bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP53: New Diagnosis of Cancer and the Risk of Subsequent Arterial Thromboembolic Events
Authors: Navi Babak B , Howard George , Howard Virginia J , Zhao Hong , Judd Suzanne E , Elkind Mitchell S , Iadecola Costantino , DeAngelis Lisa M , Kamel Hooman , Okin Peter M , Gilchrist Susan , Soliman Elsayed Z , Cushman Mary , Safford Monika , Muntner Paul
Published: January 2019

Background:
Retrospective studies have reported an association between cancer and arterial thromboembolism risk. We sought to confirm this in a prospective cohort with adjudicated cardiovascular outcomes.

Methods:
We analyzed data from participants enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who had Medicare coverage for 365 days before their baseline study visit in 2003-2007. Participants with prevalent cancer, coronary heart disease, or cerebrovascular disease were excluded. Medicare claims were used to identify new cancer diagnoses during follow-up. Using incidence-density sampling, participants who developed cancer were matched by age, sex, race, and education level 1:4 to participants who hadn’t developed cancer. Participants were prospectively followed through September 30, 2015 for an adjudicated arterial thromboembolic event, defined as fatal or nonfatal acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent arterial thromboembolic events. To fulfill the proportional hazard assumption, follow-up time was modeled in discrete time periods.

Results:
In this analysis, 836 REGARDS participants with incident cancer were matched to 3,339 participants without cancer. During median follow-up of 3 years, 63 (7.5%) participants with cancer and 216 (6.5%) participants without cancer had an arterial thromboembolic event. Compared to non-cancer controls, participants with incident cancer had an increased risk of arterial thromboembolic events in the first 30 days after diagnosis (HR, 5.2; 95% CI, 2.1-12.7). This association persisted after adjustment for demographics, region of residence, and cardiovascular risk factors (HR, 5.8; 95% CI, 2.1-15.9). Cancers with known metastases and types considered high-risk for venous thromboembolism had the strongest associations with arterial thromboembolic events. There was no association between cancer diagnosis and arterial thromboembolic event risk beyond 30 days.

Conclusions:
Incident cancer, particularly when metastatic, is associated with an increased short-term risk of arterial thromboembolic events independent of vascular risk factors.
Abstract WMP58: Sex Differences in Risk Factors for Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis
Authors: Rehman Sabah , Sahle Berhe , Chandra Ronil V , Thrift Amanda G , Callisaya Michele , Dwyer Mitchell , Breslin Monique , Phan Hoang T , Otahal Petr , Gall Seana
Published: January 2019

Background:
Aneurysmal subarachnoid hemorrhage (aSAH) disproportionally affects women. The etiology of this is unclear, and the contribution of sex differences in aSAH risk factors is unknown. We aimed to identify sex differences in aSAH risk factors in a systematic review and meta-analysis.

Methods:
A systematic search was conducted using the Pubmed, Scopus, Embase, and Medline databases from inception to November 2017 to identify studies that included aSAH risk factors stratified by sex. aSAH risk factors were assessed using meta-analysis with pooled odds ratios (OR) calculated for risk factors with at least 2 studies.

Results:
There were 34 eligible case-control studies; however, 15 did not report sex specific findings with 19 were included. Hypertension (men pooled OR
adjusted
3.13 [95% CI 2.26-4.34]; women pooled OR
adjusted
3.65 [95% CI 2.87-4.63], p=0.18), smoking (men pooled OR
adjusted
2.96 [95% CI 1.68-5.21]; women pooled OR
adjusted
3.11 [95% CI 1.21-7.97], p=0.95),

family history of aSAH, increased systolic blood pressure, age, angiotensin-converting enzyme gene polymorphism and variation in a protease gene had the same odds for aSAH in both sexes. Alcohol intake (men pooled OR
adjusted
1.50 [95% CI 1.04-2.17], women pooled OR
adjusted
0.83 [95% CI 0.48-1.45], p=0.003), high alanine aminotransferase levels, and endothelial nitric oxide synthase gene variant were associated with higher odds of aSAH in men than women. Cold temperature, polymorphisms in factor XIII gene and genetic variation on chromosome 9p21 increased the odds of aSAH in women but not men. High aspartate aminotransferase levels were associated with a reduced risk in men while diabetes mellitus decreased the risk in women (men pooled OR
adjusted
0.57 [95% CI 0.32-1.01], women pooled OR
adjusted
0.24 [95% CI 0.13-0.43], p=0.017).

Conclusion:
Except for alcohol intake and diabetes mellitus, the magnitude of aSAH risk associated with most common risk factors were similar for both sexes. We advocate for re-analysis of existing studies with regard to sex differences.
Abstract WMP59: Association of Glycated Hemoglobin Testing Interval on Stroke and Cardiovascular Disease Among Newly Diagnosed Type 2 Diabetes Patients
Authors: Choi Seulggie , Cho Jung Jin , Park Sang Min , Kim Kyuwoong , Cho Mi Hee , Yoo Jung Eun , Kim Kyae Hyung , Jeong Young-Jin , Kim Soo Young , Park Minseon
Published: January 2019

Background:
Although guidelines recommend regular glycated hemoglobin (HbA1c) testing every 6 months for type 2 diabetes patients, whether adherence to these guidelines leads to improved health outcomes is unclear. We aimed to determine the association of HbA1c testing intervals on stroke and cardiovascular disease (CVD) risk among newly diagnosed type 2 diabetes patients.

Methods:
The study population consisted of 31,041 newly diagnosed type 2 diabetes patients during 2003-2011 from the Korean National Health Insurance Service. Average HbA1c testing interval was calculated during 3 years after type 2 diabetes diagnosis. Participants were categorized into average HbA1c testing intervals of ≤6, >6 to ≤12, >12 to ≤18, and >18 months, after which they were followed-up for stroke and CVD until 2015. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazards regression for the risk of stroke and CVD according to HbA1c testing interval.

Results:
Compared to patients with HbA1c testing intervals of ≤6 months, patients with >6 to ≤12 (aHR 1.40, 95% CI 1.10-1.78), >12 to ≤18 (aHR 1.43, 95% CI 1.12-1.84), and >18 (aHR 1.64, 95% CI 1.32-2.04) month intervals had elevated risk for stroke (
p
trend
<0.001). Similarly, patients with >12 to ≤18 (aHR 1.28, 95% CI 1.10-1.50), and >18 (aHR 1.38, 95% CI 1.21-1.58) month intervals had increased risk for CVD (
p
trend
<0.001) compared to those with intervals of ≤6 months. There was no significant association between HbA1c testing intervals of ≤3 and >3 to ≤6 months on stroke and CVD risk. The risk-increasing effect of stroke and CVD by longer HbA1c testing intervals was preserved among subgroups divided by fasting serum glucose, initial diabetes medication, outpatient department visits, and Charlson comorbidity index.

Conclusions:
HbA1c testing interval of more than 6 months was associated with increased risk of stroke and CVD among newly diagnosed type 2 diabetes patients. Type 2 diabetes patients who undergo biannual HbA1c testing may benefit from reduced stroke and CVD risk.
Abstract WMP6: Door to Revascularization in Less Than 60 Minutes a Cost Benefit Analysis
Authors: Frei Donald , Kaminsky Ian , Atchie Ben
Published: January 2019

Background:
Our level 1 stroke center has developed a standardized protocol, which has allowed us to achieve a median door-to-recanalization time of less than 60 minutes. In order to achieve such rapid recanalization rates, the neuro-interventional team is called in to meet the stroke patient upon their arrival to the hospital. We will describe our protocol for achieving rapid recanalization, and we will discuss the cost.

Methods:
For the last 18 months, while performing more than 300 thrombectomies, we have achieved a median door-to-recanalization time of < 60 minutes. Standardized protocols have contributed to this rapid time metric, but the most important contribution to time savings was calling in the neuro-interventional team to meet the patient upon their arrival to the emergency room. The neuro-interventional team called in to meet the patient includes: 1 RN, 2 technologists, 1 anesthesiologist and 1 neurointerventional surgeon. We will analyze time metrics, the percent of neuro-interventional stroke alerts that proceed to thrombectomy and the personnel costs for this protocol in this consecutive cohort of patients.

Results:
From 1/1/2017 – 3/31/2018, there were 1162 ELVO activations of the neuro-interventional team. Of these alerts, 314 proceeded to thrombectomy, equal to a 27% rate of thrombectomy. This rate was 21% during weekday working hours, 43% after 5 PM on weekdays, and 29% on weekends. If a thrombectomy is not performed, the RN and technologists are each paid 2 hours of overtime pay. Not counting hours lost in daytime productivity, physician time, and hours of lost sleep, there were more than 5000 hours paid to the RNs and technologists for these alerts that did not proceed to thrombectomy, totaling > $200,000.00 in overtime pay. The median time from patient arrival to recanalization was 52 minutes. The median time from door to groin puncture was 34.5 minutes, and from groin puncture to recanalization was 17.5 minutes.

Conclusion:
Rapid and safe revascularization helps achieve the best clinical outcomes in ELVO patients, and our stroke systems of care need to be streamlined to achieve these rapid time metrics, but it comes at a cost. Cost benefit analysis suggests in house neurointerventional teams may be needed to take care of these patients best.
Abstract WMP60: Adiponutrin Gene Polymorphism is Associated With Unexplained Embolic Covert Brain Infarction in the Northern Manhattan Study
Authors: Parikh Neal S , Dueker Nicole , Varela Dalila , Rundek Tatjana , Wright Clinton B , Sacco Ralph , Elkind Mitchell S , Gutierrez Jose
Published: January 2019

Introduction:
Adiponutrin, encoded by the patatin-like phospholipase domain-containing 3 gene (
PNPLA3
), is involved in lipid metabolism. The
PNPLA3
gene rs738409 C>G single nucleotide polymorphism (SNP), particularly when homozygous, is strongly associated with non-alcoholic fatty liver disease, which has been associated with vascular disease. We hypothesized that this
PNPLA3
SNP is associated with covert brain infarction (CBI).

Methods:
We performed a cross-sectional analysis of individuals with rs738409 genotype data in the Northern Manhattan Study MRI sub-study. The exposure was rs738409 allele frequency; noncarriers (CC genotype) served as the reference. The primary outcome was the presence of any CBI. Secondary outcomes were independently adjudicated CBI mechanism categories based on available baseline and follow-up history and imaging data: large artery atherosclerosis, cardioembolism, small vessel disease, and embolism of unknown source (EUS). Multivariable logistic regression was used to assess the relationship between SNP frequency and CBI. Principle component analysis was used to account for population-specific variations in SNP distributions. Models were adjusted for principal components, demographics, vascular risk factors, and alcohol, statin, and antiplatelet use.

Results:
The sample included 1,063 Northern Manhattan Study participants (mean age 70 ± 9 years, 61% women). The G allele frequency was 24%, with 381 GC heterozygotes and 67 GG homozygotes. The prevalence of CBI was 18% (N=185): 10% (N=19) large artery atherosclerosis, 12% (N=22) cardioembolism, 16% (N=30) small vessel disease, and 62% (N=114) EUS. Individuals heterozygous for the G allele were not at greater odds of any CBI (OR 0.8; 95% CI 0.6-1.2) or any individual type of CBI, compared to CC homozygotes. The odds of any CBI were also not increased among GG homozygotes (OR 1.6; 95% CI 0.8-3.2). However, GG homozygotes were at higher odds of EUS (OR 2.3; 95% CI 1.1-4.8), but not CBI due to other mechanisms.

Conclusion:
Homozygosity for the
PNPLA3
rs738409[G] SNP was associated with greater odds of EUS and may account for some unexplained strokes. Further study is warranted to understand the contribution of
PNPLA3
variants to cerebrovascular disease.
Abstract WMP64: Global Longitudinal Peak Strain to Predict Atrial Fibrillation in Ischemic Stroke
Authors: Ryu Wi-Sun , Bae Eun-Kee
Published: January 2019

Cerebral infarction due to atrial fibrillation is more severe and has a higher risk of death than other stroke subtypes. Anticoagulation reduces the risk of recurrence in patients with atrial fibrillation, and so it is crucial to find atrial fibrillation in stroke patients. In the present study, we investigated whether left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) on speckle echocardiography could discriminate a high-risk group of atrial fibrillation in stroke patients. We prospectively enrolled 678 ischemic patients. Stroke subtypes were determined by the consensus of experienced neurologists, using a validated MRI-based algorithm. Left ventricular GLPS was measured averaging by speckle tracking imaging echocardiography from 4-chamber, 2-chamber, and the apical longitudinal long-axis view with breathing hold and an echocardiogram recording. To evaluate the predictability of LAVI and GLPS for the presence of atrial fibrillation, we used the optimism-corrected c-statistics and the net reclassification improvement with prespecified atrial fibrillation risk categories of low (10%), intermediate (10% to 30%), and high (≥30%). Patients with atrial fibrillation were likely to be older and to have more vascular risk factors. LAVI (74 ml/m
2
vs. 42 ml/m
2
) and GLPS (-14% vs. -17%) were higher in patients with atrial fibrillation. Age (adjusted odds ratio 1.04, 95% confidence interval 1.02-1.07), LAVI (1.07, 1.06-1.09), and GLPS (1.08, 1.03-1.12) were independently associated with atrial fibrillation. As a base model, age and LAVI had a C-statistics of 0.89 (95% confidence interval 0.86 - 0.93). When GLPS levels were added to a base-model, net reclassification improvement was 6.1% (p = 0.03), albeit area under curve marginally improved (C-statistics = 0.90, 95% confidence interval 0.87 - 0.93, p = 0.058) compared to a base model. In patients with ischemic stroke, GLPS levels combined with LAVI were associated with the presence of atrial fibrillation. Our data imply that rigorous screening tests to detect atrial fibrillation may be warranted for the patients with high LAVI and GLPS levels.
Abstract WMP67: Incidental DWI Lesions in Patients With Recent Small Subcortical Infarctions
Authors: Arsava Ethem M , Yilmaz Ezgi , Topcuoglu Mehmet A
Published: January 2019

Background:
Incidental acute ischemic lesions distinct from the primary neurological insult are identified on diffusion weighted imaging (DWI) in a number of conditions where cerebral microvascular pathology plays a central role, like ICH or cerebral amyloid angiopathy. Another major manifestation of cerebral small vessel disease is ischemic stroke secondary to small artery occlusion, classically known as lacunar stroke and named as recent small subcortical infarction (RSSI) in the present-day nomenclature. In this study, we identified the prevalence and predictors of remote DWI lesions in patients with RSSI.

Methods:
Consecutive acute ischemic stroke patients with neuroimaging evidence of perforating arteriole territory ischemia were retrospectively analyzed. Patients with additional DWI lesions, apart from the ischemic lesion pertaining to clinical symptoms, were identified, and their clinical features together with imaging markers of chronic small vessel disease (lacunes, microbleeds, perivascular spaces, white matter hyperintensities) were compared to those patients with no such lesions.

Results:
Incidental acute ischemic lesions remote from the symptomatic subcortical infarction were identified in 9% of 367 patients included into the study. The lesions were linear or punctate in morphology, ≤20 mm in diameter, primarily located in ipsilateral or contralateral white matter (76%) and multiple in 47% of the cases. Patients with incidental DWI lesions were more likely to be active smokers, have history of hypertension and hyperlipidemia, and show evidence of chronic lacunes and microbleeds on imaging studies. Smoking (OR 2.2; 1.0-5.0), hyperlipidemia (OR 2.5; 1.1-5.3) and chronic lacunes (OR.6.0; 2.2-14.1) stood out as features significantly associated with incidental DWI lesions in multivariate analysis.

Conclusions:
Our study discloses that acute ischemic lesions involving other perforator arteriole territories can be incidentally detected in approximately 10% of patients suffering a stroke secondary to RSSI. This observation not only emphasizes the widespread nature of cerebral small vessel pathology, but also highlights that the course might be more active, temporally and spatially, in a distinct subgroup of patients.
Abstract WMP7: Poor Reperfusion After Endovascular Therapy is Associated With Worse Outcomes Than No Intervention in the HERMES Analysis of Seven Randomized Trials
Authors: Brown Scott , Liebeskind David S , Hill Michael D , Dippel Diederik W , Campbell Bruce C , Muir Keith W , Demchuk Andrew M , Bracard Serge , Davalos Antoni , Guillemin Francis , Jovin Tudor G , Menon Bijoy K , Mitchell Peter J , White Philip , Majoie Charles B , Saver Jeffrey L , Goyal Mayank
Published: January 2019

Introduction:
Although the role of successful reperfusion in improved outcome after endovascular treatment (EVT) for stroke is known, there has been limited evaluation of the effects of poor reperfusion. We compared results in the HERMES collaboration between standard care and those in the EVT group with poor reperfusion.

Methods:
Patient-level data were pooled in this meta-analysis of seven randomized trials comparing endovascular thrombectomy with standard care in anterior ischemic stroke. Functional outcome was assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days, comparing standard care versus EVT subjects achieving mTICI of 0 or 1 post-procedure. Analyses were adjusted for baseline prognostic variables to correct for potential imbalances.

Results:
The meta-analysis included 877 subjects in the standard care group and 78 in the EVT group with mTICI 0-1 per the HERMES central imaging core laboratory. At baseline, the EVT cohort had higher NIHSS (median 19 vs 17, p=0.011), but was not significantly different from standard care in other characteristics including age, sex, ASPECTS, time to randomization, site of occlusion and alteplase administration. Subjects with poor reperfusion in the EVT group had worse mRS at 90 days than standard care, unadjusted (p=0.003) and after adjustment for baseline characteristics (common odds ratio 0.59 (0.38-0.91), p=0.016). Fewer subjects in the EVT poor-reperfusion cohort achieved mRS 0, mRS 0-1 and all other dichotomized mRS cutpoints (Figure 1). Symptomatic intracranial hemorrhage was not different between groups (3.9% vs 3.5%, p=0.75).

Conclusion:
In recent endovascular trials, poor reperfusion after EVT was associated with worse outcomes than standard care in recent endovascular trials. This suggests that additional efforts to achieve reperfusion by EVT should be encouraged if deemed safe to do so.
Abstract WMP72: High Risk Left Atrial Appendage Morphology (LAA-H) is Associated With Cardioembolic and Embolic Stroke of Unknown Source Subtypes
Authors: Yaghi Shadi , Chang Andrew , Akiki Ronald , Collins Scott , Novack Tracy , Schomer Ashley , Hemendinger Morgan , Mac Grory Brian , Cutting Shawna , Burton Tina , Song Christopher , Poppas Athena , McTaggart Ryan , Merkler Alexander , Di Biase Luigi , Kamel Hooman , Elkind Mitchell S , Furie Karen , Atalay Michael
Published: January 2019

Background:
The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation (AF); biomarkers of LAA dysfunction are associated with ischemic stroke (IS) risk in patients with AF. We hypothesized that high risk LAA features [High risk morphology (LAA-H), LAA volume (LAAV), and LAA orifice surface area (LAAOSA)] would be more prevalent among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with non-cardioembolic stroke (NCS).

Methods:
Consecutive patients with IS from a prospective comprehensive stroke center registry who previously underwent a clinically-indicated qualifying chest CT were included. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology [Low risk morphology was defined as two lobes with an acute angle between them or chicken wing morphology and LAA-H defined as all others], LAAOSA (measured in a plane parallel to the left atrium), and LAAV (measured using a volumetric analysis software) were determined using contrast enhanced thin-slice chest CT (≤2.5 mm thickness) by investigators blinded to stroke subtype.

Results:
Of 1234 patients with ischemic stroke, 329 (26.7%) patients had a qualifying chest CT performed (126 CE, 116 ESUS, and 87 NCS). The baseline characteristics of patients with and without chest CT were similar. When compared to NCS, LAA-H was more prevalent in ESUS (86.4% vs. 70.1%, p=0.018) and CE stroke (82.5% vs. 70.1%, p=0.042). The LAAOSA and volume did not significantly differ between the 3 groups (Table).

Conclusion:
LAA characteristics associated with cardioembolic stroke are also more prevalent in patients with ESUS. Larger studies are needed to confirm that LAA features are a risk factor for stroke among patients without AF, and whether anticoagulation is effective in patients with high-risk LAA features.
Abstract WMP74: Resuscitation Fluid With Drag Reducing Additive Reduces Microthrombosis and Oxidative Stress After Traumatic Brain Injury Complicated by Hemorrhagic Shock
Authors: Bragin Denis E , Bragina Olga A , Berliba Lusy , Nemoto Edwin M
Published: January 2019

Objective:
Traumatic brain injury (TBI) is frequently accompanied by hemorrhagic shock (HS) significantly worsening morbidity and mortality. Existing colloid or crystalloid resuscitation fluids (RF) for volume expansion do not adequately mitigate impaired microvascular cerebral blood flow (mCBF) and causes post-reperfusion mitochondrial oxidative stress. We previously showed that resuscitation fluid with drag reducing polymers (DRP-RF) improves CBF by rheological modulation of hemodynamics. In this work, we have evaluated the efficiency of DRP-RF in the reduction of microthrombosis and post-reperfusion mitochondrial oxidative stress.

Methods:
TBI was induced in rats by fluid percussion (1.5 ATA, 50 ms) and followed by controlled hemorrhage to a mean arterial pressure (MAP) =40 mmHg. DRP-RF or Lactated Ringers (LR-RF) was infused to MAP =60 mmHg for one hour (pre-hospital), followed by blood re-infusion to a MAP=70 mmHg (hospital). In vivo 2-photon laser scanning microscopy over the parietal cortex was used to monitor microvascular blood flow, tissue hypoxia (NADH) and level of superoxide in the cortex as a measure of mitochondrial oxidative stress (i.v. hydroethidine [HEt], 1 mg/kg) for 5 hours after TBI/HS, followed by DiI vascular painting during perfusion-fixation. Temperatures, MAP, blood gases and electrolytes were monitored.

Results:
TBI/HS compromised CBF leading to capillary microthrombosis and tissue hypoxia. As in our previous work, DRP-RF better than LR-RF improved mCBF and tissue oxygenation (p<0.05). Reperfusion-induced oxidative stress, reflected by HEt fluorescence, was 32 ± 6% higher in LR-RF vs. DRP-RF (p < 0.05). Post-mortem whole-brain visualization of DiI painted vessels revealed multiple microthromboses in both hemispheres that were 29 ± 3% less in DRP-RF vs. LR-RF group (p < 0.05).

Conclusions:
Resuscitation after TBI/HS using DRP-RF effectively restores mCBF, reduces hypoxia, microthrombosis formation and mitochondrial oxidative stress compared to conventional volume expansion with LR-RF. Supported by DOD DM160142.
Abstract WMP76: Sexually Dimorphic Response to Stroke of miR-181a and miR-200c in Aged Mice
Authors: Griffiths Brian B , Arvola Oiva , Bhutani Anvee , Pastroudis Jason , Xu Lijun , Stary Creed
Published: January 2019

Background:
Stroke is a sexually dimorphic disease with age-dependent sex differences in incidence, prevalence, and outcome. Delineating the molecular mechanisms that determine sexual dimorphism in stroke is necessary to overcome translational barriers and advance the development of novel stroke treatments. Non-coding RNAs, including microRNAs (
miRs
), are upstream regulators of genes that regulate cell survival. In young adult male animals,
miR-181a
and
miR-200c
have been established as central regulators in the cellular response to stroke, however their role in females or aged animal cohorts represents a critical knowledge gap. Therefore, in the present study we investigated the response of miR-181a and miR-200c in the brain after stroke in aged male and female mice.

Methods:
Aged (20 month old) male and female mice were subjected to 1h middle cerebral artery occlusion (MCAO) followed by 24h reperfusion. RT-qPCR, fluorescent
in situ
hybridization (FISH) and immunohistochemistry (IHC) were used to quantify and localize post-MCAO cellular expression of miR-181a and miR-200c.

Results:
There was no baseline difference in miR-181a between sexes, however miR-200c expression was ~3-fold higher at baseline in female animals versus males. MCAO induced ~2-fold increase in miR-181a in male animals but post-MCAO expression remained unchanged in females. In contrast, miR-200c expression increased by ~16-fold in males and ~4-fold in females. At baseline, miR-181a and miR-200c primarily localized to cortical neurons (NeuN+). In response to MCAO astrocyte reactivity (GFAP+) coincided with robust expression of miR-200c in both males and females.

Conclusions:
MiR-181a and miR-200c exhibit sexual dimorphism in response to stroke. Augmented expression of miR-200c appears secondary to astrocyte reactivity. Future experiments will determine if inhibition of miR-181a and miR-200c are protective against ischemic stroke in aged animals.
Abstract WMP79: Phosphatidylserine-containing Liposomes Pretreatment Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury
Authors: Huang Lei , Sherchan Prativa , Boling Warren , Tang Jiping , Zhang John
Published: January 2019

Introduction:
Surgical brain injury (SBI), exclusively attributable to the neurosurgical procedure itself may cause postoperative complications. Neuroinflammation plays an important patholgoical role in the setting of SBI. Previous study demonstrated that the phosphatidylserine-containing liposomes (PS) pretreatment promoted ischemic retinal neuron survival by suppressing pro-inflammatory markers. In the present study, we investigated the anti-neuroinflammation effects of PS pretreatment in a rat model of SBI.

Methods:
Total of 60 adult male Sprague-Dawley rats were used in the following groups of Sham (n=18), SBI+vehicle (n=18), SBI+PS 0.17mg (n=6) and SBI+PS 0.5mg (n=18). SBI rats were subjected to partial right frontal lobe corticotomy. Shams were subjected to the same surgical procedure without undergoing corticotomy. Phosphatidylserine-containing liposomes (PS) or phosphatidylcholine-containing liposomes (PC, as vehicle control) were administered via intranasal route at 24h and 1h in prior to SBI induction. Outcomes assessments included 1) modified Garcia neurobehavioral test and brain water content at 24h and 72h post-SBI; and 2) western blot for pro/anti-inflammatory cytokines at 24h post-SBI.

Results:
All the rats survived except that 3 SBI rats died within 24h post-surgery. PS pretreatment at dose of 0.5mg significantly reduced peri-resection brain water content and improved neurological deficits associated with SBI at 24h and 72h post-injury (Fig.1). Consistently, western blot showed that there were less pro-inflammatory cytokines, but higher level of anti-inflammatory cytokine TGF-β1 within peri-resection brain regions of PS pretreated rats at 24h post-SBI.

Conclusion:
Our findings suggest that phosphatidylserine-containing liposomes may be a novel approach to ameliorate SBI by its anti-inflammation effects.
Abstract WMP81: High-Dimensional Analysis of Immune Cell Characterization in Ischemic Postconditioning
Authors: Yao Yang , Li Yaning , Feng Liangshu , Zhao Heng
Published: January 2019

Background:
Ischemic postconditioning (IPostC), an emerging concept for stroke treatment, refers to a series of brief occlusions of the cerebral blood vessels after reperfusion. A precise understanding of immune response in IPostC is very important. We describe an approaching to identify immune cells and characterize their distinct functions within IPostC by using high parametric mass cytometry (CyTOF).

Methods:
Leukocytes were isolated from the ischemic brain and peripheral blood of ischemic stroke mice. These cell samples were simultaneously stained with 25 antibodies, including 16 cell surface antibodies, and an additional 9 antibodies against key molecules in cell signaling pathways. The samples were detected by CyTOF and analyzed using the Cytobank program.

Results:
We demonstrated that stroke resulted in significant increases of microglia, monocyte-derived macrophages (MoMΦs), natural killer (NK), conventional DCs (cDCs), B cells, CD4
+
T, CD8
+
T cells, effector memory CD4 T (CD4Tem) cells, effector memory CD8 T (CD8Tem) cells and regulatory T (Treg) cells (p<0.05). Additionally, the increase of brain-infiltrating leukocyte subsets was accompanied with a decrease of corresponding leukocyte subsets in the peripheral blood. IPostC decreased the counts of brain-infiltrating MoMΦs, CD4
+
T, CD4Tem, CD8Tem and NK cells (p<0.05). In addition, SAPDE analysis showed that individual leukocytes in the ischemic brain had higher protein expressions of CD45, CD11b, CD11c, B220, CD4, CD8, CD44, and CD49b than sham brains, suggesting that these proteins may be actively involved in brain injury. We can see that IPostC downregulated these protein expressions. Our results revealed differences in endogenous signaling tone within ischemic stroke and IPostC, including increased AKT, EGFR, P38 phosphorylation and IκBa in microglia and MoMΦs, and decreased in IPostC.

Conclusions:
We revealed the phenotypic ranges of immune cells and identified cell surface receptors in individual leukocytes. The approach enabled us to know more about the phenotypical and functional characteristics of immune populations in the brain and peripheral blood after IPostC. It is expected to serve as a resource for understanding immune response within IPostC.
Abstract WMP83: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke in Female Mice
Authors: Shvedova Maria , Roberts Jesse D , Huang Paul L , Feil Robert , Atochin Dmitriy N
Published: January 2019

Introduction:
The role of cGMP-dependent protein kinase I (cGKI) in regulating vascular smooth muscle cells (SMC) during stroke has not been completely clarified. We showed that SMC cGKI has protective effect against stroke in male mice. To elucidate whether cGKI in SMC renders its protective effect on stroke outcome by sex-dependent mechanism, we conducted study on female mice. Animals: We used a novel tamoxifen-inducible SMC-specific gene knockout mice, that expresses CreER
T2
recombinase under the control of smooth muscle alpha-actin promoter. SMA-CreER
T2
_cGKIfloxflox adult 12-14 weeks-old female mice after tamoxifen (TAM) administration (100 μl TAM solution (1 mg/ml) i.p. per day for 5 consecutive days at the age 5-6 weeks) were used as experimental animals (cGKI SMKO mice). Control animals consisted of three types of female mice: (1) C57BL/6 (WT) mice without TAM treatment; (2) SMA-CreER
T2
_cGKIfloxflox mice without TAM treatment (cGKI control); (3) cGKIfloxflox mice (without SMA-CreER
T2
transgene) treated with TAM (cGKI control TAM).

Methods:
Mice (n=12/group) were anesthetized (1.5% of isoflurane in 30% of O
2
and 70% of N
2
O), body temperature was maintained (36.5-37.0
0
C) during 30-min filament-mediated middle cerebral artery occlusion (MCAO) and 30 min of reperfusion. Cerebral laser-Doppler flowmetry was utilized during the surgery to evaluate the regional cerebral blood flow (CBF).

Results:
The cGKI SMKO mice revealed greater cerebral infarct volume (93±12 mm
3
, Mean±SD) than WT (64±14), cGKI control (62±14), and cGKI control TAM (68±10) mice (TTC staining, indirect calculation, p<0.001, one-way analysis of variance with Bonferroni correction). Neurological deficit by 4-point scale was worse in the cGKI SMKO mice (2.3 points) as compared with WT (1.5), cGKI control (1.2), and cGKI control TAM (1.3) mice (p<0.05). The CBF during reperfusion was less in cGKI SMKO mice (44±19%) than in control groups (70±16 in WT; 81±33 in cGKI control; 70±19 in cGKI control TAM (15-th minute of reperfusion), p< 0.05). In conclusion, cGKI in SMC protects against stroke injury in female mice in a similar way that we previously detected in male mice. These results suggest that cGKI in SMC should be targeted in studies designed to protect brain tissue against stroke.
Abstract WMP84: Predicting Cortical Selective Neuronal Loss Using
11
C-flumazenil PET After Temporary Focal Ischemia in Spontaneously Hypertensive Rats
Authors: Baron Jean Claude , Hughes Jessica , Beech John , Jones Simon , Wang Dechao , Nadot Théotime , Menon David , Aigbirhio Franklin , Fryer Tim
Published: January 2019

Background:
Predicting ischemic brain damage early after stroke is an important goal. T2-Weighted MRI >3hrs after stroke onset accurately predicts infarction but is insensitive to selective neuronal loss (SNL). Chronic-stage
11
C-flumazenil PET (FMZ-PET) is a positive marker of SNL in rats (Ejaz,
Neurobiol. Dis.
2013), and previous studies in man, baboons and cats suggest early-stage FMZ-PET could predict infarction. Here we assessed whether early FMZ-PET quantitatively predicts SNL.

Methods:
Six adult male spontaneously hypertensive rats underwent 45min distal MCA occlusion, and dynamic FMZ-PET was obtained at 1hr and 48hrs post-reperfusion to map distribution volume (DV), which reflects specific binding. Following perfusion-fixation at Day 14, immunohistochemistry using NeuN as neuronal marker was performed. Comparison of normalized FMZ DV to %NeuN loss (determined visually) was done by means of Pearson correlations across 44 cytoarchitectonic ROIs from 8 coronal sections spanning the hemisphere and matching Paxinos atlas, according to previously published methods (Hughes,
NeuroImage
2012; Emmrich,
JCBFM
2015).

Results:
NeuN revealed cortical infarction and isolated SNL in 1 and 5 rats, respectively. 1-hr post-reperfusion FMZ-DV was unaffected and did not predict tissue outcome. In contrast, 48-hr FMZ-DV was significantly increased and across the 44 ROIs negatively predicted SNL intensity both individually in 3/5 rats (r range: 0.38-0.60; trend in 2/5 rats) and across the 5 rats (r=0.59, p <0.001), i.e. the higher the DV, the more severe the SNL; similar but stronger correlation (r=0.76) was found in the rat with infarction.

Conclusion:
The lack of FMZ changes 1hr after reperfusion suggests post-synaptic GABA-
A
receptors are still present onto dying neurons. Regardless of the underlying mechanism, e.g. receptor upregulation or increased binding via BBB damage, the FMZ binding increase present at 48hrs - which is consistent with earlier rat studies - was predictive of tissue outcome, including SNL - a new finding with potential clinical relevance.
Abstract WMP85: Clinical Effectiveness of Direct Oral Anticoagulants (DOACs) vs. Warfarin in Older Ischemic Stroke Patients With Atrial Fibrillation: Findings From Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study
Authors: Xian Ying , Xu Haolin , O’Brien Emily C , Shah Shreyansh , Thomas Laine , Pencina Michael J , Fonarow Gregg C , Olson DaiWai M , Schwamm Lee H , Bhatt Deepak L , Smith Eric E , Hannah Deidre , Lindholm Brianna , Maisch Lesley , Lytle Barbara L , Peterson Eric D , Hernandez Adrian F
Published: January 2019

Introduction:
Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for secondary prevention in ischemic stroke patients with atrial fibrillation. Despite demonstrated efficacy in clinical trials, there are few real-world experiences of DOACs vs. warfarin in community practice.

Methods:
We analyzed ischemic stroke survivors with atrial fibrillation discharged from the Get With The Guidelines Stroke hospitals between 2011-2014 and linked to Medicare claims for longitudinal outcomes through 2015. A propensity score overlap weighting method was used to compare DOACs vs. warfarin. The primary outcomes were major adverse cardiovascular events (MACE) and home time, a patient-centered outcome reflecting desire of “being alive at home, without recurrent stroke, or being hospitalized for complications.”

Results:
Among 11,662 stroke survivors (median age 80), 4,041 (34.7%) were discharged on DOACs (dabigatran, rivaroxaban, or apixaban) and 7,621 on warfarin. Except for NIHSS (median 4 [IQR 1-9] vs. 5 [2-11]), baseline demographics, medical history, and clinical characteristics were similar between two cohorts. Compared with warfarin, patients discharged on DOACs were less likely to experience MACE (33.95% vs. 40.36% per year, adjusted hazard ratio 0.89, 99% CI 0.83-0.96) and had more days at home (mean 287 vs. 263 days during the first year post discharge, adjusted difference 15.6 days, 99% CI 9.0-22.1) (
Table
). Additionally, there were fewer deaths, all-cause readmissions, cardiovascular readmissions, hemorrhagic strokes, and bleeding hospitalizations in DOAC-treated patients, although no significant differences in fatal bleeding, ischemic stroke readmission, systemic embolism, pneumonia, or sepsis (two negative outcome controls) between the two cohorts.

Conclusions:
In ischemic stroke survivors with atrial fibrillation, DOACs were associated with improved long-term clinical outcomes compared with warfarin.
Abstract WMP86: Infection During Delivery Hospitalization is Associated With Increased Risk of Readmission for Postpartum Stroke
Authors: Miller Eliza C , Medina Jessica , Friedman Alexander M , Elkind Mitchell S , Boehme Amelia K
Published: January 2019

Introduction:
Postpartum stroke is a rare and unpredictable complication of pregnancy. Infections have been associated with an increased risk of stroke in young people. We hypothesized that infections diagnosed during delivery hospitalizations would be associated with an increased risk of postpartum readmission for stroke.

Methods:
We conducted a weighted analysis of the 2013 Healthcare Cost and Utilization Project National Readmissions Database to assess the relationship between infection during a delivery hospitalization and 30-day readmission for a stroke. Delivery hospitalization, stroke and infections, and comorbidities were identified using ICD-9 diagnosis codes. We created survey design logistic regression models to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between infections and 30-day readmission for stroke, adjusting for disease severity, length of delivery hospitalization, and age.

Results:
There were 3,512,350 delivery hospitalizations, with 79,656 subsequent readmissions, including 225 for stroke. Compared with all other women who delivered, women with infections during the delivery hospitalization had higher odds of readmission for postpartum stroke (adjusted OR 5.7, 95%CI 2.4-13.6). When compared to women who were readmitted for non-stroke reasons, women who were readmitted for stroke had higher odds of an infection during the delivery hospitalization (adjusted OR 3.5, 95%CI 1.9-6.5). The effect of infection on postpartum stroke risk was present in women both with and without hypertensive disorders of pregnancy (Table).

Conclusion:
Infections diagnosed during delivery hospitalizations were associated with an increased risk of readmission for postpartum stroke. Women who are diagnosed with infections during delivery admissions should be educated on signs and symptoms of stroke and when to seek emergency medical attention.
Abstract WMP87: Incidence and Clinical Predictors of Late Seizures in Survivors of Ischemic Stroke Using a Linking Stroke Registry With Administrative Claims Data
Authors: Oh Mi Sun , Kim Tae Jung , Lee Ji Sung , Kim Ji-woo , Yoon Byung-woo , Lee Byung-Chul
Published: January 2019

Purpose:
To describe the epidemiology and clinical predictors of late (>7 days) seizures in survivors of acute ischemic stroke (AIS) using the linkage between a national stroke registry and administrative claims databases.

Methods:
We performed a retrospective cohort study using a big linking database of the Health Insurance Review and Assessment Service (HIRA) claim database during 2007-2017 matched for ischemic stroke patients registered in the Clinical Research Center for Stroke (CRCS) registry from July 2007 to December 2014. Outcome was late seizures occurring after 7-day of the index AIS onset. Post stroke seizures were defined as any inpatient or outpatient treated antiepileptic drug medication with a diagnosis code for epilepsy or seizure after the index stroke based on linking database. We included patients who had 1) AIS within 7 days after symptom onset, 2) no history of previous stroke, 3) no history of seizures and prestroke antiepileptic drug use, 4) no history of potentially epileptogenic comorbidities. Kaplan-Meier methods and Cox Models were used to assess incidence and predictors of late seizures in survivors of AIS.

Results:
Of 35,106 patients included in this study, 5,279 (15%) patients had late seizures. The cumulative incidence of late seizures after AIS was 7.5% after 1 year, 11.4 % after 3 years, 13.7% after 5 years, 15.8% after 7 years, and 18.3% after 10 years. The crude incidence rate of late seizures after AIS was 26.6 cases per 1,000 person-years in our linking database. Late seizure occurrence tended to be more prevalent in patients having severe stroke (the National Institute of Health Stroke Scale score ≥ 4) and early seizures (≤ 7 days). Small vessel occlusion was less associated with a subsequent late seizure after AIS compared with other etiologies.

Conclusions:
We found that almost 15 % of patients with AIS developed late seizures within a decade. Severe stroke, early seizure, and ischemic stroke etiology seem to confer the predictors of developing late seizures.
Abstract WMP90: Association Between Post-Discharge Complications and One-Year Mortality After Ischemic Stroke
Authors: Lichtman Judith H , Leifheit Erica C , Wang Yun , Goldstein Larry B
Published: January 2019

Background:
Post-stroke complications influence mortality, but the assessment of complications is often restricted to the index hospitalization. Information on complications that occur after discharge is limited and the association of such events with mortality is not well described. We assessed the impact of complications occurring after hospital discharge for stroke on mortality within 1 year.

Methods:
We identified fee-for-service Medicare beneficiaries aged ≥65 years who were discharged with a primary diagnosis of ischemic stroke in 2011-2012. We evaluated four potential complications within the first year after discharge (urinary tract infection, acute myocardial infarction, pulmonary embolism, and decubitus ulcer; chosen via stepwise modeling of 11 complications). We fit a Cox extension model for 1-year all-cause mortality, with the first occurrence of a post-discharge complication as a time-varying variable and adjustment for age, race, sex, and 27 baseline clinical characteristics (e.g., hypertension, diabetes, renal failure, congestive heart failure).

Results:
There were 437,961 patients discharged with ischemic stroke in 2011-2012 (mean age 78.9y, 55.2% female, 85.4% white). Common baseline comorbidities included hypertension (79.3%), chronic atherosclerosis (34.4%), diabetes (32.8%), anemia (18.6%), and chronic obstructive pulmonary disease (15.7%). The mean index hospital stay was 4.3 days, and 53.1% of patients were discharged home or with home care. The 1-year mortality rate among discharged stroke patients was 23.7%. Post-discharge urinary tract infection (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.17-1.21), myocardial infarction (HR 1.27, 95% CI 1.22-1.32), pulmonary embolism (HR 1.42, 95% CI 1.34-1.49), and decubitus ulcer (HR 1.65, 95% CI 1.60-1.69) were associated with increased risk of death within 1 year.

Conclusion:
Post-discharge complications were associated with 1-year mortality after ischemic stroke. Complications related to stroke events reflect aspects of quality of care throughout recovery, not just the index hospitalization. Future analyses of 1-year mortality should consider dynamic changes in post-discharge events that modify risk profiles during the recovery period.
Abstract WMP96: Predictors and Outcomes of Stroke Following Coronary Artery Bypass Graft Surgery in California
Authors: Wang Limin , Hoegh Holly , Holliday-Hanson Merry , Krawczyk Christopher
Published: January 2019

Objectives:
- Stroke following Coronary Artery Bypass Graft (CABG) surgery is one of the most devastating complications of the procedure. Previous studies on predictors of postoperative stroke were limited to patients’ pre-existing conditions and comorbidities. California CABG Outcomes Reporting Program (CCORP) data was linked with patient discharge data (PDD) to investigate the predictors of stroke, including patient demographics and risk factors, as well as hospital characteristics and region. In addition, outcomes (e.g. other complications, mortality) were evaluated.

Methods:
- A total of 64,426 patients undergoing CABG surgery in California hospitals from 2013 to 2016 were included in the study. Data from CCORP were linked to PDD and California death certificate records. Predictors of stroke were identified by logistic regression analysis.

Results:
- The overall incidence of in-hospital stroke following CABG surgery was 1.7%. Among predictors, significant correlates of stroke included age >75, female, Asian, expected payer-Medicare, patients living in the Sacramento Valley, rural hospitals, emergent operation, CABG type, recent MI, previous stroke, cardiogenic shock, CPB utilization, carotid artery disease, low cardiac output, atrial fibrillation, high pulmonary artery pressure, diabetes, and renal insufficiency (all factors P<0.001, except rural hospitals P=0.007). Hospital size, teaching or for-profit status, and history of cardiac surgery were not significant. Patients with postoperative stroke were more likely to have deep sternal wound infection, infectious endocarditis, postoperative atrial fibrillation/renal failure, re-operation for bleeding/tamponade/graft occlusion, as well as higher operative mortality and 30-day readmission rates compared to those without stroke (P<0.001).

Conclusions:
- Stroke following CABG is associated with patients’ demographics, location and pre-existing vascular diseases as well as high rates of complications, mortality and readmission, while stroke is not related to hospital size or teaching or for-profit status. The findings provide important insights into postoperative stroke, potentially allowing hospitals and local healthcare agencies to develop preventive strategies.