bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P227: Analysis of Gender and Time to Arrival Among Ischemic Stroke Patients in the Greater Cincinnati/ Northern Kentucky Stroke Study
Authors: Madsen Tracy E , Sucharew Heidi , Katz Brian , Alwell Kathleen A , Moomaw Charles J , Kissela Brett M , Flaherty Matthew L , Woo Danielle , Khatri Pooja , Ferioli Simona , Mackey Jason , Martini Sharyl , De Los Rios La Rosa Felipe , Kleindorfer Dawn
Published: March 2022

Background/ Purpose:
Some studies of stroke patients report longer pre-hospital delays in women but vary in their inclusion of factors such as living situation and stroke severity. Other literature suggests gender differences in pre-hospital delays are more prominent in older age groups. The aim of our study was to investigate the relationship between gender and time to ED arrival and the influence of age and stroke severity on this relationship.

Methods:
Ischemic stroke patients ≥20 years old presenting to 16 area hospitals within a 5 county region of Greater Cincinnati/ Northern Kentucky during 2010 were included. Data on time from symptom onset to ED arrival and covariates were abstracted by study nurses and reviewed by study physicians. Data were analyzed using logistic regression with time to arrival dichotomized at ≤ 3 hours, overall and stratified by NIHSS and age categories.

Results:
2026 strokes (54% women, 22% black) were included. Time to arrival was not significantly different in women (geometric mean 335 minutes (95% CI 306 - 368) vs. 302 (95%CI 273 – 334), p =.14), and 24% of women vs. 27% of men arrived within 3 hours (p=0.20). More women lived alone (30% vs. 23%, p<.01). Women had a higher median age (74, IQR 60 - 84 vs. 67, IQR 57 – 79, p<.01) and were less likely to have mild stroke (NIHSS≤5) (67% vs. 74%, p<.01). Gender was not associated with delayed time to arrival (OR=1.00, 95%CI 0.79 - 1.27), after adjusting for age, NIHSS, race, insurance status, marital status, living situation, EMS use, pre-stroke mRS, wake-up stroke, night arrival, and prior stroke. Interactions between gender and age and gender and NIHSS were not significant. Those with NIHSS≤5 or who lived alone were less likely to arrive within 3 hours (Table).

Conclusions:
After adjusting for factors including age, NIHSS, and living alone, women and men with ischemic stroke had similar times to arrival. The relationship between gender and time to arrival did not change significantly across age or NIHSS categories.
Abstract W P236: Role of Leukocyte Cathepsin G in an Atherothrombotic Stroke Model
Authors: Schunke Kathryn J , Koehler Raymond C , Faraday Nauder
Published: March 2022

The majority of ischemic strokes in humans are caused by atheroemboli that originate from extracranial vessels, activate platelets and produce thrombi that occlude intracranial vessels. Most of the current stroke models do not simulate the mechanisms of endogenous thrombus interaction with blood elements, the vascular wall and its extracellular matrix, and thus do not translate well for the study of atherothrombotic mechanisms. To overcome these shortcomings, we developed an atherothrombotic stroke model. We used this model to determine the pathophysiologic role of leukocyte cathepsin G, a serine protease with pro-thrombotic properties, in stroke and to determine its suitability as a molecular target for therapy. We hypothesized that deficiency of cathepsin G will reduce intravascular thrombus formation, decrease infarct volume and improve neurobehavioral deficit in a mouse atherothrombotic stroke model.

Male C57Bl/6 (WT) and cathepsin G knockout mice (CG-/-) were used. A PE8 catheter was advanced into the ICA near the MCA origin and a reduction in cortical laser-Doppler flow was induced after a series of intra-arterial injections of collagen, a platelet activator and component of ruptured atherosclerotic plaque. Mice were sacrificed 3h post-collagen injection for histologic examination, or 48h post-collagen for infarct volume quantification and neurobehavioral assessment.

Gross examination of excised brains 3h post-collagen revealed thrombi within the main ICA in 71% (5/7) of WT mice and 0% of CG-/- mice (p=0.005), branches of the ICA in 0 WT mice and 29% (2/7) of CG-/- mice (p=0.13), in the main MCA in 43% (3/7) of WT mice and 0 CG-/- mice (p=0.05), and distal branches of the MCA in 100% (7/7) of WT and CG-/- mice. Immunofluorescence microscopy confirmed that platelets and fibrin were major components of these thrombi. Cerebral infarct in WT mice was 33% ± 9% of hemispheric volume and 19% ± 1% in CG-/- mice (p=0.02). Neurobehavioral deficit 48h post-collagen was reduced in CG-/- mice compared to WT.

Using a novel atherothrombotic stroke model, these data reveal an important role of cathepsin G in cerebrovascular thrombus formation and a novel mechanism linking inflammatory cells to ischemic brain injury- a link commonly observed in human clinical studies.
Abstract W P239: Exposure to Airborne Particulate Matter from Vehicular Exhaust Results in Progression of Brain Injury Following Experimental Stroke
Authors: LIu Qinghai , Radwanski Ryan , Babadjouni Robin , Baumbacher Peter , Russin Jonathan , He Shuhan , Morgan Todd , Sioutas Constantinos , Finch Caleb , Mack William
Published: March 2022

Inflammation is believed to play an important role in the progression of acute stroke. Air pollution is a potent environmental source of inflammation and oxidative stress. We sought to examine the impact of inhalation of airborne particulate matter (PM) derived from urban traffic on the progression of brain injury following acute stroke. Urban PM was collected with a particle sampler situated near the CA-110 Freeway in Los Angeles. Collected aerosols represented a mix of fresh PM, predominantly from vehicular traffic. These samples were then distilled to pollutant nanoparticles (<200 nm) and re-aerosolized for administration to mice through exposure chambers. Adult mice were exposed to aerosolized PM (n=12) or filtered air (n=12) for forty-five cumulative hours and then underwent middle cerebral artery ischemia (35 minutes)/ reperfusion (I/R). Infarct volumes and neurological function were compared between mice exposed to PM and filtered air on postoperative day 1. Reperfusion was assessed by percent recovery of blood flow on laser Doppler flowmetry (LDF). Following cerebral I/R, mice exposed to PM demonstrated larger infarct volumes [20.6 ±6.4% (n=8) vs. 11.3 ±6.6% (n=9); p=0.018] and less favorable neurological scores [5.8 ±2.96 (n=12) vs. 3.2 ±2.4 (n=12); p=0.019] when compared to mice exposed to filtered air. Mortality was higher for the PM cohort (8.3% vs. 0%, p=ns) Further, LDF demonstrated decreased reperfusion in the cohort of mice exposed to PM (64 ±39%, n=10) when compared to those exposed to filtered air (86 ±24%, n=10, p=ns). This data establishes a detrimental effect of particulate matter in the setting of acute stroke and suggests a potential inflammatory mechanism of action.
Abstract W P242: Role of Hippocampal Estrogen Receptor α and Src in Sexually Differential Phosphorylation of Tyrosine kinase-B receptors
Authors: Cengiz Pelin , Cikla Ulas , Chanana Vishal , Kinter Douglas , Sun Wendy , Udho Eshwar , Otles Arel , Ferrazzano Peter , Shaphiro Robert , Levine Jon
Published: March 2022

Introduction:
Male neonate brains are more susceptible to the effects of hypoxic ischemic encephalopathy (HI) as compared to females with comparable brain injury. Our recent findings reveal that HI induces an increase in phosphorylation of tyrosine kinase-B receptors (TrkB) in female hippocampi and TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), exerts profound early and late neuroprotective effects in female but not in male neonates. We hypothesized that differential TrkB phosphorylation seen in females is associated with increased hippocampal estrogen receptor α (ERα) expression and src (Src family kinase) phosphorylation resulting in decreased apoptosis post-HI.

Methods:
WT (ERα+/+) and KO (ERα-/-) P9 male and female mice pups were subjected to Vannucci’s neonatal HI model by left common carotid artery cauterization and exposure of the pups to 10% O2 at 37°C for 50 min. Pups were either sham or HI operated and given PBS or 7,8-DHF (5 mg/kg in PBS, ip.) starting at 10 min, then at 24 h, and 48 h post HI. Hippocampi were dissected out for either immunoblotting or qRTPCR 3d post-HI. We assessed the effects of sex (M vs F), treatment (PBS vs 7,8-DHF) and HI (sham vs HI) on immunoblotting band densities [pTrkB)/full length TrkB, ERα/actin, p-src/total src, cleaved caspase 3 (cc3)/actin ratios] and qRTPCR results using ANOVA analysis.

Results:
HI and 7,8-DHF differentially increase p-TrkB and p-src in WT female hippocampi 3 d post-HI (p < 0.0001). HI induces a 2.3 fold increase in ERα mRNA and protein expression in female hippocampi compared to the males 3d post-HI (p=0.002). HI and 7,8-DHF fail to increase p-TrkB and p-src in KO male and female mice suggesting that the TrkB and src phosphorylation are dependent on the ERα signaling in the neonatal hippocampi post-HI. Cc3 levels are found to be increased in KO mice while the 7,8-DHF treated WT female hippocampi had decreased cc3 expression.

Conclusion:
Sexually differential phosphorylation of TrkB and src are abolished in KO mice suggesting an important role of ERα in TrkB phosphorylation and src activation resulting in decreased apoptosis in female hippocampi post-HI. This mechanism might be one of the mechanisms that makes the male neonate brains more susceptible to the effects of HI.
Abstract W P256: Voxel-by-Voxel Distribution Pattern of Estimates of Vascular Volume and that of Blood-to-brain Forward Volume Transfer Constant are different in Experimental Embolic Stroke
Authors: Nagaraja Tavarekere N , Aryal Madhava P , Keenan Kelly , Ewing James R , Knight Robert A
Published: March 2022

Background and Purpose:
Changes in vascular indices such as blood-to-brain forward volume transfer constant (Ktrans) and plasma distribution volume (vp) are considered as potential predictors of impending hemorrhage in acute stroke. However, few studies have reported their spatial distributions and variability within a given stroke lesion. This study examined the voxel-by-voxel distributions of vp and Ktrans within a region of interest (ROI) and the overall mean for the entire ROI to investigate their possible inherent variability.

Methods:
Male Wistar rats (~300 g; N=6) were subjected to embolic occlusion of the middle cerebral artery for 2 h followed by treatment with recombinant tissue plasminogen activator (rTPA) treatment for thrombolysis. Measurements of vp and Ktrans were made in the ischemic lesion after rTPA infusion using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Data were generated using two approaches. In the first, voxel-by-voxel values of moments about the mean viz., median and skewness. In the second, values were summed across the ROI producing a mean and standard deviation. Differences between the two means were assessed by t-tests and significance inferred at p≤0.05.

Results:
The voxel-by-voxel estimates of vp were larger (0.025+0.008) than the summed mean (0.016+0.005), the difference being marginally significant (p=0.05). A positive skew value of 1.88 was obtained for the data and accordingly the median value (0.019) was lower than the mean. In contrast, voxel -based estimate of Ktrans (0.002+0.001) was not different from the summed mean (0.002+0.001; p>0.05). The median value for Ktrans (0.002) was not significantly different from the mean (p>0.05) suggesting a more uniform distribution of the data across the voxels with a very low skewness (0.05).

Conclusions:
These observations suggest that the voxel-by-voxel distributions can be dissimilar for the different indices of vascular injury within a given ischemic lesion. Such variations may be representative of varying degrees of damage and, consequently, may also represent the effects of a putative treatment. Understanding the tissue pathology determining these variations can assist in employing them as biomarkers of injury and response to treatment.
Abstract W P257: Progesterone Improves Long-term Neurobehavioral Outcome in Models of Intracerebral Hemorrhage (ICH)
Authors: James Michael L , Lei Beilei , Sheng Huaxin , Dawson Hana , Jeong Seongtae , Hsieh Justin , Laskowitz Daniel T , Warner David S
Published: March 2022

Introduction:
Progesterone is known to improve recovery in traumatic and ischemic brain injury models. For potential translation, the present study sought to define efficacy of exogenous progesterone administration in murine models of ICH.

Methods:
Young and aged C57/Bl6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.075U) or autologous whole blood (35ul) injection. Mice were randomized to receive progesterone at pre-specified doses (4-16 mg/kg), administered SQ at 2 and 5 hours after injury and then daily for 3 days. Rotorod (RR) and water maze (WM) latencies were measured by blinded observers on Days 1-7 and Days 28-31 after injury, respectively. Hematoma volume, brain water content, stereology of complementary immunohistochemistry, and multiplex cytokine arrays were measured at pre-specified time points after injury.

Results:
Progesterone (4mg/kg) administration after injury increased RR and decrease WM latencies (See Figure), decreased cerebral edema (p=0.03), and decreased microglial proliferation and activation in young and aged male and OVX, but not female mice, while maintaining stable hematoma volumes. Progesterone (4mg/kg) administration also increased RR latencies and decreased cerebral edema in male mice after autologous blood injection. In male mice only, progesterone (4mg/kg) reduced brain IL6, TNF-α and KC/GRO production in multiplex cytokine measurement after injury.

Conclusions:
Progesterone improves neurobehavioral recovery in male and OVX, but not gonad-intact female, mice by modulating neuroinflammation after ICH. Future study should address timing and length of administration prior to translation to clinical trial.
Abstract W P258: Alpha-2-antiplasmin Inactivation Reduces Brain Injury, Hemorrhage and Death Following Ischemic Stroke
Authors: Reed Guy , Houng Aiilyan , Wang Dong
Published: March 2022

INTRODUCTION:
High levels of a2-antiplasmin (a2AP) have been linked to failure of tissue plasminogen activator therapy, but the overall role of a2AP in ischemic stroke is poorly understood. HYPOTHESIS: We examined the hypothesis that a2AP may contribute to the pathogenesis of ischemic stroke. METHODS: The effects of a2AP blood levels and a2AP inactivation on stroke outcomes were examined in a model of middle cerebral artery thromboembolism. RESULTS: There was a dose-dependent relationship between a2AP blood levels and stroke outcomes. Deficiency of circulating a2AP had protective effects in ischemic stroke; it increased dissolution of the culprit middle cerebral artery thromboembolus (p<0.001), enhanced hemispheric blood flow and markedly reduced brain injury (p<0.001). Increased a2AP levels had opposite and harmful effects; it reduced middle cerebral artery thrombus dissolution (p<0.001), worsened brain injury (p<0.001) and swelling (p<0.001). Higher levels of a2AP significantly increased, and a2AP deficiency significantly reduced, microvascular thrombosis in the ischemic hemisphere. Treatment of mice with a monoclonal antibody that inactivated a2AP, either in the form of whole IgG or Fab, significantly reduced brain infarction, swelling and hemorrhage by comparison to controls, or to treatment with tissue plasminogen activator. Treatment with an a2AP inactivating antibody after cerebral thromboembolism also prevented death and disability. CONCLUSIONS: In cerebral thromboembolism, a2AP has dose-related, injurious effects that increase ischemic brain injury, hemorrhage, microvascular thrombosis and brain swelling. Therapeutic inactivation of a2AP markedly reduced these injurious effects and saved lives after ischemic stroke.
Abstract W P259: Selective Intra-arterial Administration of Verapamil is Neuroprotective in Acute Ischemic Stroke
Authors: Maniskas Michael E , Bix Gregory J , Fraser Justin F
Published: March 2022

Despite the urgent need for better stroke therapies, experimental stroke treatments have largely failed to translate to stroke patients. In an effort to bridge this translational gap, we have concentrated our efforts on drugs that are already FDA approved and associated with treating stroke-associated pathophysiology, such as cerebral artery vasospasm, with the goal of repurposing them to protect brain tissue from ischemic injury. Verapamil, a calcium channel blocker, is one such drug that is often infused intra-arterially by neurosurgeons treating vasospasm that results in ischemia. In demonstrating a reliable and reproducible stroke mouse model ( transient middle cerebral artery occlusion, MCAo) with the addition of a retro-engineered IA drug delivery model mimicking the human condition, we were able to optimize the injection volume and flow rate for pharmacotherapy administration of verapamil. Through this direct route of administration we have shown a significant decrease (P<0.001) in infarct volume and trending towards significance an increase in behavioral outcome when comparing treated animals versus control. Perfusion studies did not show significant differences in perfusion to account for vasomotor changes as the likely mechanism for ischemia reduction. To further explore this, after 1 hour MCAo in three month old C57/Bl6 mice, we examined the potential neuroprotective effects of verapamil on post stroke day 3. Whole brains were harvested and flash frozen for cryostat sectioning and cellular staining to compare apoptosis, appearance of mature neurons, astrocyte activation and synaptic stability. Results suggest that IA administration of verapamil, more specifically than reducing infarct volume, is directly neuroprotective on brain parenchymal tissue at risk.
Abstract W P264: Imaging Cerebrovascular Reserve using Blood Flow and Oxygenation Level Dependent: A Study using Acetazolamide Challenge
Authors: Qiu Deqiang , Nahab Fadi , Dehkharghani Seena
Published: March 2022

Introduction:
Cerebrovascular reserve (CVR) capacity in patients with chronic stenosis or occlusion of major arteries including the carotid provides valuable information in predicting their risks of developing strokes subsequently1. In the current study, we compared CVR assessment using two MRI methods ASL (arterial spin labeling) and BOLD (blood oxygenation level dependent) with the injection of acetazolamide (Diamox).

Method:
A multi-delay ASL (10 post-label delays, first TI=300ms, increment=300ms) sequence was acquired before the injection of Diamox, the BOLD sequence was started for continuous acquisition, 1-5 minutes of baseline images were acquired before the 3-minute infusion, the BOLD sequence ends 15 minutes from the start of Diamox injection. A post-Diamox ASL was then acquired. The CVR was then measured using two metrics for both ASL (CVRasl) and BOLD (CVRbold) to compare the agreement between the two methods.

Results & Discussions:
CVR metrics using both ASL and BOLD were reliably obtained in nine patients. Results showed complementary values of both ASL and BOLD CVR measurement. Figure 1(a-f) shows the ASL and BOLD maps as well the CVR metrics in one of the patients. CVRasl map suggests that there is an augmentation deficit in the left posterior region of the brain (arrows in Figure 1g), while strong augmentation was observed in BOLD signal, consistent with high CBF values observed in the DSC CBF map (Fig. 1d). In agreement with hypothesis, BOLD provides complementary information in such regions. Interestingly, in both cases we observed a transient reduction of BOLD signal following the injection of Diamox (see Figure 1f), possibly due to transient increase of the CBV due to the effects of Diamox, similar to the classic observation of “initial dip” of BOLD signal due to task. In conclusion, combining CBF measurement using ASL and BOLD is a promising MR method for assessing cerebrovascular reserve capacity.

References:
1. Gupta A. Stroke. 2012; 43:2884-91.
Abstract W P268: Language Discordance Between Patient and Treating Physician Does Not Delay Time to Thrombolysis
Authors: Rostanski Sara K , Williams Olajide , Marshall Randolph S , Stillman Joshua , Willey Joshua Z
Published: March 2022

Introduction:
Shorter door-to-needle time (DNT) is associated with better outcomes in acute ischemic stroke. Reducing door-to-CT time is a major focus of national quality improvement initiatives designed to reduce DNT, however time from CT-to-tPA administration has received far less attention. Recent data suggests that the CT-to-tPA interval contributes to significant delays in DNT. We hypothesized that language barriers between patients and treating neurologists would lead to longer CT-to-tPA times at a single stroke center serving a large Spanish-speaking population.

Methods:
We retrospectively reviewed the electronic medical record (EMR) on all patients who received IV-tPA in the emergency department over 2.5 years (July 2011 to December 2013). Patient’s primary language was obtained from the EMR; language fluency of treating neurologists was self-reported via standardized questionnaire. We compared baseline characteristics and relevant time intervals between encounters where the treating neurologist and patient spoke the same language (concordant group) versus those where they spoke a different language (discordant group). Means were compared with t-tests, medians with Mann-Whitney U tests, and dichotomized variables with Fisher exact tests.

Results:
A total of 199 patients received IV-tPA during the study period. English was the primary language for 110, Spanish for 83, and other languages for 6; of these, 120 cases were classified as concordant and 79 as discordant. There were no significant differences in mean age (67 vs. 69, p=0.3), male sex (37.5% vs. 24.1%, p=0.06), and median NIHSS (7 vs. 6, p=0.9) between concordant and discordant groups. We found no differences between median onset-to-arrival (68 vs. 71, p=0.3), door-to-CT (25 vs. 25, p=0.8), CT-to-tPA (33 vs. 29, p=0.2) and DNT (61 vs. 60, p=0.3) in minutes. There was a trend towards a greater proportion of patients with CT-to-tPA time under 30 minutes in the discordant group (52% vs. 38%, p=0.08).

Conclusion:
At our institution, language discordancy did not contribute to delays in CT-to-tPA nor overall DNT. CT-to-tPA time represents a largely unexplored contributor to overall delays in DNT that warrants further investigation.
Abstract W P277: 30 Day Readmission Rates are Higher at Primary Stroke Centers than at Comprehensive Stroke Centers
Authors: Diebolt Elizabeth , Song Sarah , Ouyang Bichun , Cutting Shawna
Published: March 2022

Objective:
To compare readmission rates between The Joint Commission designated Primary and Comprehensive Stroke Centers.

Background:
The Joint Commission (TJC) designations of Primary Stroke Center (PSC) and Comprehensive Stroke Center (CSC) certification recognize best practices in stroke patient care. TJC introduced the CSC designation to recognize programs that provide a higher level of care than PSCs, including 24-hour MRI, specialized neuro-intensive care units, and 24-hour endovascular treatment. It is unknown whether clinical outcomes, such as readmission rates and length of stay, differ between PSCs and CSCs.

Methods:
The University HealthSystem Consortium (UHC) is made up of 120 member academic medical centers who share hospital level data. Using UHC’s Clinical Database, we assessed 30 day readmission rates at PSCs and CSCs for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage patients for 2013, along with length of stay (LOS), ICU admission, and overall mortality rate. UHC’s expected mortality rate was derived using an algorithm based on clinical factors including severity of illness, co-morbidities, and patient demographics; this expected mortality rate was used as a measure of patient acuity. Ischemic stroke patients’ 30 day readmission rates, LOS, ICU admission, overall mortality rate, and expected mortality rate were also compared between PSCs and CSCs.

Results:
There were a total of 54,962 patients admitted to 75 PSCs and 38 CSCs. 30 day readmission rates were 2.70% for PSCs and 2.39% for CSCs (p=0.03). LOS was longer at CSCs than at PSCs (8.07 vs. 7.51 days, p<0.001). PSCs had a lower proportion of ICU cases (43.34% vs 58.57%), a lower mortality rate (9.20% vs. 11.05%), and a lower expected mortality rate than CSCs (p<0.001 for all). When analyzing only ischemic strokes, the 30 day readmission rate remained higher at PSCs (2.65% vs 2.13%, p=0.001) with shorter LOS (5.63 vs. 5.97 days, p<0.001).

Conclusion:
In our study, CSCs had statistically significant lower 30 day readmission rates than PSCs. However, stroke patients at CSCs had longer hospital stays and required a higher acuity of care. Future research is needed to define aspects of hospital care at designated CSCs that could lead towards reduced readmissions.
Abstract W P279: Cost-efficiency of Prehospital Stroke Treatment
Authors: Fassbender Klaus C , Walter Silke , Ragoschke-Schumm Andreas , Haass Anton , Dietrich Martin
Published: March 2022

Background:
In acute stroke, time until treatment is crucial for good outcome. Recently, we and others showed that prehospital stroke treatment, based on an ambulance equipped with a CT scanner, point-of-care laboratory and telemedical capabilities, markedly reduces delay until thrombolysis of acute stroke. However, high costs are a major criticism of this novel stroke management strategy.

Methods:
We simulated costs of prehospital stroke treatment based on data of the first randomized trial (Walter et al., Lancet Neurology 2012) and on secondary data. We assumed a regional specific incidence rate per year and combined current NNT results and estimations of total direct cost per year from secondary sources with results from the controlled trial. Based on these assumptions a range of probable benefit-cost ratios was calculated.

Results:
Based on different economic assumptions and on statistical projections from the study sample upon the relevant population our estimations indicate that on a one year basis the economic benefit outweighs the cost of the intervention in a range of benefit-cost ratios between 2.7 and 7.3. Due to the relatively high rate of utilization cost-efficiency might be higher in urban than in rural regions, although underserved rural regions might have an especially high medical benefit. As further key factors in cost-efficiency we also identified the size and configuration of the ambulance staff and cost of the ambulance itself.

Conclusion:
Prehospital stroke treatment is not only efficient in saving crucial time until treatment but also can be cost-efficient. Key factors are, apart from the frequency of utilization, expenses for the staff and for the ambulance. In the future, technical progress of telemedical interaction between ambulance and hospital could allow further reduction of costs.
Abstract W P282: Delays in Presentation to Stroke Prevention Clinic after TIA or Minor Stroke are Associated with Increased Recurrent Events, Hospitalization and Mortality
Authors: Blacquiere Dylan , Perry Jeff , Stotts Grant , Bourgoin Aline , Pugliese Michael , Sutherland Jane , Van Gaal Steven , Dowlatshahi Dar , Sharma Mukul
Published: March 2022

Background:
Prompt assessment in a stroke prevention clinic (SPC) reduces the risk of recurrent stroke after transient ischemic attack (TIA) or minor stroke. However, not all patients are seen rapidly, even in high-risk TIAs with speech deficits or unilateral weakness. The effects of delays on patient outcomes are not clear. We examined the records of patients referred after TIA/minor stroke to determine frequency, degree and reasons for delays in evaluation and carotid revascularization, as well as the effect of delays on patient outcomes.

Methods:
Records were obtained for all referrals to a regional SPC over 3 years. Target times were based upon triage symptoms, with highest-risk patients (unilateral weakness/speech deficits) being seen 2 days from receipt of referral, moderate-to-high risk within 7 days, and others within 30 days. Data regarding presentation, triage/referral, appointment, investigations and carotid revascularization were obtained. Delays between time points were calculated, and delay reasons were adjudicated. 90-day outcomes including death, recurrent stroke/TIA, and hospital readmission were determined, and comparisons made between patients with and without assessment delays.

Results:
Between 2009-11, 3492 patients were referred. 1420 (35.8%) were seen beyond suggested dates; the most common reason was scheduling issues (74.2%) followed by patient cancellation (7.9%) and hospitalization (6.0%). The average delay was 2.63 days (SD 7.48), increasing to 3.75 days (SD 5.35) in highest-risk patients. 79 (2.26%) patients had carotid revascularization; of these, 71 (90%) had surgery more than two weeks after onset. Delays were most often due to logistical issues (42.3%). Overall, assessment delays were associated with an absolute increase of 3.7% in 90-day hospitalization (p=0.001), 2.0% in recurrent stroke/TIA (p=0.013) and 0.8% in mortality (p=0.013).

Conclusions:
Delays in assessment after TIA/minor stroke are common and often due to potentially preventable system factors. These delays are associated with an increased absolute risk of recurrent stroke/TIA, hospitalization, and death. Avoiding delays between referral and assessment may provide opportunities to reduce adverse outcomes in this population.
Abstract W P285: Novel Imaging Technology to Select Patients with a Recent Transient Ischemic Attack or Minor Ischemic Stroke for Carotid Endarterectomy: The Relationship between Test Performance and Cost-Effectiveness
Authors: Buisman Leander R , Rijnsburger Adriana J , Koudstaal Peter J , Redekop William K
Published: March 2022

Background and Purpose:
Non-invasive molecular imaging tests are being developed to improve the ability to predict future strokes in patients with a recent transient ischemic attack (TIA) or minor ischemic stroke. Greater predictive ability can improve patient management, e.g., by identifying which patients will benefit more from a carotid endarterectomy than from medication alone. We estimated the minimum performance (i.e., sensitivity and specificity) that a new test must have in order for it to be cost-effective versus currently available strategies.

Methods:
We compared the cost-effectiveness of using a new imaging test (as a confirmatory test after an initial duplex ultrasonography) with a guidelines-based strategy and three strategies found in daily practice. Cost-effectiveness modelling was used to estimate the long-term costs and health outcomes of each strategy. A willingness-to-pay threshold of є30,000 per QALY gained was used to evaluate cost-effectiveness. We examined the results in two hypothetical populations (60-year-old and 80-year-old men) and varied the sensitivity and specificity to estimate the minimum test performance needed in order for the new strategy to be cost-effective versus the alternatives.

Results:
A perfect confirmatory test (100% sensitivity and specificity) at a cost of є390 is cost-effective for 60-year-old men versus all comparators. A test that is 100% sensitive must be at least 71% specific to be cost-effective versus the guidelines. A test that is 100% specific must be at least 52% sensitive to be cost-effective. Assuming 90% sensitivity, a test must have a specificity of at least 77% to be cost-effective. The minimum required performance for 80-year-old men was higher; e.g., a test that is 100% sensitive must be 88% (vs. 71%) specific to be cost-effective.

Conclusions:
A new strategy that improves risk prediction in patients with a recent TIA or minor ischemic stroke may help to reduce the risk of recurrent stroke and thereby improve health outcomes and cost-effectiveness. However, the minimum required performance may not be achievable in all patient subgroups.
Abstract W P290: Left Ventricular Diastolic Dysfunction Deters Functional Recovery After Acute Ischemic Stroke
Authors: Park Hong-Kyun , Kim Beom Joon , Yang Mi Wha , Kim Seongheon , Han Moon-Ku , Bae Hee-Joon
Published: March 2022

Background:
Diastolic dysfunction of left ventricle (LV) is associated with heart failure symptoms and restricts exercise capacity even in patients with preserved LV ejection fraction. LV diastolic dysfunction is readily evaluated by the conventional Doppler echocardiography. We hypothesized that LV dysfunction may deter functional recovery and increase vascular events in acute ischemic stroke patients.

Methods:
From a total of 4808 patients who admitted to a tertiary academic hospital between August 2007 and June 2013, we selected image-documented cases (N=3858) and subjects with echocardiographic evaluation within 1 month before or after the index stroke (N=3175; 66% of the eligible population). We excluded cases without adequate echocardiographic data for evaluation of LV diastolic dysfunction (N=213) and mRS score at 3 months (N=17). LV diastolic dysfunction was graded into 4 groups in accordance with the current guideline: normal (including restricted patterns), grade 1, grade 2 and grade 3 dysfunction. Recurrent vascular events and mRS score at 3 months were collected prospectively as a quality improvement program of stroke care. Functional dependency or death was defined as a mRS score 2 - 6.

Results:
Among the 2945 included subjects, male was 1784 (61%) and the mean age was 67 ± 13 years. Recurrent events until 3 months included 197 (7%) recurrent strokes and 246 (8%) composite events. Functional dependency or death at 3 months was documented in 1384 (47%) cases. Cases with LV diastolic dysfunction were more likely to be female, old, higher prevalence of vascular risk factors, and more severe neurological deficit at admission. A multivariable logistic regression model taking functional dependency or death as a dependent variable showed that LV diastolic dysfunction remained significant after adjusting for relevant covariates as follows: grade 1 dysfunction (adjust OR [95% CI]; 1.23 [1.01 - 1. 50]), grade 2 (1.24 [0.92 - 1.68]) and grade 3 (1.76 [1.19 - 2.60]). However, there was no association between LV diastolic dysfunction and vascular events.

Conclusion:
LV diastolic dysfunction may independently hinder functional recovery after ischemic stroke.
Abstract W P294: Balancing Autonomy and Beneficence in Acute Stroke Therapy: Neurologist Attitudes Toward Delaying Thrombolysis in Order to Obtain Informed Consent
Authors: Kaplan Brett D , Cranston Jessica , Ali Latisha K , Saver Jeffrey L
Published: March 2022

Background:
In clinical practice, when no consent provider is immediately available to authorize start of thrombolytic stroke therapy, acute stroke physicians face a fundamental conflict between the ethical principles of autonomy (respect for persons) and beneficence (maximizing benefit). Delaying therapy to reach a consent provider maximizes autonomy but reduces benefit. Physician attitudes toward resolving this conflict have not previously been delineated.

Methods:
A 6 item internet-based survey was administered to US academic stroke neurologists. Respondents were asked to indicate how much time (minutes), patients (number who fail to benefit due to delay), and brain (neurons lost due to delay) they would spend trying to reach consent provider for an aphasic acute stroke patient before proceeding with treatment under the doctrine of presumed consent.

Results:
Survey responses were received from 103 of 332 academic stroke neurologists. All respondents were engaged in stroke clinical care, with cerebrovascular disease accounting for more than half of practice time in over 70%. Career duration was substantial, with over 72% having been in practice for more than 5 years. In the time tradeoff framework, respondents indicated they would spend a median of 1.75 minutes (interquartile range, IQR, 0 - 10.0 minutes) trying to contact a consent provider before proceeding with thrombolysis. In the patient tradeoff framework, they would accept a median of 0 (IQR 0-0) per 1000 treated patients failing to benefit from therapy before proceeding. In the brain tradeoff scenario, they would accept a median of 0 (IQR 0-1) neurons lost before proceeding. Converting all choices to time, respondents indicated they would trade off shorter times in the patient framework (0 minutes) and the neuron framework (0 minutes) than in the time framework (1.75 minutes).

Conclusion:
Vascular neurologists indicate they emphasize beneficence over autonomy in deciding when to forego further attempts to reach consent providers to proceed with thrombolytic therapy under the doctrine of presumed consent. Their preference for rapid intervention is magnified when decisions are framed in person failure to benefit and neuron loss, compared with simple chronologic time.
Abstract W P306: Novel Oral Anticoagulant Initiation Within 14 days of Stroke Is Not Associated with Excess Hemorrhagic Transformation Rates
Authors: Phoa Keith , Kate Mahesh , Gioia Laura , Buck Brian , Butcher Kenneth
Published: March 2022

Introduction:
The risk of early recurrent stroke after a cerebrovascular event is elevated. Despite a lack of safety data related to oral anticoagulation (OAC) after TIA/stroke in patients with atrial fibrillation (AF), particularly with respect to novel OACs (NOACs), many physicians do initiate therapy within 14 days of symptom onset. We aimed to assess current practice patterns and hemorrhagic transformation rates associated with early OAC use in AF patients. Methods: We conducted a retrospective chart review of AF patients admitted to a single stroke unit over a 24-month period. OAC agents and time from onset to initiation were recorded. Hemorrhagic transformation (HT) was assessed on CT scans and graded using the ECASS classification system (Hemorrhagic Infarction; HI and Parenchymal Hemorrhage; PH). Results: A total of 402 AF patients, with a mean age of 78.0±11.4 years (196 female), were included. OACs were initiated in 233 (58.0%) patients within 14 days of symptom onset. Of these 233 patients, warfarin was started in 136 (58.4%), dabigatran in 52 (22.3%), rivaroxaban in 40 (17.2%), and apixaban in 5 (2.1%). The median(IQR) number of days from onset to OAC initiation was similar between patients treated with warfarin (2.0(6.0)), dabigatran (2.0(3.8)), rivaroxaban (3.0(6.8)), and apixaban (3.0(5.5), P=0.44). HT was found in 10 patients, 7 (5.1%) of whom were initiated on warfarin and 3 (5.8%) on dabigatran (λ2= 2.9, P=0.14). Of the 7 warfarin related HT cases, 6 were asymptomatic HI and 1 was a symptomatic PH. All 3 dabigatran related HT cases were asymptomatic HI. HT was detected at a median of 3(4) days following OAC initiation. Systemic bleeding was seen in 7 patients, all of whom were taking warfarin (4 gastrointestinal bleeds, 2 retroperitoneal, and 1 ureteral hematoma). Conclusion: Off-label use of NOACs in acute stroke is common. Although hemorrhagic transformation rates appear to be no higher than those associated with warfarin, early NOAC initiation after stroke should be studied in a prospective fashion.
Abstract W P327: Quantitative Localization and Predictive Performance of Intracranial Hemorrhage
Authors: Muschelli John , Ullman Natlie , Hanley Daniel , Crainiceanu Ciprian
Published: March 2022

Background and Purpose:
Current studies of association between intracranial hemorrhage (ICH) localization and stroke severity present conflicting evidence. Using advanced registration techniques on computed tomography (CT) scans, we provide detailed quantification of ICH location and its association with stroke outcomes.

Methods:
We analyzed 111 scans from 111 patients enrolled in the MISTIE (Minimally Invasive Surgery plus recombinant-tissue plasminogen activator for Intracerebral Evacuation) trial. We registered CT scans to a CT template, estimated a 3-dimensional map of where ICH engagement occurs, and derived regions predictive of 2 severity scores: the National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores. We compared the prediction performance of these regions compared to using location information determined by human readers using the adjusted R2 from linear regression models.

Results:
In this sample, ICH is primarily located in deep brain nuclei and lobar white matter, including the superior corona radiata and the thalamus (Figure 1), is related to severity scores. The prediction performance was twice as good for the image-based model compared to the reader-based model (adjusted R2: 0.254 vs. 0.129 for NIHSS, 0.214 vs. 0.069 for GCS).

Conclusions:
Measures of ICH location and engagement using advanced CT imaging processing provide finer, more quantitative, and more predictive anatomic information than that provided by expert human readers. These findings suggest that important anatomic relationships may play biologically plausible roles in determining the severity of a particular ICH and can be estimated using this analytic platform.
Abstract W P33: Long-term Survival and Outcome Anticipation Based on Simple Grading of MR Perfusion in Severe Stroke Patients Due to the Carotid-Middle Cerebral Artery Occlusion
Authors: Mori Takahisa , Iwata Tomonori , Tanno Yuhei , Kasakura Shigen , Aoyagi Yoshinori , Yoshioka Kazuhiro
Published: March 2022

Introduction:
It is difficult to anticipate long-term survival rate (SR) in an acute stroke stage. The aim of our study was to investigate whether or not simple probable CBF grading of MR perfusion was useful for anticipating long-term SR in severe acute stroke patients due to the carotid-middle cerebral artery occlusion.

Methods:
Included were patients 1) who were admitted to our institution within 24 hours of onset between Jan 2005 and May 2014, 2) who underwent MRA displaying neither the internal carotid artery (ICA) nor the middle cerebral artery (MCA) in the affected side and 3) who were treated without any reperfusion therapy. We evaluated CBF grades, any death within 120 days and clinical outcome at 90 days. CBF grade was calculated by using bilateral time-intensity curves (TICs) of MR perfusion. TICs were generated on region of interests set at symmetrical positions of the bilateral MCA territories. According to the time to peak (TP) and the peak signal (PS) comparing the affected side (a) with the contralateral side (c), we regarded the affected-sided PSa divided by TPa as possible CBFa and the contralateral-sided PSc divided by TPc as possible CBFc. CBF grade 1 was defined as CBFa divided by CBFc (CBF%) less than 0.2, grade 2 as CBF% of 0.2 or more and CBF% less than 0.5 and grade 3 as CBF% of 0.5 or more.

Results:
Sixty-three patients were analyzed. There were 25, 25 and 13 in grade 1, 2 and 3. Thirty-five patients (55.6%) died within 120 days, most of them (28 patients, 44.4%) died within 10 days. In grade 1, 2 and 3, 20, 12 and 3 patients died within 120 days, and SR of the Kaplan-Meier method at 120 days was 20%, 50.4% and 76.2% (p<0.001), respectively.

In grade 1, there were 0 patient in mRS of 0-2, 1 in mRS of 3-4 and 24 in mRS of 5-6 at 90 days, in grade 2, there were 0 in mRS of 0-2, 7 in mRS of 3-4 and 18 in mRS of 5-6, in grade 3, there were 1 in mRS of 0-2, 8 in mRS of 3-4 and 4 in mRS of 5-6 (p<0.001).

Conclusion:
Simple grading of MR perfusion was useful for anticipating long-term survival rate and clinical outcome in acute stroke stage. We can realize that patients with grade 1 must be rescued and clinical outcome of patients with grade 2 or 3 must be improved
Abstract W P334: Admission Blood Pressure Predicts The Number Of Medications Upon Discharge In Patients With Primary Intracerebral Hemorrhage
Authors: Khawaja Ayaz , Boehme Amelia K , Albright Karen C , Bavarsad Shahripour Reza , Kumar Gyanendra , Shiue Harn , Lyerly Michael , Hays Angela , Harrigan Mark
Published: March 2022

Background and Purpose:
Previous studies have shown that controlling blood pressure (BP) may limit hematoma expansion in primary ICH. We hypothesize that aggressive management requires multiple BP medications and sought to evaluate what factors are associated with the number of BP medications at discharge.

Methods:
Patients with primary ICH admitted to our center from 2008-2013 were included. Patients whose care was transitioned to palliative medicine were excluded. Primary outcome of interest was the number of BP medications at discharge. Poisson distribution was used to assess the relationship between baseline variables and number of BP meds at discharge.

Results:
A total of 288 patients met eligibility criteria. The median age of the population of 62, 44.2% females, and 47.9% patients of African-American ethnicity. There were 236 patients (81.9%) with a history of hypertension (HTN). Patients with HTN had a higher admission systolic blood pressure (SBP) compared to those without HTN (180 vs. 157; p=0.0001). Number of BP medications at discharge ranged from 0-7, with the majority of patients discharged on 3 or more meds (29.9%). Only 4% of patients were discharged with no BP medications, whereas 7.3% were discharged on 5 or more. The only baseline variables that were significantly associated with number of BP meds on discharge in univariable analyses were a history of HTN (p<0.0001) and admission SBP (p<0.0001). In patients without a history of HTN, every 10-point increase in SBP on arrival resulted in an increase in 0.5 BP meds at the time of discharge (p=0.0011). For patients with a history of HTN, each 10-point increase in SBP on arrival resulted in an increase in 1.3 BP meds at the time of discharge (p=0.0012).

Conclusions:
A history of hypertension and admission systolic blood pressure were significant predictors of the number of BP medications at discharge. Admission SBP was also significantly associated with the number of BP medications on discharge for patients without a history of hypertension. Further research is needed to assess if the BP elevation is a stress response in patients without hypertension, or an indicator of uncontrolled hypertension in patients with a history of hypertension.