bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 105: Iodinated Contrast Does Not Alter Clotting Dynamics in Acute Ischemic Stroke as Measured by Thromboelastography
Authors: McDonald Mark M , Sangha Navdeep , Wetzel Jeremy , Riney Stephen A , Cherches Matt F , Guthrie Greer J , Parker Stephanie A , Roper Tiffany C , Kawano-Castillo Jorge F , Peng Hui , Pandurengan Renga , Hassler Amanda A , Grotta James C
Published: March 2022

Introduction:
Modern treatment of acute ischemic stroke (AIS) has increasingly incorporated multimodal CT imaging. Data illustrating that radiographic contrast agents alter fibrin fiber characteristics and decrease fibrinolysis by thrombolytic agents are potentially concerning. Thromboelastography (TEG) provides an integrated, dynamic view of coagulation and has recently been correlated with thrombolysis in AIS patients. This is the first study to examine the effects of contrast agents on tPA-induced clot lysis using TEG. We hypothesized that receiving computed tomography angiography (CTA) prior to tPA will impair thrombolysis as measured by TEG.

Methods:
AIS patients receiving 0.9 mg/kg tPA within 4.5 hours of symptom onset were enrolled. For CTA, iohexol dose was calculated using Medrad’s P3T software. Blood was drawn for TEG prior to CTA or tPA treatment and again 10-minutes after tPA bolus. TEG values, time of TEG draw and tPA administration, and CTA times were recorded. TEG values in patients having CTA prior to tPA were compared with patients in whom a CTA was performed either after tPA or not at all. Results were analyzed using Mann-Whitney U Test.

Results:
100 AIS patients received tPA. Of these, 17 patients had CTA prior to TEG blood draws and tPA bolus. 57 patients had either CTA following tPA or no CTA. The median change in clot lysis (LY30) following tPA was 94.8% in the contrast group vs. 94.5% in controls (p = 0.84). The median reduction in clot strength (G) was -8.8 dyn/cm
2
in the contrast group vs. -8.6 dyn/cm
2
in controls (p = 0.51). Pre-tPA G appeared to be attenuated by contrast (7.7 vs. 5.9 dyn/cm
2
) when corrected for platelet activity; however, this difference was not significant (p = 0.14). There was no effect of contrast on any other pre-tPA TEG value.

Conclusion:
The current data do not support any impairment of tPA-induced clot lysis by contrast agents. Baseline TEG also appears to be unaffected by contrast, but more patients are needed to better examine a possible interaction between clot strength and contrast agents.
Abstract 116: Statin Therapy Is Associated With Decreased Risk of First Intracerebral Hemorrhage and Reduced 30-day Fatality: Results of a Nationwide Case-control Study Including 7696 Cases and 14 670 Controls
Authors: Åsberg Signild , Eriksson Marie
Published: March 2022

Introduction:
Statin therapy prevents vascular events, but an increased risk of intracerebral hemorrhage (ICH) has been reported. We assessed the hypothesis that statin therapy was associated with increased risk of ICH and increased mortality after ICH.

Methods:
Using data from comprehensive national registers in 2006 to 2009, we identified 7696 cases with first-event ICH in the Swedish Stroke Register and 14 670 sex- and age-matched stroke-free controls in the Swedish Population Register. Drug therapy at the time of ICH was identified through the Swedish Drug Prescription Register. The risk of ICH with statins was estimated using conditional logistic regression, adjusted for explanatory factors, such as hypertension, diabetes, and use of antithrombotic therapy. We investigated the association between statins and 30-day mortality among the 7696 ICH-cases using logistic regression analyses, adjusted for age and sex in addition to the other explanatory factors.

Results:
Statins were used by 1276 (16.6%) of the ICH-cases and by 2552 (17.4%) of the controls. The crude and adjusted odds ratios (OR) of ICH with statins were 0.94 (95% CI, 0.87-1.02) and 0.70 (95% CI, 0.64-0.76), respectively. The 1276 ICH-cases with statins at stroke onset were 2 years older, more often men and had more risk factors for stroke than the 6420 ICH-cases without stroke therapy. In the crude model, statins were not associated with decreased risk of 30-day mortality (1.13; 95% CI, 0.99-1.29). But in the adjusted model, statins were associated with reduced likelihood of death at 30 days (OR 0.80; 95% CI 0.69-0.94).

Conclusions:
This nationwide study demonstrates an association between statin therapy and decreased risk of ICH and short-term mortality. Given the widespread use of statin therapy in prevention of coronary heart disease, these findings are reassuring even though randomized trials of statin therapy in secondary stroke prevention still is required.
Abstract 118: Burden of Blood Pressure-Related Alleles is Associated with Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage
Authors: Falcone Guido J , Biffi Alessandro , Devan William , Brouwers H. B , Anderson Christopher , Valant Valerie , Ayres Alison M , Schwab Kristin , Rost Natalia S , Goldstein Joshua N , Viswanathan Anand , Greenberg Steven M , Selim Magdy , Meschia James F , Brown Devin L , Worral Bradford B , Silliman Scott L , Tirschwell David L , Rosand Jonathan
Published: March 2022

Purpose:
Intracerebral hemorrhage (ICH) is the acute manifestation of a progressive disease of the cerebral small vessels. The severity of this disease appears to influence not only risk of ICH, but also the size of the hematoma. As the burden of high blood pressure(BP)-associated alleles is associated with hypertension-related end-organ damage, we sought to determine if this burden influences ICH admission hematoma volume (AHV).

Methods:
Prospective study undertaken in 441 ICH patients of European ancestry (210 deep and 231 lobar intracranial hematomas). Forty-three single-nucleotide polymorphisms (SNPs) known to be associated with high BP were genotyped in Illumina610-Quad. Single-SNP association analyses with AHV were performed using linear regression. Subsequently, a genetic risk score was calculated as the sum of the products generated by multiplying, at each of the 43 loci, the number risk alleles times the reported effect of that allele on BP. The score was utilized as the independent variable of univariate and multivariate regression models for 2 outcomes: AHV and poor clinical outcome (modified Rankin Scale 3-6). Principal components analysis was utilized to account for population structure.

Results:
Individually assessed, no single SNP was associated with AHV. In univariate linear regression, the genetic risk score was associated with AHV in all (deep and lobar) and deep locations (Figure 1), but not in lobar hemorrhages.

In multivariate regression analyses, each additional standard deviation of the genetic risk score increased mean deep AHV by 21% (or 2.7-milliliter increase, beta=0.21, standard error=0.08, p=0.01) and risk poor clinical outcome by 55% (odds ratio=1.55, 95% confidence interval 1.05-2.28, p=0.03). No significant associations were observed when considering all (deep and lobar) and lobar hemorrhages.

Conclusion:
In deep ICH, increasing numbers of high BP-related alleles are associated with larger AHV and poor clinical outcome.
Abstract 122: AMES Treatment of Severe Hand Impairment Following Stroke
Authors: Wolf Steven L , Lou Jau-Shin , Bogey Ross , Hayes John , Roth Elliot , Cordo Paul J
Published: March 2022

The objective of this study was to determine whether AMES (Assisted Movement with Enhanced Sensation), a novel therapeutic intervention that addresses impairments, rather than function, can reduce impairment and restore lost function in persons with a severely disabled hand. Forty-three participants with stroke (>1 yr post-injury) were provided with thirty 30-min AMES treatments over 10 weeks. Of these participants, 24 had no baseline active extension of any finger of the affected hand. Participants were randomized to 1 of 2 treatment groups differentiated by the kind of biofeedback (active torque or EMG) associated with the AMES intervention. During treatment, a robotic device cyclically opened and closed the hand (5 deg/s, ±15 deg) while the participant assisted this movement using visual biofeedback, and while vibration (60 pulses/s, 2 mm) was applied to the lengthening muscles. Participants were evaluated twice, before and after the treatment period, with the Fugl-Meyer Assessment (FMA-UE), Stroke Impact Scale (SIS), and Box-and-Block Test. In addition, during each treatment session, the AMES robot tested each participant’s strength of thumb-and-finger flexion and extension. Both torque and EMG were recorded during this Strength Test in participants assigned to the EMG-biofeedback group. The results showed overall a significant increase in the FMA-UE score (t-test, p<0.001), SIS score (t-test, p<0.05), and Box-and-Block Test score (Wilcoxon, p<0.005), without any difference between the 2 treatment groups. Four of the 24 initially plegic participants recovered the ability to move one or more blocks; however, all participants showing improvement in the Box-and-Block Test had a baseline FMA score of ≥17. Analysis of EMG during the hand-opening part of the Strength Test showed that AMES treatment of the EMG-biofeedback group significantly increased the amplitude of extensor activity (t-test, p<0.001) and decreased flexor co-contraction (t-test, p<0.05). We conclude that AMES coupled with either type of biofeedback may be effective at reducing impairment and increasing function in the severely impaired hand following stroke.
Abstract 127: The Influence of Neighborhood on Emergency Medical Services Use for Acute Stroke - A Population Based Cross Sectional Study
Authors: Meurer William J , Levine Deborah A , Kerber Kevin A , Burke James , Baek Jonggyu , Sanchez Brisa , Smith Melinda A , Morgenstern Lewis B , Lisabeth Lynda
Published: March 2022

Introduction:
The identification of neighborhood level factors that are associated with use of EMS for acute stroke could identify novel targets for interventions to improve EMS activation and access to stroke treatment.

Objective:
To investigate the association between neighborhood level factors and use of EMS for acute stroke.

Methods:
We identified 2905 neurologist-adjudicated cases of ischemic stroke and intracerebral hemorrhage that presented to the emergency department in the bi-ethnic Brain Attack Surveillance in Corpus Christi stroke surveillance project (2000-2008). Cases were geocoded by home address and assigned to census tracts (proxies for neighborhoods). Clinical information and use of EMS were abstracted from medical records. Census tract data were obtained from the 2000 US Census and the Corpus Christi Police Department. The association of census tract level factors (frequencies of age over 65 years, violent crime, Hispanic ethnicity, and household income) with EMS use was estimated using hierarchical logistic regression after accounting for known patient-level predictors of EMS use for stroke.

Results:
49% of stroke cases arrived by EMS. The proportion arriving by EMS ranged from 10% to 86% across census tracts (figure); however, in the fully adjusted model, only 0.3% (95% CI 0-1.1%) of the variance in use of EMS was explained by census tract. Violent crime level within census tract and all patient-level factors (except history of stroke/TIA) were associated with greater EMS use (table). Higher median income and older average age of census tract residents were associated with lower EMS use.

Conclusions:
While some neighborhood-level factors were associated with EMS use, nearly all variability in EMS use for stroke was explained by patient-level factors. In this community, attempts to increase EMS use should target individuals that are less likely to use EMS, such as younger adults, women, and Mexican Americans, rather than entire neighborhoods.
Abstract 129: Enrolling Spanish-Speaking Subjects into Prehospital Research: The FAST-MAG Spanish Line Experience
Authors: Sanossian Nerses , Starkman Sidney , Ali Latisha K , Restrepo Lucas , Valdes-Sueiras Miguel , Liebeskind David S , Chatfield Fiona , Hodgson T. Keta , Cherin Samantha , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: March 2022

Background:
Clinical trials should enroll diverse subjects who are representative of the general population. Enrollment in other languages requires substantial effort, including language-specific consent forms and physician-investigators fluent in language of consent. We describe the yield of a dedicated 24-hour Spanish prehospital research enrollment line.

Methods:
FAST-MAG is a phase 3, NIH-funded, randomized, placebo-control study of prehospital magnesium sulfate within 2 hours of stroke onset. The study is being conducted in Los Angeles and Orange Counties, home to 12.9 million people of whom just under half (44.8%) identify as Hispanic or Latino. Each of the 353 study ambulances carries: 1) 8 consent forms, 4 in English and 4 in Spanish, for the vehicle’s 4 most common destination hospitals; and 2) a cell phone with a quick-dial button for English and Spanish-speaking physician-investigator.

Results:
Data was available on 854 consecutive enrolments of whom 141 (17%) were via the Spanish and 713 (83%) via the English line. Patients enrolled via the Spanish line were younger (65 vs 70 years, p<0.001), less often women (33% vs. 43%, p=0.040), more often self-identifying as Latino (98% vs 16%, p<0.001), and more likely to be of White race vs other (98% vs 72%, p,0.001). Spanish-line enrollments trended to more severe stroke deficits (NIHSS 13.5 vs 11.7, p=0.08), were far more likely to have intracerebral hemorrhage on initial imaging (35% vs. 20%, p<0.001) and to have higher pre-hospital blood pressure (166/94 vs. 159/90, p=0.012). Spanish-line enrolments were more likely to be diabetic (36% vs. 23%, p=0.003), and less likely to have atrial fibrillation (16% vs 27%, p=0.012). Times from paramedic arrival to start of study infusion were only slightly longer in Spanish-line patients (24.6 vs 22.9 minutes, p=0.045).

Conclusions:
The FAST-MAG Spanish language enrolling line has accounted for 17% of enrollments and has enrolled a group of subjects distinct from the standard, English language enrolling line. The Spanish language enrollment process has doubled the number of Hispanic/Latino patients enrolled in the trial, allowing the study to more closely reflect the population of Southern California.
Abstract 131: Interrater Reliability of the ABCD
2
Score
Authors: Ishida Koto , Kasner Scott E , Messe Steven R , Mullen Michael T , Cucchiara Brett L
Published: March 2022

Background:
The ABCD
2
score is increasingly used for risk stratification of TIA patients, but little is known about the interrater reliability of the score.

Methods:
Patients presenting to the emergency department with suspected TIA (symptom duration <24 hours) were prospectively evaluated. Only those asymptomatic at the time of enrollment were eligible. Patients verbally consented to questioning by multiple raters. We compared ABCD
2
scores determined by raters of different medical specialties to the “gold standard” score of neurovascular attending physicians. Raters were given a worksheet with basic ABCD
2
scoring instructions to complete for each subject; all scores were based on history obtained directly from the patient by each rater. Estimated component, total scores, and ABCD
2
risk category (0-3, 4-5, 6-7) were compared both between raters and with the neurovascular attending score. Reliability was assessed using unweighted kappa statistics.

Results:
A total of 46 patients were assessed, with each scored by a mean of 3.3 raters. In addition to the neurovascular attending, scores were generated by neurology junior (n=37) and senior residents (n=9), and internal medicine (n=36) and emergency medicine residents (n=36). Based on neurovascular attending scores, 35% of patients were categorized as low-risk (ABCD
2
score 0-3), 50% as moderate risk (4-5), and 15% as high risk (6-7). Interrater reliability was limited for ABCD
2
total score (κ=0.28) and category (κ=0.39). Interrater reliability of the component scores was near perfect for age (κ=1) and diabetes (κ=0.94) and substantial for blood pressure (κ=0.66), but only moderate for clinical features (κ=0.54) and duration (κ=0.59). Agreement between ABCD
2
risk category scored by the neurovascular attending and that determined by other raters was as follows: 73% (95%CI:58-88%) for neurology junior residents, 89% (CI:63-100%) for neurology senior residents, 58% (CI:41-75%) for internal medicine residents, and 70% (CI:48-92%) for emergency medicine residents.

Conclusions:
The interrater reliability of the ABCD
2
score is poor. Clinical symptoms (C) and duration (D) displayed the greatest variability among ABCD
2
components.
Abstract 141: Stroke Trends in Mexican Americans and non Hispanic Whites
Authors: Morgenstern Lewis B , Sánchez Brisa N , Smith Melinda A , Baek Jonggyu , Garcia Nelda , Lisabeth Lynda D
Published: March 2022

Objective:
As a primary, pre-specified objective of the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project we studied trends in stroke occurrence among Mexican Americans (MAs) and non Hispanic whites (NHWs) in Corpus Christi, Texas. Previous work suggested higher stroke rates in MAs compared with NHWs.

Methods:
We performed active and passive surveillance, and using source documentation, validated all stroke cases from January, 2000-December, 2010 in this community. Yearly population counts were obtained from the 2000, 2010 US Census and intercensal estimates. Incidence rates of total stroke (completed ischemic and intracerebral hemorrhage) were calculated per 10,000 population. Poisson regression models using the stroke counts within categories of race/ethnicity, age (45-59; 60-74, and 75+) and sex as the outcome and (log) population counts as the offset were used to estimate adjusted rates, rate ratios and time trends. Time trends were modeled as a linear term of years since 2000. The models used data from the entire study period to estimate incidence rates in 2000 and 2010.

Results:
There were 3,086 strokes in MAs and 2,328 in NHWs. Between 2000 and 2010 stroke incidence declined by 3.8% per year (95%CI: 3.0%, 4.6%) (see Figure). In 2000 the incidence rate was 54.2/10,000, it was 35.9/10,000 in 2010. For those aged 45-59; 60-74, and 75+, the yearly declines were 0.6% (95%CI: 1.2%, 2.3%); 6.1% (95%CI: 4.8%, 7.5%); and 3.9% (95%CI: 2.6%, 5.1%) per year, respectively. The decline in stroke incidence was not significantly different by ethnicity in any age group. Within each age category, the ethnicity rate ratios in 2000 vs. 2010 were: 45-59, 2.23 vs 2.15 (p=0.87); 60-74, 1.58 vs 1.77 (p=0.45); and 75 or older, 1.17 vs 1.02 (p=0.29).

Conclusions:
Stroke occurrence rates have declined dramatically in the last decade in both MAs and NHWs, particularly in those 60 and older. However, the disparity between MA and NHW stroke rates persists among those <75.
Abstract 152: Unleashed intracellular Ca2+ Releases From Ryanodine Receptor-2 Plays An Important Role In Diabetic Cerebral Vasoconstriction
Authors: Zheng Yun-Min , Wang Yong-Xiao
Published: March 2022

Many devastating cerebral vascular diseases occur due to abnormally increased [Ca
2+
]
i
and associated contraction in cerebral artery smooth muscle cells (CASMCs); however, the underlying molecular mechanisms are largely unknown. In this study, we assessed the novel hypothesis that FK506 binding protein 12.6 (FKBP12.6) is dissociated from ryanodine receptor-2 (RyR2), leading to unleashed intracellular Ca
2+
release in diabetic CASMCs and thus cerebral vasoconstriction. Using Förster resonance energy transfer and other biochemical assays, we have found that FKBP12.6 was tightly associated with RyR2 in mouse CASMCs. The association of these two Ca
2+
signaling molecules was disrupted in diabetic cells. Investigations using a laser scanning confocal microscope have revealed that targeted gene knockout (KO) of FKBP12.6 significantly increased local intracellular Ca
2+
release (Ca
2+
spark). A similar change in local intracellular Ca
2+
release was observed in diabetic cells. FKBP12.6 KO and diabetes did not produce additive effects. Global (whole-cell) intracellular Ca
2+
release following activation of RyRs with caffeine was increased to a similar extent in both FKBP12.6 KO and diabetic CASMCs. The increased caffeine-induced intracellular Ca
2+
release was not further enhanced in diabetic/FKBP12.6 KO cells. Stimulation of -adrenergic receptors with norepinephrine could result in a large increase in local and global intracellular Ca
2+
release with the same degree in FKBP12.6 KO, diabetic and diabetic/FKBP12.6 KO. FKBP12.6 KO, diabetic and diabetic/FKBP12.6 KO mice were all hypertensive, and their hypertensive levels were similar. In conclusion, we have, for the first time, provided compelling evidence that FKBP12.6 is dissociated from RyR2, which leads to unleashed intracellular Ca
2+
release through RyR2 in CASMCs and associated cerebral vasoconstriction, thereby playing an essential role in the development of diabetic and other cerebral vascular diseases.
Abstract 153: The Role of Contralateral Cerebrovascular Myogenic Dysfunction in Hyperglycemic Stroke
Authors: Coucha Maha M , Li Weiguo , Hafez Sherif , Fagan Susan C , Ergul Adviye
Published: March 2022

Admission hyperglycemia worsens clinical outcomes in acute ischemic stroke (AIS) but the mechanism remains controversial. Our previous studies showing that even a modest acute elevation in blood glucose amplifies vascular injury and neurological deficit emphasize the importance of an intact cerebrovasculature in functional outcomes. Given that stroke lowers perfusion even in the nonischemic hemisphere, the impact of hyperglycemic AIS on cerebrovascular reactivity in the contralateral hemispheres needs to be determined.

Hypothesis:
Acute hyperglycemia exacerbates cerebrovascular myogenic dysfunction in the contralateral hemisphere causing cerebral blood flow (CBF) impairment and worsening stroke outcomes.

Methods:
Weight-matched male Wistar rats (n=6-8) were subjected to 30 min middle cerebral artery occlusion (MCAO)/45 min reperfusion after administration of saline or 40 % glucose solution 10 min before procedure. Myogenic tone of isolated MCAs was determined across the pressure range. In another set of animals (n=5), infarct size, edema and neurologic deficit were measured in rats exposed to 30 min hyperglycemic MCAO/24 h reperfusion. Cerebral perfusion was evaluated with laser Doppler flowmetry.

Results:
The myogenic tone was decreased in both ischemic and nonischemic sides albeit to a different degree (at 80mmHg 5±0.85† and 7.8±0.7*, respectively vs sham 9.4±0.9). Interestingly acute hyperglycemia exacerbated myogenic dysfunction (at 80mmHg 4.8±0.3***) and amplified CBF reduction in the nonischemic hemisphere (MCAO 4.5±3.1% vs hyperglycemic MCAO 22.3±7.1% *p<0.05). When ischemic injury was superimposed with acute hyperglycemia, this led to infarct size expansion (35.6±6.1% vs 15.7±1.6 % *p<0.05), increased edema (15±2.7% vs 7.2±1% *p<0.05) and more pronounced neurological deficit (#p<0.001).

Conclusion:
Our results provide evidence that there is early loss of tone in the contralateral hemisphere, augmented myogenic dysfunction in hyperglycemia is associated with poor stroke outcomes, and that the nonischemic hemisphere may be a novel target for the management of AIS. (†P<0.001, *P<0.05 vs sham, ***p<0.001 vs nonischemic hemisphere)
Abstract 160: Frequency of Ideal Cardiovascular Health Metrics in the SAMMPRIS Trial
Authors: Nahab Fadi , Turan Tanya , Lynn Michael , Chaturvedi Seemant , Derdeyn Colin , Fiorella David , Janis Scott , Lane Bethany , Montgomery Jean , Chimowitz Marc
Published: March 2022

Purpose:
The number of ideal cardiovascular health metrics as defined by the American Heart Association (AHA) Life’s Simple 7 has previously been associated with a significantly lower risk of cardiovascular disease and stroke in community studies. The objective of our study was to determine the frequency of ideal cardiovascular health metrics at baseline among participants enrolled in the SAMMPRIS trial and to compare metrics by race and sex.

Methods:
SAMMPRIS randomized 451 patients with symptomatic 70%-99% intracranial stenosis to aggressive medical management or stenting plus aggressive medical management at 50 US sites. We evaluated seven modifiable cardiovascular disease risk factors at baseline and categorized them as ideal based on criteria modified from the AHA definition of Life’s Simple 7. Baseline metrics were compared by race and sex using Fisher’s exact test.

Results:
The frequency of ideal health metrics is shown in Table 1. Of participants with data available on all metrics, the majority (57%) had 0-1 ideal AHA metrics. Non-whites were less likely than whites to have ideal nonsmoking behavior (56% vs 68%, p=0.017) and ideal fasting glucose (21% vs 36%, p=0.046). Women were less likely than men to have ideal physical activity status (15% vs 27%, p=0.002) but more likely to have ideal nonsmoking behavior (70% vs 61%, p=0.035).

Conclusions:
At baseline, participants enrolled in the SAMMPRIS trial had a low frequency of ideal cardiovascular health metrics. Future analyses will relate the frequency of these metrics to outcomes in the trial.
Abstract 161: Do Baseline Risk Factor Differences Explain the Variation in Results Between SAMMPRIS and WASID?
Authors: Chaturvedi Seemant , Lynn Mike , Turan Tanya , Lane Bethany , Montgomery Jean , Derdeyn Colin , Fiorella David , Janis Scott , Chimowitz Marc ,   for the WASID and SAMMPRIS Study Groups
Published: March 2022

Introduction:
When enrollment in SAMMPRIS was stopped, the 30-day rate of stroke or death and the 1-year rate of the primary endpoint in the medical arm were 5.8% and 12.2%, respectively. The comparative rates in patients in WASID who met the SAMMPRIS entry criteria were 10.6% and 21.9%. While the lower rates in the SAMMPRIS trial have been attributed to aggressive medical management, an alternative hypothesis is that SAMMPRIS patients may have been at lower risk due to a lower burden of vascular risk factors.

Methods:
We compared risk factors at study entry in the 227 patients in the medical arm of SAMMPRIS with the 143 patients in WASID who met the SAMMPRIS entry criteria.

Results:
Compared with WASID patients, SAMMPRIS patients were younger (mean age 59.5 years vs. 62.5 years; p=0.009) but had higher percentages of hypertension (89% vs. 76%; p<0.001)*, hyperlipidemia (89% vs 69%; p<0.001)*, stenosis in the 80-99% range (55% vs. 35%; p<0.001), anterior circulation stenosis (68% vs. 48%; p<0.001), white race (71% vs. 61%; p=0.06), and on an antithrombotic agent at the time of the qualifying event (62% vs. 52%; p=0.08). SAMMPRIS patients had higher mean systolic blood pressure (146.8 mmHg vs. 139.1, p< 0.001), higher body mass index (30.7 kg/m
2
vs. 29.4, p=0.045) but lower LDL (98 mg/dl vs. 125, p<0.001). There were no significant differences in the frequency of female gender, stroke as the qualifying event, diabetes, smoking, history of previous stroke, time from qualifying event to study entry, and history of CAD.

Conclusion:
Compared to WASID patients meeting the SAMMPRIS entrance criteria, SAMMPRIS patients were slightly younger but had a higher burden of other important vascular risk factors including severity of stenosis, which was the most important predictor of subsequent stroke in WASID. These data suggest that the improved prognosis in the medical arm of SAMMPRIS compared with WASID patients is related to the aggressive medical management used in SAMMPRIS and not to a lower burden of risk factors in SAMMPRIS patients. * the increased frequency of hypertension and hyperlipidemia in SAMMPRIS might reflect the change in the JNC definition of hypertension after the start of WASID and the fact that many more patients are prescribed statins now than when WASID was done
Abstract 163: TICI Success Rates In Swift: Comparison Between Randomized Arms And Correlation To 90 Day Neurologic Outcome
Authors: Jahan Reza , Liebeskind David , Nogueira Raul , Saver Jeffrey ,   for SWIFT Investigators
Published: March 2022

Background and Purpose —
TICI scores are used to assess recanalization in clinical settings. We evaluated TICI outcomes in the SWIFT randomized controlled trial of mechanical thrombectomy in ischemic stroke along with their association with outcomes.

Methods —
One hundred and thirty four subject angiograms were analyzed and TICI scores assessed by an independent core laboratory. Successful recanalization was defined as either TICI 2a, 2b or 3, TICI 2b or 3 or alternatively as TICI 3 alone. These success definitions were compared between subject groups in the study after use of randomized device and post rescue therapy. For the entire study population of 134 subjects, TICI success was associated with 90-day functionally independent outcome, defined as modified Rankin Score (mRS) zero to 2.

Results —
Table 1 shows TICI success rates after use of randomized device and post rescue therapy. Post randomized device use, significantly greater rates of TICI 2b-3 and TICI 3 success were observed in the Solitaire FR group than in the MERCI group. Under the alternative definition of success as TICI 2a-3, a trend toward significance persisted post randomized device use. Post rescue therapy, significantly greater TICI 3 rates were observed and a trend toward significance was seen in favor of Solitaire FR in TICI 2b-3 success. Among all subjects including roll-ins (who were treated with Solitaire FR), functionally independent outcome was strongly associated with successful recanalization using the 2b-3 definition (48.7% vs. 17.4%, p=0.0005), the 2a-3 definition (44.9% vs. 15.2%, p=0.0028) and TICI 3 alone (52.1% vs. 20.7%, p=0.0071).

Conclusions —
TICI scores after mechanical thrombectomy device use were better among subjects randomized to Solitaire FR than in those randomized to MERCI. Good clinical outcome defined using mRS at 90 days was strongly associated with successful recanalization using three different TICI success definitions.
Abstract 181: MR Oxygen Metabolic Index (OMI) Thresholds for Delineating Core, Penumbra, and Oligemia in Acute Ischemic Stroke Patients
Authors: An Hongyu , Ford Andria L , Chen Yasheng , Vo Katie D , Powers William J , Lee Jin-Moo , Lin Weili
Published: March 2022

Background:
PET cerebral oxygen metabolic rate (CMRO
2
) provides a measure of tissue viability during acute ischemic stroke. Oxygen metabolic index (OMI), an MR-derived parameter closely related to CMRO
2
, was developed as a more accessible imaging approach for acute stroke patients.

Methods:
38 acute ischemic stroke patients were imaged at 3.0 hours (tp1), 6.2 hours (tp2), and 1 month (tp3) after onset. Dynamic susceptibility contrast method measured CBF. An asymmetry spin echo sequence was used to calculate OEF; OMI=CBFxOEF. Co-registered voxels were normalized to the non-ischemic hemisphere. Two OMI thresholds to distinguish core from penumbra and penumbra from oligemia were derived by separating brain tissue into 4 groups: (1) tissue that died regardless of reperfusion (
core
); (2) tissue that died without reperfusion (
nonreperfused_penumbra
); (3) tissue that survived with reperfusion (
reperfused_penumbra
); and (4) tissue that survived regardless of reperfusion (
oligemia
). An exhaustive search method was used to determine an optimal pair of core/penumbra and penumbra/oligemia thresholds for each patient by minimizing the “average prediction error (APE)”, a metric averaging the differences for each tissue group’s actual infarct probability (IP) from the ideal IP (Table). The predictive abilities of the thresholds were tested in the same cohort using “leave-one-out” cross-validation, and the APE averaged across the population.

Results:
The core/penumbra OMI threshold and the penumbra/oligemia OMI threshold ranged from 0.21-0.22 and 0.41-0.43, respectively. The median IP’s [IQR] for the 4 tissue groups are shown (Table). The population averaged APE was 15% [5%, 24%].

Conclusions:
OMI thresholds delineated the ischemic penumbra with high predictive ability: reperfused penumbra demonstrated low IP (6.79%), while non-reperfused penumbra demonstrated high IP (73.57%). These thresholds will require further testing in independent patient cohorts.
Abstract 195: Reducing Frequency of Symptomatic Intracranial Hemorrhage in Patients With Acute Ischemic Stroke Treated by Recombinant Tissue-Plasminogen Activator; Interim Result of a Prospective Observational Cohort Study
Authors: Yamaguchi Takenori , Yamada Teruyuki , Hirota Toshinobu , Tanabashi Norio
Published: March 2022

[Introduction]
Combination therapy with rt-PA and edaravone, a free radical scavenger, has become a prevalent treatment for acute ischemic stroke in Japan. PROTECT4.5 (Post marketing Registry OnTreatment with Edaravone in acute Cerebral infarction by the Time window of 4.5 hours) is a prospective observational cohort study to evaluate the efficacy and safety of the combination therapy.

[Hypothesis]
We assessed the hypothesis that combination therapy will reduce frequency of symptomatic intracranial hemorrhage in patients with acute ischemic stroke.

[Methods]
Patients treated by rt-PA and edaravone within 4.5 hours after onset of ischemic stroke were enrolled. The primary endpoints were proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 3 months after onset, and frequency of symptomatic intracranial hemorrhage (sICH) within 36 hours after initiating treatment. Mortality at 3 months after onset was assessed as a secondary endpoint.

[Results]
Between Apr 2010 and May 2012, 2814 patients from 839 institutes received combination therapy with edaravone and rt-PA. The mean age was 71.9 years old; 62.2% were male. The median score of NIHSS at baseline was 13 and the median time from onset to treatment with rt-PA was 2.25 hours. The most common type of stroke was cardioembolic (57.7%). Concomitant hypertension was present in 58.3% and diabetes mellitus in 17.1%. Estimated glomerular filtration rate < 60 mL/min/1.73m
2
was observed in 34.2% of patients. The proportion of patients with mRS 0-1 was 38.8% [709/1826, 95%Confidence Interval 36.6-41.1%]. Frequency of sICH and mortality were 1.7%[48/2814, 1.3-2.3%] and 8.9%[162/1826, 7.6-10.3%], respectively.

[Conclusions]
The severity and the proportion of mRS 0-1 in the patients enrolled in PROTECT4.5 were similar to those in the prospective single-arm open-label trial and the previous observational studies of rt-PA [J-ACT (Stroke 2006; 37:1810-1815), CASES (CMAJ 2005; 172:1307-12), STARS (JAMA 2000; 283:1145-50)], but frequency of sICH and mortality were lower.
Abstract 199: Stroke After Aortic Valve Surgery: Results From A Prospective Cohort
Authors: Messe Steven R , Acker Michael A , Kasner Scott E , Bilello Michel , Fanning Molly , Giovannetti Tania , Floyd Thomas F
Published: March 2022

Introduction:
Aortic valve disease is increasing in prevalence as the population ages. The reported risk of stroke complicating surgical aortic valve repair has ranged widely from 2-10% and its impact on outcome is not well characterized as prior data have come from single centers without systematic evaluation by neurologists. We hypothesized that stroke complications of aortic valve repair have been underestimated in prior cohorts.

Methods:
We performed a prospective cohort study of patients ≥ 65 years old undergoing open surgical aortic valve repair for calcific moderate to severe aortic stenosis. Patients underwent pre- and post-operative MRI, and were evaluated by neurologists at post-operative day 1, 3, and 7. Cerebrovascular endpoints were independently adjudicated by two vascular neurologists. Clinical stroke was defined as new focal neurologic symptoms lasting > 24 hours determined to be of vascular origin, TIA as neurologic symptoms lasting < 24 hours and without evidence of infarction, and silent infarct as imaging evidence of acute infarct without clinical symptoms.

Results:
Over a 4 year period, 184 subjects were enrolled, age 75.7 ± 6.3 years, 36% female, and 5% non-white. Clinical strokes were identified in 30 (16%) patients, TIA in 4 (2%), and in-hospital mortality occurred in 9 (5%) of patients. Most strokes were mild; the median NIHSS was 3 (IQR 1 - 9). Clinical stroke was associated with increased length of stay, median 12.5 vs 10 days, p=0.006. Moderate or severe stroke (NIHSS≥10) which occurred in 7 (4%) was strongly associated with in-hospital mortality 43% vs 3%, p =0.003. Post-op MRI was not obtained in 55 subjects, often due to concomitant illness; of those, 15 (27%) had clinical strokes and 8 (15%) died. Of the 114 stroke-free subjects with post-op imaging, silent infarct was identified in an additional 49 (43%). Silent infarct was not associated with in-house mortality or length of stay.

Conclusions:
Cerebral infarction was detected in over 40% of patients undergoing aortic valve repair. Clinical stroke complicating valve surgery is associated with increased length of stay and mortality.
Abstract 201: Effect of Statin Treatment Before and After Hospitalization on Mortality Following Acute Ischemic Stroke: Importance of Confounding by Stroke Severity and Palliative Care
Authors: Reeves Mathew J , Kapral Moira , Fang Jiming , Smith Eric E , Dowlatshahi Dar , Sharma Mike
Published: March 2022

Background:
Statins may improve outcomes following acute ischemic stroke (AIS), but studies often fail to account for confounders such as stroke severity and palliative care. We examined the effect of statin treatment both before and after hospital admission in AIS.

Methods:
Data were prospectively collected from 10646 AIS admissions to 11 hospitals participating in the Registry of the Canadian Stroke Network between 2003-2008. The effect of statins taken before and after admission on stroke mortality was determined using multivariable logistic regression. We repeated analyses using oral hypoglycemic agents as a marker of the avoidance of oral agents in the acute setting.

Results:
Pre-admission 31% of patients were taking statins. Severe stroke (Canadian Neurological Scale < 5) was slightly lower in patients using statins pre-admission (19.2% vs. 20.9%). Pre-admission statins were associated with significantly lower adjusted mortality at 180-days (OR=0.82, 95% CI 0.69, 0.97), but not at 30-days (OR=0.90, 95% CI 0.73, 1.11). Post-admission 65% of patients received statins. Patients who were on statins pre-admission but off statins post-admission (i.e., ‘On-Off’ or discontinuation) had strikingly higher mortality, however, this effect was markedly attenuated after adjustment (Table). Stroke severity and palliative care were identified as major confounders. Continuing or initiating statin treatment post-admission was associated with significantly lower mortality compared to patients who were never treated with statins, however, oral hypoglycemic agents exhibited similar associations (Table).

Conclusions:
Pre-admission statin use was associated with lower 6-month mortality. Stroke severity and palliative care confounded the relationships between post-admission treatment and mortality, especially for patients in whom statins were discontinued. Well conducted RCTs are needed to quantify the benefits of statins in the acute setting.
Abstract 204: Blood Pressure Reduction And Stroke Recurrence: The Progress Trial
Authors: Arima Hisatomi , Anderson Craig , Omae Teruo , Woodward Mark , MacMahon Stephen , Mancia Giuseppe , Bousser Marie-Germaine , Tzourio Christophe , Harrap Stephen , Neal Bruce , Chalmers John
Published: March 2022

Background:
A recent observational analysis of a large-scale randomized controlled trial identified a “J-curve” phenomenon such that low and high blood pressure (BP) levels are associated with increased risks of recurrent stroke among patients with recent ischemic stroke. The objective of the present analysis was to determine whether larger reduction in BP associated with treatment increases the risks of recurrent stroke among patients with cerebrovascular disease.

Methods:
This is a subsidiary analysis of the PROGRESS trial, a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in secondary prevention of stroke. A total of 6105 patients with prior stroke or transient ischemic attack were randomly assigned to either active treatment (perindopril ± indapamide) or matching placebo(s). There were no BP criteria for entry. BP was measured at every visit and groups of participants defined by reduction in systolic BP (SBP) from baseline (<0, 0-9, 10-19 and ≧20 mm Hg) were used for these analyses. Outcomes of the present analyses were recurrent hemorrhagic and ischemic stroke.

Results:
During a mean follow-up of 3.9 years, 111 hemorrhagic stroke and 565 ischemic stroke events were observed. There were clear inverse associations between SBP reduction and the risk of hemorrhagic stroke even after adjustment for age, sex, region, baseline SBP, diabetes, current smoking and randomized treatment: adjusted annual incidence rates were 0.08%, 0.06%, 0.05% and 0.03% for participant groups defined by reduction in SBP levels of <0, 0-9, 10-19 and ≧20 mm Hg, respectively. The lowest risks of hemorrhagic stroke were observed among patients who achieved ≧20 mm Hg reduction in SBP associated with treatment. Annual incidence of ischemic stroke was 2.19%, 1.74%, 1.73% and 1.72% for the same participant groups. Compared with patients who did not achieve any SBP reduction, the decreases in the risk of ischemic stroke were similar in the groups achieving SBP reductions of 0-9, 10-19 and ≧20 mm Hg.

Conclusions:
The present analysis provided no evidence of increase in recurrent stroke associated with larger reduction in SBP produced by BP lowering treatment among patients with cerebrovascular disease.
Abstract 206: Cerebrovascular Events In Patients With Chronic Kidney Disease On Erythropoiesis Stimulating Agent
Authors: Rad Ali , Misra Shubham , Karapetyan Karine , Garg Rajan
Published: March 2022

Title:
Cerebrovascular Events in Patients with Chronic Kidney Disease on Erythropoiesis Stimulating

Authors:
Ali M Rad, MD, MPH; Shubham Misra,MD;Rajan Garg, MD;Karine Karapetyan, MD;Sheila Roxana Safar, MD; Daniel Goldsmith, MD

Background:
Anemia is associated with an increased risk of cardiovascular events among patients with Chronic Kidney Disease (CKD). Guidelines have been developed for hemoglobin (Hgb) targets. Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin level in CKD patients. The recent TREAT study found an increased incidence of stroke and cancer when maintaining the Hgb level at 12.5 g/dl. In the opposite, Watanabe et al showed no significant increase in risk of developing stroke in a Japanese population.

Methods:
All patients with chronic kidney disease who admitted between Jan 2009 till June 2011 were selected. Patients are categorized to 2 groups, CKD patients with cerebravascular events and CKD with no cerebrovascular events. Binary logistic regression was used for analysis. All results were adjusted for age and gender.

Results:
A total of 4926 patients were recognized. 348 out of 4926 had cerebrovascular events in their admissions between Jan 2009 till June 2011. 241/341 had ischemic cerebrovascular events, and the remainder had hemorrhagic events. Using binary logistic regression, our study shows a significant association between ESA injections and cerebrovascular events after adjusting for age, sex and Hgb level (p < 0.001).

Conclusions:
We showed there is significant association between ESA use and cerebrovascular events adjusting for hemoglobin level, age and sex. Even though there was association between Hgb level and cerebrovascular events in our preliminary data, after adjusting for ESA injections, there was no association between Hgb level and cerebrovascular events. This suggests less of an association between Hgb level and stroke than use of an ESA and stroke. Based on these results, we recommend considering iron replacement and blood transfusion in the treatment of anemia and CKD. More studies should be done to establish possible causation and pathophysiology between ESA injections and cerebrovascular agents which may include evaluating for any dose related association.
Abstract 215: The Prognostic Significance of Subendocardial Myocardial Infarction in Patients Undergoing Carotid Endarterectomy or Carotid Artery Stent Placement
Authors: Khan Amir , Adil Malik M , Chaudhry Saqib A , Suri M Fareed K , Qureshi Adnan I
Published: March 2022

Background:

The use of subendocardial myocardial infarction [MI] (non-ST-elevation or non-Q wave MI) as an endpoint following carotid endarterectomy (CEA) or carotid angioplasty and stent placement (CAS) within and outside clinical trials is debated.

Objective:

To identify the frequency of subendocardial MI and impact on outcomes related to CEA or CAS in patients treated in a large national cohort.

Methods:

We determined the frequency of subendocardial MI and associated in-hospital outcomes using data from the Nationwide Inpatient Survey (NIS) data files from 2002 to 2010. We ascertained the affect of subendocardial MI on in-hospital mortality and composite end point of stroke, cardiac events, and death after adjusting for potential confounders using multivariate analysis.

Results:

Of the 1,083,688 patients who underwent CEA or CAS, 11341 (1%) developed subendocardial MI within the same hospitalization. The in-hospital mortality (6.2% versus 0.4%, p<0.0001) and neurological complications (6% versus 1.4%, p<0.0001) were significantly higher among patients who developed subendocardial MI. The hospitalization charges ($113,317 versus $29,160, p<0.0001) and mean [±SD] hospital days [12.2±9.0 versus 2.8±4.0 p<0.0001) were significantly higher among patients with subendocardial MI. After adjusting for age, gender, presence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, and renal failure, subendocardial MI was associated with higher rates of in-hospital mortality (odds ratio [OR] 8.6, 95% confidence interval [CI] 7.0- 10.7)(p=<0.0001) and composite end point of stroke, cardiac events, and death (OR 14.6, 95% CI 13,0 - 16.5)(p=<0.0001).

Conclusions:

Our results contradict the notion that subendocardial MI is a relatively benign entity after CEA or CAS. It remains unclear whether subendocardial MI is a marker or cause of high rates of adverse outcomes and resource utilization following CEA or CAS.