bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP263: Identification and Functional Analysis of Circrna Profile in Penumbra Zones of Mice Following Middle Cerebral Artery Occlusion
Authors: Lu Dan , Xu Anding
Published: June 2021

Circular RNAs (circRNAs) are highly abundant in the brain, and exert regulatory roles during post-transcriptional process. Recently, deregulations of circRNA expression have been proven to be involved in hypoxia cells in
vitro
. However, the circRNA profiles of penumbra closely related to the prognosis of acute ischemic stroke (AIS) remain unclear. Herein, 12876 circRNAs based on circBase database were detected by microarray hybridization with blood RNA samples of Balb/c mice, including the sham group and groups of 5 min, 3 hr and 24 hr after middle cerebral artery occlusion (MCAO). Three comparison groups were set as sham vs 5 min (311 circRNAs up-regulated, 566 circRNAs down-regulated), sham vs 3 hr (513 circRNAs up-regulated, 207 circRNAs down-regulated), sham vs 24 hr (1079 circRNAs up-regulated, 1230 circRNAs down-regulated) (≥2.0 fold, p<0.05). Meanwhile, using RNA-sequencing technology, we profiled circRNA expressional signatures of mice brain tissues from normal zones, penumbra and infract zones of MCAO 3 hr groups. 553 of the total 23980 circRNAs changed significantly between the differential expression profiles of penumbra vs normal and penumbra vs infract core. Among them, two circRNAs sequence were aligned with the blood data by Pairwise Sequence Alighment (SIMILARITY=100%, IDENTITY=100%). Moreover, human-mouse alignments of the two circRNAs were computed on circBase database (IDENTITY >94.8% and IDENTITY=100%). Bioinformatics tools and databases were employed to explore the potential circRNAs functions. These findings are the first to identify MCAO-responsive circRNAs, which suggest potential pathological roles and may be as potential markers for penumbra progress in AIS.
Abstract TP266: Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Ischemia/Reperfusion Injury
Authors: An Hong , Wright Joshua , Duan Yunxia , Wu Di , Ji Xunming , Ding Yuchuan
Published: June 2021

Introduction:
Hypothermia is an effective neuroprotectant against stroke, but its application is limited by delayed onset, prolonged duration, and significant complications. Mild hypothermia is more clinically practical but offers weaker neuroprotection. This study investigated whether the neuroprotective effects of mild hypothermia can be enhanced by phenothiazine neuroleptics (chlorpromazine and promethazine), which were reported to have depressive or hibernation-like roles on the CNS. We also worked to elucidate the role of the PI3K/Akt signaling pathway in this protective mechanism.

Methods:
A total of 131 adult male Sprague-Dawley rats were randomly divided into 6 groups: sham, stroke without treatment (2-hour right middle cerebral artery occlusion), and 4 treatment groups with 1) mild hypothermia (anal temperature 33-35
0
C), 2) phenothiazines (1mg/kg chlorpromazine & 1mg/kg promethazine, anal temperature 37.8-38.3
0
C), 3) combination of mild hypothermia and phenothiazines, and 4) both therapies with the addition of a p-Akt antagonist (LY294002 was injected into the lateral ventricle 30 minutes before ischemia). Infarct volume, neurological deficit, and apoptotic cell death were determined 24h post reperfusion. Expression of p-Akt, cleaved Caspase-3, pro-apoptotic (AIF & Bax) and anti-apoptotic proteins (Bcl-2 & Bcl-xL) was assessed by Western blot at 6h and 24h after reperfusion.

Results:
The combination of hypothermia and phenothiazines decreased (P<0.01) infarct volume and neurological deficit. This change was associated with a reduction (P<0.01) of apoptotic cell death. Each treatment alone did not induce significant neuroprotection. The combination therapy, but not each alone, promoted (P<0.01) the expression of p-Akt, accompanied with increased expression of anti-apoptotic proteins and decreased expression of pro-apoptotic proteins. The neuroprotective effects were blocked by p-Akt inhibition.

Conclusion:
Mild hypothermia-induced neuroprotection was enhanced by phenothiazines in an experimental ischemia/reperfusion injury model. This study supports the involvement of the PI3K/Akt signaling pathway. This novel therapeutic strategy could be developed as an effective treatment for acute ischemic stroke.
Abstract TP267: Protein Kinase C Epsilon-activation Mediates Ischemic Neuroprotection by Activating an Activity-regulated Cytoskeleton-associated Protein-dependent Mechanism
Authors: Cohan Charles H , Stradecki Holly M , Morris-Blanco Kahlilia C , Khoury Nathalie , Koronowski Kevin B , Youbi Mehdi , Wright Clinton B , Perez-Pinzon Miguel A
Published: June 2021

Introduction:
Cerebral ischemia can trigger cell death in the CA1 region of the hippocampus, an area important for memory. Protein kinase C epsilon (PKCε) activation prior to ischemia protects the CA1 from injury by modulating neurotransmission. The underlying mechanism needs further study.

Hypothesis:
PKCε-induced neuroprotection increases latency until anoxic depolarization (AD) through an activity-regulated cytoskeleton-associated protein (arc)-dependent mechanism of regulating AMPAR currents.

Results:
In vivo
activation of PKCε by the PKCε-activator ψε-Receptor of Activated C Kinase (ψεRACK) increased BDNF 5.99 +/- 0.11 fold and TrkB phosphorylation levels 2.94 +/- 0.32 fold (enhancers of arc protein levels) (n = 4, p < 0.005, t-test). Arc mRNA and protein was increased 143.97 +/-7.68 % and 1.91 +/- 0.22 fold (n = 9, p < 0.005, t-test). Inhibition of arc using antisense oligodeoxynucleotides (arc AS ODNs) in cultured slices blocked PKCε-mediated neuroprotection against lethal oxygen and glucose deprivation (OGD) from 35.91 +/- 5.97 to 74.93 +/- 4.24 % cell death (n = 6, p < 0.005, ANOVA, Bonferroni). ΨεRACK decreased AMPAR-mediated mEPSC amplitude to 12.75 +/- 0.35 pA from 14.80 +/- 0.39 pA (n = 20, p < 0.01, ANOVA, Bonferroni). This effect was arc-dependent. Additionally, ψεRACK treatment increased latency until AD from 29.27 +/- 3.6 min 50.77 +/- 5.08 min (n = 13, p < 0.01, ANOVA, Bonferroni). This increase was arc-dependent, and required AMPAR internalization. Inhibiting internalization reduced AD latency from 54.5 +/- 8.40 min to 22.3 + 5.17 min (n = 6, p <0.005, t-test).

Conclusion:
Arc expression is necessary for neuroprotection afforded by PKCε-activation, modulates excitatory synaptic strength, and increases latency until AD.

Methods:
Western blot:
Proteins (40 μg) were separated on a 12% SDS-PAGE gel.
Immunofluorescence
: 30 μm sections were incubated with 1:500 NeuN and 1:50 arc in PBS with 0.8% triton.
Cultured slices preparation
: sections from P9-11 rats were plated on inserts and cultured for 14 days.
PI measurements of cell death
: Slices were incubated in medium with 2 μg/mL PI.
mEPSC measurements
: Whole-cell voltage clamp was performed.
AD:
OGD, perfusate was switched to glucose free media, and bubbled with a 95% N
2
and 5% CO
2
gas.
Abstract TP272: Calcium Release-activated Calcium (CRAC) Channel Inhibition Protects Against Brain Injury and Neuronal Death Induced by Activated Microglia
Authors: Kacimi Rachid , Kim Jong Youl , Stauderman Ken , Dunn Michael , Hebbar Sudarshan , Yenari Midori A
Published: June 2021

Inflammatory responses following ischemia can worsen neurological outcome, and represent a potential target for therapeutic intervention. Store-operated Ca
2+
entry (SOCE) mediated by CRAC channels contribute to calcium signaling in immune cells. CRAC channels consist of the endoplasmic reticulum resident Ca
2+
-sensing protein stromal interaction molecule 1 (STIM1) and the calcium channel protein ORAI1 located in the plasma membrane. Prolonged Ca
2+
entry through CRAC channels activates, via calcineurin, nuclear factor of activated T cells (NFAT), involved in T cell proliferation and cytokine expression. Microglia mediate inflammation in the injured brain, but little is known about the role of CRAC channels in this process. We studied novel CRAC channel inhibitors to explore their therapeutic potential in microglia-mediated injury. A neuron cell line (Neuro-2A, N-2A) was cultured alone or with microglial BV2 cells then exposed to 2h oxygen glucose deprivation (OGD). Some cultures were treated with a novel CRAC channel inhibitor. Toll-like receptor (TLR) -3, -4 agonists or IFNγ were also used to activate microglia. Western blots revealed the presence of CRAC channel proteins STIM1 and ORAI1 in microglia. CRAC channel inhibition decreased NO release and inflammatory proteins iNOS and COX-2 expression in activated microglia, but did not affect STIM1 or ORAI1 expression. CRAC channel inhibitors also reduced agonist induced intracellular calcium accumulation in BV2 cells. Agonists also activated JNK1/2 kinase, NFAT, NF-κB, CREB & STAT1 in microglia, but only JNK1/2 kinase & NFAT were attenuated by inhibitor. OGD decreased N2A neuronal cell viability, further exacerbated by BV2 cells, but neuronal cells were protected by CRAC channel inhibition (n=5, *p<0.05). We then treated male C57/BL6 mice exposed to experimental brain trauma (TBI) and found that CRAC channel inhibition led to decreased lesion size, brain hemorrhage and improved neurological deficits (n=6-7/grp, *p<0.05). We suggest a novel anti-inflammatory approach for treating acute brain injury. Our observations also shed light on new calcium signaling pathways, not previously described in brain injury models.
Abstract TP278: Positive Impact of a Stroke Bundle Program
Authors: Murphy Deborah , Boyle Colleen , Della Monica Elissa , Peiritsch Heather , Schmidt Laura , Gzesh Dan
Published: June 2021

Introduction:
There are limited comparative data on the impact of a stroke bundle program on patient outcomes. We aimed to assess the magnitude of change that could occur during transitions of care process by implementation of a stroke bundle program.

Methods:
Six skilled nursing facilities (SNF) participated with a Joint Commission certified Comprehensive Stroke Center to implement a Bundled Payment Care Initiative (BPCI) program. The stroke leadership developed a charter and additional support teams (care coordination and SNF). Three smart goals were identified and reflected organizational strategic goals: reduction of the number of stroke patients that are admitted to a SNF by 5% (baseline 27.9%); reduction of preferred provider SNF days for stroke patients by 10% (baseline 35.5%) and reduction of hospital readmissions for stroke by 5% (baseline 31.5%). A strong infrastructure supported the care coordination teams including the hiring of a full time stroke nurse navigator. The kick off for the program was October 1, 2015. Several strategic and operational initiatives were developed and successfully implemented at SNFs: utilization of stroke clinical practice guidelines: stroke education programs; stroke summit for all SNF administrators, physicians and staff; bi-monthly, face to face/conference call meetings with SNF administrators and bundle team leadership; case reviews between caregivers at acute setting and SNF; SharePoint site to enhance communication; stroke nurse navigator interaction with patients, families, SNF staff, 90 day follow up and readmission case reviews.

Results:
Smart goal achievement over a 6 month period demonstrated: reduction of the number of stroke patients that were admitted to SNF by .4% (21.9%); reduction of preferred provider SNF days for stroke patients by 16% (16%) and reduction of hospital readmissions for stroke by 7% (23.3%). Comparison of hospital length of stay variance between bundle (3.78) and non-bundle patients (5.08) patients was 1.3%.

Conclusions:
A stroke bundle program impacts positively on transitions of care at preferred provider SNF facilities. Standardization of care and a unified care team attributes to stroke patients returning to their life at home in a much more efficient and timely manner.
Abstract TP279: Evaluation of Exclusions for Endovascular Intervention to Identify Clinical Practice Patterns
Authors: Patterson Michele , Birnbaum Lee , Motz Deb , Moore Tracy , Huey Dicky , Cline Beth , Austin Tommye
Published: June 2021

Background:
Our five-hospital Comprehensive Stroke Program utilizes a standardized large vessel occlusion (LVO) triage that includes NIHSS >10 and last known well <6 hours. When these criteria are met, the ED Physician and Neuro-interventionalist determine endovascular thrombectomy (ET) eligibility. If ET is not performed, standardized exclusion criteria is documented

Purpose:
To evaluate patterns in exclusions for ET and identify opportunities to expand treatments.

Methods:
A retrospective chart review of patients who arrived within 6 hours of symptom onset over a 4- month period was conducted. Patients were divided into two groups: those who received ET and those who did not. Documented exclusions were evaluated to identify clinical practice patterns.

Results:
Of the 52 patients who arrived within 6 hours of symptom onset, 81% (n=42) did not receive ET. Fifty-seven percent (n=24) were excluded due to deficits too mild (NIHSS < 10) and 43% (n=18) had NIHSS > 10 with documented exclusions. Exclusions included 1) Lack of LVO 56% (n=10); 2) Rapid improvement or mild symptoms 6% (n=1); 3) Refusal by the patient/family 11% (n=2); 4) Other reasons documented by the physician 27% (n=4). Other reasons included CTP findings of complete infarct (1), poor collaterals with large clot extension (1), unable to access common carotid occlusion (2). None of the patients were excluded due to elevated creatinine or advanced age. Exclusions were documented by 1) Neuro-interventionalist 72% (n=13;) 2) ED Physician 6% (n=1;) 3) Primary Care 6% (n=1); 4) Radiology CTA report 16% (n=3).

Conclusions:
The most common reasons for ET exclusion in our cohort are non-modifiable: absence of LVO and unfavorable imaging characteristics. We identified patient/family refusal as a less common exclusion reason but one that may warrant education. Continued data collection is needed to further understand exclusion patterns and improve identification of patients that could benefit from ET.
Abstract TP288: Overcoming Obstacles Making People Healthy (OOMPH): A Patient Centered Post Discharge Follow-up Program for Stroke Patients
Authors: Muller Jonathan , Gatton Barbara , Fox Linda , Bove Joseph A , Donovan Turner Johanna , Spadaro Matthew , Aggarwal Sanket , Melville Laura , Melniker Lawrence , Gaeta Theodore , Bove Joseph , Salgado Miran
Published: June 2021

Background and Purpose:
At least 12% of stroke patients are readmitted to a hospital within 30 days of discharge. We know that patients hospitalized for other conditions are less likely to be readmitted within 30 days if they are seen by their PCP shortly after discharge. However, less than a third of patients in the New York metropolitan area admitted for heart failure, heart attacks, and pneumonia see their PCP within 14 days after discharge and nearly 40% of patients do not adhere to their prescribed regimen. In the case of cerebrovascular diseases, outpatient follow-up may prevent the majority of avoidable readmissions. The purpose of this project is to identify and reduce unnecessary, unplanned hospital readmissions after stroke. Our goal is to encourage patient adherence to prescribed medication and other therapies, as well as to ensure timely follow-up with their PCP.

Methods:
Stroke and transient ischemic attack (TIA) patients with a disposition of either home or short-term rehabilitation are visited and offered enrollment. Participants are given a kit which includes a personalized binder (to manage essential medical information) and a 28-slot pill box. Each patient then receives 3 phone call interviews at 7, 21 and 32 days after discharge. The aim of the phone calls is to identify obstacles to compliance with treatment regimen and follow-up care.

Results:
From January 2015 to June 2016, 247 patients were enrolled and followed up. Within 30 days of discharge, 10% were readmitted and 50% of all readmissions occurred within the first 7 days. Of those readmitted, 19% were due to an injury from physical therapy. Data from follow-up phone calls revealed that 83% were taking all prescribed medications, 89% had completed a follow-up with any physician, 69% were using the binder, and 61% had done all three.

Conclusions:
While we have not enrolled enough patients to see a statistically significant reduction in readmissions, our interviews showed that weather, depression, as well as a lack of insurance, family support, and a home health aide are all determinants on how patients will follow their prescribed regimen. The results of this study have allowed us to begin implementing stroke support groups and pre-discharge follow-up appointment scheduling.
Abstract TP291: Swallow Screens: A Hard Act to Follow a Collaborative Effort Between the Stroke Program and the Emergency Department
Authors: Paletz Laurie B , Eichelzer Gregory , Ip Herbert , Steiner Nili , Robertson Betty , Wolber Nicole , Guerra Sonia
Published: June 2021

Background:
After stroke, up to 65 percent of stroke patients suffer dysphagia, with increased risk of aspiration pneumonia and disability. Aspiration risk is reduced by swallow assessment on every acute ischemic stroke (AIS) prior to medication or food intake. Annually, about 88,000 patients enter the Cedars-Sinai Emergency Department (ED).
Although only 1% of these patients are AIS, 100% of these patients require a swallow screen.
In busy EDs where stroke is infrequent, swallow screens are missed. Jointly with our ED Educator and our Electronic Information Systems (EIS) application specialist we created a user-friendly, reliable solution to improve swallow screen compliance in the ED.

Purpose:
To implement a valid swallow screening tool and optimize nurse awareness and compliance in a busy, urban ED.

Method:
We emphasized educating and listening to staff concerns and requests and collaboration with EIS. The Barnes Jewish Hospital stroke screening tool is a validated, evidence based screening tool for assessing swallowing. We defined “fall outs” as patients who received anything by mouth prior to a swallow assessment. EIS created an electronic alert linked to chief complaints that fired in response to a wide range of stroke symptoms. The alert was also linked to the medication administration record.

Result:
Prior to deployment, fall outs ranged from 40 to 65% of cases. Following deployment of the alert fall out numbers decreased (see graph) significantly (Chi-Square p<0.001 for trend), despite an overall increase in AIS volumes. While education was somewhat successful, linking the alert to the MAR prompted the nurse to complete the swallow screen prior to administering oral medications.

Conclusion:
We successfully improved ED compliance with swallow screening in a busy urban ED in which AIS represents less than 1% of the annual volume. A similar strategy should work well in a variety of other hospitals and medical centers.
Abstract TP292: Patient Reported Outcomes in Stroke Clinical Trials
Authors: Carr Christopher , Reddy Laya , Hussain Azad , Murray Sean , Vazirani Neha , Bazzano Lydia , Price-Haywood Eboni
Published: June 2021

Stroke is the 5
th
-leading cause of death in the US and the major cause of disability. Many patients who have suffered from strokes are left with permanent neurological deficits, new occupational and social difficulties, and reductions in quality of life that may be idiosyncratic or vary considerably from patient to patient. Solicitation of patient reported outcomes (PROs) in the treatment and recovery from strokes is therefore imperative. We examined a list compiled in 2013 for
Stroke
by Magin et al. of representative stroke-related, randomized clinical trials published in 10 high-impact journals between 2002 and 2012 to assess whether PROs were collected and which constructs were reported. We categorized PRO measures as stroke-specific (e.g. Stroke Impact Scale), health profile and utility scales (e.g. Beck Depression Scale), or general (e.g. pain visual analog scale). Two reviewers independently abstracted PRO measures from each article and disagreements were resolved by consensus. Fisher’s exact test was used for statistical analyses. Of the 99 articles that met study inclusion criteria, 20% concerned prevention, 22% acute treatment, and 58% rehabilitation. A plurality of trials were European (43%) followed by studies based in the US (25%), Asian countries (10%), and Australia (10%). Altogether, 37% of studies used a PRO of any kind. Stroke-specific PROs were collected in 17% of studies, health profile and utility scales were used in 17%, and general PROs were used in 23%. There were no significant differences in PRO use with regards to year of publication or study location. Health profile and utility scales (p=0.01) and unclassified PROs (p<0.001) were most-commonly reported in rehabilitation trials. Stroke-specific PROs were most commonly published in the journals
Brain
and
Journal of Stroke and Cerebrovascular Diseases
(p=0.001). Overall, our review and analysis detected a low prevalence and a large degree of heterogeneity of PRO measures reported in stroke-related clinical trials. Future stroke research must routinely incorporate PROs into the study design to help patients, caregivers, and providers make informed decisions about stroke prevention, treatment, and rehabilitation options that yield outcomes of greatest importance to them.
Abstract TP293: Errors in Estimation of Body Weight in Thrombolysis for Acute Ischemic Stroke
Authors: Lee Vivien H , Cutting Shawna , Cherian Laurel , Conners James J , Song Sarah Y , Ouyang Bichun , Garg Rajeev , Bleck Thomas P , Osteraas Nicholas D
Published: June 2021

Introduction:
Intravenous tissue plasminogen activator (IVtPA) is a proven treatment in acute ischemic stroke but relies on weight-based dosing in a time sensitive manner. Errors in body weight estimation are common and may result in over or under-dosing of IVtPA.

Methods:
With IRB approval, we prospectively screened 99 consecutive patients who received IVtPA for suspected acute ischemic stroke from November 1, 2015 to July 1, 2016 as part of a prospective IVtPA study. Patients were included in this analysis who had complete data. Data was collected on patient demographics, National Institutes of Health Stroke Scale (NIHSS), body weight, and times of last known normal (LKN) and IVtPA administration. A significant error in IVtPA dosing was defined as a >10% difference in actual versus calculated IVtPA dose.

Results:
Among 42 patients prospectively enrolled, the mean age was 65.8 years (range, 32 to 89) and 30 (79%) of patients were transfers from outside Emergency Rooms. Mean time from LKN to IVtPA administration was 2.4 hours (range. 0.7 to 4.8). Initial pre-IVtPA mean NIHSS was 14 (range, 3 to 26). The mean % error in IVtPA dose was +1.9% (range, -29% to + 21%). Ten patients (24%) had a significant error in IVtPA dosing of > 10% of the dose, and 8 (80%) were over-doses. Patients with significant IVtPA dosing error did not differ in terms of age (65.8 vs 65.8, p 0.99), sex (female 55.6% vs 38.9%, p 0.45), race (white 70% vs 47%, p 0.28), height (164.8 vs 171.0 cm, p 0.1), or time from LKN to IVtPA (2.8 vs 2.3, p 0.15). Patients with significant IVtPA dosing errors had significantly lower baseline weight (70.3 vs 90.0 kilograms, p 0.029) and higher NIHSS (18.7 vs 12.6, p 0.018).

Conclusion:
Dosing errors of > 10% of the calculated IVtPA dose occur in nearly one-quarter of acute stroke patients treated in the community, and patients with lower weight and higher NIHSS were at higher risk of dosing errors.
Abstract TP294: Effect of Educational Level on Atrial Fibrillation Patients’ Knowledge and Perceptions About Oral Anticoagulation Therapy: Results From an International Study
Authors: Lane Deirdre A , Meyerhoff Juliane , Rohner Ute , Lip Gregory Y
Published: June 2021

Introduction:
Previous research has demonstrated that patients with atrial fibrillation (AF) have limited knowledge of AF, stroke and oral anticoagulant (OAC) treatment. This analysis assessed the effect of educational level on stroke knowledge, AF perception, concern about stroke, OAC treatment preferences and adherence.

Methods:
This was a cross-sectional, prospective survey of 936 adult patients (mean (SD) age 54.3 (16.6) yrs; 37.2% female) with AF on OACs in the USA, Canada, Germany, France and Japan. Three groups were included: AF with recent stroke (≤ 6 m); new onset AF (≤ 6 [ ≤ 12 m in Japan]) without recent stroke; established AF (7-24m [1-3yrs in Japan]) without recent stroke. Open-ended questions determined stroke knowledge, assessed according to a predefined scoring system. Patients were grouped according to educational level: no school-leaving certificate (low), high school diploma, community college and university/technical college.

Results:
Stroke knowledge was similar in all patients regardless of educational level.

A greater proportion of patients with college education were ‘always’ or ‘often concerned’ about stroke, whereas a greater proportion of those with low levels of education were ‘never concerned’ about stroke (or didn’t know).

Educational level had no effect on self-reported OAC adherence or patient preference to be involved in OAC treatment decisions. Patients with no school leaving certificate perceived taking medication (all drugs) as a ‘major burden’ (25.9%), while significantly more patients with college/university education did not view taking medication as burdensome (38.5% and 50.4% versus 37.0%, respectively; Table).

Conclusions:
Education influenced patients’ perceptions of the seriousness of AF, frequency of concern about stroke and perceived burden of medication. Educational attainment did not affect level of stroke knowledge, OAC adherence and desire to be involved in OAC treatment decisions.
Abstract TP299: Development and Validation of a Patient Centered Young Stroke Outcome Measure Tool
Authors: Duda Julian , Duda Viktoriya , Suttman Erin , Kodumuri Nishanth , Giamberardino Lauren D , Edmunds Amy L , Sen Souvik
Published: June 2021

Introduction:
Stroke is a leading cause of adult disability that has long-term impact on outcome of patients. The current outcome measures are felt to be inadequate in measuring the impact of stroke in young patients (≤65) in midst of managing education, career, and family.

Methods:
This study assessed the reliability and discriminate validity of the young stroke questionnaire (YSQ). The development framework of the YSQ involved a two-step process. Initial feedback from stroke survivors and healthcare providers via multiple focus groups helped identify questions used to measure impact of stroke on 4 patient-centered domains: work and leisure, relationships, wellbeing, and healthcare resources. A subsequent focus group prioritized and refined items on the final YSQ. To determine the reliability and discriminate validity of YSQ, 25 young stroke survivors were consented at the Neurology Clinic. Standardized clinical assessments completed included the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and the Stroke Impact Scale (SIS). Additionally, all patients were asked to complete the patient-centered questionnaire, YSQ.

Results:
Of 48 ischemic stroke patients screened, 25 (Mean age ± SD = 51 ± 9.2, 36% Males, 40% African-American, 56% White) patients qualified for enrollment into the young stroke questionnaire validation study. Using Levene’s test for equality of variance to compare YSQ and standardized clinical assessments, the YSQ was more likely to detect patient-centered disabilities post stroke in the following domains: relationships (α = 0.035) and healthcare resources (α = 0.027). Reliability of the summary measure was assessed using Cronbach’s alpha and found to be high (α = 0.903), indicating that the index created by summing the 4 dimensions is internally consistent and reproducible.

Conclusions:
Standardized clinical assessments are not sensitive to disabilities in young stroke survivors. When compared to standardized clinical assessments, the young stroke questionnaire is significantly capable of differentiating the young survivor perspective of the impact of stroke, specifically in area of relationships and healthcare resources.
Abstract TP316: Early Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Infarction in Asian Patients
Authors: Paliwal Prakash R , Yeo Leonard L , Chan Bernard P , Teoh Hock L , Seet Raymond , Lwin Sein , Yeo Tseng T , Chou Ning , Sharma Vijay K
Published: June 2021

Background and purpose:
Decompression craniectomy in acute malignant middle cerebral artery (MCA) ischemic stroke (IS) reduces mortality. However, its role in reducing disability in this group of patients is often questioned in the stroke community since previous studies have employed variable time intervals for surgical decompression as well as criteria for defining severe disability. We evaluated our Asian cohort of acute IS patients for determining the factors associated with favorable functional outcome.

Methods:
Data for all acute IS patients hospitalized to our tertiary center were entered into a prospectively maintained registry. In this retrospective analysis, data for all malignant MCA IS patients who underwent decompressive hemicraniectomy were extracted. Various demographic, clinical and neuroimaging factors were analyzed for identifying independent predictors of favorable functional outcome at 6 months, which was defined as modified Rankin Scale of 0-3.

Results:
From January 2005 to December 2014, a total of 75 patients with anterior circulation IS underwent decompressive hemicraniectomy. Median age was 55 years (IQR 44-64) with male preponderance (66%) and median NIH Stroke Scale (NIHSS) score 21 points (IQR 18-24). Considerable proportion of them (60%) received intravenous thrombolysis with tissue plasminogen activator (IV-tPA). Majority (70%) of patients suffered from acute right MCA IS and median time from symptom-onset to surgery was 31 hours (range18-51). Decompressive surgery was performed within 48 hours of symptom-onset in 50 (67%) of the patients. Favorable functional outcome was achieved by 25 (33.3%) patients at 6 months. Right sided stroke (OR 5.333; 95% CI 1.359- 20.927, p=0.016 ) and early decompression surgery (performed within 48 hours from symptom-onset (OR 3.636; 95% CI 1.032- 12.809, p=0.045 ) were independent predictors of favorable functional outcome at 6 months.

Conclusion:
Early decompression craniectomy, especially in right MCA ischemic stroke is associated with better favorable functional outcome at 6 months.
Abstract TP334: Admission Neutrophilia is Not a Predictor of Hematoma Expansion in Deep Nuclei or Lobar Supratentorial Intracerebral Hemorrhage
Authors: Ryder Jessica A , Iwuchukwu Ifeanyi , Feliciano Philip , Mahale Nikit , Jennings Bethany , Nguyen Doan , Sulaiman Olawale
Published: June 2021

Background and Purpose:
Hematoma expansion of intracerebral hemorrhages (ICH) is associated with poor patient outcomes. However, the true mechanism remains unclear. Previous studies have investigated the role of admission leukocytosis and neutrophilia in predicting poor outcomes in patients admitted with ICH. In these studies, deep and lobar ICH, which have different pathophysiologies, were not distinguished. In our study, we aim to investigate the value of admission neutrophilia (AN) in predicting hematoma expansion in patients with deep ICH and lobar ICH.

Methods:
We performed a retrospective review of a prospective database of patients admitted with ICH between November 1, 2012 and March 31, 2016. We included patients with ICH confirmed by CT imaging admitted for a minimum of 24 hours. Patients were excluded if etiologies included trauma, primary or metastatic brain tumors, evidence of hemorrhagic conversion from ischemic stroke, and vascular malformations. In addition to demographic and clinical data, we collected data on primary ICH location and volume, volume after 24 hours, and admission leukocyte and neutrophil counts. We defined AN as a neutrophil count >7.7 K/μL. Hematoma expansion was defined as an increase of >30% on the 24 hour repeat imaging. Basal ganglia and thalamic ICH were classified as deep ICH.

Results:
Of the 573 patients admitted with ICH, 432 who met inclusion criteria were included for our analysis. 153 (41.3%) had deep ICH and 217 (58.6%) had lobar ICH. The presence of AN was significantly different between deep vs lobar ICH (47.7% vs 27.6% p=0.0001). Among these patients, larger initial hematoma volume was found in lobar ICH as compared with deep ICH (67.2ml (SD 51.0) vs 44.6ml (SD 50.5) p=0.003). However, the frequency of hematoma expansion was not significantly different between groups (12.3% vs 15.2% p=0.87). On multivariate analysis, AN was not an independent predictor of hematoma expansion in deep, lobar or both groups combined.

Conclusion:
Contrary to previous reports, AN is not an independent predictor of hematoma expansion. This suggests that the pathophysiological process leading to hematoma expansion is likely multifactorial.
Abstract TP339: Simultaneous Multiple Intracerebral Hemorrhages (SMICH)
Authors: Wu Teddy , Yassi Nawaf , Shah Darshan , Ma Minmin , Sharma Gagan , Putaala Jukka , Strbian Daniel , Campbell Bruce , Tatlisumak Turgut , Desmond Patricia , Davis Stephen , Meretoja Atte
Published: June 2021

Background and Purpose:
Simultaneous multiple intracerebral hemorrhages (SMICH) are uncommon. Few single center studies have analyzed characteristics and outcome of SMICH. We analyzed clinical characteristics and outcome of SMICH patients from two comprehensive stroke centers.

Methods:
Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study were screened for SMICH. ICH etiology was classified according to the SMASH-U classification system. ICH due to trauma, tumor and aneurysmal rupture were excluded. Baseline clinical and radiological characteristics and 90-day mortality were compared between SMICH and single ICH patients. Association of SMICH with 90-day mortality was assessed in multivariable logistic regression models adjusted for predictors of ICH outcome.

Results:
1452 patients were included in the analysis and 85 (5.9%) were classified as SMICH. SMICH were more often female (58% vs 42%;p=0.004), had lower baseline Glasgow Coma Scale (12 vs 14;p=0.008), and more frequent lobar location (59% v 34%;p<0.001) compared to single ICH. The SMASH-U etiology of SMICH patients was less often hypertensive (20% vs 37%;p=0.001), more other systemic coagulopathy (12% vs 3%;p<0.001) and trended towards more cerebral amyloid angiopathy (32% vs 23%;p=0.071). SMICH was not associated with 90-day mortality on univariate (37% vs 35%;p=0.635), multivariable (OR 0.783 95%CI 0.401-1.529;p=0.473), or propensity score matched analyses (OR 0.817 95% CI 0.400-1.668,p=0.578).

Conclusion:
SMICH occurs in approximately 1 in 20 ICH with more often lobar located hematomas, less often hypertensive and associated with more systemic coagulopathy. The mortality is similar to single ICH. Given varied etiologies, SMICH management should target the underlying pathology.
Abstract TP344: Stat6 Signaling in Microglia/macrophage is Critical for Functional Recovery After Intracerebral Hemorrhage
Authors: Xu Jing , Cai Wei , Zhang Kai , Liu Huan , Shi Yejie , Pu Hongjian , Hu Xiaoming , Chen Jun
Published: June 2021

Objective:
Intracerebral hemorrhage (ICH) is a devastating medical condition that remains a leading cause of death and long term disability in the US. Hematoma triggers a cascade of signaling events resulting in secondary brain injury and severe neurological deficits. Microglia and macrophage are activated within minutes after ICH, which may influence stroke outcome by clearing the hematoma and regulating neuro-inflammation. However, the molecular mechanism underlying the functional regulation of microglia and macrophages in ICH is poorly understood. The current study was designed to test the role of signal transducers and activators of transcription 6 (STAT6) in microglia/macrophage functions in a mouse model of ICH.

Methods:
Male adult WT and STAT6 KO mice were subjected to intrastriatal collagenase (0.075U) injection. Spatial and temporal profiles of STAT6 activation after ICH were determined by double-label immunostaining of phospho-STAT6 and cell markers. Neurobehavioral performances were assessed using rotarod, foot fault and water maze tests up to day 21 after ICH. Gray and white matter injury was examined quantitatively on sections stained with antibodies against MAP2/NeuN and MBP, respectively. Microglial phagocytosis of fluorescent labeled-red blood cells was evaluated
in vitro
by immunofluorescence and flow cytometry.

Results:
Robustly enhanced expression of phospho-STAT6 was found predominantly in Iba1
+
cells, starting at day 1, peaking at day 5, and lasting for at least 14 d after ICH. STAT6 KO mice exhibited exacerbated sensorimotor and spatial learning and memory deficits compared to WT mice (
P
<0.05). STAT6 KO mice also showed larger neuronal tissue loss and more severe white matter injury (
P
<0.01). Hematoma resolving was slower in STAT6 KO mice than WT mice (
P
=0.03). In cultures, primary microglia derived from STAT6 KO mice had 52.6% reduction of phagocytic activity compared to WT microglia (
P
=0.006).

Conclusions:
STAT6 is activated in microglia/macrophage after ICH and plays a critical role in ameliorating gray and white matter injury and facilitating post-stroke neurological recovery. STAT6-afforded neuroprotection against ICH may be attributable, at least in part, to the enhanced hematoma clearance by phagocytes.
Abstract TP348: Quantitative Serial Neuroimaging of Iron in the Intracerebral Hemorrhage Pig Model
Authors: Haque Muhammad E , Gabr Refaat E , Zhao Xiurong , Hasan Khader M , Narayana Ponnada A , Nghiem Duyen M , Savitz Sean I , Aronowski Jaroslaw
Published: June 2021

Objective:
To serially quantify changes of iron concentration within hematomas in the intracerebral hemorrhage (ICH) pig model using non-invasive R2* and quantitative susceptibility mapping (QSM) MRI methods.

Introduction:
Hemolysis-related release of hemoglobin/heme/free iron after ICH causes cytotoxic injury. An accurate post hemorrhage assessment of iron would be valuable to develop strategies to prevent secondary damage. The T2* relaxation rate (R2* =1/T2*) on MRI depends on the regional oxy- versus deoxyhemoglobin. Post-ICH excess of deoxyhemoglobin has been applied as a quantitative marker to estimate iron in the brain. However, quantitative susceptibility mapping (QSM) is a new MRI technique that can quantify iron concentration within the hematoma by measuring induced magnetic susceptibility. Using R2* mapping and QSM in a large animal ICH model, we measured spatiotemporal changes in iron concentration in the brain.

Methods:
Lobar ICH was induced by infusion of 2.5 ml autologous blood in 8 Yorkshire pigs with average age/wt of 4-6wk/12.5±2.5kg. MRI was obtained at days 1 and 7. A 3D anatomical and multi-echo gradient echo images were obtained on a clinical 3.0 T Philips Ingenia MRI system. Parametric R2* and susceptibility maps were generated. Regions of interest were placed within hematoma and contralesional CSF.

Results:
R2* measurements in the hematoma at day 1 and day 7 were 41.3 ± 7.3 and 37.7 ± 7.7 s
-1
, respectively, whereas the corresponding susceptibility measurements were 0.75± 0.3 and 0.70 ± 0.5 ppm. The CSF R2* were 5.53 ± 2.1 and 6.85 ± 2.4 s
-1
, whereas susceptibility showed 0.06 ± 0.16 and 0.02 ± 0.03 ppm at the two time points. Both R2* and QSM showed no significant change in iron concentration within the hematoma ROI with p-value of 0.18 and 0.72 over a week. Absence of hyperintense regions remote from the hematoma in susceptibility maps suggested lack of diffuse iron deposition. Good correlation was observed between R2* and QSM (correlation coefficient 0.83 and 0.78 within hematoma, and -0.66 and -0.07 within CSF, at day 1 and 7, respectively).

Conclusion:
R2* and especially QSM, with their ability to provide quantitative iron content, are valuable tools to test new ICH treatments particularly targeting iron in this large animal model.
Abstract TP351: Axl/Mer Receptor Tyrosine Kinase Mediates Erythrophagocytosis-Induced Macrophage Reparative Phenotype and Brain Recovery in Experimental Intracerebral Hemorrhage
Authors: Chang Che-Feng , Thomas Brittany A , Askenase Michael , Steinschneider Arthur F , Ai Youxi , Taylor Roslyn , Rothlin Carla V , Love Christopher J , Sansing Lauren H
Published: June 2021

Introduction:
Local inflammation contributes to both brain injury and recovery after intracerebral hemorrhage (ICH). Our previous studies have shown brain-infiltrating macrophages (BIMs) aggravate early brain injury after ICH; however, BIMs increase scavenger receptor CD36 levels over time, and hematoma clearance is delayed in the absence of BIMs. The mechanism that mediates BIMs phenotypic change in the ICH brain is elusive. In this study, we delineate the dynamic transcriptome profile of BIMs after ICH and test potential mediator that might modulate BIMs polarity in ICH.

Methods:
Autologous blood injection ICH model and thrombin-treated bone marrow-derived macrophages (BMDM) were used to mimic ICH
in vivo
and
in vitro
. BIMs were isolated by FACS, and the 780 transcriptome of BIMs were determined using NanoString. Flow cytometry and RT-qPCR were performed to detect the frequency of phosphatidylserine-positive (eryptotic) RBCs and to assess BIMs phenotype in the perihematomal tissue. Erythrophagocytosis of eryptotic RBCs was identified by immunofluorescence and microscopy. Neurologic deficit was evaluated by cylinder test. Axl/Mer receptor tyrosine kinase double knockout (AM DKO) mice, AM DKO bone-marrow chimeras, and AM DKO BMDM were used to evaluate the function of Axl/Mer on macrophage phenotype and on brain recovery after ICH.

Results:
BIMs highly expressed proinflammatory transcripts such as
cd86
,
tlr2
,
nlrp3
, and
tnf
at days 1 and 3 post-ICH; these were decreased at days 7 and 10. Transcripts relevant to efferocytosis (
axl
) and lysosome formation (
cd63
) increased from days 3 to 10 post-ICH. At days 1 and 3, phosphatidylserine levels was increased on RBCs in the ICH brain. Engulfment of eryptotic RBCs reduced proinflammatory phenotype of BMDM. Thrombin-stimulated AM DKO BMDM had reduced erythrophagocytosis ability and increased
tnf
and
il-6
gene expression. AM DKO mice and AM DKO chimeras had low CD36 and high MHC II levels on BIMs and had worse functional outcome after ICH.

Conclusions:
BIMs initially express proinflammatory phenotype and then switch to a reparative phenotype after ICH. Axl/Mer is involved in regulation of macrophage polarity through modulating erythrophagocytosis ability and contributes to ICH brain recovery.
Abstract TP366: Improving Transitions of Care with a Daily Rounding Tool
Authors: Richardson Melissa , Clarke Tyan
Published: June 2021

Background:
Patients who experience acute stroke often have complex discharge planning needs that impact transitions of care. The hectic acute care hospital environment is not always conducive to addressing these needs in a standardized fashion.

Purpose:
To improve communication among team members and identify potential post-acute needs early in the hospital stay. Ultimately we hoped to have a positive impact the readmission rate and the patient experience.

Methods:
We designed a structure for daily rounds, identifying who would attend, setting clear expectations, and having a consistent schedule. We piloted a paper based check list that would serve as a guide to the dialogue during daily rounds to ensure that the team addressed key issues in a step wise, standardized fashion. This process also included the patients and families and their goals of care.

Results:
Readmissions were reduced from 15.4% to 10.9%. HCAHPS scores improved, specifically "Discharge Information" from 70% to 94% and "Communication with Nurses" from 46% to 83%.

Conclusions:
For a patient population with complex discharge needs, transitions of care can be improved by implementing a daily rounding checklist. This could positively impact the readmission rate and the patient experience.
Abstract TP369: EMS and ED Feedback Tool: Improving Metrics and Patient Outcome
Authors: Russell Angelia F , Tilem Matthew E , Voetsch Barbara V
Published: June 2021

Background:
Prompt recognition by emergency medical services (EMS) and emergency department (ED) triage is paramount in the treatment and survival of the stroke patient. We hypothesized that providing prompt feedback to EMS and ED on stroke care may improve EMS and hospital metrics and raise the hospital’s defect free care.

Objective:
To determine if the feedback provided to EMS and ED would improve the metrics and patient outcome.

Method:
A retrospective analysis comparing the percent of patients met the metrics prior to and after initiation of the feedback tools. Feedback forms were developed May 2015, education provided on forms Jun 2015, and implemented Jul 2015. Feedback was provided on all patients called in as a SA, BA on arrival, and/or patients with a discharge diagnosis of stroke.

Results:
Comparing the first six months prior to the feedback tool (127 BA in ED and 31 EMS SA) with the six months after (173 BA in the ED and 79 EMS SA) the Get with the Guideline (GWTG) timeline goals in the ED improved (Time of Arrival (TOA) to MD, goal 10 minutes, May 2015 35% to Dec 2015 100%; TOA to Neurology Consult, goal 15 minutes, May 2015 65% to Dec 2015 82%; TOA to Cat Scan (CT), goal 25 minutes, May 2015 41% to Dec 2015 79%; TOA to CT read, goal 45 minutes, May 2015 12% to Dec 2015 71%; TOA to t-PA, goal 60 minutes, May 2015 0% to Dec 2015 80%; CT ordered as a stroke, May 2015 21% to Dec 2015 84%; dysphagia screening prior to by mouth, May 2015 29% to Dec 93%) and the number of stroke alerts increased (pre-notification rates Q1/Q2 26.3%; Q3/Q4 56.8%). The hospital’s stroke defect free care in Q1/Q2 (77.3%) increased in Q1/Q2 2016 (97.2%). With the improvements in the EMS, ED, and hospital metrics, length of stay (LOS) decreased (Q1/Q2 5.77 days to Q3/Q4 5.05 days) and more patients were discharged with a lower modified Rankin Scale (mRS) (Q1/Q2 mRS 0-3 33%; Q3/Q4 mRS 0-3 48%).

Conclusion:
The EMS and ED metrics improved and continue to improve despite a growing and thriving neurology service. By providing the stroke care feedback, EMS and ED developed a more vested interested in the patient’s outcome. Based on the response from the EMS and ED staff on the stroke feedback tools, it is the most expedient and efficient way to communicate and continually educate on the care of the stroke patient both pre-hospital and in hospital.