bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 216: Impact of Warfarin Use in Patients with End Stage Renal Disease and Atrial Fibrillation
Authors: Lee Meng , Saver Jeffrey L , Hong Keun-Sik , Wu Yi-Ling , Ovbiagele Bruce
Published: March 2022

Background:
Although warfarin is a standard therapyfor atrial fibrillation (AF) patients to prevent stroke, and AF is a frequent comorbidity of patients with end stage renal disease (ESRD), warfarin administration to ESRD patients is viewed with caution because these patients are already at high risk for systemic hemorrhages. Results of studies on the efficacy and safety of warfarin use in patients with ESRD and AF have been inconsistent.

Objective:
To qualitatively and quantitatively evaluate the risk-benefit profile of warfarin for patients with ESRD.

Methods:
Pubmed and EMBASE from 1966 to May 2014 were searched to identify relevant studies. Inclusion criteria were cohort studies, patients with ESRD and AF at baseline, assess stroke and/or death as an endpoint during the follow-up period, and reported quantitative estimates of the multivariate adjusted relative risk (RR) and 95% confidence interval (CI) for future stroke and/or death associated with warfarin use. We combined log RR and standard errors using the inverse variance approach.

Results:
We identified 8 cohort studies with 11773 patients with ESRD and AF. Among 8 studies, 7 reported an estimate of stroke and 4 reported an estimate of death. Pooling the results showed that warfarin use was associated with a neutral effect on stroke (RR 0.91, 95% CI 0.59 to 1.41, P=0.66, Figure) and death (RR 0.68, 95% CI 0.42 to 1.10, P=0.12). There were substantial heterogeneities among these studies. Warfarin use was associated with fewer ischemic stroke events (5 studies, RR 0.57, 95% CI 0.34 to 0.95, P=0.03) and not associated with increased risk of major bleeding (5 studies, RR 1.13, 95% CI 0.83 to 1.52, P=0.44).

Conclusion:
This meta-analysis of cohort studies suggests warfarin use is neither beneficial nor unsafe in patients with ESRD and AF. However, randomized controlled trials are needed to definitively clarify the effects of anticoagulant agents in this patient population.
Abstract 217: Impact of the New Aha/asa Definition of Stroke on the Outcome of The SAMMPRIS Trial for The SAMMPRIS Investigators
Authors: Al Kasab Sami , Lynn Michael J , Turan Tanya N , Derdeyn Colin P , Fiorella David , Lane Bethany F , Montgomery Jean , Janis Scott , Chimowitz Marc I
Published: March 2022

Background:
The AHA/ASA have recently recommended that cerebral infarction associated with temporary symptoms or signs (CITS) lasting < 24 hours should be considered a stroke. We analyzed the impact of including CITS in the territory of the symptomatic artery as a primary endpoint on the results of the SAMMPRIS trial.

Methods:
We compared the outcome of patients in the medical vs. stenting (PTAS) groups in SAMMPRIS using the following primary endpoint: any stroke, CITS or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during follow up or stroke or CITS in the territory of the qualifying artery beyond 30 days. We also compared the use of brain MRI after TIAs in both treatment groups.

Results:
The Kaplan-Meier curves for these events in the two groups were significantly different (p = 0.009) with the following rates in the medical group versus PTAS group: 6.7% versus 15.6% at day 30 (p=0.002), 16.3% versus 25.1% at year 1 (p=0.022), and 19.4% versus 30.3% at year 3 (p=0.009). The percentage of patients with reported TIAs who underwent brain MRI was 69% (34/49) in the medical group and 61% (28/46) in the PTAS group (p=0.40).

Conclusion:
CITS in the territory occurred more frequently during follow-up in the PTAS group than in the medical group, which cannot be attributed to imaging ascertainment bias. These results imply an even higher benefit from medical therapy over stenting and a higher risk of symptomatic cerebral infarction in both groups than originally described in SAMMPRIS.
Abstract 218: Relationships Between Telomere G-tail Lengths, Inflammation, Oxidative Stress and Endothelial Function in the Patients With Carotid Atherosclerosis
Authors: Nezu Tomohisa , Hosomi Naohisa , Aoki Shiro , Takahashi Tetsuya , Anno Kumiko , Maruyama Hirofumi , Hayashi Tomonori , Tahara Hidetoshi , Matsumoto Masayasu
Published: March 2022

Background and Purpose:
Telomere length of leukocytes is associated with cardiovascular risk. Recently, telomere G-tails, which are extensions of a guanine-rich single-stranded 3’-overhang, are thought to be key structures that protect telomere DNA from DNA damage. The aim of this study was to investigate the associations between telomere G-tail lengths, total telomere lengths and clinical factors, including biological inflammation and oxidative stress markers.

Methods:
Patients with history of cerebrovascular diseases and comorbidities were enrolled in this study (n=102; 69 males, 70.1±9.2 years). Total telomere lengths and telomere G-tail lengths were measured by hybridization protection assay (Tahara H et al. Nat Methods. 2005). Serum reactive oxygen species (ROS) levels were measured by using the total ROS assay system (Hayashi I et al. Mutat Res. 2007). Endothelial function was evaluated by ultrasound assessment of brachial flow-mediated dilation (FMD) as an index of endothelium-dependent vasodilation.

Results:
Telomere G-tail length (13653.0±2787.4 RLU/μg DNA) was positively correlated with total telomere length (176698.3±20308.0 RLU/μg DNA; R2=0.156, P<0.001). In addition, telomere G-tail length was negatively correlated with age (R2=0.075, P<0.001). Telomere G-tail lengths were not associated with the serum ROS levels or hs-CRP levels, although there was a significant association between serum hs-CRP levels and ROS levels (R2=0.336, P<0.001). Telomere G-tail lengths were positively correlated with FMD values (R2=0.074, P=0.006), although total telomere lengths were not correlated with those values (R2=0.026, P=0.105). On multivariate regression analysis, longer telomere G-tail lengths (standardized partial regression coefficient [β] 0.219; P=0.018), higher age (β -0.209; P=0.031), and male (β -0.264; P=0.004) were independently associated with FMD values.

Conclusion:
Telomere G-tail lengths were independently related to the endothelial function after adjustment for vascular risk factors, chronic inflammation and oxidative stress. Telomere G-tail lengths might be more useful marker for the endothelial function which was evaluated by FMD than total telomere lengths.
Abstract 223: Elevated Mip-1b, Peripheral Arterial Disease, and Antiplatelet Medication Use Predict Cognitive Function Among Asymptomatic Patients Referred for Carotid Doppler Evaluation
Authors: Kirkpatrick Angelia , Vincent Andrea , Csiszar Anna , Dale George , Prodan Calin
Published: March 2022

Background:
Vascular cognitive impairment (VCI) includes the entire spectrum of cognitive disorders associated with cerebrovascular disease, ranging from mild cognitive impairment to vascular dementia. Our incomplete understanding of vascular and inflammatory mechanisms involved limits the ability to prevent cognitive impairment. We explored whether inflammation may be associated with cognitive function among subjects at risk for cerebrovascular disease.

Methods:
Sixty consecutive patients without dementia or stroke referred for carotid Doppler evaluation were screened for cognitive impairment using the Montreal Cognitive Assessment (MoCA). Serum was obtained for measurement of inflammatory markers using the Bio-Plex Pro Human Cytokine 27-plex Assay kit (Bio-Rad Laboratories). Hs-CRP was also measured. Inflammatory markers were analyzed according to quartiles of marker concentration for association with MoCA score. Backward stepwise regression was conducted to find the best combination of predictors. Markers having bivariate correlations at the 0.25 significance level were included as potential predictors. Relevant demographic and comorbid factors were also considered. Variables with p values <0.05 were retained in the final model.

Results:
Fifty-eight percent of patients (35/60) had cognitive impairment (MoCA<26, range 19-25). Stepwise multiple regression analysis revealed inverse correlations between three variables and MoCA scores: Macrophage Inflammatory Protein-1b - MIP-1b (b= -0.99, SE = 0.30, p=0.0016), use of antiplatelet medications (b= -1.96, SE = 0.93, p=0.039), and peripheral arterial disease - PAD (b= -1.53, SE = 0.73, p=0.041), overall model R2 = 0.26, F = 6.5, p=0.0007.

Conclusions:
Elevated MIP-1b, presence of PAD, and use of antiplatelet medications were associated with lower cognitive performance among patients at risk for cerebrovascular disease. The range of abnormal MoCA scores (19-25) and high prevalence of vascular risk factors among this group suggest that the cognitively impaired subjects have early VCI. These data suggest that MIP-1b should be further explored as a potential link to mechanisms for development of VCI.
Abstract 27: Unique ASPECTS of Conditioning? Prior TIA or Atrial Fibrillation and Early CT Findings in FAST-MAG
Authors: Liebeskind David S , Sanossian Nerses , Starkman Sidney , Villablanca Pablo , Burgos Adrian M , Scalzo Fabien , Johnson Mark S , Eckstein Marc , Stratton Sam , Pratt Frank , Conwit Robin , Hamilton Scott , Saver Jeffrey L ,   on behalf of the FAST-MAG Investigators
Published: March 2022

Background:
Ischemic conditioning, or endogenous protection of brain tissue, may be elicited by prior TIA or absent due to sudden cardioembolic occlusion in atrial fibrillation (AF). We hypothesized that such specific co-morbidities may be manifest by the extent of early ischemic changes, or ASPECTS score, on CT in the prehospital NINDS FAST-MAG trial.

Methods:
All FAST-MAG subjects with a final diagnosis of cerebral ischemia were included in these analyses of baseline clinical variables and ASPECTS, scored on the initial non-contrast CT acquired at ED arrival. The relationship between prior medical conditions and total ASPECTS score was determined by bivariate analyses, Mann-Whitney U, and Kruskal-Wallis tests.

Results:
1,240 patients (mean age 69 SD 13; 45% women) had ASPECTS scored on initial imaging, CT in 1227 (97%), MRI in 42. ASPECTS (median 10, range 1-10) was notably higher, signifying less ischemic changes in those with history of prior TIA, median 10 (IQR 10-10) vs. 10 (8-10), p=0.012 by Mann-Whitney, whereas prior history of stroke revealed no difference. Conversely, substantially lower ASPECTS or greater ischemic changes were noted in those with history of AF, median 10 (7-10) vs. 10 (8-10), p=0.010) and presence of AF on EKG in ED, median 10 (6-10) vs. 10 (8-10), p=0.041. Interestingly, other cardiac history and all other co-morbidities demonstrated no relationship with ASPECTS. Elevated prehospital systolic blood pressure was linked with higher ASPECTS (r=0.098, p=0.001), as was the change in blood pressure from field to ED (ANOVA, p=0.049). Initial ASPECTS was linked with 90-day mRS outcomes (r=-.259, p<0.001).

Conclusions:
Prior TIA and AF exhibit striking, yet opposite relationships with the extent of early CT findings in this large cohort of patients enrolled in a prehospital stroke trial. These findings suggest that patient-specific factors, such as conditioning, may be pivotal in the course of cerebral ischemia.
Abstract 29: Calcium/calmodulin-dependent Protein Kinase Kinase β (CaMKK β) is Neuroprotective in Stroke in Aged Mice
Authors: Liu Lin , Yuan Hui , Denton Kyle , Li Xue-jun , McCullough Louise , Li Jun
Published: March 2022

Background:
CaMKK β is a major kinase activated by elevated levels of intracellular calcium. Our previous data has suggested that CaMKK β is neuroprotective after stroke in young mice as inhibition of this kinase aggravated stroke outcome. As aging is an important determinant of stroke outcomes, here we evaluated the functional role of CaMKK β in stroke in aged mice.

Methods:
Aged wild type (WT) males received intracerebral injections of lentiviral vectors carrying either CaMKK β (LV-CaMKK β) or GFP (LV-GFP) 7 days before middle cerebral artery occlusion (MCAO, 90 minutes). Acute infarcts and neurological deficits scores were then analyzed at 72 hours post MCAO. In chronic survival studies, aged male CaMKK β knockout (KO) and WT mice were subjected to 60 minutes MCAO. Following stroke, long-term behavioral assessments were continuously performed for 3 weeks in KO and WT mice until the sacrifice for tissue loss assessments.

Results:
Baseline levels of CaMKK β in aged brain were significantly lower when compared to that in young mice measured by Western Blots (Aged WT 0.66±0.06 vs. Young WT 1.00±0.05, n=3 p/g, p<0.05). Administration of LV-CaMKK β to WT mice increased levels of this protein in brain (LV-CaMKK β 1.65±0.11 vs. LV-GFP control 1.07±0.05, n=3 p/g, p<0.05). Further, LV-CaMKK β treatment reduced infarcts assessed 3 days after stroke (total: LV-CaMKK β 16.76± 3.16% vs. LV-GFP control 26.43±4.30%, n=7 p/g, p<0.05) and neurological deficits [LV-CaMKK β 1(1) vs. LV-GFP 2(1), median (interquartile range), n=7 p/g, p<0.05]. In chronic survival experiments, CaMKK β KO mice showed increased tissue loss in ipsilateral hemispheres measured at 3 weeks after stroke (tissue loss: Aged KO 20.59±1.90% vs. Aged WT 11.89±1.00%, n=6 KO, 7 WT, p<0.05). Additionally, KO mice had worsened functional recovery when compared to WT controls during 3 weeks survival measured by rotarod test, locomotor activity in an open field, and in the novel object recognition test.

Conclusions:
Our studies demonstrated that CaMKK β is neuroprotective in stroke in the aged. As the elderly population has worse functional recovery after stroke, our data suggested that this protein may be a potential target for reducing long term disability of stroke patients.
Abstract 33: Vagus Nerve Stimulation for Acute Stroke Treatment: Role of Cholinergic Anti-Inflammatory Pathway
Authors: Ay Ilknur , Nasser Rena , Ay Hakan
Published: March 2022

Introduction:
Electrical stimulation of the cervical vagus nerve is neuroprotective after MCAO in rats; decrease in infarct volume ranges from ~40% (using surgically implanted electrodes) to ~30% (using clinically applicable non-invasive devices). The exact mechanism of vagus nerve stimulation (VNS)-induced neuroprotection is not known, but so far cerebral blood flow-related mechanism has been eliminated. VNS attenuates systemic inflammation via activation of alpha7 nicotinic acetylcholine receptors (α7 nAChR) on macrophages. We hypothesized that α7 nAChR -mediated anti-inflammatory effect plays a mechanistic role in VNS-induced neuroprotection after cerebral ischemia.

Methods:
Focal ischemia was induced by 2 hour transient MCAO in Wistar rats and verified by >60% drop in baseline cerebral blood flow. Methyllycaconitine (MLA; 10 mg/kg, IP) was used to block α7 nAChRs. Animals were randomly assigned to one of four experimental groups: sham stimulation/vehicle, sham stimulation/MLA, VNS/vehicle, VNS/MLA (n=6 in each). VNS was initiated 30 minutes after MCAO and delivered for 1 hour via implanted electrodes, using previously published stimulation parameters. Animals were euthanized 24 hours later to measure infarct volume by TTC. In separate cohorts, immunohistochemistry was used to assess the changes in brain levels of α7 nAChR-related cytokines, TNF-α and high mobility group box protein 1 (HMGB1), in sham-stimulated and VNS groups.

Results:
Mean infarct volume in sham-stimulated and VNS groups were 43.83 ± 1.53% and 25.33 ± 3.39%, respectively (p<0.05). MLA abolished the neuroprotective effect of VNS; after MLA treatment mean infarct volume in sham-stimulated and VNS groups were 45.24 ± 4.78% and 48.58 ± 2.78%, respectively (p=n.s.). MLA alone had no effect on ischemic outcome; there was no difference in infarct volume between MLA- treated and untreated sham-stimulated animals (p=n.s.). Ischemia-induced elevation in TNF-α and decrease in HMGB1 levels were completely reversed by VNS as early as 3 hours after ischemia.

Conclusion:
This study shows that anti-inflammatory mechanisms via nicotinic acetylcholine receptor-mediated signaling play a role in protective effect of VNS against ischemic tissue damage.
Abstract 4: A Functional Variant in the 3’-utr of Vegf Might Affect Stroke Functional Recovery by Interfering With the Binding Efficiency of Microrna
Authors: Zhao Jing , Wu Hui
Published: March 2022

Background and purpose:
While remaining the second most common cause of death worldwide, stroke is also a leading cause of significant disability. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis and neurovascular during stroke functional recovery . Therefore, we hypothesized that variants of the microRNA-binding site in VEGF would affect its expression and functional outcome of stroke. However, the effect of VEGF gene 3'UTR polymorphisms on the prognosis in patients with acute ischemic stroke(IS) in Chinese has not been reported.
Methods:
The association of VEGF gene 3'UTR variant with IS was investigated in 494 patients and 330 controls. IS was classified into subtypes using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) at the time of admission. Patients were assessed 90 days post-stroke using the Modified Rankin Scale (MRS) to determine stroke outcome. The bioinformatics analysis suggested that the 3′-UTR of VEGF may increase miR regulation of VEGF gene expression, Then we construct luciferase reporter gene vectors containing VEGF gene 3'UTR site and detect microRNA binding stability.
Results:
The TT genotype resulted in a significant increase in ischemic stroke [OR, 1.679 (95% CI, 1.101-2.554), P 0.015]. But no association between genotypes and TOAST subtypes was shown. The novel finding was that the TT genotype of the VEGF was associated with poor outcome of recovery 3 months after stroke onset [OR, 2.143 (95% CI, 1.108-4.145), P 0.022]. MiR-199a could inhibit the expression of VEGF by directly binding to 3’UTR and C→T may influence the stability of this binding.
Conclusions:
IS patients with the TT genotype in the 3′-UTR of VEGF might affect stroke functional recovery by interfering with the binding efficiency of microRNA
Abstract 41: Mixed Vasopressin Antagonism as a Directed Therapy for Cerebral Edema in Acute Stroke Patients
Authors: Hedna Vishnumurthy S , Qureshi Mushtaq H , Mohammad Najwa S , Qureshi Adnan I
Published: March 2022

Introduction:
Conivaptan, a mixed vasopressin receptor (V1a and V2) antagonist approved by FDA for use in hypervolemic/euvolemic hyponatremia, reduces early cerebral edema in experimental stroke models through regulation of plasma osmolality and AQ-4/GFAP modulation

Hypothesis:
To evaluate the safety and effectiveness of conivaptan in reducing midline shift, brain volume, and neurological deficits in acute stroke patients.

Methods:
We analyzed clinical and radiological data collected from a prospective protocol. Patients (n=8) with acute stroke who demonstrated neurological deficits secondary to cerebral edema and demonstrated lack of improvement with hypertonic saline and serum sodium of 145 mmol or greater were included. Intravenous conivaptan 40 mg per day was administered and daily CT scans obtained for 3 days. Daily GCS score, fluid input/output, net brain volume, pineal shift and septum pellucidum shift were ascertained to assess the effectiveness of conivaptan. Since brain edema is maximum at 3-4 days of stroke onset, subgroup analysis of stroke patients (n=4) in whom time interval between symptom onset and conivaptan administration was in that range was undertaken.

Results:
Analysis revealed mean age 56 ± 15 years and gender ratio of 1 with average pineal shift increase from 2.42mm to 2.87mm, decrease in average septum pellucidum shift from 4.17mm to 3.29mm and improvement in mean GCS score from 7.25 to 9.12. Subgroup analysis of 4 patients who received conivaptan within 4 days demonstrated a decrease in the average pineal shift from 2.32mm to 2.02mm; average septum pellucidum shift decrease from 2.68mm to 2.48mm. Average GCS score of patients improved from 5.75 to 9.25. No significant changes were noted in the overall net brain volume.

Conclusions:
We observed clinical and radiological improvement after early administration (<4 days) of conivaptan in acute stroke patients as evidenced by reduction in the mean pineal gland and septum pellucidum shift and significant improvement in GCS. Further clinical safety trials are underway to study the efficacy of conivaptan in treatment of brain edema in acute ischemic and hemorrhagic stroke.
Abstract 46: Obstructive Sleep Apnea (OSA) Accelerates Cerebral Pathology in Spontaneously Hypertensive Stroke Prone Rat (SHRsp)
Authors: Lloyd Eric E , Durgan David J , Phillips Sherry C , Bryan Robert M
Published: March 2022

Cerebral small vessel disease (CSVD) and its pathological changes in small vessels in brain, is responsible for lacunar infarcts, white matter lesions, hemorrhages, microbleeds, and cognitive impairment. Although it has been suggested that OSA has a role in CSVD, there are no controlled studies relating OSA to CSVD and it pathological consequences. We tested the hypothesis that OSA in SHRsp rats, a model for CSVD, accelerates the development of associated brain pathologies. Chronic intermittent airway obstructions (termed OSA, 10 sec in duration, 60/hr, during 8 hr of the sleep cycle) were induced by remotely inflating balloons implanted in the tracheas of SHRsp and their parent strain, Wistar Kyoto rats (WKY). Studies were conducted at 12 and 20 weeks of age after being subjected to 14 days of OSA. Sham rats had balloons implanted but without inflations to occlude the airway. Systolic blood pressure was significantly increased in SHRsp with OSA by 58 ± 15 and 32 ± 7 mm Hg at 12 and 20 weeks respectively compared to SHRsp sham rats (n=7-10, p<0.05). Working memory as assessed by novel object recognition was impaired in the SHRsp with OSA at both 12 and 20 weeks (n=6, p<0.01). IgG extravasation, a measure of blood brain barrier integrity, was significantly increased (n=6, p<0.05) in small vessels of the 12 and 20 week SHRsp OSA groups. In the 12 week SHRsp OSA group the IgG extravasation was mainly present in the white matter small vessels, while in the 20 week SHRsp OSA group, which contained far greater (p<0.05, n=6) IgG positive small vessels, the majority of the IgG extravasation was found in the grey matter. Activation of microglia in the external capsule (as determined by morphometric analysis) was significantly greater in the SHRsp OSA group compared to all other groups of rats (n=6 each group, p<0.05). There was a significant loss of white matter as indicated by a 192 ± 10% increase (n=6, p<0.05) in the breakdown products of myelin basic protein in the SHRsp OSA group at 20 weeks but not at 12 weeks. We conclude that OSA in the SHRsp accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease.
Abstract 47: Renal Function, MRI Brain Changes and Post-stroke Cognitive Impairment
Authors: Auriel Eitan , Kliper Efrat , Shenhar-Tsarfaty Shani , Mike Anat , Ben-Bashat Dafna , Shopin Ludmila , Korczyn Amos D , Bornstein Natan M , Ben-Assayag Einor
Published: March 2022

Background and Purpose:
Limited data exist regarding the relationship between chronic kidney disease (CKD) and post-stroke cognitive impairment. We aimed to evaluate the impact of impaired renal function on markers of cerebral small vessel disease, brain pathology and cognitive decline in a longitudinal post-stroke cohort.

Methods:
The TABASCO study is a prospective cohort of mild-moderate ischemic stroke/TIA patients, who underwent a 3T MRI, and were assessed for their cognitive function at hospital admission, 6, 12 and 24 months following stroke, using the Montreal Cognitive Assessment (MoCA) and a computerized cognitive testing battery. Estimated renal function was evaluated at admission using the Cockcroft Gault creatinine clearance (CCl) equation. The volume and integrity of preexisting white matter hyperintensity (WMH), ischemic lesions and brain atrophy on MRI were measured.

Results:
Baseline data were available for 462 subjects (mean age 67.4 years, 60.4% males). Participants with a CCl <60 ml/min performed significantly worse in all cognitive tests over time (p<0.001) than those with a CCl ≥60 ml/min. CKD was also associated with enlarged WMH volume (p<0.001), cortical atrophy (p=0.002) and smaller hippocampal volume (p<0.001).

After the 2-years follow-up, 16% of the participants developed cognitive impairment.

Multiple logistic regression analysis controlling for traditional risk factors, including cardiovascular, showed a significant association of CCl <60 ml/min at baseline with development of cognitive impairment at the end of follow-up [odds ratio: 2.99 (95% confidence interval: 1.08-8.27), p = 0.035].

Conclusions:
Decreased renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor of lower performances in cognitive tests and cognitive decline 2 years after stroke/TIA. CKD may contribute to cerebral small vessel disease that underlies post-stroke cognitive decline, suggesting a new target for early intervention.
Abstract 69: Stroke Family Caregiver Perceptions of Palliative and End of Life Care Needs
Authors: McLennon Susan , Bakas Tamilyn , Jessup Nenette M
Published: March 2022

Background:
The purpose of palliative care is to reduce suffering and improve the quality of life of patients with serious illness and their families. Deaths and disability from stroke are anticipated to continue to increase because of the aging population. The palliative and end of life care needs for stroke survivors and their caregivers require greater attention.
Purpose: T
o describe stroke family caregiver perceptions of palliative and end of life care needs as they provided care for survivors who died within one year post-stroke.
Methods:
A subset of stroke caregivers enrolled in the Telephone Assessment and Skill-Building Intervention Study (TASK II) (NINR R01# NR010388) were analyzed for self-identified needs and concerns during the year before the survivor’s death (n=12). Caregivers averaged 58 years of age (Range 26-75), and most were female (75%), white (58%), and spouses (66%) who provided an average of 11 caregiving hours/day (Range 2-24). Stroke survivors were 50% female with a mean age of 71 years (Range 50-90). A qualitative content analysis of audio-recorded telephone interviews was performed and combined with caregiver descriptive data on needs and concerns.
Results:
The most frequently identified needs focused on the survivor’s care were managing medications (n=8; 67%), communicating with the survivor (n=6; 50%), getting the survivor to eat (n=3; 25%); and dealing with the survivor’s thinking and emotions (n=3; 25%). The most frequently identified needs focused on the caregiver’s own needs included managing their own emotions (n=6; 50%); taking care of their own health (n=5; 42%); managing cost of care (n=5; 42%); dealing with other things within one’s life (n=4; 33%); and finding books or resources that help (n=3; 25%).
Conclusions:
Palliative and end of life care should focus both on the survivor’s care, as well as the caregiver’s own needs. The caregiver’s perception of palliative and end of life care needs will become increasingly important in today’s health care system and will provide important areas to consider for future palliative and end of life care interventions. Further research is warranted to further explore palliative and end of life care needs from the perspective of stroke family caregivers.
Abstract 7: Dose Response Relationship in Transcranial Direct Current Stimulation Stroke Motor Recovery Studies
Authors: Feng Wuwei , Enabore Jan a , Kautz Steve , Adams Robert J , Chhatbar Pratik
Published: March 2022

Background:
Dozens of clinical trials investigated the potential efficacy of transcranial direct current stimulation (tDCS) in post-stroke motor recovery. Various current levels, pad size, number of sessions were used in different studies with mixed results in motor outcomes. We aimed to investigate a dose/current-response relationship by pooling published studies.

Methods:
We identified relevant studies in Pubmed, EMBASE and clinicaltrials.gov from January 1990 to June 2014. We included sham-controlled randomized or quasi-randomized studies with ≥5 tDCS sessions and derived percent improvement in primary endpoint (percent improvement in treatment group - percent improvement in sham group) from each study. We plotted current, current density, charge per session, charge density per session, total charge and charge density with percent improvement. To assess the dose-response relationship, we conducted regression analyses where studies were weighed by the number of participants (sample size).

Results:
We identified 8 studies with 272 subjects in total comparing active stimulation (anodal, cathodal or bi-hemispheric) with sham stimulation in terms of motor improvement. Pooling the results from these studies shows a positive dose/current-response relationship. Pearson’s correlation coefficients between percent improvement and current, current density, charge per session, charge density per session, total charge and charge density are –0.12, 0.2, 0.15, 0.27, 0.34 and 0.21, respectively.

Conclusion:
By pooling studies, a dose response relationship is revealed and is best demonstrated by charge density per session. Phase II trials may be considered to formally assess this relationship in stroke patients towards determination of optimal dose in large clinical trials.
Abstract 77: Histopathological Characteristics Of Iv Recombinant Tissue Plasminogen Resistant Thrombi In Patients With Acute Ischemic Stroke
Authors: Qureshi Mushtaq H , Lobanova Iryna , Suri Fareed K , Khan Asif A , Bologna Steve , Jahangir Nauman , Thompson Michelle , Qureshi Adnan I
Published: March 2022

Background:
It remains unclear whether certain thrombus characteristics in patients with acute ischemic stroke result in lack of lysis with IV rt-PA. We performed this study to evaluate the histopathological characteristics of in vivo thrombi retrieved from acute ischemic stroke patients resistant to IV rt-PA prior to endovascular treatment.

Methods:
The thrombus was removed from the device or retrieval catheter by gentle disassociation and processed for paraffin section preparation and hematoxylin and eosin (H&E) staining. Each slide was reviewed by an independent pathologist and classified as RBC dominant, fibrin dominant, and mixed based on the content. The characteristics were compared with thrombi retrieved from IV rt-PA naïve patients.

Results:
Thrombi were retrieved from a total of 19 patients (mean age±SD; 73.4 ±14.8 years) who underwent mechanical thrombectomy. IV rt-PA resistant thrombi were retrieved in 9 of 19 patients with a time interval (min±SD) between IV rt-PA initiation and thrombus retrieval of 174±48 mins. The IV rt-PA resistant thrombi were characterized as: RBC dominant (n=4), fibrin dominant (n=2), and mixed (n=3). The proportion of mixed thrombi were lower in those who did and who did not receive IV rt-PA prior to endovascular treatment (3 of 9 versus 5 of 10, p=0.2). The rates of partial or complete recanalization were similar between RBC dominant (8 of 9), fibrin dominant (2 of 2), and mixed thrombi (8 of 8, p=0.5). The time interval between symptom onset and thrombus retrieval was 349±98 min±SD for RBC dominant, 242±15 (min±SD) for fibrin dominant, and 456±313 (min±SD) for mixed thrombi (p=0.3).

Conclusions:
In our preliminary observations, we did not find any differences in histomorphology of IV rt-PA resistant and naïve thrombi in acute ischemic stroke patients.
Abstract 80: Trends in Anticoagulant-Associated Intracerebral Hemorrhage and Cardioembolic Ischemic Stroke
Authors: Flaherty Matthew L , Sekar Padmini , Alwell Kathleen , Moomaw Charles J , Ferioli Simona , Adeoye Opeolu , Martini Sharyl , Khoury Jane , Mackey Jason , De Los Rios La Rosa Felipe , Khatri Pooja , Woo Daniel , Broderick Joseph P , Kleindorfer Dawn , Kissela Brett M
Published: March 2022

Background:
The incidence of anticoagulant-associated intracerebral hemorrhage (AAICH) quintupled in our population in the 1990s, while rates of ischemic stroke attributed to atrial fibrillation remained stable. We now extend our study to examine incidence trends for these stroke subtypes through 2010.

Methods:
We identified all patients presenting to an emergency department or hospitalized with first-ever ICH in the Greater Cincinnati/Northern Kentucky region during 1988, from 7/93-6/94, and during 1999, 2005, and 2010. AAICH was defined as ICH in patients receiving warfarin, heparin, or a direct thrombin inhibitor. Patients from the same region presenting to an emergency department or hospitalized with first-ever ischemic stroke were identified during 1993/4, 1999, 2005, and 2010. Incidence rates were calculated and adjusted to the 2000 United States population. Estimates of warfarin distribution (in the form of “counting units”) in the United States were obtained for the years 1988 through 2010 from the MIDAS database of IMS Health, Inc.
Results:
AAICH occurred in 9 of 184 ICH cases (5%) in 1988, 23 of 267 cases (9%) in 1993/4, 54 of 311 cases (17%) in 1999, 63 of 320 cases (20%) in 2005, and 53 of 303 cases (17%) in 2010 (p < .001 for trend). The annual incidence of AAICH increased in the 1990s but remained stable from 1999 to 2010 (p = .29, see table). Incidence rates of ischemic stroke due to atrial fibrillation were stable in the 1990s but increased from 1999 to 2010 (p = .03, see table). Warfarin distribution in the United States quadrupled on a per-capita basis between 1988 and 1999 and grew at a slower rate thereafter.
Conclusions:
The incidence of AAICH quintupled during the 1990s but stabilized in the 2000s. The incidence of ischemic stroke due to atrial fibrillation has not declined in our population in the last two decades, despite increasing warfarin use.
Abstract 87: Prehospital Treatment with Magnesium Does not Prevent Ultra-Early Clinical Deterioration in Stroke
Authors: Sanossian Nerses , Liebeskind David S , Strakman Sidney , Eckstein Marc , Stratton Samuel , Pratt Franklin D , Hamilton Scott , Conwit Robin , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: March 2022

Background:
We had previously reported that deterioration of the clinical examination between paramedic evaluation and Emergency Department (ED) evaluation was associated with worse outcome in hyperacute stroke patients. Prehospital treatment with magnesium (Mg), a neuroprotective agent, may reduce rates of ultra-early clinical deterioration (UECD).

Methods:
All subjects from the NIH Field Administration of Stroke Therapy- Magnesium phase 3 clinical trial were randomized to intravenous Mg (4gm field loading dose followed by 16gm over 24 hours) or placebo and evaluated in the field by paramedics and in the ED by study nurses. UECL was defines as a worsening in the GCS by >=1 point. Outcome was assessed at 3 months using the modified Rankin score (mRS)

Results:
Among the 1700 enrolled patients (857 magnesium group, 843 placebo group), mean age was 69 (SD±13), 42.6% were female, final diagnosis of the presenting event was cerebral ischemia (CI) in 73.3%, intracranial hemorrhage (ICH) in 22.8%, and mimic in 3.9%. Median time from last known well to initial paramedic evaluation was 23 minutes (IQR 14-42) and to ED nurse evaluation was 150 minutes (120-180). UECD was noted in 311 (18%). Treatment with Magnesium did not affect rates of UECD in the overall population (19% vs. 17% p=0.307), those with CI (13% vs. 12%, p=0.318) and those with ICH (40% vs. 37%, p=0.557). Patients with UECD had very low rates of good outcome (mRS 0-2) overall (18% vs. 60%, p<0.001), in CI (23% vs. 63%, p<0.001) and ICH (11% vs 41%, p<0.001).

Conclusions:
Rates of ultra-early clinical deterioration were high, particularly among ICH patients presenting <2 hours from symptom onset. Treatment with magnesium had no effect on ultra-early clinical deterioration, which was associated with poor outcome. Future studies of prehospital therapy in stroke may consider using UECD as an outcome measure.
Abstract 91: Prehospital Blood Pressure Differentiates Acute Stroke From Mimics
Authors: Gioia Laura C , Zewude Rahel T , Kate Mahesh P , Liss Kim , Rowe Brian H , Butcher Ken
Published: March 2022

Introduction:
Elevated hospital admission blood pressure (BP) in acute stroke is common and associated with poor outcomes. The natural history of BP in suspected stroke patients in the prehospital setting is unknown. We tested the hypothesis that prehospital BP values are higher in acute stroke patients, relative to stroke mimics.

Methods:
We conducted a retrospective analysis of a prospectively-maintained centralized database of electronic patient health care reports (ePCR), including serial BP measurements, of all patients transported by Emergency Medical Services (EMS) to the Emergency Department (ED) of a single hospital with acute stroke symptoms during an 18-month period. All patients with an EMS dispatch code for suspected stroke were included. Hospital charts and neuroimaging review were utilized to determine final diagnosis of ischemic stroke, transient ischemic attack (TIA), intracerebral hemorrhage (ICH) or stroke mimic. BP data was analyzed by one-way ANOVA followed by Tukey’s test for independent comparisons.

Results:
A total of 877 patients were transported by EMS to the ED with suspected stroke. Median (IQR) time from symptom onset to first BP measurement was 70.5 (204) minutes. The final diagnosis was stroke in 524 (59.7%) patients (41.0% ischemic stroke, 11.7% TIA, 7.0% ICH) and 354 (40.4%) were considered mimics. Mean ± SD prehospital SBP was higher in acute stroke patients (155 ± 31 mmHg) compared to stroke mimics (143 ± 32 mmHg), p<0.001). Mean prehospital SBP was higher in ICH (171 ±33 mmHg, p=0.001) than both ischemic stroke (155 ± 27 mmHg) and TIA (153 ± 23 mmHg). SBP remained stable during EMS transport in all patients (median -3 (22) mmHg), p=0.16). Mean prehospital SBP was correlated with ED SBP (R=0.85, p<0.001). Mean SBP at ED arrival was higher in acute stroke patients (ICH: 170 ± 34 mmHg, ischemic stroke: 154 ± 30 mmHg, TIA: 153 ± 26 mmHg) than stroke mimics (142 ± 28 mmHg), p<0.001).

Conclusion:
Higher prehospital SBP differentiates acute stroke from stroke mimics. Blood pressures are highest in ICH patients. Prehospital BP remains stable until ED arrival. Elevated prehospital BP may help identify patients with acute stroke. Acute BP elevation may also represent an acute prehospital treatment target.
Abstract 97: Ischemic Lesions in Intracerebral Hemorrhage Associated with Drop in Blood Pressure and Poor Outcomes in the ERICH Study
Authors: Kidwell Chelsea S , Norato Gina , Osborne Jennifer , Worrall Bradford B , James Michael L , Elkind Mitchell S , Flaherty Matthew , Rosand Jonathan , Vashkevich Anastasia , Langefeld Carl D , Moomaw Charles J , Woo Daniel
Published: March 2022

Background:
Up to 1/3 of patients with primary intracerebral hemorrhage (ICH) have acute ischemic lesions remote from the hematoma visualized on diffusion-weighted MRI (DWI). Prior reports associated these lesions with large blood pressure fluctuations in the acute hospital setting. Here, the Ethnic/Racial variations of Intracerebral Hemorrhage (ERICH) study explored predictors of ischemic lesions in primary ICH and their impact on long-term outcomes.

Methods:
ERICH is a multi-center, prospective study of ICH among white, black, and Hispanic patients. At least every 5th patient undergoes a study MRI interpreted by a central core blinded to clinical data. We calculated change in mean arterial pressure (delta MAP) by taking the difference in highest and lowest blood pressure prior to MRI.

Results:
For the 601 cases with a DWI MRI, mean±SD age was 61±14 years, mean ICH volume was 16±18 cc, 55% were male, 79% had hypertension and 26% had ≥1 DWI lesions. The frequency of DWI lesions differed by ethnicity (blacks 33%, Hispanics 24%, whites 20%, overall p=0.005). The multivariable logistic regression analysis identified lower age (10 year OR=0.68, p<0.001), higher delta MAP (10 unit OR=1.16, p<0.001), higher WMD score (1 unit OR=1.164, p<0.001) and presence of microbleeds (OR=2.122, p=0.001) as predictors of DWI lesions. After controlling for age, ICH volume, IVH and admission GCS, presence of DWI lesions was associated with 6 month poor outcome (MRS 4-6, OR=1.25, p=0.02; Figure).

Conclusions:
The ERICH study confirms that large fluctuations in blood pressure during the acute hospitalization period predict DWI lesions, and that DWI lesions predict poor outcomes. We hypothesize that substantial reductions in blood pressure precipitate acute small vessel ischemia in those ICH patients with a more severe underlying diseased vasculature. Further studies are needed to determine whether there is a level of acute blood pressure reduction at which the risks outweigh the benefits.
Abstract NS12: Is Online NIHSS Certification Enough Training
Authors: McDavid John C , Bellamy Lisa M , Thompson Christa J
Published: March 2022

Background:
The NIHSS is used for the initial assessment of patients with acute stroke for hospitals seeking Primary Stroke Center certification by The Joint Commission. There is a gap between online education and performance at the bedside. By implementing face-to-face instruction, scenario based return competency and remediation, we can we can narrow the gap between e-learning and application.

Methods:
In a rural hospital pursuing Primary Stroke Center certification, nurses from the ED, ICU, Medical-Surgical, and the Float Pool were required to complete NIHSS training within 6 weeks. The training was divided into multiple phases. During the first phase, the nurses completed the online NIHSS certification appropriate for their respective group to complete. In addition to the mandatory online certification course, face-to-face instruction was offered to supplement the online training. In the second phase, the nurses’ competency was evaluated in a simulated scenario. The third phase was reserved for the nurses that failed the competency evaluation. They were required to receive face-to-face instruction as a remedial measure and repeat the competency evaluation. All nurses received the training from the same two nursing educators with a critical care background.

Results:
Of the 114 nurses that completed the first two phases of training 36 (32%) failed the competency in phase two. The total of failure per specialty in the overall group that failed: Med-Surg 19 (53%), ICU 10 (28%), ED 5 (14%), and Float Pool 2 (0.06%). Eight (89%) of nurses that voluntarily completed the face-to-face instruction in phase one passed the evaluation in phase two. In the third phase, 36 (100%) nurses that received remedial face-to-face instruction passed the repeat competency evaluation. Failure rate according to level of group certification was NIHSS Group A 35 (97%) and Group B 1 (0.03%).

Discussion:
Face-to-face instruction clearly enhances stroke assessment. Every nurse (n=36) passed the competency evaluation after receiving remedial face-to-face instruction, and of those nurses who opted to supplement their online training with face-to-face instruction before their initial competency evaluation, 8 (89%) passed.
Abstract NS17: Caregiving Needs of Family Caregivers of Latino Stroke Survivors
Authors: Vaughn Stephanie
Published: March 2022

Background/purpose:
Latinos are at higher risk for stroke at a younger age due to multiple factors and stroke care is usually provided by family members in the home setting (familism). Caregiver information is procured in various ways; more often via “word of mouth” from family/friends versus healthcare providers. Culture, religion, and knowledge of stroke/resources or lack thereof, all impact the Latino caregiver. The purpose of this study was to examine perceived needs and resources of family caregivers of Latino stroke survivors.

Method:
Ethnography was used to examine the perspectives/practices of Latino stroke caregivers. Participants were solicited from a Stroke Support Group in Southern CA. Data were collected via a focus group interview of six family caregivers in Spanish/English after informed consents were signed. Interview data/field notes were recorded. Thematic analysis of the interviews /notes was performed.

Results:
The mean age of the caregivers was 35 years. The average number of daily care hours was reported as 10-12. All were new caregivers within the last 12 months. Three themes were revealed. The first theme was, “caring for family.” All caregivers received some information; however few sought outside resources related to language, finances, distrust of outside caregivers, or transportation. Caregivers served as “gatekeepers” regarding the stroke survivors’ health. Another theme was, “hope for survivor’s recovery.” Although some caregivers experienced fatigue and stress, they were optimistic for their loved one’s recovery. The third theme was, “what’s next?” Caregivers often did not know where to access resources beyond the MD office or clinic; expressed anxiety about outside services, and usually relied solely on family/friends for information and support.

Conclusions:
Stroke family caregivers need providers to look “within culture “and be sensitive to the needs of the Latino family; provide caregiver classes in Spanish/English that highlight stroke/caregiver information, identify informal support, and seek affordable community options for services, such as stroke support groups in Latino communities; all of which can enhance the caregiver’s experience and promote positive stroke outcomes.
Abstract NS24: Algorithm Development to Improve Transient Ischemic Attack Outcomes
Authors: Marshman Mary
Published: March 2022

Background and Purpose:
Management of care for the patient experiencing a transient ischemic attack (TIA) is inconsistent and compromises patient outcomes. This is due to the absence of a clearly defined protocol for TIA aimed at expediting care to reduce delays in diagnosis and treatment. The purpose of this study was to establish an evidence-based method for early identification, assessment, and consistent treatment of TIA.

Methods:
A TIA algorithm was designed and implemented based on translation of current evidence. Effectiveness of the algorithm was determined by comparing two separate groups using secondary data analysis of patients presenting to emergency department triage diagnosed with TIA six months prior to implementation of the algorithm (n= 80) and six months following implementation (n= 67). Patients in the implementation group received the evaluation and treatment outlined in the algorithm as the new standard of care. Primary outcomes were analyzed using a Chi-Square test of independence to evaluate recurrent ischemic events post-index TIA and independent samples
t
-tests for measuring length of stay (LOS) and total direct costs of care.

Results:
Significant reductions in overall direct costs of care [
t
(121) = 7.23,
p
= .001,
d
= 1.20] and LOS [
t
(142) = 2.40,
p
= .018,
d
= 0.40] associated with consistency in diagnostic testing and patient disposition were found. Recurrent TIA [

X
2

(1, N = 147) = 1.52,
p=
.22,
r
2
= 0.01] and stroke [

X
2

(1, N = 147) = 2.83,
p=
.093,
r
2
= 0.02] events post-index TIA were noted within the implementation group. Although not significant in this sample size, the clinical importance of findings demonstrated a 7.2% difference in overall stroke events with no recurrence of TIA as evaluated at 2, 30, 60, and 90-day time intervals.

Conclusions:
Findings from this study demonstrated that the use of a TIA algorithm was successful in guiding the interdisciplinary team to impact outcomes for the patient at risk for stroke. Recommendations for further testing of the algorithm in a multi-site cohort study would allow for a larger sample to evaluate this disease specific care model.