bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 93: Trends in Intravenous Alteplase Use and Mortality Among Medicare Beneficiaries With Acute Stroke: A Eight-Year Retrospective Analysis
Authors: Meng Tong , Trickey Amber , Govindarajan Prasanthi
Published: June 2021

Timely stroke treatment with intravenous alteplase (IV-tPA) reduces functional dependence and mortality. Therefore, communities have taken tremendous efforts to increase IV t-PA use through better access to emergency services and stroke centers and through efficient processes at stroke centers. Our objective is to examine the cumulative effect of these processes over an 8-year period on IV-tPA use and mortality in a national sample of Medicare beneficiaries.

Methods:
Within a sample of Medicare claims from 2007-2014, we identified patients aged 66+ and evaluated the first hospitalization per patient with primary diagnosis of ischemic stroke. Outcome measures were emergency department (ED) -administered IV-tPA and 30-day mortality. We excluded patients without continuous prior 1-year enrollment in Parts A+B and those not treated in the ED. IV-tPA was identified using ICD-9 procedure 99.10 and CPT 37195. Mortality was derived from the Medicare Beneficiary Summary File. We calculated Cochran-Armitage trend tests to assess outcomes over time and chi-square tests to compare outcomes by patient and hospital characteristics.

Results:
Among 240,486 patients, there was a significant increase in IV-tPA use from 2.8% to 7.7% (p<0.001). IV-tPA utilization was higher in urban areas (5.5% vs. rural 3.7%, p<0.001) and for patients arriving by ambulance (6.7% vs. 2.5%, p<0.001), with the highest IV-tPA rates observed among urban ambulance-transport patients (Figure). Patient demographics were associated with IV-tPA (all p<0.001); younger (age 66-75) and Non-Hispanic White patients were most likely to receive IV-tPA. During the study period, 30-day mortality decreased from 15.7% to 14.5% (p<0.001).

Conclusions:
Although we observed tripling of IV t-PA during this period, rural areas had lower use when compared with the urban areas. In this ongoing multi-year study, we will investigate enablers and barriers to IV t-PA use within pre-hospital and hospital systems of care.
Abstract NS1: Implementation Science Study Suggests That Key Concepts of Systems of Stroke Care Are Missing or Not Fully Implemented
Authors: Monk Lisa , Shah Shreyansh , Ehrlich Matthew , Kolls Bradley , Jollis James , Graffagnino Carmelo
Published: June 2021

Background and Purpose:
The timely integration of high quality scientific evidence into daily patient care practices is an issue that has been around for decades. Newer research says it may take even longer for practitioners to stop unnecessary practices. What is evident is that there is a need to shorten the time from discovery to practice with an expectation of improved outcomes and control of heath care spending. Understanding the extent to which concepts (research) of stroke systems have been implemented (practice) within a region, can result in meaningful system improvement. We sought to evaluate the current state of systems in the southeastern United States to inform the development of a large-scale implementation science system of care improvement program.

Methods:
An 85 question, internet-based survey was developed to obtain information on current practices in sites located in the southeastern US. Data was collected in October, 2017. A total of 13 stroke centers from 3 states participated. We used the Research Electronic Data Capture (REDCap) data base; simple calculations were used where appropriate.

Results 911:
50% of sites knew that 911 used a stroke screening tool.

EMS:
69% allowed EMS bypass of Emergency Department (ED) to the Computerized Tomography (CT) scanner, 67% of EMS have destination plans, and 33% have stroke severity scales.

ED:
50-86 % of victims arrive by EMS, 62% allowed the Register Nurse (RN) to activate the code, and 62% have CT scanners in ED.
Reversal Agents:
20% of sites have available in ED.

Transfer:
24% of transfer patients go directly to Interventional Radiology (IR) lab for Suspected LVO, 33% track door in door out at the referral center, 31% transport time, and 31% first hospital to groin.

QI:
83% collect pre-hospital metrics manually, 42% have data immediately available, and 67% have regional meetings.

Conclusions:
The American Heart Association outlines key concepts for Systems of Stroke Care for adoption but few have been able to fully implement the recommendations. The survey results demonstrate application of key components are still missing or not fully implemented. Implementation science programs have the tools to mentor sites into full application of the systems recommendations which will ultimately improve outcomes.
Abstract NS5: Use of a Multidisciplinary Approach to Successfully Improve Inpatient Diabetes Self-Management Education and Diabetes Medication Reconciliation at Discharge for Persons With Diabetes and Stroke at a Major Academic Medical Center
Authors: Stone Suzanne , Drobycki Nancy , Johnson Mark
Published: June 2021

Background:
Persons with diabetes are 1.5 times more likely to have a stroke. Research shows that there is a correlation between increasing diabetes and stroke. Education for stroke patients, however, continues to focus on medication management and blood pressure reduction. American Diabetes Association indicates, “There should be a structured discharge plan tailored to the individual patient with diabetes.” Transitioning from the acute care is risky for diabetics, recommendations now include individualized education for diabetics with stroke. 40% of the stroke population at our institution showed risk factors for diabetes, yet 11% received diabetes education, and only 59% had diabetes medication pre-prescribed at discharge. The stroke team initiated an inpatient diabetes education to increase patient awareness and medication adherence.

Purpose:
The purpose of this project was to identify and address barriers related to the provision of individualized inpatient diabetes education and outpatient diabetes medication reconciliation for persons with diabetes and stroke.

Method:
The Endocrinology team was consulted for patients with diabetes and stroke with an A1c level of 7%. These team worked collaboratively to establish a consult process. Endocrinology APPs provided diabetic education and advised the Neurology team on the appropriate discharge medication regimen and follow-up. The stroke coordinator provided reminders during rounds to assure that consults were ordered for patients with diabetes having A1c 7% or greater.

Results:
Inpatient diabetes education improved from 11% in 2017 to 96% in 2019. Diabetes medication reconciliation, with listing of diabetes medications on the after visit summary at discharge increased from 59% in 2017 to 93% in 2019.

Conclusions:
Both metrics reflect improvement over a 2-year period, showing that collaboration between the Endocrinology and Neurology teams is key to effective discharge planning, diabetes medication reconciliation and outpatient follow-up.
Abstract NS8: Increasing Discharges to Acute Rehabilitation With a Multidisciplinary Task Force
Authors: Mortin Melissa M , Perrinez Emily , Sharp Simpson , Donnelly Sarah , Hemmen Thomas , Smith Robin , Renshaw Nancy , Nabulsi Mohammed , Agrawal Kunal , Ziemba Michelle
Published: June 2021

Background:
Patients with Acute Ischemic Stroke recover function better when discharged to inpatient rehabilitation (IRF) over skilled nursing facilities (SNF). We aimed to increase discharge to IRF over SNF at two Comprehensive Stroke Centers (CSC) within our care network.

Methods:
We reviewed the discharge pattern at our CSCs compared to comparable centers using GWTG benchmarking and designated a multidisciplinary task force aiming to meet discharge patterns at our centers to nationwide trends. The task force used Lean Methodology to identify barriers for IRF discharge recognition and placement.

Results:
The taskforce identified non-modifiable barriers such as socioeconomic determinants, insurance status, family/social support; and modifiable barriers such as inconsistencies in therapist recommendations and notations, limited access to case management, and lack of provider knowledge about IRF admission criteria. Beginning November 1, 2018, the following interventions were used to achieve increased IRF referral and admission rates: educating therapists to provide more specific and consistent documentation; thorough therapist, case management, and provider education on IRF admission criteria; cohorting patients on dedicated neurology units; and daily multidisciplinary team meetings (consisting of a therapist, case management, and the primary provider) on the neurology units. IRF admission rates were then collected retrospectively. Between Novembers 1, 2018 to April 30, 2019, the rate of admissions to IRF for the UCSD Health System increased from 7.7% to 13.5% (see Table).

Conclusions:
Using Lean Methodology we identified and reduced barriers for IRF referral after stroke. This suggests IRFs are underutilized when disposition is not effectively streamlined. Further studies are needed to understand which interventions had the highest impact of increasing IRF admission and referral rate.
Abstract NS9: Screening for Spatial Neglect in a Ward-based Environment Within Two Weeks From Stroke Onset: Preliminary Results of a Pilot Study
Authors: Klinke Marianne , Matijosaitis Vaidas , Hjaltason Haukur
Published: June 2021

Background and purpose:
Spatial neglect (SN) occurs frequently in patients with stroke, resulting in worse recovery. Without screening, the presence of SN may remain undetected and prevent initiation of alleviating strategies. There is limited evidence available to suggest bedside identification of SN in the subacute phase following stroke. Thus we set out to identify effective screening tests for SN.

Method:
The following index tests were used; (a) six conventional subtests of The Behavioural Inattention test (BIT), (b) an additional figure copying test, (c) a newly developed neglect experience questionnaire, and (d) an additional component added to the National Institute of Health Stroke Scale (NIHSS). The Catherine Bergego Scale (CBS) functioned as a reference frame to ascertain the presence of SN.

Results:
Consecutive stroke patients (N=125) were included from the Neurological Department of Landspitali University Hospital in Iceland, within two weeks following stroke. Of those 30 patients had SN. If all subtests of the BIT were administered, approximately 35% of stroke patients without SN would be incorrectly identified with the disorder. Statistically more patients without SN were identified as having SN if ≥ three tests of the BIT was administered (p=0.002). If patients did not, at stroke onset, comprehend why they had to go to the hospital, this was correlated to the presence of SN. The star cancellation and figure copying were the most sensitive paper-and pen tests to identify SN. Inclusion of an additional item to NIHSS correctly identified SN in 86% instances.

Conclusion:
Results contests the common belief that use of more tests increase identification of SN. Rather we found that the use a large test battery decreases sensitivity in the subacute phase following stroke. A short question about patients’ experiences of stroke onset and adding a novel item to the NIHSS provided new pragmatic ways of identifying SN. Results have been used to inform a larger cross-country study between Iceland and Lithuania, where psychometric properties of screening strategies are being further validated.
Abstract TMP11: Endovascular Treatment for Acute Ischemic Stroke in the Within 6-Hour versus 6-24-Hour Window: Simple Imaging Protocol
Authors: Nguyen Trung , Nguyen Huong , Nguyen Thanh , Ngo Triet , Pham Binh , Nguyen Thang H
Published: June 2021

Introduction:
DAWN and DEFUSE 3 trials utilized advanced imaging to prove the benefit of endovascular treatment (EVT) in patients within 6-24 hours. There is increasing evidence to suggest the limitations of advanced imaging in real-world practice. Non-contrast-enhanced computed tomography (NCCT) has proved with good sensitivity and specificity in the definition of infarct core. It is still unknown if a simpler and faster protocol may adequately select patients within 6-24 hours for EVT.

Hypothesis:
To compare outcomes of patients submitted to EVT presenting within 6 hours or 6-24 hours, selected using simple imaging protocol.

Methods:
An observational study was performed, which included consecutive patients with anterior circulation ischemic stroke eligible for EVT within 6 hours or 6-24 hours. Patients within early window received routine treatment, while patients presenting within late window were treated if they had a mismatch between the clinical deficit, the infarct volume, and collateral blood blow: (NIHSS score was ≥10 and ASPECTS was ≥7) or (ASPECTS was =6, and the collateral score was ≥2). ASPECTS of NCCT/DWI-MRI and collateral status on CTA/DSA were assessed by a blinded neuroradiologist. The collateral grading system was scored on a scale of 0-3 as in the ESCAPE trial.

Results:
Of the 184 patients were included, 77 (41,8%) received thrombectomy in late window, 107 (58,2%) received acute treatment in early window. Baseline characteristics were similar between groups, except for longer onset to groin puncture time (median, 300 vs 705 min; P<0,0001), higher admission NIHSS (median, 13 vs 16; P<0,0001), lower in ASPECTS (median, 9 vs 8; P<0,0001), and large artery atherosclerosis etiology (61,7 vs 72,7%, P=0,002) in the late window group. No significant differences in successful reperfusion rate and rates of parenchymal hematoma type 2 (81,3 vs 83,1%, P=0,75; 4/107 vs 4/77, P=0,63, respectively). Functional independence (mRS 0-2) and mortality at 90 days did not differ significantly (65,4 vs 57,1%, P=0,25; 10,3 vs 6,5%, P=0,43; respectively).

Conclusions:
This real-world observational study suggests that EVT may be safe and effective in patients presenting within 6-24 hours selected using clinical-core mismatch and collateral blood blow.
Abstract TMP119: Incidence, Presentation and Outcomes of Brain Arteriovenous Malformations in Adult Population in United States
Authors: Balasetti Vamshi , Huang Wei , Kumar Nitish , Lobanova Iryna , Siddiq Farhan , French Brandi R , Gomez Camilo R , Qureshi Adnan I
Published: June 2021

Background:
Data regarding national estimates of brain arteriovenous malformation (BAVM) among adults in United States data are scant, often biased by limitations of single center and regional studies. Identification of such patients in nationally representative datasets was not possible until recently due to a new specific ICD-10 code.

Objective:
To characterize inpatient burden, expenditures, associated comorbidities (including intracerebral hemorrhages and seizures) and treatments of BAVM among adults in United States.

Methods:
Patients with BAVM were identified from the Nationwide Inpatient Sample (NIS) database for the year 2016 using ICD-10 diagnostic code (Q28.2). The primary outcome was to determine the prevalence of BAVM in the adult (18 and above) in-patient population in the United States. Secondary outcomes included determining inpatient mortality, morbidity, comorbidities, hospital length of stay (LOS) and total hospital charges. Outcome was classified by discharge disposition into none to minimal and moderate to severe disability.

Results:
Of the total 7,135,090 reported hospital discharges in 2016, an estimated 1733 (0.02%) had the diagnosis of BAVM; 1547 were adults with ages 18 or greater (mean age [SD] 54 (18); 783 (50.6%) were men). Patients with BAVM were whites (n= 921, 59.5%), African-Americans (n=224, 14.4%) and Hispanic (n=212, 13.7%). Underlying hypertension was identified in 677 (43.1%) patients. Clinical presentation was intracerebral hemorrhage (n=260, 16.8%), seizures (n=234, 15.1%) and subarachnoid hemorrhage (n=75, 4.8%). Endovascular treatment was performed in 272 (17.5%) patients and surgical treatment was performed in 45 (2.9%) patients. None to minimal disability was seen in 1023 (66.1%) and moderate to severe disability was seen in 469 (30.3%) of the patients. In hospital mortality was 2.59% (n=40). Average LOS (SD) was 4 days (8.6) with mean hospitalization charges (SD) of $121,186 (153553.1).

Conclusion:
There are 1547 hospital admissions for BAVM among adults in United States every year. The overall outcomes were good with high rates of none to minimal disability but the hospitalization charges were higher than expected and may be important for resource allocation.
Abstract TMP14: Contemporary Use of IV Alteplase in Acute Ischemic Stroke Beyond 4.5 Hours of Stroke Onset in Clinical Practice is Rare
Authors: Schwamm Lee H , Xu Haolin , Matsouaka Roland , Shah Shreyansh , Sheth Kevin , Saver Jeffrey , Xian Ying , Fonarow Gregg , Smith Eric
Published: June 2021

Introduction:
Two RCTs conducted from 2010-2018 showed benefit in ischemic stroke (IS) of IV tPA >4.5 h from last known well (LKW) using advanced imaging selection. Many subjects were wakeup strokes treated
<
4.5 h of symptom discovery (SxD). We assessed the frequency of IV tPA > 4.5 h in the national GWTG-Stroke clinical registry during the same period as the RCTs were performed.

Methods:
We analyzed all IS hospitalizations between 1/1/09 - 10/1/18 at fully participating GWTG-Stroke sites to identify 219,565 patients at 1919 sites who received IV tPA (no thrombectomy) and had valid LKW, SxD and treatment times recorded. Table shows significant covariates (standardized differences >10%)

Results:
Treatment beyond 4.5 h from LKW was rare, occurring in 2.19% (n=4798) of all tPA cases, and 50% of those treated were still within 4.5 h from SxD. The distribution of time to treatment in minutes was similar when stroke onset was defined by LKW compared to SxD (median (IQR) 134 (100-174) vs. 125 (94-163)) (Fig). The use of IV tPA at >4.5 h from LKW as a proportion of all tPA cases treated varied substantially across sites (median (IQR) 1.7% (0-3.1%)) but fewer than ~10% of sites had more than 5% of their tPA use occurring beyond 4.5 h. Compared to
<
4.5 h, patients treated >4.5 h differed in age, AF, arrival mode/time, stroke severity and hospital region (Table).

Conclusions:
During the past decade and prior to published RCT evidence that extended window IV tPA was effective, US sites in GWTG-Stroke rarely treated patients beyond the guideline-approved window of 4.5 h. It will be important to monitor adoption of extended window thrombolysis in the US, and determine if additional RCT data are required to change practice.
Abstract TMP23: Inflammasome-derived Caspase-1 is Elevated in the Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients and Correlated to Outcome
Authors: Hirsch Yonatan , Geraghty Joseph R , Katz Eitan A , Loeb Jeffrey A , Testai Fernando
Published: June 2021

Introduction:
The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome.

Methods:
SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA).

Results:
Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004).

Conclusions:
The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.
Abstract TMP24: Soluble St2 Links Innate Inflammation to Secondary Injury After Stroke and Subarachnoid Hemorrhage
Authors: Bevers Matthew , Sastre Cristina , Lissak India , Rosenthal Eric , Kimberly W. Taylor
Published: June 2021

Background:
We recently found that soluble ST2 (sST2) is a plasma marker that predicts neurological outcome after ischemic stroke and aneurysmal subarachnoid hemorrhage. We sought to extend these findings by studying sST2 associations with markers of secondary brain injury and peripheral innate immunity.

Methods:
We studied 241 acute ischemic stroke (AIS) patients with sST2 level measured on admission (7.4 ± 3.7 hrs after stroke onset) and at least one follow-up brain imaging study, obtained at a mean of 2.2 ± 1.4 days after stroke onset. A subgroup (n=147) had a second sST2 measurement at a mean of 2.1 ± 1.7 days after stroke onset. A separate cohort of 110 subarachnoid hemorrhage (SAH) patients were studied who had plasma sST2 measured at approximately 3.5 ± 1.2 days after ictus. Markers of secondary brain injury included edema after AIS (midline shift), and delayed cerebral ischemia (DCI) or epileptiform discharges on EEG after SAH. The relationships between sST2 level and outcome measures were assessed. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry to phenotype the peripheral immune response.

Results:
In the AIS cohort, baseline plasma sST2 level was associated with the presence of midline shift (46.1 vs. 41.8 ng/mL, p=0.017), which further increased at 48 hr after stroke onset (50.6 vs. 38.4 ng/mL, p=0.006). In the SAH cohort, median sST2 in patients who developed new epileptiform abnormalities was higher compared to patients who did not (114.8 ng/ml vs. 74.7 ng/ml, p=0.024). Higher median sST2 concentration was also observed in those patients with DCI (90.8 vs 53.7ng/mL, p=0.003). In patients with high sST2, flow cytometry identified a peripheral monocyte population with decreased expression of CD14 (4.27x105 ± 2950 A.U. vs. 5.64x105 ± 1290 A.U., p<0.001), and increased expression of CD16 (39,960 ± 272 A.U. vs. 34,869 ± 183 A.U., p<0.001).

Conclusion:
Plasma sST2 independently predicts edema after stroke, and DCI and epileptiform abnormalities after subarachnoid hemorrhage. Elevated sST2 is also associated with changes in peripheral innate immune cells. These data suggest that sST2 links the innate immune response to secondary brain injury.
Abstract TMP30: M2 Microglia Derived Exosomes Promote White Matter Repair and Long-Term Functional Recovery After Focal Cerebral Ischemia in Mice
Authors: Li Yongfang , Luo Longlong , Zhang Zhijun , Tang Yaohui , Yang Guo-Yuan
Published: June 2021

Objectives:
White matter injury aggravates neurological and cognitive impairment in experimental ischemic stroke. M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair. However, the molecular mechanism is unclear. Here, we explored the effect and mechanism of M2 microglia-derived exosomes on white matter repair after focal cerebral ischemia in mice.

Methods:
Microglia BV2 cells were polarized to M2 phenotype by IL-4 stimulation. Exosomes were isolated from M2 microglia (M2-Exo) and unstimulated microglia as a control (M0-Exo). M2-Exo and M0-Exo (100 μg) were intravenously injected after 90-minute middle cerebral artery occlusion in mice (n=72). Brain atrophy volume and neuro behavioral outcomes were examined in 28 days following focal cerebral ischemia. Oligodendrocyte precursor cells survival, differentiation and white matter integrity were evaluated. Exosomal miRNA and target gene were further examined to explore molecular mechanism.

Results:
M2-Exo treatment promoted sensorimotor and memory function recovery (
p
<0.05), and further reduced brain atrophy compared to the M0-Exo control group (
p
<0.001). Immunostaining showed that M2-Exo increased the number of BrdU
+
/Pdgfr-α
+
and BrdU
+
/adenomatous polyposis coli
+
cells, enhanced myelin basic protein fluorescence-intensity compared to the control (
p
<0.05). M2-Exo increased oligodendrocyte precursor cell survival under OGD in vi
tro
, (
p
<0.05) and differentiation (
p
<0.05). Exosomal miRNA sequencing and PCR identified that miR-23a-5p was enriched in M2-Exo.

Conclusion:
Our results showed that M2-Exo treatment enhanced oligodendrocyte precursor cell survival and differentiation, further promoted white matter repair and long-term functional recovery, suggesting that M2-Exo is a novel therapeutic strategy for the white matter repair after ischemic brain injury.
Abstract TMP33: Repair of Ischemic Intestinal Epithelial Stem Cells: Potential Therapy to Improve Stroke Outcomes
Authors: Mani Kathiresh Kumar , Sohrabji Farida
Published: June 2021

Background:
Nearly 50% of all stroke patients experience “leaky” gut, gut hemorrhage and gut epithelium damage. Gut leakiness may increase circulating inflammatory cytokines and other gut products such as endotoxins, which can impair stroke recovery. Here we tested the hypothesis that normalizing gut function via transplantation of intestinal epithelial stem cells (IESC) after stroke may stimulate repair of gut structures and improve stroke outcomes.

Methods:
Reproductive senescent female Sprague-Dawley rats used for this study and assigned to the following groups: Control (no stroke); stroke with sham transplant (vehicle); stroke with IESC transplantation. Rats were subjected to stereotaxic surgery to occlude the left middle cerebral artery by using Endothelin-1. Primary IECs were isolated from young female rats to prepare organoids cultures. Dissociated organoids were labeled with PKH26 and injected iv either once (48h after stroke) or 3 times (4h/24h/48h after stroke). Behavioral assays and saphenous blood draws were performed pre-stroke, 2d and 5d after stroke. Trunk blood, brain tissue and a segment of small intestine was collected at termination and processed for the expression of the stem cell marker Lgr5+, Na/K ATPase-α, and tight junction proteins.

Results:
Significant deterioration of the gut architecture was observed after stroke, including blunted or absent villi and irregular crypts. In animals that received PKH26-labeled organoid tranplants at 48h post stroke, labeled cells were seen in the center of the villus and a few organoid cells were immunositve for Lgr5+. Animals that received 3 organoid injections showed PKH26-labeled cells incorporated in both the villus and crypts. In these animals, villus were well formed and appeared no different from non-stroke controls. Sensory motor function assessed by adhesive removal test on the side contralateral to the infarction was severely impaired in the stroke/no transplant animals (120+secs/timed out), while this impairment was attenuated in the group that received 3 organoid injections (31±11 secs).

Conclusion:
These data suggest that transplantation of IESC after stroke may promote repair of gut villus and crypts, with a concomitant improvement in sensory motor function.
Abstract TMP36: Exogenous Oxytocin Confers Significant Neuroprotective Effects and Improves Recovery in Young and Aged Animals After Stroke
Authors: Lee Juneyoung , Xu Yan , Morales Scheihing Diego , McCullough Louise , Venna Venugopal Reddy
Published: June 2021

Introduction:
Oxytocin (OXT) is a highly evolutionary conserved neuropeptide and an important modulator of inflammation in response to stressors such as ischemia. Recent studies have implicated OXT signaling in neuroprotection in young mice after ischemic injury, but it is not known if OXT is efficacious in aged animals. In our ongoing studies, we found that OXT levels decline after stroke and with age. Therefore, we tested if exogenous OXT administration could provide beneficial effects and improve recovery in aged animals.

Methods:
Aged (18-20m) C57BL/6 male mice were purchased from Jax Labs and aged in house. Stroke was induced by a right MCAO-60min. Mice were randomly assigned to receive OXT or Atosiban, an OXT antagonist (OXTA) (0.5mg/kg) or vehicle. In the first set of experiments, aged mice were pre-treated with OXT, vehicle, or OXTA for 10 days before stroke. Infarcts were quantified 7-days after stroke (n=6-9/grp). In a second set, we tested the efficacy of delayed treatment, at 3hrs after stroke, and OXT was administered intranasally or i.p.. Functional and behavioral recovery and brain infarct size was assessed 7-day post-stroke. OXT levels 24hrs after stroke in human plasma were measured.

Results:
OXT treatment (0.5mg/kg/i.p. QD) prior to stroke led to significant neuroprotection in aged male mice, whereas OXTA treatment significantly increased infarct (p<0.05, n=6-9/grp) compared to control group (total: 39.4±2.9% control; 20.8±3.1% OXT; 51.3±2.8% OXTA). Importantly, no differences in cerebral blood flow or temperature were seen between groups. Interestingly, the neuroprotective effect of OXT treatment was observed even when treatment was initiated 3hrs (administered either i.p. or nasally) after stroke onset. Also, we observed a significant decrease in circulating OXT levels at 24hrs in stroke patients (n=26) compared to healthy controls, highlighting the translational relevance of this pathway.

Conclusions:
We found that OXT treatment either before or after stroke is neuroprotective in aged mice and both i.p. and nasal OXT administration improves recovery in parallel to reductions in brain injury. Given that intranasal formulations of OXT are approved for human use, our proposed strategy of supplementing OXT is highly translatable.
Abstract TMP38: Web Based Testing of Upper Extremity Movement for Patients Recovering After Stroke
Authors: Sloane Kelly , Lin David , Duffy Amanda , DiCarlo Julie , Cloutier Alison , Gupta Anoopum , Gajos Krzysztof , Hochberg Leigh
Published: June 2021

Background:
Studies of movement of the upper extremity for stroke patients currently require assessments with special equipment and trained assessors, limiting the accessibility. Hevelius is an experimental online platform designed to study human interaction with technology at a large scale. Our aim was to demonstrate the feasibility of using Hevelius for testing arm kinematics in stroke patients.

Methods:
Stroke patients (time from stroke 6 weeks to 1 year) with upper extremity weakness with an NIH Stroke Scale contralesional arm motor (5A or 5B) score of 2 or less were tested on Hevelius. Participants engaged in a Point-And-Click task. Thirty-two kinematic features of movement from continuous, target-driven mouse movement were collected in the arms contralesional and ipsilesional to stroke and compared to data from with health controls. Upper extremity Fugl-Meyer (UE-FM), NIH Stroke Scale (NIHSS), 9-Hole-Peg as well as patient reported outcomes (via Stroke Impact Scale) were collected during the same research visits.

Results:
In a total sample of N = 19 patients with upper extremity weakness after stroke who performed Hevelius testing, the median age was 66 (range 47 - 81) with 70% male participants. Nine participants had strokes affecting their dominant arm. LASSO method was used for regression to simultaneously performs feature selection and fitting of a linear model. Score estimates on Hevelius platform correlated strongly on linear regression modeling with clinical scores (from r=0.675 for arm portion of NIHSS ). There was also correlation with 9-Hole-Peg (r=0.581) and no clear correlation with UE-FM, modified Rankin score and Stroke Impact Scale. Five of the 9 patients with dominant arm affected by stroke had NIHSS of 0 and UE-FM of 66. Abnormal movement kinematics were detected in both the contralesional and ipsilesional arms when compared to healthy controls.

Conclusions:
Characteristics of arm movement are essential to the understanding of motor recovery after stroke. Our study demonstrates subtle deficits of arm movement in task-directed testing that were not captured with traditional measures of stroke recovery.
Abstract TMP41: Early Mobility Initiated at 12 Hours Post Thrombolytic Therapy for Stroke Increases Likelihood for Discharge to Home
Authors: Gwilliam John , McNicholas Mechelle
Published: June 2021

Purpose:
To assess patient safety and discharge outcomes of initiating early mobility after 12 hours of receiving thrombolytic therapy (tPA) for stroke at a Primary Stroke Center.

Background:
Patients receiving tPA are traditionally maintained on bedrest for 24 hours due to an alleged risk of increased complications or falls, however this standard is not supported by data. Prior data among patients receiving tPA supports the concept of providing early mobility before 24 hours without an increased risk of falls or other adverse response. There is also evidence that early mobility in other critical care populations has positive impact on discharge disposition and decreasing the length of stay (LOS).

Methods:
A validated Early Mobility Protocol was implemented within 24 hours for all patients receiving tPA for stroke with a focus to progress each patient through the stages of the mobility protocol based on clinical presentation. Data from pre-implementation (January – May 2018) and post implementation (June 2018-December 2018) were compared for outcomes, including discharge disposition, adverse responses and LOS. T-test and Chi-square were used to determine significant difference in outcomes between groups.

Results:
Between January to December 2018 44 patients received tPA (18 pre-implementation and 26 post implementation). For the post implementation group 18/26 early mobility was initiated with 24 hours, 4/26 were placed on comfort care and 4/26 were transferred to a comprehensive stroke center. Among the early mobility group, there were no falls or adverse physiological events. Patients that participated with early mobility were more likely to discharge home, 46.15% vs 33.33%, less likely to require post-acute services, 15.38% vs 27.78%, and less likely to require transfer to a higher level of care, 15.38% vs 33.78%. There was not a significant difference in LOS.

Conclusion:
Providing early mobility to patients post thrombolytic therapy between 12-24 hours does not cause an increase in adverse physiological events. Additionally, providing early mobility has a positive impact on patient discharges to home. Further study may include initiating mobility at an early timeframe to examine the correlation to LOS and discharge outcomes.
Abstract TMP44: Ethnic Differences in Informal Caregiving After Stroke: The Brain Attack Surveillance in Corpus Christi (BASIC) Project
Authors: Hollenhorst Cecilia N , Lisabeth Lynda D , Gallo Linda C , Hsu Chia-Wei , Kim Sehee , Case Erin , Morgenstern Lewis B
Published: June 2021

Background and Aims:
We studied informal (non-paid) caregiving after stroke in a population-based study to determine if differences occurred between Mexican Americans (MAs) and non-Hispanic whites (NHWs). MAs are a less affluent population than NHWs. Family members who provide caregiving may need to interrupt educational and occupational goals to provide this care, which may perpetuate socioeconomic disparities between minority and majority populations.

Methods:
Between October, 2014 and December, 2016, stroke subjects in Texas, USA, were interviewed 90 days after stroke to determine if family or friends provided informal, unpaid caregiving, and for which activities of daily living (ADLs) they required help. Chi-square tests were used to assess the association of ethnicity and whom provided the caregiving, as well as ethnicity and the ADLs for which they required help. Ethnic differences between MAs and NHWs in receiving informal caregiving were determined using logistic regression. The odds ratio (OR, 95% CI) is reported with NHW as the referent group.

Results:
473 subjects answered the caregiving questions. There were no significant differences among the two ethnic groups with respect to age, sex, NIHSS score, marital status, or insurance. MAs were more likely to require help compared with NHWs for walking (p=0.0008), bathing (p=0.0004), hygiene (p=0.0018), eating (p=0.0059), dressing (p<0.0001), moving (p=0.0015) and toileting (p=0.0007). Among all subjects, 144 (30%) received informal caregiving (35% of 300 MAs versus 22% of 173 NHWs). There were no significant ethnic differences among which family member provided the caregiving. MAs were more likely to have informal caregiving OR=1.87 (95% CI 1.11-3.13) adjusted for age, sex, NIHSS, education, insurance and marital status.

Conclusions:
In this population-based study, MAs required more help than NHWs for assistance with ADLs, and MAs were more likely to receive this help through informal, unpaid caregiving than NHWs. Efforts to help minority and low-resource populations provide stroke care are needed.
Abstract TMP48: Effect of Pre-Morbid Antianxiety and Antidepressant Medications on Ischemic Stroke Functional Outcome
Authors: Peterson Cecilia , Wong Ka-Ho , Dela Cruz Michael , Taylor Kirby , Majersik Jennifer J , de Havenon Adam H
Published: June 2021

Introduction:
Antianxiety and antidepressant medications have shown some neuroprotective effects following stroke. However, the effect of premorbid use of these medications remains unclear.

Hypothesis:
Pre-morbid exposure to antianxiety or antidepressant medications will negatively impact recovery from acute ischemic stroke, measured by modified Rankin scale (mRS) at 90 days after stroke onset.

Methods:
This is a secondary analysis of the Albumin in Acute Ischemic Stroke (ALIAS) 2 trial. The primary outcome is 90-day mRS 0-1. The exposure is premorbid antidepressant or antianxiety medication. We fit univariate and multivariate logistic regression models to our outcome, with covariates chosen using a stepwise backwards interactive selection.

Results:
We included 806 patients with a mean (SD) age of 64.4 (12.8) years. The median (IQR) NIH Stroke Scale was 11 (8, 17) and 54.3% were male, 75.6% were Caucasian, 88.8% received tPA, 72.5% had hypertension, and 20.3% had diabetes. A total of 140/806 (17.4%) of patients took either an antidepressant or antianxiety medication, of which 91 took an antidepressant, 34 took an antianxiety medication, and 15 took both. The median (IQR) mRS Scale was one point higher in patients on antidepressant or antianxiety medication pre-stroke (3 vs. 2, p=0.019). The primary outcome of mRS 0-1 was seen in 37.7% of all patients. Taking an antidepressant or antianxiety medication was associated with lower odds of a good outcome in univariate (OR 0.61, 95% CI 0.41-0.91, p=0.015) and multivariate models (aOR 0.62, 95% CI 0.40-0.95, p=0.027) (Table 1).

Conclusion:
Pre-morbid exposure to antianxiety or antidepressant medications is associated with a worse outcome after acute ischemic stroke. This may be due to a negative impact of pre-stroke anxiety and depression that outweigh any neuroprotective factors of these medications.
Abstract TMP52: The Hidden Burden of Ischemic Stroke, Transient Ischemic Attack, and Atrial Fibrillation Hospitalizations Among Elderly Women
Authors: Lichtman Judith H , Leifheit Erica C , Wang Yun , Howard Virginia J , Goldstein Larry B
Published: June 2021

Background:
US women have a greater lifetime risk of stroke than men. Risk factors such as pregnancy and hormones influence sex differences in stroke at younger ages, but less is known about hospitalization rates and the proportion of hospitalizations for ischemic stroke (IS), transient ischemic attack (TIA), and atrial fibrillation (AF) by sex in different age groups. We assessed IS, TIA, and AF hospitalizations by sex and age.

Methods:
IS (ICD-9 433, 434, 436), TIA (435), and AF (427.31) hospitalizations were identified in the 2014 National Inpatient Sample (NIS). Hospitalization rates per 100,000 population aged ≥18y were calculated using age- and sex-specific Census population denominators and NIS sampling weights to obtain national estimates. We also determined the proportions of condition-specific hospitalizations by sex.

Results:
There were 338,654 (49.8% women) patients hospitalized for IS, 90,812 (58.0% women) for TIA, and 284,770 (49.9% women) for AF. For IS, TIA, and AF, respectively, the mean ages for women were 72.7y, 71.4y, and 74.0y vs 68.8y, 69.1y, and 66.2y for men. Hospitalization rates were higher for men than women at most ages for IS and AF; however, AF rates were higher in women beginning with age 80-84y (figure). Women represented a greater proportion of hospitalizations among those aged ≥75y for all 3 conditions (58% of IS, 62.5% of TIA, and 64.7% of AF events). The proportion of women hospitalized for TIA was higher in most age groups, but for IS and AF, the proportions of women exceeded those of men beginning at ages 75-80y and 70-75y, respectively.

Conclusion:
Women were older when hospitalized for IS, TIA, and AF, and women aged ≥75y comprised the majority of these hospitalizations. This highlights the need for early detection of AF and IS risk in elderly women and underscores the importance of treating modifiable conditions to decrease the burden of vascular illness in women. This is critical given the overrepresentation of women among the very elderly.
Abstract TMP73: Early Neurological Improvement: A Search for a Definition
Authors: Mulpur Bhageeradh , Handshoe Lacy , Andrapalliyal Nirmal , Hussain Muhammad
Published: June 2021

Background:
Early neurological improvement (ENI) is a metric that has been increasingly used to prognosticate favorable long-term clinical outcome following emergent large vessel occlusion (ELVO) treated by mechanical thrombectomy (MT). However, there is no clear consensus on what definition of ENI most accurately portends favorable long term clinical outcome. Definitions have varied from absolute differences in NIH Stroke Scale (NIHSS) to percentage reduction of NIHSS shortly after mechanical thrombectomy. In our analysis, we compared different definitions of ENI and how accurately they predicted favorable long-term clinical outcome.

Methods:
A review of all patients presenting to a comprehensive stroke center from January 2016 to December 2018 with ELVO treated by MT. Inclusion criteria were patients treated with MT for ELVO and who had documented admission NIHSS, NIHSS at day 0, NIHSS at day 1, and modified Rankin score (mRS) at 90 days. ENI definitions examined were: 1) reduction of day 1 NIHSS by
>
8 compared to admission NIHSS or day 1 NIHSS of
<
2, 2)
>
30% reduction of NIHSS at day 0 compared to admission NIHSS, and 3)
>
40% reduction of NIHSS at day 1 compared to admission NIHSS. Favorable long-term outcome was defined as mRS of 0-2 at 90 days. Positive predictive values (PPV), sensitivities, and specificities were calculated for each of the three definitions for favorable long term outcome.

Results:
A total of 227 patients met inclusion criteria for this study. Favorable long term clinical outcome was met in 126/227 (55.5%). Definition 1 had a sensitivity of 62.38%, specificity of 67.46%, and PPV of 60.58%. Definition 2 had a sensitivity of 45.54%, specificity of 77.78%, and PPV of 62.16%. Definition 3 had a sensitivity of 69.31%, specificity of 69.84%, and PPV of 64.81 %.

Conclusion:
In our cohort, ENI as defined by
>
40% reduction of NIHSS at day 1 from admission NIHSS, was most predictive of favorable long term clinical outcome
Abstract TMP75: Average Medicare Reimbursement for Stroke Care Has Decreased From 2000-2019
Authors: Pines Andrew R , Haglin Jack , Demaerschalk Bart
Published: June 2021

Introduction:
There is a lack of data regarding financial trends for procedural reimbursement in stroke care. An understanding of such trends is important as progress is made to advance agreeable reimbursement models in the care of stroke patients. The purpose of this study was to evaluate monetary trends in Medicare reimbursement rates for commonly utilized procedures in stroke care from 2000 to 2019.

Methods:
Reimbursement data for Current Procedural Terminology (CPT) codes was extracted from the Centers for Medicare & Medicaid Services. CPT codes were determined by frequency of procedures for Stroke-related ICD codes at our institution. All monetary data was adjusted for inflation to 2019 US dollars utilizing changes to the United States consumer price index.

Results:
After adjusting for inflation, the average reimbursement for all four included procedures within hemorrhagic stroke (ICD I60-I62) decreased by 18.4% from 2000 to 2019. The average reimbursement for two procedures within ischemic stroke (ICD I63), craniotomy and thrombectomy, increased by 3.5% (2003 -2019) and increased 3.0% (2016-2019), respectively. Data was not available for craniotomy prior to 2003, and not available for thrombectomy prior to 2016. Further, the adjusted reimbursement rate for included telestroke codes decreased by 12.1% from 2010-2019. All other included procedures decreased by 3.5% throughout this time. The difference in reimbursement rate between telestroke and other stroke-related procedures was statistically significant (p < .0001).

Conclusion:
To our knowledge, this is the first study to evaluate trends in Medicare reimbursement for stroke care. When adjusted for inflation, Medicare reimbursement for included procedures has steadily decreased from 2000 to 2019. Increased awareness of these trends is important to assure continued access to quality stroke care in the United States.