bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P339: Pharmacogenetics Guided Algorithm Including Factors of Renal Impairment and Vitamin K Intake for Accurate Predicting of Individual Warfarin Dose in a Genetically Homogeneous Population
Authors: Tanaka Tomotaka , Miyata Shigeki , Kada Akiko , Yamamoto Haruko , Miyata Toshiyuki , Nagatsuka Kazuyuki
Published: March 2022

Warfarin is an efficacious anticoagulant because it can be tailored for therapy using PT-INR. However, highly variable interindividual dosing requirement becomes a problem in empirical dosing or dosing using only clinical characteristics. Thus, several pharmacogenetics-guided algorithms (PGAs) have been proposed.

We aimed to establish a PGA including factors of renal impairment and vitamin K (VK) intake and to evaluate its efficacy for more accurately predicting individual warfarin dose in genetically homogeneous population.

We studied a single-center prospective cohort study of 176 Japanese patients on stable, therapeutic doses of warfarin to establish a PGA in which VK intake and renal impairment were considered to predict individual maintenance dose. We used another data set of 157 Japanese patients obtained from a multicenter prospective cohort study and compared our results with the results of 2 previously proposed PGAs applied to the same database; one, from the International Warfarin Pharmacogenetic Consortium (IWPC) (N Engl J Med, 2009), which considered race (but not renal function or VK intake), and the other reported by Limdi et al. (Am J Kidney Dis, 2010), which considered renal function (but not race or VK intake).

Genotyping results showed that 80% patients had the homozygotes of
CYP2C9
wild-type allele and
VKORC1
-1639A variant, indicating the high genetic homogeneity in Japanese population. The mean observed maintenance doses (3.17 ± 1.09 mg/day) was compatible with that estimated by our algorithm (O: 3.13 ± 0.97) but was higher or lower than that by IWPC (I: 2.65 ± 0.71) or Limdi (L: 5.36 ± 0.92), respectively, although all algorithms showed similar coefficients of determination (O: 0.62, I: 0.67, L: 0.61). Our algorithm also revealed excellent results compared with others in terms of mean absolute error (O: 0.67 ± 0.63 mg/day, I: 0.75 ± 0.60, L: 2.19 ± 0.88) and the percent of patients whose doses were estimated within ±1.0 mg/day of the observed maintenance dose (O: 77.5%, I: 73.3%, L: 9.0%).Race seemed to be one of the most critical factors for PGA, and PGA including VK intake and renal impairment as factors appeared to be more accurate to predict individual warfarin dose in a genetically homogenous population such as Asians.
Abstract T P343: Resveratrol Rescues Neuron Survival in Pimary Postnatal Cultures
Authors: Agrawal Megha , Dore Sylvain
Published: March 2022

Objective:
Our goal is to identify supplements that can improve neuronal survival of postnatal neuronal cultures. Here, we hypothesize that resveratrol could rescue neurons that are stressed during the brain dissociation and plating procedures.

Background:
The standardized B27 supplement with neurobasal medium has been used to facilitate neuronal growth and attenuates glial proliferation. We have documented that resveratrol (3,4’5 trihydroxystilbene), a natural polyphenol and a bioactive component of red wine, have numerous neuroprotective properties both in vivo and after oxygen-glucose deprivation protocols. We have proposed that this stilbene would not likely act as a direct antioxidant but act as a bioactive agent capable to induce an intracellular cytoprotective cascade.

Methods:
Postnatal cultures of cortical neurons were derived from 0- to 1-day-old C57BL/6 mice. Brains were dissociated and neurons plated and maintained in three different media: neurobasal medium without any supplement (NBM), neurobasal medium without any supplement but containing resveratrol 10μM (NBM+R10μM), and neurobasal medium with B27 supplement (NBM+B27). Neuronal survival was assessed with the live/dead cell calcein AM/EthD-1), lactate dehydrogenase (LDH) and (MTT) assays after plating in these three different media.

Results:
Significant increase in live cells (52.9+/-5.5% and 53.6+/-4.5%, p<0.0001) was recorded in cultures incubated in NBM+R10μM and NBM+B27 respectively, when compared to NBM by calcein-AM assay and increase in viability (50.8+/-8.5% and 54.3+/-6.5%) by MTT assay. Significant decrease in dead cells (73.9+/-6.3% and 74.7+/-5.3%, p<0.0001) was recorded in cultures incubated in NBM+R10μM and NBM+B27 respectively, when compare to NBM by EthD-1 assay and decrease in cytotoxicity (17.9+/-2.5% and 19.4+/-2.8) by LDH assay.

Conclusions:
Results indicated that growth of primary neurons in resveratrol containing medium was most effective suggesting that resveratrol itself is sufficient to enhance neuronal attachment and survival during plating. Efforts are currently being conducted to characterize the mechanism by which resveratrol can limit cell death and increase neuron survival.
Abstract T P357: Low Baseline Urine Creatinine Excretion Rate Independently Predicts Severe Disability or Death among Critically Ill Acute Stroke Patients
Authors: Hsu Chia-yu , Wu Yi-Ling , Huang Ying-Chih , Lee Jiann-Der , Lee Ming-Hsueh , Wu Chih-Ying , Hsu Huan-Lin , Lin Ya-Hui , Huang Yen-Chu , Yang Hsin-Ta , Yang Jen-Tsung , Lee Meng , Ovbiagele Bruce
Published: March 2022

Background:
Urinary creatinine excretion rate (CER) is an established marker of muscle mass and by extension possibly an indicator of physical fitness and cardiovascular structure or function. Low CER has been linked to poor coronary artery disease outcomes, but a link between CER and acute stroke prognosis has not been previously explored.

Objective:
To evaluate whether low baseline CER is associated with poor outcomes among critically ill acute stroke patients.

Methods:
We prospectively collected data from patients with acute stroke (ischemic or hemorrhagic) within 24 hours from symptom onset, admitted to a Neurological and Neurosurgery Intensive Care Unit in a hospital in Taiwan between September 2007 and October 2010. Baseline CER (mg/d) was calculated based on 24-hour urine volume and urine creatinine data. Patients were divided into 3 groups according to highest, middle, and lowest CER. Primary endpoint was poor outcome defined as modified Rankin Scale 3-6 at 6 months. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the 6-month mRS were computed using backward stepwise regression analysis.

Results:
Among 167 critically ill acute stroke patients meeting study entry criteria, 102 (61%) were men, mean age was 68.7 years, 93 (56%) patients had ischemic stroke. Compared to patients in the group with the highest CER levels, patients in the group with the lowest CER levels were older, and had lower body mass index. Patients with lowest CER had poor 6-month outcomes after adjustment for relevant covariates (OR 4.48, 95% CI 1.22 to 16.43, P = 0.024) (Table).

Conclusions:
Among critically-ill acute stroke patients, low baseline CER was independently associated with poor 6-month outcomes. Validation in other patient populations and a better understanding of the pathophysiologic mechanisms at play is warranted.
Abstract T P358: Impact of Clipping Versus Coiling on Postoperative Hemodynamics and Pulmonary Edema after Subarachnoid Hemorrhage
Authors: Horie Nobutaka , Ishizaka Shunsuke , Izumo Tsuyoshi , Hayashi Kentaro , Suyama Kazuhiko , Nagata Izumi
Published: March 2022

Introduction:
Volume management is critical for assessment of vasospasm after aneurysmal subarachnoid hemorrhage (SAH). We compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema.

Methods:
This multicenter prospective cohort study measured hemodynamic parameters in patients with SAH using a transpulmonary thermodilution system (PiCCO Plus) from days 1 to 14. Parameters were compared according to treatment strategy.

Results:
This study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF), cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, the pulmonary parameters, extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI), were significantly higher in the clipping group during the spasm period. Postoperative C-reactive protein (CRP) level was higher in the clipping group and correlated significantly with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema (P=0.001 and P=0.004, respectively), and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the spasm period, suggesting non-cardiogenic edema (P=0.022, P=0.001, and P=0.507, respectively).

Conclusions:
Postoperative hemodynamics were similar in both groups in the early period, but afterload mismatch may occur in the spasm period. Clipping affects postoperative CRP level and may thereby enhance non-cardiogenic pulmonary edema in the spasm period. Postoperative CRP level may predict pulmonary complications.

Trial Registration:
University hospital Medical Information Network: UMIN000003794.
Abstract T P359: Regulation of Cerebral Ceramide Levels after Subarachnoid Hemorrhage
Authors: Testai Fernando D , Xu Haoliang , Kilkus John , Gorshkova Irina , Berdyshev Evgeny , Pelligrino Dale A , Dawson Glyn
Published: March 2022

Background:
Ceramide (Cer) participates in neuronal and oligodendroglial cell death and neuroinflammation. We have previously shown that Cer levels increase in the cerebrospinal fluid (CSF)of patients with subarachnoid hemorrhage (SAH). The goal of this study is to further characterize the origin of Cer after SAH.

Methods:
Cer and dihydroceramide (DHC) levels as well as the activity of Acid (ASMase) and Neutral sphingomyelinase (NSMase) were measured in the CSF of SAH patients and controls. The de novo synthesis of Cer was estimated by correlating Cer with DHC levels using Spearman correlation. The activity of intracellular enzymes that regulate Cer homeostasis including ASMase, NSMase, sphingomyelinase synthase (SMS) and glucosylceramide synthase (GCS) was investigated using the rat model of SAH. Brain homogenates were used for in vitro enzyme activity measurement. The results were compared using non-parametric analysis.

Results:
A total of 26 SAH patients and 8 controls were included in the study. Compared to controls, SAH patients had higher Cer (12.4±8.8 vs. 53.8±48pmol/ml; p=0.001) and DHC (1.4±1.1 vs. 4.7±3.4pmol/ml; p=0.001) in the CSF. In the SAH group, Cer correlated well with DHC (rho=0.91; p<0.001) suggesting a substantial contribution of the
de novo
pathway to Cer production. ASMase activity in the CSF of human subjects was higher in SAH than in controls (15.04±4.75 vs.9.62±3.88 IF/μl.min; p=0.017) indicating an increased turnover of sphingomyeline into Cer. Additionally, compared to the controls (n=4), brain samples from SAH animals (n=5) had higher ASMase (15.7±2.1 vs. 9.55±1.53 IF/μg.min; p=0.025) and GCS (1.38±0.35% vs. 0.70±0.04%; p=0.025) enzyme activity. On the other hand, NSMase (1.78±0.55 vs. 1.02±0.75 IF/μg.min; p>0.05) and SMS (7.1±0.9% vs. 9.1±3.8%; p>0.05) activities were similar in both groups.

Conclusions:
The increase of Cer after SAH may be explained by the elevation in both ASMase activity and the
de novo
Cer biosynthetic pathway. GCS transforms Cer into less toxic glycosphingolipids, suggesting that this enzyme may constitute an endogenous Cer detoxifying mechanism.
Abstract T P360: Risk Factors Underlying Recurrent Subclinical Subcortical Cerebrovascular Lesions in Elderly Patients
Authors: Nagata Ken , Yamazaki Takashi , Takano Daiki , Maeda Tetsuya , Sato Yuichi , Fujimaki Yumi
Published: March 2022

Background and Purpose:
Subclinical subcortical cerebrovascular lesions (SSCLs) are very common in elderly people. Accumulation of SSCLs may have additive or even synergic effects to the coexisting brain lesions such as Alzheimer’s pathology or symptomatic cerebrovascular lesions in elderly patients, but the mechanisms underlying the recurrence of SSCLs remains to be clarified. The present study was conducted to elucidate the contributing risk factors to the recurrent SSCLs.

Subjects and Methods:
The present study was based on 96 cases (55 men and 41women) with subcortical lesions, including 49 cases with symptomatic lacunar infarction, 36 cases with asymptomatic lacunar infarction, and 11 cases with symptomatic intracerebral hemorrhage. The mean age was 70.9 years. MRI studies were repeated with an average interval of 416 (248-822) days. Numbers of lacunar infarcts (LIs) and microbleeds (MBs) were counted in all MR slices, and the degree of white matter lesions (WMLs) was evaluated according the Fazekas’ categories, and those parameters were compared between the baseline and follow-up images. Laboratory studies included high sensitivity CRP (hsCRP), interleukin-6 (IL-6), serum lipid profile, glucose and brain natriuretic peptide (BNP).

Results:
The number of LIs increased in 16 cases whereas unchanged in 80 cases. The number of MBs increased in 16 cases, whereas unchanged in 80 cases. There was a deterioration in the degree of WMLs in 7 cases, whereas no change in 89 cases. Those with recurrent LIs had significantly greater number of LIs in the baseline MRI (p<0.005), and those with recurrent MBs had greater numbers of LIs and MBs at baseline MRI (p<0.005). Those who showed deterioration in WMLs had greater number of MBs and higher total cholesterol, LDL-cholesterol and lower HDL-cholesterol at baseline. Six cases showed combined recurrent vascular lesions, and had significantly elevated hsCRP and IL-6, and greater number of LIs and MB at baseline as compared with those with recurrence in single vascular lesions.

Conclusion:
The present result suggest that multiple subcortical vascular lesions are already a strong risk for the recurrence, and chronic inflammation may have additional risk for the combined vascular lesions.
Abstract T P364: Longitudinal Evaluation of Functional Magnetic Resonance Imaging on Working Memory in Patients after Transient Ischemic Attack
Authors: Guo Jian , Cheng Ning , Zhou Muke , He Li
Published: March 2022

OBJECTIVE:
Transient ischemic attack (TIA) can increase the risk of cognitive decline, especially in attention-executive-psychomotor functioning. However, whether TIA patients have altered patterns of brain activation during this function, and whether there is a dynamic change on cerebral activity patterns, have not been examined to date. This study is designed to using functional magnetic resonance imaging (fMRI) to investigate longitudinal changes in brain activation during a verbal working memory (VWM) task in patients with TIA.

METHODS:
The current study included 25 patients with first-ever TIA in right hemisphere and 25 healthy volunteers. N-Back VWM task-related fMRI were conducted one week and three months after TIA onset. The brain activity evoked by n-back task in the patients was assessed and compared with that of the controls. Significant changes in cerebral activation over time were also observed in TIA patients.

RESULTS:
The groups did not differ on any demographic, cognitive and task performance variables. Compared with healthy subjects, patients at one week after TIA demonstrated increased activity in bilateral inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex (DLPFC), insula, inferior parietal lobe (IPL) and cerebellum during the task. However, at 3-month follow-up, the task-related brain activity in patients was clearly less recruited, and only right IFG still exhibited increased activity. Moreover, a direct comparison of fMRI data between one week and three months after TIA showed that there was increased activation in bilateral middle temporal gyrus (MTG), right DLPFC, IPL, cerebellum and left IFG in patients at one week after TIA.

CONCLUSIONS:
These findings support the hypotheses that the patterns of brain activity during VWM performance may change for a period of time post-TIA despite the cessation of clinical symptoms. They also provide evidence of a progressive normalization of the VWM activation pattern after transient episodes of ischemia in patients with first-ever TIA.
Abstract T P46: Absence of a Very Low Cerebral Blood Volume (VLCBV) Lesion Identifies Patients Who Are Unlikely to Have Hemorrhagic Transformation After Delayed Endovascular Reperfusion
Authors: Mishra Nishant K , Christensen Soren , Straka Matus , Mlynash Michael , Kemp Stephanie , Bammer Roland , Marks Michael , Albers Gregory W , Lansberg Maarten
Published: March 2022

Objective:
Ischemic stroke patients with areas of VLCBV on baseline imaging are at increased risk for hemorrhagic transformation following iv tPA induced reperfusion. The underlying hypothesis is that regions of low CBV are highly susceptible to reperfusion injury. We examined the DEFUSE 2 study data, and tested whether the presence of VLCBV assessed with an automated software tool predicts the risk of hemorrhagic transformation in patients treated with endovascular therapy up to 12 hours.

Methods:
Patients who reperfused following endovascular therapy and who had technically adequate PWI and DWI data were included. Presence of parenchymal hematoma (PH 1 or 2) was assessed blinded to clinical data by a neuroradiologist at the core lab. RAPID, a fully automated image processing program, was used for coregistration of the DWI and PWI images, removal of large vessels, processing of CBV maps, and calculation of relative CBV (rCBV) defined as a ratio of the original and the mirrored CBV maps. We first determined the rCBV threshold within the DWI lesion that had the highest area under the ROC curve (AUC) for predicting PH. We then determined the rCBV lesion volume at this threshold which best predicted PH.

Results:
60 patients (82.6%) were included in this analysis, the median time between symptom onset and femoral puncture was 6.5 hours (PH vs. no PH 6.1 vs. 6.6; p = 0.5). Patients with PH and no PH had similar DWI volumes (p=0.08) and NIHSS scores (p=0.23) at baseline. Among patients who reperfused, the greatest AUC for predicting PH was present at an rCBV threshold of 0.3 (AUC 0.707). At this threshold, an rCBV volume of >0.86 ml optimally predicted PH with a sensitivity of 0.93 (95%CI 0.66 - 1.0), specificity of 0.52 (95%CI 0.37 - 0.67), negative predictive value of 0.89 (95%CI 0.71-0.98) and positive predictive value of 0.35 (95%CI 0.23-0.49).

Conclusions:
PH following endovascular reperfusion can be predicted with high sensitivity and high negative predictive value with an automated image processing tool. The optimal threshold for predicting PH is an rCBV(<30%) lesion volume of ≥0.86 ml. Patients with rCBV(<30%) lesions smaller than this threshold are very unlikely to suffer a parenchymal hematoma following reperfusion.
Abstract T P54: Generalized Application of SMART (Simplified Management of Acute Stroke using Revised Treatment) IV Thrombolysis Criteria in Acute Ischemic Stroke (AIS) Patients is Safe and Effective
Authors: Sørensen Sigrid B , Barazangi Nobl , Chen Charlene , Wong Christine , Grosvenor David , Hove Jens D , Rose Jack , Bedenk Ann , Tong David C
Published: March 2022

Introduction:
Common IV rt-PA exclusion criteria may limit its use. The SMART criteria expand eligibility by reducing exclusions and can increase thrombolysis rates. However, applicability of SMART criteria to non-specialized centers is uncertain. We hypothesized that it is safe and efficacious to use SMART criteria in a wide range of hospital settings.

Methods:
Retrospective study of 539 consecutive acute ischemic stroke (AIS) patients receiving IV rt-PA using SMART criteria. Patients receiving IV rt-PA at a Comprehensive Stroke Center (CSC; n=267) versus Outlying Spoke Hospital (OSH; n=272) prior to transfer to the CSC were compared. There were 35 OSH (25-500+ beds) encompassing 120,000 sq miles in Northern California. The CSC neurologist was consulted by telephone (64%) or telemedicine (36%) in all cases. Primary outcomes were symptomatic intracranial hemorrhage (sICH) rate and favorable discharge outcome (mRS ≤ 1). Secondary measures were mortality and number of common rt-PA contraindications.

Results:
OSH patients were younger, had lower baseline mRS, and were clinically more severe. 90% had contraindications to rt-PA, the most common being mild symptoms (49%) and age ≥ 80 (37%). CSC had more contraindications than OSH patients (median (2(1-3) vs. 1(1-2), p < 0.001). Favorable outcome (45% vs. 37%; OR, 0.7[95% CI, 0.5-1.1]), sICH rate (2.6% vs. 5.1%; OR, 2.0[95% CI, 0.8-5.1]), and mortality (9% vs. 14%; OR, 1.6[95% CI, 0.95-2.8]) were not significantly different between groups. After baseline factor adjustment, OSH rt-PA treatment was not associated with increased sICH (adjusted OR, 0.6[95% CI, 0.2-2.0]) or reduced favorable outcome (adjusted OR, 0.97[95% CI, 0.5-1.8]).

Conclusion:
Generalized application of SMART criteria is safe and effective. Current rt-PA criteria may unnecessarily exclude patients from thrombolysis and need revision.
Abstract T P56: M1 Proximal SVS Should Be a Strong Predictor for Poor Outcome after tPA Therapy
Authors: Aoki Junya , Kimura Kazumi , Shibazaki Kensaku , Nagai Koichiro , Saji Naoki , Uemura Jyunichi , Sato Takahiro , Ebata Takuya
Published: March 2022

BACKGROUND AND PURPOSE:
Although intravenous thrombolysis using tPA can improve the clinical outcome in patients with acute ischemic stroke, a half of the patients complains of poor outcomes at 3 months. We previously reported that the susceptibility vessel sign (SVS) shown on MRI T2* at the proximal portion of the middle cerebral artery is a strong predictor for no early recanalization. The aim of the present study is to evaluate the impact of the M1 proximal SVS on poor outcome in acute patients with anterior-circulation stroke. METHODS:Consecutive patients treated with tPA were enrolled. Patients treated with intra-arterial intervention were excluded. Initial neurological deficit was assessed using the NIHSS score. The extent of the early ischemic change was evaluated using the DWI-ASPECTS. The presence of M1 proximal SVS was assessed before tPA therapy. Poor outcome at 3 months was defined as a mRS of 4 to 6.

Results:
One-hundred and sixty patients (median age, 76 years [67-83], male; 91 [57%]) were enrolled. Seventy-four (46%) patients had poor outcome (P group), and 86 (54%) had a non-poor outcome (NP group). Patients in the P group were older than those in the NP group (77 [69-84] versus 74 [64-81], p=0.010). NIHSS score was higher in the P group than the NP group (17 [13-20] vs. 8 [5-13], p<0.001). Regarding the imaging parameter, 16 (22%) patients in the P group and only 1 (1%) in the NP group had M1 proximal SVS (p<0.002). Patients in the P group had lower initial DWI-ASPECTS compared to those in the NP group (7 [5-9] versus 9 [7-10], p<0.001). Internal carotid artery occlusion was seen in 19 (26%) patients in the P group and 6 (7%) in the NP group (p=0.002). The glucose level was slightly higher in the P group compared to the NP group (140 mg/dl [120-182] vs. 130 mg/dl [116-164], p=0.076). Multivariate regression analysis revealed that proximal M1-SVS (OR:14.17, 95%CI:1.47-136.42, p=0.022) was the strong predictor for poor outcome, followed by NIHSS score ≥14 (OR:7.95, 95%CI:3.26-19.37, p<0.001), and glucose ≥125 mg/dl (OR:2.83, 95%CI:1.22-6.57, p=0.016) after adjusting age, onset treatment time, DWI-ASPECTS, cardioembolic stroke, and internal carotid artery occlusion.

Conclusions:
M1 proximal SVS should be a strong predictor for poor outcome after tPA therapy.
Abstract T P6: Is HbA1c a Predictor of Outcome in Ischemic Stroke Patients Who Undergo Intra-Arterial Treatment?
Authors: Tita Anne C , Jumaa Mouhammad A , Shah Kavit B , Zaidi Syed F
Published: March 2022

Objective:
Elevated blood glucose levels adversely affect the outcome of patients with acute ischemic stroke (AIS). We sought to study the predictive value of admission hemoglobin A1c (HbA1c) in AIS patients’ outcomes following intra-arterial stroke treatment (IAT).

METHODS:
We reviewed records of AIS patients who underwent IAT at our center from July 2012 - July 2013. The following data were collected and analyzed: patients’ demographics, baseline characteristics, treatment times and methods, rate of symptomatic and asymptomatic intracerebral hemorrhage, and favorable clinical outcome defined as modified Rankin score (mRS) ≤ 2 at 90 days or at last observation for patients treated within the last 90 days. HbA1c level was checked as part of routine stroke admission orders on all patients.

RESULTS:
Seventy consecutive patients who underwent IAT were identified. There were 42 (60%) females with mean cohort age of 64.4. The median ASPECT score was 9 (IQR 8-9) and baseline median National Institute of Health Stroke Scale Score was 18 (IQR 14-21). Overall 33 (47.1%) patients had favorable outcome. There were 15/70 (21.4%) asymptomatic and 2/70 (2.8%) symptomatic hemorrhages following IAT. Patients who developed hemorrhagic complications (17/70, 24%) following IAT had higher mean HbA1c levels (6.5 vs 5.9), however this finding was not statistically significant (ttest, p=0.09). Patients with favorable outcomes had lower mean admission HbA1c 5.9 (95% CI 5.6-6.2) versus 6.4 (95% CI 5.9-6.8). This finding was statistically significant (t-test, p 0.04). Multivariate logistic regression model identified low age (OR 0.93, 95%CI 0.88-0.99, p=0.03) as the only predictor of favorable outcome.

CONCLUSION:
Our study results indicate that admission HbA1c is a predictor of outcome in patients undergoing IAT for AIS. The value of this finding should be explored in a larger cohort.
Abstract T P66: Analysis of Tissue Plasminogen Activator (rt-PA) Eligibility by Gender in the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Madsen Tracy E , Khoury Jane C , Alwell Kathleen A , Moomaw Charles J , Khatri Pooja , Kissela Brett M , De Los Rios La Rosa Felipe , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L , Ferioli Simona , Kleindorfer Dawn O
Published: March 2022

Background/Purpose:
It is unknown whether eligibility for rt-PA differs by gender and whether this contributes to the gender differences in rt-PA administration present in some populations.

Methods:
We included all ischemic stroke patients ≥18 years old among residents of the Greater Cincinnati/Northern Kentucky Stroke region (5 counties) who presented to emergency departments of the 17 area hospitals in 2005. Data regarding rt-PA exclusion as defined by the 2007 AHA Guidelines and ECASS III were abstracted by study nurses and reviewed by study physicians. Outcomes included rt-PA eligibility and exclusion criteria by gender. Data are reported as raw counts and weighted percentages. Chi-square tests and generalized linear models were used, as appropriate.

Results:
Our sample included 1838 ischemic strokes; 57.9% were women, 24.3% were black. Mean age was 72.2 yrs for women and 66.1 yrs for men. Overall eligibility for rt-PA did not differ by gender (6.7% for men vs. 6.2% for women, p=.61), even after adjusting for age (7.0% vs. 6.0% p=.36). Exclusion criteria are listed in the table. Similar proportions of women and men arrived beyond 3 and 4.5 hours of symptom onset, but more women had SBP>185 or DBP>110, still significant after adjusting for age. In terms of ECASS III criteria, more women were over 80 years old and had NIHSS>25.

Conclusions:
Within a large, biracial population, similar proportions of women and men with ischemic stroke were eligible for rt-PA. However, women were more likely be >80 years old and have NIHSS>25, suggesting that women may benefit less from the ECASS III criteria. Further research is needed to investigate gender differences in rt-PA exclusion criteria.
Abstract T P71: Meningeal-Derived IL-6 Exacerbates Post-Stroke Inflammation and Pathology
Authors: Arac Ahmet , Grimbaldeston Michele A , Olayiwoya Oluwatobi , Tsai Mindy , Galli Stephen J , Bliss Tonya M , Steinberg Gary K
Published: March 2022

Background:
Inflammation critically contributes to post-stroke brain damage and consequently there is much interest in factors that influence stroke-induced brain inflammation. Interleukin 6 (IL-6) has been heralded as an important predictor of stroke outcome, however there are conflicting reports describing detrimental, beneficial and even no effects of IL-6 on stroke pathology. This has led to the suggestion that the post-stroke effects of IL-6 may be dependent on its cellular location. We report that IL-6 produced by meningeal resident mast cells (pro-inflammatory effector cells) significantly exacerbates brain inflammation and pathology after stroke. These are the first data to identify the role in stroke pathology of IL-6 derived from a specific cell type in a particular anatomic location in vivo.

Methods:
A mast cell (MC) ‘knock-in’ mouse model was used where MC-deficient mice (KitW/W-v) were repaired of their MC deficiency by engraftment of in-vitro-derived MCs. MCs from wild-type (WT) or IL-6 knock-out mice were engrafted into the meninges. Mice were subjected to 30 min middle cerebral artery occlusion. Brain swelling and infarct size were assessed by T2-weighted MRI and histology. The immune response was quantified by flow cytometry.

Results:
CNS distribution analysis of MCs in wild-type and MC-engrafted mice revealed equivalent numbers of MCs in meninges in all groups but almost no MCs in brain parenchyma of the MC-engrafted groups. At 3d post-stroke, wild-type mice and MC-deficient mice engrafted with WT MCs exhibited significantly greater brain swelling, larger infarcts, and more brain granulocytes and activated macrophages than MC-deficient mice. These findings indicate that meningeal MCs exacerbate stroke outcome. In contrast, the pathology in IL6-KO MC-engrafted mice resembled that in MC-deficient mice, with significantly less brain swelling, smaller infarcts and fewer granulocytes and activated macrophages than in the WT MC-engrafted mice. This indicates that MC-secreted IL-6 contributes importantly to the detrimental effects of MCs.

Conclusions:
IL-6 produced by mast cells in the meninges is detrimental to stroke outcome. Thus, intrathecal targeting of meningeal inflammation may offer a novel therapeutic strategy for stroke.
Abstract T P83: The CYP Epoxygenase Metabolite of Arachidonic Acid 14,15- Epoxyeicosatrienoic Acid: a Novel Therapeutic Target in Neuroprotection
Authors: Gebremedhin Debebe , Rarick Kevin , Harder David R
Published: March 2022

Background:
Neuronal cells rely on their metabolic coupling with astrocytes, which release factors that affect phenotype of brain cell types. Both astrocytes and neuronal cells express the CYP epoxygenases that metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs), including 14,15-EET. Circadian rhythms are evident in daily variations of cardiovascular function and in stroke incidence. Ischemic stroke is associated with increased production of H2O2 that causes cellular oxidation and neuronal death. The purpose of this study is to investigate neuroprotective effects of 14,15-EET against oxidative damage.

Methods:
We investigated the circadian pattern of production and neuroprotective effects of 14,15-EET against H2O2-induced oxidative damage in co-cultures of astrocytes and neurons.

Results:
We found significant 24h rhythms in 14,15 EET production in astrocytes. Stimulation of neuronal cells with H2O2 (0.1 and 1 mM, 1h) elicited lower cell viability compared to vehicle treated group. Co-culturing of neuronal cells with astrocytes prevented neuronal death induced by H2O2 (0.1 and 1 mM, 1h) application. Pretreating neuronal cells with 14,15-EET (0.1-30 μM, 30 min) before stimulation with H2O2 increased neuronal cell viability. Preincubation of the co-cultured cells with the soluble epoxide hydrolase (sEH) inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) (8-800 nM, 1h) increased endogenous 14,15-EET in the media and protected against H2O2 (1 mM, 1h) induced damage. In contrast inhibition of endogenous EETs production by miconazole (1-20 μM, 1h) before stimulation of cells with H2O2 (1 mM, 1h) elicited decreased cell viability and increased neuronal death. Treatment with 14,15-EET increased formation of the prosurvival phospho-Akt in co-cultures of astrocytes and neurons.

Conclusions:
These findings indicate that 14,15-EET is released from astrocytes in a circadian manner and is neuroprotective against oxidant damage that could prevail in incidences of ischemic stroke. The findings further suggest that activation of phospho-Akt could be the underlying mechanism for the neuroprotective effects of 14,15-EET, and a novel therapeutic target for stroke related neuronal disorders.
Abstract T P87: Does an Increased Pulsatility of the Intracranial Blood Flow Spectral Waveform on Transcranial Doppler (TCD) Point to Peripheral Arterial Disease in Stroke Patients?
Authors: Barlinn Kristian , Kolieskova Stanislava , Shahripour Reza Bavarsad , Kepplinger Jessica , Boehme Amelia K , Puetz Volker , Bodechtel Ulf , Albright Karen C , Alexandrov Andrei V
Published: March 2022

Background:
Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia, yet little testing, if any, is done during in-hospital stay. The pulsatility index (PI) from the systolic and diastolic velocity measurements on TCD is routinely used in stroke patients to assess resistance to flow and thereby intracranial atheromatous disease. We sought to explore whether the PI can indirectly predict the presence of PAD in these patients.

Methods:
We prospectively evaluated consecutive patients with acute cerebral ischemia by TCD and ankle-brachial-index (ABI) measurements. Clinical variables were collected at baseline. On TCD, peak systolic, end-diastolic and mean flow velocities in both middle cerebral and basilar arteries were manually measured. According to a complete four-cardiac cycle sweep without arrhythmias, PI was automatically calculated for each of the 3 arteries and the average was used for analysis. Bilateral brachial, tibial and pedal systolic blood pressures were measured using a 4-MHz continuous-wave Doppler (average over two measurements). ABI 0.91 to 0.99 was considered as borderline, ABI <=0.9 as abnormal and predictive of PAD. All examinations were done in supine position.

Results:
We enrolled a total of 53 patients: 68% ischemic stroke, 32% TIA, 60% Caucasians, 42% male, mean age 64±10 yrs, median NIHSS 4 (range 0-20). ABI was borderline or abnormal in 26/53 (49%) including 12/53 (23%) patients with ABIs consistent with PAD. Baseline characteristics were similar between patients with and without PAD. The mean PI did not differ among patients with and without PAD (0.92±0.08 vs. 1.01±0.04, p=0.24). The PI was not found to be an independent predictor of PAD (OR=0.21, 95% CI 0.01-3.64, p=0.285). Similarly, the PI did not predict ABI (p=0.96). PI strongly predicted history of arterial hypertension (OR=530.04, 95%CI 5.18-54215.57, p=0.008).

Conclusions:
Our findings do not suggest that the presence of PAD can be inferred from intracranial flow parameters predictive of atheromatous disease and risk factors such as hypertension among patients with acute cerebral ischemia. However, the high frequency of PAD in these patients warrants further investigation to facilitate routine and early detection of this disease.
Abstract T P92: Paraoxonase Gene Polymorphism and Carotid Atherosclerosis in Acute Ischemic Stroke
Authors: Ha Yeon Soo , Shin Byoung-Soo , Chang Hyuk , Cheong Jin Sung , Lee Hak-Seung , Park Hyun-Young , Cho Kwang Ho
Published: March 2022

Background:
Atherosclerosis in the carotid artery is one of the main causes of acute ischemic stroke. Lipid oxidation has been known to play an important role in the pathogenesis of atherosclerosis. Paraoxonase (PON) is involved in lipid oxidation and has anti-atherogenic activity. PON single-nucleotide polymorphism (SNP) is associated with serum concentration, the activity of paraoxonase, and an increased risk of vascular disease. The purpose of this study was to investigate the association between four genetic variations of PON SNPs and carotid atherosclerosis (CA) in Korean stroke patients.

Methods:
Acute stroke patients with cardioembolism, other etiologies, and undermined etiologies were excluded to avoid mistaking embolic occlusive lesion for true atherosclerotic lesion. We included 656 subjects who met the inclusion criteria among acute ischemic stroke patients. One hundred and eighty-six subjects had LAA subtype of stroke, and 468 had SVO stroke. All subjects were categorized four subgroups based on the angiographic findings as follows: (1) the No ECIC+ICIC group (those without significant stenosis in the intracranial and extracranial carotid arteries); (2) the ECIC group (those with significant stenosis in the extracranial carotid arteries, but with no significant stenosis in the intracranial carotid arteries); (3) the ICIC group (those with significant stenosis in the intracranial carotid arteries, but with no significant stenosis in the extracranial carotid arteries); and (4) the ECIC+ICIC group (those with significant stenosis in the intracranial and extracranial carotid arteries). All enrolled patients were genotyped with the four genetic variations of PON SNPs (PON1 L55M, PON1 Q192R, PON2 A1148G, and PON2 C311S).

Results:
There were no significant associations between the four PON SNPs of each subgroups according to CA. In cases of LAA stroke, patients with CA had a significantly higher frequency of the PON2 148 AA and PON2 311 CC genotype than those without CA (p=0.021).

Conclusion:
We found an association between PON SNPs and carotid atherosclerosis in LAA stroke. But there was no significant difference in distributions of PON SNPs between intracranial CA and extracranial CA.
Abstract W MP1: Leadership + Education = Quality
Authors: Motz Deb S , Sharp Johanna A , Garcia Thelma , Huey Dicky , Czekaj Lori , Austin Tommye
Published: March 2022

Background:
Baptist Health System (BHS) leadership is invested in “education and training activities that are relevant to the program’s scope of service” as required by Primary Stroke Center Certification. BHS is a five hospital system which reports as one program in five locations. There are 20 stroke-specific nursing departments, with over 700 practitioners and 1,500 stroke admissions annually. This complex system presents unique challenges when developing an education plan to meet Stroke Certification requirements.

Purpose:
The purpose is to describe a stroke education plan which offers a variety of learning modalities reflecting the complexity of stroke care while meeting the learning needs of nurses in diverse clinical areas.

Methods:
The BHS Stroke Education Council was developed as a subcommittee of the Regional Stroke Committee and includes representation from all the clinical departments. The education plan was developed based on identified knowledge deficits, leadership feedback and performance outcomes. The education content addresses scope of service, stroke pathophysiology, assessment, diagnostics, treatments, policies and protocols. The content is presented in a variety of learning modalities including self -paced learning, interactive classes with NIHSS skills check off, stroke hymnal, and in-services. As a result of staff evaluations the education plan was restructured to meet the learning needs of the participants. The Stroke Education Council meets monthly and the plan is revised annually to address educational opportunities.

Results:
The success of this plan is reflected by a 92% practitioner completion rate. In addition, there was a 10% increase in compliance of all required stroke performance measures over a three month period following implementation of the stroke education plan.

Conclusion:
In conclusion, the results are due to the support of BHS leadership who recognize that staff education drives superior care as reflected in quality data indicators and the overall success of the stroke program. The skills and knowledge of the nursing staff is recognized through the achievement of the AHA/ASA Gold Plus and Target Stroke Honor Roll hospital awards in August 2012 and in August 2013.
Abstract W MP103: Stroke Patients with Atrial Fibrillation Who Had Left Atrial Thrombus Are Likely to Have Increased Recurrence in the Long Term
Authors: Yamashita Shinji , Matsumoto Noriko , Saji Naoki , Uemura Jun-ichi , Shibazaki Kensaku , Kimura Kazumi
Published: March 2022

Background and objective:
This study retrospectively investigated long term recurrence rate in stroke patients with atrial fibrillation (AF) who had left atrial thrombus (LAT).

Methods:
Participants compromised 359 consecutive stroke patients with AF less than 7 days after onset who had undergone transesophageal echocardiography. Patients were divided into LAT and non-LAT groups based on the presence or absence of LAT. Clinical background, neurological findings, imaging findings and stroke recurrence within 3 years of discharge were then compared between the two groups.

Results:
Fifty-nine patients were classified into the LAT group and 300 patients into the non-LAT group. Median age of the LAT and non-LAT groups was 78 and 76 years, respectively (p=0.57), and the LAT group had a higher proportion of females (53% vs. 39%, p=0.06) and hypertension (81% vs. 69%, p=0.06). CHADS2 score was higher in the LAT group than in the non-LAT group (median score: 3 vs. 2; p<0.01). Median National Institute of Health Stroke Scale score for the LAT and non-LAT groups was 7 vs. 4 (p=0.05). The proportion of patients with a maximum cerebral infarction diameter ≥3 cm was also greater in the LAT group (61%) compared to the non-LAT group (37%; p=0.02). The recurrence rate (RR) during hospital stay was 3.4% vs. 7.3%, respectively (p=0.40). However, cumulative RR for the 3-year period after discharge was significantly higher in the LAT group (25%) than in the non-LAT group (12%; HR, 2.61; p=0.03; Fig.1).

Conclusion:
Compared to patients without LAT, stroke patients with AF who previously had LAT are more likely to have increased recurrence in long term, but not in the short term.
Abstract W MP107: An Updated Cost-Effectiveness Analysis of r-tPA for Acute Ischemic Stroke Treated Within 3 Hours of Symptom Onset
Authors: Boudreau Denise , Guzauskas Gregory F , Chen Er , Tayama Darren , Fagan Susan , Veenstra David L
Published: March 2022

Background:
A recently completed meta-analysis by Wardlaw and colleagues, including the results of the IST-3 trial, provides more precise estimates of the efficacy and safety of r-tPA in the treatment of acute ischemic stroke (AIS) within 3 hours of symptom onset. No economic analyses have been conducted for r-tPA in the 0-3 hour treatment timeframe since 1998, and changing healthcare costs and better estimates of long-term disposition offer an opportunity to reassess the value of r-tPA in AIS.

Objective:
To evaluate the cost-effectiveness of r-tPA within 3 hours of symptom onset compared to no r-tPA among patients with AIS using updated efficacy, safety, and healthcare cost data.

Methods:
A Markov decision model compared r-tPA treatment within 3 hours of symptom onset vs. no treatment in a hypothetical cohort of r-tPA-eligible AIS patients. Key model inputs (efficacy, safety, and mortality associated with each health state parameter) were varied based on the NINDS and ECASS III clinical trials and a recent meta-analysis of all trials, including the newly published IST-3 trial. Patients with modified Rankin scores of 0-1, 2-5, and 6 were classified into health states of non-disabled, disabled, or dead, respectively. Costs and utilities (patient preferences) associated with each health state were derived from the literature. The primary outcomes were incremental quality-adjusted life years (QALYs) gained and lifetime healthcare costs from a payer perspective.

Results:
Treatment with r-tPA was associated with increased QALYs between 0.14 and 0.46. The cost-effectiveness results ranged from a cost savings of $2700 to $25,000 per QALY gained in a worst-case scenario. Major drivers of results were efficacy, cost of r-tPA, disabled patient mortality, disabled patient quality of life, and risk of recurrent stroke.

Conclusion:
Economic analyses based on current clinical and cost data suggest that r-tPA is highly cost effective in the treatment of AIS across numerous efficacy, safety, and mortality estimates. Further research on differences in long-term mortality in disabled and non-disabled patients will refine these estimates.
Abstract W MP112: Factors Associated With Increased In-Hospital Mortality Among Children With Intracerebral Hemorrhage
Authors: Adil Malik M , Qureshi Adnan I , Beslow Lauren A , Malik Ahmed A , Jordan Lori C
Published: March 2022

Objective:
Prior reports have noted that intracerebral hemorrhage (ICH) volume and altered mental status predict poor outcome in children but assessment of other predictors has been limited by sample size. We assessed predictors of mortality and potential targets for intervention in a large national sample of children with non-traumatic ICH.

Methods:
Using the Healthcare Cost and Utilization Project Kids’ Inpatient Database, ICD-9-codes (431, 432.9) identified children 1-18 years with non-traumatic ICH in years 2003, 2006 and 2009. Children with ICD-9 codes for trauma (800s) were excluded. Step-wise logistic regression determined factors associated with mortality. The Cochran-Armitage trend test determined the change in annual average mortality and hospitalization days from 2003 to 2009.

Results:
ICH was the primary diagnosis for 2346 children over the 3-year sample (Table). The most common comorbidities included coagulopathy (11.4%), AVM (10.5%) and hypertension (8%). Overall, 8.7% died in the hospital. Factors associated with mortality included Hispanic ethnicity (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-2.8), older age 11-18 years (OR 1.7, 95% CI 1.2-2.5), coagulopathy (OR 3.8, 95% CI 2.4-6.1), hypertension (OR 2.1, 95% CI 1.2-3.9) and coma (OR 12, 95% CI 5.3-30.7). Mortality decreased from 10.6% in 2003 to 7.2% in 2009 (p<0.01). Mean length of stay increased from 7 days (95% CI 6-9 days) in 2003 to 9 days (95% CI 8-10 days) in 2009 (p<0.001).

Conclusion:
Coma, coagulopathy, and hypertension demonstrated a strong association with mortality among children with ICH and may represent potential targets for therapeutic intervention.