bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 141: The Microrna 17-92 Cluster in Neural Progenitor Cells is Required for Stroke-induced Neurogenesis and Gliogenesis
Authors: Pan Wanlong , Liu Xianshuang , Zhang Xiaoming , Wang Xinli , Hu Jiani , Zhang Ruilan , Chopp Michael , Zhang Zheng Gang
Published: June 2021

Background:
Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. The microRNA 17-92 cluster (miR17-92) regulates proliferation and differentiation of adult neural progenitor cells (NPCs). The present study investigated whether the miR17-92 cluster in NPCs is required for stroke-induced neurogenesis.

Methods and Results:
Mice with inducible and conditional knockdown of the miR17-92 cluster in nestin lineage NPCs (nestin-CreER
T2
/miR17-92
-/-
, 17-92-cKO, n=9) and wild-type litters (WT, n=9) were treated by tamoxifen. Administration of tamoxifen resulted in more than 60% reduction of individual members of the miR-17-92 cluster (miR-17: 1.0 vs 0.4; miR-19a: 1.0 vs 0.3; miR-19b: 1.0 vs 0.2; miR-20a: 1.0 vs 0.4; miR-92a: 1.0 vs 0.4 fold in WT, p<0.05) in NPCs localized to the subventricular zone (SVZ). Two days after termination of tamoxifen treatment, these mice were subjected to permanent right middle cerebral artery occlusion (MCAO) and sacrificed 28 days post-MCAo. Compared to WT mice, 17-92-cKO mice exhibited significant (p<0.05) reduction of proliferation of NPCs measured by the number of Ki67
+
cells (226±43 vs 471±100 cells/mm
2
) and the number of DCX
+
neuroblasts (11±2% vs 24±4% ) in the ischemic SVZ. Cultured NPCs harvested from ischemic cKO mice showed significant (p<0.05) reduction of BrdU
+
cells (37±2% vs 61±4% WT , n=3/group), Tuj1
+
neuroblasts (5±0.2% vs 9±0.4% ), GFAP
+
cells (33±3% vs 53±2% ), and NG2
+
oligodendrocyte progenitor cells (OPCs, 3±0.1% vs 5±0.5%). These in vivo and in vitro data indicate that reduction of the miR17-92 cluster suppresses stroke-induced neurogenesis and gliogenesis. Western blot analysis showed that miR17-92 cKO significantly (p<0.05) increased and reduced a cytoskeleton-associated protein, Enigma homolog1 (ENH1, 1.6 vs 1.0 fold), and its down-stream transcription factor, inhibitor of differentiation1 (ID1, 1.0 vs 0.6 fold), respectively. ENH1 is a putative target of the miR17-92 cluster.

Conclusion:
Our data indicate that the miR17-92 cluster in adult nestin lineage NPCs is required for stroke-induced neurongenesis and gliogenesis, and that the miR17-92 cluster possibly targets ENH1/ID1 signaling.
Abstract 146: Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Contributes to Cerebral Reperfusion after Stroke
Authors: Hong Sung-Ha , Marrelli Sean P
Published: June 2021

Introduction:
The TRPV1 channel is a non-selective ion channel that is activated by capsaicinoids, temperature (>43 °C), and multiple factors produced during inflammation or injury. At this time, there is very little reported regarding a role of this channel in regulation of cerebral blood flow. Here we provide new evidence for TRPV1 in promoting microvascular reperfusion following stroke.

Hypothesis:
Endothelial TRPV1 channels contribute to cerebral reperfusion following ischemic stroke.

Methods:
Experiments were performed in male WT and TRPV1 knockout mice of C57BL/6 background. Immunofluorescence was performed in brain sections with TRPV1 and Pecam-1 antibodies. Pressurized artery preparations were performed with isolated superior cerebellar arteries. Relative cerebral blood flow measurements were performed by laser Doppler and laser speckle flowmetry in mice before, during, and after MCAO (20 or 30 min). Reperfusion was monitored continuously for 2-3 hours and again at 24 hours.

Results:
TRPV1 expression was positively detected by immunofluorescence in the cerebral microvasculature, as assessed by Pecam-1 co-localization. TRPV1 KO mice were used as a negative control. Pressurized cerebral arteries demonstrated modest vasodilation to TRPV1 agonist (capsaicin) that was significantly potentiated with H
2
O
2
pre-treatment. The potentiated component of vasodilation was lost with removal of the endothelium, demonstrating the endothelial source of the response. Following brief MCA occlusion (20 or 30 min), WT mice demonstrated an initial return of cerebral perfusion followed by a transient drop in perfusion (~25% drop). This drop in perfusion started at 20-30 minutes into the reperfusion phase and lasted approximately one hour, at which point perfusion was restored to pre-stroke baseline value. In TRPV1 KO mice, the drop in perfusion was more profound (~65% drop) and persisted through 3 hours. By 24 hours, flow was restored to baseline in both groups.

Conclusions:
These data demonstrate a functional role for TRPV1 channels during reperfusion. We speculate that endothelial TRPV1 channels are functionally potentiated during injury and contribute to the vasodilatory capacity of the cerebral microvasculature following stroke.
Abstract 152: Risk of Arterial Thromboembolic Events After Intracerebral Hemorrhage
Authors: Murthy Santosh , Merkler Alexander , Gialdini Gino , Iadecola Costantino , Navi Babak , Kamel Hooman
Published: June 2021

Introduction:
Ischemic stroke and myocardial infarction (MI) have been reported as frequent complications after intracerebral hemorrhage (ICH), but the magnitude and duration of this risk is unclear.

Methods:
We performed a cohort-crossover study using inpatient and outpatient claims data from a nationally representative 5% sample of Medicare beneficiaries from 2008 through 2014. We included patients ≥66 years of age hospitalized for ICH. Our primary outcome was a composite of ischemic stroke or MI. We used validated
ICD-9-CM
diagnosis codes to identify predictors and outcomes. To avoid inclusion of patients with ICH as a complication of stroke or MI, we excluded ICH patients with a concurrent stroke or MI during the index ICH hospitalization. We compared the risk of stroke and MI during the 12 weeks after ICH versus the corresponding 12-week period 6 months later. To avoid immortal time bias, we limited our cohort to patients who remained alive and insured throughout the 9-month study period. Odds ratios (OR) and absolute risk differences were calculated using the Mantel-Haenszel estimator for matched data.

Results:
We included 1,817 ICH patients. In the 12-week period after discharge, 130 (7.1%) patients had a stroke or MI versus 13 (0.7%) in the corresponding 12-week period 6 months later. The absolute risk increase for ischemic stroke or MI was 6.4% (95% CI, 5.1-7.7%) during this period, with a corresponding OR of 10.0 (95% CI, 5.6-19.3). The absolute risk increase was 4.8% (95% CI, 3.7-5.8%) during the first 4 weeks, and 1.0% (95% CI, 0.3-1.7%) during weeks 5-8.

Limitations:
First, we lacked data on antithrombotic drug use, so further work is needed to distinguish how much of the heightened risk was due to the effect of ICH versus the effect of antithrombotic cessation. Second, we included only patients who survived at least 9 months; however, this would be expected to select for a less sick cohort and therefore decrease any apparent associations with these serious complications.

Conclusions:
There appears to be a heightened short-term risk of arterial thromboembolic events after acute ICH. This underlines the importance of studies and trials to identify optimal strategies for resuming antithrombotic medications in survivors of ICH.
Abstract 157: Nur77 Ameliorate Brain Ischemic Injury Through Polarize Microglia From M1 to M2 Phenotype
Authors: Chen Yan , Zhan Hui , Jin Yuexinzi , Xu Yun
Published: June 2021

Introduction:
The immune response to cerebral ischemia is a major contributor to stroke pathobiology in which microglia play a crucial role. Microglia are present in the classical M1 pro-inflammatory and the alternative M2 anti-inflammatory microglia. The Nur77 is a member of orphan nuclear receptor family, has been implicated in the regulation of macrophage M1/M2 polarization. However, the function of Nur77 in microglia and stroke pathology has not been studied yet. We investigated the role of Nur77 in modulating microglial M1/M2 polarization and improve brain injury.

Methods:
Wild type and Nur77
-/-
mice were subjected to right middle cerebral artery occlusion (MCAO). Behavior test, infarction volume, inflammation factors, and microglial phenotypes were determined at 1d, 3d, 7d after MCAO.
In vitro
, wild type and Nur77
-/-
microglia were simulated with conditional medium of oxygen glucose deprivation neuron. M1/M2 markers were measured at different time points. To explore mechanisms, proteomics analysis was conducted. Then we induced a lentivirus into the microglial cells for abrogation of Nur77 downstream protein in Nur77
-/-
microglia.

Results:
Nur77 expression in ipsilateral peri-infarction is markedly decreased. Nur77 deficiency enlarged infarction size, exacerbated sensorimotor and cognitive function, increased the expression of pro-inflammatory mediators (COX-2, TNFα), and decreased anti-inflammatory mediators (IL-4, IL-10) at 3d and 7d after MCAO. Nur77
-/-
mice present more CD16
+
Iba-1
+
and CD86
+
Iba-1
+
M1 microglia and less CD206
+
Iba-1
+
M2 microglia than wild type mice.
In vitro
conditional medium treated Nur77
-/-
primary microglia express more pro-inflammation mediators and less anti-inflammation factors. LPS-treated Nur77
-/-
and wild type microglia was used for mass spectrometry and we found that Nur77 down-regulate the expression of dedicator of cytokinesis 2 (DOCK2), which promote release of proinflammation mediators in microglia. After knockdown of DOCK2 in Nur77
-/-
microglia, up-regulated pro-inflammation mediators in Nur77
-/-
microglia have been reversed.

Conclusions:
Nur77 protects against ischemic brain injury by promoting M2 polarization, which probably be mediated by DOCK2-dependent pathway.
Abstract 167: An Innovative mHealth-based Care Model for Improving Hypertension Control in Stroke Survivors
Authors: Lakshminarayan Kamakshi , Westberg Sarah , Ezzeddine Mustapha , Speedie Stuart , Fuller Candace , Grimm Rich
Published: June 2021

Background:
Hypertension (HTN) is the most important modifiable risk factor for stroke prevention. Unfortunately, HTN is considerably under-treated in stroke survivors.

Purpose:
Our AHRQ funded study (R21 HS021794) examined the usability and feasibility of a mHealth (mobile health technology) based care model for improving HTN control rates in stroke survivors.

Methods:
Design was a 2 group randomized controlled trial. Total study duration was 120 days. HTN control was defined as Systolic BP (SBP) less than 140 mm Hg based on the AHA stroke guidelines. HTN control was evaluated in participants at study enrollment and completion.

Intervention Group:

Patients used a smart phone and wireless BP monitor to measure their BP. Patients were requested to measure their BP daily which was transmitted automatically to the study database. Study investigators (Physician + PharmD) reviewed BP weekly and, made needed medication adjustments bi-weekly. Primary care providers (PCP) were involved in the decision making via the electronic medical record.

Control Group:

Patients received a digital BP monitor and were educated on the importance of HTN control and asked to follow up with their PCP as usual (usual care). Intervention patients completed a Marshfield System Usablity Survey. Possible responses to usability questions were 1=strongly disagree, 2=agree, 3=neither agree or disagree, 4=agree, 5=strongly agree.

Results:
Total 50 patients completed the study (Table). Intervention patients transmitted BP a total of 92% of observation days and, rated mHealth as highly usable, Mean Marshfield System Usability Survey question response “I thought the system was easy to use” was 4.7. HTN control was significantly more effective in the intervention group (Table).

Conclusion:
A mHealth based model of HTN care was highly feasible and clinically more effective than usual care in stroke survivors. We propose that this care model be evaluated at a health system level.
Abstract 168: Differences in Description of Patent Foramen Ovale Influence Choice of Treatment
Authors: Wheeler Natalie C , Scherer Aaron M , Zikmund-Fisher Brian J , Zahuranec Darin
Published: June 2021

Background:
Clinical trials of patent foramen ovale (PFO) closure for stroke prevention have produced controversial results. We investigated differences in presenting the net benefits of PFO closure or description of the PFO in a randomized vignette-based internet survey.

Methods:
Adults aged 18 to 60 inclusive were recruited via Amazon’s Mechanical Turk. Participants read a vignette asking them to imagine that they had a minor stroke. The vignettes included three randomized factors in a 2 x 2 x 3 factorial design: a) benefit of PFO closure (no proven benefit versus ~3% absolute risk reduction, analogous to difference in individual trials versus subsequent meta-analysis); b) normalization intervention (PFO described as very common and benign for most individuals versus no such description); and c) labeling of the PFO (?PFO? versus ?hole in the heart? versus ?difference in heart structure?). Participants were then asked their choice of treatment (PFO closure or aspirin). Secondary outcomes included self-perceived stroke risk and level of anxiety about the PFO diagnosis. Regression analysis was used to assess predictors of treatment choice (logistic) and secondary outcomes (linear).

Results:
2157 participants completed the survey (54.6% female, 76.2% non-Hispanic white, median age 32 with IQR 27 – 41). Participants shown data suggesting 3% absolute risk reduction for PFO closure were more likely to choose PFO closure (30.9% vs. 7.5%, p < 0.001). The normalization intervention decreased anxiety about the PFO. The labeling intervention increased self-perceived stroke risk and had differential effects on patient anxiety (see Table for details).

Conclusion:
Differences in how information is presented can influence choice of treatment, perceived stroke risk, and level of anxiety surrounding PFO-associated stroke. Future work should address the impact of information presentation on potential variability in use of PFO closure and patient psychological outcomes.
Abstract 178: Infarct Growth Rate Depends on Collateral Status in Acute Ischemic Stroke Patients
Authors: Hakimelahi Reza , Buch Karen A , Leslie-Mazwi Thabele M , Hirsch Joshua A , Rabinov James D , Gonzalez R. Gilberto , Schaefer Pamela
Published: June 2021

Introduction and Hypothesis:
Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients.

Methods:
We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but < contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis.

Results:
In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p<0.0004 for all group comparisons). Patients with good collaterals were younger (p=0.004 and p=0.018 compared to poor and intermediate groups respectively) and had lower NIHSS scores (p< 0.001). Time after stroke onset, gender, or occlusion site (ICA vs MCA) were not significantly different among different collateral groups. There was no correlation between time and DWI volume (r2=0.02, p=0.8) or collateral status (r2=0.05, p=0.6). There was significant correlation between collateral status and infarct growth (r2=-0.6,p<0.0001).

Conclusion:
AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.
Abstract 184: Intravenous Thrombolysis for Acute Ischemic Stroke in the “Golden Hour”: a Propensity-matched Analysis of SITS-EAST Registry
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Kadlecova Pavla , Czlonkowska Anna , Kobayashi Adam , Brozman Miroslav , Švigelj Viktor , Csiba Laszlo , Fekete Klara , Kõrv Janika , Demarin Vida , Demarin Vida , Vilionskis Aleksandras , Jatuzis Dalius , Krespi Yakup , Liantinioti Chrissoula , Giannopoulos Sotirios , Mikulik Robert
Published: June 2021

Background & Purpose:
There are scarce data regarding outcomes of AIS patients treated with IVT within 60 min from symptom onset (“golden hour”). We sought to compare outcomes between AIS patients treated within (OTT≤60 min) and outside (OTT: 61-270min) the “golden hour” [GH(+) & GH (-)] using a propensity score matching approach.

Methods:
Patients were evaluated during a 12-year period in a large, international, prospective registry of IVT (SITS-EAST). They underwent serial NIHSS-score assessments at baseline, 2 hrs and 24 hrs following tPA-bolus. Clinical recovery (CR) at 2 and 24 hrs was defined as a reduction of ≥10 points in NIHSS-score compared with baseline, or a NIHSS-score of ≤3 at 2 and 24 hrs respectively. A relative reduction in NIHSS-score of ≥40% at 2 hrs was predictive of complete recanalization (CREC). sICH was defined using SITS-MOST criteria; 3-month favourable functional outcome (FFO) was defined as a mRS-score of 0-1. The two groups were matched for demographics, risk factors, baseline NIHSS, admission blood pressure and serum glucose.

Results:
Out of 19.077 tPA-treated AIS patients, 71 patients in GH(+) group [mean age 67±13 years; median NIHSS-score 12 points (IQR 10); median onset to treatment time (OTT) 55min, (IQR 10)] were matched to 6882 patients in GH(-) group (mean age 67±12 years; median NIHSS-score 11 points (IQR 9); median OTT 155min (IQR 55)]. The two groups did not differ in any of the matched characteristics (p>0.1). GH(+) had significantly (p<0.05) higher rates of 2hr (31% vs. 12%) and 24hr (41% vs. 27%) CR, CREC (39% vs. 21%) and 3-month FFO (47% vs. 34%). The rates of sICH (0% vs. 2%) and 3-month mortality (9% vs. 13%) were similar (p>0.2) in the two groups. GH(+) was independently (p<0.05) associated with 2hr CR (OR:5.5; 95%CI: 2.6-12.0), 24hr CR (OR:2.0; 95%CI: 1.1-3.6), CREC (OR:2.4; 95%CI: 1.4-4.3), and 3-month FFO (OR:2.3; 95%CI: 1.3-4.1) in multivariable logistic regression analyses adjusting for potential confounders.

Conclusions:
AIS patients treated with IVT within the GH have substantially higher odds of early CR and FFO. These findings highlight the potential of mobile stroke units to further improve AIS outcomes by increasing the rates of tPA delivery within the GH.
Abstract 187: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator
Authors: Dornbos David L , Harris Hallie , Gnyawali Surya , Wheeler Debra G , Huttinger Allyson , Venetos Nicholas , Talentino Spencer , Vaccaro Hope , Musgrave Nicholas , Jones Cheyenne , Amaya Pedro , Rink Cameron , Zweier Jay L , Sen Chandan K , Nimjee Shahid M
Published: June 2021

Introduction:
While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, few patients are eligible for treatment, and recanalization is only seen in 25-50%. Von Willebrand Factor (VWF) inhibition may play a role in thrombolysis.

Hypothesis:
VWF inhibition with an RNA aptamer lyses arterial thrombus and decreases ischemic injury. Furthermore, aptamer reversal with an antidote oligonucleotide ameliorates intracranial hemorrhage (ICH).

Methods:
Adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. Baseline carotid flow was obtained using a Doppler flow probe, and thrombotic occlusion was induced with a ferric chloride patch. After clot stabilization, mice were administered vehicle (platelet binding buffer, n=11), no infusion (n=8), rTPA (n=5) or VWF aptamer (n=5). Carotid flow was monitored for an additional 100 minutes. In a second cohort of mice, a 6-0 nylon suture was advanced within the carotid artery to generate vascular injury and ICH. Mice were given vehicle (n=16), rTPA (n=11), VWF aptamer (n=9) or aptamer/antidote (n=8). An MRI was obtained after 90 minutes to assess stroke and ICH volumes.

Results:
VWF aptamer successfully restored carotid blood flow 45 minutes following carotid occlusion (Figure 1) compared to controls (p<0.01*) and rTPA (p<0.05
+
). Stroke volume was significantly decreased in mice treated with VWF aptamer (23.03 ± 6.81 mm
3
) and aptamer/antidote (12.48 ± 5.68 mm
3
) compared to vehicle (45.25 ± 4.14 mm
3
, p<0.01). ICH volumes in mice treated with rTPA (2.64 ± 0.84 mm
3
) were trending higher than vehicle (1.51 ± 0.17 mm
3
), VWF aptamer (1.92 ± 0.22 mm
3
) or aptamer/antidote (1.31 ± 0.35 mm
3
).

Conclusions:
Aptamer inhibition of VWF is a potent thrombolytic agent with greater efficacy compared to rTPA. VWF inhibition appears safe with a trend toward lower ICH volumes in animals treated with aptamer and aptamer/antidote compared to rTPA.
Abstract 203: Safety And Efficacy Of WEB
®
Aneurysm Treatment: Combined Analysis 0f WEBCAST, French Observatory, And WEBCAST2 Studies - Final Results.
Authors: Pierot Laurent , Byrne James , Molyneux Andrew
Published: June 2021

Purpose:
WEB Flow disruption is an innovative endovascular treatment for wide-neck bifurcation aneurysms. Safety and efficacy are analyzed in the cumulated population of 3 prospective multicenter GCP (Good Clinical Practice) studies conducted in Europe (WEBCAST, French Observatory, WEBCAST2).

Methods:
Patients with wide neck bifurcation aneurysms were included in these 3 studies. An independent medical monitor independently analyzed adverse events. An independent expert in Interventional Neuroradiology evaluated anatomical results at 12 months using the 3 grades scale: complete occlusion, neck remnant, and aneurysm remnant.

Results:
A total of 168 patients with 169 aneurysms including 14 ruptured (8.3%) were included in the 3 studies. Eighty-six out 169 aneurysms were located at middle cerebral artery (50.9%), 36/169 at anterior communicating artery (21.3%), 30/169 at basilar artery (17.8%), and 17/169 at internal carotid artery terminus (10.1%). Placement of the WEB device was feasible in 163/169 aneurysms (96.4%). Morbidity and mortality at one month were reported in 4/168 patients (2.4%) and 0/168 patients (0.0%), respectively. Anatomical results at 12 months were complete aneurysm occlusion in 82/149 aneurysms (55.0%), neck remnant in 38/149 aneurysms (25.5%), and aneurysm remnant in 29/149 aneurysms (19.5%).

Conclusion:
This analysis in the large cumulated population of 3 GCP studies confirms the high safety of WEB treatment with low morbidity and mortality. At 12 months, adequate occlusion (complete occlusion and neck remnant) was obtained in a high percentage of aneurysms (80.5%).
Abstract 210: Is Endovascular Treatment Beneficial in Acute Ischemic Stroke Patients With M2 Segment Middle Cerebral Artery Occlusion?
Authors: Qureshi Adnan I , Saleem Muhammad A
Published: June 2021

Background:
The benefit of endovascular treatment in acute ischemic stroke patients with occlusion of distal middle cerebral artery (M2 segment) is unclear.

Methods:
We analyzed data from subjects with occlusion of M2 segment of middle cerebral artery confirmed with computed tomographic (CT) angiogram who were randomized to either intravenous (IV) recombinant tissue plasminogen activator (rt-PA) alone or in combination with endovascular treatment. We compared the rates of neurological deterioration within 24 hours; symptomatic intracranial hemorrhage (ICH) within 30 hours; good quality of life (defined by EQ-5D index score of ≥0.6) and functional independence (defined by modified Rankin scale of 0-2) at 3 months among subjects who underwent endovascular treatment with subjects who received IV rt-PA alone.

Results:
Of these 51 subjects (mean age ±SD; 68.3±11.8 years) with M2 segment occlusion, 34 and 17 subjects received IV rt-PA followed by endovascular treatment and IV rt-PA alone, respectively. There was a non-significantly lower rate of neurological deterioration (14.7% versus 25.0%) and symptomatic intracranial hemorrhages (5.9% versus 17.6%) among subjects who received IV rt-PA followed by endovascular treatment. At 3 months, the rates of independent functional outcome (52.9% versus 41.2%, odds ratio [OR] 1.6; 95 % confidence interval [CI] 0.5-5.2;
P
= 0.46) and good quality of life (50.0% vs 35.3% OR 1.9; 95% CI 0.5-7.2; p=0.37) were non-significantly higher among subjects with M2 segment occlusion who received IV rt-PA followed by endovascular treatment. The rate of death within 3 months was significantly lower among those who received IV rt-PA followed by endovascular treatment (5.9% vs 35.3%; OR 0.2; 95% CI 0.1-0.9; p=0.048).

Conclusions:
A randomized clinical trial should be considered based on the significant reduction in mortality and non-significant increase in functional independence and good quality of life following endovascular treatment in among acute ischemic stroke patients with M2 segment occlusion.
Abstract 22: Satisfaction With the Stroke Caregiver Telephone Assessment and Skill-Building Kit
Authors: Bakas Tamilyn , McLennon Susan M , Miller Elaine T
Published: June 2021

Background and Purpose:
Stroke family caregivers commonly neglect their own needs while providing care resulting in depressive symptoms, negative life changes, and poor health. Intervention programs that address stroke caregiver needs should not only be efficacious, but also be useful, easy to use, and acceptable to caregivers. The purpose of this study was to determine caregiver satisfaction with the Telephone Assessment and Skill-Building Kit (TASK II) compared with an Information, Support, and Referral (ISR) group.

Methods:
TASK II involved a mailed Resource Guide with 8 weekly calls from a nurse to address caregiver needs through skill-building. ISR involved a standard stroke caregiver brochure with information, support, and referral provided through active listening. In a randomized controlled clinical trial, 216 stroke caregivers provided satisfaction ratings for either TASK II (
n
=104) or the ISR intervention (
n
=112) using the Satisfaction Scale (usefulness, ease of use, acceptability). Data were analyzed using descriptive statistics, independent samples
t
tests, and Cohen’s
d
.

Results:
On a scale from 1 to 5, with 5 representing strongly agree, caregivers rated both interventions as highly satisfactory [Usefulness (TASK II
M
=4.4,
SD
=.5; ISR
M
=4.1,
SD
=.5); Ease of use (TASK II
M
=4.4,
SD
=.5; ISR
M
=4.2,
SD
=.5); Acceptability (TASK II
M
=4.3,
SD=
.6; ISR
M
=4.1,
SD
=.6); Total satisfaction (TASK II
M
=4.4,
SD
=.5; ISR
M
=4.2,
SD
=.5)]. Significant differences using Bonferroni correction (alpha=.05/4 comparisons=.0125) were found with moderate effect sizes favoring the TASK II over the ISR for the Usefulness subscale [
t
(214)=3.72,
p
=.00,
d
=.51] and for the Total Satisfaction Scale [
t
(214)=3.75,
p
=.00,
d
=.52].

Conclusions:
Both TASK II and ISR were highly rated by caregivers. TASK II was found to be more useful and satisfactory than simply providing information, support, and referral. Addressing stroke caregiver needs though skill-building strategies (e.g., problem solving and stress management) is perceived as being more useful and satisfactory for caregivers than other standard methods.
Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain
Authors: Rzechorzek Wojciech J , Buckley Brian K , Hua Kunji , Pomp Daniel , Zhang Hua , Faber James E
Published: June 2021

Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p<0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.
Abstract 223: Brain-derived Neurotrophic Factor Promotes Regenerative Functions of Human Endothelial Progenitor Cells - Roles of miRNAs
Authors: He Tongrong , Katusic Zvonimir
Published: June 2021

Our previous study has demonstrated that brain-derived neurotrophic factor (BDNF) enhances anti-oxidant capacity of endothelial progenitor cells (EPCs). Since BDNF is produced in cerebrovascular endothelial cells, and functions as a vasoprotective molecule, we hypothesized that BDNF might enhance regenerative capacity of EPCs. Early EPCs (circulating angiogenic cells) were derived from healthy male subjects (48±1.5 years old, n=10). EPCs were treated with BDNF 100 ng/ml for 7 hours, and miRNA transcriptome was examined using Affymetrix miRNA array (version 3.0). BDNF significantly changed 31 miRNAs (n=4, P<0.05, fold-change cut off=1.5). Notably, miR-181c level was increased by 1.9 fold (P<0.05) after BDNF treatment. Since miR-181c is known to down-regulate TNF-α expression, BDNF may protect EPCs by promoting anti-inflammatory phenotype. We also found that BDNF decreased miR-433 level by 1.6 fold (P<0.05). We further evaluated miR-433 function in human early EPCs. Knock-down of miR-433 in EPCs using siRNA significantly increased expression of guanylate binding protein 2 (GBP2) (n=6, P<0.05), an established direct target for miR-433. In contrast, treatment with miR-433 mimic significantly reduced GBP2 protein expression in EPCs (n=4, P<0.05). Since GBP2 has been shown to play an important role in the growth and colony formation of hematopoietic progenitors, BDNF/miR-433/GBP2 signaling may enhance angiogenic capacity of EPCs. In addition, neither miR-433-siRNA nor miR433 mimic significantly changed protein expressions of other targets such as growth factor receptor-binding protein2, cAMP response element-binding protein-1, cyclin-dependent kinase 6, and γ glutamyl cysteine synthetase (n=4-6, P>0.05). In summary, changes in miRNA transcriptome induced by treatment with BDNF may promote anti-inflammatory and angiogenic phenotype of EPCs. These effects of BDNF may have important implications for therapeutic enhancement of regenerative capacity of EPCs.
Abstract 23: Reducing Stroke Readmissions Utilizing a Home Care Based Transitions Coaching Program
Authors: Leonhardt Caprio Ann M , Burgen Denise M , Benesch Curtis G
Published: June 2021

Background:
The Center for Medicare and Medicaid Services (CMS) has instituted utilization of all-cause, unplanned 30 day hospital readmissions following discharge for ischemic stroke as part of the Hospital Inpatient Quality Reporting Program. While readmission reduction following stroke is a hospital imperative, there is minimal evidence on stroke-specific readmission reduction programs.

Purpose:
We sought to reduce 30 day readmissions following ischemic stroke through utilization of an established care transitions program in collaboration with our institution’s affiliated home care agency.

Methods:
Our institution’s home care agency has reduced readmission rates in the general medical population utilizing the Coleman Care Transitions Model
©
. This model incorporates motivational interviewing in visits prior to hospital discharge, with a home visit 24 to 48 hours after discharge, and by telephone at least weekly by a trained transitions coach. The coach ensures understanding of medications, follow up visits, and recognition of red flag symptoms. A one year pilot program for stroke patients utilizing this established program was initiated in October 2015. Basic stroke training was provided for all coaching staff. Quarterly readmission rates for 1 year prior to the intervention and 6 months following were analyzed.

Results:
During the first 6 months of the pilot program 18.2% of patients discharged with a diagnosis of ischemic stroke qualified for and completed the coaching program. Of those in the program 3.3% were readmitted. Overall, there were 15 readmissions in 13 patients, 85% of whom did not receive transitions coaching services. The readmission rate in the year prior to intervention was 7.8%, in the 6 months following 4.5%. These findings represent a 42.7% overall reduction in readmissions (p = 0.06) and a treatment effect of 1.7.

Conclusions:
Utilizing the Coleman Care Transitions Model
©
led to a meaningful reduction of hospital readmissions for patients with ischemic stroke in this pilot program. In an area in which readmission reduction has proven challenging, expanding the availability of a home care based program for specific patient populations may be an effective strategy.
Abstract 30: Door-to-puncture and First Pass Times for Endovascular Thrombectomy: Predictors and Changes Over Time in GWTG-stroke
Authors: Menon Bijoy K , Cox Margueritte , Saver Jeffrey L , Goyal Mayank , Xian Ying , Peterson Eric D , Matsouaka Roland , Hernandez Adrian F , Jahan Reza , Yavagal Dileep , Gupta Rishi , Mehta Brijesh , Bhatt Deepak L , Fonarow Gregg C , Schwamm Lee H , Smith Eric E
Published: June 2021

Background and Purpose:
Endovascular thrombectomy (EVT) is now standard of care in eligible patients with acute disabling ischemic stroke, and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can also be achieved in routine clinical practice. Here, we describe interval times from stroke onset to patient arrival in emergency room (door) to first pass/initiation of treatment in patients receiving EVT within Get With The Guidelines-Stroke hospitals (GWTG-S).

Methods:
Data are from sites participating fully as Comprehensive Stroke Centers within GWTG-S from 8/2014-3/2016. Analyzed work flow times include stroke onset to door , door to imaging, imaging to arterial access, arterial access to first pass time (defined as the earliest of either deployment of a mechanical reperfusion device or intra-arterial alteplase initiated) and the composite door-to-first-pass time. Data are described overall and analyzed by calendar year quarters. Trends are tested using the Cochran-Mantel-Haenszel test.

Results:
Data are reported from 1891 patients from 172 hospitals. Median time from stroke onset to door was 77 mins (IQR 46-144 min), imaging to arterial access was 91 min (64-126 min), and arterial access to first pass time was 18 min (4-31 min) (Figure). Median door-to-first-pass time was 129 min (IQR 97-171 min). Only 5.3% had a door-to-first-pass time <60 minutes while 15.1% achieved this time in <90 minutes. Slight improvements were noted in door-to-first pass (p=0.01) and imaging to arterial access time (p=0.04) by calendar quarter. Provision of IV alteplase was associated with longer imaging-to-arterial access time (median 96 vs. 85 minutes, p<0.001).

Conclusion:
Although workflow is improving, efforts need to continue on streamlining workflow and saving time so that the true potential of EVT is realized. These data may inform benchmark goals for EVT workflow times.
Abstract 4: Statin Pretreatment and Microembolic Signal Burden in Patients With Acute Large-artery Atherosclerotic Stroke: A Dose-dependent Effect
Authors: Tsivgoulis Georgios , Safouris Apostolos , Sharma Vijay K , Katsanos Aristeidis H , Faissner Simon , Roussopoulou Andromachi , Zompola Christina , Ioakeimides Michael , Kargiotis Odysseas , Deftereos Spyridon , Giannopoulos Georgios , Kneiphof Janina , Triantafyllou Nikos , Voumvourakis Konstantinos , Vadikolias Konstantinos , Krogias Christos
Published: June 2021

Background & Purpose:
Although statin pretreatment (SP) is associated with better early outcomes in acute ischemic stroke (AIS) patients, there are limited data regarding the underlying mechanism of this beneficial effect. We sought to evaluate the potential association between SP and microembolic signal (MES) burden in patients with acute cerebral ischemia (ACI) due to large-artery atherosclerosis (LAA).

Methods:
We prospectively evaluated consecutive patients admitted with first-ever ACI due to LAA in three tertiary stroke centers over a two-year period. LAA was diagnosed according to TOAST criteria. LAA location (extracranial vs. intracranial, posterior vs. anterior) was confirmed using CT or MR angiography. All patients underwent continuous 1-hour TCD monitoring of affected vessel at baseline (≤24 hrs from symptom onset) to identify both the presence and number of MES (MES burden). SP was recorded and dichotomized as high (rosuvastatin 40mg or atorvastatin 80mg) or low-to-moderate dose (HD &LMD). Functional outcome (FO) at 1 month was evaluated using the modified Rankin Scale (mRS).

Results:
SP was documented in 43 (41%) out of 106 LAA patients (mean age 65±10 years; 72% men; median NIHSS-score: 2, interquartile range: 0-4; LMD 32%, HD 8%). There was a significant (p=0.022) dose-dependent effect between SP and prevalence of MES on TCD: no SP (37%), SP with LMD (18%) and SP with HD (0%). Similarly, a significant (p=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with LMD (0.7±1.6) and SP with HD (0±0). Patients with SP had better FO (median mRS-score: 1, interquartile range: 0-2) than patients without SP (median mRS-score:0, interquartile range: 0-2, p=0.004 by Cochran-Mantel-Haenszel test). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, LAA location, stroke severity, and other prevention therapies (antiplatelets, antihypertensives, antidiabetics) only SP (OR=0.29, 95%CI: 0.09-0.92, p=0.036) and current smoking (OR=3.09, 95%CI: 1.05-9.07, p=0.040) were associated with MES presence.

Conclusion:
SP in patients with acute LAA is associated with reduced MES presence and lower MES burden. This effect appears to be dose-dependent.
Abstract 67: Blood Biomarkers for Prediction of Cardiac Complications in the Stroke Unit
Authors: Bustamante Alejandro , López-Cancio Elena , Giralt Dolors , Cardona Pere , García-Berrocoso Teresa , Canovas David , Garces Moises , Terceño Mikel , Serena Joaquín , Baldrich Eva , Rubiera Marta , Dávalos Antoni , Montaner Joan
Published: June 2021

Introduction:
Cardiac complications such as acute coronary syndrome (ACS) or acute congestive heart failure (ACHF) account for 2-6%of mortality after stroke. Early detection of the patients at the highest risk to suffer from cardiac complications could be of interest to indicate a closer monitoring or therapeutic measures. We aimed to test whether a panel of blood biomarkers could predict the development of cardiac complications during stroke unit admission.

Methods:
The StrokeChip was a prospective, observational study, conducted at six Hospitals in Catalonia. Patients with suspected stroke were enrolled at Emergency Departments. Blood samples were obtained within the first six hours after symptom onset to measure a 21-biomarker panel. In-hospital development of cardiac complications (ACS and ACHF) was recorded. The association between the measured biomarkers and the development of complications was assessed by logistic regression analysis.

Results:
From August-2012 to December-2013, 941 out of 1308 patients enrolled were ischemic strokes. Cardiac complications were developed by 25 patients, including 19 ACHF and six cases of ACS. Due to the small number of ACS, just ACHF were further analyzed. Patients with ACHF had higher baseline levels of D-dimer, endostatin, VAP-1, NT-proBNP, FasL and vWF, and lower levels of IGFBP-3. After logistic regression analysis, NT-proBNP [OR=3.56(1.17-10.84)], FasL [OR=4.94(1.60-15.26)], VAP-1 [OR=6.56(2.21-19.46)] and IGFBP-3 [OR=0.21(0.07-0.67)] were independently associated with ACHF after adjustment by clinical predictors such as stroke severity, previous disability or history of coronary disease. Addition of the biomarker panel over clinical predictors resulted in improved accuracy (AUC from 0.808 to 0.925, p=0.05).

Conclusions:
Baseline measurement of blood biomarkers in acute stroke could be useful to predict the development of cardiac complications during stroke unit admission.
Abstract 7: Higher Prevalence of High-t1w-signal Plaques on the Symptomatic Side in Patient with Recent Ischemic Stroke
Authors: Fan Zhaoyang , Yang Qi , Yang Yujiao , Song Shlee , Bi Xiaoming , Guo Xiuhai , Li Debiao
Published: June 2021

Introduction:
Inversion-recovery prepared variable-flip-angle 3D FSE (IR-SPACE) was recently proposed as a whole-brain vessel wall MRI method to assess intracranial vessel wall (IVW) abnormalities. Compared with conventional SPACE or 2D FSE, it provides more heavily T1 weighted (T1w) contrast that, based on extensive research on carotid atherosclerosis, is highly sensitive to vulnerable atherosclerotic plaque features - intraplaque hemorrhage and inflammation. It was hypothesized that, using the new approach, the prevalence of HT
1
S plaques is higher in the symptomatic side in patients with recent anterior circulation ischemic stroke.

Methods:
From Oct 2015 to Aug 2016, 33 patients with ischemic stroke (<14 days) and an intracranial stenosis of > 50% were consecutively recruited. The MRI protocol included regular brain MRI and intracranial MRA followed by pre- and post-contrast IR-SPACE. After excluding those with nonatherosclerosis etiology (5) and uninterpretable images (3), 25 patients were available for image review by two independent blind readers. Plaques defined as eccentric wall thickening with or without luminal stenosis were first identified and were then categorized as either hyper-intense or iso-intense using adjacent normal vessel wall for reference.

Results:
In 25 patients, 65 plaques were identified, with 40 and 25 at the symptomatic and asymptomatic side, respectively. HT1S was shown in 32 plaques on pre-contrast IR-SPACE and in 23 plaques on post-contrast IR-SPACE on the symptomatic side, with 22 plaques in both scenarios. On the asymptomatic side, the incidence of HT1S was lower (i.e. 7 on pre-contrast, 4 on post-contrast, 1 in both).

Conclusion:
In the current study, IR-SPACE revealed higher prevalence of HT1S in the symptomatic side. Pre-contrast scans identified more HT1S plaques than post-contrast scans, and almost all (22/23) of these HT1S plaques shown on post-contrast images also demonstrated HT1S feature on pre-contrast images. Further classification of these HT1S plaques according to the likelihood to cause stroke will help elucidate the clinical relevance of the above findings and this analysis is underway.
Abstract 70: Importance of Both Self-consent and Proxy- consent Enrollments to Avoid Bias in Acute Stroke Randomized Trials
Authors: Shkirkova Kristina , Wu Nelson , Starkman Sidney , Sanossain Nerses , Hamilton Scott , Liebeskind David , Eckstein Mark , Stratton Samuel , Pratt Frank , Sharma Latisha , Restrepo Lucas , Valdes-Sueiras Miguel , Kim-Tenser May , Conwit Robin , Saver Jeffrey L
Published: June 2021

Background:
Informed consent options for acute stroke randomized trials include self-consent from patients with retained competency, proxy consent from a legally authorized representative (LAR), and exception from informed consent in emergency circumstances (EFIC). Mechanisms other than self-consent trespass upon the ethical principle of autonomy (respect for persons), and should be used only if self-consent alone would bias the patient population.

Methods:
We analyzed acute stroke patients enrolled within 2h of symptom onset in the NIH Phase 3 Field Administration of Stroke Therapy - Magnesium (FAST-MAG) trial, comparing entry characteristics and outcomes with different consent mechanisms.

Results:
Among 1700 patients, median time from onset to study entry was 45 min (IQR 35-62). Overall, 60% of patients were competent and provided self-consent, 39% noncompetent and enrolled by proxy consent from an on-scene LAR, and 1% noncompetent enrolled using EFIC/delayed consent. Compared to self-consented patients, proxy-consented patients were: older, 73.8 vs 66.5, p<0.001; more often female, 47% vs 40%, p<0.02; and a higher frequency of several vascular risk factors, including hypertension, 81% vs 76%, p<0.05, diabetes, 26% vs20%, p<0.01, atrial fibrillation, 29% vs 17%, p<0.001, and coronary artery disease, 24% vs 19%, p<0.01. Proxy consent patients had more severe initial stroke deficits, prehospital LAMS, 4.1 vs 3.5, p<0.001. Proxy consent patients with acute cerebral ischemia had more advanced initial ischemic stroke lesions, ASPECTS 8.3 vs 9.3, p<0.001, and received tPA more often, 35% vs 20%, p<0.001. Proxy consent patients with intracerebral hemorrhage patient had larger initial hemorrhage volume (cc), 42.2 vs 22.6, p<0.001. Proxy consent patients had worse final outcomes, with freedom from disability (mRS 0-1) at 90d, 23.6% vs 44.3%, p<0.001.

Conclusions:
Proxy-informed consent patients differ systematically from self-consent patients, with older age, more comorbidities, more severe deficits, and worse long term outcomes. To ensure that acute stroke trial cohorts are representative of the general stroke population, it is important that enrollment mechanisms include proxy and/or deferred consent.