bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP31: Endovascular Treatment Decision Making in Octo- and Nonagenarians: Insights From UNMASK EVT, an International Multidisciplinary Study
Authors: Kashani Nima , Ospel Johanna M , Almekhlafi Mohammed , Menon Bijoy , Singh Ravinder , Saposnik Gustavo , Hill Michael D , Goyal Mayank
Published: June 2021

Background and Purpose:
Efficacy and cost effectiveness of EVT in elderly stroke patients (≥80 years) is controversial, since they were underrepresented in randomized trials. We sought to explore how physicians approach endovascular therapy decision-making in octo- and nonagenarians under their current local resources and investigated how they would change their treatment decision under assumed ideal conditions, i.e. without external (monetary or infrastructural) limitations.

Methods:
In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 out of a pool of 22 case-scenarios with different evidence levels for EVT, 4 of which involved octogenarians and 2 nonagenarians, and asked how they would treat the patient in the given scenario A) under their current local resources and B) under assumed ideal conditions, i.e. with no external restraints. Decision rates were calculated and clustered multivariable regression analysis performed to determine adjusted measures of effect size.

Results:
Most physicians across the world decided to treat patients > 80 years with EVT (figure). In octogenarians, physicians decided in favor of EVT in 76.7% (all of which were level 2B evidence scenarios) under current local resources and in 80.2% under assumed ideal conditions. In nonagenarians, 74.0% decided in favor of EVT under current local resources (level 1A scenarios: 87.7%, level 2B scenarios: 60.3%) and 79.2% would offer EVT under assumed ideal conditions (level 1A scenarios: 91.3%, level 2B scenarios: 67.2%). Age was not a significant predictor for treatment decision under current local resources (OR 1.00, p=.317) and under assumed ideal conditions (OR 1.00, p=.708).

Conclusion:
The vast majority of physicians participating in this survey decided to offer EVT to acute ischemic stroke patients above 80 years.
Abstract WP311: Bilateral Common Carotid Artery Stenosis Induces Cardiac Dysfunction in Mice Which is Exacerbated in Mice Deficient in Endothelial Nitric Oxide Synthase
Authors: An Lulu , Chopp Michael , Shen Yi , Venkat Poornima , Chen Zhili , Zacharek Alex , Li Wei , Qian Yu , Landschoot-Ward Julie , Chen Jieli
Published: June 2021

Background:
We investigated whether bilateral common carotid artery stenosis (BCAS) induces cardiac dysfunction in the absence of primary cardiac disease in mice, and whether deficiency of endothelial nitric oxide synthase (eNOS) exacerbates cardiac dysfunction in mice subjected to BCAS.

Methods:
Male, middle-aged (6-8 month), wild type (WT) and eNOS knockout (eNOS-/-) mice were subjected to sham surgery or BCAS using microcoils (0.16mm internal diameter)(n=6 per group). Cardiac function was measured at day 30 after surgery using echocardiography. Immunostaining was employed to assess inflammatory factor expression in the heart.

Results:
1) Compared to WT-control mice, WT-BCAS mice exhibited significant cardiac dysfunction identified by decreased Left Ventricular Ejection Fraction (LVEF) and Ventricular Ejection Fractional Shortening (LVFS), increased cardiomyocyte apoptosis and CD45+ inflammatory cell infiltration.2) Compared to WT-BCAS mice, eNOS-/-BCAS mice exhibited significantly exacerbated cardiac dysfunction identified by decreasing LVFS, increased CD45+ inflammatory cell infiltration into heart tissue, and decreased CD206+ anti-inflammatory cell expression in the heart.

Conclusions:
BCAS induces cardiac dysfunction in the absence of primary cardiac disease in mice, and mice deficient of eNOS subjected to BCAS exhibit exacerbated cardiac dysfunction and inflammatory factor expression.
Abstract WP313: Liposomes With Anti-Fibrin Protein Binders to Target Clot in Stroke
Authors: Mikulik Robert , Petroková Hana , Mašek Josef , Kuchar Milan , Vítecková Wünschová Andrea , Štikarová Hana , Bartheldyová Eliška , Kulich Pavel , Hubatka František , Kotoucek Jan , Turánek Knotigová Pavlína , Vohlídalová Eva , Macaulay Stuart , Dyr Jan E , Raška Milan , Malý Petr , Turánek Jaroslav
Published: June 2021

Introduction:
Direct clot targeting represents attractive concept for clot imaging as well as targeted delivery of drugs, e.g. thrombolytics. Small protein binders attached to nanoliposomes may target thrombi and deliver drugs although selective affinity to fibrin and not fibrinogen is the main challenge.

Methods:
For identification and preparation of fibrin-specific artificial protein binders derived from scaffolds of albumin-binding domain (ABD) of streptococcal protein G, a highly complex ABD-derived combinatorial library in combination with ribosome display selection was used. In vitro models were used to document delivery of nanoliposomes to human thrombi.

Results:
A recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptides of the Bβ chain fused to TolA protein carrying polyhistidylated tag and Avitag was constructed. Ribosome display was followed by large-scale ELISA screening of protein binders. Only four protein variants had selective affinity to human fibrin - see figure 1A. The most selective, variant D7, was modified by C-terminal FLAG/His
6
or His
6
/His
6
tag in order to be attached onto the surface of nanoliposomes. The electron microscopy then confirmed the structure of nanoliposome-binder particles. Isothermal titration calorimetry provided dissociation constant for liposome-binder metallochelating bond in the range 10
-7
to 10
-9
for mono- and double-HisTag forms. In vitro, in silicone replica of small diameter artery, the confocal and scanning electron microscopy confirmed a successful binding of D7-attached- to-nanoliposomes to fibrin fibres, see figure 1B.

Conclusions:
We developed binders relatively selective to fibrin, attached them to nanoliposomes, and documented targeting of fibrin in vitro. As the next step, selectivity needs to be now documented in animal studies.
Abstract WP318: Prediction of Leptomeningeal Collateral Recruitment in Experimental Ischemic Stroke by Cerebrovascular Reactivity to Carbon Dioxide
Authors: Christoforidis Gregory A , Saadat Niloufar , Jeong Yong , Mira Liu , Niekrasz Marek , Carroll Timothy
Published: June 2021

Purpose:
Immediate pial collateral recruitment during acute ischemic stroke is an endogenous response limiting permanent tissue damage due to proximal cerebral artery occlusion. There is presently no known way to predict the degree of pial collateral recruitment. This work sought to determine if cerebrovascular reactivity (CVR) to CO
2
predicts pial collateral recruitment in an experimental model of cerebral ischemia.

Methods:
Eight mongrel dogs underwent cerebral blood flow (CBF) measurements using stable isotope neutron activated microspheres during normocapnia (PaCO
2
30-35mmHg) using medical air, and subsequently during hypercapnia (PaCO
2
60-70mmHg) using 7% CO
2
. Anesthesia (propofol, remifentanil, rocuronium and 1% isofluorane) and normal range physiologic parameters were maintained to avoid undue influence on CO
2
reactivity. Animals underwent middle cerebral artery occlusion using a previously described endovascular method. Pial collateral recruitment was angiographically assessed using a previously published 11-point scale. Animals subsequently underwent MRI to derive 4-hour infarct volumes calculated using an automated threshold technique using mean diffusivity maps. Bivariate linear fit analyses were used to assess correlations between CVR versus pial collateral score and infarct volume.

Results:
CBF values derived from cortical gray matter during simultaneous CO
2
challenge demonstrate a statistically significant correlation to infarct volumes (p=0.0041, r
2
adj= 0.734) and pial collateral recruitment (p=0.0006, r
2
adj= 0.856) (figure 1). CBF at PaCO
2
of 65mmHg was secondarily found to correlate with infarct volume (p=0.0013, r
2
adj= 0.817) and pial collateral recruitment (p=0.0005, r
2
adj= 0.862).

Conclusion:
Preliminary data presented suggest that cerebrovascular reactivity to CO
2
may be predictive of pial collateral recruitment and infarct volumes during acute ischemic stroke
Abstract WP319: miRNA Screening of Natural Killer Cell Identifies miR-1224 as a Post-Transcriptional Regulator of NK Cell Function After Ischemic Stroke
Authors: Feng Yan , Zhao Hui , Shi Fu-Dong , Jin Weina
Published: June 2021

Objectives:
To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke.

Methods:
Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot.

Results:
Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway.

Conclusion:
The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.
Abstract WP323: Genetic Knockout of CD38 in Mice Protects Against Ischemic Stroke With Smaller Infarct Volumes and Decreased Motor Impairment
Authors: Hannawi Yousef , Gnyawali Surya , Ewees Mohamed G , Balch Maria H , Harris Hallie , Rink Cameron , Nimjee Shahid , Zweier Jay L
Published: June 2021

Introduction:
Endothelial dysfunction is an important mediator of post ischemic injury of the heart and brain following ischemia/reperfusion (I/R). We have reported that CD38 activation in heart I/R models leads to NADPH depletion with endothelial nitric oxide synthase (eNOS) impairment, loss of endothelial-mediated coronary dilatation and increased myocardial infarction. While CD38 knockout or inhibition prevents this dysfunction and decreases myocardial infarction, the role of CD38 in ischemic stroke remains uncertain.

Hypothesis:
We hypothesize that loss of CD38 expression and activity through gene knockout is protective with smaller infarct volume.

Methods:
15 week-old male CD38 knock out (KO) n=12 and wild type (WT) mice n=12 underwent middle cerebral artery occlusion (MCAO) for 60 minutes. Stroke volume was calculated using T2 MRI sequences on a 9.4 T MRI system acquired 48 hours post stroke with images analyzed using Osirix software. The ratios of the stroke volume to the affected hemisphere volume and the compensated swelling infarction volume percentage of normal hemisphere were calculated using established methods. Open field test to measure motor impairment was performed at baseline and 48 hours post stroke (KO, n=12, WT n=6). Statistical analysis was completed in STATA using Man-Whitney U test and T-test to compare infarct volumes and cognitive parameters. Values are shown as mean ± SD. P value < 0.05 was considered significant.

Results:
At 48 hours, brain MRI showed a smaller percentage of cerebral hemisphere affected by stroke in CD38 KO compared to WT (25.9±3.7 vs 41.1±9.4, respectively P=0.0001) and a smaller percentage of compensated swelling infarction volume of normal hemisphere in KO mice compared to WT (19.6±3 vs 33.5±9, respectively P=0.0001). Open field test showed significant post stroke motor impairment in WT compared to CD38KO mice (distance travelled 1.8±1 m vs 4.7±3 m, P=0.04, respectively and average speed 0.006±0.003 m/s vs 0.016±0.01m/s, P=0.04, respectively).

Conclusions:
Infarct volumes are smaller and motor impairment is decreased in CD38 KO mice compared to WT demonstrating that gene knockout of CD38 confers neuroprotection against acute ischemic brain injury.
Abstract WP329: The Role of miR-34b/c in Global Ischemic Stroke
Authors: Byun Hyae-Ran , Porch Morgan , Pontarelli Fabrizio , Court Vazquez Brenda L , Zukin R.Suzanne , Hwang Jee-Yeon
Published: June 2021

Transient global ischemia arising as a consequence of cardiac arrest in humans causes selective, delayed death of hippocampal CA1 pyramidal neurons and cognitive impairment. Effective treatments to ameliorate the neurodegeneration and cognitive dysfunction associated with global ischemia are an unmet need. Emerging evidence points to a widespread role for microRNAs (miRNAs) as key modulators of target gene expression in neurons. Accordingly, dysregulation of miRNAs are implicated in the pathophysiology of neurodegenerative disease and neurological disorders. Our findings, derived
via
miRNA-seq, indicate that expression of a subset of microRNAs are altered in postischemic CA1 including miR-34b/c, miR-21, miR-331, miR-181 and miR-29. Ingenuity pathway analysis reveals that miR-34b/c is the leading miR candidate implicated in cell death and survival. A role for miR-34 in the pathogenesis of global ischemia is, as yet, unclear. Here we show ischemia induces p53-dependent activation of miR-34b/c and downregulation of its target genes Bcl-2 and Sirt1, which together promote neuronal death in selectively vulnerable hippocampal CA1
in vivo
. Consistent with this, inhibition of miR-34b/c affords neuroprotection, rescues impaired synaptic plasticity and reduces memory deficits in global ischemia. These findings document a causal role for p53-dependent activation of miR-34b/c in neuronal death and identify a novel therapeutic target for amelioration of the neurodegeneration and cognitive deficits associated with ischemic stroke.
Abstract WP333: The Impact of External Facilitation on Implementation: Findings From the Protocol-Guided Rapid Evaluation of Veterans PREVENT Quality Improvement Program
Authors: Damush Teresa M , Homoya Barbara , Penney Lauren , Miech Edward , Rattray Nicholas , Cheatham Ariel , Myers Jennifer , Myers Laura , Austin Curt , Baird Sean , Bravata Dawn
Published: June 2021

Background and Aims:
In the Veterans Administration, we found an absence of acute TIA care protocols and broad clinician uncertainty. To address these gaps, the PREVENT program was implemented in a stepped-wedge trial involving 6 medical facilities. To promote local adaptation, we employed external facilitation (EF) delivered by nurse as a key implementation strategy. The specific aim of this evaluation was to examine the effect of EF strategy on PREVENT implementation.

Methods:
We adapted an EF tracking template to prospectively monitor facilitation type, dose and temporality. We defined 17
apriori
facilitation EF activity codes based upon the PREVENT protocol, and Consolidated Framework for Implementation Research (CFIR). We evaluated the EF activities delivered at each site over a 1 year and how the EF dose corresponded to the number of implementation activities completed and the level of team cohesion (beginning, developing, basic, intermediate, advanced) for providing and improving TIA care.

Results:
A total of 1209 EF activities delivered were delivered to QI teams and most frequently to the clinical champions; with a mean number of 242 EF activities per facility (range 182-295). Facility-level clinical champions were most likely to participate in EF activities compared to other team members. The most common EF activities delivered were: education (mean=34.3); planning (mean=27.8); overcoming barriers (mean=22.2) and ongoing quality process monitoring (mean=32.3). Teams with high initial team cohesion,
>
intermediate level, used EF early in the implementation process while teams that gradually developed cohesion over time, developing to basic levels of team cohesion, utilized EF later. QI teams with greater success in implementation activities had far more implementation activities completed (IA= 29-39) than EF activities related to barriers (B=18-28). However, QI teams with the least success in implementation activities (IA=11-25) had similar levels of EF activities related to barriers or higher (B=18-25).

Conclusions:
EF impacts real-world implementation by facilitating team education; planning; navigating the barriers; and enhancing the champions' skills. Early team cohesion was related to greater implementation success.
Abstract WP34: The Relationship Between Reperfusion and Intracranial Hemorrhage After Thrombectomy
Authors: Desai Shashvat M , Tonetti Daniel A , Morrison Andrew A , Gross Bradley A , Jankowitz Brain T , Jovin Tudor G , Jadhav Ashutosh P
Published: June 2021

Introduction:
Symptomatic intracerebral hemorrhage (sICH) is a devastating complication after endovascular thrombectomy (EVT). Prior reports have demonstrated that TICI ≥2b reperfusion is protective against sICH. We aimed to further examine the relationship between reperfusion grade and sICH, to elucidate whether a difference between TICI 2b and 3 exists, and to determine whether this relationship holds true for patients undergoing delayed thrombectomy (6-24 hours).

Methods:
We performed a single-center retrospective review of prospectively-recorded data for patients undergoing EVT for large vessel occlusion (LVO) between January 2015 and February 2018. Multivariable logistic regression analyses were performed to identify predictors of PH and sICH (NINDS, SITS-MOST, ECASS III criteria) and to identify the role of reperfusion grade. This analysis was repeated for delayed thrombectomy patients.

Results:
Five-hundred-and-twenty-eight patients were included. Mean age was 71.5 and 43% were male. Median NIHSS and TLSW to treatment were 17 and 4.8 hours, respectively. Successful recanalization was achieved in 94%. On multivariable analyses, ASPECTS was a predictor of PH [p=0.002, OR-0.7 (0.57-0.87)] for patients achieving any reperfusion grade. For patients achieving successful reperfusion, lower ASPECTS was a predictor of PH [p=0.005, OR-0.72 (0.58-0.89)]) and of sICH (ECASS III) [p=0.04, OR-0.67 (0.45-0.98)]; in addition, TICI 2b as compared to TICI 3 was a predictor of PH [p=0.04, OR-2.1 (1-4.4)] and of sICH (NINDS) [p=0.05, OR-7.5 (1-57)]. TLSW to treatment was not an independent predictor of PH or sICH.

Conclusion:
Higher baseline ASPECTS and higher degree of reperfusion following EVT is associated with reduced likelihood of PH and sICH.
Abstract WP349: Sex-Based Claims Models for the Prediction of 1-Year Mortality After Ischemic and Hemorrhagic Stroke
Authors: Lichtman Judith H , Leifheit Erica C , Wang Yun , Goldstein Larry B
Published: June 2021

Background:
Claims-based models have been developed to predict 30-day mortality after ischemic and hemorrhagic stroke, yet few models are available for predicting 1-year post-stroke mortality among discharged patients. Moreover, there are limited data on whether factors associated with 1-year mortality differ for women and men. We developed claims-based models to predict 1-year mortality after hospital discharge for ischemic and hemorrhagic stroke stratified by sex.

Methods:
We identified fee-for-service Medicare beneficiaries aged ≥65y who were discharged alive with a principal diagnosis of ischemic (ICD-9 433, 434, 436) or hemorrhagic (ICD-9 430, 431) stroke in 2014. We fit Cox regression models with Markov-chain Monte Carlo simulation to identify risk factors for 1-year all-cause mortality; variables with a posterior probability ≥0.95 of being associated with 1-year mortality were considered significant and included in the models for the overall samples and for each sex.

Results:
The study included 235,737 ischemic (53% women; mean age 80.3y [women] and 77.2y [men]) and 43,084 hemorrhagic (52% women; mean age 80.0y [women] and 77.8y [men]) stroke patients. One-year mortality was 27.9% (95% CI 27.7%-28.2%) for women and 22.0% (21.8%-22.3%) for men who had an ischemic stroke and was 50.8% (50.2%-51.5%) for women and 46.4% (45.7%-47.1%) for men who had a hemorrhagic stroke. The c statistics for the models in the overall samples were 0.79 for ischemic stroke and 0.76 for hemorrhagic stroke (Figure). Although there were small differences in the variables included in the models by sex, the c statistics were comparable.

Conclusions:
One-year claims-based models can be used by hospitals to predict the risk of death for patients discharged after stroke. The models identified many risk factors common to women and men that can inform strategies to improve the clinical management of stroke patients during the first year of recovery.
Abstract WP362: Over-Utilization of Studies to Detect Deep Venous Thrombosis in Stroke Patients With Patent Foramen Ovale
Authors: Samuel Sophie , Nguyen Thuy , Reddy Sujan T , Parsha Kaushik N , Savitz Sean I
Published: June 2021

Introduction:
Cryptogenic stroke may result from paradoxical embolism through a patent foramen ovale (PFO). However, the association between deep vein thrombosis (DVT) and cryptogenic stroke has not been proven. The objective of our study is to compare the incidence of DVT in young and old patients who presented with acute ischemic stroke and were found to have a PFO.

Method:
We conducted a single-centre retrospective study from January 2014-December 2018. Patients over the age of 18 with ischemic stroke and PFO, who underwent magnetic resonance venography (MRV) of the pelvis and venous doppler ultrasonography (VDU) for assessment of DVT were included. Primary endpoint was the incidence of DVT in patients that were age ≤ 60 (young group) compared to those age > 60 (old group). We further analyzed the incidence of DVT in cryptogenic stroke vs determined origin; and based on the Risk of Paradoxical Embolism (ROPE) score.

Results:
We included 327 patients: 200 were young (Y) and 127 were old (O). Incidence of DVT was similar for patients in Y versus those in O group (7% vs 8%). A significantly higher ROPE score ≥ 6 was seen in the Y group (71% vs 9%; p<0.001). However, there was no difference in the incidence of DVT in patients with high (9%) or low ROPE scores (8%); OR 0.75, 95% CI (0.32-1.76) p=0.517. Among cryptogenic stroke with high ROPE score and young, incidence of DVT was (7% vs 9%) in determined origin; OR 0.74, 95% CI (0.28-1.96) p=0.557. MRV pelvis detected a clot in 5% of all patients. In a multivariable regression analysis; age, gender, and presence of PFO was not associated with the incidence of DVT. Length of stay and mRS at day 7 were the same between Y and O groups.

Conclusions:
Detection of DVT was not associated with PFO, high ROPE scores or cryptogenic strokes. Our data indicate an over-reliance of testing for DVT, particularly MRV pelvis with contrast, in patients with PFO. Clinical studies are needed to identify other factors predictive of DVT in patients with ischemic stroke and PFO.
Abstract WP364: Utilization of End-of-Life Care Services in Stroke Patients Across a Large Health System
Authors: Toumbs Randi R , Dao Thanh , Zhu Liang , Savitz Sean
Published: June 2021

Background:
Patients presenting to hospitals with devastating strokes have high mortality rates (a national quality metric) and significant needs for end-of-life (EOL) care including palliative care (PC) and hospice services. Appropriate utilization of PC/hospice services across a health system can improve timeliness of care delivery and inpatient mortality rates. Our hospital system consists of 11 hospitals; 1 tertiary academic center (TAC)/comprehensive stroke center (CSC) and 10 community hospitals of which 3 are CSCs and 5 are primary stroke centers. In-house hospice is based in a community CSC and not the TAC. We investigated mortality, early death, and PC/hospice utilization to understand whether EOL services are effectively used across our system.

Methods:
Stroke patients (by DRG) and EOL utilization (defined by PC/hospice ICD 10 codes or MD specialty) were identified from January-December 2018. The TAC data were compared to the combined data of the other 10 system hospitals. Outcomes include EOL utilization, PC/Hospice utilization rates, and early deaths (deaths within 48 hours of admission). Chi-square was used to analyze categorical variables. Significance level was set at p<0.05. Analyses were performed using SAS 9.4

Results:
Total stroke volume was 4,062: 1228 presented to the TAC and 2,834 to the 10 other system hospitals. The TAC and system mortality is 12% and 6% respectively. The EOL utilization rate at the TAC (19%) is significantly higher (p<0.0001) than across the system (8%). PC utilization (TAC 18% vs system 6%, p<0.0001) and hospice utilization (TAC 7% vs system 4%, p=0.0009) are significantly higher at the TAC. At the EOL, the TAC (37%) had significantly fewer (p=0.0004) patients with hospice involvement compared to the system (53%). Early deaths occurred significantly more (p<0.0001) at the TAC (7%) than across the system (2%).

Conclusions:
Stroke mortality and EOL needs are concentrated at our TAC while hospice care is based at and more utilized in the community hospitals. Our data supports implementing a hospice service at the TAC to enhance PC delivery for high mortality stroke volume and developing an EOL Stroke Pathway to standardize care delivery.
Abstract WP370: Inpatient Outcomes and Resource Utilization Among Patients With Large Hemispheric Infarction Who Developed Cerebral Edema: An Analysis of U.S. Real-World Data
Authors: Chen Shih-Yin , Thompson-Leduc Philippe , Sawyer Robert N , Macheca Monica , Fakih Iman , Cheung Hoi Ching , Kirson Noam Y , Torbey Michel
Published: June 2021

Introduction:
Patients with large hemispheric infarction (LHI) may suffer from life-threatening complications, including cerebral edema. Published data among these patients in real-world settings are limited. This study describes inpatient outcomes and resource utilization associated with cerebral edema among hospitalized patients with LHI.

Methods:
A retrospective cohort study was conducted using the MarketScan Hospital Drug Database (2015Q3-2017Q4). As infarct volume is not captured in the data, patients were included based on diagnosis codes for infarction of the middle cerebral artery or carotid artery, which are most closely associated with LHI. Within this group, cerebral edema was determined based on a diagnosis code of cerebral edema (ICD-10-CM G93.6) or herniation (G93.5), or a craniectomy procedure. Logistic regressions, comparing patients with edema vs. those without edema, were used to estimate the odds ratio of death, ICU admission, and tracheostomy/intubation during the hospital stay. Linear regression models were used to estimate the mean difference in length of hospital stay, length of ICU stay, and hospital charges. All models controlled for age, sex, and admission type.

Results:
A total of 11,772 patients were designated as likely LHI cases; 869 (7%) were identified with cerebral edema.
Table 1
compares inpatient outcomes and resource utilization in patients with vs. without cerebral edema. Patients with cerebral edema had significantly higher odds of death, ICU admission and tracheostomy/intubation. They also had longer hospital stays, longer stays in the ICU, and higher hospital charges.

Conclusion:
This study provides evidence in a real-world setting, highlighting the substantial clinical and economic burden associated with cerebral edema among patients hospitalized with LHI. Given the unmet needs, management strategies and interventions focusing on reducing cerebral edema among patients with LHI are warranted.
Abstract WP372: Hydration Status and Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy
Authors: Bahouth Mona N , Gottesman Rebecca
Published: June 2021

Introduction:
Impaired hydration measured by elevated blood urea nitrogen (BUN) to creatinine ratio has been associated with worsened outcome after acute ischemic stroke. Whether hydration status is relevant for patients with acute ischemic stroke treated with mechanical thrombectomy remains unknown.

Materials and Methods:
We conducted a retrospective review of consecutive acute ischemic stroke patients who underwent endovascular procedures for anterior circulation large artery occlusion at Johns Hopkins Comprehensive Stroke Centers between 2012 and 2017. A volume contracted state (VCS), was determined based on surrogate lab markers and defined as blood urea nitrogen (BUN) to creatinine ratio greater than 15. Endpoints were achievement of successful revascularization (TICI 2b or 3), early re-occlusion, and short term clinical outcomes including development of early neurological worsening and functional outcome at 3 months.

Results:
Of the 158 patients who underwent an endovascular procedure, 102 patients had a final diagnosis of anterior circulation large vessel occlusion and met the inclusion criteria for analysis. Volume contracted state was present in 62/102 (61%) of patients. Successful revascularization was achieved in 75/102 (74%) of the cohort. There was no relationship between VCS and successful revascularization, but there was a 1.13 increased adjusted odds (95% CI 1.01, 1.27) of re-occlusion within 24 hours for every point higher BUN/creatinine ratio in the subset of patients who underwent radiological testing for pre-procedure planning (n=57). There was no relationship between VCS and clinical outcomes including early neurological worsening and 3 month outcome.

Conclusions:
Patients with VCS and large vessel anterior circulation stroke may have a higher odds of early re-occlusion after mechanical thrombectomy than their non-VCS counterparts, but no differences in successful revascularization nor clinical outcomes were present in this cohort. These results may suggest an opportunity for the exploration of pre-procedure hydration to improve outcomes.
Abstract WP380: Thyrotoxicosis is Associated With Worse In-Hospital Mortality in Patients With Ischemic Stroke
Authors: Isa Sakiru O , Buhari Olajide , Changezi Hameem
Published: June 2021

Introduction:
Hyperthyroidism increases the basal metabolic rate and affects most systems in the body. Patients with hyperthyroidism have been shown to have a higher incidence of ischemic stroke. There is a paucity of information regarding its effects on the short-term outcomes of patients admitted with ischemic stroke.

Hypothesis:
Hyperthyroidism is associated with worse in-hospital outcomes in patients admitted for ischemic stroke.

Methods:
We queried the National Inpatient Sample to identify adult patients(aged 18 and above) admitted for ischemic stroke between January 2011 and December 2014. We compared those with a history of hyperthyroidism (group 1) and thyrotoxicosis on admission (group 2) with the rest of the patients (group 3). The main outcome was in-hospital mortality. Secondary outcomes included the length of hospital stay and cost of hospitalization. We used the logistic regression model and adjusted for baseline characteristics and co-morbidities.

Results:
There were 643,786 patients in the study, 0.44% had a history of hyperthyroidism, and 0.01% had thyrotoxicosis at the time of presentation. The odd of mortality in group 1 compared to group 3 was 0.89, 95% CI 0.75-1.05, p=0.16 while in group 2 compared to group 3, it was 2.42, 95% CI 1.29-4.52, p<0.006. The mean length of stay was also longer in group 2 with a mean difference of 8.06, 95% CI 4.74 - 11.39, p<0.0001.

Conclusion:
From the study, there was no significant difference in in-hospital mortality between patients with previously diagnosed hyperthyroidism and those without diagnosed hyperthyroidism. Patients who had thyrotoxicosis on admission, on the other hand, had worse outcomes compared to patients without thyrotoxicosis.
Abstract WP383: Intraoperative Strokes in Patients Who Underwent Transcatheter and Surgical Aortic Valve Replacement
Authors: Zhang Lucy Q , Santucci Josh , Kapadia Samir , Uchino Ken
Published: June 2021

Introduction:
Perioperative ischemic stroke is a complication of transcatheter and surgical aortic valve replacement (TAVR/SAVR). We compared characteristics of perioperative stroke in TAVR and SAVR.

Methods:
Between January 2012 to December 2017, 9069 patients underwent TAVR or SAVR at single tertiary center. ECMO patients, with ventricular assist devices, or those who underwent concurrent cardiac procedures other than coronary revascularization were excluded. A patient was presumed to have an “intraoperative” stroke if last known normal (LKN) was immediately before surgery. If LKN was after surgery, then the stroke was considered be “postoperative”. Time of stroke discovery was defined as time of neurologic symptom onset. If symptom onset time was unknown, then time of initial CT brain was used.

Results:
One hundred seven patients with perioperative strokes met inclusion for analysis. Twenty-eight TAVR patients developed a perioperative stroke, compared to 79 SAVR patients. Strokes were intraoperative in 48 (44.9%) and postoperative in 59. No difference was found in the occurrence of intraoperative strokes between TAVR (15/28, 31.3%) and SAVR (33/79, 41.8%, p=0.28). Time from LKN to discovery of intraoperative stroke was median 606 minutes in TAVR and 1359 minutes in SAVR (p=0.049). Median time from LKN to discovery of a postoperative stroke was no different between TAVR and SAVR groups (median 120 minutes TAVR, 173.5 minutes SAVR p=0.57). Among 48 patients who had an intraoperative stroke, only TAVR patients (n=2) received acute reperfusion therapy.

Conclusion:
Intraoperative strokes were discovered sooner in patients who had undergone TAVR than SAVR. Early detection of perioperative strokes may allow for more opportunities for reperfusion therapy.
Abstract WP385: Delirium Significantly Contributes to Longer Hospitalization and Higher Post-Discharge Costs for Stroke Patients: An Analysis of Nationwide Data
Authors: Kumar Aditya , Bambhroliya Arvind , Meeks Jennifer , Zha Alicia , Sheth Sunil A , McCullough Louise D , Savitz Sean I , Vahidy Farhaan S
Published: June 2021

Background:
Healthcare costs related to delirium in the elderly and in the post-operative patient populations exceed $150 billion a year. Stroke patients are at a higher risk of developing delirium, which can significantly increase their healthcare costs. Incremental hospitalization and post-discharge costs associated with delirium have not been described in stroke patients.

Methods:
We analyzed Nationwide Readmission Data from 2010 - 2015 and identified adult (≥18) ischemic and hemorrhagic stroke patients. In-hospital delirium was identified using a validated algorithm. Patients who died during index hospitalization were excluded. Costs for index hospitalization and readmissions were determined using cost to charge ratios, and inflation adjusted to 2015 USD. We used generalized linear models to compare costs between delirious and non-delirious patients adjusting for demographics, comorbidities, illness severity, treatment intensity, in-hospital complications, and surgical procedures.

Results:
A total of 2,853,175 stroke discharges were included among whom 7.1% were documented to havein-hospital delirium on index admission. Delirious patients had a longer mean length of stay (12.01 vs 7.38 days), and higher 30-day readmission rates (16.7% vs 12.2%). At index admission, delirious patients had 9.9% higher adjusted costs of hospitalization as compared to non-delirious patients. For all admissions (including readmissions), delirious stroke patients had 12.3% higher adjusted costs of hospitalization, which translates into an additional $10,544.2 (2015) per hospitalization. (Figure)

Conclusion:
Our analyses highlight the potential cost savings in stroke care associated with prevention, recognition, early mitigation and effective management of delirium. Even though delirium prevalence may be underestimated in administrative data, these results indicate potential annual nationwide cost savings of more than $350 million for stroke care.
Abstract WP395: Detection of Hemorrhagic Expansion With Ai
Authors: Nagamine Masaki , Kohanteb Paul , Yu Wengui , Bardis Michelle , Wu Te-Chang , Su Lydia , Chow Daniel , Chang Peter , Chen Jeon , Soun Jennifer
Published: June 2021

Background and Purpose:
Intracerebral hemorrhage (ICH) expansion is an independent predictor of mortality and functional outcome with each milliliter of expansion increasing the chance of functional dependence by up to 7%. Unfortunately, detection of ICH expansion is often subjective, inaccurate, and may misguide treatment pathways. Artificial intelligence with convolutional neural networks (CNNs) represents a powerful new technology for image analysis and quantification. This study compares the accuracy, sensitivity, and specificity between a CNN optimized for ICH volume quantification and a traditional ABC/2 method.

Materials and Methods:
We performed a retrospective analysis of ICH patients who have had at least one follow-up non-contrast head CT (NCCT) within 24 hours. ICH expansion was defined as >33% volume of expansion, corresponding to a 10% increase in diameter. Each ICH was manually segmented, which served as ground truth measurements. Comparison of ICH expansion was made using (1) a traditional ABC/2 estimative approach and (2) a previously validated hybrid 3D/2D mask ROI-based CNN for ICH evaluation, which was trained previously on over 10,000 patients. Accuracy, sensitivity, and specificity of the CNN and ABC/2 approaches were then compared.

Results:
A total of 230 patients were included for a total of 460 NCCTs. The average ICH volume was 44.8 mL. The average ICH volume for the CNN was 45.3 mL (Pearson 0.99) and for ABC/2 was 60.4 mL (Pearson 0.81). Accuracy, sensitivity, and specificity for ICH expansion detection was 100%, 100%, and 100% for the CNN and 93.0%, 74.2%, and 96.0% for ABC/2. On visual inspection, cases of false positives by ABC/2 approaches tended to demonstrate eccentric expansion (Figure 1).

Conclusions:
A customized deep learning tool is highly accurate in the detection of ICH expansion. This may have important implications clinically for management and surveillance as well as in a clinical trial setting.
Abstract WP396: Analysis of Patients With Excessively High Pre-Randomization Systolic Blood Pressure and Effect of Intensive Systolic Blood Pressure Reduction in Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) 2
Authors: Qureshi Adnan I , Foster Lydia D , Lobanova Iryna , Huang Wei , Suarez Jose I , Palesch Yuko Y
Published: June 2021

Background:
Current guidelines recommend for intracerebral hemorrhage (ICH) patients with the systolic blood pressure (SBP) >220 mmHg, unlike those with initial SBP 150-220 mm, Hg, the efficacy of aggressive reduction of SBP is less well established and further studies are recommended.

Methods:
We analyzed data from ATACH 2 trial which randomized patients with initial SBP >180 mm Hg to intensive (goal 110-139 mmHg) and standard (goal 140-179 mmHg) SBP reduction using IV nicardipine within 4.5 hours of symptom onset. We compared the characteristics and outcomes between patients with pre- randomization SBP ≥220 mm Hg and those with initial SBP <220 mm Hg. We analyzed the modifying effect (interaction test) of pre-randomization SBP ≥220 mm Hg on treatment effect (intensive versus standard) on death or disability (score 4-6 on modified Rankin scale) at 3-months post-randomization ascertained by a blinded investigator.

Results:
Of 1000 randomized subjects, 48 subjects had a pre-randomization SBP ≥ 220 mm Hg (mean age 57.8 years, 65% men); 24 were assigned to intensive-treatment and standard-treatment each. The rate of death or disability at 3 months (47.9% versus 37.7%, odds ratio (OR): 1.52, 95% confidence interval (CI): 0.43 to 1.5, 0.85 to 2.72) and hematoma expansion within 24 hours (30.0% versus 21.2%, OR: 1.60; 95% CI: 0.80 to 3.20) was not different among subjects with SBP≥220 mm Hg SBP and those with SBP < 220 mm Hg. Rates of hematoma expansion (19% and 27.3%, OR: 0.63; 95% CI: 0.15 to 2.6) and neurological deterioration (8.7% versus 17.4%, OR: 0.45; 95% CI: 0.07 to 2.8) within 24 hours were not different between those randomized to intensive treatment and those to standard treatment in patients with SBP≥220 mm Hg. The interaction between initial SBP ≥220 mm Hg and treatment effect on death or disability was significant (p=0.0111).

Conclusions:
Patients with pre-randomization SBP ≥220 mm Hg did not have higher rates of hematoma expansion or death or disability compared to those with SBP <220 mm Hg. The interaction of pre- randomization SBP ≥220 mm Hg with the treatment effect and a non-significantly higher rate of death or disability associated with intensive treatment requires further studies.
Abstract WP398: Occurrence of Acute Kidney Injury in Patients With Intracerebral Hemorrhage Undergoing Systolic Blood Pressure Reduction
Authors: Qureshi Adnan I , Huang Wei , Lobanova Iryna , Aslam Hunain , Zafar Werdah
Published: June 2021

Background:
Aggressive systolic blood pressure (SBP) reduction may precipitate acute kidney injury (AKI) because of underlying hypertensive nephropathy, in subjects with intracerebral hemorrhage (ICH). Rate and determinants of AKI during acute hospitalization among ICH subjects were analyzed using a post hoc analysis of randomized, multicenter, two-groups, open-label clinical trial.

Methods:
Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) 2 trial data was analyzed. Subjects with ICH (volume <60 cm
3
) and a Glasgow Coma Scale (GCS) score of 5 or more were randomized to a SBP target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment). IV nicardipine was given within 4.5 hours of symptom onset to lower SBP. Serum creatinine was ascertained at baseline, 24, 48 and 72 hours after randomization. AKI was classified based on increase in serum creatinine levels from baseline, stage 1 ≥ 0.3 mg/dl (≥ 26.4umol/L) or (>1.5 to 2-fold), stage 2 (>2 to 3-fold) and stage 3 (>3-fold) were identified.

Results:
Of 1000 randomized subjects, 158 developed AKI (65% were men; mean age of 61.5±13.2 years). Severity of AKI was grade I, II, III in 15.3%, 0.1%, and 0.4% patients, respectively. The rate of AKI was similar in intensive and standard treatment group (16.4% versus 15.2%, P=N.S). AKI incidence was significantly higher in subjects with baseline creatinine greater than 1.2 mg/dl (36% compared to 14%, OR 3.4, 95% CI 2.3-4.9, P= <0.0001). There was no significant association between subjects with AKI and hypertension (RR 1.1, 95% CI 1-1.2, P=0.15) or diabetes mellitus type 2 (RR 0.72, 95% CI 1.5-1.1, P=0.12). Patients with GCS ≤ 12 had significantly lower chances of developing AKI (RR 0.5, 95% CI 0.4-0.9, P=0.01). The incidence of hematoma expansion (OR 2.5, 95% CI 0.6-11, P=0.2) was not significantly higher in the subjects with AKI. No significant association was observed between occurrence of AKI and death or disability (modified Rankin score 4-6) at 3 months post randomization (RR 1.1, 95% CI 0.9-1.3, P=0.44).

Conclusions:
Mild AKI is frequent among intracerebral hemorrhage subjects undergoing SBP reduction. However, the rate of AKI was not different between subjects who were randomized to intensive or standard treatments.
Abstract WP402: Risks and Benefits of Selective Serotonin Reuptake Inhibitor Use Among Survivors of Intracerebral Hemorrhage
Authors: Kubiszewski Patryk P , Kourkoulis Christina , DiPucchio Zora , Schwab Kristin , Gurol Mahmut E , Greenberg Steven M , Viswanathan Anand , Anderson Christopher D , Rosand Jonathan , Biffi Alessandro
Published: June 2021

Introduction:
Selective Serotonin Reuptake Inhibitors (SSRIs) are widely used to treat post-stroke depression, but they increase Intracerebral Hemorrhage (ICH) incidence in the general population. ICH survivors must therefore balance ICH recurrence risk with depression treatment benefits when considering SSRI use. We sought to determine risks and benefits of SSRI use among survivors of primary ICH.

Hypothesis:
SSRI exposure following ICH is associated with increased recurrent ICH risk and decreased depression severity.

Methods:
We analyzed data from the MGH-ICH study. We collected baseline patient information (demographics, race/ethnicity, medical history), ICH characteristics (location, size, associated functional impairment) and determined genetic (APOE e2/e4) and MRI markers of underlying small vessel disease. Participants were followed by phone and EMR review to determine: 1) recurrent ICH events; 2) onset and severity of depression (using the GDS-4 scale). We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity as a function of SSRI exposure. We conducted a subset analysis for patients with one or more of the following characteristics associated high ICH recurrence risk: 1) probable or possible CAA diagnosis (Boston criteria); 2) presence of APOE e2/e4 gene variants; 3) prior history of ICH/TIA/ischemic stroke; 4) black or Hispanic race/ethnicity.

Results:
We enrolled and followed longitudinally 1010 ICH survivors. SSRI exposure was associated with both ICH recurrence (HR 1.22, 95% CI 1.06 - 1.40) and improvement of depressive symptoms (OR 0.73 for increase in GDS-4 score quartiles, 95% CI 0.59 - 0.90). Among individuals at high ICH recurrence risk SSRI use was associated with higher risk for ICH recurrence compared to all other ICH survivors (interaction p = 0.012). SSRI effect on depressive symptoms did not differ between high ICH recurrence risk individuals and all other participants.

Conclusions:
SSRI exposure is associated with both improvement in depressive symptoms after ICH and with increased hemorrhage recurrence risk. Clinical history, neuroimaging data and genetic biomarkers may represent viable tools to identify ICH survivors more likely to safely tolerate SSRI use.