bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P23: Endovascular Treatment of Stroke in Elderly Patients: Comparison With Conventional Thrombolysis and Best Medical Treatment
Authors: El-Ghanem Mohammad H , Prestigiacomo Charles J , GANDHI Chirag D , Duffis E. Jesus
Published: March 2022

Background and Purpose:
Elderly patients have often been excluded from randomized stroke trials. The benefit of endovascular treatment of stroke in these patients remains uncertain. We sought to evaluate the outcomes of elderly patients treated endovascularly compared to those treated with conventional thrombolysis or best medical therapy.

Methods:
We retrospectively reviewed all stroke patients admitted to our center between 2008-2011. We included all patients age 75 or older with large vessel occlusion presenting within 8 hours of stroke onset. We evaluated outcomes at discharge including modified rankin score (mRS) and mortality as well as symptomatic intracerebral hemorrhage (sICH) within 24 hours for patients receiving endovascular treatment (EVT) with or without conventional thrombolysis , intravenous thrombolysis (IVT) or best medical treatment (BMT). Good outcome was defined as mRS of 3 or less at discharge.

Results:
A total of 91 patients met the inclusion criteria. 41 patients underwent EVT, 19 received IVtpa, and 31 BMT. Baseline NIHSS was not significantly different between the groups (17 SD 7, 16 SD 5, 14 SD 8 respectively). There was no difference in good outcomes between patients undergoing EVT compared to BMT (unadjusted OR 1.46, 95% CI 0.44-4.9), IVT compared to BMT (OR 2.4, 95% CI 0.62-9.36), or EVT compared to IVT (OR 0.61, 95% CI 0.18-2.06). There was no difference in mortality for the EVT, IVT, and BMT groups (22%, 26%, and 16% respectively, chi square p=0.79 for intergroup differences). Similarly there was no difference in rates of sICH 12%, 11%, and 3% p=0.41.

Conclusion:
Despite similar mortality and cerebral hemorrhage rates, we found no difference in good outcome for elderly patients treated with endovascular therapy or intravenous thrombolysis compared to best medical treatment within 8 hours of stroke onset. Larger studies are needed to clarify the role of intervention in elderly stroke patients.
Abstract T P234: Cell Cycle Inhibition via Blocking Src Family Kinases Promotes Hippocampal Neuron Survival and Improves Cognitive Function after Intraventricular Hemorrhage
Authors: Liu DaZhi , Ander Bradley P , Van Ken , Izadi Ali , Zhan Xinhua , Stamova Boryana , Jickling Glen C , Berman Robert F , Lyeth Bruce G , Sharp Frank R
Published: March 2022

Intraventricular hemorrhage (IVH) is one of the most serious hemorrhagic brain diseases being associated with blood brain barrier (BBB) disruption, brain edema, neuron loss, cognitive impairment and high mortality in humans. Increasing evidence suggests that neuronal cell death ensues when neurons attempt to re-enter the cell cycle. Our previous study has demonstrated that cell cycle inhibition via blocking Src family kinases (SFKs) prevents neuronal cell death. However, one of the concerns with cell cycle therapy might be that it would inhibit proliferation of neural progenitor cells (NPCs) and that inhibiting neurogenesis would produce cognitive effects related to the therapy itself.

Using the rodent in vivo IVH model we show that i.p. injection of SFK inhibitor (PP2) prevents IVH-induced death of hippocampal neurons and cognitive deficits assessed on the Morris Water Maze. Moreover, PP2 (i.p.) alone did not affect proliferation of NPCs and did not affect cognition. Since there are several SFK gene family members in brain, we targeted specific SFK subtypes (e.g. Fyn, Lck and c-Src) using a newly developed in vivo nanoparticle-based siRNA transfection system. We show that nanoparticle-siRNA-Fyn plus nanoparticle-siRNA-Src attenuate IVH-induced neuron loss and cognitive deficits. Nanoparticle-siRNA-Fyn nor nanoparticle-siRNA-Src had no significant affects on population of NPCs or cognitive side effects, possibly because the nanoparticle-based siRNA transfection system only produces transient knockdown of the gene targets. This could provide a novel therapy for treating IVH patients as the nanoparticle-based siRNA approach provides heightened specificity for specific SFK gene(s) with less off target effects and this approach has been used in humans.

Acknowledgements:
This study was supported by AHA Beginning Grant-in-Aid 12BGIA12060381 (DZL) and NIH grant NS054652 (FRS). There were no conflicts of interest.
Abstract T P247: An Interdisciplinary Approach Using a Root Cause Analysis to Decrease Door to IV tPA Times
Authors: Ballard Kimberly , Weinhardt Janice
Published: March 2022

Background and Issues:
The benchmark goal for stroke treatment is door to IV tPA in 60 minutes.

In 2010, average door to IV tPA treatment time for acute stroke patients at our acute care, tertiary teaching hospital was 87 minutes.

Purpose:
As a TJC certified primary stroke center, our purpose was to improve door to IV tPA times.

Methods:
Causes for lengthy tPA treatment times were identified by the stroke interdisciplinary team using a root cause analysis approach. Identified delays included: lab turn-around times, order entry, clinical decision making time, and tPA preparation, delivery, and administration.

Process improvement initiatives for order entry included revisions to electronic order sets to auto-populate and enhance efficiency and safety of order entry. Lab audits revealed that the BMP took the most time to process, resulting in initiation of point of care testing. For clinical decision making delays by neurology, immediate feedback was provided to the neurologist after each tPA administration. A year end summary was compiled showing door to tPA times for each attending neurologist. In addition, 3 APNs completed a neurovascular advanced practice fellowship program. Pharmacy instituted a tracking log to audit prep-to-delivery time which encouraged earlier notification and faster delivery times. Mixing of tPA was changed from (2) 50mg vials to reconstitution of (1) 100mg vial. Nurses who administer tPA were re-competencied using a simulation lab. Patients were triaged to a room in ED closer to the CT scanner. And, a count-down clock was initiated upon patient arrival to ED to enhance time awareness for all stroke team members.

Results:
Average door to tPA time has decreased from 87 minutes in 2010 to 50 minutes YTD 2013, a 37 minute improvement. In addition, volume increased by 25 more tPA administrations in 2012. Chi square comparisons of discharge dispositions showed no statistical differences for 2010 vs 2013 (p=.56) or 2012 vs 2013 (p= .18). Our hospital has received the American Stroke Association’s Target Stroke award for the past 2 years.

Conclusions:
An interdisciplinary approach using a root cause analysis is effective in identifying and implementing process improvements, ultimately leading to decreased door to IV tPA times.
Abstract T P252: Improving Quality of Care and Outcomes in the Community Through the Inclusive Collaboration Between a Certified Comprehensive Stroke Center and Regional Hospitals
Authors: Mazabob Janine M , Styron Suzan , Brown Gerard , Jones-Brown Monica , Suarez Jose , Bershad Eric , Venkatasubba Rao Chethan
Published: March 2022

Background:
and Issues As a certified Comprehensive Stroke Center (CSC) it is our obligation to the community and regional hospitals to improve the quality of care and stroke patient outcomes. The spokes are interdependent components of our CSC program; they seek a shared value in improving the delivery of stroke care in their community. Many areas utilize telemedicine without an inclusive operational model to deliver care. Our approach to advance stroke care was to cultivate relationships between staff, physicians, Emergency Medical System (EMS) personnel and hospital administrators.

Purpose:
Construct a stroke care model, utilizing an inclusive collaborative team that consists of EMS, spoke hospitals, and regional communities.

Methods:
W. Edwards Deming’s and John A Woods’s work served as the framework for our stroke and telemedicine programs. Leaders must function with an attitude of inclusiveness, resulting in no subordinates or superiors within the multidisciplinary team. Breaking down barriers and building a shared vision in the delivery of stroke care and recognizing that each department serves the other results in shared objectives. Utilizing tele-health cloud software enhances clinical collaborations. Elimination of fear creates an environment of no-blame, permitting everyone to work at their highest potential through approachable leadership. Analyzing each step and the resultant effect involves an in-depth evaluation of processes with implementable solutions and training and education.

Results:
Results of this inclusive collaboration included: an 85% increase in administration of tissue plasminogen activator at the spoke hospitals; EMS education of over 2000 personnel; physician-driven quarterly spoke hospital case study reviews; implementation of standardized stroke order sets and algorithms; and four spoke hospitals awarded primary stroke certification and state designation.

Conclusions:
Through an inclusive quality culture and a passionate stroke team, improving regional stroke care is achievable and sustainable. A reliable cloud-based network plays a role, but leadership in collaboration with the regional entities is the strength of the program.
Abstract T P257: Intramural Competition Significantly Reduces Door-to-Needle Time: Results From Adventist National Stroke Forum Door-to-Needle Time Challenge Process Improvement Project.
Authors: Allen Evan , Lovec Rhonda , Jones Cason , Acosta Indrani , Lubben Kathyrn , Grace Melissa , VanCattenburch Barbara , Jocson Michelle , Claunch Joshua D , Richards Donald , Garrett Paul , Qureshi Adnan I
Published: March 2022

Background:
Lower Door-to-needle times (DTNT) are associated with better outcomes. The Adventist National Stroke Forum (ANSF) was formed in 2011 to improve stroke care throughout Adventist hospitals.

Methods:
In 2011, ANSF completed a 4-month regional DTNT reduction competition among 7 Orlando Adventist hospitals. In 2013, ANSF conducted a 6 month national DTNT Competition following : Shawnee Mission Medical Center (KS), Florida Hospital Zephyrhills, Adventist Hinsdale Hospital (IL), Florida Hospital East Orlando, Glendale Adventist Medical Center (CA), Florida Hospital Orlando, and Florida Hospital Altamonte. Stroke teams implemented ways to reduce DTNT. Parenchymal hemorrhage type 2 (PH2) rates and percentage of stroke mimics treated with IV tPA were measured 4-6 months before and 4-6 months during both competitions. Comparison of DTNT between televideo and non-televideo cases is being completed in the national competition.

Results:
From 6/2011 to 10/2011 the regional study compared data from 27 tPA cases 4 months “before” the study to 28 tPA cases “during” the study. Regional DTNT “before” average (103 min) and median (95 min) times dropped 26% and 18% respectively to “during” average (76 min) and median (76 min). The odds of a DTNT of <60 minutes increased from 7% pre- competition to 33% during the regional competition in Orlando Adventist hospitals (2 of 28 vs. 9 of 27, OR=6.5, 95% CI 1.26 to 33.7). There was no regional increase in either PH2 or treated stroke mimics rates (1 of 28 before vs. 0 of 27 during for both PH2 and stroke mimics treated, OR=2.8947, 95% CI 0.11 to 74.2).

Conclusion:
A regional DTNT competition among Adventist hospitals produced a significant increase in percentage of patients receiving tPA with DTNT <60 min with no increase in PH-2 or number of stroke mimics treated. Final national competition results will be presented to determine 1) if regional DTNT competition benefits can be generalized nationally, 2) if 2011 Regional DTNT competition gains were sustained among Orlando Adventist hospitals, and 3) if televideo was associated with lower DTNT's.
Abstract T P273: Development and Impact of the Midwest Stroke Action Alliance
Authors: Kim Elizabeth , Klassman Lynn , Jennrich Mary Kay , Rossman Deborah , Hoelzel Sandra , Masor Minna B , Reilly Ginger , O'Neill Kathleen ,   on behalf of the Midwest Stroke Action Alliance
Published: March 2022

Background:
Illinois has approximately 54 certified stroke centers serving the metropolitan Chicago area. It is understood that certified centers impact stroke care and community outreach, but a greater impact could be gained through collaboration and shared resources.

Purpose:
To describe the development and contributions of the Midwest Stroke Action Alliance (MSAA) around the Chicago metropolitan area.

Methods:
In 2007 an informal group gathered to promote stroke community awareness. In 2011 the group decided a greater impact could be made on the community and stroke care through incorporation, formalizing membership and setting goals. Membership was individual, not tied to organizations. An election for the board/committee chairs took place and committees (quality improvement, professional growth/networking, and education) were established.

Mission:
The MSAA is dedicated to utilizing evidence based practice to reduce the risk and burden of stroke by increasing stroke awareness in the broader community and providing a strong united voice for stroke advocacy.

Goals:
1).Support quality stroke care through evidence based practice and clinical research, 2).Provide coordinated professional and community education,and 3).Provide an environment that promotes professional growth and problem solving.

Results:
As of July 2013 MSAA has 42 active members and 52 members at large. Membership includes representation from acute care, rehabilitation, industry and stroke advocacy. MSAA meets quarterly and the board/committees meet monthly. To date, the impact of MSAA on community and quality of stroke care includes: Biannual education/networking events, Annual conference for stroke care professionals, GWTG-Stroke registry benchmark group, Best practice sharing, Stroke Awareness month and National Stroke Alert Day activities, and 2012 & 2013 “Strike Out Stroke” Cellular Field-Chicago White Sox.

Conclusions:
The development of the MSAA has lead to improved collaboration through use of pooled resources in the Chicago metropolitan area and resulted in enhanced community outreach and professional development. The GWTG-Stroke benchmark group will continue to measure the overall impact on stroke care.
Abstract T P297: The Minimum Data Set: A Tool for Nationwide Assessment of Readmission After Ischemic Stroke
Authors: Fehnel Corey R , Lee Yoojin , Mor Vincent
Published: March 2022

Background:
Hospital readmission is a primary focus for health care quality improvement, and a key provision in the Affordable Care Act. Current models predicting risk for readmission are limited by a lack of individual level data. The Minimum Data Set (MDS) for nursing home resident assessment offers a unique opportunity to better understand individual risk factors for readmission. An analysis was performed to evaluate whether sufficient and reliable data exist for further study.

Methods:
Medicare inpatient hospital discharge claims for the year 2008 among persons more than age 65 discharged to Skilled Nursing Facilities were used to identify cases by ICD-9 codes for Acute Ischemic Stroke (430.x, 431.x, 433.x, 434.x, and 436.x). Linkage of the sample to full MDS records was performed by matching Medicare claim number, social security number, and date of birth. Demographic characteristics of the sample were ascertained by linking inpatient claims with Medicare Enrollment Files. Mortality and readmission rates were determined using hospital claims and the enrollment record for the analytical sample at intervals of at 30, 60, and 90 days post-hospital discharge.

Results:
Among 410,825 subjects meeting study inclusion criteria, unique record linkage with the Minimum Data Set was available for 143,150 subjects. Mean age was 82.1(± SD 7.8), and 63% were female. Unadjusted mortality rates among Medicare Part A claims at 30, 60, and 90 days were 14%, 16%, and 17% respectively. Unadjusted mortality rates among MDS records at 30, 60, and 90 days were 10%, 13%, and 14% respectively. Readmission rates among Medicare Part A claims at 30, 60, and 90 days were 14%, 21%, and 26% respectively. Readmission rates among MDS records at 30, 60, and 90 days was 23%, 32%, and 39% respectively.

Conclusions:
A large nationwide sample representing 35% of Medicare ischemic stroke discharges is available through the MDS. A higher proportion of new onset ischemic stroke patients require skilled nursing facility admission than indicated by previous studies in smaller cohorts. Mortality is lower, but readmission is higher among skilled nursing facility residents after ischemic stroke. Future study will utilize the MDS to further define individual risk factors predictive of readmission.
Abstract T P300: Stroke after Aortic Valve Surgery Increases Billing and Length of Stay
Authors: Messe Steven R , Acker Michael A , Kasner Scott E , Bilello Michel , Szeto Wilson Y , Woo Y. Joseph , Bavaria Joseph E , Fanning Molly , Giovannetti Tania , Floyd Thomas F ,   the Deteremining Neurologic Outcomes from Valve Operations (DeNOVO) investigators
Published: March 2022

Background and Purpose:
Aortic valve disease is increasing in prevalence as the population ages. We previously presented a prospective cohort of patients undergoing open surgical aortic valve replacement (AVR) and established that stroke is a frequent complication. However, the impact of stroke on the cost and length of hospitalization is not well characterized.

Methods:
We performed a prospective cohort study of patients ≥ 65 years old undergoing open surgical aortic valve replacement for moderate to severe calcific aortic stenosis at two hospitals in our health system. Subjects were evaluated by neurologists at post-operative days 1, 3, and 7. Hospital billing charges, length of stay in the intensive care unit (ICU), and total hospital length of stay were compared between patients with and without stroke using rank sum. Correlations between stroke severity and hospital billing charges, length of stay in the ICU, and total hospital length of stay were evaluated using Spearman correlation.

Results:
Complete hospital billing and length of stay data were available for 174 subjects, mean age 76 (standard deviation 6) years, 35% female, 6% non-white. Clinical stroke occurred in 28 (16%), median National Institutes of Stroke Scale (NIHSS) 3, interquartile range (IQR) 1 - 13. In-hospital mortality occurred in 9 (5%). Stroke was associated with increased total hospital billing charges, median $281,012 (IQR $218,754 - $304,031) vs $209,807 (IQR $175,163 - $273,755) for those without stroke, p=0.003. Clinical stroke was also associated with increased length of stay in the ICU, median 3 days (IQR 2 - 5) vs 1 day (IQR 1 - 2), p =0.0006, and total length of stay, 12 days (IQR 9 - 15) vs 10 days (IQR 8 - 13), p=0.01. Clinical stroke severity based on NIHSS was moderately correlated with total hospital billing charges (rho=0.49, p<0.0001), length of stay in the ICU (rho=0.53, p<0.0001), and total hospital length of stay (rho=0.36, p<0.0001). Excluding patients who died in the hospital did not change any of the findings.

Conclusions:
Clinical stroke complicating valve replacement is associated with increased hospital billing charges, length of stay in the intensive care unit, and total hospital length of stay, all related to stroke severity.
Abstract T P301: Annual Ischemic and Hemorrhagic Stroke Costs in an Atrial Fibrillation Population from a Health Plan Perspective
Authors: Sussman Matthew , Lin Iris , Kwong Winghan J , Munsell Michael , Friedman Mark , Selim Magdy , Menzin Joseph
Published: March 2022

Background:
Limited data evaluating the economic burden of ischemic stroke (IS), relative to that of hemorrhagic stroke (HS) from a population management perspective exist. This study estimates the 1-year stroke-related cost to manage IS and HS events in an adult population with atrial fibrillation (AF).

Methods:
An incidence-based model was developed using published AF prevalence rates and stroke incidence/mortality rates observed in the MarketScan databases (2005-2011). Medical and pharmacy claims data for adult patients who had ≥1 inpatient or ≥2 outpatient claims for AF and ≥1 primary inpatient claim for stroke were analyzed. Adjusted mean costs for IS and HS index event hospitalizations and follow-up care during the 1 year following index stroke event were estimated using generalized linear models controlling for demographics, stroke type, comorbidities, and oral anticoagulant use.

Results:
In a typical health plan with 1 million enrollees, we estimated that 9,500 patients would have AF. Annual stroke incidence rates among AF patients varied by age and ranged from 0.23-3.57 (IS) and 0.06-0.49 (HS) per 100 person-years, resulting in approximately 176 and 33 new cases of IS and HS in 1 year respectively. Mortality rates during IS and HS hospitalizations were 5.6% and 23.2%, respectively. Adjusted mean healthcare cost for patients who died during hospitalization was higher for IS than HS ($29,810 [95% CI $27,784-$31,987] vs. $23,492 [$21,779-$25,339], P<0.0001), while adjusted mean 1-year cost associated with IS was lower than HS among those who survived their index admission ($25,635 [95% CI $25,104-$26,173] vs. $48,850 [$46,351-$51,483], P<0.0001). Total annual stroke-related healthcare costs for the health plan were $5,991,423, with 76% of costs attributable to IS due to its higher incidence and lower mortality rate.

Conclusion:
Patients with a history of AF are at risk for IS and HS, with IS accounting for more annual healthcare costs to a health plan due to its higher incidence than HS. These data may be useful in assessing the risk-benefit of anticoagulation therapy for stroke prevention in AF patients from a health plan perspective.
Abstract T P311: Prospective Assessment of Medical Decision-Making Capacity in Stroke Patients using a Rapid Standardized Questionnaire: Can My Patient Consent for Treatment or Clinical Trial?
Authors: Feng Kimberly , Person Cheryl , Phillips-Sabol Jacqueline , Williams Bethany R , Cai Chunyan , Jacobs Amber , Indupuru Hari , Aramburo-Maldonado Linda , Shen Loren , Grotta James C , Barreto Andrew D
Published: March 2022

Background and Objective:
Stroke deficits frequently alter patient medical decision-making capacity (
MDC
) resulting in lost trial recruitment and reducing validity of qualitative outcome measures. Since no standardized tool exists for MDC evaluation in stroke, we tested a validated standardized questionnaire used for medical patients, the Aid to Capacity Evaluation (
ACE
), vs. independent clinician assessment in mild-to-moderate severity stroke patients. We hypothesized that the ACE would show similar agreement with clinicians and therefore be appropriate for rapid bedside screening for MDC.

Methods:
Ischemic or hemorrhagic stroke patients underwent 3 independent capacity assessments by a medical student (ACE), psychiatrist (
PS
) and neuropsychologist (
NP
). Inter-rater reliability was assessed using intraclass correlation (
ICC
) and Cohen’s kappa. Assuming the clinician as the gold-standard, we tested sensitivity and specificity vs. ACE.

Results:
All planned 30 patients (90% ischemic; mean age 67.8; 60% male; median NIHSS = 6) were prospectively enrolled between 7/13- 8/13. The median time from stroke onset to first capacity assessment was 3.3 days. 11 (37%) had aphasia and/or neglect and 38% had left hemispheric stroke (see table). ACE agreed with PS and NP in 59% (kappa 0.293; 95% CI 0.08-0.51) and 76% (kappa 0.494; 95% CI 0.19-0.80) of cases, respectively. Despite low sensitivity and NPV, specificity and PPV of ACE vs. clinicians ranged 88-100%; only classifying 1 patient capable when clinicians scored incapable. ICC among all raters was 0.474 (95% CI 0.25-0.68).

Conclusions:
There was fair overall agreement between a standardized questionnaire and expert clinicians. The ACE was highly specific in identifying mild-to-moderate severity stroke patients who lacked MDC. The ACE might be a useful screening tool to determine

lack
of capacity

in stroke patients, but low sensitivity for identifying

presence
of capacity

warrants caution and further study.
Abstract T P327: The Association of Neighborhood and Transcranial Doppler Screening Among Children with Sickle Cell Disease
Authors: Reeves Sarah L , Dombkowski Kevin J , Fullerton Heather , Braun Thomas , Lisabeth Lynda D
Published: March 2022

Background:
Although Transcranial Doppler (TCD) screening is recommended to assess the need for stroke prevention efforts among children with sickle cell disease (SCD), screening rates are low. Few individual level factors that impact screening have been identified, and little is known regarding the degree to which neighborhoods may influence screening. We sought to identify neighborhoods with low TCD screening rates and neighborhood-level factors related to screening among children with SCD to inform the utility of community level interventions to improve TCD screening.

Methods:
Children ages 2-16 years with SCD (HbSS, HbBeta-Thalessemia) were identified in Michigan Medicaid (2007-2011) through newborn screening records and were continuously enrolled for ≥1 year; each child could contribute multiple years. We determined receipt of ≥1TCD screening (y/n) each year from claims. Neighborhood of residence was defined by census tract on January 1 of each year and proportion of children receiving TCD in the tract was calculated. Tracts were investigated for clustered areas of screening globally (Moran’s I) as well as for local areas (Gi* statistic). Median household income, % unemployment, and % black residents for each tract were ascertained from the American Community Survey. Logistic regression with generalized estimating equations was used to model the association between TCD screening and each neighborhood-level factor, adjusted for age.

Results:
In 2007, there were 218 children with SCD in Michigan Medicaid (50% female, 98% black, 87% HbSS) with a total of 1,008 person-years eligible for analysis in 293 census tracts. Median and mean screening rate in tracts were 0% and 21%. Screening rates were spatially random in the study area (p=0.60). No tracts were identified with locally lower screening rates than the mean, but 27 tracts showed locally higher screening rates (Gi*>1.96). No neighborhood factors were associated with receipt of screening when adjusted for age.

Conclusion:
Neighborhood factors were not found to be associated with receipt of TCD, although some neighborhoods showed higher than average screening rates. Further investigation of the characteristics of these neighborhoods may suggest ways to improve screening in surrounding areas.
Abstract T P346: Anticoagulation Intensity of Low-dose Rivaroxaban for Japanese Patients With Nonvalvular Atrial Fibrillation
Authors: Okata Takuya , Toyoda Kazunori , Okamoto Akira , Miyata Toshiyuki , Nagatsuka Kazuyuki , Minematsu Kazuo
Published: March 2022

Objective:
In Japan, low-dose rivaroxaban [15 mg o.d. and 10 mg o.d. only for CCr 30-49 mL/min] was approved for clinical use to NVAF patients, because of its unique pharmacokinetics in Japanese subjects showing higher rivaroxaban concentration than Caucasian subjects when using the same dosage and the results of the J-ROCKET AF trial (Hori M, et al: Circ J 2012). We aimed to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese NVAF patients, especially in those taking crushed tablets.

Methods:
Consecutive stroke patients with NVAF admitted between July 2012 and July 2013 were studied. Prothrombin time (PT, Recombiplastin/HemosIL®), activated partial thromboplastin time (aPTT, Actin/Sysmex®), and anti-Xa chromogenic assay (Stago®) were measured just before and 4h and 9 h after the administration at the steady state of rivaroxaban (mean 6th day). We calibrated its plasma concentration based on anti-Xa assay.

Results:
Of 104 patients (32 women, 74±9 y.o., BW 59±11 kg) involving 36 with CCr <50 ml/min (Cockcroft-Gault), 57 took 15 mg o.d. of rivaroxaban and 46 took 10 mg o.d. Median PT, aPTT, and concentration were 12.8s, 31s, and 13.5 ng/ml just before administration, 19.3s, 42s, and 170.5 ng/ml at 4h, and 15.8s, 37s, and 63.0 ng/ml at 9h. Both PT and aPTT were positively correlated with concentration (r=0.88, 0.74, respectively). Age, BW, CCr, and rivaroxaban dosage were not associated with concentrations at 4h and 9h, though they were associated with concentration just before administration. In 10 patients taking crushed tablets, including 5 patients via a nasogastric tube, median PT (15.8s vs. 19.7s, p<0.001), aPTT (33s vs. 42s, p=0.012) and concentration (53 ng/ml vs. 186 ng/ml, p<0.001) at 4h were lower than the remaining 94 patients. Crushed tablets were independently associated with lower anticoagulant intensity.

Conclusion:
Nearly peak concentration of rivaroxaban was similar or a little lower than that in the ROCKET AF and J-ROCKET AF trials (Kaneko M, et al: Drug Metab Pharmacokinet 2013). Tablet crushing may decrease anticoagulation intensity.
Abstract T P365: Does Stroke Contribute to Racial Differences in Cognition?
Authors: Levine Deborah A , Kabeto Mohammed U , Langa Kenneth M , Lisabeth Lynda D , Rogers Mary A , Galecki Andrzej T
Published: March 2022

Objective:
Although dementia prevalence is higher in blacks than whites, it is unknown whether blacks’ elevated risk of dementia is due to racial differences in acute stroke, the impact of stroke on cognitive health, or other factors. We determined whether racial differences in cognitive function are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition.

Methods:
The study population was a prospective cohort of 5,126 white or black adults aged ≥65 years responding to the Health and Retirement Study in 1998 and followed through 2006. Cognitive function was assessed at 2-year intervals with a modified version of the Telephone Interview for Cognitive Status (TICS-m). Acute strokes were identified using linked Medicare claims. Adults with cognitive impairment (TICS-m<7) in 1998 were excluded. We examined changes in cognitive function over time by race, before and after adjusting for time-dependent acute stroke using linear mixed effects models that also included baseline values of age, sex, education, self-reported history of stroke, depressive symptoms, TICS-m, and random effects for intercept and slope. We then added a race-by-stroke interaction in the model.

Results:
There were 5,126 adults with ≥1 follow-up TICS-m measure, of whom 490 had acute stroke (466 whites and 24 blacks; P=0.39). Blacks had lower adjusted TICS-m scores than whites (mean difference, -1.41 points; 95% CI, -1.67 to -1.16 points; P<0.001), and this racial difference persisted after adjusting for acute stroke (Table). Acute stroke was associated with average acute decreases in TICS-m scores of about 1.17 points. The association of acute stroke with change in cognition did not differ by race (P for race-by-stroke interaction=0.62).

Conclusions:
In this nationally representative cohort of older adults, acute stroke did not explain black-white differences in cognition or impact cognition differently by race.
Abstract T P76: Human Neural Stem Cells Rapidly Ameliorate Symptomatic Inflammation In Ischemic-Reperfusion Cerebral Injury
Authors: Huang Lei , Snyder Evan , Lee Jean-Pyo
Published: March 2022

Ischemic stroke injury results not only from ischemia but also from reperfusion. Stroke causes a loss of cerebral parenchyma and its associated cells, disruption of neuronal connections, compromise of the blood-brain barrier, and inflammation. We tested whether exogenously engrafted human neural stem cells (hNSCs) could migrate rapidly and extensively to damaged regions following intracranial transplantation and counteract a number of these pathological processes. We used a stroke mouse model with middle cerebral artery occlusion (MCAO) to induce focal ischemia followed by reperfusion. We transplanted hNSCs 24 hours after MCAO to correspond to the upregulation of endogenous proinflammatory cytokines, which can act as stem cell-recruiting factors. We found that 24 hrs post-transplantation, engrafted hNSCs had migrated extensively to the lesion, brain infarct volume was reduced, and behavioral function was significantly improved compared to MCAO controls. Because the time course of this repair was too short for cell replacement, we hypothesized that the mechanisms of therapeutic action are anti-inflammatory. Microglial activation and proinflammatory gene expression (TNF-α, IL-6, and IL-1β) were reduced, and blood-brain barrier damage was ameliorated in hNSC-transplanted mice. Our findings demonstrate clear benefits of transplanting hNSCs during the early stages of ischemic stroke.
Abstract T P93: Cerebral Artery Calcification is Associated with Deep Cerebral Microbleed
Authors: Shin Dong-Woo , Chung Pil-Wook , Park Kwang-Yeol , Kim Jeong-Min , Ha Sam-Yeol
Published: March 2022

BACKGROUND:
Cerebral arterial calcification has been reported to be associated with lacunar infarction and white matter hyperintensities. The aim of the present study was to determine the association between arterial calcification and cerebral microbleed (CMB) which is a small hemorrhagic lesion in the brain and is known to be associated with small vessel disease (SVD).

METHODS:
We identified 834 consecutive patients with acute ischemic stroke who visited a tertiary university hospital within 7 days of symptom onset and underwent both CT angiography and brain MR imaging. Calcifications in the intracranial internal carotid artery (ICA) were graded on CT angiography. CMBs were counted relative to their location on susceptibility-weighted imaging. The association between ICA calcification and CMB was tested using logistic regression analysis.

RESULTS:
The patients ranged in age from 26 to 111 years (67 ± 12.7 years, mean ± standard deviation). ICA calcification and CMB were found in 660 patients (79.1%) and 335 patients (40.2%), respectively. On multivariable analysis, ICA calcification was associated with CMB of any location (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.31 - 2.36 for mild calcification; OR 2.86, 95% CI 2.01 - 4.08 for severe calcification, respectively). More robust association was found between calcification and CMB in the basal ganglia, thalamus, or brainstem (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.27 - 2.44 for mild calcification; OR 3.51, 95% CI 2.39 - 5.14 for severe calcification, respectively). However, ICA calcification was not associated with CMB strictly located in the lobar area.

CONCLUSIONS:
ICA calcification is an independent predictor for deep CMB but not for a strictly lobar CMB. Our findings add evidence to the hypothesis that cerebral arterial calcification is associated with SVD and might contribute to the elucidation of the pathogenesis of SVD.
Abstract W MP110: Stimulant Medications as a Risk Factor for Childhood Stroke
Authors: Hills Nancy K , Sidney Stephen , Finley Patrick R , Fullerton Heather J
Published: March 2022

Background:
The association of stimulants and stroke in adults has raised concerns about attention deficit hyperactivity disorder (ADHD) medications prescribed to children. A large retrospective cohort study found no increased risk for serious cardiovascular events but was limited in how stroke was identified. We examined the association between stimulant medications and stroke in a case-control study with cases rigorously detected.

Methods:
This study was nested in a cohort of 2.5 million children (<20y) enrolled in a large integrated health care plan, 1993-2007. Cases of hemorrhagic and ischemic stroke at ≥2 years of age were identified from searches of radiology reports in addition to diagnostic codes, and confirmed through independent chart review; 4 controls per case were randomly selected, matched by age, year of enrollment and primary care facility. The cohort was linked to electronic pharmaceutical records to collect data on ADHD medications prior to stroke (index date for controls). Analyses using conditional logistic regression focused on current use (at time of event), use within the past 6 months (at least 2 sequential prescriptions), and ever use. Length of most recent continuous exposure was compared between groups. Our study was powered to detect an OR as low as 4.4 for current exposure and 3.7 for 6-month exposure.

Results:
We identified 258 cases and 1030 controls. No measured exposures significantly differed between the two groups in adjusted analyses (Table). The median (IQR) length of continuous exposure for those using stimulants within the prior 6 months was 322 days (100, 187) for cases and 377 days (198, 821) for controls (p=0.10).

Conclusions:
No significant associations were found between stroke and use of ADHD stimulants in this study rigorously identifying pediatric stroke outcomes over a 14-year period. The OR for current use was similar to that found in a large cohort study.
Abstract W MP119: Features of Capillary Malformation-Arteriovenous Malformation Syndrome Associated Cerebral Vascular Anomalies
Authors: Fifi Johanna , Ortega-Gutierrez Santiago , Altschul David , Paramasivamn Srinivasan , Berenstein Alejandro
Published: March 2022

Background:
Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant disorder caused by mutations in the RASA1 gene. The hallmark is cutaneous capillary malformations. High flow AVMs occur in about 1/3 of patients, with cerebral malformations in about 10%. We evaluate the clinical and radiographic features of cerebral malformations in CM-AVM patients.

Methods:
Since 2006, pediatric patients presenting to our center with head and neck high flow vascular malformations have been screened for capillary malformations. Our database of pediatric head and neck vascular malformations was reviewed for patients with capillary malformations. Patients with only facial arteriovenous malformations were excluded. Clinical and radiographic features were reviewed.

Results:
9 patients were found to have high flow head and neck malformations and CM. 1 patient with an ear AVM was excluded. Of the remaining, 4 patients had confirmed positive genetic mutation in the RASA1 gene. All four of these patients had complex pial arteriovenous fistulas - One was supratentorial and three were in the posterior fossa. One premature infant with a complex posterior fossa lesion and heart failure died shortly after birth. One infant with mild heart failure is on medication and awaiting treatment. The other two were asymptomatic and treated with embolization. These patients are neurologically intact and reaching developmental milestone. 3/4 patients had first degree relative with CM with or without AVM. One patient with vein of Galen malformation and CM has tested negative for RASA1 mutation. The other three patients have not yet been tested. Of these, two have pial arteriovenous fistula which have been treated. One 2 year old had a multifocal dural arteriovenous fistula.

Conclusion:
Cerebral vascular anomalies in CM-AVM syndrome are often complex lesions. Thus far, all confirmed RASA1 mutation patients at our center have pial arteriovenous fistulas. Vein of Galen malformation and dural AVM may also be associated. Pediatric patients with these diagnoses should be screened for CM. The diagnosis of CM-AVM with RASA1 mutation plays a role in family planning and screening of other family members.
Abstract W MP43: Fetal and Maternal Microchimeric Responses to Ischemic Stroke
Authors: Patel Anita , Ritzel Rodney , Pan Sarah , McCullough Louise
Published: March 2022

Background and Purpose:
Ischemic stroke is a sexually dimorphic disease. Events that occur during pregnancy can have lasting implications on both the mother and fetus for decades after parturition. In particular, fetomaternal microchimerism, the bidirectional exchange and persistence of cells between a pregnant female and her fetus, has been shown to play a role in various disease pathologies but has not been well studied in the brain. We hypothesized that microchimeric cells (MCs) home to sites of injury as part of the immune response to stroke and display a stem cell phenotype with potential to aid in repair.

Methods:
C57Bl/6 mice were bred with GFP transgenic mice using specific mating paradigms to generate fetal and maternal microchimeras. Young 10-12 week old maternal-microchimeric mice and 12-14 week old parous fetal-microchimeric mice were subject to a 90 min MCAO or sham surgery and sacrificed at 72hr or 30 day post-reperfusion (n=10). Blood, bone marrow (BM), and brain tissue were analyzed by co-labeling with anti-GFP antibody using immunohistochemistry, flow cytometry, and cytospin preparations. RNA was extracted from GFP+ cells in situ by laser capture microdissection to further characterize MCs.

Results:
At 72hrs after stroke, clusters of MCs were present in the ischemic area. Flow cytometry of maternal blood and BM identified a rare cell population (0.01-0.001%) of GFP+CD45+CD34+, indicative of umbilical cord stem cells. Engrafted MCs with stem-like phenotypes were also found in cytospin preparations of blood and BM. At 30 day after stroke, MCs in the brain displayed mature endothelial morphology in 60% of animals. This was validated by RT-qPCR, confirming the presence of MCs in the ischemic brain.

Conclusions:
We have shown that MCs display stem cell phenotypes, are actively recruited to the ischemic brain, and selectively aggregate at sites of injury. Our data show that MCs are mobilized in BM and blood early after stroke and later give rise to endothelial cells, indicating a potential angiogenic role in promoting revascularization. Further characterization of the functional contribution and mechanisms that underlie these responses may prove useful in assessing female responses to brain injury.
Abstract W MP45: Longitudinal MEG Measures for Cortical Reorganization Underlying Paretic Hand Recovery After Subacute Stroke
Authors: Tang Chih-Wei , Lee I-Hui
Published: March 2022

Background:
Post-stroke cortical reorganization in relation to sensorimotor recovery has been largely recognized by functional magnetic resonance imaging. However, altered hemodynamics in cerebrovascular diseases may hamper the results based on blood oxygen level-dependent signals. Magnetoencephalography (MEG) directly measures neural activities with high temporal resolution, but very few studies in stroke patients are available. In this study, we sought to characterize MEG sensorimotor oscillations and sensorimotor network during post-stroke recovery.

Subjects and Methods:
We longitudinally assessed patients with first-time, unilateral, ischemic subcortical stroke in the middle cerebral artery territory with mild to moderate hand weakness for upper extremity motor function scales, unilateral finger lifting-related MEG and functional connectivity analysis at 2, 4 and 8 weeks after stroke in comparison with healthy controls. All stroke patients received standardized intensive rehabilitation during post-stroke 2-4 weeks. Minimum-norm estimate was used for MEG source reconstruction.

Preliminary Results:
Compared with the controls (n=13), the stroke patients (n=15) had markedly reduced task-related desynchronization and synchronization in mu (8-13Hz) and beta (16-30Hz) rhythms. At sensor level, the induced activities shifted spatiotemporally from the ipsilesional primary sensorimotor cortex towards the supplementary motor and even contralesional areas. After rehabilitation, the patients had significant functional improvements in correlation with increased beta rhythm functional connectivity at the ipsilesional somatosensory cortex and the contralesional premotor cortex. More delicate anatomic information provided by MEG souce projection was established and under final analysis.

Conclusions:
The results provide neurophysiological measures of cortical plasticity and insights into target regions for neuromodulation strategies after stroke.
Abstract W MP8: The Natural History of Acute Ischemic Stroke from Large Vessel Proximal Occlusion: A Comparison with the IMS III Patients
Authors: Janardhan Vallabh , Venizelos Alex , Gianatasio Ryan M , Chen Sherman H , Bhuva Parita , Murray Mark M , Vijayappa Madhu B , Hansen Paul A , Guthmann Anita , Cheung Raymond , Leung Thomas , Ammar Lynne , Myer Denise , To Christina , Kuo Sophia S , Buell Hope , Barraza Leticia , Bose Arani , Sit Siu Po ,   Penumbra FIRST Trial Investigators
Published: March 2022

Purpose:
The recent termination of the IMS III trial due to futility has led to further controversies surrounding the use of IA endovascular therapy for stroke intervention. But since not all IMS patients had confirmed large vessel occlusion, it remains unclear if the study population was appropriate for endovascular therapy. The purpose of this study was to assess the natural history of a stroke cohort eligible for IA intervention and compare its outcome with the IMS III results.

Methods:
The FIRST Trial is a prospective natural history study of a stroke cohort eligible for but untreated by endovascular therapy and ineligible or refractory to IV rtPA. The primary endpoint is functional outcome as defined by 90-day mRS ≤2. All patients were assessed for 90 days from stroke onset.

Results:
Among the 62 patients who met entry criteria, mean age was 68 ± 16 years; median admission NIHSS was 18 (IQR 14-22). Occlusions were in the ICA (31%), MCA (66%) and other (3%). At admission, the TIMI 0-1 rate was 100%, and the TICI 0-1 rate was 98%, with 52% refractory to IV rtPA. Spontaneous recanalization to TIMI 2-3 or TICI 2a-3 was only seen in 10% or 13%, respectively. Good 90-day outcome was achieved in 21%; 42% died. When compared to the FIRST patients, the IMS III IA-treated group had significantly higher recanalization (p<0.0001) and functional independence (p=0.00363) rates; and lower mortality (p=0.00013). The IV control group also had a higher rate of recanalization and 90-day functional independence, and a lower rate of mortality. In another analysis, pooled patients (N=942) treated by the aspiration-based Penumbra System had a higher rate of recanalization (p<0.0001), lower mortality (p=0.00052) and greater functional independence at 90 days (p=0.00719).

Conclusion:
These results indicate selection of an appropriate study population is important in assessing the safety and effectiveness of endovascular therapy in large vessel occlusion.