bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP291: Stochastic Methods Can Resolve the Dilemma of Emergency Stroke Transport
Authors: Paydarfar Daniel A , Paydarfar David , Mucha Peter J , Chang Joshua
Published: June 2021

Introduction:
Drip and Ship (DNS) and Mothership (MS) are well-known emergency transport strategies in acute stroke care, but the criteria for choosing between the two is widely debated. Existing models define time-dependent outcomes but cannot resolve this debate with statistical significance because the independent variables are deterministic. We propose a novel stochastic framework that quantifies statistical significance between DNS and MS in a network of primary and comprehensive stroke centers.

Methods:
We represented the physiology of ischemic core growth as a stochastic first-order differential equation, enabling infarct volume at time of reperfusion to be calculated and mapped to 90-day mRS. Using Texas as a case study, we configured the state’s stroke network within 15,811 geographic blocks as defined by census data. For each block, we ran Monte Carlo simulations to generate Beta distributions of large- and small-vessel infarct volumes, which were then translated into cumulative distribution functions of mRS. A two-sample Kolmogorov-Smirnov test for significance, and Cohen’s d effect size statistic for practical significance were computed between each DNS and MS pair. Stable effect sizes were assured by sampling
>
5,000 total infarct volumes for each block. All model parameters were established from large cohort studies or trials.

Results:
Of the 13,113 blocks where the primary stroke center is the closest hospital from origin, DNS produces significantly better stroke outcomes than MS in 79.0% (0.3% SEM;
P
< 0.05; 0.2 < d < 0.5). For the subset of patients with large-vessel strokes, MS produces significantly better outcomes in 44.6% of blocks (1.3% SEM;
P
< 0.05; 0.4 < d < 0.85).

Conclusion:
Stochastic methods enable the use of clinically relevant metrics for comparative significance of DNS and MS in a geographic region. This formalism, which has not been incorporated in previous models, can be further generalized beyond stochastic infarct volumes if sufficiently large datasets become available. For example, the kinetic growth model can integrate the statistical distributions of times (pre-hospital and hospital) leading up to intervention, and patient attributes that affect outcomes, such as the degree of collateral flow and comorbidities.
Abstract WP297: National Estimates of Recurrent Intracranial Hemorrhage Among Patients With Ruptured Intracranial Aneurysms
Authors: Chaudhry Saqib A , Akhtar Iqra A , Zafar Werdah , Fang Yun , Hassan Ameer E , Chaudhry Mohammad Rauf A , Gill Mohsain , Qureshi Adnan I
Published: June 2021

Background:
The estimates of recurrent intracranial hemorrhage in the post-hospitalization period among patients treated for ruptured intracranial aneurysms are not available outside clinical trials.

Objective:
To determine the rates of recurrent intracranial hemorrhage related hospitalization within 3 month post-hospitalization for treatment of ruptured intracranial aneurysm in a nationwide cohort of patients admitted for subarachnoid hemorrhage (SAH).

Methods:
We identified all readmissions related to new SAH or intracerebral hemorrhage in the nationally representative data for all patients hospitalized for SAH using the Nationwide Readmissions Database (NRD) 2013 and 2014 who had undergone endovascular or surgical treatment. Cox proportional hazards analysis was used to assess the relative risk (RR) of recurrent intracranial hemorrhage for patients in treatment cohorts after adjusting for potential confounders. The 1-year survival was estimated for both treatment groups by using the Kaplan-Meier survival method.

Results:
A total of 8,619 patients with SAH were treated with either endovascular (n = 4,102, 47.6%) or surgical treatment (n =4,517; 52.4%).. The estimated 3 months recurrent intracranial hemorrhage survival was 99.4% and 98.4% in patients who underwent surgical and endovascular treatments, respectively (p=0.0024). After adjusting for age>65, and APDRG severity score, the RRs of recurrent any intracranial hemorrhage was higher with endovascular treatment (RR, 3.0; 95% confidence interval (CI), 1.4 -6.7 p=0.0052).

Conclusion:
Although the rates of recurrent intracranial hemorrhage related hospitalization were low among patients with ruptured intracranial aneurysms, there was a higher rate among patients treated with endovascular treatment.
Abstract WP298: Feasibility of a Large-Scale Teleneurology Network for Thrombolysis Administration in a Heterogeneous Multihospital Population
Authors: Morton Johanna L , Northington Diamond K , Jolly B. Tilman
Published: June 2021

Background:
Administration of alteplase is the standard of care for eligible patients presenting with symptoms of acute ischemic stroke (AIS). Telemedicine is increasingly being used to deliver acute stroke care to patients without in-person access to stroke expertise. This study reviews the thrombolysis experience of the largest known teleneurology network spanning 39 states and distributed across a heterogeneous multihospital population throughout the nation.

Methods:
Data was abstracted from internal medical records systems and relevant medical records obtained from partner hospitals. A retrospective analysis on the prospectively maintained database of patients who have received alteplase was performed. Data was collected from December 1, 2015 to May 31, 2019. Outcome analysis was restricted to those patients with available complete discharge data.

Results:
The analysis revealed 8,399 patients as having received alteplase during the study period. Of these, 56.7% had discharge information available. The mean patient age was 68.5 years, with a mean age of 70.5 years for females and 66.5 years for males. The median initial NIHSS score was 7, with 31.2% of patients presenting with an initial NIHSS score ≤4, and 8.7% presenting with an initial NIHSS score ≥21. The transfer rate to another facility was 31.0%. There were 2,417 home discharges (48.2%), 1,057 acute rehabilitation discharges (21.1%), and 478 skilled nursing facility discharges (9.5%). There were 28 patients who left against medical advice (0.6%). The symptomatic hemorrhage rate in this population was 1.1% (92), and there were 234 patient deaths (4.7%).

Conclusion:
A large-scale teleneurology platform for the emergent treatment of patients presenting with AIS symptoms is both safe and feasible. Due to the heterogeneity of this patient and hospital population, higher level refinement of this analysis to include hyperacute metrics, transfer data, and more comprehensive clinical and functional outcomes is warranted.
Abstract WP30: Delay and Dispersion Correction Leads to More Accurate Core Estimation for Endovascular Thrombectomy Patients
Authors: Gunasekera Lakshini , Churilov Leonid , Bivard Andrew , Mitchell Peter J , Parsons Mark W , Yan Bernard
Published: June 2021

Objective:
Endovascular thrombectomy (EVT) significantly improves clinical outcomes in acute ischemic stroke with large vessel occlusion. Clinical benefits are inversely proportional to size of the pre-treatment ischemic core. Therefore, accurate measurement of the size of core is critical in selecting patients for EVT. Different post-processing perfusion algorithms for automated core calculation on perfusion CT (CTP) are based on variations of deconvolution of the tissue concentration time curve with the arterial input function (single value decomposition, or SVD). In this study, we compared ischemic core estimated by two different CTP automated algorithms to the final infarct volume as demonstrated by follow up diffusion weighted imaging (DWI).

Methods:
We performed a retrospective analysis of patients who underwent EVT. Inclusion criteria were CT perfusion scan prior to EVT, successful EVT with mTICI 2b-3 reperfusion, and DWI scan 24-48 hours post-EVT. CTP data were processed by two different post-processing algorithms: ‘delay-insensitive’ single value decomposition (DISVD) and delay and dispersion corrected single value decomposition (ddSVD) using the respective commercially available automated CTP software. CTP core volumes from both methods were compared with DWI final infarct volumes using an independent software (MRIcron) for concordance. The agreement between a given algorithm and MRI was estimated using Lin’s concordance coefficient and further investigated using reduced major axis regression.

Results:
One hundred and three patients who underwent EVT and achieved successful mTICI 2b-3 reperfusion were included. Both algorithms had excellent agreement with MRI (Lin’s concordance coefficients: DISVD 0.8 (95% CI: 0.73; 0.87), ddSVD 0.92 (95% CI: 0.89; 0.95). Compared to ddSVD (reduced major axis slope = 0.95), DISVD exhibited larger extent of proportional bias (slope = 1.12).

Conclusion:
Both algorithms showed excellent agreement with FIV calculated on MRI but DISVD post-processing overestimated the larger ischemic cores, which may lead to unnecessary exclusion of patients from EVT due to a 'large core'.
Abstract WP301: Telestroke Consultation Can Accurately Diagnose Ischemic Stroke Mimics
Authors: Poon Jason T , Tkach Aleksander , DeHavenon Adam H , Smith Jaleen , Hannon Peter M , Chung Lee S , Majersik Jennifer J
Published: June 2021

Introduction:
Telestroke (TS) networks have become standard in many areas of the US, increasing thrombolysis rates in patients with acute ischemic stroke (AIS). By providing an early, accurate diagnosis, patients with stroke mimics may also benefit from TS consultation and avoid unnecessary treatments and transfers. However, despite TS systems having up to 50% mimic rates, it is unknown if TS can accurately diagnose patients with stroke vs stroke mimics.

Methods:
This was a retrospective review of consecutive TS consults at the University of Utah Hospital to 27 TS sites in 6 states from Jan-Dec 2018. Clinical information and diagnosis were extracted from discharge records and compared to those from the TS consult. Discharge diagnosis was determined by the discharging physician, recorded by the TS coordinator, and verified and coded into 12 categories by 2 physicians. Cases without a clear discharge diagnosis were excluded. When multiple TS diagnoses were listed without priority, the first one was used as the diagnosis. We report agreement and a Cohen’s kappa between TS and discharge diagnoses for the category of AIS/TIA versus stroke mimic.

Results:
We reviewed 476 TS cases (mean age 66 years; 54% women); 71 were excluded for lack of discharge diagnosis leaving 405 cases for analysis. Of these, there were 225 TS diagnoses of AIS/TIA; 102 (45%) received IV tPA. Our study demonstrated high diagnostic agreement for AIS/TIA (88%) with a kappa of 0.75 for stroke and mimics. Of the 180 patients diagnosed with a stroke mimic on TS, 27 (15%) were diagnosed with AIS/TA by discharge . (Figure 1 ). TS mimic diagnosis had a PPV of 85% and NPV of 90%; TS diagnosis of stroke/TIA had PPV 90%, NPV 85%. Only 3% of stroke mimics were transferred.

Conclusion:
The Utah TS system has excellent correlation between TS and discharge diagnoses for patients with both stroke and stroke mimics. This suggests that TS systems can accurately assess a wider variety of patients with acute neurologic syndromes other than AIS.
Abstract WP304: Real-World Experience with the RAPID Platform to Screen Acute Ischemic Stroke Patients at a U.S. Comprehensive Stroke Center
Authors: Assadi Rami-James , Henn Julia , Varmaz Ajlana , Panagos Peter , Miller-Thomas Michelle , Ford Andria , Goyal Manu , Kansagra Akash P , Heitsch Laura
Published: June 2021

Introduction:
Mechanical thrombectomy (MT) is an important part of acute ischemic stroke (AIS) treatment. Recent trials of MT beyond the 6-hour window have utilized RAPID perfusion imaging for patient selection. The utility of this method is established in patients with large vessel occlusions (LVO) but screening efficiency in real-world practice remains unknown. We present the experience of a single, large volume, Comprehensive Stroke Center (CSC) utilizing RAPID to screen patients for LVO and MT.

Methods:
We performed a retrospective analysis of prospectively collected consecutive patients who presented to our emergency department (ED) between 01/2018 to 06/2019 with suspected LVO. Protocol was based on 2018 AHA guideline Level IA recommendations and followed DAWN and DEFUSE-3 time and imaging parameters. Patients who underwent RAPID imaging were selected for inclusion.

Results:
865 patients met criteria for RAPID perfusion imaging (median age 67, females 52%, outside hospital transfers 29%). Of these, 178 (21% of total) were confirmed to have an LVO (40% ED presentation, 10% inpatient, 50% transfer). For patients presenting to the ED (N=509), 14% had an LVO (median NIHSS 13 [IQR 8-19]), of which 41% underwent MT. Mean CTP core and penumbra volume was 25mL and 100mL respectively. Number needed-to-screen in the ED cohort was 7 to detect LVO and 17 to perform MT. Transfer patients showed no significant difference in LVO detection or MT rates compared to ED patients (56%, p=0.3).

Conclusions:
In ED-presenting patients at a CSC, the number of RAPID perfusion imaging studies needed to detect an additional case of LVO was 7.1, and to perform an additional MT was 17.4. Current AHA Class IA recommendations for evaluation and treatment of AIS yield a reasonably high rate of LVO detection and subsequent MT in real-world practice. Additional multicenter data will be useful to establish benchmarks and improve screening efficiency.
Abstract WP305: Discriminating Hemorrhagic and Ischemic Stroke Using a Novel, Non-Invasive, Point-of-Care Neuromonitoring Platform
Authors: Berti Liam , Maza Andrew , Wilcox Madeleine , Kesinger Matthew
Published: June 2021

Study Objectives:
Tissue plasminogen activator (tPA) may improve ischemic stroke outcomes if administered soon after symptom onset. A computed tomography (CT) scan is required to exclude hemorrhagic stroke. The purpose of this study was to evaluate the feasibility of using an experimental, non-invasive, point-of-care electroencephalography (EEG)-based platform to identify hemorrhage in suspected stroke subjects presenting to the emergency department (ED).

Methods:
During a study that took place between May 2018 and July 2019, a sensor was added to the EEG-based platform that was hypothesized could differentiate between hemorrhagic and ischemic stroke. Eligible subjects presented within 24 hours of symptom onset and had a National Institute of Health Stroke Score (NIHSS) greater than 1. The performance of an artificial intelligence (AI) algorithm was assessed using five-fold cross validation.

Results:
Starting in December 2018, 88 subjects were enrolled with the additional sensor. The median (IQR) age was 68 (56 - 78), 56 subjects (64%) were male, and the distribution in terms of ethnicity was 44% white, 38% African American, and 18% non-black latino. There were 14 (16%) intracerebral hemorrhages (ICH) and 52 (59%) ischemic strokes. Median (IQR) time last known well time was 430 (193 - 574) minutes. Performance is shown in Table 1.

Conclusion:
Preliminary results from a small sample are encouraging. More hemorrhagic stroke patients are expected to improve performance.
Abstract WP306: Disparities in Stroke Code Activation Times
Authors: Mortin Melissa M , Hailey Love , Meyer Brett , Meyer Dawn
Published: June 2021

Background:
Early activation of the stroke code system allows for rapid treatment and potentially better outcomes. Multiple disparities have been identified in standard time metrics of acute stroke care. The purpose of this study was to determine if hospital arrival to stroke code activation (SCA) time was significantly different based on age, sex, or race/ethnic differences in an academic, Comprehensive Stroke Center.

Methods:
We retrospectively assessed prospectively collected data from the UCSD Stroke registry from June 2003 to July 2019 for all patients for whom a stroke code was activated. Stroke code time metrics, demographics, initial and final diagnosis, treatment, medical history, baseline vital signs, and baseline NIHSS were assessed. Continuous variables were assessed by Spearman rho, Pearson correlation and t test. ANOVA was used for ordinal variables. A linear regression model was built in a stepwise method. Analysis were done unadjusted and adjusted for baseline NIHSS and baseline blood glucose.

Results:
Of the 5,881 total subjects, 2,954 had a final diagnosis of stroke. The overall mean age was 66.4 (18-103 years, SD 16.7) and 69.1 (18-103 years, SD 15.4) for subjects with final diagnosis of stroke. The overall mean time to SCA was 5.2 minutes (-20 to 5,746, SD 124.5). Arrival to SCA was not significantly different with respect to age in unadjusted (rs=-0.13, p=0.08) and adjusted (rs=-0.14, p=0.46) analysis. Time was not significantly different with respect to sex in both unadjusted (p=0.30) and adjusted (p=0.24) analyses. Arrival to SCA time was not significantly different with respect to race in both unadjusted (p=0.99) and adjusted (p=0.99) analyses. Arrival to SCA time was not significantly different with respect to Hispanic ethnicity in both unadjusted (p=0.09) and adjusted (p=0.07) analysis. In a linear regression model, arrival by ambulance (t 3.10, p<0.001) was the only independent predictor of arrival to SCA time.

Conclusion:
There were no significant differences in time to SCA based on sex, age, or race at our academic, Comprehensive Stroke Center. Arrival by ambulance was the only independent predictor of lower arrival to SCA times. Protocols and education in acute stroke management in this setting have reduced disparities in SCA.
Abstract WP309: Hypertensive Stimuli Promote Brain Inflammation and Cognitive Impairment in a Pressure-Dependent Manner
Authors: Sobey Christopher G , Dinh Quynh Nhu , Vinh Antony , Drummond Grant R , De Silva Michael
Published: June 2021

Background:
Hypertension increases the risk for stroke and cognitive impairment, and is strongly associated with inflammation of the vasculature and kidneys. However, it is unclear whether there is inflammation and immune cell infiltration in the brain during hypertension.

Aims:
To test whether chronic infusion of angiotensin II causes brain inflammation and cognitive dysfunction, and whether its effects are blood pressure-dependent.

Methods:
Male C57Bl/6 mice were administered vehicle or angiotensin II (Ang II, 0.7 mg/kg/d
s.c.
) via osmotic minipumps. A subset of mice also received hydralazine (50 mg/kg) in their drinking water after minipump implantation. We measured systolic blood pressure by tail cuff plethysmography, immune cell numbers using flow cytometry and recognition memory using the novel object recognition test.

Results:
Ang II infusion increased blood pressure and promoted accumulation of leukocytes in the brain, including neutrophils, monocytes, T cells and B cells, all of which were elevated by ~2.5-fold compared to vehicle-treated mice (n=6-8, P<0.05). Co-administration of hydralazine prevented the pressor response to Ang II and reduced neutrophil and monocyte infiltration (n=7-8, P<0.05), however, hydralazine had no effect on T or B cell numbers (n=7-8). Ang II impaired recognition memory and this was prevented by administration of hydralazine (n=11-12, P<0.05).

Conclusions:
Our data indicate that inflammation occurs in the brain during Ang II-dependent hypertension and this is associated with impaired recognition memory. Reducing blood pressure reversed these effects. Chronic brain inflammation may be a contributing factor to the increased stroke risk and cognitive impairment during hypertension and may be mitigated by blood pressure reduction.
Abstract WP314: Reduced Post-Ischemic Brain Tissue Injury Following Transient Focal Cerebral Ischemia in
Transient Receptor Potential Vanilloid 4
Knockout Mice
Authors: Tanaka Koji , Matsumoto Shoji , Yamada Takeshi , Yamasaki Ryo , Kido Mizuho A , Kira Jun-ichi
Published: June 2021

Background:
In the acute phase of ischemia-reperfusion, post-ischemic delayed hypoperfusion in microvascular regions contributes to post-ischemic brain tissue injury. Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel expressed on astrocyte endfeet regulating vascular tone, which may contribute to ischemia-induced brain tissue injury.

Objective:
To clarify whether brain tissue injury following transient middle cerebral artery occlusion (tMCAO) is ameliorated by
Trpv4
knockout (
Trpv4

-/-

).

Methods:
tMCAO was induced by an insertion of silicon-coated filament from right common carotid artery to occlude right MCA for 30 minutes for wild type (WT) and
Trpv4

-/-

mice aged 8-10 weeks (median [interquartile] weight: 23.3 [21.7-24.9] g for WT mice and 24.1 [20.8-26.2] g for

Trpv4
-/-

mice). Ischemia-induced lesion volume was evaluated by 2,3,5-Triphenyltetrazolium chloride staining at 24 hours post-tMCAO, and tissue water content and Evans blue leakage in the ipsilateral hemisphere alongside 18-point neurological score were evaluated at 48 hours post-tMCAO. Transmission electron microscopy (TEM) was performed to assess the morphological changes in the microvasculature in the ischemic lesions at 6 hours post-tMCAO.

Results:
Compared with WT mice,
Trpv4

-/-

mice showed reduced ischemia-induced lesion volumes (median 40 mm
3
vs. 53 mm
3
, p < 0.05) at 24 hours and reduced tissue water content by subtraction of the contralateral from the ipsilateral hemisphere (median 4.9% vs. 2.8%, p < 0.05) and Evans blue leakage by ratio of ipsilateral to contralateral hemisphere (median 2.3 vs. 3.2, p < 0.05) alongside milder neurological score (median 12 vs. 10, p < 0.01) at 48 hours post-tMCAO. TEM revealed that parenchymal microvessels in the ischemic lesion were compressed and narrowed by the swollen endfeet of astrocytes in a WT mouse, whereas those were markedly reduced in a
Trpv4

-/

-
mouse.

Conclusions:
Trpv4

-/-

mice showed reduced post-ischemic brain tissue injury. Suppressing the astrocyte endfeet swelling shortly after reperfusion is one of the key neuroprotective mechanisms of TRPV4 inhibition, which is a promising target for the treatment of acute ischemic stroke.
Abstract WP317: Neutrophil Subtypes and Nets Changes in Diabetes With Acute Ischemic Stroke
Authors: Liu Sanxin , Cai Wei , Hu Mengyan , Lu Zhengqi
Published: June 2021

Objective:
Ischemic stroke (AIS) is a globally high-risk cerebrovascular disease. Diabetes can aggravate ischemic stroke, while its mechanism is still unknown, Neutrophils are the first peripheral immune cells that break through the blood-brain barrier and infiltrate the brain after AIS. They have two polarization states of N1 and N2 subtypes. N1 subtype neutrophils can release neutrophil extracellular traps (NETs) containing a large number of pro-inflammatory factors and exacerbate the neuroinflammatory response. This study will explore the immunological mechanisms of diabetes exacerbating ischemic stroke.

Methods:
Patients with acute ischemic stroke who were admitted to hospital from Jan 2012 to Dec 2018 were collected, compared blood neutrophil count and neutrophil/lymphocyte ratio in diabetic and non-diabetic AIS patients at 1 day; Middle cerebral artery infarction (MCAO) mice was used for animal model of AIS, high-fat diet and STZ-induced type 2 diabetes model. The neurological deficit score, TTC staining, flow cytometry and immunofluorescence staining were used to observe the infarct volume, neutrophil subtypes and NETs changes between AIS with and without diabetes.

Results:
The neutrophil count of AIS patients with diabetes was higher than that of non-diabetic AIS patients. Animal experiments found that AIS with diabetes increase neurological deficit score and infarct volume. Flow cytometry and immunofluorescence staining found that AIS with diabetes mice can promote neutrophils infiltration into the brain and promote the polarization of neutrophils to N1 subtype and increase NETs formation.

Conclusion:
Diabetes can promote the neutrophil polarization of N1 subtype which leads to increased NETs formation and exacerbate ischemic stroke.
Abstract WP321: The Role of Neuronal Sirt1 in Ischemic Stroke: Regulation of the Metabolic Imbalance
Authors: Li Ge , Ren Xiu-Jun , Cho Su-In , Zhong Wenliang , Ahn Yong-Joo , Bae Jaeho , Qian Jiao , Kwon Ye-Rim , Kim Maya Hwewon , Hwang Seo-Kyoung , Koong HwaSoo , Jang Dongyeol , Yang Chengxian , Kim Hyung-Hwan
Published: June 2021

Introduction:
Sirt1 is a NAD+ dependent deacetylase that is known as an important metabolic regulator for type 2 diabetes melitus. To determine the role of Sirt1 in ischemic stroke-induced metabolic imbalance, we generated the neuronal specific Sirt1 knock-in (nSirt1 KI) and knock-out (Sirt1 KO) mice and examined its effect and mechanism.

Methods:
To determine the role of Sirt1 in ischemic stroke-induced impaired metabolic actions including insulin and glucose abnormality, we tested the pharmacological effects of Metformin and Sirtinol as Sirt1 activator and inhibitor. To determine the genetic role of neuronal Sirt1 in the brain, we generated the nSirt1 KI mice and Sirt1 KO. We used the Ischemia/Reperfusion (I/R: 1h middle cerebral artery occlusion (MCAO)/23h reperfusion) injury model to induce the abnormal metabolic changes. Infarction volume was measured by TTC staining and we determined neurological deficit score (NDS) at 23h after 1h MCAO. The level of glucose and insulin were measured by a drop of tail blood using test-strip and ELISA Kit before, during (every 10 minutes interval), and after MCAO.

Results:
Metformin reduced infarction volume and Sirtinol worsened the infarction volume via Sirt1 signaling pathway. Heterozygous Sirt1 KO (Sirt1 +/-) mice showed decreased relative cerebral blood flow (rCBF) and worsen infarction volume in ischemic areas, whereas nSirt1 KI mice exhibited increased rCBF, improved NDS, regulating abnormal blood glucose and insulin, and reduced infarction volume by 42% compare to that of littermate control in I/R injury model (n=7, p<0.05). Based on western blotting analysis of brain lysates in nSirt1 KI mice, the expression of Sirt1 was significantly increased. Glucose regulation by overexpression of Sirt1 and reduced infarction volume in nSirt1 KI mice were reversed by Sirtinol.

Conclusion:
These findings indicate that the important neuroprotective effect of neuronal cells is mediated by Sirt1 overexpression and suggest that upregulation of neuronal Sirt1 may be an important therapeutic target for ischemic stroke via regulating metabolic imbalance.
Abstract WP325: X, but Not Y, Sex Chromosome Contributes to Stroke Sensitivity in Aged Mice
Authors: Qi Shaohua , Al Mamun Abdullah , Sharmeen Romana , Ngwa Conelius , D. McCullough Louise , Liu Fudong
Published: June 2021

Introduction:
Stroke is a sexually dimorphic disease. Women are protected against ischemia compared to men before menopause due to estrogen’s neuroprotection; after menopause the elderly women become vulnerable to stroke attack. Our previous studies with four core genotype mice found a chromosomal effect (either X or Y) in stroke sensitivity. Recently, we found two X-linked genes (
Kdm6a
and
Kdm5c
) that escape from X chromosome inactivation (XCI) are higher expressed in aged female vs. male microglia after stroke. KDM6A and KDM5C are histone demethylases that modify gene expression of inflammatory mediators. By these early studies, we hypothesized that the second X chromosome contributes to stroke sensitivity in aged mice through immune responses mediated by KDM6A and KDM5C.

Methods:
XY* aged (18-22 months) mice (natural menopause cohort) that have four genotypes (XO, XX, XY, XXY) were subjected to middle cerebral artery occlusion (MCAO). Another cohort of gonadectomized XY* mice were also used as the “surgical menopause” cohort. Infarct volumes and behavior deficits were quantified 3 days after MCAO. KDM6A and KDM5C localization with microglial marker TMEM119 was examined by IHC. Plasma inflammatory cytokine (IL-1β, TNF-α, IL-6, IL-4, TL-10, etc.) levels were analyzed with MultiPlex. The contribution of the second X-chromosome to stroke sensitivity was determined by comparing XX vs. XO or XXY vs. XY mice, and the effect of the Y-chromosome was evaluated by a comparison between XY vs. XO and XXY vs. XX mice.

Results:
In both surgical and natural menopause cohorts, XX and XXY mice showed worse stroke outcomes compared to XO or XY mice respectively; however, no significant difference was found between XX vs. XXY or XO vs. XY mice. IHC results showed higher expression of KDM6A and KDM5C in TMEM119 positive cells in mice with two vs. one copy of X chromosome. XXY mice had significantly higher levels of circulating TNF-α and IL-6 than XY mice.

Conclusion:
The second X chromosome contributes to stroke sensitivity in mice. Kdm6a and Kdm5c may play important roles in mediating post-stroke inflammation. Future work will genetically manipulate the expression of
Kdm6a and Kdm5c
in microglia to examine the roles of the two XCI escapee gene in stroke.
Abstract WP326: Cortical Border Zones Are More Vulnerable to Spreading Depression-Induced Capillary Flow Disturbances
Authors: Taskiran-Sag Aslihan , Iversen Nina Kerting , Gutiérrez-Jiménez Eugenio , Østergaard Leif , Dalkara Turgay
Published: June 2021

Cortical spreading depression (SD) is a major metabolic challenge to the brain and is followed by a unique hemodynamic response. It has been suggested that the oligemic phase of this response is accompanied by a mild to moderate capillary dysfunction. To test this hypothesis, we directly investigated microcirculatory flow changes during and after SD at the territory of major arteries as well as their hemodynamically vulnerable watershed zones. Swiss mice (n=6) under isoflurane anesthesia were tracheotomized, mechanically ventilated, and imaged under two-photon microscopy through a closed cranial window. Mean transit time (MTT), capillary transit time heterogeneity (CTH) and relative transit time heterogeneity (RTH) were calculated based on an indicator-dilution method using intravenous boluses of Texas-red dextran fluorescent dye (70,000 MW; 0.5%). Boluses were performed at the steady-state and 1 min, 5 min and 30 minutes after potassium chloride-induced SD. MTT, CTH, and RTH were estimated within the territory and border zone of major arteries to reveal any regional differences. Physiological parameters were monitored and kept within normal limits throughout the experiments. Both MTT and CTH increased following SD in the territorial zone from 1.07±0.03 to 1.67±0.15 s (mean±SEM;p<0.01) and from 0.51±0.03 to 0.94±0.07 s (mean±SEM;p<0.01), respectively. However, RTH was only mildly increased in this region from 0.49±0.04 to 0.59±0.06 (p=0.03). In the watershed area, all three parameters showed a more prominent increase following SD and RTH rose from 0.64±0.06 to 1.25±0.22 at 30 minutes (p=0.04). These findings provide direct experimental evidence for prolonged capillary flow disturbances induced by cortical SD, which may account for some lasting neurological symptoms after aura. The particular vulnerability of border zones to SD-induced flow disturbances may be involved in the pathogenesis of some of the white matter MRI lesions observed in migraineurs.
Abstract WP328: Afilbercept, a Vegf-trap, Reduces Vascular Permeability and Stroke-induced Brain Swelling in Obese Mice
Authors: Kim Il-doo , Shakil Faariah , Cho Sunghee
Published: June 2021

Introduction:
Brain swelling is a pathological event of ischemic stroke that progresses the enlargement of the brain injury, especially in comorbid conditions. In our previous study, we reported that diabetic obese mice had disproportionately increased stroke-induced brain swelling and that VEGF signaling was involved in this pathophysiology. Aflibercept (VEGF-Trap), an FDA approved drug that targets vascular endothelial growth factor receptor (VEGFR), has been used to treat patients with age-related macular degeneration and metastatic colorectal cancer. This study addressed whether Aflibercept can be used to reduce brain swelling in obesity stroke.

Methods:
HUVECs were cultured and treated with rVEGF (50 ng/ml) in the presence or absence of VEGF-Trap (1 ug/ml). Permeability was assessed by the incubation with FITC-dextran. Tube formation was also assessed. Diet-induced obese mice were generated by feeding a high-fat diet (HFD) for 8 weeks for males and 12 weeks for females to achieve similar insulin resistance. Their body weight gain and glucose clearance by glucose tolerance test was evaluated. Obese mice were subjected to transient MCAO. VEGF-Trap (10 mg/kg) or IgG (Fc control) was injected intravenously at 3h post-MCAO. VEGFR2 and VEGF-A gene expression was measured by realtime RT-PCR. Infarct size, brainswelling and neurological score were determined.

Results:
VEGF-Trap reduced rVEGF-A-mediated permeability by 50.0±10.7% (p<0.01, n=7) and tube formation by 28.5±3.5% (p<0.001, n=6) in HUVEC cultures. Stroke-induced VEGFR2 and VEGF-A gene expression was reduced in the mice that received VEGF-trap (38.9±1.0% (VEGFR2) and 34.1±1.4% (VEGF-A), p<0.05, n=7/group). Compared to IgG control, treatment of VEGF-Trap reduced brain swelling (25.3±3.5 % (IgG, n=20) vs 17.3±1.7 % (VEGF-Trap, n=22), p<0.05) and neurological score without reaching a statistical significance (p=0.06). There was no difference in infarct size between the two groups (33.0±3.9 mm
3
(IgG) vs 40.0±4.8 mm
3
(VEGF-Trap), ns).

Conclusion:
The study demonstrates that targeting VEGF signaling effectively reduces stroke-induced brain swelling in obese mice. The observed benefit suggests the repurposing of VEGF-Trap as a potential therapy in treating stroke in obese subjects.
Abstract WP331: Does Successful Reperfusion Mean Successful Outcome in Elderly Stroke Patients?
Authors: Ruiz Amber N , Cardentey Agnelio , Longstreth WT , Tirschwell David L , Creudtzfeldt Claire J
Published: June 2021

Background:
Randomized clinical trials (RCTs) suggest a benefit of mechanical thrombectomy (MT) even for individuals ≥ 80 years of age; however, this population has not been consistently included in RCTs, and the eldest (≥85 years) are underrepresented. Small observational studies suggest that elderly patients experience a higher proportion of in-hospital complications, mortality, and poor functional outcome defined as modified Rankin Scale Score (mRS) ≥4. While MT is generally recommended in this population, little is known about how decisions are made to undergo MT or subsequently to withdraw or withhold life-sustaining treatments (WoLST). The goal of this study was to describe a single center experience of elderly patients who underwent MT.

Methods:
We identified all patients admitted to our comprehensive stroke center from June 2016 - June 2018 who were ≥85 years old and underwent successful MT, defined as TICI 2a to 3. We collected data from the electronic medical record, including WoLST. A good outcome was defined as a mRS of 0-2 at 90 days.

Results:
We identified a total of 29 patients with successful MT with a mean age of 88.4 years (SD=3.6); 66% were women. Only one patient (3.4%) achieved a good outcome, while 65.5% died (see figure). Among decedents, 47.4% expired during their initial hospitalization, while 15.8% were discharged to hospice. A decision for WoLST was made in 11 patients, 88.9% of in-hospital decedents.

Discussion:
In our retrospective study of 29 elderly patients who underwent successful MT, only one achieved good functional outcome, and most died in the setting of WoLST. These observations may raise the question about the appropriateness of MT in this cohort, emphasizing the need for further research aimed (1) to identify determinants of outcome and MT success specific to elderly MT candidates and (2) to better understand the process of clinical decision making for this growing, vulnerable population of elderly patients.
Abstract WP338: The Impact of Social Determinants of Health on 30-Day Readmission After Ischemic Stroke
Authors: Kovi Shivakrishna , Man Shumei , Uchino Ken , Tang Anne S. , Lopez Rocio
Published: June 2021

Objective:
Readmission after ischemic stroke presents immense social and financial burden on the patient, family and society. The impact of social determinants of health on post-stroke readmission have not been well studied. This study aimed to examine association of patient social determinants with 30-day readmission risk after ischemic stroke.

Methods:
We examined patients who were hospitalized for acute ischemic stroke (ICD-9 codes 433.1, 434, and 436) in the state of Florida and New York from February 2012 to November 2013, with a 30-day run-in time and 30-day follow up time. Data were obtained from the State Inpatient Database which was then linked with Census data on social determinants at zip code level. Multivariate logistic regression models were generated to study the association of patient factors with 30-day readmission, after adjusting for patient characteristics, in-hospital infection, hemiplegia, and 16 comorbidities. All statistical analyses were conducted using SAS Version 9.4 software (SAS Institute).

Results:
A total of 127,290 patients were included in the study. The overall 30-day readmission rate was 23%. The 30-day readmission rates differed by race, insurance but not age, sex or household income at zip code level. The 30-day readmission rate was higher amongst black (27%) and Hispanics (25%), and lower in Native American (17%) and White (22%). Comparable to older age groups, patients who suffered a stroke at young age (<50 years old) had 23% readmission rates at 30 days. In the multivariate logistic regression model, age was not a risk factor for readmission [adjusted odds ratio (OR) 1.0, 95% confidence interval (CI) 1.0-1.0]. Compared to white, black race had higher risk of 30-day readmission (OR1.2, 95% CI 1.1-1.2), as well as Hispanic race (OR1.1, 95% CI 1.1-1.2). Compared to Medicare insurance, patient on Medicaid had higher risk of 30-day readmission (OR 1.1, 95% CI 1.1-1.2). Self-pay patients had lower risk of readmission (OR 0.6, 95% CI 0.5-0.7).

Conclusion:
Race and medical insurance, not age, sex, or household income, has significant influence in30-day readmission risk after ischemic stroke. This will allow further targeted intervention for readmission reduction.
Abstract WP339: Validation of the Fast-ed Scale Use by Paramedics in a Mobile Stroke Unit
Authors: Haussen Diogo C , Nogueira Raul G , Bhatt Nirav , Flemming Carol , Bianchi Nicolas , Chester Katleen , Morgan Olivia , Navalkele Digvijaya , Frankel Michael
Published: June 2021

Introduction:
FAST-ED scale is a helpful tool to triage stroke patients in the field. However, data on the accuracy of the scale in the pre-hospital setting is lacking. We aim to validate the use of FAST-ED by paramedics in a mobile stroke unit (MSU) covering a metropolis.

Methods:
As part of standard operating MSU procedures, paramedics clinically evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic (in-person) upon patient contact, and independently by a vascular neurologist (telemedicine) immediately after the paramedic evaluation. An MSU nurse determined the NIHSS. This will allow testing of the inter-rater agreement of the FAST-ED scoring performance between on-site pre-hospital providers and remotely located vascular neurologists.

Results:
In the first 13 months of the MSU’s activity 193 stroke-alert patients were evaluated. 103 (53%) patients had a final diagnosis of stroke/TIA (75/28, respectively), 21 (11%) intracranial hemorrhage, and 69 (36%) were considered stroke mimics. 28 (14%) patients received intravenous alteplase. In the first 48 patients, FAST-ED was only scored by the paramedic and in 145 patients by both the physician and paramedic. FAST-ED scores matched perfectly amongst paramedics and physicians in 77 (53%) instances, while there was only 1-point difference in 51 (35%), 2-point difference in 10 (6%) and 3-point difference in two. Correlation between physician and paramedic FAST-ED scores was highly positive (rho 0.898; 2-sided p<0.001), as well as the correlation between physicians FAST-ED score and NIHSS (rho 0.853; 2-sided p<0.001). When the physician recorded FAST-ED score≥3 (n=62), the paramedics also scored FAST-ED≥3 in the vast majority of instances (n=55; 89%). After hospital arrival, cerebrovascular imaging was deemed necessary and performed in 144 patients within 24 hours of arrival. A visible large vessel occlusion was identified in 30 patients; 18 occlusions were identified with a FAST-ED≥3 while 12 were missed (10/12 had NIHSS≤5).

Conclusion:
The correlation of the FAST-ED scoring between vascular neurologists and paramedics was highly positive, indicating that FAST-ED is accurately and reliably utilized by paramedics in the pre-hospital setting.
Abstract WP344: Total Healthcare Costs Before and After Stroke in Non-Valvular Atrial Fibrillation (NVAF) Patients Who Initiated Treatment With Rivaroxaban or Warfarin
Authors: Lin Jennifer H , Milentijevic Dejan , Shrivastava Shubham , Kogan Emily , Sjoeland Erik , Alberts Mark
Published: June 2021

Introduction:
Healthcare expenditures remain unclear in NVAF patients initiating anticoagulation therapy.

Objective:
To compare total healthcare cost in pre- and post-stroke periods between rivaroxaban- and warfarin-treated NVAF patients.

Methods:
This retrospective study using de-identified IBM MarketScan Commercial and Medicare databases (2011-2019) included patients initiating rivaroxaban or warfarin within 30 days after a 1
st
observed NVAF diagnosis who later developed ischemic or hemorrhage stroke. Patients had ≥6 months continuous health plan enrollment, CHA
2
DS
2
-VASc score ≥2 and no history of stroke or anticoagulation therapy. Inpatient stroke diagnosis was identified by ICD-9/-10 code, and stroke severity status was defined by National Institutes of Health Stroke Scale (NIHSS) score, imputed by a random forest method. Total per-patient per-year (PPPY) cost of care was calculated pre- and post-stroke (from treatment initiation to time of stroke and from stroke until end of study enrollment, respectively). Cost increases pre-/post-stroke were compared within each treatment cohort.

Results:
During a mean follow up of 25 and 30 months for rivaroxaban and warfarin respectively, 272 (2.0%) and 1,303 (3.3%) patients, respectively, developed stroke. For the rivaroxaban cohort, the pre-/post-stroke cost increase was lower than that for warfarin (1.79-fold vs 3.08-fold, respectively); for more severe stroke (NIHSS ≥6), the cost increase for rivaroxaban was half that of warfarin (3.19-fold increase vs 6.37-fold increase, respectively).

Conclusions:
The study showed a substantial increase in total cost of care following stroke, especially among patients with severe strokes. Warfarin patients had a much higher increase in post-stroke costs relative to rivaroxaban patients, suggesting a benefit of rivaroxaban in preventing strokes with poor outcomes that are costly.
Abstract WP356: Unbundling Care Transitions and Cost After Stroke: Results From the BPCI-Advanced Program
Authors: Sanfillippo Geri , Olkowski Brian , Schumacher Hermann Christian , Dafilou David , Bowski Colleen , Gilli Maria , Demirjian Johanna
Published: June 2021

Introduction:
The Centers for Medicare and Medicaid Services bundled payment for care improvement advanced (BPCI-A) program incentivizes providers to better coordinate care, reduce expenses, and improve quality. The purpose of this study was to determine the impact of improving post-acute care coordination after stroke on quality and resource utilization in the BPCI-A program.

Methods:
Capital Health collaborated with post-acute providers to improve communication, identify criteria for early supported discharge to the community, expedite home health and outpatient services, reduce readmissions, and initiate advanced care planning. The redesigned post-acute care coordination program was implemented at Capital Health’s primary and comprehensive stroke center. Quality outcomes and resource utilization measures for patients enrolled in the BCPI-A program were compared to BPCI-A eligible patients prior to program implementation.

Results:
Forty-three patients enrolled in the BCPI-A program were compared to 77 patients eligible for enrollment. Clinical and demographic characteristics were similar (p>.05). After program implementation, 21.5% fewer patients were discharged to an inpatient rehabilitation facility (p=.024) and 14% more patients were discharged to inpatient hospice (p<.001). On average, post-acute cost decreased $16,608 per patient (p=.007) resulting in a $16,820 reduction in the 90-day cost per episode (p=.011). The 90-day hospital readmission rate decreased insignificantly by 14.1% from 23.4% to 9.3% (p=.056). Hospital cost, hospital length of stay and the 90-day mortality rate were unchanged (p>.05).

Conclusion:
The coordination of post-acute services facilitates care transitions after stroke. The identification of patients meeting criteria for early supported discharge to the community or admission to inpatient hospice helped reduce post-acute cost without increasing 90-day readmission or mortality.
Abstract WP367: Effect of Early Blood Pressure Reduction on Infarct Size in Patients With Large Vessel Occlusion
Authors: Baker David , Jillella Dinesh , Shimoyama Takashi , Uchino Ken
Published: June 2021

Introduction:
In patients with large vessel occlusion presenting with acute ischemic stroke, cerebral perfusion is a major determinant of stroke severity. However, limited data exists to guide hemodynamic management of these patients early after presentation. In this study, we aim to evaluate the effect of blood pressure reductions during the hyper-acute period on infarct size.

Methods:
From a clinical stroke registry at a single comprehensive stroke center, we reviewed patients with middle cerebral artery (M1) or internal carotid artery occlusion who underwent hyperacute magnetic resonance imaging (MRI) for endovascular treatment decision in 2018. Infarct volume was determined by area of reduced apparent diffusion coefficient using RAPID software. Collateral circulation was scored based on baseline CT angiogram (good collaterals constituted >50% filling, poor collaterals ≤50% filling). Average mean arterial pressure (MAP) readings from the first hour of presentation were compared to average MAP readings from the hour prior to magnetic resonance imaging. For the purposes of our study, a drop of > 20% in the average MAP was regarded as a significant decrease. We hypothesized that both significant drop in MAP and the presence of good collateral circulation were independent predictors of infarct volume expressed as a logarithmic value in multivariable regression model.

Results:
Of the 35 patients (mean age 67, mean NIHSS 16) meeting inclusion criteria, 11% of patients experienced an early significant drop in MAP prior to time of MRI. Among patients with a significant drop in MAP, the average decrease was 35 mm Hg ±3.3 among those with significant drop from a baseline mean MAP of 125 mm Hg. In the multivariable analysis adjusting for collateral status, a significant drop in average MAP was independently associated with an increase in infarct volume (β = -0.727, p=0.0306). Collateral status also independently predicted infarct size (β=0.775, p=0.0007).

Conclusion:
Among ischemic stroke patients with large vessel occlusion, a >20% drop in MAP during the hyper-acute period is associated with larger infarct volumes. Further studies are needed to optimize early blood pressure management in these patients.