bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 215: The Prognostic Significance of Subendocardial Myocardial Infarction in Patients Undergoing Carotid Endarterectomy or Carotid Artery Stent Placement
Authors: Khan Amir , Adil Malik M , Chaudhry Saqib A , Suri M Fareed K , Qureshi Adnan I 
Published: March 2022

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

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

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

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

Conclusions:
Our results contradict the notion that subendocardial MI is a relatively benign entity after CEA or CAS. It remains unclear whether subendocardial MI is a marker or cause of high rates of adverse outcomes and resource utilization following CEA or CAS.
Abstract TMP67: Microglia Transplantation Reduces Stroke Injury
Authors: Shimizu Takeru , Mader Sarah , Koerner Ines P 
Published: March 2022

Microglia are activated after stroke and may contribute to ischemic brain injury by producing mediators such as inflammatory cytokines and free radicals that are toxic to neurons. Microglia are also likely responsible for the influx of peripheral immune cells after stroke, which further exacerbate injury. In contrast, there is increasing evidence that microglia can also be protective, as ablating microglia before stroke increases infarct size (1) and arterial injection of microglia during global ischemia reduces neuronal death (2). We tested whether increasing the number of resident microglia by transplantation would convey protection from ischemic stroke.
We injected 20,000 primary cultured microglia into the striatum of adult male C57Bl/6 mice. Control groups were injected with a similar number of cultured astrocytes or received no injection. Additional mice were injected with eGFP expressing microglia to allow visualization of transplanted cells. After 14 days recovery, mice underwent 60 minutes of transient middle cerebral artery occlusion. Cerebral blood flow was monitored by laser Doppler. Infarct size was measured by TTC staining 24 hours after reperfusion and expressed as % of contralateral structure.
Transplanted microglia survived and were present in the striatum 14 days after the injection. Infarct size was significantly reduced by microglia transplantation, both in the infarct core (striatum, 69% vs. 80% control) as well as the penumbra (cortex, 42% vs. 52%, P<0.05). Transplantation of astrocytes, in contrast, had no effect on infarct size. Cerebral blood flow was not different between groups.

The number of resident microglia in mouse brain can be increased by transplantation of microglia, which survive for several weeks after injection. Infarct size is reduced after transplantation of microglia. This is likely caused by increased microglial production of neuroprotective and anti-inflammatory mediators after stroke, such as insulin-like growth factor (1) or interleukin-10. Further studies will identify the microglial mediators that are responsible for the observed protection. They may offer new therapeutic options to reduce injury after stroke.

Lalancette-Hebert et al. J Neuroscience 2007

Imai et al. JCBFM 2007
Abstract TP194: Internet-based Control Recruitment for a Case-Control Study of Major Risk Factors for Stroke in Korea: A Failure and Lessons Learned from the Experience
Authors: Park Jong-Moo , Cho Yong-Jin , Lee Kyung Bok , Park Tai Hwan , Lee Soo Joo , Han Moon-Ku , Ko Youngchai , Lee Jun , Cha Jae-Kwan , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Lee Ji Sung , Lee Juneyoung , Bae Hee-Joon 
Published: March 2022

This study aimed to estimate the population attributable risks (PARs) of major risk factors for stroke in Korea through an internet-based case-control study and test the feasibility and validity of this approach.
Control subjects were recruited by a web-based questionnaire from April 2008 to September 2009. Cases were consecutive stroke patients hospitalized to during the same period. Each control was matched with 2 cases for age and sex. The presence of hypertension, diabetes, hypercholesterolemia, smoking, atrial fibrillation, coronary heart disease, history of stroke, family history of stroke and obesity were investigated. Age-standardized prevalence, adjusted odd ratios (ORs) and PARs for 9 risk factors for stroke were calculated.
One thousand forty one control subjects were matched with 2,082 cases. Adjusted ORs for stroke were 2.80 for hypertension, 3.56 for diabetes, 3.65 for smoking, 3.95 for history of stroke, and 1.25 for obesity. Risk of atrial fibrillation, coronary heart disease, and family history of stroke were not significant, while hypercholesterolemia showed inverse correlation. PARs for stroke were 16.3% for hypertension, 9.4% for diabetes, 23.6% for smoking, 5.84% for stroke history, and 4.18% for obesity. Comparisons of education level and religion between the control group and the national census data for validating its representativeness revealed significant discrepancy.
In conclusion, internet-based control recruitment for a case-control study of stroke risk factors may be feasible; however, careful approaches for reducing selection and reporting biases are essential.
Abstract TP216: Cardio-Ankle Vascular Index (CAVI) Is A Novel Parameter To Predict Aortic Arch Plaque Causing Atherothrombotic Stroke
Authors: Sasaki Shintaro , Nishiyama Satoshi , Watanabe Tetsu , Tamura Harutoshi , Wanezaki Masahiro , Sato Chika , Kubota Isao 
Published: March 2022

Aortic arch plaque is an important cause of atherothrombotic stroke. The cardio-ankle vascular index (CAVI) has been reported as a novel parameter for aortic stiffness, and high CAVI implies progression of carotid and coronary arteriosclerosis. However, it remains to be determined whether CAVI is associated with arch plaques.
We performed CAVI and transesophageal echocardiography in 290 subjects (197 males, 65 ± 12 years), including 29 patients with the history of atherothrombotic stroke. We defined arch plaque as wall thickness ≥ 4 mm and the presence of ulceration or mobile plaque in aortic arch.
CAVI showed a good correlation with age, systolic blood pressure, fibrinogen, von Willebrand factor, carotid plaque score and arch wall thickness. CAVI was higher in subjects with following risk factors than in those without; hypertension, diabetes mellitus, and dyslipidemia. CAVI was higher in subjects with ulceration or mobile plaques than in those without. CAVI was higher in subjects with atherothrombotic stroke than in those without (10.5 vs. 8.6, P<0.001). The subjects with CAVI ≥ 9 had higher risk for atherothrombotic stroke compared with those with CAVI < 9 in univariate logistic regression analysis (odds ratio 5.07, 95% confidence interval 2.16-11.91). Multivariate logistic regression analysis revealed that CAVI was an independent risk factor for atherothrombotic stroke.
In conclusion, CAVI is a novel parameter predicting aortic arch plaques, which cause atherothrombotic stroke.
Abstract 161: Effects of Radiation Dose on Gene Expression in Cultured Murine Brain Endothelial Cells
Authors: Raoufi-Rad Newsha , Ukath Jaysree , Stoodley Marcus Andrew 
Published: March 2022

Brain arteriovenous malformations (AVMs) are direct connections between arteries and veins that allow high pressure arterial blood to flow into fragile cerebral veins. AVMs are the leading cause of hemorrhagic stroke in children and young adults. Treatment of large and deep AVMs is challenging; new treatment methods are required. It is proposed that stereotactic radiosurgery could be used to selectively alter the AVM endothelial cell phenotype, allowing targeted molecular therapies which stimulate thrombosis.
We have previously shown that irradiation of endothelial cell cultures with 25Gy results in up-regulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study we hypothesise that a lower dose of radiation is similarly effective at causing up-regulation in ICAM-1 and VCAM-1 expression. Murine brain endothelial cell cultures were irradiated with 15Gy (n = 4) or 25Gy (n = 4) using a linear accelerator; non-irradiated cells were used as controls (n = 4). The relative gene expression at 96, 120, 144 and 168h after radiation was measured by quantitative real-time PCR. Genes encoding for ICAM-1 and VCAM-1 were found to be significantly up-regulated post-radiation with either 15Gy or 25Gy (p <0.001). Maximum gene expression of ICAM-1 and VCAM-1 was observed at 144h (7-fold) and at 120h (23-fold), respectively. There was no significant difference between the two doses. These results support the hypothesis that a 15Gy dose is as effective as a 25Gy dose. Therefore a lower dose of radiation might be equally effective at causing changes in endothelial cell phenotype. This is important from a clinical perspective because lower doses of radiation will be safer for the treatment of large AVMs.
Abstract 215: Hyperhomocysteinemia as a Model of Vascular Dementia and Its Effects on Amyloid Pathology in a Transgenic Mouse Model
Authors: Lee Tiffany , Weekman Erica , Wilcock Donna M 
Published: March 2022

Vascular dementia is the second leading form of dementia after Alzheimer’s disease. There is a relative lack of animal models in which to study the mechanisms underlying cerebrovascular disease leading to dementia. In addition, cerebrovascular disease is a common co-morbidity in Alzheimer’s patients, yet its impact on Alzheimer’s pathology and clinical outcome is unknown. We aimed to develop a model of vascular dementia that could allow us to create a model of cerebrovascular disease / amyloid pathology co-morbidity.
We Induced hyperhomocysteinemia through dietary deficiency of B-vitamins and enrichment of methionine in 3 month old wildtype mice for fourteen weeks. We also used the same methods to induce hyperhomocysteinemia in 6 month old APP/PS1 mice for four and six months. We performed T2* MRI, histology and biochemistry to assess outcomes.
In the wildtype mice on diet for fourteen weeks we observed significant microhemorrhages by T2* MRI imaging that was confirmed by Prussian blue staining. We found that the MRI detects a smaller number of microhemorrhages than does the Prussian blue staining. The hyperhomocysteinemic mice had significant neuroinflammation, as demonstrated by increased expression of IL-1β, TNFα, IL-6 and IL-12. Importantly, we found increased expression and activity of the matrix metalloproteinases MMP2 and MMP9.
In the APP/PS1 mice we have found that hyperhomocysteinemia induces an increase in total brain Aβ, detected both biochemically and immunohistochemically. Of note, was a greater increase in Aβ1-40 than Aβ1-42. We have also found increased cerebral amyloid angiopathy with hyperhomocysteinemia, and an exacerbated neuroinflammatory response. The numbers of microhemorrhages were comparable between wildtype and APP/PS1 hyperhomocysteinemic mice, but the microhemorrhages appear larger in the APP/PS1 mice.
Overall, we believe our data indicates that cerebrovascular disease co-morbid with amyloid pathology, exacerbates the cerebrovascular amyloid pathology and could have implications to therapeutic development for the treatment of Alzheimer’s disease.
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 W MP46: Beyond the Brain: Stroke Induces Vascular Breakdown and Unique Profiles of Peripheral Inflammatory Response in the Eye and Spinal Cord
Authors: Pan Sarah , Ritzel Rodney , Patel Anita , Lieberman Richard , McCullough Louise 
Published: March 2022

Ischemic stroke, a leading cause of death and long-term disability, has far-reaching effects across the CNS beyond the region of infarct. As extensions of the brain, neural networks of the eye and spinal cord are affected by cerebral ischemia through the transmission of inflammatory and degenerative changes. Although neuropathological effects of MCAO have been reported in both regions, the contribution of the peripheral inflammatory response to the evolution of injury in these CNS regions is unknown. We evaluated local glial responses, vascular integrity, leukocyte infiltration, and cytokine expression after stroke in the eye and spinal cord.
Adult male C57Bl/6 WT or GFP+ bone marrow chimeric mice were subjected to 90-min MCAO or sham surgery (n=3-6). Imaging of the retinal vasculature was performed by ophthalmoscopy. At 8h, 24 and/or 36h, 72h and 7d post-stroke mice were perfused with PBS and sacrificed. Organs were harvested for immunohistochemistry, Evans blue extravasation, flow cytometry, and RT-qPCR.
Early (8h) after MCAO, over four-fold increases in TNFα and IL-1β gene expression were observed in the ipsilateral eye relative to sham (4.64±1.21, 1±0.17; 11.03±7.75, 1±0.21). Microglial activation indicated by increased CD11b, CD45, and cell granularity at 36h was accompanied by an influx of peripheral leukocytes predominantly comprised of neutrophils (81%). In contrast to BBB breakdown which was highest at 24h, blood-retinal barrier breakdown peaked in the ipsilateral eye at 36h, shown by a twelve-fold increase in Evans blue concentration (sham, 24h, 36h: 0.16, 0.41, 1.95 ug/mg tissue wet weight). Similarly, major blood-spinal cord barrier breakdown occurred at 36h (0.32 vs 0.052 ug/mg). This was followed by a largely monocytic response with corresponding increases in TNFα, IL-1β, and IFNγ gene expression.
Together, our data show robust unilateral peripheral inflammatory responses after stroke in CNS regions outside of the brain. In addition, blood-parenchymal barrier permeability peaks later in the eye and spinal cord than in the brain. Given the distinct time course and inflammatory components associated with each region, these findings may have wide implications for treatments attenuating CNS-wide inflammatory damage after stroke.
Abstract W P298: Retrospective Review of Inpatient CODE STROKE and Evaluation of the Implementation and Outcomes
Authors: Curtis Adam , Radtke Jennifer , Day Theresa , Blair Sabrina , Henry Jennifer , Heidel Robert E 
Published: March 2022

Background /Purpose:
The goal of this study is to evaluate the effectiveness of an inpatient code stroke (ICS) process in achieving benchmarks. This study investigated the effects of an ICS on:

•Discovery to CT result (DCT)
•Discovery to MD evaluation (DMD)
•Documentation of last known normal (LKN) and NIH stroke scale (NIHSS)
The expected results are decreased DCT and DMD times, and increased compliance with documentation of NIHSS and LKN.

Methods:
A multidisciplinary team developed the ICS by integrating the existing ED code stroke and rapid response team processes. All staff received education on recognition of stroke warning signs and activation of ICS prior to implementation. A retrospective case control analysis between subjects with pre and post protocols as the primary predictor and DCT as the primary outcome endpoint. An independent sample t-test between DCT and DMD time (in minutes) was conducted. Unadjusted odds ratios were calculated to assess associations in categorical variables.

Results:
A total of 82 records (pre n=25, post n=57) of inpatients experiencing acute onset of stroke symptoms were examined revealing mean DCT times pre/post-protocol, respectively, of 53.3 (SD 27.6) and 49.7 (SD 18.1). No statistically significant improvement (p=.54) was identified. DMD evaluation time also failed to demonstrate a significant difference between pre/post-protocol times (9.3, 11.3, p=.45). Post-protocol documentation of the NIHSS revealed no significant change (p=.27); however, documentation of LKN was 14.4 times more likely (95% CI 3.98-51.83).

Conclusion:
Implementation of the ICS resulted in a two-fold increase in identification of acute onset of stroke like symptoms. Compliance with documentation of LKN increased significantly which may be the result of the educational initiative and contributed to our increased volume of ICS. In conclusion, though the results of DCT and DMD are not statistically significant, they are promising. The 4 minute decrease in DCT time and narrowing SD suggest that the process has improved flow for in-house acute stroke patients.
Abstract W P79: Computational Fluid Dynamics Analysis in Roles of Hemodynamic Factors on the Development of Cerebral Aneurysms
Authors: Fukuda Shunichi , Shimogonya Yuji , Tsukahara Tetsuya , Imoto Yasuhide , Fukuda Miyuki 
Published: March 2022

Cerebral aneurysms are known to be more induced in the asymmetric-shaped circle of Willis, suggesting that hemodynamic stress is involved in aneurysm development. We have made a series of reports on an animal model of experimentally induced cerebral aneurysms, which are induced in the circle of Willis where blood flow is increased in compensation for ligation of unilateral common carotid artery and renal hypertension. Our morphological and molecular studies suggest that enhanced wall shear stress (WSS) at the local area in the circle of Willis initiates aneurysm development (Fukuda S, Circulation 101:2532-2538). We examined here roles of hemodynamic factors on the development of cerebral aneurysms with computational fluid dynamics (CFD) techniques using 3-dimentional CT angiographic images of human cerebral aneurysms.
In order to clarify the effect of hemodynamic factors on aneurysm growth, we virtually reconstructed arterial geometry of human middle cerebral and internal carotid artery aneurysms just before the development of aneurysms by artificial removal of the aneurysm as we reported previously (Shimogonya Y, J Biomech 42:550-554), and compared values of hemodynamic factors between aneurysm-developed side and non-developed normal side. Time-averaged WSS gradient was significantly higher in the aneurysm-developed side than normal side. The data suggest that an increase in wall shear stress be associated with an early stage of the aneurysm formation, which is consistent with our previous data using an animal model.