eric M , Hurtado Rocio M , Singhal Aneesh B
Published: June 2021

Background:
Stroke is a major complication of infective endocarditis (IE). The features and predictors of ischemic and hemorrhagic stroke subtypes are unknown.

Methods and Results:
In this retrospective study (1980-2011) we used original Duke criteria to diagnose IE in 1149 episodes (1081 patients; 81% definite, 80% native valve). Neuro complications occurred in 28% including infarcts (17.6%), ICH (4.6%), meningitis (4%), brain/spinal abscess (8%), and seizures (2%). Ischemic stroke was the isolated presenting symptom in 11%; its most frequent presentations were total/partial anterior-circulation syndrome (47%) and embolic encephalopathy (21%). On DWI, infarcts were disseminated small (45%) or multi-sized (31%), single (16%), or territorial (9%). Disseminated infarcts were associated with poor outcome (p=0.026). Post-ischemic hemorrhage occurred in 6.4%. Primary ICH was evident on admission in 55% including 36 parenchymal (92% lobar), 13 SAH (69% convexal) and 4 SDH. As compared to the non-stroke group (n=885), the ischemic (n=202) and hemorrhagic stroke (n=53) groups had higher rates of complications (e.g., meningitis, seizures, sepsis, renal failure), longer LOS, higher mortality, and lower rates of home discharge (all p<0.05). Both stroke groups had higher rates of
S. viridans
and Group B strep infections and more valvular vegetations; the ischemic stroke group had more intracardiac thrombi, and the hemorrhagic stroke group had more mechanical valve infection (all p<0.05). Heparin use was associated with a higher rate of new infarcts (12% vs. 5%, p=0.027) but not ICH (2.4% vs. 1.4%, p=0.6). Overall mortality (14.6%) was higher in both stroke groups, however both groups had similar neurological mortality. Mitral valve involvement, sepsis, and strep infections were independent predictors of both ischemic and hemorrhagic stroke. Age, renal failure, heart failure, sepsis, and
Staph aureus
endocarditis were independent predictors of non-home discharge. Over three decades the LOS decreased, ischemic stroke rates increased, but there was no change in ICH or mortality rates.

Conclusion:
Endocarditis-related ischemic and hemorrhagic stroke subtypes have overlapping risk factors, predictors, clinical phenotypes, and effects on outcome.
Abstract 86: Progress in Achieving More Rapid Door-to-Needle Times in Acute Ischemic Stroke: Interim Findings From Target: Stroke Phase II
Authors: Fonarow Gregg C , Cox Margueritte , Smith Eric , Saver Jeffrey , Reeves Mat , Bhatt Deepak , Xian Ying , Hernandez Adrian , Peterson Eric , Schwamm Lee
Published: June 2021

Background:
The benefits of intravenous tPA in acute ischemic stroke are time-dependent and hospitals participating in Target: Stroke have substantially improved the proportion of patients being treated with door-to-needle (DTN) times of ≤60 minutes. However, very few patients were treated with DTN times of ≤45 or ≤30 minutes during Target: Stroke Phase I (2010-2013). This study aims to assess whether there have been greater achievement of DTN times ≤45 and ≤30 minutes since the launch of Target: Stroke Phase II in Q2 2014.

Methods:
Target: Stroke Phase II identified and disseminated additional best practice strategies, provided updated clinical decision support tools, and set new hospital recognition goals. Rates of DTN times ≤45 and ≤30 minutes were compared prior to Target: Stroke (2003-2009), during Phase I (2010-2013), and during Phase II (Q2 2014-present) by weighted linear regression.

Results:
There were 131,166 intravenous tPA treated patients from 1397 GWTG-Stroke hospitals. Patient characteristics were similar during the study periods. Median DTN time declined from Phase I to Phase II: 66 minutes (IQR 51-87) to 54 minutes (IQR 41-71) and % of patients with DTN times ≤60 minutes increased from 42.0% to 62.7%, (P<0.0001). The % of patients with DTN times ≤45 minutes increased from Phase I to Phase II: 17.3% to 33.9%, absolute difference +16.6%, (P<0.0001). The % of patients with DTN times ≤30 minutes also increased from Phase I to Phase II: 4.1% to 10.3%, absolute difference +6.2%, (P<0.0001). The estimated annual rate of increase in patients with DTN times ≤45 minutes was 0.25% per year pre-Target Stroke, 3.5% per year during Phase I, and 7.7% per year during Phase II (P<0.0001) (Figure).

Conclusions:
There has been accelerating progress in achieving more rapid DTN times for tPA administration among GWTG-Stroke hospitals participating in Target: Stroke Phase II. Nevertheless, opportunities remain to further improve the timeliness of care and clinical outcomes.
Abstract 87: Centralization of Acute Stroke Treatment was Associated With a Reduction in Length of Acute Hospital Stay
Authors: Hastrup Sidsel , Johnsen Soeren Paaske , von Weitzel-Mudersbach Paul , Simonsen Claus Ziegler , Hjort Niels , Møller Anette Torvin , Harbo Thomas , Poulsen Marika Suzuki , Ruiz de Morales Ayudarte Noelia , Damgaard Dorte , Andersen Grethe
Published: June 2021

Introduction:
In 2012 a centralization and specialization of stroke services was implemented in Central Region Denmark (CRD) (n= 1.3 million inhabitants). It implied that acute stroke care was to be provided at only 2 units with re-vascularization therapy.

Objective:
The impacts on length of acute hospital stay (AHS), rate of thrombolysis (IV tPA), evidence-based clinical care and mortality.

Methods:
Population-based before-and-after registry study. The study cohort included all stroke cases in Denmark, with patients outside CRD being used as comparison to account for general changes in stroke care. The period before (May 2011- April 2012) was compared to after (May 2013 - April 2014) using regression methods, including difference-in-differences (DID) analysis. Potential confounders included age, gender, civil status, previous strokes, diabetes, atrial fibrillation, smoking, alcohol, stroke severity, hypertension and type of stroke.

Results:
Baseline data in Figure 1. Median length of AHS (days) in CRD decreased from 5 (IQR 7) to 2 (3) vs. from 5 (9) to 5 (8) in the rest of Denmark. IV tPA rates increased from 16% (95CI 14-17) to 19% (17-21) of all acute ischemic strokes in CRD and from 9% (8-10) to 14% (13-15) in the rest of Denmark (DID RR 0.77 (0.66-0.91)). All-or-none rates of 11 process performance measures of in-hospital care increased from 51% (49-53) to 63% (61-65) in CRD vs. 49% (48-50) to 60% (59-61) in the rest of Denmark (DID RR 0.99 (0.93-1.05)). Adjusted 30-days mortality rate decreased non-significantly and comparable to the rest of the country; OR 0.97 (0.71-1.32) vs. OR 0.91 (0.77-1.07) (DID OR 1.03 (0.75-1.41)).

Conclusions:
Centralization of acute stroke care was associated with a significant reduction in length of AHS when compared to the development in the rest of Denmark. The use of IV tPA and the quality of acute stroke care also improved, but the trend was not different from the rest of Denmark. No changes in the adjusted 30-days mortality were observed.
Abstract 96: Effects of Exercise on Post-stroke Cognitive Function
Authors: Oberlin Lauren E , Bernhardt Julie , Cumming Toby B , Marsland Anna L , Erickson Kirk I
Published: June 2021

Objective:
The aim of this meta-analysis was to provide an updated comprehensive analysis of the extant literature on physical activity (PA) training and cognitive performance post-stroke. We also sought to explore study and sample characteristics that may moderate the effects of PA training on cognition.

Methods:
We synthesized data from 639 participants included in 13 intervention trials that involved PA training and assessments of neurocognitive function. Intervention effects were represented by Hedges’ g, calculated separately for intervention and control conditions within each trial. Effect size data were subjected to moderation analyses using the between-group heterogeneity (Q
B
) test. Data were analyzed using random and mixed-effects approaches.

Results:
A positive, moderate effect size was observed for PA training on a domain general estimate of global cognition (Hedges’ g [95% Confidence Interval] = 0.56 [0.41; 0.70], p < .001). Furthermore, a mixed-effects analysis indicated that PA training led to significantly greater cognitive gains relative to controls (Q
B
= 9.26, p = 0.002). Among those that received PA training, performance improvements were observed in all neurocognitive domains assessed, including working memory (Hedges’ g = 0.65 [0.19; 1.12]; p = .006), executive function (Hedges’ g = 0.24 [0.10; 0.38]; p = .001), and attention and processing speed (Hedges’ g = 0.31 [0.10; 0.51]; p = .004). The effects of PA training on cognition were not moderated by intervention length or time from stroke to initiation of the intervention.

Conclusions:
The effects of PA training on cognition post-stroke are moderate in magnitude, and are apparent across numerous neurocognitive domains. These findings support the application of physical activity training to reduce the burden of cognitive impairment in stroke survivors.
Abstract NS10: Patients with Mild and Moderate Stroke Have Frequent, Severe, and Persistent Impairment in Information Processing Speed
Authors: Alderman Susan , Armstrong Terri , Wood Geri , Savitz Sean , Breier Joshua
Published: June 2021

Background:
One year after stroke 50-70% of survivors have information processing speed (IPS) impairment. IPS is a complex, elemental cognitive function with close but separate relationships with memory, attention, executive function, reading, and writing. IPS impairment can be devastating, even without physical deficits.

Hypothesis:
The frequency and severity of IPS impairment in patients with acute stroke is unrelated to stroke severity.

Methods:
In a longitudinal study, 30 adults with acute mild (NIHSS <5) versus moderate stroke (NIHSS 5-12) were assessed for IPS and memory impairments at three time points (< 72 hours, Week 3, and Week 12). The Symbol Digit Modalities Test (SDMT) was the primary IPS instrument, scores below the norm (51-62 points) indicate impairment.

Results:
Using linear mixed model regression, no significant difference was noted between patients with mild and moderate stroke in frequency and severity of IPS impairment (p=0.2). All patients had baseline abnormal SDMT scores, improving 21% by Week 12 (p=.005) with one patient scoring as unimpaired (51 points). Patients with mild stroke (n=18) had baseline scores on average 53% lower than SDMT norm (mean score 24 (12), [95% CI] 6 [18, 30], Standard Error (SEM) 3) and 32% lower at Week 12 (mean 34 (11), [95% CI] 5 [29, 40], SEM 3). Patients with moderate stroke (n=12) had baseline SDMT scores 60% lower than norm (mean 21 (11), [95% CI] 6 [15, 27], SEM 3) and 39% lower by Week 12 (mean 31 (12), [95% CI] 7 [25, 38], SEM 3). Memory impairment at enrollment (<72 hours post stroke) was noted in 100% of patients with moderate stroke and 78% of patients with mild stroke; at Week 12 the frequency of memory impairment was equal in both groups (67%).

Conclusion:
IPS were critically impaired, in both mild and moderate stroke, with minimal spontaneous recovery at Week 12. IPS impairment is clinically significant during stroke recovery. IPS impairment should be considered in the planning of healthcare of stroke victims even with mild stroke.
Abstract NS11: Identifying Discharge Needs for Stroke Patients Using the Montreal Cognitive Assessment
Authors: Djoeva Sanny , Angulo Melissa , McGee Kay , Testai Fernando , Hillmann Maureen
Published: June 2021

Background:
Patients who develop a stroke are at high risk for cognitive decline. The Montreal Cognitive Assessment (MOCA) is a validated tool for assessing cognitive function within this patient population prior to discharge. An important limitation of the MOCA is that often times there is no pre-morbid score for comparison. Despite this, consideration of occupational and cognitive therapy is important in this population because of the high risk for cognitive decline.

Methods:
A total of 231 patients were treated on the stroke unit from December 2015 to June 2016, of these 149 patients were excluded due to activity intolerance, severe communication barriers, patient refusal, or cognitive deficits exceeding the limit of the screening tool. A retrospective chart review was conducted on the 82 patients and data on demographics, stroke risk factors, stroke type (ischemic, subarachnoid hemorrhage, or intracerebral hemorrhage), MOCA scores, and discharge disposition (home or acute/subacute rehabilitation) was extracted.

Results:
Of the 82 patients in the study, 45 (55%) were male, with an average age of 54.9 years. Thirty-eight (46%) of these patients suffered hemorrhagic strokes. Average MOCA scores for hemorrhagic stroke patients who were either discharged home versus a rehab setting were similar when compared to the ischemic stroke population (20.1 and 18.2 versus 21.3 and 16.9, respectively). However, when subcategorized by stroke subtype, the subarachnoid hemorrhage population exhibited higher MOCA scores for those who were discharged home or to rehab versus the patients with ICH who were discharged home or to rehab (21.9 and 25.4 versus 19.1 and 13.6, respectively). Interestingly, the patients within the SAH cohort who were discharged to rehab had a higher MOCA average than those who were discharged home.

Conclusion:
Many patients who suffer hemorrhagic strokes in this population are discharged home despite having a MOCA score below normal (<26). This may demonstrate residual cognitive deficits as a result of their disease process. Despite a patient’s ability to be functionally and physically able to return home, there is an identified need for addressing cognitive deficits in order to improve quality of life.
Abstract NS8: Male Caregivers Report Problems and Successes Caring for Wives/Partners
Authors: Pierce Linda L , Steiner Victoria
Published: June 2021

Background:
Stroke is sudden/often traumatic; its results affect both the person with stroke and family members providing care. Transitioning from the non-caregiver role to caregiver for a spouse who recently had a stroke may be unsettling, particular for men.

Purpose:
Guided by Friedemann’s framework of systemic organization,
t
his secondary data analysis examined problems and successes reported by males caring for partners (wife or long-time friend) in the first year after stroke. According to this framework, these men are driven by the desire for success, resulting in health/ well-being or congruence in caring. Whereas incongruence or poor health can result from problems experienced in caring.

Method:
Using a descriptive design with IRB approval, caregivers (n=73) participated in bimonthly telephone interviews for one year. These caregivers were asked open-ended questions about problems and successes experienced in caring in the past two weeks. For this analysis, only the males caring for a partner (n=12 wives; n=1 friend) were examined. These data were analyzed using Colaizzi’s rigorous method of content analysis.

Results:
The caregivers were white men with an average age of 62 years. Most were high school graduates, employed full-time, rated their health as very good/excellent, and spent 2-16 hours caring each day. There were 275 problems and 393 successes in caring reported. Five problem themes emerged: 1) adjusting to multi-tasking in everyday living, 2) recognizing physical and mental disabilities, 3) dealing with outside forces and limited resources, 4) struggling to return to normal, and 5) feeling physically, mentally and emotionally exhausted. These problem themes demonstrated incongruence as the men sought to maintain their prior lives. Three success themes appeared: 1) gaining confidence through functional improvement, 2) fostering success through mutually positive attitudes, and 3) resuming normal roles. The success themes demonstrated how these men were able to find a level of well-being/congruence in caring.

Conclusions:
Theory-based themes of male stroke caregivers’ problems and successes were uncovered that can be used to target interventions to help them achieve balance between incongruence and congruence in their lives.
Abstract TMP101: Mail Order Pharmacy Use is Associated With Greater Adherence to Secondary Preventive Medications and Lower Hospital Readmission Among Stroke Patients
Authors: Neil William P , Shiokari Chrislynn E , Burchette Raoul J , Stapleton David B , Ovbiagele Bruce
Published: June 2021

Background:
Mail order pharmacies (MOP) are increasingly being used to deliver medications for chronic disease management. Their use is linked to similar or greater medication adherence than local pharmacy (LP) use. Medication adherence is associated with improved outcomes, including reduced cardiovascular events, health care costs, and mortality. We are unaware of any studies that have evaluated the association of MOP use with medication adherence among stroke patients.

Objective:
To investigate whether stroke patients who use MOPs were more likely to have good medication adherence than those who used LPs and whether adherence was associated with 90 day hospital re-admission after stroke.

Methods:
We conducted cross-sectional analyses of patients discharged with ischemic stroke from 24 hospitals who received a new anticoagulant, antiplatelet, antiglycemic, antihypertensive, and/or lipid-lowering medication between 01/JAN/2007 and 30/JUL/2016. We compared adherence between MOP users (at least 66% of refills by mail) and LP users (all refills in person). Adherence was calculated by using the Continuous Medication Gap (CMG) methodology, which determines the cumulative period that no medication was available to the patient. The number of days for which the patient did not have the medication is divided by the number of days in the study window for that patient. A CMG adherence score of 0 meant that the patient had no overall gaps in their medications (perfect adherence), a negative number meant that the patient had more medication than days, and a positive number meant that the patient did not have enough medication for the days they should be taking their medication (poor adherence).

Results:
A total of 44,658 eligible patients refilled an index medication. Of these, 13,676 in the LP and 6,907 in MOP group met inclusion criteria. CMG adherence was 0.28 in the LP group and 0.11 in the MOP group ( p < 0.001). At 90-days there were 893 hospital readmissions for the LP group and 375 for the MOP group for a rate of 0.073 vs. 0.058 (p < 0.001).

Conclusions:
Stroke patients who obtain medication by mail are more likely to have good adherence, and less likely to be readmitted than those who obtain medications from their local pharmacies.
Abstract TMP103: A Culturally-tailored, Skills-based Intervention to Reduce Vascular Risk in a Multi-ethnic Group of Mild/Moderate Stroke Survivors: An Interim Analysis from the DESERVE Trial
Authors: Boden-Albala Bernadette , Goldmann Emily , Lord Aaron S , Parikh Nina S , Kuczynski Heather M , Tuhrim Stanley
Published: June 2021

Introduction:
Secondary stroke prevention strategies have proven suboptimal in underserved communities and minority populations.

Methods:
The Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial tested the efficacy of an innovative skills-based intervention focused on risk perception, medication adherence, and patient-physician communication (vs. usual care enhanced with educational material [EUC]) on blood pressure (BP) reduction among mild/moderate stroke (NIH Stroke Scale ≤ 15) or TIA patients at 1 year post discharge. Study participants were stratified by interview language (English/Spanish) and randomized to intervention or EUC. BP reduction was the difference between systolic BP at baseline and 1-year post-discharge. We assessed differences in baseline characteristics and mean BP reduction between trial arms, overall and by race/ethnicity. Linear regressions evaluated mean difference in blood pressure reduction between trial arms, adjusting for characteristics that differed between trial arms at baseline and language of interview.

Results:
To date, 290 of 552 stroke/TIA patients recruited at baseline (25% white, 32% black, 36% Hispanic) were evaluated at 1 year (n=145 in each arm). Overall, there was a trend toward greater mean BP reduction in the intervention vs. EUC group (9.3 vs. 6.0 mmHg, p=0.259). Mean BP reduction was significantly greater in the intervention vs. EUC group among Hispanics (9.9 vs. -0.7 mmHg, p=0.040). Among Hispanics, after adjusting for interview language, sex, and place of birth, mean BP reduction was 10.9 mmHg greater in the intervention vs. EUC group (p=0.041). Mean BP reduction did not differ significantly between trial arms among non-Hispanics. We are currently gathering information to evaluate the impact of the intervention on secondary stroke incidence.

Conclusions:
Few behavioral intervention studies in stroke survivors have reported significant differences in vascular risk reduction in the longer term, and fewer have focused on a skills-based approach. Culturally-tailored, skills-based interventions may be more useful than knowledge-focused interventions in achieving sustained vascular risk reduction and addressing race/ethnic disparities in stroke.
Abstract TMP120: Genetic, Environmental and Stochastic Factors Contribute to Variation in the Posterior Communicating Collaterals of the Circle of Willis
Authors: Faber James E , Rzechorzek Wojciech , Dai Kathy Z , Summers Benjamin T , Blazek Cooper N , Hedges Samuel J , Zhang Hua
Published: June 2021

Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in severity of tissue injury in obstructive disease. The “extent” of PCom collaterals (lumen diameter &/or number—ie, presence bilaterally, unilaterally or absent) varies widely in humans and other species due in part to developmental differences, since well-known patterns of variation are present at birth. However, mechanisms underlying this variation have not been examined. Herein we used angiography to probe involvement of genetic, environmental and stochastic factors. PCom extent varied widely among 7 mouse strains with different genetic backgrounds that was unrelated to differences in PCA diameter or brain weight. The pattern differed strongly from that previously reported by us for differences in extent of pial collateral arterioles. Like pial collaterals, PCom diameter was reduced by advanced aging (-28±3%, n=11-16, p<0.01; opposite seen for PCA diameter) and hypertension (-14±8%, n=7-9, p<0.05; -18% for PCA diameter). In contrast to pial collaterals, obesity, hyperlipidemia, metabolic syndrome and diabetes had no effect on PCom extent (or PCA diameter). Intrauterine growth restriction reduced PCom diameter 55±4% (n=6-17, p<0.05; -24% for PCA) in the adult despite catch-up growth of brain after birth, while pial collaterals were unaffected. Compared to pial collaterals (and PCA), PCom extent evidenced >8-fold larger stochastic variation (n=16, p<0.01). In addition, PComs underwent outward remodeling after MCA occlusion that varied with genetic background (12-133% lumen enlargement among 5 strains; n=5-14, p<0.05-0.001) and was greater on the side of occlusion in most strains. In conclusion, variation in number and diameter of PCom collateral arteries arises from genetic, environmental and stochastic factors. The responsible genetic polymorphisms appear to differ from those that contribute to variation in extent of pial collateral arterioles. Extent of PComs is also adversely affected by intrauterine growth restriction, aging and hypertension. These findings suggest possible sources of PCom variation in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.
Abstract TMP13: Safety and Efficacy of Lower Dose versus Standard Dose r-tPA: A Meta-Analysis
Authors: Dong Yi , Chhatbar Pratik Y , Liu Shimeng , Dong Qiang , Ovbiagele Bruce , Feng Wuwei
Published: June 2021

Introduction:
Intravenous r-tPA at a dose of 0.9 mg/kg of body weight is an established effective treatment for acute ischemic stroke with increased risk for symptomatic intracranial hemorrhage(sICH); however, r-tPA at dose <0.9 mg/kg has been investigated in different studies with mixed results in terms of safety and efficacy. We aimed to conduct a meta-analysis on existing clinical trials that compare the standard dose (0.9 mg/kg) with the low-dose group.

Hypothesis:
Patients receiving intravenous low dose r-tPA will have equivalent favorable outcomes, lower risk of sICH and mortality rate as compared with standard dose.

Methods:
We searched Pubmed from 1992 to 2015 with terms of “low dosage”, “tPA” and “ischemic stroke” (Fig 1A). Inclusion criteria are: 1) randomized or non-randomized studies with two arms (0.9 mg/kg vs. <0.9 mg/kg); 2) mortality was available in the manuscript; 3) modified Rankin Scale(mRS) was used as the primary or secondary outcome at 3 months; 4) published in English language. Data were extracted and summary odds ratios were calculated for sICH, the mortality rate, favorable outcome (mRS of 0-1).

Results:
Ten clinical studies met inclusion criteria and were included with 14,321 subjects among which 43.7% were females. Low-dose groups ranged from 0.5 to 0.85 mg/kg. The summary odds ratio for low-dose group vs. standard dose group is 1.02 [0.36-2.85, p=0.97] for sICH; 1.20 [0.81-1.78, p=0.65] for mortality rate; 0.88 [0.77-0.95, p=0.004] for favorable outcome at 3 months.

Conclusions:
Our results from meta-analysis show that low dose of r-tPA is less likely associated with favorable outcome at 3 months, although the risk of sICH and mortality rate are equivalent as compared with the standard dose group.
Abstract TMP17: Safety of Thrombolysis for Acute Ischemic Stroke in Patients with Recent Stroke
Authors: Salehi Omran Setareh , Merkler Alexander E , Gialdini Gino , Lerario Michael , Yaghi Shadi , Elkind Mitchell S , Navi Babak B
Published: June 2021

Background:
The safety of intravenous tissue plasminogen activator (IV-tPA) is uncertain in acute ischemic stroke patients (AIS) with recent stroke because these patients were generally excluded from randomized stroke trials evaluating IV-tPA. We aimed to determine whether history of stroke within the previous 3 months is associated with an increased risk of intracerebral hemorrhage (ICH) or death after thrombolysis for AIS.

Methods:
Using previously validated ICD-9-CM codes, we retrospectively analyzed all adult patients with AIS who received IV-tPA in nonfederal EDs or acute care hospitals in CA, FL, and NY from 2005-2013. The primary outcome was the development of ICH (ICD-9-CM code 431) during index hospitalization for AIS. The secondary outcome was inpatient death. Logistic regression was used to compare the rate of ICH and death in patients with previous ischemic stroke within 3 months of IV-tPA therapy for AIS to all other patients treated with IV-tPA for AIS.

Results:
We identified 34,461 AIS patients treated with IV-tPA, including 454 with prior ischemic stroke in the past 3 months. Patients with recent stroke were on average younger and had more vascular risk factors and Elixhauser comorbidities than patients without recent stroke. The ICH rate after IV-tPA was similar in patients with AIS within the previous 3 months (6.6%, 95% CI 6.3-6.8) compared to patients without recent AIS (6.8%, 95% CI 4.5–9.1), but the rate of death was higher in those with AIS within the previous 3 months (16.5%, 95% CI 13.1-19.9 vs. 11.1%, 95% CI 10.7-11.4, p<0.001). After adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index, the risk of ICH following IV-rPA in patients with AIS in the previous 3 months was not different from those without recent AIS (OR=1.0, 95% CI 0.7-1.5, p=0.90), although the risk of death remained higher in patients with AIS in the previous 3 months (OR=1.6, 95% CI 1.2-2.1, p<0.001). Our results were unchanged in sensitivity analyses excluding patients with other approved indications for thrombolysis (e.g., MI, PE, and hemodialysis).

Conclusions:
In a large, multistate cohort, prior stroke within 3 months of receiving IV-tPA for AIS was not associated with an increased risk of ICH but was associated with a higher risk of death.
Abstract TMP18: An Analysis of Fixed Dose IV Recombinant Tissue Plasminogen Activator (rtPA) and Clinical Outcome in Acute Ischemic Stroke Patients with Body Weight >100 kg: Pooled Data From Three Randomized Clinical Trials
Authors: Majidi Shahram , Leon Guerrero Christopher , Burger Kathleen , Qureshi Adnan
Published: June 2021

Background:
The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous recombinant tissue plasminogen activator(rt-PA) for acute stroke patients weighing more than 100 kilograms(kg). Previous analyses in small studies have suggested that the magnitude of benefit with IV rt-PA is lower in patients with body weight >100 kg. We determined if body weight >100 kg(and receiving <0.9 mg/kg dose) independently influence patient clinical outcomes following IV rt-PA treatment.

Methods:
We pooled data from IV rt-PA treatment arms from 3 randomized controlled trials; NINDS IV rt-PA study, IMS-III and Albumin Treatment of Acute Ischemic Stroke(ALIAS part 1 and 2). Patients demographic, stroke severity, comorbidities, hospital outcome and 90-day modified Rankin Scale(mRS) were compared between patients >100 kg and those ≤100 kg body weight(defined by estimated weight). Multivariate logistic regression model was used to identify independent effect of >100 kg body weight on 90-day favorable outcome(defined as mRS 0-2). An ordinal analysis of the mRS was also performed.

Results:
Among 977 patients treated with IV rt-PA, total of 111 subjects had body weight >100 kg(11% of all patients). The mean age(±SD) for the patients with weight >100 Kg was significantly lower(60±11 versus 68±13, p<0.0001). The median admission NIHSS score was not different between the two groups(12 versus 13, p=0.08). Patients with weight >100 kg had higher rates of history of hypertension, diabetes mellitus, and hyperlipidemia. Patients with body weight >100 kg had longer period(days±SD) of hospitalization(11±14 versus 8±7, p=0.04). Compared with patients with ≤100 kg body weight, the rate of favorable outcome at 90 days was not significantly different among patients with >100 kg body weight[OR; (95% CI): 0.99 (0.91-1.04)p=0.91], after adjusting for potential confounders. The ordinal analysis did not showed any significant shift in the distribution of scores on the mRS in patients with >100 kg body weight(OR, 0.93; 95% CI, 0.64 to 1.37; P = 0.74).

Conclusion:
Body weight >100 kg(and receiving <0.9 mg/kg dose) did not reduce the benefit of IV rt-PA treatment in acute ischemic stroke patients. Our results support the current recommendations in the ASA/AHA guidelines.
Abstract TMP19: Intravenous Recombinant Tissue-type Plasminogen Activator Use in Young Adults With Acute Ischemic Stroke
Authors: Dodds Jodi A , Xian Ying , Sheng Shubin , Fonarow Gregg , Matsouaka Ronald A , Bhatt Deepak L , Peterson Eric , Schwamm Lee H , Smith Eric E
Published: June 2021

Background:
Intravenous recombinant tissue-type plasminogen activator (rt-PA) administration improves outcomes in acute ischemic stroke. However, young patients (<40 years old) presenting with stroke symptoms may experience delays in treatment due to misdiagnosis or a reluctance to treat since they do not fit the profile of a typical stroke patient.

Methods:
We analyzed data from the large national Get With The Guidelines–Stroke registry for acute ischemic stroke patients hospitalized between January 2009 and September 2015. Multivariable models with generalized estimating equations (GEE) were used to test for differences between younger (age 18-40) and older (age > 40) acute ischemic stroke patients, controlling for patient and hospital characteristics including stroke severity.

Results:
Of 1,320,965 AIS patients admitted to participating hospitals, 2.3% (30,448) were aged 18-40. Among these patients, 12.5% received rt-PA versus 8.8% of those aged >40 (p<0.001). Of patients arriving within 3.5 hours of symptom onset without contraindications, 68.7% of younger patients received IV rt-PA versus 63.3% of older patients (adjusted OR [aOR] 1.30, 95% CI 1.21 to 1.40), without evidence that age-related differences varied by sex (interaction p-value 0.25). Odds ratios of achieving target door-to-CT times and door-to-needle (DTN) times, and outcomes of rtPA-treated patients, are shown in the Table.

Conclusions:
Young acute ischemic stroke patients did not receive rt-PA treatment at lower rates than older patients. Outcomes were better and the rate of symptomatic intracranial hemorrhage was lower in the young patients. However, younger patients had significantly longer door-to-CT and DTN times, providing an opportunity to improve the care of these patients.
Abstract TMP24: Analysis of Adjudicated Edema Endpoints in the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial
Authors: Kimberly W. Taylor , von Kummer Ruediger , Demchuk Andrew , Romero Javier , Elm Jordan J , Hinson Holly , Molyneaux Bradley J , Sheth Kevin
Published: June 2021

Background:
Patients with large hemispheric infarction are at high risk for cerebral edema and death. Here we report pre-specified adjudicated edema endpoints in the GAMES-RP trial.

Objective:
The primary objective of this pre-specified analysis was to evaluate the effect of intravenous (IV) glyburide treatment on mortality and malignant edema.

Design:
The GAMES-RP trial was a prospective, double blind, randomized, placebo-controlled phase 2 study. Blinded adjudicators assigned designations for hemorrhage and edema-related death using
a priori
definitions.

Population studied:
Patients age 18 to 80 years who presented to 18 U.S. centers with baseline stroke lesion volumes between 82cc-300cc on MRI were randomized 1:1 to study drug or placebo within 10 hours from stroke onset. The per protocol group, which included all treated subjects with a baseline stroke lesion volume between 82cc and 300cc, was the primary analysis.

Outcome measure:
The adjudication outcomes were mortality due to all causes, and death due to cerebral edema. Secondary adjudication outcomes included the incidence of parenchymal hematoma and incidence of malignant edema defined as an increase in NIHSS ≥4 were also compared between treatment arms.

Results:
Subjects treated with intravenous glyburide had a trend toward lower all-cause mortality at one year (weighted log-rank test, p=0.052). Treatment with IV glyburide reduced the proportion of deaths due to cerebral edema [2.4% (N=1) with IV glyburide vs. 22.2% (N=8) with placebo, p=0.007). The frequency of parenchymal hematoma was not statistically different between treatment arms [2.4% (N=1) in IV glyburide versus 5.6% (N=2) in placebo, p=0.60]. The incidence of malignant edema was also similar [46.3% (N=19) in RP-1127 versus 47.2% (N=17) in placebo].

Conclusions:
Our data provide supporting evidence that intravenous glyburide may reduce edema-related deaths, but not malignant edema defined as an increase of ≥4 points in the NIHSS score. Future study is required to confirm the effect of IV glyburide on clinical outcome.