bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 64: Glucocorticoid-associated Worsening in Reversible Cerebral Vasoconstriction Syndrome (RCVS):
primum non nocere!
Authors: Singhal Aneesh B , Topcuoglu Mehmet A
Published: June 2021

Objective:
Factors predicting poor outcome in RCVS are not fully identified.

Methods:
We retrospectively analyzed clinical, imaging and angiography data in 162 RCVS patients. Uni- and multi-variable analysis were performed to identify predictors of persistent (non-transient) clinical worsening, radiological worsening, early angiographic progression, and poor discharge outcome (modified Rankin Scale score 4-6).

Results:
The mean age was 44±13 years, 78% women. Persistent clinical worsening occurred in 14% at 6.6±4.1 days after symptom onset; radiological worsening in 27% (mainly new infarcts), and angiographic progression in 15%. Clinical worsening correlated with angiographic progression and new non-hemorrhagic lesions. Age and gender did not independently predict any type of worsening. Infarction on baseline imaging predicted poor outcome. Prior serotonergic antidepressant use predicted clinical and angiographic worsening but not poor outcome. Intra-arterial vasodilator therapy independently predicted clinical worsening and poor discharge outcome but was offered to more severe cases. Glucocorticoid treatment was an independent predictor of clinical worsening (OR 10.2, 95% CI 3.3-31.6) as well as imaging and angiographic worsening and poor discharge outcome. Of N=23 with clinical worsening, 17 received glucocorticoids (15 within prior 2 days - FIGURE). There were no significant differences in baseline brain lesions and angiographic abnormalities between glucocorticoid-treated and untreated patients. Clinical worsening occurred in 37% of 46 treated vs. 5% of 116 not treated (p<0.001); discharge mRS 4-6 occurred in 47% treated vs. 17% not-treated, and 61% of treated patients developed new brain lesions.

Conclusion:
Worsening in RCVS can be predicted from certain baseline features. Empiric glucocorticoids "
until vasculitis is ruled out
" is best avoided esp. since RCVS can be accurately diagnosed upon admission using our recent criteria.
Abstract 66: Dynamics of Statin Use and Outcomes After Recanalization Treatment for Acute Ischemic Stroke: When, How Much and for Whom?
Authors: Jeong Han-Gil , Kim Beom Joon , Yang Mi-Hwa , Han Moon-Ku , Bae Hee-Joon
Published: June 2021

Introduction:
Statin has the potential to be effective in the early phase of recanalization. However it is largely unknown in which group, when, and at what doses statin use is beneficial after recanalization.

Methods:
From a total of 7663 stroke cases of Seoul National University Bundang Hospital between July 2007 and Dec 2015, we collected eligible cases with the following inclusion criteria; (1) Lesion-documented ischemic stroke (N=6151); (2) received recanalization treatment (N=908). We excluded cases with missing in (1) the time information (N=26) and (2) modified Rankin Score (mRS) at 3 months (N=1). We gathered the exact timing, type, dose of statin use from a database of electronic bar-code medication administration system. Multivariable ordinal logistic regression was performed for mRS at 3 months (improved outcome).

Results:
Of the 881 analyzable cases (male, 58%; mean age, 68.9; median initial NIHSS score, 12), recanalization treatment consisted of 33% of IV-only, 33% of IA-only and 34% of combined IV-IA strategies. Stroke mechanisms were 26% of large artery atherosclerosis (LAA), 49% of cardioembolism (CE) and 25% of non-LAA/CE. Statins were administered in the acute phase (within 7 days) in 68% (n=598) patients (<24 hours in 35% [n=307] and 24-72 hours in 43% [n=170]). High intensity statins (atorvastatin 40-80 mg or rosuvastatin 20 mg) were used in 72% (n=429) and low-to-moderate intensity statins in 28% (n=169). Multivariable analyses revealed acute statin (within 7 days) was associated with improved outcome, especially in patients with IA treatment or when used within 24 hours. Low-to-moderate intensity statin was associated with improved outcome, but high intensity statin was not.

Conclusions:
Acute statin use after recanalization treatment may positively influence functional outcome, more in patients with IA treatment or when used within 24 hours. Low-to-moderate intensity statin may be as beneficial as high intensity statin after recanalization.
Abstract 68: Bedside Dysphagia Screening Tool Validation Study
Authors: Meighan Melissa M , Schumacher Finnegan Barbara A , Warren Noelani C , Lipiz Jorge , Nguyen-Huynh Mai N
Published: June 2021

Background:
Dysphagia or difficulty swallowing occurs in up to 50% of patients with acute stroke symptoms. Dysphagia screening is considered standard stroke care. Few dysphagia screening tools have been well validated with high sensitivity and specificity.

Purpose:
The purpose was to validate our system’s dysphagia screening tool.

Methods:
From August 17, 2015 through September 30, 2015, bedside dysphagia screening was prospectively performed by 2 blinded nurses on all patients age ≥18 years admitted through the emergency department with stroke symptoms at 22 stroke centers in an integrated healthcare system. The tool consisted of three parts: history, physical exam and progressive testing from ice chips to water. A speech language pathologist blinded to the results performed an evaluation on the same patient. Patients with a feeding tube or intubation on arrival, treated with alteplase, or were discharged with a diagnosis other than stroke were excluded from final study analyses. The study quantified the reproducibility of the dysphagia screening tool by computing the percent agreement and kappa score for inter-rater reliability. Validity of dysphagia screening tool was determined using the speech pathologist evaluation as the reference standard. We assessed the sensitivity, specificity, and negative (NPV) and positive predictive values (PPV) for the dysphagia screening tool. The point estimate and 95% confidence interval (CI) were calculated.

Results:
Dysphagia screening was performed in 726 patients with stroke symptoms. There were 370 patients included in the analysis. Average age was 70 ± 14 years, and 48.2% female. Inter-rater reliability of the dysphagia screen was excellent between both raters at 93.5% agreement (k’= 0.83). The screen performed well when compared to speech language pathologist evaluation, demonstrating both high sensitivity (86.4%, CI: 73.3% to 93.6%) and high NPV (93.6%, CI: 86.8% to 97.0%).

Conclusion:
Our bedside dysphagia screening tool is highly reliable and valid. The tool had been used in over thirty-five facilities since 2007. The hospital acquired pneumonia rate for ischemic stroke patients has averaged 2-3% a year. This dysphagia screening tool requires minimal training and is easily administered in a timely manner.
Abstract 72: Procedural and Long Term Safety of PFO Closure in Cryptogenic Stroke: Insights from the RESPECT Trial
Authors: Smalling Richard W , Carroll John , Saver Jeffrey , Thaler David , Bull Todd , Bauer Kenneth , McDonald Lee , Marks David , Tirschwell David
Published: June 2021

Background:
Complications of percutaneous patent foramen ovale (PFO) closure using the Amplatzer
TM
PFO Occluder were reported in 2012 after a median follow-up of 2.1 years. The FDA requested an analysis of long-term device safety observed in the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial.

Methods:
We randomized patients with cryptogenic stroke and PFO in a 1:1 ratio between PFO closure and medical management alone (MM). Post procedure medical management in the closure arm was 30 days of aspirin
and
clopidogrel followed by 5 months of aspirin alone and continued medical therapy as per the site neurologist. Medical treatment in the MM arm was a guideline-directed antiplatelet regimen or warfarin. An independent data and safety monitoring board adjudicated all adverse events as serious (SAE) or non-serious, and as procedure, device or protocol related.

Results:
We enrolled 980 patients (mean age, 45.9 years) at 69 sites who were followed for a median of 5.9 years (IQR 4.2-8.0). Follow-up was unequal – 3141 patient-years in the closure arm vs. 2669 in the MM arm, due to a higher dropout rate in the MM arm. There was less warfarin use in the closure arm vs. the MM arm (109 vs 578 patient-years). There were no study-related deaths. Two patients had procedure-related ischemic strokes (7 days and 3 months post-procedure). SAEs were equally distributed between the two arms: 13.7 in the closure arm vs. 12.4 per 100 patient-years in the MM arm, p=0.17. There was no device thrombus or erosion. The incidence of post procedure AF was not increased in the closure arm. Venous thromboembolic events (VTE) occurred at a higher rate in the closure arm, 0.87 per 100 patient-years vs. 0.22 in the MM arm, p=0.0008. In univariable logistic regression modeling, a remote history of DVT prior to randomization was a significant predictor of VTEs in the closure arm. No VTEs occurring beyond 6 months were attributed to the procedure or the device.

Conclusions:
These new long-term data reaffirm that the Amplatzer
TM
PFO Occluder has a low rate of procedure (2.4%) and device (2%) related SAE’s. A small subset of cryptogenic stroke patients have an underlying proclivity to VTE and may need long-term anticoagulation.
Abstract 74: Obesity and the Risk of Recurrent Vascular Events in Patients with Ischemic Stroke: Insights from the Insulin Resistance Intervention after Stroke (IRIS) Trial
Authors: Dearborn Jennifer L , Viscoli Catherine M , Inzucchi Silvio E , Young Lawrence H , Kernan Walter N
Published: June 2021

Background:
In epidemiologic research, patients with obesity have, on average, a lower risk for recurrent cardiovascular events after ischemic stroke compared with non-obese patients. Despite this “obesity paradox,” we hypothesized that clinical features associated with more severe metabolic disease would identify overweight and obese stroke patients at high risk for recurrent vascular events.

Methods:
The
IRIS
trial examined the efficacy of pioglitazone compared with placebo, for prevention of stroke/ myocardial infarction (MI) among non-diabetic insulin resistant patients with a recent ischemic stroke or TIA. Patients were followed for a median of 4.8 years. Among 3,707 participants, we first examined risk of recurrent stroke/MI by obesity status at baseline (overweight or obese [BMI ≥25] vs <25) using Cox proportional hazards models with and without adjustment for sociodemographic factors, smoking and vascular disease history. Next, for 3,142 participants with BMI ≥ 25, a Cox model including 7 baseline features (systolic blood pressure, C-reactive protein, HOMA-IR, hemoglobin A1C, waist circumference, triglycerides and high density lipoprotein) was used to stratify patients into tertiles of “metabolic risk”. The hazard of stroke/MI was then calculated across risk tertiles(T).

Results:
Overweight and obese participants had a lower incidence of stroke or MI compared with non-obese patients (10.1% vs.12.6%; hazard ratio [HR] 0.77, [0.59-0.99]) and the difference was attenuated after adjustment (HR 0.85 [0.66-1.11]). Among overweight and obese patients, a metabolic risk score identified patients at higher risk of stroke or MI (T3 12.2%, T2 9.2%, T1 9.0%; T3 vs. T1 HR 1.40 [1.08, 1.83]). This association remained significant after adjustments (HR 1.33 [1.02, 1.75]).

Conclusion:
Although overweight and obese patients may on average have lower risk of recurrent stroke or MI after an ischemic stroke or TIA compared with non-obese individuals, those with advanced metabolic impairment also have a high absolute risk of recurrence.
Abstract 75: Bleeding and Ischemic Stroke Risk in Patients with Atrial Fibrillation Standard or Low Dose Dabigatran and Concomitant P-gp Inhibitors
Authors: Vaughan Sarrazin Mary , Mazur Alexander , Jones Michael P , Chrischilles Elizabeth
Published: June 2021

Background:
Guidelines for dabigatran in patients with atrial fibrillation (AF) recommend dose reduction in patients with impaired renal function and concomitant use of strong P-gp inhibitors. However, there are limited data regarding the safety and efficacy of concomitant use of dabigatran and p-gp inhibitors. We evaluated risk of major bleeding and stroke in patients with AF taking low (75 mg) or standard (150 mg) dose dabigatran with concomitant use of strong or moderate p-gp inhibitors and no history or renal disease.

Methods:
We identified Medicare beneficiaries age 66 and older with new AF diagnoses during 2011-2013 who received dabigatran within 90 days of AF diagnosis and had concurrent use of a P-gp inhibitor (droneradarone, amiodarone, ketoconazole, quinidine, verapamil, and clarithromycin). We excluded patients with existing renal disease, based on ICD-9-CM codes. We also excluded patients with recent hip surgery or recent embolism, to ensure that the purpose of dabigatran was long term stroke prevention. Of the 7,077 patients meeting inclusion criteria, 1,125 (16%) received dabigatran 75 mg; the remaining received 150 mg. We matched each patient taking low dose dabigatran to a single patient taking standard dose using an optimal propensity matching algorithm. Proportional hazards regression further controlled for patient attributes that may confound the relationship between dose and likelihood of stroke or bleeding. Matching and modeling steps were repeated 1000 times using bootstrapping. We then calculated the mean (and 95% confidence intervals) risk-adjusted stroke and bleeding rates per person-year.

Results:
There was a significant reduction in bleeding risk with use of low dose dabigatran, compared to standard dose, with an absolute reduction in bleeding risk of 23 per 1000 patient-years (95% CI, 1 to 45 per 1000 patient years). In contrast, the risk of stroke did not differ significantly among patients taking low or standard dose dabigatran (2 more strokes per 1000 patient-years with low dose dabigatran; 95% CI, -7 to 10).

Conclusions:
Use of low dose dabigatran in patients taking a P-gp inhibitor may result in fewer bleeding events compared to standard dose, without compromising the protective effect against ischemic stroke.
Abstract 77: Intensity of Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Meta-regression Analysis of Randomized Clinical Trials
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Filippatou Angeliki , Manios Efstathios , Deftereos Spyridon , Parissis John , Frogoudaki Alexandra , Vrettou Agathi-Rosa , Ikonomidis Ignatios , Pikilidou Maria , Kargiotis Odysseas , Voumvourakis Konstantinos , Alexandrov Anne W , Alexandrov Andrei V
Published: June 2021

Background & Purpose:
Current recommendations do not specifically address the optimal blood pressure (BP) cut-off for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and meta-regression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized-controlled clinical trials (RCTs) of secondary stroke prevention.

Methods:
For all reported events during each eligible study period we calculated the corresponding risk ratios (RRs) to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. Based on the reported BP values, we performed univariate meta-regression analyses according to achieved BP values under the random-effects model (Method of Moments) for those outcome events reported in ≥10 total subgroups of included RCTs.

Results:
In pairwise meta-analyses of 14 RCTs comprising 42,736 patients antihypertensive treatment lowered the risk for recurrent stroke (RR=0.73, 95%CI: 0.62-0.87, p<0.001), disabling or fatal stroke (RR=0.71, 95%CI: 0.59-0.85, p<0.001) and cardiovascular death (RR=0.85, 95%CI: 0.75-0.96, p=0.010). In meta-regression analyses systolic BP reduction was linearly related to lower risk of recurrent stroke (p=0.049; Figure A), myocardial infarction (p=0.024), death from any cause (p=0.001) and cardiovascular death (p<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (p=0.026; Figure B) and all-cause mortality (p=0.009). Funnel plot inspection and Egger’s statistical test revealed no evidence of publication bias.

Conclusion:
The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebro- and cardio-vascular events. Strict and aggressive BP control appears to be essential for effective secondary stroke prevention.
Abstract 80: Left Atrial Structural and Functional Parameters in Ischemic Stroke Patients Show Differences in Cardioembolic versus Embolic Strokes of Unknown Source (ESUS) and Other Determined Causes: Rethinking Whether ESUS Patients Should be Treated as Cardioembolic Equivalents
Authors: Winningham Melanie , Rangaraju Srikant , Mahmoud Ghada A , Raza Syed Ali , Salinger Maggie , Belagaje Samir , Bianchi Nicolas , Anderson Aaron , Frankel Michael , Nahab Fadi
Published: June 2021

Background:
The role of anticoagulation in patients with embolic strokes of unknown source (ESUS) remains controversial. Left atrial (LA) structural and functional parameters on transthoracic echocardiography (TTE) may predict ESUS patients who are likely to develop subsequent paroxysmal atrial fibrillation (PAF).

Hypothesis:
LA parameters in ESUS patients will be similar to cardioembolic (CE) stroke patients and different from patients with strokes due to other determined cause (ODC).

Methods:
Patients admitted to a stroke center from June 1 to November 30, 2015 with acute ischemic stroke were included in this analysis. Baseline characteristics and results of inpatient diagnostic workup including neuroimaging, echocardiography, and cardiac telemetry were reviewed retrospectively to classify patients into three subtypes: CE, ODC or ESUS. LA diameter, LA volume index (LAVI), mitral valve early (MV E) and late filling peak (MV Peak A) velocities were compared between the 3 subtypes.

Results:
Of 131 patients (mean age 67 ± 16, 47% female, 45% white), 35 (27%) were classified as CE, 62 (47%) ODC and 34 (26%) ESUS. Baseline characteristics were similar between groups except that ODC patients were less likely to be female than CE and ESUS patients (p=0.05). LAVI, MV E and MV Peak A were all significantly different in CE compared with ODC and ESUS patients (p<0.05), with LA diameter showing a trend toward significance (p=0.058) (Figure). ESUS patients had LA diameter, LAVI, MV E and MV Peak A that were more similar to ODC than CE patients.

Conclusions:
LA structural and functional parameters among CE patients in our cohort were significantly different from those of ESUS and ODC patients, suggesting that ESUS patients may have lower risk of AF (and therefore lower likelihood of benefit from preemptive anticoagulation). Our study suggests that ESUS patients may benefit from long-term cardiac monitoring prior to initiation of anticoagulation therapy.
Abstract 93: Newly-diagnosed Depression Precedes Cognitive Impairment Following Intracerebral Hemorrhage
Authors: Biffi Alessandro , Kourkoulis Christina , Schwab Kristin , Ayres Alison M , Gurol M. Edip , Greenberg Steven M , Viswanathan Anand , Anderson Christopher D , Rosand Jonathan
Published: June 2021

Introduction:
Survivors of Intracerebral Hemorrhage (ICH) are at high risk for developing long-term incident cognitive decline and depression. However, owing largely to limited data on long-term post-ICH depression risk, the degree to which these two forms of post-hemorrhage clinical deterioration overlap is unknown.

Hypothesis:
post-ICH depression is highly incident, and associated with long-term cognitive decline risk.

Methods:
We followed longitudinally 695 ICH survivors with no prior history of depression. Exposures of interest included clinical information, known genetic risk factors for ICH / post-ICH dementia (APOE ε2/ε4), and imaging manifestations of cerebral small vessel disease on CT (CT-defined white matter disease [CT-WMD]). We captured outcomes (incident depression and dementia) during follow-up using validated scales administered via telephone every 6 months.

Results:
A total of 271/695 ICH survivors (40%) developed new-onset mood disorder during a median follow-up time of 49.6 months (Figure). We estimated an incidence rate of 6.9% yearly (95% CI 5.5-8.8%) for post-ICH depression. Independent risk factors for post-ICH depression included lower educational achievements, APOE ε4, and moderate/severe CT-WMD (all p<0.05). Depression and dementia were co-diagnosed in 135/214 individuals (63%). Depression preceded post-ICH dementia in 108/135 cases (80%, 95% CI 71-88%, p = 0.002), with median anticipation of 17.5 months (IQR = 12.8-23.9).

Conclusions:
we conducted the first-ever systematic evaluation of long-term post-ICH depression, which affects a large proportion of ICH survivors and shares risk factors (education, APOE genotype, CT-WMD severity) with risk for ICH recurrence and post-ICH dementia. Newly diagnosed depression often signals impending onset of dementia after ICH.
Abstract 95: Nutrition and Cognitive Decline Over 21-years: Results from the Atherosclerosis Risk in Communities Study (ARIC)
Authors: Dearborn Jennifer L , Wu Aozhou , Steffen Lyn M , Knopman David S , Mosley Thomas H , Gottesman Rebecca F
Published: June 2021

Background:
A healthy diet may be protective against cognitive decline by mechanisms that involve improved vascular risk factors such as hypertension and dysglycemia, and reduced systemic inflammation. In this population-based study, we hypothesized that midlife diet pattern would be associated with cognitive decline over 21-years.

Methods:
This study included 13,603 participants in the ARIC population-based cohort recruited from four U.S. sites who were aged 45 to 64 at baseline (1987-89) when diet was measured. Participants recorded diet using a 66-item food frequency questionnaire. Two dietary patterns, called “Meat and Fried” and the “Balanced Diet”, were named after the most representative foods that emerged from constructs derived from a principal component analysis of 30 food groups. A higher diet pattern score represented greater adherence. Cognitive testing, including the digit symbol substitution, the word fluency and delayed word recall tests, were combined to a z-score at each visit (visits 2, 1990-92; 4, 1996-98 and 5, 2011-2013). Test scores for participants not attending subsequent visits were imputed using Multiple Imputation by Chained Equations to account for cohort attrition. Cognitive performance at visit 2 was compared by tertile (T) of each diet pattern. Using mixed effects models with a random slope and intercept , we determined the 21-year change in cognitive function by diet pattern tertile, adjusting for demographics and medical history.

Results:
At visit 2, adherence to the Meat and Fried pattern was associated with lower cognitive test scores (z-score T3: -0.172, SD 0.985; T1: 0.149, SD 0.981, p-trend <0.001). Adherence to the Balanced Diet was not associated with differences in cognitive performance (z-score T3: 0.013, SD 0.988; T1 -0.036, SD 1.001, p-trend 0.10). 21-year change in cognitive function did not differ by adherence to diet pattern with adjustments (difference of the change in z-score for Meat and Fried, T3 vs. T1: 0.02, [CI -0.05 to 0.08]; Balanced Diet T3 vs. T1: -0.03, [CI -0.09 to 0.02]).

Conclusion:
Although participants with a diet pattern high in meat and fried foods had lower cognition at time of first assessment, diet patterns at midlife did not carry independent associations with cognitive decline.
Abstract 97: Increased Plasma Level of ApoCIII-rich Electronegative HDL May Contribute to Cognitive Impairment in Alzheimer’s Disease
Authors: Chan Hua-Chen , Lu Hsiao-Ting , Chou Mei-Chuan , Tsai Ming-Hsien , Chen Wei-Hsiang , Law Shi-Hui , Chan Hsiu-Chuan , Chang Chuan-Fa , Liu Ching-Kuan , Shin Shyi-Jang , Rudd Pauline M. , Ke Liang-Yin , Chen Chu-Huang
Published: June 2021

Background:
High-density lipoprotein (HDL), the only lipoprotein class that can cross the blood brain barrier bidirectionally, is positively associated with cognitive functions. To delineate HDL’s role in Alzhenimer’s disease (AD), we analyzed the chemical properties of plasma HDL from AD and healthy normal adult (control) subjects.

Methods and results:
By using anion-exchange chromatography, we divided HDL into 5 increasingly electronegative subfractions, H1-H5. Compared to the control cohort (4.24±3.22%; n=20), HDL from AD patients (23.48±17.83%; n=30) had a 5.5-fold increase of H5 (
P
<0.001;
Figure
), accompanied by a decreased protein/lipid ratio attributed to a significant reduction of albumin essential for prevention of amyloid beta (Aβ) aggregation. As determined by LC/MS
E
and ProteinLynx Global SERVER (PLGS), AD-HDL was had a rich content of apolipoprotein (apo)CIII, but diminished amounts of sphingosine-1-phosphate (S1P)-associated apoM and antioxidative paraoxonase 1 (PON1). Exposure of murine RAW 264.7 macrophages to H5 induced vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts, alongside a concomitant increase of TNF-α detectable in the cultured medium (
Figure
). LC/MS
E
examination localized posttranslational oxidation exclusively in ApoA1 residues of H5 in AD-HDL, which exhibited a compromised cholesterol efflux capacity.

Conclusions:
Plasma HDL from AD patients has a high proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated reduction in functional (albumin, S1P, apoM) and increase in proinflammatory (apoCIII, PON1, TNF-α) components may favor Aβ assembly and neuroinflammation. Additionally, a compromised cholesterol-efflux capacity of AD-HDL may also contribute to vascular cognitive impairment.
Abstract NS5: Implementing NICE (Neurological Intensive Care Evaluation) in the CVICU to Identify Neurological Dysfunction More Rapidly in Post-Operative Cardiac Surgery Patients
Authors: Esdale Taylor , Davis Grace , Harvey Brooke , Lachiewicz Heather , Brecher Jennifer , Mcgriff Stacia , Bailey Whitney , Camp Deborah , Woessner Heidi
Published: June 2021

Background:
Piedmont Atlanta Hospital identified cardiothoracic surgical (CTS) outcome metrics that were not meeting benchmarks established by the Society for Thoracic Surgeons (STS). Post-operative permanent stroke occurred in 1.303% (8 out of 616 cases) of coronary artery bypass-only patients at Piedmont Atlanta Hospital (PAH) during Fiscal Year 2015. The STS benchmark for all hospitals is 1.3%. Initially, the goal was to reduce the number of post-operative strokes to the standard of care but while reviewing this data, it was noted that there was significant delay in discovering the occurrence of stroke in this patient population. Traditional neurological assessments and stroke scales are difficult to apply to post-operative open heart patients due to intubation, variation in anesthesia recovery times, and the effects of pain management medications. To improve patient outcomes, PAH researched alternatives to standard post-operative neurological assessments to rapidly identify strokes and potential interventional candidates, ultimately reducing the frequency of disabling stroke.

Method:
A CTS Stroke Pathway was created that included the Neurologic Intensive Care Evaluation (NICE), a novel assessment tool performed by the critical care nurse. NICE was chosen because of the ease of use on post-anesthesia patients. Neurological state was assessed based on the ability to complete one-step commands up to six hours post-op.

Results:
Prior to NICE being implemented, stroke symptoms were discovered on average 40 hours from last known time well (LKTW). After NICE being implemented, Code Strokes (notification of neurological dysfunction) were initiated on average four hours from patients LKTW. In the first month of utilizing the NICE tool, one of three post-operative stroke patients was able to be transferred to a comprehensive stroke center for a mechanical thrombectomy.

Conclusion:
Implementing NICE as the standard neurological assessment for immediate post-operative cardiac surgery patients significantly reduced the time to identify neurological changes indicating a stroke. This may lead to more rapid treatment or intervention, reducing the post-operative rate of permanent stroke.
Abstract NS6: Born to Run: Advanced Practice Provider-Led Mobile Stroke Unit Care Measures Up to Vascular Neurologists’ Diagnosis and Management
Authors: Alexandrov Anne W , Dusenbury Wendy , Swatzell Victoria , Rike Joseph , Bouche Andrew , Crisp Ira , Jestice Michael , Fletcher Joshua , Crockett Mathew , Ware Tyrone , Stacks William , Barber Ian , McDevitt Patrick , McDaniel Stephen , Mathenia Thomas , Orr James , McKendry Chris , Novak Ted , Bey Stanley , Bullock Charles , Harrold James , Crockett Christopher , McCormick Sarah L , Rogers Keri M , Carlow Jordan S , Malkoff Marc , Arthur Adam , Alexandrov Andrei V
Published: June 2021

Background:
Mobile Stroke Units (MSU) are growing in numbers throughout the U.S. and abroad, with numerous staffing configurations, telemedicine, and differing imaging capabilities. We aimed to test the diagnostic accuracy and treatment safety, alongside time to diagnosis and treatment delivery of a novel advanced practice provider (APP) led MSU team.

Methods:
We launched an MSU housing a hospital-grade Siemens Somatom CT with CTA capabilities, and hired APPs with advanced neurovascular practitioner board certification to lead field medical diagnosis and order/initiate treatment for encountered stroke patients. Consecutive MSU patients were evaluated for differences between APPs and Vascular Neurologists (VNs) diagnosis and management, and scene diagnosis and treatment times were collected.

Results:
Agreement between APP field medical diagnosis and MD hospital diagnosis was 100%; stroke mimic diagnosis agreement was 98%. Overall agreement for field interpretation of CT/CTA was 97%, with discrepancies not associated with stroke treatment decisions. MDs’ agreement with APPs’ identification/treatment of ICH was 100%, and IVtPA treatment decisions 98% (APPs more conservative). Scene arrival to medical diagnosis (including clinical exam and imaging completion/interpretation) ranged from 7-10 minutes, of which 4 minutes were CT/CTA start to finish times. Scene arrival to IVtPA bolus ranged from 16 minutes to 33 minutes and was driven primarily by need for control of excessive hypertension, with scene arrival to start of nicardipine premix infusion ranging from 10-14 minutes.

Conclusions:
Use of an APP-led MSU is safe and non-inferior to VN diagnosis/management, and may be faster than telemedicine guided MSU treatment.
Abstract TMP1: Distal Hyperintense Vessels Score on Flair is a Marker of Collateral Flow Grade and Outcomes in Patients with Acute Ischemic Stroke After Endovascular Therapy
Authors: Miura Masatomo , Nakajima Makoto , Kanamaru Takuya , Uchida Kazutaka , Shirakawa Manabu , Ando Yukio , Yoshimura Shinichi
Published: June 2021

Background:
Distal hyperintense vessels (DHV) on fluid-attenuated inversion recovery imaging (FLAIR) is a noninvasive and useful imaging marker that reflects leptomeningeal collateral flow. We investigated relationship between DHV and collateral grade on cerebral angiography, and clinical outcome after endovascular therapy (EVT) in patients with AIS.

Methods:
We retrospectively analyzed the patients with AIS in two comprehensive stroke centers from October 2013 to February 2016. We selected the patients who underwent FLAIR sequence before EVT. DHV score (range 0-6) was evaluated based on the presence of DHV in each ASPECTS territory (M1-M6). Collateral grades on cerebral angiography were assessed with the American Society of Interventional and Therapeutic Neuroradiology Collateral Grading System (grade 0-4). Favorable clinical outcomes was defined as modified Rankin Scale [mRS] of 0-2 at 90 days.

Results:
A total of 60 patients (aged 71.2 ± 10.5 years; initial NIHSS score, 15 ± 8; median DWI-ASPECTS, 7) were included. DHV was detected in 42 patients (70%); median DHV score was 2 (IQR, 1-4). Higher DHV score was significantly related to better collateral flow grade (
p
<0.001), and favorable outcome (
p
<0.001). In multivariate analysis, DHV score predicted favorable outcome (OR 2.83 per 1 point; 95% CI 1.71-5.48;
p
<0.001), independent of stroke severity or successful reperfusion.

Conclusions:
DHV score on FLAIR is a marker of collateral flow status and can predict better clinical outcome in patients with AIS after EVT.
Abstract TMP102: Inappropriate Dosing of Oral Anticoagulants among Patients With Non-Valvular Atrial Fibrillation
Authors: Shrestha Sulena , Baser Onur , Zhou Xinxiang , Kwong W J
Published: June 2021

Introduction:
Non-vitamin K antagonist oral anticoagulants (NOACs) are fixed dose regimens indicated for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary in patients with renal insufficiency to optimize efficacy and safety.

Objective:
To assess NOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients.

Methods:
Adult NVAF patients with ≥1 NOAC claim from 1/1/2013 to 12/31/2014, who were continuously enrolled for ≥12 months after index NOAC claim and had a documented creatinine clearance (CrCl) within 3 months before index date in the Optum/Humedica SmartFile™ database were eligible. NOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per U.S prescribing information (USPI). Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate NOAC dosing while adjusting for baseline characteristics.

Results:
Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed. Rivaroxaban was the most commonly prescribed NOAC and had the highest inappropriate dosing rate (19.9% of 251 pts), followed by dabigatran (15.5% of 58 pts), and apixaban (12.7% of 79 pts). Most inappropriately dosed patients (73.9%) were under-dosed. Inappropriately dosed patients were older (p<0.0001), more likely to be female (p=0.008), had body weight ≤60kg (p=0.005), higher mean CHA
2
DS
2
-VASc scores (4.3 vs. 3.1, p<0.001), and higher mean Charlson Comorbidity Index (3.7 vs. 2.4, p<0.001). Inappropriately dosed patients had higher bleeding risk (15.9% vs. 5.6%, p=0.003) and similar stroke risk (7.2% vs. 5.3%, p=0.483) compared to appropriately dosed patients. Over-treated patients had a higher elevated risk of bleeding relative to appropriately dosed patients (HR=5.4, p=0.006) than under-dosed patients (HR=3.1, p=0.025). Risks of stroke for under-treated patients (HR=2.1, p=0.259) and over-treated patients (HR=0.6, p=0.690) were similar to appropriately dosed patients.

Conclusion:
Inappropriate dosing occurred in both patients with normal and insufficient renal function. Consideration of other factors beyond renal function is necessary to reduce bleeding risk associated with NOAC therapy.
Abstract TMP104: The Effect of Hypothetical Lifestyle Strategies on the Long-term Risk of Stroke
Authors: Jain Priyanka , Suemoto Claudia K , Rexrode Kathryn , Danaei Goodarz , Hernan Miguel A
Published: June 2021

Randomized trials have examined the short-term effects of lifestyle interventions on the risk of stroke. Using observational data to estimate the long-term effect of such strategies requires valid adjustment for time-varying confounders- such as hypertension- that are affected by prior lifestyle risk factors.

We estimated the long-term effect of hypothetical lifestyle strategies on risk of stroke using data from the Nurses’ Health Study, a prospective cohort. We followed 60,390 women, aged 52 years on average at baseline, from 1986 to 2010. We used a Monte Carlo simulation to estimate the 24-year risk of stroke had all participants followed three non-dietary lifestyle strategies: smoking cessation, exercising (≥30 minutes/day), reducing body mass index (BMI) by 5% every two years if overweight/obese; as well as several dietary strategies including: eating ≥ 3 servings/week of fish, eating ≤ 3 servings/week of unprocessed red meat, eating no processed red meat, eating ≥ 5 servings/day of fruits and vegetables, among others. We used the parametric g-formula to adjust for baseline and time-varying confounders, comparing the estimated risk of stroke under our specified strategies of interest to the same had all participants followed a “do-nothing” strategy.

The observed 24-year risks of total, ischemic and hemorrhagic stroke in this cohort were 2.9%, 2.2% and 0.6%. The estimated risk of total stroke was 25% lower (95% CI: 5% to 46%) under a combination of all three non-dietary strategies, the most effective being exercise (19% lower risk) and smoking cessation (5% lower risk). Of the dietary strategies, eating ≤ 3 servings of unprocessed red meat reduced the estimated risk of total stroke by 4% (1% to 7%). The risk of ischemic stroke under all three non-dietary strategies was 36% lower (15% to 59%), but risk of hemorrhagic stroke did not materially change. Exercise reduced the estimated risk of ischemic stroke by 29% (7% to 56%) and lowering BMI by 4% (0% to 8%). Additionally, ischemic stroke risk was lowered by 9% (0% to 19%) by decreasing intake of processed red meat and 6% (2% to 10%) by decreasing intake of unprocessed red meat.

In summary, lifestyle modifications were estimated to reduce the 24-year risk of total stroke by up to 25% in this population of middle-aged women.
Abstract TMP106: Relationship Between Smoking and the Development of Extracranial and Intracranial Arteriosclerotic Stenosis
Authors: Ji Ruijun , Wang Yongjun
Published: June 2021

Background and purpose:
to investigate the relationship between active cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS).

Methods:
We analyzed patients enrolled in the Chinese Intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS.

Results:
A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9±11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR=1.47, 95% CI=1.09-1.99, P<0.01). In addition, with one year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR=1.011; 95% CI=1.003-1.019; P=0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR=1.010; 95% CI=1.001-1.020; P=0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR=1.007; 95% CI=1.002-1.012; P<0.01). However, no similar significant association was found between smoking status and the occurrence of ICAS.

Conclusion:
A paradoxical dose-response relationship between cigarette smoking and the occurrence of ECAS and ICAS was identified. Further studies on molecular mechanisms were warranted. 
Abstract TMP107: Regular Dental Care Reduces the Risk for Ischemic Stroke: Atherosclerosis Risk in Communities (ARIC) Study
Authors: Giamberardino Lauren , Offenbacher Steven , Moss Kevin , Rosamond Wayne , Sen Souvik
Published: June 2021

Introduction:
Prior epidemiological studies have shown that periodontal disease (PD), also referred to as gum disease, is an independent risk factor for ischemic stroke. We assessed the hypothesis that users of regular dental care may have a lower risk for incident ischemic stroke and specific stroke subtype when compared with users of episodic dental care.

Methods:
In this prospective, longitudinal community-based cohort study, participants without prior stroke were assessed for dental care utilization represented by patient-reported responses to questionnaires. The pattern of dental care utilization was classified as regular use (every year), episodic use (as needed), or no use (never). Episodic visits, or visits as needed, are considered signs of inadequate utilization of dental care. These participants were followed for incident ischemic strokes. Ischemic stroke diagnoses were defined as sudden onset of neurological deficit(s) lasting ≥24 hours along with neuroimaging confirmation. Strokes were further classified according to etiologic subtype as thrombotic, lacunar, or cardioembolic stroke subtype according to criteria adopted from the National Survey of Stroke.

Results:
Of 11,242 participants (mean age±SD=62.8±5.6, 56% female, 78% white and 22% African-American) assessed for dental care utilization at the fourth ARIC visit (1996-1998). Over a 15-year follow-up period a total of 583 participants had incident ischemic stroke events, of who 19% were lacunar, 29% were cardioembolic and 45% were of the thrombotic stroke subtype. After adjustment for confounders (race/center, age, gender, BMI, hypertension, diabetes, LDL level, smoking, and education), regular dental care utilization was associated with lower risk for ischemic stroke overall compared with episodic dental users (adjusted HR 0.77, 95% CI 0.63-0.94). Regular dental care specifically lowered the risk of thrombotic stroke subtype (adjusted HR 0.75, 95% CI 0.56-0.99).

Conclusions:
Results from this prospective cohort study demonstrates an independent association between regular dental care utilization with a lower ischemic stroke risk. Further, we report the highest impact of regular dental care in lowering risk of the thrombotic stroke subtype.
Abstract TMP111: Thalidomide and Lenalidomide Treatment Reduces Microhemorrhage in Brain Arteriovenous Malformation in Mice Through Increasing Mural Cell Coverage
Authors: Zhu Wan , Zou Dingquan , Chen Wanqiu , Bao Chen , Zhang Rui , Zhan Lei , Li Zhengxi , Zhang Meng , Winkler Ethan , Lawton Michael T. , Su Hua
Published: June 2021

Introduction:
Brain arteriovenous malformations (bAVMs) have an abnormal vessel wall and are prone to rupture. The mechanism of bAVM rupture is unclear. In
Alk1
-deficient mice, bAVM vessels have fewer mural cells. In endoglin-deficient mice, thalidomide increases mural cells in retina AVM vessels. We hypothesize that thalidomide and its less toxic analogue, lenalidomide, improve vessel mural cell coverage and reduce microhemorrhage in
Alk1
-deficient bAVM.

Methods:
Brain AVMs were induced in adult
Alk1
2f/2f
mice through induction of focal
Alk1
gene deletion and angiogenic stimulation. Thalidomide was injected intraperitoneally (i.p.) twice per week for six weeks, starting either 2 weeks after model induction when bAVMs were beginning to develop or 8 weeks after when bAVMs were fully developed. Lenalidomide treatment was started 8 weeks after model induction through i.p. injection daily for six weeks.

Results:
Thalidomide treatment starting 2 weeks after bAVM induction reduced the number of abnormal vessels and microhemorrhage and increased vascular smooth muscle (vSM)-coverage. Thalidomide also increased the expression of platelet-derived growth factor b (pdgfb) and its receptor (pdgfr beta), indicating that pdgfg/pdgfr beta signaling is one of the mechanisms responsible for the improvement of mural cell coverage. Thalidomide and lenalidomide treatment started at the later time point also improved vSM-coverage and showed a trend toward reduction of microhemorrhage and abnormal vessel count.

Conclusions:
Thalidomide and lenalidomide stabilize the bAVM vessel wall and reduce microhemorrahge. Further studies are needed to determine whether these agents have a possible therapeutic value for patients.
Abstract TMP113: Deletion of Alk1 Gene in Bone Marrow-Derived Endothelial Cells is Sufficient to Cause Brain Arteriovenous Malformation in Mice
Authors: Luo Man , Li Qiang , Ma Li , Zhang Rui , Zhan Lei , Lawton Michael T. , Su Hua
Published: June 2021

Introduction:
In humans,
Alk1
deficiency causes arteriovenous malformations (AVMs) in multiple organs. Endothelial deletion of
Alk1
in adult mice leads to AVM formation in multiple organs and the brain angiogenic region, and endoglin-deficient bone marrow (BM) transmits abnormal brain vascular phenotype to wild-type (WT) mice. We hypothesize that
Alk1
deletion in BM-derived endothelial cells (BMDECs) is sufficient to induce AVM in the brain angiogenic region in adult mice.

Methods:
Adult
pdgf
b-iCreER;
Alk1
2f/2f
mice that have
Alk1
exons 4-6 flanked by loxP sites and a transgene expressing tamoxifen (TM)-inducible cre recombinase in the endothelial cells were used as BM donor. BM isolated from these mice was transplanted to lethally irradiated 8-week-old WT mice. Brain angiogenesis was induced through an intra-brain injection of an adeno-associated viral vector expressing VEGF 4 weeks after the BM transplantation. Two weeks later,
Alk1
deletion was induced through an intra-peritoneal injection of TM (2.5 mg/20g body weight). Vascular morphology was analyzed using latex casting 6 weeks later.

Results:
Peripheral blood cell counts fully recovered in the recipients 4 weeks after BM transplantation. Mice transplanted with
pdgfb
-iCreER;
Alk1
2f/2f
BM developed AVM in the brain angiogenic region. BM-derived endothelial cells were detected in brain AVM vessels. Unlike
pdgfb
-iCreER;
Alk1
2f/2f
mice that died 2 weeks after TM treatment due to bleeding from intestinal AVM, mice with
pdgfb
-iCreER;
Alk1
2f/2f
BM stayed alive within a 6-week period after TM treatment, suggesting that their intestinal AVM was less severe than in
pdgfb
-iCreER;
Alk1
2f/2f
mice.

Conclusion:
BMDECs play a significant role in brain AVM development. Transfusion of endothelial progenitor cells or stem cell-derived endothelial cells could be a potential therapy for brain AVM patients.