bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3122: Delays in Warfarin Reversal following Intracerebral Hemorrhage: A Population-Based Study
Authors: Flaherty Matthew L , Haverbusch Mary , Comeau Mary , Moomaw Charles J , Brown Mark , Langefeld Carl , Adeoye Opeolu , Broderick Joseph P , Woo Daniel
Published: July 2021

Introduction:
Warfarin anticoagulation worsens outcomes following intracerebral hemorrhage (ICH), in part by increasing risk of hematoma expansion. Prompt reversal of warfarin anticoagulation is therefore imperative. We documented patterns of anticoagulant reversal following ICH in a large, population-based stroke study.

Methods:
As part of the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study, we identified all patients who presented with an ICH to an emergency room in the five-county Greater Cincinnati/Northern Kentucky region from July 2008 through December 2009. Patients from outside the five-county region were excluded. We recorded all INRs, medications used to reverse coagulopathy, and mortality. For patients with warfarin-associated ICH and initial INR > 1.4, we determined the time from presentation to initiation of warfarin reversal and time to achievement of INR ≤ 1.4. We also compared times to warfarin reversal in centers with and without emergency medicine residency training programs (“academic” vs. “community” hospitals).

Results:
There were 403 cases of ICH identified at 13 local hospitals, including 67 cases of warfarin-associated ICH. After exclusion of patients with INR < 1.4 upon arrival, patients with stroke in the hospital, and patients who were made “comfort-care” within one hour of arrival, there were 53 cases of warfarin-associated ICH for analysis. Times of anticoagulation reversal are displayed in the
table
. Cryoprecipitate was given to one patients and platelets to two patients. No patients received promthrombin complex concentrates or recombinant activated factor VII. Use of FFP did not differ between academic hospitals and community hospitals, nor did time to FFP administration. Among 31 patients with documented reversal of anticoagulation to INR ≤ 1.4, time from FFP administration to INR normalization was less at academic centers, but this may have been a function of frequency of INR testing. Thirty-day mortality among the 53 analyzed cases was 49%.

Conclusions:
Reversal of coagulopathy was significantly delayed in our population, with a median time of > 3 hours from ED arrival to initiation of FFP. Only 31 of 53 analyzed cases had documented reversal of INR to ≤ 1.4, and this took a median of 11 hours. Improvements in time to warfarin reversal via streamlined systems or alternative medications such as prothrombin complex concentrates may improve patient outcomes.
Abstract 3126: Ischemic Postconditioning Facilitates Brain Recovery After Stroke by Promoting mTOR Activity
Authors: Wang Peng , Xie Rong , Ji Xunming , Zhao Heng
Published: July 2021

Introduction:
Ischemic postconditioning represents a series of brief occlusions of blood flow before complete restoration of reperfusion after brain stroke. We have shown that ischemic postconditioning reduces infarct size in focal ischemia in rats and improves neurological deficits, but the underlying protective mechanisms are not fully understood. The mammalian target of rapamycin (mTOR) pathway plays a key role in cell growth, differentiation and survival. We studied the hypothesis that the mTOR pathway is involved in the protective effect of ischemic postconditioning and brain recovery after stroke in rats.

Methods:
Focal ischemia was induced by 30 min of bilateral CCA occlusion and permanent distal MCA occlusion in rats. Ischemic postconditioning was induced by 3 cycles of 30 sec reperfusion and 10 sec occlusion at the end of stroke. Rapamycin, an mTOR inhibitor, was injected into the left lateral ventricle 1 hour before stroke onset. For the behavior test, home cage and vibrissa-elicited limb use tests were used and performed until 21d after stroke. Peri-infarct tissues were collected 1 and 3 weeks after stroke for Western blotting and immunostaining. Molecular markers related with synaptic transmission and neuronal growth and plasticity, including Gap-43, synaptophysin, MAP-2 and PSD-95 proteins were detected. Protein levels of phosphorylated mTOR (p-MTOR) and 4EPB-1 in the mTOR pathway, and the upstream molecule, Akt, were also measured.

Results:
Ischemic postconditioning improved neurological function when measured 2 weeks after stroke (n=6, p<0.05), and reduced brain injury size by 34.2% (P<0.05). These protective effects were abolished by rapamycin treatment. The results of Western blotting showed that postconditioning substantially promoted the protein level of Gap-43, MAP-2 and PSD-95, but not synaptophysin. Rapamycin significantly inhibited Gap-43 levels at 1 and 3 weeks after stroke, and inhibited Map-2 level at 1 week (P<0.05). Postconditioning significantly increased the protein levels of p-Akt, p-mTOR, p-4EBP-1 compared with control ischemia (p<0.05) at 1 week after stroke injury. Rapamycin attenuated p-mTOR levels 1 and 3 weeks after stroke, and inhibited p-4EBP-1 level at 1 week (p<0.05), but had no effects on the expression level of p-Akt and Akt.

Conclusion:
Ischemic postconditioning improved brain function, which is consistent with the improved expression of proteins related with synaptic function and brain plasticity. This protection appears to be achieved by the enhanced mTOR activity.
Abstract 3147: Community Socioeconomic Status: Effect on the Knowledge of Stroke
Authors: Mehta Dhwani , Khoury Jane , Alwell Kathleen , Flaherty Matthew , Woo Daniel , Adeoye Opeolu , Khatri Pooja , Kissela Brett , Kleindorfer Dawn
Published: July 2021

Background and Purpose
- Despite numerous public awareness campaigns, knowledge about stroke warning signs, risk factors, and treatments remains poor. Previously we described racial disparities in stroke knowledge. We now explore the impact of community socioeconomic status (SES) on stroke knowledge within a large, bi-racial population.

Methods
-Survey respondents were contacted via a random-digit dial telephone survey in 2005 from the Greater Cincinnati/Northern Kentucky population. Respondents were asked open-ended questions about stroke with regard to warning signs, risk factors, and treatment with rt-PA. Answers were adjudicated by study physicians.. Community SES was defined as the percentage below poverty level within a respondent’s census tract of residence. There are 346 census tracts in the region. For analysis the SES was stratified into quartiles (percent of residents in census tract living below poverty of <5%. 5%-10%, 10%-25%, and >25%. Univariate and multivariate analyses were performed. Potential covariates were race, sex, education, age, smoking, prior stroke or TIA, and history of high blood pressure, high cholesterol, diabetes, or heart attack. Responses regarding 3 warning signs, 3 risk factors, and knowledge of rt-PA were compared among the different poverty groups.

Results
- There were 2156 respondents to the stroke survey. The demographics of the respondents was 24.5 % black, 61.6% women, mean age of 61.5 years. Adjusted odds ratios and 95% confidence intervals are presented in the
table
. There were no significant differences by community SES of respondents in knowledge of 3 stroke warning signs, 3 risk factors, or of rt-PA.

Conclusion
- Community SES does not appear to exert an independent effect on knowledge of stroke warning signs and risk factors, or knowledge of rt-PA as a treatment for stroke. It is likely that education and individual experiences with stroke are more important than community poverty for stroke knowledge. This should inform future interventions for improving stroke knowledge.
Abstract 3148: Self Reported Quality of Life After Intracerebral Hemorrhage: Is a Modified Rankin Scale Score of 4 Worth it?
Authors: Kleinman Jonathan T , Snider Ryan W , Eyngorn Irina , Thai Demi , Komshian Sevan R , Venkatasubramanian Chitra , Finley-Caulfield Anna , Wijman Christine A
Published: July 2021

Background:
Intracerebral hemorrhage (ICH) trials often define poor outcome as a modified Rankin Scale Score (mRS) ≥4. While mRS score thresholds are important for demonstrating treatment effect, they do no tell physicians if a treatment outcome is “worth it.” Little self-reported quality of life (QOL) data exists to guide physicians, so opinions during academic discussions and/or family meetings may be driven by personal bias. We sought to describe both self and surrogate reported QOL in ICH survivors in relation to mRS score.

Methods:
Consecutive ICH patient were prospectively enrolled in the NIH-funded DiAgnostic Utility of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study. Survivors were followed up at 3 months in clinic and at 12 months by telephone. At each time point, patients or surrogates were asked to rate the patient’s QOL as: excellent, good, fair, or poor. mRS scores were determined by an investigator through a semi-structured interview.

Results:
Self reported QOL was available in 95 patients with 143 QOL ratings, and surrogate reported QOL in 66 patients with 84 QOL ratings. Of self-reporters with a mRS of 4, 29% reported at least a good QOL, and 93% rated at least a fair QOL (
Figure

1). Of self-reporters with a mRS of 3, 58% reported at least a good QOL, and 97% rated at least a fair QOL. Patients with a mRS of 4 were less likely to report a poor QOL than surrogate raters (χ
2
=3.9, p=0.05,
Figure

2). In all patients, both self-reported and surrogate reported QOL were only loosely associated with mRS (R
2
=0.25 and R
2
=0.12, respectively). Forty-eight patients had self-reported QOL at 3 and 12 months. In these patients mRS improved in 16 (33%) patients without an associated improvement in QOL. Seven patients (15%) reported an improvement in QOL, but only 3 had an improvement in their mRS between 3 and 12 months. In 3 (6%) patients, the mRS worsened while QOL remained unchanged. No change in mRS was seen in 8 (17%) patients who reported worse QOL at 12 than at 3 months.

Conclusions:
Self reported QOL is only loosely correlated with mRS for the individual patient. Patient surrogates are more prone to rate QOL of patients with a mRS of 4 as poor than patients themselves. These data are clinically relevant as mRS alone may not capture the satisfaction of the individual patient with their outcome.
Abstract 3158: Presence of Underlying Metastatic Malignancy Increases the Risk of Intracerebal Hemorrhage after Endovascular Treatment of Acute Ischemic Stroke.
Authors: Hassan Ameer E , Tariq Nauman , Rostambeigi Nassir , Chaudhry Saqib , Rodriguez Gustavo , Suri Fareed , Qureshi Adnan
Published: July 2021

Background:
The effect of pre-existing malignancy with or without metastasis on angiographic and clinical success of endovascular treatment in acute ischemic stroke patients has not been previously studied. The procoagulant states in patients with pre-existing malignancy may lead to suboptimal results after endovascular treatment.

Objective:
To determine the effect of underlying malignancy with or without metastasis on angiographic recanalization and clinical outcomes among acute ischemic stroke patients undergoing endovascular treatment.

Methods:
We reviewed consecutive acute ischemic stroke patients treated with endovascular treatment over a 5-year period. Demographics characteristics, NIHSS score before and after the procedure, and discharge modified Rankin scale (mRS) were collected. An improvement of 1 point or more on the Qureshi grading scale was used to define angiographic recanallization. Primary malignancy and evidence of metastasis was obtained by individual chart review. We analyzed whether the presence of malignancy with or without metastasis was associated with angiographic recanalization, favorable clinical outcome, intra-cerebral hemorrhage (ICH), and length of stay (LOS) after age and NIHSS score adjustment.

Results:
We analyzed 186 patients undergoing endovascular treatment, mean age + SD: 65+16 years, 100(54%) men, and mean admission NIHSS score ± SD: 15.3+8. Of these, 34 patients (18%) had underlying malignancy [20 were men] with 16 patients with documented metastatic disease. The mean age was higher in the malignancy group (72 versus 64 years, p=0.014). LOS was similar (11 days versus 9, p=NS). Adjusting for age and admission NIHSS score, regression analysis showed no impact from malignancy with or without metastatic disease on recanalization rate (odds ratio [OR]=0.5, p=NS) or discharge mRS (p=NS). A total of 37 patients developed ICH after endovascular therapy (38% and 18% in patients with or without underlying malignant disease, respectively). The presence of malignancy wih or without metastatic disease was associated with significantly higher ICH rates (OR=3, p=0.05) after endovascular treatment.

Conclusion:
Underlying malignancy with or without metastasis in patients undergoing endovascular procedure for acute ischemic stroke is not associated with lower rates of angiographic recanalization or poor outcomes but increases the rates of post-procedural ICH by 3 fold.
Abstract 3174: Intravenous Thrombolysis in 3-4.5 hours: Utilization and outcomes Analysis of the Minnesota Stroke Registry
Authors: Tekle Wondwossen G , Chaudry Saqib I , Hassan Ameer , Peacock James , Lakshiminarayan Kamakshi , Tsai Albert , Luepker Russell , Anderson David , Qureshi Adnan I
Published: July 2021

Background:
The results of the third European Cooperative Acute Stroke Study (ECASS 3) demonstrated that intravenous (IV) thrombolysis for acute ischemic stroke (AIS) improved patient outcomes when administered within 3-4.5 hours (hrs) after symptom onset. We analyzed data from the Minnesota Stroke Registry to assess the rates of IV thrombolytic utilization in this expanded window and examine outcomes of patients treated within the 3-4.5 hrs window.

Methods:
We identified patients who had received IV recombinant tissue plasminogen activator (rt-PA) at any of the 19 participating hospitals from Jan 1, 2008 till Dec 31, 2010. Treatment groups were those actually treated by IV rt-PA in 0-3 hrs and those treated by IV rt-PA in 3-4.5 hrs. We compared the rates of unfavorable outcome (inability to ambulate independently with or without assisting device at discharge) and in-hospital mortality among patients treated with IV rt-PA within 3-4.5 hrs to those who received IV rt-PA within the conventional 0-3 hrs window.

Results:
Out of the total 519 patients who received IV rt-PA for AIS, 433 (83%) were treated within 0-3 hrs and 86 (17%) within 3-4.5 hrs. Adjusting for age, sex, and “adverse initial examination findings” (reduced level of consciousness, aphasia, and weakness), there was a trend towards higher rates of unfavorable outcome at discharge among those treated within 3-4.5 hrs compared to those treated within 0-3 hrs time window (Odds ratio [OR], 1.76; 95% confidence interval [CI], 0.95 to 3.26). In hospital mortality did not differ between the 3-4.5 hrs groups and 0-3 hrs groups (OR, 1.05; 95% CI, 0.38 to 2.96). Incidence of symptomatic intracerebral hemorrhage was non-significantly lower in the 3-4.5 hrs group compared to the 0-3 hrs group (2.3% vs.4.6%, p=0.34).

Conclusion:
Patients who received IV rt-PA within the 3-4.5 hrs window comprised 17% of all IV rt-PA cases treated in the MSR hospitals after guidelines recommended time window expansion. Outcomes of these patients were comparable to those treated within 3 hours of symptom onset.
Abstract 3208: Sensitivity and Reliability of SWI Compared to T2* GRE MRI for Detection of Microbleeds in Cerebral Amyloid Angiopathy
Authors: Cheng Ah-Ling , McCreary Cheryl R , Lauzon M. L , Frayne Richard , Goyal Mayank , Smith Eric E
Published: July 2021

Introduction:
Case examples and small case series suggest that MRI susceptibility weighted imaging (SWI) may be more sensitive for cerebral microbleed (CMB) detection compared to MRI T2* gradient-recalled echo (GRE). However, there are few data on CMB counts measured by SWI vs. GRE, or inter-rater reliability, in groups of patients with cerebral small vessel disease. We used data from a prospective cohort study of cerebral amyloid angiopathy (CAA), a cerebral small-vessel disease marked by high numbers of CMBs, to quantify the sensitivity and reliability of SWI vs. GRE for CMB detection.

Methods:
Nine patients with symptomatic CAA (mean age 71±8.3; 7 males and 2 females) and 21 healthy non-CAA controls (mean age 68±6.3; 10 M/11 F) underwent T2* GRE and SWI on a 3.0T MR scanner. Probable CAA was diagnosed according to the Boston criteria prior to study entry using information from clinical MRI with GRE sequences. Two raters (labeled 1 and 2) independently interpreted the GRE and SWI scans blinded to clinical information. The phase-filtered magnitude image was used for SWI interpretation. Agreement reliability was assessed using the kappa coefficient (where a kappa of ≥0.60 indicates good agreement) or the intraclass correlation coefficient (ICC).

Results:
Overall, the raters identified 1,432 CMBs in the 9 CAA cases (range 1-434 per patient) and 8 CMBs in the healthy controls (range 0-3). Rater 1 identified CMBs in 5/21 healthy controls on SWI and 5/21 on GRE, while rater 2 identified CMBs in 4/21 on SWI and 3/21 on GRE (kappa 0.70 for GRE and 0.57 for SWI). In CAA cases more CMBs were seen on SWI compared to the GRE sequence but the difference was significant only for rater 1 (rater 1: on average 85% more per patient on SWI than on GRE, p=0.008; rater 2: 19% more, p=0.25). Among CAA cases the reliability between raters was poor for GRE (ICC 0.36) but excellent for SWI (0.94, p<0.05 for comparison with GRE). Review suggested that the differing reliability was because rater 1 was less likely than rater 2 to identify faint lesions on GRE as CMB, whereas these lesions were more conspicuous on SWI. If SWI rather than GRE were used to determine CAA status according to the Boston criteria, all 9 CAA cases would remain classified as probable CAA but 2/21 controls would be reclassified as either possible (n=1) or probable (n=1) asymptomatic CAA based on the detection of one or more lobar microbleeds on SWI.

Conclusions:
SWI confers greater reliability as well as greater sensitivity for CMB detection compared to GRE, and should be the preferred sequence for quantifying CMBs. SWI may more frequently identify lobar microbleeds that could represent asymptomatic CAA. Further research is needed to determine whether the Boston criteria require revision to take into account the greater sensitivity of SWI for CMB detection.
Abstract 3220: Does Multimodality MRI have Added Benefit in the Diagnosis and Management of “Classic” Hypertensive Intracerebral Hemorrhage?
Authors: Venkatasubramanian Chitra , Fischbein Nancy , Finley-Caulfield Anna , Snider Ryan W , Eyngorn Irina , Buckwalter Marion , Hanley Daniel , Kase Carlos , Gean Alisa , Zaharchuk Greg , Wintermark Max , Wijman Christine
Published: July 2021

Introduction:
It is unclear whether MRI adds benefit to non-contrast head CT (CT) in the diagnosis and management of patients with “classic” hypertensive intracerebral hemorrhage (HICH) on CT, and whether this additive information justifies MRI costs. We sought to answer this question using a prospective cohort of 159 consecutive patients with spontaneous ICH who systematically underwent CT and multimodality MRI.

Methods:
ICH etiology was classified in one of 12 predefined categories along with diagnostic certainty (highly probable, likely and possible), by two blinded neuroradiologists based on CT review (“CT diagnosis”). Two other blinded neuroradiologists reviewed in addition the MRI and determined the most likely diagnosis (“MRI diagnosis”). The “final” diagnosis was used as the reference standard and was assigned by two external, independent and blinded ICH clinician-experts who evaluated all clinical and imaging data including the initial and a 3 month MRI, CT angiography, contrast angiography, pathology and follow-up clinic visits, as available.

Results:
Of 159 patients, 86 (54%) had HICH as the final diagnosis. CT and MRI correctly identified 63 (73%) and 78 (91%) of these patients, respectively (P=0.005). Notably, MRI correctly classified eight of nine patients (89%) who had an “unknown” diagnosis by CT. Conversely, 74 patients were classified as HICH by the blinded CT review, and 64 (86%) of these patients had HICH as the final diagnosis. If the CT diagnosis was categorized as highly probable HICH (n=42), then it was almost always correct (98%). If the CT was categorized as likely (n=18) or possible (n=14) HICH, then it was correct in only 72% of cases. MRI increased diagnostic yield in the likely and possible categories by identifying one cavernous malformation (3%) and by improving diagnostic confidence in 19 patients (59%). MRI was wrong in three instances, all in the highly probable category (4%) by incorrectly classifying the etiology of intracerebral hemorrhage due to a possible vascular malformation (n=2) or coagulopathy (n=1).

Conclusions:
MRI is more accurate in correctly classifying hypertensive intracerebral hemorrhage than non contrast CT. MRI has significant additive yield over non contrast CT by improving diagnosis and diagnostic confidence in patients for whom the CT diagnosis is of intermediate or low certainty, but not for those diagnosed with a hypertensive intracerebral hemorrhage with high confidence.
Abstract 3225: Gross Domestic Product and Health Expenditure Associated with Incidence, 30-Day Fatality and Age at Stroke Onset: A Systematic Review
Authors: Sposato Luciano , Saposnik Gustavo
Published: July 2021

Background:
Differences in definitions of socioeconomic status (SES) and between study designs hinder their comparability across countries. We aimed to analyze the correlation of three widely used macro-SES indicators with stroke incidence and age at stroke onset.

Methods:
We selected population-based studies reporting incident stroke risk and/or 30-day case fatality according to pre-specified criteria. We used three macro-SES indicators that are consistently defined by international agencies: per capita gross domestic product adjusted for purchasing power parity (PPP-aGDP), total health expenditures per capita at purchasing power parity (PPP-aTHE) and unemployment rate. We used two-tailed Spearman’s test and scatter-plots for analyzing the correlation of each macro-SES indicator with incident risk of stroke, 30-day case fatality rates, proportion of hemorrhagic strokes and age at stroke onset.

Results:
Twenty-three manuscripts comprising 30 population-based studies fulfilled the eligibility criteria. Age-adjusted incident risk of stroke using standardized World Health Organization World population, 30-day case fatality rates, proportion of hemorrhagic strokes and age at stroke onset were associated to lower PPP-aGDP and PPP-aTHE (
Table
1 and
Figures
2 and 3). There was no correlation between unemployment rates and outcome measures.
Table
1. Correlation Analyses of Macro-Indicators of Socioeconomic Status
Figures
1. Scatter Plots for PPP-aGDP
Figures
2. Scatter Plots for PPP-aTHE

Conclusions:
Lower PPP-aGDP and PPP-aTHE were associated with higher incident risk of stroke, higher case fatality, greater proportion of hemorrhagic strokes and lower age at stroke onset. As a result, these macro-SES indicators may be used as proxy measures of quality of primary prevention and acute care and considered as important factors for developing strategies aimed at improving worldwide stroke care.
Abstract 3253: The Predictability of C-reactive Protein, Lipoprotein-Associated Phospholipase A2, and Depression on Later Health Outcomes in Patients Experiencing a First-Time Stroke
Authors: brethour mary K , Albright Karen C , Vance David E , Alexandrov Andrei V , Alexandrov Anne W
Published: July 2021

Background:
Strokes trigger an acute inflammatory response prompted by brain tissue injury at the infarct site and the surrounding ischemic penumbra. CRP and Lp-PLA2 have been significantly correlated in some studies with infarct size and post-stroke complications, and up to 60% of stroke survivors experience depression which may contribute to poor health outcomes. We sought to examine interaction effects between baseline CRP and Lp-PLA2 levels with depression in patients with a first-ever ischemic stroke.

Methods:
Baseline levels of CRP, Lp-PLA2 and depression were measured in 24 consecutive stroke patients presenting to the ED within 24 hours of symptoms onset. Depression levels, NIHSS, mRS, and quality of life (SF-36) were re-measured at 3 months post-stroke. Hierarchial multiple regression models were used to assess each outcome measure; Spearman correlations were used to reduce the number of predictor variables.

Results:
The median age of the participants was 62 (range 45 - 85); 62% were male, 25% African American, and 75% Caucasian. Stroke subtypes were 62% lacunar, 4% large vessel; and 33% cardioembolic; 45% were taking a statin prior to admission and mean baseline LDL was 108.6 + 33.8mg/dL (range 66-189). Of the 24 participants enrolled, 20 completed the study. At 3 months post-stroke, 92% were taking a statin; mean LDL was 89.71. The median admission NIHSS score was 3.1 (range 0-15), and 17% were treated with IV t-PA Baseline CRP values ranged from <0.1 to 34.9 with a median of 0.3. Baseline Lp-PLA
2
values ranged from 85 to 617 with a median of 194. The mean Beck Depression Inventory score on admission was 5.9 + 4.6. Neither the biological markers of CRP and Lp-PLA
2
nor the interaction between CRP and Lp-PLA2 and depression were significant independent predictors of health outcomes at 3 months post-stroke. Depression, however, was a significant independent predictor of functionality (p=.009) and quality of life (p=.02) at 3 months post-stroke.

Discussion:
The impact of depression on 3 month outcomes is significant. While these 2 biomarkers were unreliable at predicting health outcomes, providers should standardize their assessment of depression to ensure proper detection and treatment that may improve health outcomes post-stroke.
Abstract 3260: A Systematic Analysis of Endovascular and Intravenous Therapy for Ischemic Stroke Based on Time Window Using a Novel Outcome Model
Authors: Mandava Pitchaiah , Shah Shreyansh , Sarma Anand K , Murthy Santosh B , Kent Thomas A
Published: July 2021

Introduction:
Although intra-arterial/endovascular (IA) stroke therapies are widely employed, there has been a paucity of randomized clinical trials (RCT) to support their use. In lieu of RCT’s, case series are often compared to each other or to other RCT’s. However, stroke outcome is highly dependent on baseline factors such as severity and age. Because those factors have a complex relationship, comparisons are often unreliable. Even with the inclusion of a control arm, imbalances often complicate valid conclusions. In order to provide meaningful comparisons, we developed pPREDICTS©, that generates a surrogate control outcome function based on the baseline factors and outcomes of the placebo arms of published RCT’s (Mandava & Kent Stroke 2009). pPREDICTS© now includes 24 RCT’s representing 7400 subjects and explains more than 80% of the variance of mortality and functional outcome (mRS). In this study, we applied pPREDICTS© to published IA series and calculated benefit/risk for each based on differences from predicted outcome at comparable baseline NIHSS and age. We performed the same analysis with intravenous (IV) thrombolytic RCT’s in order to gauge relative efficacy.

Methods:
We identified 51 IA and 22 IV studies that included baseline NIHSS, age, time window, and outcomes (mRS 0-2 and mortality) and with N > 10. Proportions of subjects that died or achieved mRS 0-2 were subdivided by time window. Publication bias, the apparent greater benefit in those trials with smaller N, was corrected by ‘trim and fill’ using the pPREDICTS© outcome as the surrogate baseline (Mandava & Kent Neurology 2007). Data is represented as mean + 95% confidence interval.

Results:
The IA series had a higher baseline NIHSS than the IV trials (17.7+3.2 vs 12.5+3.2; p<.001), so likely represented a different set of patients. We found frequent instances of publication bias, particularly in the IA trials at 6 hrs. When compared to the predicted outcome for each trial at its comparable baseline factors, odds ratios for both IV and IA showed decreasing, but significant improvement in mRS without excess mortality (
Figure
) up to 6 hour time period. However, beyond 6 hours there was excess mortality seen with IA therapy.

Conclusion:
Unlike other systematic or meta-analysis, by comparing individual treatment arms to a continuous placebo outcome model at baseline factors similar to their own we avoided the need to adjust for imbalances. Decreasing, but potential benefit of both IA and IV therapies was found up to 6 hours, but with higher mortality for IA at > 6 hrs. Analysis will be presented of which clinical factors predicted the best outcomes.
Abstract 3266: Nadir Hemoglobin Predicts Poor Functional Outcome and Death in ICH Patients
Authors: Chang Tiffany R , Boehme Amelia K , Aysenne Aimee A , Albright Karen C , Burns Christopher , Beasley T. M , Martin-Schild Sheryl
Published: July 2021

Background:
Anemia has been associated with increased mortality in ICU patients and with poor outcomes in patients with intracerebral hemorrhage (ICH). This study investigates the relationship between hemoglobin (Hb) values and outcomes in ICH patients.

Methods:
Consecutive patients with spontaneous ICH admitted to the Tulane Stroke Center between July 2008 and December 2010 were evaluated. Records were reviewed for demographic and clinical information. Patients were divided into two groups based on admission Hb (low vs. normal based on laboratory reference range for gender). Baseline characteristics were compared between groups using chi-square, t-tests and Wilcoxon Rank Sum tests. Outcomes included length of stay, discharge NIHSS, discharge modified Rankin Scale (mRS) (mRS 0-3 vs. 4-6), and in-hospital mortality. Cumulative logit models were used to assess the relationship between baseline and nadir hemoglobin with outcomes adjusting for age, baseline NIHSS score, transfusion status, INR and length of stay.

Results:
Of the 109 patients, 28% (n=30) were anemic on admission. Baseline characteristics and outcomes are shown in
Table
1. Patients with baseline anemia had significantly longer stays in the hospital (13.5 vs. 7 days, p=0.037). There was no significant association between admission Hb and discharge NIHSS, mRS, or mortality. Nadir Hb was associated with poor functional outcome (OR=1.58, 95%CI 1.31-1.90, p<0.0001) and remained significant after adjusting for age, baseline NIHSS, transfusion, and length of stay (OR=1.43, 95%CI 1.06-1.94, p=0.02).

Conclusion:
Low admission Hb values are associated with longer lengths of stay in the hospital. This study suggests that nadir Hb, not admission Hb, can be used to predict poor functional outcome and death. Nadir Hb is lowest in patients with baseline anemia may serve as a surrogate marker for medically complex patients and/or complications.
Abstract 3268: Ct Perfusion As A Tool To Predict The Risk Of Hemorrhagic Transformation In Ischemic Stroke Treated With Tissue Plasminogen Activator: A Single Center Experience.
Authors: Kass-Hout Tareq , Mokin Maxim , Kass-Hout Omar , Nourollahzadeh Emad , Wack David , Siddiqui Adnan , Levy Elad , Snyder Kenneth
Published: July 2021

Objective:
To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume (CBV) and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis.

Methods:
Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 - 2011 within 3 hours after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates CBV and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow up CT head without contrast, done within 36 hours of the thrombolysis therapy. Clinical, demographic and CTP variables were compared between the HT and non-HT groups using logistic regression analyses.

Results:
HT developed in 8 (40%) patients. Patients with HT had lower ASPECT score (
P
=.03), higher NIHSS on admission (
P=
.01) and worse outcome (
P=
.04) compared to patients who did not develop HT. Baseline blood flow defects were comparable between the two groups. The mean PS for the HT group was 0.53 mL/min/100g brain tissue, which was significantly higher than that for the non-HT group of 0.04 mL/min/100g brain tissue (
P
<.0001). The mean area under the curve was 0.92 (95% CI). The PS threshold of 0.26 mL/min/100g brain tissue had a sensitivity of 80% and a specificity of 92% for detecting patients with high risk of hemorrhagic transformation after intravenous thrombolysis.

Conclusions:
Admission CTP measurements might be useful to predict patients who are at higher risk to develop hemorrhagic transformation after acute ischemic stroke therapy.
Abstract 3274: Early Symptom Onset to Arterial Puncture Time in the Endovascular Management of Acute Ischemic Stroke Predicts Successful Revascularization
Authors: Jung Richard S , Sharma Jitendra , Shams Tanzila , Chitravas Numthip , Blackham Kristine A
Published: July 2021

Background:
As is seen in the early door-to-needle times of intravenous thrombolysis in the treatment of acute ischemic stroke (AIS), prior endovascular management trials have demonstrated early revascularization can lead to improved outcomes. We aimed to study the relationship of the time from acute stroke onset to the time of arterial groin puncture (OTP) as a possible predictor of successful revascularization.

Methods:
We retrospectively analyzed 149 patients who presented to our hospital with AIS and underwent emergent endovascular treatment from January 1, 2008 to March 31, 2011. Charts were reviewed for baseline characteristics, OTP times, and endovascular therapies employed. Primary outcomes included successful revascularization (TIMI 2 to 3 flow), improvement of baseline NIHSS ≥ 4, symptomatic ICH (increase of NIHSS ≥ 4), in-hospital mortality, and mRS two or less at discharge. We excluded patients with OTP times greater than eight hours to ensure consistency with approved usage of mechanical thrombectomy devices. Independent samples T-tests were performed to determine relationships of OTP with our primary outcomes.

Results:
Of the 149 patients who underwent endovascular therapy, 120 had OTP times less than eight hours. Of these 120, 44% were male, median age was 73 years (range 17, 93), median baseline NIHSS was 18 (range 5, 28), 53% received intravenous tissue plasminogen activator (tPA), 69% received intra-arterial tPA, and mechanical thrombectomy was performed in 69%. Internal carotid artery occlusions were seen in 32% of patients, 50% had M1 segment occlusions, and only five patients had posterior circulation occlusions. Successful revascularization was achieved in 70% of interventions, 10% of patients had mRS ≤ 2 at discharge, symptomatic hemorrhage was 18%, and in-hospital mortality was 24%. Patients with TIMI 2 to 3 flow had significantly shorter mean OTP times (3.9 vs 4.5 hours; p=0.024). No significant associations of mean OTP times were found with symptomatic hemorrhage rate (4.4 vs 4.0; p=0.628), in-hospital mortality (4.0 vs 4.0; p=0.677), improvement in NIHSS (3.9 vs 4.2; p=0.283), or a mRS ≤ 2 at discharge (3.7 vs 4.1; p=0.185).

Conclusions:
The recanalization rate in our study is comparable to prior endovascular trials. Patients with OTP times less than 3.9 hours were more likely to result in successful revascularization. Onset to groin puncture did not predict in-hospital mortality, symptomatic hemorrhage, or condition at discharge in our study. Further study is needed to determine if advanced perfusion imaging prior to intervention may impact treatment time and ultimately clinical outcome.
Abstract 3284: Influence of Blood Clot Age, Density and Thrombin Content on
In Vitro
Sonothrombolysis Rate and Efficacy
Authors: Borrelli Michael J , Hamilton Eric , Hennings Leah , Bernonck Laura J , Culp William C
Published: July 2021

Sonothrombolysis (STBL) uses ultrasound to lyse thrombi that cause stroke, myocardial infarct and other vascular occlusion diseases; and efficacy is improved markedly by combining tPA and/or microbubbles (MBs) with ultrasound. The efficacy of
in vitro
STBL varies considerably depending upon how blood clots are formed. However, the relationship between the physical and chemical nature of blood clots and STBL efficacy has not been quantified. This study measured the effects that clot age, density and thrombin content had on STBL efficacy and the ability of tPA and MBs to complement STBL. Blood clots with different characteristics were produced by mixing pooled rabbit plasma with rabbit blood cells, adding varied amounts of thrombin and calcium, followed by incubation at 37
o
C in glass tubes for 3 h to 72 h. Blood clots were then cured at 5
o
C for 24 h to 72 h. The volume and mass density of the clots were measured, 9-11 mg pieces were cut from the main clot, weighed and then insonated with 1 MHz, pulsed (20% duty factor) ultrasound in a Mylar chamber through which fresh rabbit serum containing tPA and or MBs was flowed continuously past the clot. STBL efficacy was measured as % of clot mass lysed in 15 min. For clots incubated 3 h to 24 h at 37
o
C with 5 mM Ca
+
2 and 5 U of thrombin, maximal STBL with ultrasound plus tPA was observed with 0.1 mg/ml tPA for all ultrasonic intensities tested. Using MBs (1.0-2.5 x10
8
/ml) produced a comparable level of STBL. More effective STBL was produced by combining tPA with MBs, even with reduced tPA concentrations (0.006-0.01 mg/ml). However, increasing clot thrombin, up to 60 U, proportionally reduced STBL efficacy with tPA or MBs, and combining tPA with MBs no longer produced an additive STBL effect. This was also true for clots incubated with 25 mM Ca
+
2 that did not contract and thus had a fourfold lower mass density. Increasing thrombin levels produced clots whose STBL efficacy was markedly lower with either tPA or MBs, and for which combining tPA with MBs produced no additive STBL effect. Hence, the level of thrombin used during clot formation (and putatively the degree of fibrin networks) was the major factor in determined STBL efficacy and whether or not tPA combined with MBs were additive in potentiating STBL. Surprisingly, the mass density of the clot alone had no effect on STBL efficacy.
Abstract 3313: Outcomes of “Drip-and-Ship” Paradigm Among Patients with Acute Ischemic Stroke. Results of a State Wide Study
Authors: Chaudhry Saqib A , Rodriguez Gustavo J , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background:
“Drip-and-ship” denotes patients in whom intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is initiated at the emergency department (ED) of a community hospital, followed by transfer within 24 hours to a comprehensive stroke center. Although drip-and-ship paradigm has the potential to increase the number of patients who receive IV rt-PA, comparative outcomes have not been assessed at a population based level.

Methods:
State-wide estimates of thrombolysis, associated in-hospital outcomes and mortality were obtained from 2008-2009 Minnesota Hospital Association (MHA) data. Patient numbers and frequency distributions were calculated for state-wide sample of patients hospitalized with a primary diagnosis of ischemic stroke. Patients outcomes were analyzed after stratification into patients treated with IV rt-PA through primary ED arrival or drip-and-ship paradigm.

Results:
Of the 21,024 admissions, 602 (2.86%) received IV rt-PA either through primary ED arrival (n=473) or drip-and-ship paradigm (n=129). The rates of secondary intracerebral or subarachnoid hemorrhage were higher in patients treated with IV rt-PA through primary ED arrival compared with those treated with drip-and-ship paradigm (8.5% versus 3.1, p=0.038). The in-hospital mortality rate was similar among ischemic stroke patients receiving IV rt-PA through primary ED arrival or drip-and-ship paradigm (5.9% versus 7.0%). The mean hospital charges were $65,669 for primary ED arrival and $47,850 for drip-and-ship treated patients (p<0.001).

Conclusions:
The results of drip-and-ship paradigm compare favorably with IV rt-PA treatment through primary ED arrival in this state-wide study.
Abstract 3356: Half the Stroke Survivors in the United States have Poorly Controlled Hypertension
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: July 2021

Background:
National guidelines recommend antihypertensive treatment to lower the risk of secondary strokes in both hypertensive and normotensive patients. The degree to which blood pressure (BP) is treated and controlled among stroke survivors in the US has not been systematically investigated. In this analysis of a nationwide database, we assessed recent patterns, predictors, and prognoses of antihypertensive drug use among survivors of a stroke.

Methods:
We reviewed prevalence and control of hypertension among adults with a history of stroke (based on self report) who participated in the National Health and Nutrition Examination Survey 1999 to 2004 with mortality follow-up through December 31, 2006. Logistic regression was used to determine predictors of poorly-controlled BP (>140/90) and non-treatment. Cox models were used to examine the association between antihypertensive use vs. all-cause mortality, adjusting for confounders.

Results:
Among 9,145 participants aged ≥40 years, 490 reported previous stroke, corresponding to 4,755,372 (4%) of US adults. Of those with previous stroke, 72% had known hypertension, 47% had poorly controlled hypertension, and 8% had undiagnosed hypertension. Compared to those not taking antihypertensive medications, those on treatment were more likely to be significantly older, male, black non-Hispanic, diabetic, with elevated levels of BP, total cholesterol, and body mass index. In multivariable analyses, age (OR per year 1.05, 95% CI 1.02-1.09), female sex (OR 1.43, 95% CI 1.14-1.79), Hispanic ethnicity (OR 1.76, 95% CI 1.24-2.49) and diabetes (OR 2.12, 95% CI 1.50-2.99) were associated with poorly controlled BP, while subjects who had a previous myocardial infarction (OR 0.66, 95%CI 0.45-0.97), drank alcohol (OR 0.62, 95% CI 0.42-0.90) or were overweight (OR 0.62, 95% CI 0.49-0.78) were less likely to have poorly controlled BP. Among those with poorly controlled BP, hypercholesterolemia (OR 1.30, 95% CI 1.07-1.57) and male sex (OR 1.33, 95% CI 1.06-1.63) were predictors of non-treatment, whereas current smoking (OR 1.59, 95% CI 1.32-1.92) or overweight (OR 1.92, 95% CI 1.32-2.78) were linked to treatment. Those on antihypertensive medications had lower rates of all-cause mortality but this result did not reach significance (adjusted HR 0.87; 95% CI 0.33-2.32), and was not influenced by baseline BP or number of antihypertensive agents.

Conclusion:
Rates of antihypertensive therapy and BP control among stroke survivors in the United States are poor. One in two stroke survivors has poorly controlled hypertension. Several medical and lifestyle modification factors could be potential targets of intervention to bridge this evidence-practice gap.
Abstract 3371: Inherited Thrombophilias In Cryptogenic Stroke Patients Under 55 Years Old
Authors: Martinez-Sanchez Patricia , Martinez-Martinez Marta , Fuentes Blanca , Cuesta Maria Vicenta , Ruiz-Ares Gerardo , Diez-Tejedor Exuperio
Published: July 2021

Background:
inherited thrombophilias cause venous thrombotic events, however, their association with brain ischemia in adult patients is controversial. Our objective was to study the association between thrombophilia and cryptogenic stroke in patients under 55 years of age.

Methods:
prospective observational study of consecutive patients under 55 years of age who had had a brain ischemia (transient ischemic attack of brain infarction). The patients with cryptogenic brain ischemia were compared with the controls patients with brain ischemia of known cause. We examined the presence of thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations; deficiencies in protein S, protein C and antithrombin levels; resistance to activated protein C) and patent foramen ovale (PFO) in all patients.

Results:
Two hundred fifty-four patients were included, 108 with cryptogenic brain ischemia and 146 controls patients with brain ischemia of known cause. Patients with cryptogenic brain ischemia were younger (mean age 42.4 vs. 45.6 years old, P=0.002). The frequency of thrombophilia was significantly higher among patients with cryptogenic brain ischemia than those with brain ischemia of known cause (22.2% vs. 6.8%, P<0.001). Taking into account each thrombophilic disorder separately, prothrombin G20210A mutation and protein C or S deficiency were significantly higher in the cryptogenic brain ischemia group than in the known cause group (10.2% vs. 2.7% and 8.3% vs. 2.1%, respectively, P<0.05) while Factor V Leiden mutation was similar in both groups (4.6% vs. 2.7%, P NS). The frequency of PFO and PFO plus thrombophilia were higher among patients with cryptogenic brain ischemia (35.2% vs. 12.3% and 8.4% vs. 0%, respectively, P<0.001). The PFO (+) cryptogenic brain ischemia patients showed higher frequency of thrombophilia than the other patients (23.7% vs. 11.6%, P=0.043), in particular prothrombin G20210A mutation (15.8% vs. 4.2%, P=0.014). Multivariate analysis adjusted confounding factors showed than the presence of thrombophilia was independently associated with cryptogenic brain ischemia (OR 3.9; 95% CI, 1.69 - 8.97; P=0.001).

Conclusion:
there is an association between thrombophilia and cryptogenic brain ichemia in patients under 55 years old. These data suggest that systemic thrombophilic disorders are cause of thromboembolic phenomena in brain arteries