bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract W P218: Interleukin 21 receptor: A Major Modulator of Infarct Volume
Authors: Lee Han Kyu , Keum Sehoon , Lo Donald C , Marchuk Douglas A 
Published: July 2021

Using the permanent middle cerebral artery occlusion (MCAO) model of stroke, we have demonstrated that different inbred mouse strains show profound differences in infarct volume, indicating that infarction is under strong genetic control. To identify natural genetic determinants modulating infarction, we employed quantitative trait locus (QTL) linkage analysis and a genome-wide association study of cerebral infarct volume. We identified a locus on distal chromosome 7 that contributes over 50% of the variation in infarct volume, as well as other loci of smaller effect.
Using interval-specific ancestral haplotype analysis, we fine-mapped the chromosome 7 locus to only 12 candidate genes. To identify the gene(s) underlying this locus, we determined the strain-specific transcript levels of all 12 genes in relevant tissues that included P1 and adult brain cortex, and embryonic macrophages, the latter due to their importance in the development of the cerebrovascular system. One gene, interleukin 21 receptor (Il21r), showed a 7-fold expression difference between strains and harbors a coding SNP difference that segregates with infarct volume.
To determine whether Il21r is a major modulator of infarction, we examined Il21r in mice for their cerebrovascular anatomy as well as the cerebral infarct volume after MCAO. While Il21r-/- mice show a moderate reduction in collateral vessel connections compared to wild-type littermate mice cerebral infarct volume in Il21r-/- mice is increased 3-fold. This suggests that Il21r has effects on both cerebrovascular anatomy and innate neuroprotection. To examine the latter, we performed an ex vivo study of brain slices under in vitro oxygen deprivation. In this system devoid of any potential circulatory effects, but retaining appropriate tissue architecture, Il21r-/- brain slices showed an increase in oxygen-deprivation induced cell death, showing that Il21r is also involved in cerebrovascular-independent neuroprotection. Biochemical studies of the brain slices show that Il21R regulates ischemia-induced apoptosis. The identification of Il21R as a cerebrovascular-independent modulator of infarct volume provides a fundamental advance in the understanding of genetic modulation of ischemic stroke.
Abstract W P222: Activated Microglia Contribute to Neurovascular Integrity and Limit Brain Injury After Acute Neonatal Focal Stroke
Authors: Fernández-López David , Faustino Joel , Klibanov Alexander , Derugin Nikita , Akassoglou katerina , Vexler Zinaida S 
Published: July 2021

It has been recently shown that microglial cells, which for a long time were considered purely injurious in the context of cerebral ischemia, can also exert beneficial effects following stroke in both adults and neonates1,2. Lack of tools to reliably distinguish resident microglia from infiltrated peripheral monocytes has been a major obstacle on the way to understand the relative role of these subpopulations of cells of the monocyte lineage in the pathophysiology of stroke. We subjected postnatal day 10 (P10) transgenic Cx3cr1GFP/-CCr2RFP/- mice, in which resident microglia (Cx3cr1GFP) and infiltrating monocytes (CCr2RFP) can be distinctively identified, to a transient 3 hour middle cerebral artery occlusion MCAO, a model that we recently developed3. Microglial cells were left unperturbed or were selectively depleted before MCAO by intracortical injection of clodronate-encapsulated liposomes.
Depletion of microglia exacerbated injury and significantly increased infarct volume (75.9% Vs. 56.3%, p<0.01). Furthermore, compared to mice with unperturbed microglia, depletion of microglia significantly increased the number of hemorrhages in injured regions, adversely affected vascular density and decreased the number of both adherent and infiltrated monocytes. The extent of RFP+ monocyte adhesion to vessels and infiltration in the brain parenchyma was highly variable among individual mice and did not correlate with brain infarct, whereas a significant correlation between the overall extent of microglial activation (measured by morphological transformation) and the number of infiltrated monocytes was observed.
The deleterious effect of microglial depletion on vascular integrity and function and on brain injury indicates that activated microglia act as a buffering component that limits vascular degeneration and injury severity after neonatal stroke. Our data also suggest a direct and dynamic relationship between microglial activation and monocyte recruitment into acutely reperfused neonatal brain.
Support: NS55915 (ZV), NS76726 (ZV), NS080015 (ZS, KA), AHA POST10980003 (DFL).
1. Faustino J et al. J Neurosci. 2011.
2. Lalancette-Hebert M et al. J Neurosci. 2007.
3. Woo MS et al. Annals of Neurology. 2012.
Abstract W P276: Developing Excellence in Stroke Care Through Knowledge Building and Interprofessional Collaborative Processes
Authors: Fortin Joanne , Skrabka Krystyna , Avinoam Gail , Willems Jacqueline , Sharp Shelley , Linkewich Elizabeth 
Published: July 2021

Background:
As part of a system-wide collaborative change process, a comprehensive education needs assessment was conducted with 15 acute and rehabilitation stroke teams within the Toronto Stroke Networks (TSNs). Evidence-informed educational and knowledge translation (KT) approaches were planned to bridge identified gaps for successful implementation of stroke best practices and excellence in patient care.

Purpose:
The purpose of this collaborative KT process is to enable successful learning and sustained adoption of best practices for improved patient care.

Methods:
The Education and KT plan was launched in collaboration with local organization stroke champions to integrate feedback and stimulate engagement.

Health care providers (HCPs) were oriented to the newly launched online platform, the TSNs Virtual Community of Practice (VCoP), for access to resources, ongoing knowledge exchange, and cross-system collaboration from both clinical and interprofessional perspectives.
Co-creation of stroke core foundational posters facilitated team and individual competencies for select best practices and provided HCPs with an enhanced networking opportunity building virtual competence for online collaboration.
Completed best practice posters and introduction of a small group learning guide and peer mentorship initiative will be launched to facilitate a team approach and enable practice change. A scheduled interprofessional event will reinforce online networking.

Results:
Formative evaluation of the online format has led to improved utility of the VCoP. Member checking with stroke champions has resulted in an adapted communication process with regular prompting to enable progress. Development of a strategic approach for increasing front line nurse participation was also highlighted. Further evaluation will be available at time of publishing.

Conclusions:
This innovative approach to enhance patient care has shown promise as an effective collaborative process. Iterative member checking with opportunity to adapt locally is key for successful system wide change.
Abstract T MP115: Cerebral Ischemic Events Associated with Transcatheter Aortic Valve Replacement (TAVR): A Systematic Review
Authors: Herial Nabeel A , Mohammad Najwa S , Chughtai Morad , Qureshi Adnan I 
Published: July 2021

Introduction:
Transcatheter aortic valve replacement (TAVR) has recently emerged as a treatment option in patients with symptomatic severe aortic stenosis. Cerebral ischemic events are recognized events associated with TAVR, however, a detailed analysis of such events is not performed.

Methods:
We performed a literature search to identify studies reporting outcome data at different time intervals following TAVR (peri-procedural/30-days, 1, 2, and 3 yrs). Data on the incidence of stroke/TIA was extracted from studies that used the Valve

Academic Research Consortium criteria and a comparison of stroke/TIA incidence between TAVR vs. surgical AVR, transfemoral (TF) vs. transapical (TA) approach, and self-expanding vs. balloon expanding valves is reported.

Results:
Peri-procedural stroke/TIA incidence after TAVR ranged from 1.6% to 5.5%. Incidence rates from the registries and meta-analyses were lower (2.3 - 2.8%) than those reported in the randomized clinical trials (RCTs) (4.6 - 5.5%). At 1-yr, pooled incidence rates from meta-analyses and RCTs ranged from 3.8 - 4.5% and 7.6 - 8.8%, respectively. Incidence at 2 and 3 yrs was 11.2% and 8.2% as reported in the RCT.

Meta-analyses revealed no difference in incidence rates between TAVR and SAVR at 30-d or 1 yr, but one RCT suggested a higher incidence of stroke/TIA with
TAVR at both these intervals. At 3 yrs, the stroke/TIA incidence incidence rates were similar between TAVR and SAVR. No difference in stroke incidence between the TF-TAVR and TA-TAVR approaches or the valve type was noted.

Conclusions:
In comparison to SAVR, existing data indicates a marginally higher incidence of stroke with TAVR during the peri-procedural period. Inconsistencies were noted in long term clinical outcomes including stroke/TIA incidence with TAVR. Future research should focus on patient selection, improvement in valve technology and procedural techniques to minimize the observed risk.
Abstract T MP21: Administration Of Atorvastatin During Angiogenesis After Stroke Promotes Long-term Restoration Of BBB In Peri-infarct Regions Of Rat Brains
Authors: Salayandia Victor M , Yang Yi R , Yang Lisa , Thompson Jeffrey F , Yang Yi 
Published: July 2021

Our previous study shows that the newly formed vessels in peri-infarct regions of ischemic hemispheres have hyperperfusion and high blood-brain barrier (BBB) permeability at 3 weeks after stroke. This is due to lack of tight junction proteins (TJP), occludin and ZO-1, in endothelial cells of the new vessels. We proposed that at this stage pro-angiogenic agents could be used to facilitate restoration of BBB to promote functional neurovascular remodeling in peri-infarct regions. In this study, we investigated the effects of atorvastatin, as a pro-angiogenic agent, on the brain recovery stage after stroke.
Adult spontaneously hypertensive rats had a transient middle cerebral artery occlusion (MCAO) with reperfusion. Atorvastatin, at a low dose of 3 mg/kg, was delivered daily starting at 14 days after MCAO for 7 days via gavage. Multimodal MRI and behavioral test were performed at different times up to 8 weeks after MCAO. Animals were sacrificed at 8 weeks for immunohistochemical and biochemical analyses.
Multimodal MRI showed that treatment with atorvastatin reduced core-infarct size and restored cerebral blood flow compared with vehicle treated brain. RotoRod tests demonstrated that atorvastatin improves long-term behavioral outcome of the stroke rats. At 8 weeks, treatment with atorvastatin markedly increased expression of occludin and ZO-1 in pericytes and endothelial cells of angiogenic vessels in peri-infarct areas. Importantly, ZO-1, which was found in pericytes surrounding the angiogenic vessels, was seen in the endothelial cell forming continuous-line-like structure in atorvastatin treated brain. Factors associated with angiogenesis, such as VEGF-A, TGF-β1, and Alk-1, were significantly increased in atorvastatin treated group. We also found that atorvastatin significantly increased expression of connexin 43, which forms gap junctions to transfer molecules between cells, in pericytes and astrocytes surrounding the new vessels.
Our results indicate that treatment with low-dose atorvastatin during recovery can stabilize the newly formed vessels and facilitate full development of BBB. Pericytes and astrocytes play a key role in determination of functional BBB restoration.
Abstract T P144: Rural Stroke System Development and Patterns of Arrival
Authors: Torner James C , Rindels Erin , Overton Angela , Leira Enrique , Mueller Michael , Nugent Meg , Spear Brent ,   Iowa Stroke Registry Hosps
Published: July 2021

Introduction:
The Iowa Stroke Registry (ISR) is one of the Paul Coverdell Registries of the Centers for Disease Control. Its goal is to assess the performance of the Iowa Stroke System and to conduct system improvement to improve stroke care and outcomes. One of the major challenges in rural state is acute intervention in a geographically dispersed population and transport to definitive care.

Methods:
The Iowa Stroke Registry was established in 2007 with data collection from 32 comprehensive, primary and stroke capable hospitals in Iowa beginning in 2009. To date over 10,000 patients have been enrolled.

Arrival to the ISR was characterized as via EMS, private vehicle or transfer from another facility. Factors related to stroke symptoms and presentation and time to arrival from last known well were examined by arrival mode.
Categorical analysis was done using a Chi-Square Test with an alpha of 0.05.

Results:
To date 39% of patients with stroke came directly by ambulance, 35% by private vehicle and 25% transferred from local hospitals. Of EMS transported patients were 94% were admitted through the ER; 13% of private vehicle and 32% of transfer patients were directly admitted to inpatient beds. Admission symptoms were similar regardless of transport mode with 64% of patients with weakness, 10% speech difficulties, 3% vision abnormalities and 28% with aphasia. Ambulation with assistance or unable to ambulate was highest in private vehicle patients (8.6%)(p<.05). Transfer (median=347 minutes) and private vehicle (median=408) were significantly longer than EMS arrivals (median=222). As the system developed, the percentage of transfer patients significantly increased over time.

Conclusions:
With nearly one-third of patients still arriving by private vehicle there is a need for further public education. Increase in transfers demonstrate the effect of stroke system development. These data from the ISR provide information for a wide-ranging stroke education program by the Coverdell Registry and Stroke Task Force committees and stakeholders in Iowa.
Abstract T P184: The Importance of Blood Biomarkers in Penetrating Artery Territory Infarction; A Prospective Multicenter Observational Study
Authors: Kawano Tomohiro , Miyashita Kotaro , Takeuchi Mariko , Metoki Norifumi , Akaiwa Yasuhisa , Yamamoto Yasumasa , Manabe Yasuhiro , Toyoda Kazunori , Nagatuka Kazuyuki 
Published: July 2021

Objective:
Neurological deterioration in penetrating artery territory infarction (PATI) is unpredictable and associated with a worse clinical outcome. This study aimed to determine the importance of blood biomarkers to predict neurological deterioration and long-term clinical outcome.

Methods:
From November 2012 to December 2013, we performed a prospective multicenter observational study of PATI patients presenting within 2 days of stroke onset. Blood samples were obtained within 24h after admission (1st point) and on a day between 6th and 8th hospitalization (2nd point) for several biomarkers. Symptomatic progression (SP) was defined as the increase of at least one point on the National Institutes of Health Stroke Scale. Favorable outcome was defined as modified Rankin Scale score≤2 at 90 days after ictus.

Results:
25 patients (28%) showed SP in evaluated 90 patients (35 men with a mean age of 70.4 years). The patients with SP were significantly (p<0.05) more elderly, hypertensive, clinically severed than those without SP on admission.

At 1st point, the patients with SP had significantly higher serum IL-6 and lower CD34 levels as compared to those without SP (IL-6: 4.8 [2.3-7.95] vs 2.4[1.3-4.1] pg/ml (p=0.007) and CD34: 0.5 [0.31-0.88] vs 0.8[0.49-1.08] /μL (p=0.002)).
Moreover, the patients with poor outcome at 90 days had significantly higher serum IL-6 levels, higher TNF-alpha levels and lower CD34 levels as compared to those with favorable outcome. At 2nd point, the patients with poor outcome had significantly higher serum IL-6 levels, higher TNF-alpha levels, higher pro-adrenomedullin levels, and lower ADAMTS13 levels compared to those with favorable outcome .
Comparing the change of biomarker levels between two-point measurements, the significant increases of pro-adrenomedullin and oxidized LDL receptor-1, and decrease of ADAMTS13 were correlated with SP.

Conclusions:
Blood biomarkers of inflammatory and endothelial function might be valuable to predict symptomatic progression and poor long-term outcome in PATI, meaning the surrogate markers for treatment evaluation in future stroke trials.
Abstract W P191: Patient Compliance High with Long-Term Continuous ECG Monitor
Authors: Lenane Judith C , Fought Angela J , Alexander Jay H 
Published: July 2021

Introduction:
Long term ECG monitoring to detect atrial fibrillation in a cryptogenic stroke is now the emerging standard of care. The advent of patch based ECG monitors raises the question of patient compliance with this new modality.

Hypothesis:
We assessed the hypothesis that patient compliance, as measured by Leads-On detection for patch based ECG monitoring, is constant over time.

Methods:
We performed a retrospective analysis from ZIO® Patch (Patch) devices (iRhythm, San Francisco, CA). The Patch is a continuous recording single lead ECG monitor that can be worn for up to 14 days. The primary endpoint of Leads-On is the percentage of time the device is applied to the patient during the wear period, which was derived from a second channel in the device. The data are gathered by ZEUS software and exported in a CSV file. The compliance data were analyzed overall and in categories at days: 0-1, 1-2, 2 to 7, >7 to 10 and >10 to 14. A secondary endpoint, percent Analyzable Time (percentage of ECG record that was available for detection by the algorithm during the wear period and signifies signal quality), was assessed for the same time increments.

Results:
The dataset consisted of 18,885 records. The total wear time ranged from 0.10 up to 14.01 days, with a median of 12.51. The medians and interquartile ranges for the percent Leads On and percent of Analyzable Time were 100% (99.99-100%) and 97.99% (94.64-99.26%). In Table 1, the interquartile ranges for percent Leads On and Analyzable Time was wider when the Patch was worn less than a day, but remains above 74%.

Total wear time in days n Percent Leads On Percent Analyzable Time
Median Interquartile Range Median Interquartile Range
0.10-<1 105 99.65 86.52-100 92.86 74.19-96.97
1-<2 407 100 99.88-100 97.37 90.96-99.02
2-<7 4124 100 100-100 97.96 94.3-99.26
7-<10 2963 100 99.98-100 97.79 94.33-99.19
10+ 11286 100 100-100 98.07 95.00-99.29

Conclusion:
Patient compliance with long term ECG patch monitors is high as measured by Leads-On detection. High patient compliance results in a large volume of quality ECG. Further study is needed to compare patient compliance with ECG patch based monitors with other monitoring modalities, particularly in the cryptogenic stroke population.
Abstract W P41: Multimodal Imaging ASPECTS: A Predictor Of Good Prognosis Before Thrombectomy
Authors: Cardona Pedro , Quesada Helena , Cano Luis , Lara Blanca , Rubio Francisco , Aja Lucia , Barranco Roger , De Miquel M. Angeles , Escrig Ana M. 
Published: July 2021

BACKGROUND:
The goal of this study was to determine the accuracy and reliability of noncontrast CT (NCCT), perfusion CT parameters maps (CTP) an CT-angiography source images (CTASI), analyzed with ASPECTS (Alberta Stroke Program Early CT Scale), as final outcome predictors of endovascular stroke treatment.

METHODS:
Consecutive patients with ischemic stroke who received endovascular reperfusion were retrospectively analyzed (04/2009-06/2014). In acute stroke patients NCCT, CTP-CBV (maps of Cerebral Blood Volume) and CTASI was performed according to our hospital guidelines before thrombectomy. We independently applied the ASPECTS in all baselines NCCT, CBV-CTP, CTASI and follow-up NCCT 24H. Receiver-operating characteristic curve (ROC) analysis was performed to determine optimal thresholds for imaging parameters to predict dichotomized good clinical outcome (modified Rankin score ≤2, mRS).

RESULTS:
From a database containing 402 thrombectomies, 94 underwent CTP and CTA for acute cerebrovascular ischemia. Ninety-one with MCA or ICA occlusion were identified for our study (49% women, mean age 64+/-13 years; NIHSS at admission 17). Successful recanalization (TICI 2b-3) was achieved in 73/91 patients (80%).

In ROC analysis higher CBV ASPECTS was associated with 90-day mRS score 0-2 (Area Under Curve=0.72;95% CI, 0.6-0.8; P:0.001) with optimal threshold of 8 (Sensivity 83%, Specificity 77%).
The CTASI ASPECTS was highly correlated with 24h NCCT ASPECTS (r: 0.65;Spearman p:0.001). Favorable clinical outcomes (mRS 0-2) was greater in patients with CBV ASPECTS >8 compared with ≤8 (71% vs 37%;p:0.001) and CTACI ASPECTS>8 compared with ≤8 (68% vs 37%;p=0.02).
In multivariate logistic regression CBV ASPECTS was associated with significant functional and radiological outcomes after adjustment for age, sex, time from CT to groin-puncture and baseline NIHSS (OR: 2.5; 95%CI:1.8-3.5, p:0.001).

CONCLUSIONS:
These results suggest that CBV ASPECTS approach can predict a favorable clinical outcome after endovascular treatment with good sensitivity and specificity.

CTASI ASPECTS may be more sensitive for detection of infarction and more accurate for predicting the final infarct size however not to predict clinical outcome.
Abstract W P63: Intravenous Thrombolysis for Acute Ischemic Stroke in Nonagenarians
Authors: Guisado Raul , Malek Reza , Kelly-Tolley Ursula , Padidar Arash , Sachdev Harmeet 
Published: July 2021

The safety and effectiveness of intravenous thrombolysis for acute ischemic stroke (AIS) has been established for populations older than 80 years of age . However, management of AIS in nonagenerians is not clear. Previous reports suggest that the rate of ICH after i.v. alteplase is not increased and the rate of early improvement is similar in nonagenerians compared to younger groups, but there is concern with overall mortality and functional outcomes.
We report on 20 consecutive patients with AIS treated with i.v. alteplase within 3 hours of onset in two Comprehensive Stroke Centers in San Jose, CA.

Methods:
Patients were immediately evaluated by members of the Stroke Team of each hospital. . Patients were eligible if they had disabling neurological symptoms, no contraindications for i.v.alteplase and were independent in ADLs prior to the index event. Non-contrast CT brain scan, CT perfusion and CT angiography of head and neck were used to determine the presence of potentially salvageable brain.

Results (Table):
Mean age was 91 years (range 90 - 98 years). The initial NIHSS was 15.7 ± 6.8. The median NIHSS at hospital discharge was 7.4 ± 8.4 (p <0.001). The median door to needle time was 50.5 minutes (range 36 - 74 minutes). There was no hemorrhagic transformation and no in-hospital mortality. The overall mortality rate at 90 days was 30% (6 of 20 patients) and the rate of good outcome in survivors, defined as mRS ≤ 3 at 90 days was 35.7% (5 of 14 patients).

Comment:
Intravenous thrombolysis for ischemic stroke in nonagenerians is safe and effective, with good rates of immediate improvement. However, the l90 days mortality rate is high and the long term functional outcome is poor. This data can be useful in helping families make treatment decisions in the most elderly patients with acute ischemic stroke.