bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P24: Validation of the Interventional Stroke Assessment Scale for Eligibility in Endovascular Therapy (ISAS-ET)
Authors: Dababneh Haitham , Sakian Sina , Zheng Huo Xiang , Kumar Rajesh , Azhar Salman , Arcot Karthikeyan , Tiwari Ambooj , Farkas Jeffrey
Published: March 2022

Background:
Despite innovations in endovascular stroke treatment, less than 55% of patients have shown good outcomes in multiple randomized clinical trials. In this study we are validating the Interventional Stroke Assessment Scale for Eligibility in Endovascular Therapy (ISAS-ET).

Materials:
This is a retrospective analysis of all patients (n= 111) who presented to our hospital with ischemic stroke and received advanced stroke treatment between January 2013 and July 2014. Statistical analysis was performed using GraphPad Prism. The scoring system was developed with a score range (0-8), where a high score predicts a better outcome. Patients received 2,1,0 points for collateral scores of 3-4, 2, 0-1 respectively; patients received 2, 1, 0 points for NIHSS scores of 0-10, 11-20 and over 21 respectively; age <65 received 1 point; absence of AFib received 1 point; time of onset <3 hours received 1 point; no prior stroke or disability received 1 point. Statistical analysis was performed using GraphPad Prism. A modified rankin scale (mRS) of 2 or less represented a good functional outcome. Mortality was defined as a mRS score of 6 and good disposition was defined as patient discharged to home or inpatient rehabilitation. All variables were included in the analysis.

Results:
Results for 59 patients included in this study are as follows: 61% female, mean age 74.0 ± 19.1, mean NIHSS 17.8 ± 7.2, 49.1% AFib and 10.1% mortality. We found a significant correlation between the ISAS-ET score and outcome (95% CI, 3.36-4.24, P < 0.001), mortality (95% CI, 3.93-4.82, P < 0.001) as well as good disposition (95% CI, 3.68-4.56, P < 0.001). Of this group, 94% of the patients with an ISAS-ET score of 1, 2 or 3 had a poor outcome regardless of intervention. Conversely, 86% of the patients with a score of 7 or more had a good outcome.

Conclusion:
The ISAS-ET scale appears to be appropriate in this single center study at predicting outcome using parameters prior to intervention. This data may help determine the urgency of transfer for intervention in hospitals without endovascular capabilities while helping determine which patients will benefit significantly from intervention. We plan to validate these results in a prospective study.
Abstract W P241: Identification of Neural Stem Cells in Neurogenic Niche After Stroke
Authors: Zhang Rui Lan , Chopp Michael , Roberts Cynthia , Wei Min , Wang Xinli , Zhang Zheng Gang
Published: March 2022

Background:
Adult neural stem cells (NSCs) are present in the rodent ventricular-subventricular zone (V/SVZ) of the lateral ventricles. However, their in vivo role in stroke-induced neurogenesis remains uncertain. Using an anti-mitotic agent (Ara-C) in combination with phenotype markers, we examined NSCs in whole-mount preparation of the lateral ventricle of ischemic brain.

Methods and Results: Adult mice (n=28) were used. Focal cerebral ischemia was induced by occluding the right middle cerebral artery. Ara-C was infused on brain surface of mice for 7 days. BrdU was administered to label proliferating cells. Another 6 mice with non-ischemia, non-infusion were also given BrdU labeling as normal control. The architecture of NSCs identified by inhibitor of DNA binding/Differentiation 1 (Id1, a transcription factor)+/GFAP+ in the V/SVZ were examined in whole mount by means of a 3D confocal microscope. In a normal V/SVZ, 3% (at least 4,000 cells counted per each sample) cells were Id1+. Of these Id1+ cells, 16% cells were GFAP+, which were anchored by specialized apical end-feet in the center of the pinwheel of ependymal cells and they often extended basal processes at least 50 -80 um long; none of these cells were BrdU+ after 1h pulse labeling, indicating that these cells are relatively quiescent. However, 69 % of Id1+ cells were Mash+ and Olig2+ and the majority of these cells were BrdU+, indicating that these are active progenitor cells. 1h after termination of infusion, Id1+/Mash+ and Olig2+ cells were eliminated, whereas Id1+/GFAP+ cells in the center of pinwheels were not affected in non-ischemic and ischemic V/SVZ niches. At this time point, there were no actively proliferating cells measured by 1h BrdU pulse labeling. However, by 48h after termination of infusion, there were many proliferating cells with 59% and 75% of BrdU+ cells were Id1+ in non-ischemic and ischemic V/SVZ niches (p<0.05), respectively. In the ischemic V/SVZ niche, in the center of pinwheels the majority of Id1+/BrdU+ cells were GFAP+ .

Conclusion:
Our in vivo data suggest that adult V/SVZ niche GFAP+/Id1+ astrocytes are “functional quiescent” NSCs. Stroke recruits quiescent NSCs in the V/SVZ niche to an active pool for enhancing the neurogenic process in response to ischemic insult.
Abstract W P244: Inhibition of Matrix Metalloprotease 3 Reduces Vascular Injury and Improves Functional Outcomes in Hyperglycemic Stroke
Authors: Hafez Sherif , El-Shafey Sally , Fagan Susan , Ergul Adviye
Published: March 2022

Matrix metalloprotease 3 (MMP3) is a zinc endopeptidase that has a broad substrate specificity and can cause degradation of basal lamina and tight junction proteins of the blood brain barrier. MMP3 plays a critical role in mediating the tPA induced hemorrhagic transformation (HT) after stroke. We have previously shown that increased MMP3 activity was associated with greater vascular injury in hyperglycemic stroke. Thus, this study tested the hypothesis that MMP3 inhibition reduces the vascular injury and improves the functional outcomes in hyperglycemic stroke.

Methods:
Control and mildly HG rats (140-200 mg/dl, achieved by 30% glucose injection (IP) 15 min prior to surgery, n=7-9/group) were subjected to 90 min middle cerebral artery occlusion and 24 h reperfusion. In an additional group of HG rats, MMP3 inhibitor (UK 356618, Tocris Bioscience) was IV injected (15 mg/kg) at reperfusion. At 24 h, neurological deficit, infarct size, edema and HT occurrence rate (HT index) were measured. MMP3 activity in isolated cerebrovasculature and brain homogenates was quantified by FRET assay. In addition, MMP3 activity was measured in brain microvascular endothelial cells (BVEC) treated with tPA and subjected to 90 minutes hypoxia/24 h reoxygenation under normal and high glucose conditions.

Results:
MMP3 significantly reduced the vascular injury (HT index and edema) with no effect on infarct size and this was associated by improved functional outcomes (Table). tPA has significantly increased MMP3 activity in BVEC under either normal or high glucose conditions (*p<0.05 vs control).

Conclusion:
Our findings that MMP3 inhibition reduces vascular injury and improves functional outcomes identifies MMP3 as a potential therapeutic target in hyperglycemic stroke.
Abstract W P247: Reducing Hemorrhagic Complication by Rivaroxaban and Apixaban via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat
Authors: Kono Syoichiro , Yamashita Toru , Deguchi Kentaro , Yunoki Taijun , Sato Kota , Hishikawa Nozomi , Abe Koji
Published: March 2022

Background and Purpose:
This study aimed to assess the risk and benefit of tissue-type plasminogen activator treatment after oral anticoagulation with rivaroxaban or apixaban compared with warfarin or placebo.

Methods:
Pretreatment with warfarin (0.2 mg/kg per day), rivaroxaban (2 mg/kg per day), apixaban (10 mg/kg per day), or vehicle (0.5% carboxymethyl cellulose sodium salt) was performed for 7 days. Transient middle cerebral artery occlusion was then induced for 120 minutes, followed by reperfusion with tissue-type plasminogen activator (10 mg/ kg per 10 mL). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. Twenty-four hours after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and matrix metalloproteinase-9 activity was measured by zymography.

Results:
The paraparesis score was significantly improved in the rivaroxaban-pretreated group compared with the warfarinpretreated group. Intracerebral hemorrhage was observed in the warfarin-pretreated group, and this was reduced in the rivaroxaban and apixaban-pretreated groups compared with the vehicle group. Marked dissociation of astrocyte foot processes and the basal lamina or pericytes was observed in the warfarin-pretreated group, and this was improved in the rivaroxaban and apixaban-pretreated groups. Furthermore, activation of matrix metalloproteinase-9 in the ipsilateral warfarin-pretreated brain was greatly reduced in rivaroxaban- and apixaban-pretreated rats.

Conclusions:
This study shows a lower risk of intracerebral hemorrhage after tissue-type plasminogen activator treatment in rats with ischemic stroke that are pretreated with rivaroxaban and apixaban compared with pretreatment with warfarin. Reducing neurovascular dissociation by rivaroxaban and apixaban compared with warfarin could partly explain a reduction in hemorrhagic complications reported in clinical studies.
Abstract W P249: Agonism of Transient Receptor Potential Vanilloid Member 1 Induces a Protective Heat Shock Response in the Brain
Authors: Feketa Viktor V , Balasubramanian Adithya , Cao Zhijuan , Marrelli Sean P
Published: March 2022

Background:
There is a lack of widely applicable treatments of stroke. One of the potential new treatment strategies is the induction of heat shock proteins (HSPs), such as Hsp27 and Hsp70, in the brain, which was shown to confer neuroprotection from ischemia. In epithelial cells, HSPs were shown to be induced by agonists of the Transient Receptor Potential Vanilloid Member 1 ion channel (TRPV1), also known as the heat and capsaicin receptor. Therefore, our overall hypothesis is that systemic administration of TRPV1 agonist dihydrocapsaicin (DHC) induces HSPs in the brain cortical neurons and thus provides neuroprotection from stroke. In the present study we focus on the initial portion of the hypothesis, that TRPV1 agonism promotes HSP induction in the brain.

Methods:
We determined relative expression of candidate HSP genes by quantitative real-time polymerase chain reaction after DHC treatment in cultured rat primary cortical neurons as well as in cortex tissue samples of in vivo DHC-treated wild-type and TRPV1 knock-out mice.

Results:
First, we established that DHC injection (4 mg/kg i.p.) 4 hours before tissue harvest led to 3- and 5-fold upregulation of mRNA of the Hsp27 and Hsp70 respectively in the cortex of mice (compared to vehicle injection, n=3 mice per group). This effect was specific to TRPV1 channels, as it was absent in TRPV1 knock-out mice. Second, we determined that 3-hour DHC treatment led to upregulation of Hsp70 mRNA in cultured rat primary cortical neurons, which was dependent on the dose of DHC (1-1000 nM).

Conclusions:
We present the first demonstration that systemic delivery of TRPV1 agonists promotes an upregulation of neuroprotective heat shock proteins in the brain. We have further demonstrated that cortical neurons have the capacity to respond to TRPV1 agonism directly rather than through other TRPV1-mediated physiologic responses. We propose that systemic delivery of TRPV1 agonists may offer a novel treatment option in the protection or recovery from ischemic stroke.
Abstract W P252: Amylin Vasculopathy, a Novel Mechanism of Cerebrovascular Injury and Neurologic Deficits in Diabetes
Authors: Verma Nirmal , Mina Michael , Liu Miao , Nystoriak Matthew , Srodulski sarah , Peng Xiao Li , Brelsfoard Jennifer , Bachstetter Adam , Pascual Conrado , Xie Xinmin , Saatman Kathryn , Van Eldik Linda , Navedo Manuel , Despa Sanda , Despa Florin
Published: March 2022

Human amylin is an amyloidogenic hormone that forms toxic oligomers that kill the insulin-producing β-cells in the pancreas of patients with type-2 diabetes. We recently showed that the pancreatic amylin pathology is also linked with cerebrovascular dementia and diabetic heart disease by increased circulating levels of toxic oligomerized amylin. Here, we tested the hypothesis that the cerebrovascular accumulation of oligomerized amylin injures the brain, leading to neurologic deficits independently of hyperglycemia.

A diabetic rat model overexpressing amyloidogenic human amylin in the pancreas (the HIP rat) and appropriate controls were used to investigate mechanistically cerebrovascular effects of amylin accumulation. As controls, we employed wild-type (WT) littermates and age- and glucose-matched diabetic rats expressing only non-amyloidogenic WT amylin, which does not accumulate in pancreas or other organs. Compared to controls, HIP rats showed reduced exploratory drive, vestibulomotor performance and recognition memory. Cortical arteries isolated from HIP rats displayed a ~40% higher myogenic tone (P<0.05), which correlates with an increased mean arterial blood pressure by ~20% (P<0.05). We also found elevated lipid peroxidation (by 18±3%; P<0.05) and activated Ca
2+
-mediated hypertrophy signaling in cortical smooth muscle cells from HIP rats compared to control rats. Serial staining with the ED1 antibody and amylin antibody indicates possible activated microglia/macrophages which are clustering in blood vessel areas positive for amylin infiltration. Multiple inflammatory markers are expressed in HIP rat brains compared to control rats, confirming that amylin deposition induces an inflammatory response.

Overall, our data suggest that cerebrovascular amylin deposition is associated with neurologic deficits via mechanisms of vascular dysfunction, oxidative stress and neuroinflammation.
Abstract W P261: Increased Susceptibility of Blood-Brain Barrier to Ischemic Damage by a Diabetic Metabolite Methylglyoxal
Authors: Kim Kyeong-A , Shin Young-Jun , Kim Eun-Sun , Akram Muhammad , Noh Dabi , Kim Eunji , Bae Ok-Nam
Published: March 2022

Ischemic stroke is the major cause of death or disability in diabetic patients. Diabetic patients have higher incidence of stroke, however the underlying molecular mechanisms are not clear. The blood level of methylglyoxal (MG), a byproduct of glycolysis, is significantly increased in patients with diabetes. Several studies have reported that MG might play a key role in vascular dysfunction under diabetic condition. In this study, we investigated if MG disrupts blood-brain barrier (BBB) function and increases the susceptibility of BBB to ischemic damage. Treatment of MG significantly decreased cell viability of bEND.3 cells, an in vitro BBB model. MG increased the permeability in bEND.3 in a dose-dependent manner. In addition, the level of occludin, a tight junction protein, was decreased after exposure to MG. To investigate the change in susceptibility to ischemic damage under high concentration of MG, we exposed bEnd.3 cells to MG for 12 hours prior to oxygen-glucose deprivation (OGD). Cell viability assay revealed an increased ischemic cell death under high level of MG, indicating that MG increased susceptibility to ischemic damage of BBB. Taken together, we demonstrated ischemic disruption of BBB can be enhanced by exposure to MG, suggesting that MG-induced BBB disruption might be a key factor in the susceptible ischemic damage under diabetic condition.
Abstract W P262: Neuroprotective Effect of Nattokinase Mediated by Inhibition of Platelet Aggregation and Thrombosis in Photothrombotic Stroke
Authors: Ahn Yong-Joo , Kim Maya Hwewon , Kim Jihyun , An Gwangmin , Kim Dongju , Kwon Ye-Rim , Lee Angela Mingie , Kim Yun-Bae , Kim Hyung-Hwan
Published: March 2022

Background and Purpose:
Thrombolysis remains the only effective and approved medical treatment of acute ischemic stroke. Nattokinase is a potent fibrinolytic enzyme purified from the fermented soybean cheese Natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed both in vitro and in vivo. Here, we determined whether nattokinase may have a beneficial effect in photothrombotic stroke.

Methods:
The plasma fibrinolytic activity of nattokinase was measured by euglobulin clot lysis times (ECLT). Arterial thrombus formation was investigated using in vivo ferric chloride induced thrombosis model. To determine the effect of nattokinase in ischemic brain injury, we treated nattokinase at 1h, 2h, and 4h before operation and induced a photothrombotic stroke model in mice.

Results:
The ECLT was significantly shortened by administration of nattokinase. Nattokinase inhibited the ferric chloride induced arterial thrombosis. Nattokinase improved relative cerebral blood flow in both ischemic region and non-ischemic region. Nattokinase significantly reduced infarction volume at 4h treatment (26.2 ± 6.5 mm3, n=5, p=0.019) compared to that of vehicle control (42.9 ± 2.5 mm3, n=7) in photothrombotic stroke.

Conclusions:
These findings indicate that nattokinase improved blood flow by inhibiting platelet aggregation and thrombus formation and significantly induced neuroprotective effect in ischemic brain damage. These results suggest that nattokinase may have therapeutic benefits in ischemic brain injury.
Abstract W P265: Utilization of Comprehensive Stroke Center Resources by Patients with Intracerebral Hemorrhage
Authors: Nguyen Claude , Mir Osman , Vahidy Farhaan , Savitz Sean
Published: March 2022

Background:
Intracerebral hemorrhage (ICH) is a particularly devastating condition that often prompts transfer to a Comprehensive Stroke Center (CSC) in anticipation of need for higher level of care, including neurointensive care unit (NICU) monitoring, neurosurgical intervention, or enrollment in clinical trials. We hypothesized that transferred ICH patients would utilize CSC-specific resources to a greater extent than directly admitted patients.

Methods:
From a prospectively-collected stroke registry, we reviewed all spontaneous, primary ICH patients from March 2011 to March 2012, comparing those who were transferred with those who directly presented to the CSC. Primary outcome was the proportion of patients in each group who utilized at least one of these resources: NICU, neurosurgical intervention, or clinical trial enrollment.

Results:
We reviewed 362 patients, 210 (58%) of whom were transferred. A lower proportion of transferred patients (79.1%) used CSC-specific resources compared to those directly admitted (88.2%; Table 1). Fewer transferred patients required neurosurgical intervention or were enrolled in clinical trials. There was no significant difference in the proportion of patients who used NICU resources, though transferred patients had a significantly lower median NICU length of stay.

Conclusions:
Transferred ICH patients used fewer CSC-specific resources than directly admitted patients. This suggests that not all ICH patients require transfer to a tertiary care center. Further investigation is needed to identify the patients who are most likely to use higher level resources and would benefit from being transferred to a CSC.
Abstract W P271: Reasons Why rt-PA Was Not Given: Physician Documentation vs. Chart Abstraction
Authors: Eckerle Bryan , Khoury Jane , Alwell Kathleen , Moomaw Charles , Kissela Brett , Flaherty Matthew , Woo Daniel , Adeoye Opeolu , Ferioli Simona , de los Rios la Rosa Felipe , Martini Sharyl , Mackey Jason , Kleindorfer Dawn
Published: March 2022

Introduction:
Joint Commission primary stroke center (PSC) certification requires explicit physician documentation as to why rt-PA is not given to an ischemic stroke patient who presents within two hours of onset. We hypothesized that many reasons for non-treatment could be inferred from the medical record even if physician documentation was absent, and we sought to evaluate this within a large, biracial population in a region containing four PSC and eleven non-PSC hospitals.

Methods:
All ischemic stroke patients ≥20 years of age who presented to an emergency department within two hours of onset in 2010 and resided in the Greater Cincinnati/Northern Kentucky (GCNK) region were included. For each case, medical records from the acute hospitalization were retrospectively abstracted by research nurses, who recorded physician-documented reasons for non-treatment and recorded at least one exclusion criterion applicable to the patient. Chi-square test was used to compare physician documentation rates between PSC and non-PSC hospitals.

Results:
There were 374 patients included in this analysis. Mean age was 69.8 (SD 15.0), 50.8% were female, and 19.8% were black. Of the 374, 96 (25.7%) were treated with rt-PA. Of the 278 patients who were not treated, 82 presented to PSCs and 196 presented to non-PSCs. At PSCs, physicians documented exclusion criteria 58.5% of the time, while nurses abstracted exclusion criteria in 92.7%. At non-PSCs, the rate of physician documentation was 43.9% and that of nurse abstraction was 94.5%. Rate of physician documentation was statistically significantly higher at PSCs than non-PSCs (p=0.03).

Discussion:
Within our population, we found that physicians documented the rationale for non-treatment with rt-PA less than half of the time. However, study nurses were able to abstract exclusion criteria from the chart in 94% of cases. Physician documentation, though still poor, was better at primary stroke centers than other hospitals. Allowing objective rt-PA exclusions to be abstracted from the medical record may allow a more accurate understanding of reasons for non-treatment at the hospital level.
Abstract W P28: Diffusion and T2 Star Weighted MR Angiography Mismatch Predicts Ischemic Penumbra in the Acute Stage
Authors: Yamaguchi Susumu , Horie Nobutaka , Morikawa Minoru , Tateishi Yohei , Fukuda Shuji , Morofuji Yoichi , Izumo Tsuyoshi , Hayashi Kentaro , Tsujino Akira , Nagata Izumi
Published: March 2022

Introduction:
T2 star weighted MR angiography (SWAN) can detect slight changes of susceptibility caused by microbleeds. It has also been reported that SWAN can detect hemodynamic insufficiency as hypointensity area in the medullary or cortical veins. In this study, we investigate whether SWAN can help to detect ischemic penumbra in the acute stage.

Materials and methods:
Patients showing acute major vessel occlusion (internal carotid artery and middle cerebral artery) within 4.5 hours from onset were consecutively analyzed with MR imaging including SWAN, diffusion weighted imaging (DWI) and MR angiography. To evaluate ischemic area in SWAN and DWI, modified Alberta Stroke Program Early CT score (mASPECTS) was used as follows; M1~6 and basal ganglion including caudate, insula, lentiform or internal capsule. SWAN based mASPECTS was calculated with DWI based ASPECTS, and correlation between DWI-SWAN mismatch and final infarct area or outcome was evaluated.

Result:
Of 30 patients (mean age: 72.7 ± 13.3 years). Cardioembolic stroke was confirmed in 24 patients, atherothrombotic stroke was in 3 patients, and others had unknown etiology. Intravenous t-PA was performed in 17 patients, and endovascular therapy was performed in 17 patients. Overall, recanalization was achieved in 70% (21 patients) with lower modified Rankin Scale at 90 days compared with no recanalization (P=0.0004).

Interestingly, SWAN based mASPECTS was significantly correlated with mRS at 90 days (R=-0.4382, P=0.02) regardless of recanalization. Of 9 patients showing no recanalization, DWI-SWAN mismatch was significantly correlated with new infarction (R=0.8221, P=0.0065). On the other hand, patients showing recanalization showed no correlation between mismatch and new infarct.

Conclusion:
DWI-SWAN mismatch could simply predict ischemic penumbra requiring immediate reperfusion. Assessment of ischemic penumbra from venous side using SWAN is quite useful without contrast media.
Abstract W P280: Predictors of Hospitalization in Patients with Minor Stroke and TIA
Authors: Stamplecoski Melissa , Fang Jiming , Hall Ruth , Austin Peter C , Tu Jack V , Casaubon Leanne K , Kapral Moira K , Silver Frank L
Published: March 2022

Background:
Although current guidelines recommend urgent treatment for patients with TIA and minor stroke, it is unclear if hospitalization is required, and little is known about the factors that influence decisions to admit such patients. The objective of this study was to identify patient and system-level predictors of admission in patients with minor stroke and TIA.
Methods:
The Ontario Stroke Registry (OSR) was used to identify a cohort of patients with acute minor stroke or TIA who presented to any one of Ontario’s 150 acute care hospitals between April 1, 2008 and March 31, 2011. Multivariable analysis using hierarchical logistic regression modeling was performed to identify predictors of hospitalization, including patient characteristics, risk factors, presenting symptoms, features of the care encounter and hospital and system-level factors.
Results:
The final study cohort consisted of 10,890 patients with minor stroke or TIA. Overall, 48% were women and the median age was 75 years. The overall admission rate was 57% (31% for TIA and 83% for minor stroke). In the multivariable analysis, significant predictors of hospital admission included disability prior to admission, risk factors including hyperlipidemia, atrial fibrillation and smoking, presenting with weakness or symptoms persisting for more than 60 minutes and arriving to hospital by ambulance (all p<0.01). Approximately 88% of the model’s variance was attributable to patient-level factors. Stroke center designation, hospital volume, having a stroke unit on site and having access to a stroke prevention clinic were not significant predictors of hospitalization. Similar results were found when the minor stroke and TIA subgroups were analyzed separately.
Conclusions:
These results suggest that patient-level characteristics rather than system-level factors have a greater influence on the decision to admit patients with minor stroke or TIA. Given that these patients are hospitalized solely for rapid completion of investigations and initiation of secondary prevention therapies, a system change providing access to specialized urgent TIA clinics is required to avoid the unnecessary costs of hospitalization.
Abstract W P281: Improving Prediction of Readmission After Ischemic Stroke: A Nationwide Retrospective Cohort Analysis
Authors: Fehnel Corey R , Lee Yoojin , Mor Vincent
Published: March 2022

Background:
Previous models for predicting readmission after ischemic stroke rely solely on administrative claims. The Minimum Data Set (MDS) is a nationwide clinical database required for all U.S. nursing home residents. We hypothesized MDS variables would improve prediction of 30-day acute hospital readmission after ischemic stroke.

Methods:
Medicare inpatient claims for the year 2008 were used to identify ischemic stroke cases over age 65 as defined by ICD-9 principal diagnosis codes 433.x, 434.x, and 436.x. Unique individuals were linked to full MDS records. Logistic regression was used to construct risk-adjusted models of unplanned readmission 30 days post acute care hospitalization. Covariates were derived from Medicare Part A claims and clinically relevant MDS variables. Model performance was assessed through construction of receiver operator characteristic (ROC) curves.

Results:
Among 252,569 ischemic stroke admissions, there were 87,094 (36%) individuals admitted to nursing homes. The analytical sample was composed of 39,178 (14%) patients directly admitted to nursing homes. At 30-days post acute hospital discharge there were 11,648 (21%) readmissions and 6,394 (12%) deaths. Independent predictors of readmission included feeding tube (OR 1.20, CI 1.06-1.35), congestive heart failure (OR 1.18, CI 1.08-1.29), chronic obstructive pulmonary disease (OR 1.26, CI 1.15-1.39), renal disease (OR 1.26, CI 1.12-1.43), and pressure ulcers (OR 1.34, CI 1.20-1.51). Clostridium difficile infection was most strongly associated with readmission (OR 1.44, CI 1.05-1.97). Hemiparesis (34%) and aphasia (16%) were not significant predictors of 30-day readmission. Area under the ROC curve for predicting readmission at 30 days was 0.65.

Conclusions:
Nursing home admission is required for a significant proportion of stroke survivors over age 65. The addition of multiple individual clinical variables derived from the MDS resulted in a modest improvement in area under the ROC curve (.65) compared to previous models utilizing only Medicare Part A data (.60). The prediction model presented here provides novel targets for readmission reduction programs among stroke patients cared for in nursing homes.
Abstract W P283: Race-Ethnic Stroke Disparities in the Florida-Puerto Rico Collaboration to Reduce Stroke Disparities Study - The NINDS Stroke Prevention Intervention Research Program
Authors: Sacco Ralph L , Gardener Hannah , Wang Kefeng , Dong Chuanhui , Ciliberti-Vargas Maria A , Romano Jose G , Burgin W S , Carrasquillo Olveen , Garcia-Rivera Enid J , Koch Sebastian , Meschia James F , Nelson Joe A , Nobo Ulises , Robichaux Mary , Rose David Z , Santiago Fernando L , Waters Michael F , Zevallos Juan C , Rundek Tatjana ,   for the FL-PR CReSD Investigators and Collaborators
Published: March 2022

Background:
Race-ethnic disparities in stroke care can contribute to inequality in stroke outcomes. We sought to determine the disparities in stroke performance metrics by race-ethnicity in a voluntary stroke registry of Florida and Puerto Rico Get With The Guidelines-Stroke (GWTG-S) data.

Methods:
Sixty-three sites who had enrolled in the FL-PR Stroke Registry (54 FL; 9 PR) recorded 38,684 ischemic stroke cases from 2010 to 2013. Generalized linear regression models were used to evaluate race-ethnic differences in 7 pre-defined acute stroke performance measures and defect-free care (IV tPA treatment, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, and smoking cessation counseling), adjusting for age and region (FL vs. PR).

Results:
Of acute ischemic stroke cases, 63% were non-Hispanic White (NHW), 18% NH-Black (NHB), and 17% Hispanic. The mean age was 71±14 years. NHW were older (73±14), followed by Hispanics (70±14), and NHB (63±14); p<0.0001. Defect-free care was better among NHB (78%) and NHW (76%) than in Hispanics (68%), p<0.0001. Defect-free care improved over time and the race-ethnic disparity decreased (2010: NHW 61%, NHB 64%, Hispanic 46%, p<0.0001; 2013: 91%, 91%, 86%, p=0.47 respectively). NHW were most likely to receive IV tPA treatment (arrived by 2 hours and treated by 3 hours; 88%) and early antithrombotic treatment (96%). Hispanics were least likely to receive DVT prophylaxis (76%), anticoagulation (92%), statins (89%), and smoking cessation counseling (93%).

Conclusions:
Race-ethnic disparities in acute stroke care are evident yet decreasing, coinciding with improvements in quality of care over time in Florida and Puerto Rico hospitals participating in GWTG-S. Special stroke quality improvement programs to target areas where performance is less than expected and minimize race-ethnic disparities are necessary to improve stroke care for all Americans.
Abstract W P295: Admission Is Delayed in Patients with Predominantly Visual Symptoms of Ischemic Occipital Stroke
Authors: Silvennoinen Katri , Silvennoinen Heli , Gall Carolin , Rossini Paolo M , Waleszczyk Wioletta J , Sabel Bernhard A , Tatlisumak Turgut
Published: March 2022

Introduction:
Stroke patients with predominantly visual symptoms due to posterior circulation ischemia rarely receive thrombolytic treatment despite the often debilitating nature of their homonymous visual field deficits. In addition to stroke physicians’ judgment of risks and benefits, perhaps influenced also by low scores on the National Institutes of Health Stroke Scale, lack of thrombolytic treatment may be caused by delayed admission to a stroke center.

Hypothesis:
We hypothesized that patients with occipital infarcts presenting with predominantly visual field symptoms would show less direct routes and longer onset-to-admission delays to a stroke center compared to the general stroke population, of which approximately half are admitted within 4h of symptom onset.

Methods:
All patients with visual field deficits as their primary symptom of occipital infarction treated at the Helsinki University Central Hospital between 2010 and 2013 were retrospectively identified from all cases of ischemic stroke by careful review of medical records and radiological data. All patients with acute stroke within the Greater Helsinki area (catchment area of 1.5 million) are brought to our emergency room (ER). Data were gathered on admission route and length of delay from symptom onset to admission.

Results:
Of the 179 occipital ischemic stroke patients with hemianopia as their main symptom or sign, 32 (18%) were admitted within 4h of symptom onset and a further 64 (36%) within 4-24h. Only 17 patients (9.5%) arrived as pre-notified thrombolysis candidates. 10 patients (5.6%) received thrombolysis, but half of them were only recognized as thrombolysis candidates after ER admission. Of all patients, 35 (20%) arrived directly at our ER, whereas 45 (25%) had visited two or more points of care or had been initially discharged, with a significant proportion of all patients, 30%, having visited an ophthalmologist prior to admission.

Conclusions:
Recognizing ischemic stroke presenting with visual field symptoms is challenging. Complexity of patient routes and long admission delays likely contribute to the low rates of thrombolytic therapy in this patient group.
Abstract W P297: The Electronic Stroke CarePath - An Integrated Approach to Stroke Care
Authors: Katzan Irene , Fan Youran , Speck Micheal , Morton Johanna L , Uchino Ken , Griffith Sandra , Modic Michael
Published: March 2022

Background:
There is a continuous need to improve efficiency and quality of care. In response, the Electronic Stroke CarePath (ESCP) was developed for management of ischemic stroke patients. We describe the development, implementation and outcomes of the first 2 years of this initiative.

Methods:
The ESCP consists of care pathways for ischemic stroke that are integrated within the EHR (Epic) and includes systematic collection of patient-reported outcomes (PROs). Main components of the EHR integration included a navigation panel, the use of structured forms with elements that autopopulate templates, and clinical decision support. An external software platform was used to collect PROs. Inpatient mortality and length of stay (LOS) were compared before and after implementation in ischemic stroke patients and in 2 control groups: ICH and SAH patients, after adjustment for case-mix. Postdischarge functional outcomes of ischemic stroke patients were compared between the 1st 3 months of rollout and remainder of the study period.<br

Results:
The ESCP was implemented in Sep 2010 and modified over the first 3 months. Data were analyzed from Jan 2011- Dec 2012. There were 1106 patients with mean age 66.2 yrs and admission NIHSS 5; 46.1% were women.

There was a significant reduction in observed/predicted inpatient mortality after implementation of the ESCP in ischemic stroke patients (OR 0.59 [95% CI 0.42-0.83], but not in the control patients with ICH (OR 0.90 [0.59 - 1.38]) or SAH (OR 1.05 [0.67 - 1.65]). . Similarly, a significant increase in the proportion with LOS < predicted after ESCP implementation was seen only in ischemic stroke pts (51.4% vs 56.0%, p=0.047). Compared to those admitted within the 1st 3 mo of ESCP rollout, ischemic pts admitted in the remainder of the study period demonstrated nonsignificant improvements in degree of impairment (NIHSS, 3.9 to 2.7, p=0.059), IADLs (modified Rankin, 2.6 to 2.2, p=0.079) and physical function (SIS16, 67.8 - 76.0, p=0.084) at followup.

Conclusion:
Implementation of the ESCP is feasible and may be associated with a benefit in multiple different outcomes after ischemic stroke. This approach, which combines carepaths, HIT, and the systematic collection of PROs, may be an important strategy for optimizing stroke care in the future.
Abstract W P30: Implementation of a Web-based Approximate Volume Tool for Acute Stroke Lesion Measurement Using MRI
Authors: Hong Jennifer , Hsia Amie W , Benson Richard T , Edwardson Matthew A , Lynch John K , Nadareishvili Zurab , Shah Aabha A , Luby Marie
Published: March 2022

Background and Purpose:
In the clinical setting of acute stroke, determination of the amount of penumbra quickly is increasingly important for treatment decisions. The approximate ABC/2 method is an alternative when image quality restricts the usage of automated methods. Our hypothesis is that usage of a web-based ABC/2 app will increase the predictive accuracy of the users’ visual and approximate mismatch estimates.

Methods:
Ten training cases were selected retrospectively from patients diagnosed with acute ischemic stroke at Suburban Hospital or MedStar Washington Hospital Center and scanned acutely with MRI between January 1, 2014 through February 28, 2014. Image readers including four board-certified vascular neurologists and two vascular neurology fellows used DICOM software to initially perform DWI and MTT visual estimates and then to calculate the ABC/2 volumes for DWI, MTT and mismatch using a web based tool. After one month, the vascular neurologists were re-tested. The results from the initial training and re-testing were compared to calculate the agreement of visual mismatch classification versus the planimetric volume calculations, where mismatch was defined as MTT- DWI ≥50 ml across sessions. The correlations of approximate and planimetric calculations were compared for the DWI and MTT measurements.

Results:
For the DWI approximate measurements from the training to the re-testing, the Spearman correlation coefficients with the planimetric measurements increased for four out of the six vascular neurologists with r =[0.78 to 0.96], [0.81-0.88], [0.65-0.94] and [0.88-0.98]. Two readers demonstrated highly correlated DWI measurements, [0.98-0.96] and [0.99-0.93]. For the MTT, the correlations increased for three out of the six vascular neurologists with training to re-testing r =[0.76 to 0.93], [0.87-0.88] and [0.56-0.92]. Two readers demonstrated comparable MTT measurements, [0.94-0.93] and [0.92-0.87]. One reader’s MTT correlation decreased from [0.89-0.71]. The average agreement of the visual mismatch estimates increased from 63% to 70%.

Conclusions:
Using a web-based ABC/2 app was beneficial for increasing the visual mismatch agreement and accuracy of approximate measurements for multiple vascular neurologists.
Abstract W P310: Contemporary Trends In The Ischemic Stroke “Weekend Effect” On IV Thrombolytic Use, In-hospital Mortality, Discharge Disposition, Hospital Charges, And Length Of Stay - A National Perspective
Authors: Jani Vishal B , Lahewala Sopan , Arora Shilpkumar , Patel Achint , Hussain Syed , Razak Anmar , Gidwani Umesh , Hassan Ameer , Chaudhry Saqib , Suri Fareed , Kassab Mounzer , Safdar Adnan , Qureshi Adnan , Majid Arshad
Published: March 2022

Background:
We sought to check current stutus of weekend effect (differences in acute ischemic stroke (AIS) outcomes between patients admitted at the weekend versus weekday) which is the basis of many change in health policy to deal with disparities.

Objective:
To evaluate the influence of admission on a perticular day of the week (DOW) on outcomes in AIS pts.

Methods:
We reviewed the HCUP's Nationwide Inpatient Sample (NIS) database from 2008 - 11 for all emergency room (ER) admissions for AIS using ICD 9-CM code. NIS represents 20% of all US hospital. Pts aged < 18 years were excluded. After adjusting for age, gender, median income level, primary payer, hospital region, teaching status, and bed size, a Survey Logistic and Linear regression models were used to compare weekend versus weekday stroke admissions in terms of: incidence of IV thrombolytic (IVT) use, in-hospital mortality and discharge disposition. Length of stay (LOS) was calculated only in pts who survived. Cost to charge ratio files were merged with NIS to calculate cost of care. The cost of care was adjusted for inflation with reference to 2011. Chi-square was utilized for univariate analysis for categorical variable.

Results:
A total 390,401 (weighted: 1,933,243) ER admissions were studied, of which 99,968 (weighted: 494,863) were admitted on weekends. The average age of the cohort was 71 years, 53.4 % females, and 60.8% were whites. In univariate analysis, admission on weekend was associated with higher mortality (7.28% vs. 7.13%, p<0.001), higher utilization of IVT (4.10% vs. 3.72%, p<0.001) and higher discharge to long term facility (44.7% vs. 42.9%, p<0.001). After adjusting for confounders, weekend admission was associated with higher utilization of IVT (OR/days/cost, 95% CI, P-value) (OR 1.10, 1.06 - 1.14; p<0.001); increased discharge to long term facility (OR 1.08, 1.06 - 1.10; p<0.001) and have statistically shorter LOS (-0.08 days, -0.14 - -0.02; p = 0.007). There was no difference in in-hospital mortality (OR: 1.02, 0.99 - 1.05; p = 0.17) or cost of care (142$, - 5 - 288; p=0.06) for weekend admission.

Conclusion:
Admission on a weekend is a predictor of higher utilization of IVT and discharge to a long-term facility , but there was no difference in in-hospital mortality or cost of care.
Abstract W P311: Clinical outcomes among transferred children with Ischemic and Hemorrhagic stroke in the Nationwide Inpatient Sample
Authors: Adil Malik M , Vidal Gabriel A , Malik Ahmed A , Khursheed Faraz , Qureshi Adnan I
Published: March 2022

Background and Objective:
Ischemic stroke (IS) and Hemorrhagic stroke (HS) Children may require inter-facility transfer for higher level of care. We aimed to compare patient characteristics and clinical outcomes amongst transferred vs. non-transferred in children with IS and HS.

Methods:
Patients admitted to US hospitals between 2008 to 2011 with a primary discharge diagnosis of IS and HS (age 1-18 years) were identified by ICD-9 codes. Using logistic regression, we estimated the odds ratio (OR) and 95% confidence intervals (CI) for in-hospital mortality, and discharge to nursing facilities among transfer vs. non-transfers, after adjusting for potential confounders.

Results:
Of 2815 children with IS, 26.7 % were transferred. In-hospital mortality and discharge to nursing facilities were not different among transferred vs. non-transferred children. After adjusting for age, gender, and confounding factors, In-hospital mortality and discharge to nursing facilities were also not different among transferred vs. non-transferred children. Of 6,879 children with HS, 27.1 % were transferred. Transferred children had higher rates of discharge to nursing facility (25% versus 20% p=0.03) and In-hospital mortality (8% versus 4% p= 0.003) vs. non-transferred. After adjusting for age, gender, and confounding factors, In-hospital mortality [(OR) 1.5, 95% (CI) (1.1-2.4, p=0.04)] remains significantly high in transferred children compared to non-transferred. After adjusting for age, gender, and confounding factors, discharge to nursing facilities were not different among transferred vs. non-transferred children.

Conclusion:
IS was not associated with worse outcomes among inter-hospital transfer patients compared to non-transfers. HS was associated with worse outcomes among inter-hospital transfer patients compared to non-transfers. Organized stroke systems of care may need to consider pre-hospital strategies to increase direct referrals to comprehensive stroke centers and inter-hospital strategies to reduce delays to treatment.
Abstract W P312: Secular Trends of Intravenous Heparin Use for Acute Ischemic Stroke in Korea: From 2008 To 2013
Authors: Chung Jong-Won , Kim Beom Joon , Han Moon-Ku , Park Jong-Moo , Kang Kyusik , Park Tai Hwan , Park Sang-Soon , Cho Yong-Jin , Hong Keun-Sik , Lee Kyung Bok , Lee Jun , Ko Youngchai , Lee SooJoo , Kim Dong-Eog , Kim Dae-Hyun , Cha Jae-Kwan , Kim Joon-Tae , Choi Jay Chol , Shin Dong-Ick , Lee Ji Sung , Lee Juneyoung , Yu Kyung-Ho , Lee Byung-Chul , Bae Hee-Joon
Published: March 2022

Background:
Since the introduction of intravenous (IV) heparin for the treatment of acute ischemic stroke in 1941, its use has been an area of great controversy among neurologists. Current American Heart Association guideline does not recommend IV heparin for the treatment of acute ischemic stroke. We sought to obtain updated information regarding the practices of Korean neurologists with regard to acute heparin use. Methods: Based on a prospective multicenter stroke registry database (CRCS-5), we collected patients with acute ischemic stroke, arrived within 7 days of symptom onset, from 2008 to 2013. Patient’s demographics, medical history and stroke characteristics were compared between IV heparin user and non-user. Results: Total of 23,425 patients from 12 regional stroke centers or university hospitals across the nation was analyzed. The mean age was 67.8 years and 58.1% was male. Median initial NIHSS score was 4 (interquartile range, 2 - 9). Large artery atherosclerosis was the most common cause of acute ischemic stroke (37.1%), followed by cardioembolism (21.9%), and small-vessel occlusion (18.9%). During the study period, use of IV heparin decreased; 9.7% in 2008; 10.9% in 2009; 9.4% in 2010; 6.0% in 2011; 4.7% in 2012; 4.3% in 2013 (p for trend < 0.001). The most prominent reduction was observed between 2010 and 2011, just after the first release of the Korean Stroke Guidelines in October, 2009. Cardioembolism (17.1%) and stroke of two or more causes (15.3%) were associated with IV heparin, and the decrease of IV heparin use in these stroke subtypes was a major contributor of the decrease in general. Age (age ≥ 75, 7.5%; age <75, 6.6%; p = 0.014), initial stroke severity (NIHSS < 5, 5.4%; NIHSS 5 - 24, 8.7%; NIHSS ≥ 25, 9.5%; p < 0.001), and atrial fibrillation on electrocardiogram (atrial fibrillation, 19.9%; non-atrial fibrillation, 4.2%; p < 0.001) were also associated with IV heparin. Conclusions: Use of IV heparin for patients with acute ischemic stroke is decreasing in Korea, and this change may be explained by the development and spread of the national stroke guidelines in the Korean language.