bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP477: ICH in a Mid-South Mobile Stroke Unit Sample: Demographics, Clinical Findings, and Geospatial Distribution
Authors: Rhudy James P , Swatzell Victoria , Dusenbury Wendy , Hall Natalie , Wise Elizabeth , Rike Joseph , Bryndziar Tomas , Alexandrov Andrei , Alexandrov Anne W
Published: January 2019

Background:
Clinical and geospatial differences in acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) patients within stroke belt region mobile stroke units (MSU) have not been described. We sought to understand presentation differences in the Mid-South.

Methods:
Consecutive MSU patients were analyzed for demographic, call, and clinical characteristics. Cases were geocoded, spatially joined to zip code shapefile with raw counts normalized to population; incidence rates were calculated and symbolized by mathematical natural breaks.

Results:
292 AIS and 29 ICHs were transported in 52 weeks; age was similar (ICH 63
+
15 vs. AIS 64
+
15), cases were mostly female (ICH 64%; AIS 60%), with African Americans (AA) significantly more likely to have AIS (74%) compared to ICH (64%; p=0.023). Median ICH NIHSS was significantly higher (median 9.5, IQR 5.5-17) then AIS NIHSS (median 5, IQR 2-9; p<0.001), as were SBP (ICH 184
+
37mmHg vs. AIS 159
+
35mmHg; p<0.001) and DBP (ICH 104
+
21mmHg vs. AIS 91
+
21mmHg; p=0.003). ICH patients were significantly more likely to be treated within the first 60 minutes of symptom onset (p<0.001) then AIS. High incidence ICH territories were geospatially defined.

Conclusions:
Mid-South ICH MSU patients have surprisingly different demographics than National data, and were most commonly female, but less likely to be of AA. A discreet geospatial ICH pattern was identified for high ICH risk.
Abstract WP481: Telestroke Consultations in an EMS Unit to Reduce t-PA Decision Times
Authors: Turner Nancy , Debenham Ellen , Sabatino Perette , James Amanda , Hewitt Dale , Hewitt Jessica , Holmstedt Christine
Published: January 2019

Introduction:
Improving time to t-PA decision and door to needle times (DTN) is a sought after phenomenon in telestroke workflows. Timely interventions of ischemic stroke patients have shown to significantly improve outcomes and quality of life. With the goal of decreasing door to need times in the state , one academic medical center partnered with a community hospital and an EMS unit to explore the efficacy and feasibility of placing telestroke systems into the pre-hospital setting.

Methods:
An EMS unit was equipped with telehealth technology and software modalities. Stroke patients were identified in the 9-1-1 setting and a telestroke consultation was initiated by paramedics to connect to local hospital providers and neuro-specialists. An EMS algorithm was developed to capture patient medical history and assessments for expedited decision making. Upon arrival to the local emergency department, paramedics transported patients directly to radiology and t-PA was mixed, prepped, and ready for administration, if applicable. Data, generated from the telehealth platform, was analyzed to compare DTN times and door to t-PA decision times to stroke patients treated under the current protocols at the same facility. Statistical comparison included median time to treatment using the Wilxocon Rank Sum.

Results:
Between May 2017 and June 2018, 25 patients were eligible for and received tPA. Three patients (12%) were in the EMS intervention group and 22 (88%) received traditional care. Median door-to-decision time for traditional care patients was 33 minutes (IQR 28-42) and 13 minutes for EMS intervention patients (IQR 2-21) (p=0.0151). Median DTN time was 40 minutes (IQR 30-48) for traditional care versus 23 minutes (IQR 20-33) for EMS patients (p=0.12).

Conclusion:
Initiating telestroke consults in an EMS unit is a promising way to improve t-PA decision times thus reducing door to needle times. Further partnerships with local EMS and community hospitals is warranted to evaluate multiple telestroke consultations and t-PA decisions. An additional focus on cellular data and connectivity in rural areas is also necessary to activate the consult and begin assessing the emergent stroke patients.
Abstract WP482: Pragmatic Times: A Telestroke Response to the Need for Increased Large Vessel Occlusion Stroke Triage
Authors: Whitney Cynthia , Viswanathan Anand , Patel Aman B , Anderson Christopher D , Rost Natalia S , Hirsch Joshua A , Schwamm Lee H , Leslie-Mazwi Thabele M
Published: January 2019

Introduction:
Identification of patients with stroke from large vessel occlusion (LVO), including into extended time windows, is a current medical imperative. Capacity challenges limit transfer of all patients with clinical deficit to receiving hospitals, while referring hospitals desire patient retention if transfer is not indicated. The use of CT angiography (CTA) provides the most reliable option for LVO screening at the referring hospital. We evaluate the utilization of CTA within our Telestroke network.

Methods:
A CTA protocol was developed for Telestroke referring hospitals and disseminated through the network (25 centers) in a staggered fashion. CTA was encouraged for all patients with NIHSS of ≥6 and presentation <24 hours from last known well. Patients were included in this analysis if they had NIHSS of ≥6 and either Telestroke video consultation, or Telestroke telephone consultation after local Neurology evaluation.

Results:
Prior to the protocol implementation CTA was utilized at none of the Telestroke referring hospitals. The CTA protocol was disseminated by March 2018. Between March and August 2018 there were a total of 623 Telestroke consults (185 video); 75 patients met inclusion criteria. CTA was obtained by the referring hospital in 65 cases (86%). Reasons for not obtaining a referring hospital CTA were vascular anatomical complexities (aortic dissection, multiple systemic emboli) in 2 patients, medical comorbid concerns (anaphylaxis with prior contrast, endocarditis, hemodynamic instability) in 3 patients, transfer to a different facility (2 patients), declined by family, and not indicated based on Telestroke video evaluation due to lacunar syndrome (1 patient each). Of patients with CTAs, 34 remained at the referring hospital (52%) based on CTA findings.

Conclusions:
We demonstrate a pragmatic approach to the challenge of LVO triage up to 24 hours within the tele-stroke network. Our approach demonstrated high rates of CTA adoption within a short timeframe (5 months), and may provide a model to be replicated in other Telestroke environments. While retention rates of over 52% at the referring hospital are encouraging, subsequent data will provide information regarding further triage implications for these patients.
Abstract WP486: Do Social Determinants of Health Predict Recovery in the First 90 Days After Stroke?
Authors: Liskay Alice M , Love Thomas E , Brown Dena , Buttrick Maureen , Cox Robynn S , Cushler Tracy , Forrest Cassandra , Fussner Julie , Heaton Sharon , McNett Molly , Montgomery Kelly , O'Brien Amy , Reynolds Rachel , Schrock Jon W , Taylor Brett , Katzan Irene
Published: January 2019

Background:
Understanding the factors impacting recovery after stroke is a critical step in developing interventions to optimize stroke outcomes. Previous work from Ohio Coverdell Program suggested that race may be independently associated with reduced odds of improvement in the first 30 days after stroke.

Purpose:
To determine if race, household income, and insurance status are independently associated with improvement in disability in the first 90 days after hospital discharge in patients admitted to comprehensive stroke centers (CSC) who received acute intervention.

Methods:
Retrospective cohort study of patients entered into the GWTG-Stroke from 7 Ohio Coverdell CSCs from 1/1/2015 to 7/16/2018 who received IV tPA and/or acute catheter-based intervention and had a mRS score at discharge and 90 days. Multivariable linear regression was performed to examine the association of race, household income estimated by ZIP code, and insurance on improvement in mRS between discharge and 90 days after adjusting for discharge mRS, clinical characteristics and hospital management.

Results:
There were 1,140 patients in the cohort who had mean age 66.7 yrs (SD 15.0). Estimated median income was $51,190 (SD $18,050); 18.3% were nonwhite. Of the socioeconomic variables assessed, only Medicaid insurance was associated with less recovery in the first 90 days post-discharge (β = -0.40; 95% CI -0.67, -0.14).Other variables associated with recovery were discharge mRS, hospital, premorbid ambulatory status, admission NIHSS, discharge destination, and length of stay. (see Table)

Conclusion:
Race and household income were not associated with recovery in the first 90 days post-discharge in stroke patients admitted to CSCs receiving acute interventions. Patients with Medicaid insurance had reduced probability of improvement. Further evaluation is indicated to determine if the worse recovery in Medicaid patients is due to socioeconomic status or premorbid health status.
Abstract WP490: Novice to Certified: Promoting Professional Development in Nurses on a Stroke Specialty Unit
Authors: Bierley Dorri L
Published: January 2019

Background and Purpose:
This project was designed to guide the novice nurse through their first two years. A personalized growth track was developed that allowed them to prepare for submission to a Professional Nurse Development Program (PNDP) at the end of year one with the knowledge and skills needed to sit for a certification exam by the end of year two. The growth track is a slow emersion into incorporating evidence based practice, research, and professional growth into nursing practice. The track is developed during orientation and provides a roadmap to meet the requirements of advancement to a Level II professional nurse with the goal of achieving Level III after certification. Their interests are used as a personalized guide to connect the nurse with activities that develop these interests into professional practice. Steps include introduction to unit/hospital nursing congress, quality initiatives, clinical certifications, as well as professional certification, with Stroke being the preferred field. The program allows for introduction into precepting, shift leading, and participation in task force or committee work. The growth track is designed to promote confidence and critical thinking skills in the novice nurse.

Methods:
The project followed 10 new graduates on a stroke specialty unit. The growth track was initiated at the end of the unit orientation. Progression was monitored quarterly through their first two years.

Results:
All 10 progressed through the growth track program with 7 submitting for the PNDP program at the end of year 1 and achieving Level II. The other three submitted before their second anniversary. All 10 have achieved a clinical certification and have participated in a stroke certification review course, with 6 of the 10 having applied for and scheduled their stroke nurse certification exam before their second anniversary.

Conclusions:
Compared to nurses who were hired before the growth track was utilized; nurses who participated in this program reached professional milestones ahead of what was generally seen as the normal curve. Follow-up to this program will be to look closely at quality and patient satisfaction data to ascertain the effect of increased professional develop of bedside staff on quality of care.
Abstract WP498: A Nationwide Analysis of Utilization of Life-Sustaining Treatments Following Aneurysmal Subarachnoid Hemorrhage
Authors: Stanfill Ansley , Cao Xueyuan , Skolarus Lesli , Davis Robert
Published: January 2019

Introduction:
Aneurysmal subarachnoid hemorrhage (aSAH) carries high mortality and disability rates, with many patients receiving life-sustaining treatments (LST). We examined utilization of LST by demographic and regional characteristics for aSAH patients using a nationwide dataset.

Methods:
We used Cerner Health Facts, a database of de-identified, longitudinal electronic health record information. Patients with aSAH were selected by ICD-9/10 codes for inpatient admission dates between 1/2004-6/2018. Available demographics included census region, age, race, sex, and marital status. Clinical information included admission Glasgow Coma Scale (GCS) score and aneurysm treatment modality. Primary outcome was utilization of LST, defined as cardiopulmonary resuscitation, ventilation, hemodialysis, ventriculostomy, tracheostomy, or gastrostomy. Descriptive statistics were calculated and associations with LST examined using chi-squares for categorical variables and Kruskal-Wallis tests for continuous variables. A stepwise logistic regression model selection procedure included all available data, with the final model selected by Akaike information criteria (AIC). Significance was set at
p
≤0.05.

Results:
There were 34,021 patients with aSAH, with a mean age of 57.9±19.8 years. The sample was 72% Caucasian and 55% female, with a median GCS of 15 (IQR 10-15). Approximately 18% (n=6167) received one or more LST. Utilization varied by census region, age, race, marital status, and GCS (
p
for each <1E-8), with those most likely to receive support being from the West, in their 60s, non-white, single, and having lower GCS scores. Sex and aneurysm treatment method were not associated with LST (
p
=0.12 and 0.77, respectively). With stepwise logistic regression, age and GCS were found to be significant, with a likelihood ratio test demonstrating independent prognostic value for each factor (
p
<0.02).

Conclusions:
Demographic factors are associated with LST. Potential confounds include clinical indicators, patient/family preference, and individual hospital practice patterns, and future work should include additional information on these characteristics.
Abstract WP50: Histopathologic Analysis of Retrieved Thrombi in Acute Ischemic Stroke Patients With Cancer
Authors: Kataoka Yuko , Sonoda Kazutaka , Yamagami Hiroshi , Takahashi Jun C , Ishibashi-Ueda Hatsue , Toyoda Kazunori , Koga Masatoshi
Published: January 2019

Introduction:
The procoagulant state in cancer increases the thrombotic risk and underlying cancer could affect treatment strategies and outcomes in stroke patients. Therefore, it is important to detect cancer as a cause of stroke. However, the histopathologic characteristics of retrieved thrombi in cancer patients remain understudied.

Aims:
The aims of this study were to assess the histopathological difference between the thrombi in cancer patients and in non-cancer patients.

Methods:
We studied consecutive patients with acute large-vessel occlusion treated with endovascular therapy between October 2010 and December 2016 from our single-center registry. We histopathologically investigated retrieved thrombi using staining with hematoxylin and eosin and Masson’s trichrome. We observed the existence of organization and the ratios of erythrocyte and fibrin/platelet components, using a lattice composed of 10х10 squares.

Results:
Of 180 patients studied, 17 cases (8 women, 76.5±11.5 years old) had cancer and 163 cases (69 women, 74.1±11.2 years old) did not. There were no significant differences in basic clinical characteristics and cardiovascular risk factors including atrial fibrillation between the two groups. Cancer-related cases had higher proportions of fibrin/platelets (56.6±27.4% vs. 40.1±23.9%, p<0.01), less proportions of erythrocytes (42.1±28.3% vs. 57.5±25.1%, p=0.02) and higher serum D-dimer levels (5.9 ± 8.2 vs. 2.4 ± 4.3, p<0.01) than non-cancer cases. The ROC analysis showed the cut-off ratio of fibrin/platelet components related to cancer was 55.7% with a sensitivity of 74.8%, specificity 58.8%, and AUC value 0.67(95% CI: 0.533–0.813), the cut-off ratio of erythrocyte components was 44.7% with a sensitivity of 71.2%, specificity 58.9%, and AUC value 0.66(95% CI: 0.514–0.797).

Conclusion:
Cancer-associated acute large artery occlusion was relatively due to emboli with the fibrin/platelet rich component.
Abstract WP501: Stroke Code Quality Metrics and Functional outcomes: Advanced Practice Providers versus Neurology Residents
Authors: Packard Laurel , LaCroix Hattie , Tubergen Tricia , Huffman Cuyler , Raad Bassel , Zachariah Joseph , Combs Jordan , Dejesus Michelle , Sriram Ashok , Singer Justin , Scureck Raymond , Abdelhak Tamer , Khan Muhib
Published: January 2019

Background:
Advanced Practice Providers (APPs) are important members of stroke code teams. However, the impact of APP involvement on quality metrics and functional outcomes is unclear. We sought to evaluate if APPs perform similarly to neurology residents for stroke code quality metrics and functional outcome at 90 days.

Methods:
We retrospectively analyzed data of consecutive patients who received thrombolysis (rtPA) and/or underwent thrombectomy in a single center cohort. Demographics, National Institute of Health Stroke Scale (NIHSS), Last known normal (LKN) to emergency department (ED) presentation time, ED door to rtPA time, ED door to skin puncture time, recanalization (mTICI IIb/III) rates and modified rankin scale (mRS) at 90 days were compared between neurology residents and advanced practice providers. Multiple logistic regression was used to determine factors independently associated with a favorable modified rankin scale (mRS) at 90 days.

Results:
A total of 96 patients were included in the study of which 44 (46%) were managed by neurology residents. Both groups (Residents vs. APPs) were balanced for age (p=0.17), NIHSS (p=0.73), LKN to ED Door time (p=0.17), ED door to tPA time (p=0.28), ED door to skin puncture time (p=0.22) and recanalization rate (p=0.93). Using multiple logistic regression, patients who were managed by neurology residents were 4.1 times more likely to have a favorable outcome (mRS 0-2) at 90 days. (Table)

Conclusion:
Advanced practice providers (APPs) achieve similar acute stroke code metrics as compared to neurology residents. However, functional outcomes are better in patients managed by neurology residents. Further studies are needed to confirm our findings.
Abstract WP507: Improvement in Door to Needle Time to Intravenous Thrombolysis With on Site Stroke Activation Nurse
Authors: Chia Magdalene Li Jun , Wong Lily Yoke Hua , Widjaja Sutrisno Louis , Yeo Leonard Leong Litt , Teoh Hock Luen , Chan Bernard PL
Published: January 2019

Introduction:
Effectiveness of stroke thrombolysis is highly dependent on early initiation of therapy, and strategies have been developed to reduce the door-to-needle time (DTN).

Aim:
To determine the impact on DTN after introduction of stroke activation nurse (SAN) in a teaching hospital.

Methods:
Our hospital is the comprehensive stroke center serving western Singapore and admits about 900 acute ischemic stroke patients per year. Previously thrombolysis was commenced after evaluation in the Emergency Department (ED) and admission to the Neurology high-dependency unit, causing considerable delay to treatment. From May 2015, a SAN joined the stroke code and evaluated all thrombolytic candidates, obtained NIHSS scores, calculated the dose and prepared the tPA for administration in ED. From September 2016, addition of a second SAN allowed faster response, especially in simultaneous stroke activations.

From a prospective database of our patients treated with thrombolysis, we compared patient characteristics and DTN during three 16-month periods before and after SAN participation: Jan 2014-Apr 2015 (Baseline), May 2015-Aug2016 (Period 1), and Sep 2016-Dec 2017 (Period 2).

Results:
A total of 555 patients received thrombolysis, with mean age 67.5 years, 41% female, 73% hypertension, 35% diabetes mellitus, 55% hyperlipidemia and 31% atrial fibrillation.

More patients were thrombolysed after SAN participation in the stroke code, from 146 (14%) at baseline, to 191 (17.6%) in Period 1 and 218 (18.8%) in Period 2. The median (range) NIHSS scores during these periods were 16 (2-32), 13 (1-33) and 12 (2-35) respectively. Mean (SD) and median DTN at baseline was 80 ( ±32) and 77 mins, which decreased to 63 ( ±32) and 57 mins in Period 1, and 58 ( ±29) and 52 mins in Period 2 . Percentages of patients thrombolysed within 60 mins improved from 25.3% at Baseline to 56.5% and 67% during Periods 1 and 2 respectively.

Conclusions:
Our results showed that involvement of SAN was associated with decrease in DNT and enabled more patients to be treated with intravenous thrombolysis.
Abstract WP511: Using a Nurse Driven Protocol for Stroke Triage
Authors: Glidden Michele , McNew Abbie , Smith Danika , Brown Dan , Embree Jennifer
Published: January 2019

Background:
In 2013, the American Heart Association/American Stroke Association began a public awareness marketing campaign that included a tool; called F.A.S. T. The purpose was used to educate the public on stroke signs and symptoms and to go to the emergency department promptly for treatment. Prehospital personnel has stroke screening tools, such as Cincinnati Stroke Scale utilized locally. The health system stroke center utilized a nursing triage process using the acronym "FLASHED" to identify patients were exhibiting symptoms of stroke so that nurses would triage patients based on the acronym. F stands for facial asymmetry or droop; L is leg weakness or numbness. A is for arm weakness or numbness. S stands for speech deficits. H is for a severe headache without cause. E is for eyes; this includes all or part of the vision in one or both eyes. D stands for dizziness or loss of coordination if accompanied by any of the above symptoms.

Purpose:
The purpose of this study was to utilize a tool better suited for nursing for stroke identification in the ED setting. Identifying if patients that met the FLASHED criteria for stroke were appropriate for receiving an emergent evaluation for an acute stroke.

Methods:
A retrospective electronic record review of ED patients was used for this study. A content analysis included identification of symptom description and stroke one activations over a 24 month period. A patient arriving in the ED meeting FLASHED criteria resulted in stroke one activation with their last known well within 6 hours of arrival.

Results:
Over a 24 month period, nearly 500 Stroke One activations occurred. Of those activations, 3% did not meet the FLASHED criteria. 89.7% of all Stroke One Activations received a stroke workup by a neurologist. 56% of all activations resulted in the patient being discharged from either an inpatient or observation status with a stroke related diagnosis.

Conclusion:
Recognition of possible stroke patients based on symptoms upon arrival to the ED promptly is a priority for all EDs. A clear triage tool is essential to identify patients with stroke symptoms. While using FLASHED as this tool resulted in assessments, testing, and interventions further study is needed to determine the validity and reliability of the FLASHED tool.
Abstract WP520: The Role of Neighborhood Deprivation in Stroke Risk in Two Countries: France and the United States
Authors: Judd Suzanne E , Howard George , Howard Virginia J , Soliman Elsayed Z , Clarke Philippa J , Colabianchi Natalie , Letellier Noémie , Helmer Catherine , Feart Catherine , Tzourio Christophe , Berr Claudine , Lefèvre Sophie , Lackland Daniel T , Samieri Cécilia
Published: January 2019

Background and Aims:
The role of socioeconomic status in stroke has been difficult to study due to differences at both the individual and neighborhood level. We therefore sought to examine the role of neighborhood socioeconomic status on risk of stroke in two countries: the United States (US) and France.

Methods:
We used the REasons for Geographic and Racial Differences in Stroke (REGARDS) study in the US and the 3-City (3C) study in France. In both studies, we used a factor analysis to combine various socioeconomic indicators collected by the governments of the two countries (in France IRIS and in the US the census) into a score indicating the level of neighborhood disadvantage. We limited the analysis to those free from stroke at baseline and used combined outcome of ischemic or hemorrhagic stroke. Cox models were used to model the association between neighborhood deprivation and risk of stroke; all models were adjusted for components of the Framingham Stroke Risk Score (REGARDS also adjusted for race), dietary pattern, individual income and education.

Results:
There were 802 strokes in REGARDS in 17996 participants and 326 strokes in 3C in 7647 participants. In both studies neighborhood deprivation was associated with lower individual income and educational attainment as well as higher BMI and systolic blood pressure. Only in the REGARDS study was neighborhood deprivation associated with greater risk of stroke. In REGARDS, comparing the 5
th
quintile to the 1
st
quintile the hazard ratio (HR) and 95% CI was 1.36 (1.09, 1.72). In the 3C study comparing the 5
th
quintile to the 1
st
quintile, the HR (95% CI) was 1.04 (0.73, 1.47).

Conclusion:
In the REGARDS study neighborhood deprivation was associated with risk of stroke but these findings were not seen in the 3C study. Future work to further evaluate the role of diet and individual socio-economic status in mediating the findings observed in France could help to better explain the differences in these two studies.
Abstract WP523: Aerobic Training Reduces Stroke Risk in Patients With Atrial Fibrillation
Authors: Tseng Benjamin , Arce-Esquivel Arturo , Sarma Satyam
Published: January 2019

Introduction:
Atrial fibrillation (AF) is the leading cause of fatal ischemic stroke. Although stroke risk factors can be identified using available clinical assessment tools, current standard of care primarily relies on antithrombotic/anticoagulation therapy and fails to proactively modify the underlying risk factors contributing to stroke. The purpose of this study was to determine the effect of moderate-to-high intensity aerobic training in alleviating stroke risk by reducing arterial stiffness and AF burden in AF patients.

Methods:
Forty-two patients with clinically diagnosed AF between the ages of 65-75 were recruited and randomly assigned to either a 3-month aerobic training with moderate to high intensity (i.e. >80%MHR, 45 minutes, 3-4 days/week) or a health education group. Vascular integrity was evaluated by carotid-radial pulse-wave-velocity (PWVcr), carotid intima-media-thickness (cIMT) and end-diastolic velocity (EDV); AF burden was quantified using a 2-week continuous cardiac event monitor (ZioXT patch, iRhythm); stroke risk was assessed using the CHA
2
DS
2
-VASc scale. All measurements were assessed before and after training.

Results:
Thirty AF patients participated in the aerobic training group (f=18, age=70±3) and 12 participated in the health education group (f=8, age=69±4). After 3 months, the aerobic training group exhibited significant improvement in PWVcr (12.6±3.2m/s vs. 9.6±2.1m/s, p=0.001), EDV (14.3±2.5cm/s vs. 15.9±2.1cm/s, p=0.01), AF burden (84.3±12.3% vs. 66.6±1.3%, p=0.01), and CHA
2
DS
2
-VASc score (2.2±1.3 vs. 0.9±0.9, p=0.05). In addition, the change of EDV is predictive of the stroke risk (r
2
=0.32, p=0.01). No significant change was observed in the health education group.

Conclusion:
We found that 3 months of supervised aerobic training at moderate-to-high intensity level appeared to improve vascular integrity, alleviate AF burden, and reduce stroke risk in patients with AF. More importantly, the AF burden and stroke risk are modulated by improvements in vascular functions. This finding warrants future large-scale investigations to examine the dose-response relationship of exercise reducing ischemic stroke risk.
Abstract WP526: Molecular Imaging of Carotid Plaques Using a Fibrin-Binding PET Probe
Authors: Izquierdo-Garcia David , Diyabalanage Himashinie , Ramsay Ian , Rotile Nicholas , Choi Ji-Kyung , Witzel Thomas , Humblet Valerie , Brownell Anna-Liisa , Catana Ciprian , Caravan Peter , Ay Ilknur
Published: January 2019

Objectives:
We aim to develop molecular fibrin imaging as a tool to stratify high risk atherosclerotic carotid plaques. Here, we describe our results with a fibrin-specific probe [
68
Ga]CM-246 in two different experimental settings: ex vivo imaging of carotid endarterectomy specimens and in vivo / ex vivo imaging of atherosclerotic plaque rupture in rabbits.

Methods:
We incubated discarded endarterectomy specimens (n=11) from asymptomatic patients with [
68
Ga] CM-246 or a scrambled peptide control probe and measured uptake by autoradiography and a tissue binding assay. In a rabbit plaque rupture model of high cholesterol diet followed by abdominal aorta balloon injury (n=13) and subsequent pharmacological plaque rupture, in vivo and ex vivo PET-MR with [
68
Ga]CM-246 was performed. Tissues were processed for autoradiography and histology to verify presence of fibrin and plaque rupture.

Results:
Autoradiography (A-B) and tissue binding assays (C) with [
68
Ga]CM-246 with human carotid plaques show increased tissue binding compared with non-specific control probe. Carstair’s staining (D) verified the presence of fibrin in the specimens (red stained areas). Rabbits with plaque rupture had an increase in [
68
Ga]CM-246 signal in the abdominal aorta compared with the control group. At 105-120 min post probe injection, there was a clear PET uptake on the aorta in plaque rupture rabbit (E) compared with control rabbit (F). MR images were used to differentiate abdominal aorta (green arrows) and the inferior vena cava (blue arrows). T2-dark blood images confirmed the plaques in rupture (G) and control rabbits (H). ToF images were used to visualize aortic lumen in plaque rupture (I) and control rabbits (J). Ex-vivo PET imaging, autoradiography, and histology confirmed in vivo results.

Conclusions:
We demonstrated that [
68
Ga]CM-246 detects high-risk plaque in human and rabbits and can be a useful tool for the stratification of atherosclerotic plaques in patients.
Abstract WP53: Is There Clinicial Equipoise for a Randomized Trial of Anesthesia (Sedation vs. General) During Endovascular Therapy?
Authors: Chen Peng R , Sanzgiri Aditya , Sheth Sunil , Artime Carlos , Inam Mehmet , Pedroza Claudia , Savitz Sean I , Barreto Andrew D
Published: January 2019

Background and Objectives:
Retrospective case-control studies found general anesthesia (GA), compared with conscious sedation (CS), was independently associated with poor clinical outcome in acute ischemic stroke (AIS) patients receiving endovascular therapy (EVT). Conversely, recent randomized clinical trials (RCT) not only failed to demonstrate such an association, but also provided a trend toward better outcomes in GA vs. CS. We sought to describe EVT-anesthesia clinical practice and determine if clinical equipoise existed for the purposes of designing a large RCT.

Methods:
We sent an online survey to 193 SVIN (Society of Vascular Interventional Neurology) and 78 AANS-CV (American Association of Neurological Surgeons - Cerebrovascular section) physicians that routinely perform EVT. Neurointerventionalists were asked a series of questions to describe their clinical practice, determine if clinical equipoise existed for designing a large GA vs. CS RCT and enthusiasm for trial participation.

Results:
Between 3/17 and 5/17, 116 (60%) responses were received. The majority of centers had at least 3 or more interventionalists and performed at least 50 EVT procedures yearly (Table). Only 13% of respondents reported the use of GA in at least half of their EVT cases (Figure). While anesthesiologists in nearly all cases managed GA, neurointerventionalists administered CS in almost half of cases. 55% vs.45% of respondents thought a RCT was or was not necessary, respectively (Figure).

Conclusion:
Anesthesia management during EVT varies widely and substantial uncertainty among experts demonstrates clinical equipoise. A large efficacy RCT is warranted, justified and underway (SEdation vs General Anesthesia for Endovascular Therapy in Acute Ischemic Stroke [SEGA Trial] Clinicaltrials.gov NCT-03263117).
Abstract WP534: Cyanidin 3-glucoside and its Metabolites Protect Against Nonalcoholic Fatty Liver Disease: Crosstalk Between Serum Lipids, Inflammatory Cytokines and MAPK/ERK Pathway
Authors: Wu Shusong , Hu Ruizhi , Tan Jijun , He Ziyu , Liu Ming , Li Yanli , He Xi , Hou De-Xing , Luo Jiayou , He Jianhua
Published: January 2019

Background:
Serum lipids and inflammatory cytokines are considered as potential therapeutic targets for nonalcoholic fatty liver disease, which has become the most common chronic liver disease in adolescents. Cyanidin 3-glucoside (C3G) is a natural anthocyanin occurs widely in plants, and has shown potential inhibitory effect on inflammatory cytokines in our previous studies.

Methods:
First, serum levels of inflammatory cytokines including TNF-α and MCP-1 were measured in 80 adolescents (9-15 years old) selected based on their body mass index and serum levels of lipids. Second, the protective effects of C3G and its metabolites including protocatechuic acid (PCA), phloroglucinaldehyde (PGA), ferulic acid, and vanillic acid on nonalcoholic fatty liver disease were measured in a mouse model in which C57BL/6N mice (n=4 for each group) were fed a normal diet, high fat diet only, or high fat diet containing 0.4% of C3G or the four metabolites for 3 months. Finally, the regulatory effects of C3G and its metabolites on inflammatory pathways were clarified in mouse macrophages.

Results:
Compared with serum levels of MCP-1 (273.13±16.89 pg/ml, n=16) and TNF-α (26.07±1.36 pg/ml) in normal adolescents, those who were obese with abnormal high serum LDL-c/HDL-c ratio (2.88±0.11) had higher MCP-1 (345.19±11.82 pg/ml,
P
<0.05) and TNF-α (35.70±1.90 pg/ml,
P
<0.05) levels. However, no significant change was observed in MCP-1 or TNF-α levels in adolescents who had a lower LDL-c/HDL-c ratio, even though their serum levels of total cholesterol and triacylglycerol were significantly higher (
P
<0.05) than normal level. Mice experiments revealed that supplement with C3G, PCA or PGA, but not ferulic acid or vanillic acid, prevented high fat diet-induced obesity and fatty liver with lower serum LDL-c/HDL-c ratio and levels of MCP-1 and TNF-α. Cell signaling analysis indicated that C3G, PCA and PGA suppressed the activation of MAPK pathway, especially, C3G and PGA could directly bind to ERK1/2.

Conclusion:
The serum LDL-c/HDL-c ratio is closely associated with the inflammatory status in nonalcoholic fatty liver disease, and C3G can suppress the inflammation via MAPK/ERK pathway potentially through its metabolites PCA and PGA.
Abstract WP543: Apelin Impairs Endothelium-Derived Hyperpolarizing Factor (EDHF)-Induced Relaxation of Cerebral Arteries by Inhibiting Activation of Large Conductance, Calcium-Activated K (BK
Ca
) Channels in Vascular Smooth Muscle
Authors: O'Rourke Stephen T , Mughal Amreen , Sun Chengwen
Published: January 2019

Introduction:
Apelin is a peptide found in fat cells, endothelial cells and CNS neurons. Apelin levels are increased in conditions linked to cardiovascular disease (e.g. obesity, diabetes). Apelin inhibits NO-induced relaxation of cerebral arteries (CA) but its effect on relaxation to EDHF, which often compensates for impaired NO responses in diseased arteries, is unknown.

Methods and Results:
Immunoblot analysis identified apelin receptor expression in human and rat CA. In isolated rat CA, A23187 (10
-9
– 10
-6
M) caused endothelium-dependent relaxation that was unaffected by inhibitors of eNOS (nitro-l-arginine (3 x 10
-5
M), guanylyl cyclase (ODQ (10
-5
M), cyclooxygenase (indomethacin (10
-5
M) and the H
2
O
2
-scavenger, PEG-catalase (500 U/ml) (n=6). A23187-induced relaxation was attenuated by MS-PPOH (10
-5
M), a selective inhibitor of cyp450-catalyzed synthesis of epoxyeicosatrienoic acids (EETs) (pD
2
=6.86 ± 0.3 vs 5.90 ± 0.1, without and with MS-PPOH; n=6; p<0.05), and abolished by 14,15-EE(Z)E (10
-5
M), a selective EET-receptor antagonist (n=7; p<0.05). Apelin (10
-7
M) inhibited A23187-induced relaxation (pD
2
=7.08 ± 0.2 vs 6.44 ± 0.1, without and with apelin; n=7; p<0.05) as well as relaxation to 11,12-EET, 14,15-EET and NS1619 (BK
Ca
channel opener), but had no effect on relaxation evoked by levcromakalim (K
ATP
channel opener). In whole cell patch clamp studies (10mv steps from -60mv to +80mv, 200ms duration) in CA smooth muscle cells, 11,12-EET (10
-5
M), 14,15-EET (10
-5
M), and NS1619 (10
-5
M) each caused an approximately 2-fold increase in BK
Ca
peak current density (at +80 mV; n=6; p<0.05), which was completely abrogated in the presence of apelin (10
-7
M). The effects of apelin on EET-induced relaxation and activation of BK
Ca
currents were mimicked by iberiotoxin (10
-7
M) (selective BK
Ca
channel blocker) and abolished by F13A (10
-7
M), an apelin receptor antagonist.

Conclusion:
Apelin regulates CA vascular tone by inhibiting endothelium-dependent relaxation evoked by an EDHF-like mediator (possibly an EET) through a mechanism involving activation of apelin receptors and inhibition of BK
Ca
channels in CA smooth muscle cells. These effects could increase the risk of cerebrovascular dysfunction under conditions where apelin levels are elevated.
Abstract WP549: GRK5-Mediated Inhibitory Phosphorylation of the Mineralocorticoid Receptor Protects Against Aldosterone`s Stroke-Promoting Vascular Effects
Authors: Lymperopoulos Anastasios , Desimine Victoria L , Wertz Shelby L , Duarte Yanelys , Maning Jennifer , Brill Ava , McCrink Katie A , Martinez Yaimiry
Published: January 2019

Introduction:
Stroke is one of the leading causes of death in the Western world. Mineralocorticoid receptor (MR) antagonism is a potential therapy for ischemic and hemorrhagic stroke patients, since aldosterone exerts deleterious effects in the cerebral vasculature via the MR. Prominent among these is activation of epidermal growth factor (EGF)-dependent vessel wall remodeling. GRK2 and GRK5 are the most abundant G protein-coupled receptor (GPCR)-kinases (GRKs) in the heart and vessels and both phosphorylate GPCRs but also non-GPCR substrates at Ser/Thr residues. The human MR gets phosphorylated at various Ser residues, including Ser-843 in the ligand binding domain (LBD) and Ser-601 in the N-terminal domain (NTD). These Ser phosphorylations occur in the cytoplasm and result in MR inhibition via direct transcriptional activity repression or cytosolic retention, respectively.

Hypothesis:
GRK5 phosphorylates and inhibits the MR in the heart and vessels.

Methods:
We used rat cardiomyocytes (H9c2) and aortic smooth muscle cells (ASMCs). We checked for GRK interactions with the MR via co-immunoprecipitation. We measured MR phosphorylation via phospho-Ser immunoblotting and MR transcriptional activity via the luciferase reporter assay. We also measured EGF and EGF receptor (EGFR) expression via real time-PCR.

Results:
GRK5, but not GRK2, phosphorylates the MR in H9c2 cardiomyocytes. Beta2-adrenoceptor activation stimulates this non-canonical effect of GRK5. The GRK5-phosphorylated MR is incapable of activating gene transcription, since aldosterone-induced MR transcriptional activity is markedly suppressed upon GRK5 overexpression in both cardiomyocytes and ASMCs. Conversely, CRISPR-mediated GRK5 gene deletion augments cardiac and ASMC aldosterone-dependent MR transcriptional activity. Finally, beta2-adrenoceptor-stimulated GRK5 phosphorylates and inhibits the MR in ASMCs, thereby suppressing aldosterone-induced EGF and EGFR mRNA expression.

Conclusions:
GRK5 blocks the toxic MR-dependent effects of aldosterone in the heart and vascular smooth muscles. Thus, GRK5 stimulation (e.g. via beta2-adrenoceptor activation) may protect against the stroke-promoting effects of aldosterone in the cerebral vasculature.
Abstract WP55: The Successful/Partial Early Reperfusion After IV rt-PA Before Mechanical Thrombectomy
Authors: Kobayashi Kazuto , Maekawa Kota , Shibata Masunari , Yamasaki Masayoshi , Sano Takanori , Naito Yutaka , Miya Fumitaka
Published: January 2019

Background and Purpose:
Intravenous thrombolysis tissue plasminogen activator (IV rt-PA) is known as effective to improve functional outcome for acute ischemic stroke. Also, it is known that rapid endovascular treatment improve functional outcome of patients after IV rt-PA. However, the rate of early reperfusion in patients with occluded artery just after IV rt-PA remains unclear. Purpose of this study was to evaluate prevalence of the early reperfusion after IV rt-PA, before mechanical thrombectomy.

Methods:
Between January 2015 and April 2018, 1753 consecutive ischemic stroke patients who were hospitalized were identified using prospective stroke registry. Four dimensional computed tomography (4DCT) were performed to identify an occulted artery before IV rt-PA. After IV rt-PA, vessel recanalization was diagnosed using Digital subtraction angiography or MR Angiography.

Results:
Among 1753 consecutive patients, 246 (14%) patients were received IV rt-PA. 117 patients were enrolled, with a mean age of 77 years (SD, 11 years), 66 (56.4%) were male (91 patients without occlusive artery, 24 without 4DCTA before IV rt-PAand 14 with insufficient 4DCT were excluded). The locations of occlusive artery were ACA (n=2), MCA (n=75), ICA (n=23), PCA (n=7) and BA (n=10).IV rt-PAto DSA was 26 ± 22 minutes. Successful and partial reperfusions of the occluded territory were achieved in 11 (9.4%) and 18 (15.4%), respectively. Initial NIHSS of successful/partial reperfusionwas lower than no recanalization group (13.4 ± 9 vs 19.3 ± 9; P<0.05). There were no significant in the prevalence of the using antithrombotic agents before IV rt-PA, and modified Rankin scale at discharge between these 2 groups. The location of recanalization/partial recanalization cases were ACA (0/2), MCA (22/75), ICA (1/23), PCA (4/7) and BA (2/10). Seven of 23 ICA occlusions were isolated occlusion. Two of 7 patients (28.6%) with isolated occlusion became into terminus occlusion.

Conclusions:
Successful reperfusion and partial recanalization rate were 9.4% and 15.4% just after IV rt-PA therapy, respectively. IV rt-PA may promote isolated ICA occlusion worsening.
Abstract WP562: Retinal Vessel Caliber is Associated With Cognitive Function Independent of Cerebrovascular and Renal Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: El Husseini Nada K , Schaich Chris L , Craft Suzanne , Rapp Steve , Fitzpatrick Annette , Sharrett A. Richey , Klein Ronald , Klein Barbara , Cotch Mary Frances , Wong Tien Y , Luchsinger Jose A , Hughes Timothy M
Published: January 2019

Background:
Microvascular retinal abnormalities may be markers of cerebrovascular and renal microvascular disease and are associated with cognitive impairment.

Hypothesis:
Stroke and albuminuria mediate the association of retinal abnormalities with cognitive performance.

Methods:
In a racially diverse longitudinal MESA cohort, we used retinal imaging from MESA exams 2 (2002-2004) and 5 (2010-2012) to determine the association of retinal microvascular changes with global cognitive function (Cognitive Abilities Screening Instrument; CASI version 2), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) scores at MESA Exam 5 after adjusting for vascular risk factors and interactions with albuminuria at Exam 2 and incident stroke (ischemic or hemorrhagic).

Results:
A total of 4,392 participants were included. At Exam 5, the mean (±SD) age of participants was 69.5 (9.3), 46.6% were women, 41.3% were non-Hispanic White. Albuminuria was present in 373 and stroke occurred in 77 participants. Over the 8-year period, the mean change in central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) was -2.9 (11.4) μm and -7.6 (14.8) μm, respectively. The CRAE at Exam 5, change in CRAE between Exam 2 and 5, and CRVE at Exam 2 were associated with a poorer CASI score (Table). Greater CRVE at Exam 2 and 5 was associated with a poorer DSC (Table) and no associations were found with DS scores (all p>0.05). Stroke and albuminuria were associated with CASI and DSC. The interaction of stroke with the change in CRAE and with CRVE at exam 5 in predicting DSC was significant. However, albuminuria and incident stroke did not mediate or significantly interact with microvascular retinal changes to predict CASI (all p>0.05).

Conclusions:
Stroke and albuminuria do not explain the association between retinal microvascular caliber and global cognitive performance but the interaction with stroke in predicting processing speed is significant.
Abstract WP566: Vascular Regeneration Following Transient Hypertension by Perivascular Progenitor Cells and Abeta Clearance in a Transgenic Rat Model of Alzheimer’S Disease
Authors: Bazzigaluppi Paolo , Beckett Tina , Koletar Margaret , Lai Aaron , Morrone Christopher , Smolina Anastasia , McLaurin JoAnne , Stefanovic Bojana
Published: January 2019

The interplay between hypertension and amyloidogensis is understudied and lacks of preclinical model that captures both pathologies. Our therapeutic approach is designed to target the patients who present cerebrovascular injury in combination with AD pathology. We combined induced transient hypertension (via Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) in a transgenic rat model of AD that recapitulates Aβ peptide deposition and tau hyperphosphorylation in the adulthood followed by cognitive decline and neuronal loss in later life. We administered human umbilical cord perivascular cells (HUCPVC) to elicit brain vascular repair and scyllo-inositol (SI) to clear amyloid. Treatment outcomes were measured by perfusion MRI, immunohistochemistry (amyloid, tau hyperphosphorylation, vascular markers), and immunoblotting. Four weeks after the cessation of L-NAME, a single HUCPVC treatment was administered, and final imaging session conducted four weeks thereafter. Blood-flow was measured during both rest and CO
2
challenges at: baseline, immediately post-L-NAME, and at endpoint. L-NAME administration induced moderate hypertension in both TgAD-F344 and non-TgAD rats, manifested by increased systolic pressure, elevated plasminogen activator inhibitor-1, decreased vessel density and hippocampal resting perfusion reduction. Hippocampal hypoperfusion in the non-TgAD animals returned to baseline 4-weeks after cessation of L-NAME, whereas in TgAD-F344 rats it persisted until endpoint and was not rescued by HUCPVC+SI. Hippocampal vascular responsivity to hypercapnia increased twice as much in TgAD-F344 when compared to non-TgAD-F344 following L-NAME administration; it did not return to baseline levels 4-weeks after cessation of L-NAME in the vehicle-administered TgAD-F344 rats, whereas HUCPVC and HUCPVC+SI rescued hippocampal cerebrovascular hyperreactivity to baseline levels of TgAD-F344 rats. Transient hypertension caused sustained cerebrovascular dysfunction when associated with Aβ plaques, revealing an interaction between transient hypertension and AD pathology. Combinatorial treatment with SI and HUCPVC may be necessary to address cerebrovascular disease with comorbid AD.