bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 32: Optimal Threshold for Defining Early Clinical Deterioration as a Predictor of Poor Outcome in Acute Intracerebral Hemorrhage
Authors: Sanossian Nerses , Kim-Tenser May A , Liebeskind David S , Burgos Adrian M , Hamilton Scott , Conwit Robin , Eckstein Marc , Stratton Samuel , Pratt Franklin D , Starkman Sidney , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: July 2021

Background:
Many patients with acute intracerebral hemorrhage (ICH) clinically deteriorate between the time of paramedic assessment in the field and Emergency Department (ED) arrival. Cohort studies have used decline in the Glasgow Coma Scale (GCS) score from prehospital assessment to ED assessment to identify patients with early clinical deterioration (ECD), but the degree of GCS decline that best correlates with poor final functional outcome has not been delineated.

Methods:
Consecutive cases with primary ICH on initial imaging were identified from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial of intravenous magnesium vs. placebo. All subjects underwent GCS evaluation in the field by paramedics within 2 hours from symptom onset, and again in the ED by study research coordinators. Poor outcome was defined as a modified Rankin Scale of 4 to 6 at 3-months. Deteriorations in GCS from one point through 10 points were evaluated in relation to poor final functional outcome through receiver operating characteristic (ROC) and area under curve (AUC).

Results:
Among the 369 (22%) patients with primary ICH, mean [SD] age was 65 [13] years, 34% were women, 79% White race, 34% Hispanic ethnicity, 80% had pre-existing hypertension, 20% diabetes, 18% smokers. Paramedic on scene time was a median [IQR] of 23 [15-40] minutes from last known well and time of GCS assessment in the ED was a median of 140 [119-175] minutes after last known well. Glasgow Coma Scale scores were mean 14.4 (SD 1.5) and median 15 [15-15] in the field and mean 12.1 (SD 4.5) and median 15 [10-15] in the ED, and 59% had a poor outcome at 3 months. Frequency of deteriorations on the GCS included: ≥1 point - 38%, ≥2points - 31%, ≥3 points - 27%, ≥5 points - 21%, and ≥10 points - 13%. The best performing cutpoints on the the ROC for predicting poor final outcome were ECD definitions of GCS decline of >=1: sensitivity 54% and specificity 85%; and GCS decline of >=2: sensitivity 46% and specificity 91%. The c statistic for ECD defined as a 1 point GCS decline as a predictor of poor final outcome was 0.71 (95%CI 0.66, 0.76).

Conclusions:
Early clinical deterioration of GCS is common and its presence may be helpful in predicting poor outcome.
Abstract 34: Hypercoagulable Response After Intracerebral Hemorrhage Does Not Occur in Patients With Hematoma Enlargement
Authors: Kawano-Castillo Jorge , Ward Eric , Elliott Andrea , Wetzel Jeremy , Hassler Amanda , McDonald Mark , Parker Stephanie A , Archeval-Lao Joancy , Tremont Chad , Cai Chunyan , Rahbar Mohammad H , Grotta James
Published: July 2021

Background:
Intracerebral hemorrhage (ICH) has high morbidity, and hematoma enlargement (HE) causes worse outcome. Thromboelastography (TEG) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. Speed of clot formation in minutes is measured by parameters R, K, and delta, and clot strength in dynes of resistance by MA and G. We used TEG to detect changes in clotting in patients with and without HE after ICH.

Methods:
This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and 36 ±12 hours, and HE defined as total volume increase > 6cc or >33%.TEG was also obtained from 57 healthy controls. Comparisons between groups were assessed by t-test or Wilcoxon rank sum tests. Multivariable regression was performed after controlling for potential confounders.

Results:
Age and gender were not different between ICH patients and controls. Compared to controls, ICH patients demonstrated faster and stronger clot formation; shorter R and delta (p<0.0001) at baseline; and higher MA and G (p < 0.0001) at 36 hours. 11/64 (17%) patients had HE. Male sex and prior clopidrogel use were more frequent in the HE + group (p<0.05) compared to HE -. After controlling for potential confounders (age, clopidrogel, INR, platelet count), baseline K and delta were longer in HE + vs. HE - patients, indicating that HE+ patients had slower clot formation (p<0.05). TEG was not different between HE + and HE - patients at 36 hours.

Discussion:
TEG may detect important coagulation changes in patients with ICH; clotting may become faster and stronger in immediate response to ICH; a less robust response may be associated with HE. These findings may have relevance to patient management and deserve further investigation.

Delta values at baseline for controls, all hemorrhage patients, hemorrhage enlargement (HE) + and (HE) - patients.
Abstract 35: Stabilizing Bleeding Prior To Acute Therapies For Spontaneous Intracerebral Hemorrhage
Authors: Ziai Wendy , Ullman Natalie L , Thompson Carol , Betz Joshua , Lane Karen , Keyl Penelope , Vespa Paul , Martin Neil A , Zuccarello Mario , Awad Issam A , Hanley Daniel F
Published: July 2021

Objective:
Criteria for stabilizing intracranial bleeding (intracerebral (ICH), intraventricular (IVH) and external ventricular drain-related) in patients screened for acute therapies for spontaneous ICH involving surgery and/or thrombolytic therapy have not been established. We investigated the incidence, time course and factors associated with hematoma growth in the pre-randomization (PR) phase of 3 clinical trials with protocolized serial imaging.

Methods:
Serial CT assessments were performed prospectively on pre-randomization (PR) scans of 141 patients enrolled in the MISTIE II (N=117) and ICES (N=24) trials and the first 300 patients enrolled in the CLEAR III IVH trial to determine the end of ICH and IVH expansion and the occurrence of catheter tract hemorrhage (CTH). We determined ICH, IVH and CTH volumes from diagnosis up to 1st dose of study drug (CLEAR IVH) or 48 hours (MISTIE/ICES) using computerized volumetrics.

Results:
Of 117 patients enrolled in MISTIE/ICES, median [iqr] ICH volume was 38.44 [26.39] cc. PR hematoma expansion > 5cc/>33% was detected in 62 (44%)/38 (27%). Median time to hematoma stability was 14.63/19.82 hours respectively with final events at 40.65/42.60 hrs. Of 300 patients enrolled in CLEAR III, median ICH volume was 7.42[10.08] cc. Initial hematoma expansion >5cc occurred in 33 (11.0%); hematomas were stable at 46.80 hrs after diagnostic CT, the final event detected at 71.87 hrs. Median IVH volume was 26.0[27.20] cc. Initial IVH expansion > 5cc occurred in 82 (27.4%) with stability at 41.27 hrs after diagnostic CT; the final event was detected at 50.50 hrs. CTH was detected in 66 (22.1%). CTH >5cc occurred in 3 (1%). CTHs were stable at median 37.20 hrs after EVD placement, the last CTH detected at 125.50 hrs post-EVD. Only antiplatelet therapy was significantly associated with CTH. In all trials, independent predictors of ICH or IVH expansion >5cc were age, partial thromboplastin time, NIHSS and time from symptom onset to CT.

Conclusions:
CTHs rarely expand in the initial stabilization period, but may be detected after 24 hours from EVD placement. IVH expansion is significantly more common than ICH expansion in patients with severe IVH. Most bleeding events appear to stabilize within 48 hours after diagnostic CT scan.
Abstract 52: Brainstem Infarction is Associated with Sleep Apnea: The BASIC Sleep Project
Authors: Brown Devin L , McDermott Mollie , Mowla Ashkan , Chervin Ronald D , Morgenstern Lewis B , Kerber Kevin A , Hegeman Garnett , Smith Melinda A , Garcia Nelda M , Lisabeth Lynda D
Published: July 2021

Background:
Despite hypotheses that brainstem infarction is associated with sleep apnea (SA), no specific site of infarction has been associated with post-stroke SA in existing studies, which have been relatively small. Within a larger, population-based study, we assessed the association between infarction location and SA presence and severity.

Methods:
Ischemic stroke patients in the Brain Attack Surveillance in Corpus Christi (BASIC) project had SA screening performed (median 13 days after stroke) with a validated portable respiratory monitor (ApneaLink Plus) (n=355). The apnea-hypopnea index (AHI) was used to measure SA severity; SA was defined conservatively as an AHI ≥10. Acute infarction location was determined based on review of CT and MRI reports by board-certified neurologists and dichotomized into brainstem involvement or none. Logistic and linear regression models were used to test the associations between brainstem involvement and SA or AHI in unadjusted and adjusted models.

Results:
Median age was 65 (IQR: 57, 77); 55% were male. Thirty-eight (11%) had acute infarction involving the brainstem. Of those without brainstem infarction, 59% had SA; the median AHI was 13 (interquartile range (IQR) 6, 26). Of those with brainstem infarction, 84% had SA; median AHI was 20 (IQR 11, 38). In unadjusted analysis, brainstem involvement was associated with over three times the odds of SA (OR 3.71 (95% CI: 1.52, 9.13). In a multivariable model, adjusted for demographics, BMI, stroke risk factors, and stroke severity, results were similar (OR 3.76 (95% CI: 1.44, 9.81)). Similarly, brainstem infarction was associated with AHI in unadjusted (p=0.004) and adjusted models (p=0.004).

Conclusion:
Acute infarction involving the brainstem was associated with both presence and severity of sleep apnea in this population-based stroke surveillance study.
Abstract 62: Recovery-based Prediction of Who Is Using a G-tube at 6 Weeks Post-stroke
Authors: Ford Andria L , Leon-Guerrero Christopher , Chua Jasmin , Loehr Lynda , Carpenter David , Edmiaston Jeff
Published: July 2021

Background:
Decision-making regarding gastrostomy tube (G-tube) placement prolongs hospital stay in the inpatient stroke setting. Studies have predicted who receives G-tube placement at discharge, but have not assessed which factors predict who is actually using a G-tube long-term by assessing dysphagia recovery and G-tube needs in follow-up.

Methods:
Stroke patients from an inpatient stroke service were prospectively recruited if dysphagia was identified on the clinical speech therapy dysphagia test, defined as Mann Assessment of Swallowing Ability (MASA) score < 178. Variables associated with dysphagia were prospectively collected. G-tubes were placed in patients according to standard clinical practice based on speech therapy recommendations and family discussion. Follow-up included a 6 week swallowing quality of life survey (SWAL-QOL, 12 items including if a G-tube is currently being used). Univariate predictors of G-tube use at 6 weeks were assessed allowing calculation of a “G-tube Score” for prediction of who required a G-tube at 6 weeks. Score performance was measured by receiver operating characteristic (ROC) curves and area under the curve (AUC).

Results:
Of 146 dysphagic patients (median NIHSS=15), 31% were discharged with a G-tube. Of those completing 6 week SWAL-QOL (N=61), 26% of patients who had received a G-tube, no longer needed a G-tube. Univariate predictors of needing a G-tube included: age ≥ 70 (p=0.017), NIHSS ≥ 18 (p=0.006), ICU admission (p=0.007), respiratory failure requiring intubation (p=0.001), and MASA score < 110 (p<0.0001). 4 and 5 point G-tube scores performed well in predicting 6 week G-tube needs (AUCs 0.88 and 0.92, respectively). The optimal cut-off for both scores, preserving sensitivity and maintaining specificity, was a score of 2 points (Fig).

Conclusion:
Carrying 2 of the following early factors: age ≥ 70, NIHSS ≥ 18, ICU admission, and intubation, yields a high likelihood of requiring a G-tube beyond 6 weeks post-stroke.
Abstract 64: The Use of Oral Anticoagulation After Ischemic Stroke Increases, Users Have Fewer Recurrences, and Are Increasingly Likely to Survive. A Nationwide Study From Finland
Authors: Meretoja Atte , Malmivaara Antti , Roine Risto O , Hakkinen Unto , Kaste Markku
Published: July 2021

Background and Purpose:
Oral anticoagulation (OAC) is an effective secondary preventive therapy after atrial fibrillation related cardioembolic ischemic stroke. We explored the use of OAC after ischemic stroke in Finland, the country with the most rapidly aging population in Europe.

Methods:
Data from 1999 to 2010 were extracted from the PERFECT Stroke registry, a nationwide database of all incident stroke patients hospitalized in Finland. Purchase of warfarin, the only OAC available during the study period in Finland, was registered in all pharmacies in a national database. Recurrence was defined as re-hospitalization with new acute stroke diagnosis through an emergency department. Survival was tracked from the national death registry with 100% follow-up.

Results:
Among the 99,677 incident ischemic stroke cases over the study period, there were 24,327 cases surviving their initial hospitalization and using OAC for secondary prevention. This represented 24.4% of all ischemic stroke patients, increasing from 20.3% in 1999 to 26.7% in 2010. In these OAC users, 1-year recurrence rate of ischemic stroke decreased from 20.1% in 1999 to 12.5% in 2010, while 1-year hemorrhagic stroke rate remained unchanged at 0.4%. Increases in the secondary preventive use of blood pressure medications (from 83.5% to 92.7%), statins (from 32.8% to 73.5%), and a combination of these (from 28.2% to 69.0%) were observed from 1999 to 2010. One-year case-fatality of patients surviving to go home was 4.2% when no recurrences occurred. When secondary prevention failed, patients who experienced a new ischemic stroke had 11.3% likelihood of dying within a year, increasing to 42.0% after a hemorrhagic stroke. After adjusting for age, sex, and comorbidities with a logistic regression model, the odds of 1-year case-fatality decreased over time (OR 0.97; 95% CI 0.95-0.99 per year).

Conclusion:
As the population ages, the proportion of ischemic stroke patients that require oral anticoagulation increases, in our data from 20% to 27% over a period of 12 years. Secondary prevention of stroke in OAC users improved, which could be due to increased use of antihypertensives and statins, and reflected on survival. The risk of hemorrhagic stroke due to anticoagulation for ischemic stroke remains small.
Abstract 71: Refining the CT Angiography Collaterals Scoring System to Better Predict Outcome in Acute Ischemic Stroke
Authors: Sarraj Amrou , Sitton Clark W , Boehme Amelia K , Supsupin Emilio P , Bibars Wafi , Olowu Adeola , Albright Karen C , Martin-Schild Sheryl , Grotta James C , Savitz Sean I
Published: July 2021

Background:
Collateral circulation profile is an important determinant of outcome in patients with large artery occlusion (LAO). We sought to refine the collateral score (CS) to better identify patients with potential for good outcome after AIS.

Methods:
We studied 342 patients presenting to our center with AIS and LAO (MCA or ICA) from 03/05 to 04/13. We modified the CS to a 5 point scale (mCS) (fig 1). We dichotomized the score into unfavorable (0-2A) and favorable (2B-3) profiles. Logistic regression model with good and poor discharge outcome (mRS 0-2 and 4-6, respectively) was used. We performed receiver-operating characteristic (ROC) analysis to compare the mCS with the CS and with ASPECTS.

Results:
Table 1 shows the baseline characteristics. Patients with favorable mCS had a significantly higher odds of a good outcome (OR 9.61, 95%CI 2.78-33.2, p=0.0003). Moreover, patients with unfavorable profile mCS (0-2A) had greater odds of poor outcome at discharge (4-6), and this association was maintained when using more stringent criteria for poor outcome (mRS 5-6) (table 2). These results persisted after adjustment for CT early ischemic changes (ASPECTS) and stroke severity (NIHSS). The modified scale was more precise than the original CS in predicting patients’ clinical outcomes (table 2). Importantly, patients treated with IV tPA who had good collaterals showed better odds of good outcome (OR 7.07, 95%CI 1.39-35.9, p=0.02). Furthermore, mCS showed more specificity and sensitivity than the original CS and ASPECTS as illustrated on ROCs (AUC: 0.73 compared to CS 0.669 and ASPECTS 0.667) in fig 2.

Conclusion:
The modified collateral CTA score (mCS) which gives a finer gradation of the collaterals discriminates better those who have potential for good outcome compared with the CS and ASPECTS. A simple score that does not require sophisticated radiology expertise may help physicians triage patients in the acute setting by identifying patients who may achieve a good outcome.
Abstract 75: Safety of Statin Pretreatment in Intravenous Thrombolysis (IVT) for Acute Ischemic Stroke (AIS)
Authors: Tsivgoulis Georgios , Kadlecová Pavla , Czlonkowska Anna , Brozman Miroslav , Švigelj Victor , Csiba Laszlo , Kõrv Janika , Bašic Kes Vanja , Jatuzis Dalius , Rudolf Jobst , Tampaki Ekaterini-Christina , Krespi Yakup , Mikulik Robert
Published: July 2021

Background&Purpose:
A recent meta-analysis investigating the association between statin pretreatment and early outcomes in patients with AIS indicated that pre-stroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage (sICH). We sought to investigate the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT.

Subjects&Methods:
We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) on consecutive AIS patients treated with IVT during a seven-year period. We used three widely accepted definitions for sICH from NINDS-rtPA-Stroke Study, ECASS II trial and SITS registry. Dramatic clinical recovery (DCR) within 24 hours was defined as reduction in the baseline NIHSS-score of ≥10 points. Favorable functional outcome (FFO) at three months was defined as modified Rankin Scale score of 0-1.

Results:
We analyzed a total of 1660 AIS patients (mean age 67±13 years, median baseline NIHSS-score 11 points, interquartile range 5-16). Patients with statin pretreatment (n=373, 23%) had higher (p=0.019) baseline stroke severity compared to cases who had not received any statin at symptom onset. After adjusting for demographics, baseline stroke severity, onset-to-treatment time, history of previous stroke, risk factors, and admission blood pressure levels, statin pretreatment was not associated with a higher likelihood of sICH defined by the NINDS (OR: 1.41; 95%CI: 0.83-2.39; p=0.201), ECASS II (OR: 1.13; 95%CI: 0.60-2.14; p=0.712) or SITS (OR: 1.89; 95%CI: 0.75-4.77; p=0.178) criteria. Statin pretreatment was not related to three-month all-cause mortality (OR: 0.92; 95%CI: 0.57-1.49; p=0.741) or three-month FFO (OR: 0.81; 95%CI: 0.52-1.27; p=0.364). Statin pretreatment was independently associated with a higher odds of DCR (OR: 1.91; 95%CI: 1.25-2.92; p=0.003).

Conclusions:
Our findings indicate that statin therapy at symptom onset is not associated with adverse outcomes in AIS patients treated with IVT, while statin pretreatment almost doubles the likelihood of DCR during the first hours following tPA-infusion.
Abstract 76: Genome Wide Association Study of Early Neurological Deterioration after Acute Ischemic Stroke Defines the Interferon-Stimulated Gene IFIT1 as a Neuroprotective Factor
Authors: Heitsch Laura , Kraft Andrew , Guilliams Kristin , Ford Andria , Khoury Naim , Connor Lisa , Diamond Michael S , Cruchaga Carlos , Lee Jin-Moo
Published: July 2021

Introduction:
In the first hours after ischemic stroke, neurological deficits can be highly unstable. These early neurological changes are important due to their influence on long-term outcome. We performed a GWAS on

ΔNIHSS
24h
(NIHSS change from baseline to 24 hours after stroke onset)

in acute ischemic stroke patients.

Methods:
DNA from 191 stroke patients presenting within 4.5 hours of stroke onset was genotyped using an Affymetrix Exome-chip. Single variant analysis was performed using PLINK, including age, baseline NIHSS and principal component factors as covariates. European- and African-Americans were analyzed separately, with p-values combined by meta-analysis. Gene-based analysis was performed using SKAT-O, including only non-synonymous variants. Pathway analysis was performed using ALIGATOR to identify pathways with SNPs with significant associations.

IFIT1
-/-

and

IFIT1
+/+

mice underwent one-hour MCA occlusion (tMCAO) followed by 24-hour reperfusion. Brains were removed, TTC-stained, and infarcts measured.

Results:
Single variant analysis did not reveal genome-wide significant associations. One gene,
IFIT1
(interferon-induced protein with tetratricopeptide repeats), passed the gene-based genome-wide multiple test correction (A). All three polymorphic variants in
IFIT1
associated with neurologic deterioration with an average ΔNIHSS
24h
9.5 points lower in carriers versus non-carriers (B). Pathway analysis, including 21 interferon-related genes but excluding
IFIT1
, showed a highly significant association (p=2.30х10
-3
) with ΔNIHSS
24h.
Infarct volumes in

IFIT1
-/-

mice were twice the size of

IFIT1
+/+

mice after tMCAO (C, 110.6 mm
3
vs 52.8 mm
3
).

Conclusion:
These data suggest that
IFIT1
and other interferon-related genes may function in endogenous neuroprotective responses during acute ischemic stroke.
Abstract 80: Early Intervention With High-Dose Statin Decreased the Plaque in Acute Stroke Patients With Intracranial Atherosclerosis: High-Resolution MR Wall Imaging Study
Authors: Ryoo Sookyung , Kim Suk Jae , Cha Jihoon , Moon Gyeong Joon , Kim Gyeong-Moon , Chung Chin-Sang , Lee Kwang Ho , Bang Oh Young
Published: July 2021

Intracranial atherosclerosis (ICAS) is a common stroke etiology, especially in Asians. Current guidelines emphasize statin therapy with intensive lipid lowering effects for risk reduction in atherosclerotic strokes. High-dose statin therapy regress coronary, carotid and aortic atherosclerotic plaques. However the role of statin in patients with ICAS remains unknown. Thus we aimed to evaluate the impact of early intervention with rosuvastatin (20mg/day) on the symptomatic intracranial atherosclerotic plaque, using high-resolution (HR) wall MRI.

Fiffteen patients with acute infarcts caused by ICAS were enrolled. All patients were given high-dose statin, rosuvastatin 20mg/day and performed serial HR MRI with 3-T scanner including proton density/T2-weighted axial/sagittal, T1 FLAIR pre- and post-contrast sagittal/axial and 3-dimensional volumetric isotropic turbo spin echo acquisition images. Serial HR wall MRI were taken before and after 3~6 months of treatment (interval, 141±45 days). Intracranial artery at the maximal stenosis on MRA was analyzed in terms of vascular remodeling (plaque burden) and wall enhancement (plaque activation). Normal vessels were also assessed for reference values. Intracranial atherosclerotic plaques were compared before and after statin treatment.

Both intracranial atherosclerotic plaque burden and activation can be regressed by high-dose statin therapy (Figure). Wall area, a representative of plaque burden, was decreased (pre- vs. post-statin treatment, 5.74±2.63mm2 vs. 4.64±2.58mm2; p=0.027). Enhanced area within the wall, an indicator of plaque activation, was also lowered (pre- vs. post-statin treatment, 3.46±2.15mm2 vs. 2.32±1.81mm2; p=0.013). No patients stop rosuvastatin during follow-up period.

Early intervention with high-dose rosuvastatin in acute stroke patients with ICAS enabled significant reduction of the symptomatic intracranial atherosclerotic plaque during 6 months.
Abstract 83: 30-Day Mortality After Carotid Artery Stenting (CAS) in Trial Versus Real-World Settings
Authors: Jalbert Jessica J , Nguyen Louis L , Gerhard-Herman Marie D , Jaff Michael R , Seeger John D , Kumamaru Hiraku , Williams Lauren A , Liu Jun , Chen Chih-Ying , Johnston Joseph A , Aronow Herbert D , Setoguchi Soko
Published: July 2021

Background and Purpose:
Clinicians rely on randomized controlled trial (RCT) evidence to select treatments but the risk/benefit profile may differ in the real-world. We compared 30-day mortality after CAS among Medicare, contemporary US registry, and landmark RCT patients.

Methods:
We linked Medicare data (2000-2009) to CMS’s CAS Database (CAS-D; 2005-2009) and the Society for Vascular Surgery’s Vascular Registry (SVS-VR; 2005-2008) and estimated 30-day mortality among beneficiaries at least 66 years of age. We compared 30-day mortality risk among our Medicare-linked registry patients to those of landmark RCT and post-marketing commitment registries.

Results:
Average age was lower among RCT patients than among post-marketing registries or Medicare-linked registry patients while symptomatic patients were less common in post-marketing than in Medicare-linked registries or RCTs (Table). SAPPHIRE was the only RCT enrolling high-surgical risk patients but the majority of real-world patients were at high-surgical risk. RCT and post-marketing surveillance registries had minimum provider proficiency requirements while the CAS-D and SVS-VR did not. 30-day mortality risk among Medicare-linked CAS-D (n=22,516) and SVS-VR (n=1,999) was 1.7% (95% CI: 1.5-1.8%) and 1.8% (95% CI: 1.2-2.4%), respectively. 30-day mortality risks among symptomatic Medicare patients were 1.6 to 3.8 times that of RCT CAS patients and mortality risks among RCT patients were lower than among Medicare-linked asymptomatic patients. 30-day mortality risks among registries providing physician training was ~1%, between that of RCTs and Medicare-linked registry patients.

Conclusion:
Medicare CAS patients have much higher 30-day mortality risks than patients in RCTs or registries with provider training programs because of differences in age, comorbidity burden, and provider proficiency. These findings underscore the importance of evaluating CAS effectiveness in the real-world.
Abstract NS15: A Better Understanding of Readmission After Stroke by Including Stroke Survivor and Caregiver Perspectives
Authors: White Carole L , Brady Tracy L , Saucedo Laura L , Motz Deb , Sharp Johanna A , Birnbaum Lee A
Published: July 2021

Background:
At least 30% of stroke survivors (SSs) are readmitted in the first year after stroke. By identifying factors that lead to readmission, we can develop meaningful quality indicators for post-stroke care that target ways to improve health and support the SSs ability to manage at home. Objectives were to: i) estimate readmission rate in a cohort of older SSs at 1 and 6 months after stroke, ii) identify reasons for readmission, and iii) describe the experience of readmission from the perspective of the SS and family caregiver (CG).

Methods:
This mixed-methods study was undertaken utilizing electronic medical records to track readmissions and qualitative interviews were conducted with SSs and CGs. Older adults (≥ 60 years) with stroke admitted to two hospital systems were enrolled in the cohort and followed for 6 months to capture readmissions. A sample of SSs and CGs were interviewed following readmission to gain their perspective related to discharge after stroke and subsequent readmission.

Results:
Of the 310 included in the cohort (mean age 76 years, SD 9.8), 10% died prior to discharge. Within one month 10% were readmitted and 25% within 6 months. The main reasons for readmission were recurrent stroke/TIA (19%), pneumonia and urinary tract infection (19%), swallowing problems and dehydration (9%), and cardiac causes (7%). Discharge to a skilled nursing facility (p=.007) and higher Rankin score on discharge (p=.002) were associated with readmission. Semi-structured interviews conducted with 20 SSs and CGs revealed the following themes related to discharge and readmission: discharge preparation that includes their social and cultural context; need for anticipatory guidance on what to expect when home; support for self-management in the community; knowing when to request help; follow-up in the community that could lead to early identification of problems; complexity of medication management; and importance of social support.

Conclusions:
The perspective of the SS and CG is critical in identifying potential avenues for intervention, aimed at reducing preventable readmissions. Interventions aimed at the transition between hospital and skilled nursing facilities may reduce readmissions.
Abstract NS17: One Hospital's Experience in Establishing a Stroke Peer Visitor Program
Authors: Droegemueller Carol J
Published: July 2021

Background and Purpose:
Literature suggests that despite being overwhelmed during the acute phase of stroke, patients and families want and are accepting of the support a peer visitor can provide. While patients undergoing acute rehabilitation services in our organization were exposed to a stroke peer visitor network, there was no equivalent peer program for in-patient stroke survivors. Therefore, the purpose was to design, develop and implement a stroke peer visitor program for hospital in-patients.

Methods:
Using the ShareGivers
™
Peer Visiting program resources as a guide, an in-patient stroke peer visiting program was designed and implemented. Recruitment and training of stroke survivor peer mentors was followed by individualized on-site orientation and program implementation. Evaluations of the program were ongoing.

Results:
Through 23 weeks of program implementation, six stroke peer visitors contributed 111 hours making 61 patient visits. Stroke peer visitors contributed an average of 5 hours per week. Stroke in-patients welcomed the visits from the peer visitors. Feedback was positive from nursing staff, patients/families and the peer visitors. Common responses were, “I love it when the stroke volunteers are here”, “so helpful to hear from someone who’s been there”, “the patient/family had so many questions”, “had a great visit”.

Conclusions:
Participant feedback suggests peer visits in the acute phase of stroke recovery are important, beneficial and inspirational. Desire for growth of the program is reflected in requests for annual orientation, adding more peer volunteers, partnering new with experienced volunteers during training and introducing area hospitals to a central peer visiting training concept. Implication for future nursing research includes quantifying the benefits of peer visitation for stroke survivors and their families while in the acute phase of stroke recovery.
Abstract NS2: Code Neuro Nurses May Improve Door-to-Needle Times in Posterior Circulation Strokes
Authors: Summers Debbie , Rymer Marilyn , Wessol Jennifer
Published: July 2021

Background:
Posterior circulation strokes (PCS) can be more difficult to diagnose than anterior circulation strokes (ACS). Ambiguous symptoms such as isolated vertigo, non-lateralizing signs and low National Institute of Health Stroke Scale (NIHSS) scores have been shown to delay treatment with intravenous (IV) tissue plasminogen activator (tPA) and prolong Door-to-needle (DTN) times. In 2006, this institution implemented the use of Code Neuro Nurses 24/7 as part of a highly developed stroke response system of care, to expedite diagnosis and treatment of all stroke patients. As part of this program, all patients in the Emergency Department (ED) with suspected stroke are evaluated by a Code Neuro Nurse. Anecdotal evidence suggested that overall DTN times improved as a result of the Code Neuro Nurse. But were DTN times still prolonged in PCS patients compared to ACS patients?

Purpose:
The purpose of this project was to determine if DTN times in PCS were longer than times for ACS, in patients who received IV tPA.

Methods:
An IRB approved retrospective chart review of ischemic stroke cases in 2011 and 2012 found 145 patients who received IV tPA. Data analysis was performed on data elements contained in the table.

Results:
Of the 145 patients who received tPA, 15.8% (n=23) had PCS. Age and gender were similar between the two groups. Mean admission NIHSS scores in patients with PCS were lower than scores in ACS patients. There were no differences in mean DTN times for PCS compared to ACS. Mortality and disposition to home were not different between the groups.

Conclusion:
As expected, the admission NIHSS scores for PCS tended to be lower than for ACS, which can contribute to delays in DTN times. However, there was no statistical difference in DTN times between the two groups. Utilizing the expertise of the Code Neuro Nurse in the ED may be a key factor in accurately and efficiently diagnosing PCS strokes, leading to DTN times comparable to ACS cases.
Abstract NS4: The Power of Outreach: How Educating the Community Increases the Role of rtPA.
Authors: Rindels Erin , Overton Angela
Published: July 2021

Background:
Stroke is the fourth leading cause of death for all Iowans, and the third leading cause of death for women in Iowa. The certification of stroke centers has improved treatment with rt-PA, which leads to improved patient outcomes. The University of Iowa Hospitals and Clinics (UIHC) began the process of stroke certification in 2005. One of the goals of this process was to strengthen outreach to community hospitals.

Purpose:
The purpose of this project was to review how improving an outreach program assisted with increasing treatment of ischemic stroke patients with rt-PA.

Methods:
The University of Iowa (UI) stroke program collaborated with UIHC’s physician liaison department to improve outreach by increasing the number of educational visits to community hospitals. The visits were conducted by a physician and nurse coordinator from the stroke program, and a physician liaison who traveled to community hospitals. Presentations were tailored to fit the needs and questions of each individual hospital; however there was an emphasis on updates in stroke care and the new streamlined process for contacting UIHC vascular neurologists with referrals.

Results:
The following table shows treatment of ischemic stroke patients treated with rt-PA. The blue line indicates patients treated at UIHC and the red line indicates those treated at a community hospital and transferred to UIHC.

Conclusion:
In conclusion, an increase in patients treated with rt-PA was noted after improving the stroke community hospital outreach program.
Abstract T MP11: Acute Endovascular Reperfusion Therapy Has Inconsistent Results Across Randomized Clinical Trials -A Systematic Review and Meta-Analysis
Authors: Osanai Toshiya , Pasupuleti Vinary , Deshpande Abhishek , Thota Priyaleela , Roman Yuani , Hernandez Adrian V , Uchino Ken
Published: July 2021

Introduction:
Endovascular (intra-arterial, IA) therapy for acute ischemic stroke has become part of acute therapy , but limited randomized clinical trials have had inconsistent results. We sought to evaluate efficacy and safety of endovascular therapy in - randomized clinical trials .

Methods:
We performed a systematic review of literature for randomized clinical trials of endovascular therapy with thrombolytic or mechanical reperfusion compared with comparator groups without IA therapy. Use of systemic thrombolysis was not excluded. Primary outcome was modified Rankin scale of disability of 0-2 at 90 days and secondary outcomes of mortality at 90 days and symptomatic intracranial hemorrhage was noted. Two groups of independent reviewers searched and identified studies and abstracted data. Random-effects meta-analysis was performed. Subgroups were analyzed by study design characteristics.

Results:
Systematic search identified 10 studies with 1572 subjects, of which 9 studies reported the primary outcome. IA therapy was associated with good outcome at 90 days (Odds ratio (OR) =1.28; 95% CI, 1.01 to 1.62; p=0.04), but there was significant heterogeneity with p of 0.03. Among 3 trials (n=1136) comparing mechanical thrombectomy with control, mechanical thrombectomy was not superior to control with good outcome (OR=0.98; 95 % CI, 0.85 to 1.14; p=0.83). Patients with IA therapy significantly have good outcome in studies without systematic thrombolysis in the comparator (OR=1.55; 95 % CI, 1.05 to 2.29; p=0.03) and required vessel occlusion for randomization (OR=1.54; 95 % CI, 1.10 to 2.14; p=0.01). Mortality was unchanged with IA therapy (OR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in symptomatic hemorrhage (OR=1.13; 95 % CI, 0.74 to 1.74; p=0.56).

Conclusion:
IA therapy has a small but significant increase in good outcomes for patients with acute ischemic stroke without increasing mortality and symptomatic hemorrhages.
Abstract T MP111: Gpr124 Regulates Post-Stroke Cerebrovascular Integrity
Authors: Mancuso Michael , Chang Junlei , Maier-Albers Carolina , Kosinski Cynthia , Liang Xibin , Chang Pak , Andreasson Katrin , Kuo Calvin
Published: July 2021

Introduction:
GPR124/TEM5 is an orphan G-protein coupled receptor (GPCR) with a large extracellular domain. We and others have previously demonstrated that GPR124 exerts CNS-specific angiogenesis regulation with knockout mice exhibiting embryonic lethality from hemorrhagic glomeruloid vascular malformations in forebrain and neural tube (c.f. Kuhnert et al., Science
,
Nov 12;330(6006):985-9
.
(2010)).

Hypothesis:
GPR124 regulates adult angiogenesis and blood-brain barrier (BBB) integrity during homeostasis or after stroke.

Methods:
To bypass GPR124 embryonic lethality, we generated GPR124 conditional knockout (cko) mice allowing temporally-regulated deletion. Tamoxifen treatment of GPR124
flox/-
; ROSA-CreER mice versus GPR124
flox/+;
ROSA-CreER littermate controls allowed GPR124 cko versus heterozygosity, respectively, in adult mice. GPR124 deletion was followed by analyses of microvascular structure and patterning and blood-brain barrier (BBB) integrity). GPR124 cko mice versus controls were also subjected to 60 minute middle cerebral artery occlusion (MCAO) and effects on stroke volume, survival and microvascular structure assessed.

Results:
GPR124 deletion in neonatal or adult mice was well-tolerated without impairment of postnatal vascular patterning, BBB maturation or BBB integrity. However, GPR124 cko mice subjected to the middle cerebral artery occlusion (MCAO) stroke model exhibited impaired survival and a profound microvascular hemorrhagic transformation that was confined to the infarct region relative to wild-type controls. GPR124 cko stroke vasculature also exhibited numerous cellular and architectural defects relative to controls that will be discussed.

Conclusions:
GPR124 deletion is well tolerated in adult mice but results in marked hemorrhagic transformation in the MCAO stroke model. GPR124 represents a novel receptor whose function is essential for cerebrovascular integrity in the post-stroke setting, with attendant therapeutic implications.
Abstract T MP119: Forced Swim Test as an Index of Post-Stroke Depression in Rats
Authors: Kunze Allison , Zierath Dannielle , Barclay Tessa , Becker Kyra J
Published: July 2021

Background:
Depression is common after stroke. The Porsolt Forced Swim Test (FST) is used to screen for depression and response to therapy in rodent models. The duration of immobility is considered to be an indication of learned helplessness. In this study we aimed to characterize post-stroke depression using the FST.

Methods:
Male Lewis (N=6), Wistar (N=5), and Sprague Dawley (SD; N=11) rats were subjected to the FST (10 minutes) prior to 2 hours middle cerebral artery occlusion (MCAO) and then again at 28 days after MCAO. Sham-operated animals were used as controls. The latency to immobility and the duration of immobility were assessed along with the maximum velocity of movement. Blood was obtained at the time of sacrifice and assayed for interleukin (IL)-1α, IL-1β and IL-10. Statistics are non-parametric; data are displayed as median and interquartile range.

Results:
Prior to stroke, the latency to immobility was similar in all strains, but the duration of immobility was greater in Lewis rats (201 [159, 294] secs;
P
=0.039) than in Wistar (148 [106, 184] secs) and SD rats (136 [112, 200] secs). The maximal velocity of movement in Lewis rats (47 [42, 55] cm/sec;
P
=0.007) was faster than Wistar (29 [25, 41] cm/sec) and SD (39 [34, 46] cm/sec) rats. In comparison to strain matched sham-operated animals, stroke was associated with an
increase
in the period of immobility (P=0.088), a
decrease
in latency to immobility (
P
=0.019) and an
increase
in the maximal velocity of movements (
P
=0.033) in Lewis rats. No significant differences in FST behavior were seen in Wistar or SD rats. Plasma concentrations of IL-1α (P=0.001) and IL-10 (P=0.011) were highest in Lewis rats at the time of sacrifice. The duration of immobility was most highly correlated with IL-1β (r=0.663,
P
=0.003) and IL-10 (r=0.575,
P
=0.013).

Summary:
At baseline, Lewis rats exhibit more depressive behavior than Wistar and SD rats, and stroke appears to enhance these differences. The change in behavior on the FST is associated with an increase in markers of systemic inflammation. The FST could be used to study interventions for post-stroke depression.
Abstract T MP17: Reduced Lesion Volume in the rtPA-Epifibatide Group in CLEAR-ER Study
Authors: Javadi Ariyan , Adeoye Opeolu , Khoury Jane , Sucharew Heidi , Schmit Pamela , Tomsick Thomas , Pancioli Arthur
Published: July 2021

Trial Introduction/Purpose:
The
C
ombined Approach to
L
ysis Utilizing
E
ptifibatide and
r
t-PA in Acute Ischemic Stroke-
E
nhanced
R
egimen (CLEAR-ER) trial demonstrated the safety of a reduced-dose rtPA regimen (0.6mg/kg rt-PA over 40 minutes) plus eptifibatide (135mcg/kg bolus followed by a two-hour infusion at 0.75mcg/kg/min), and gave evidence of potential clinical efficacy. The purpose of our study is to examine if differences in lesion volume between the 2 groups further support better clinical outcomes as an additional outcome measure in the CLEAR-ER study.

Methods:
Lesion volumes on 24-hour CT (n=117) and MR images (n=2) from subjects with anterior circulation ischemia in the CLEAR-ER Study were calculated using HLW/2 method. Volumes were compared using multiple regression to adjust for baseline mRS, NIHSS, age, and time to IV rtPA administration. Volumes were log transformed for analysis due to the distribution. Geometric means and 95% confidence intervals are shown.

Results:
Mean lesion volumes (adjusted and unadjusted) and p value are presented in Table 1.

Discussion:
51.0 % smaller mean adjusted lesion volumes between the combined-treatment and rt-PA-only groups in the CLEAR-ER study supports the clinical benefit observed with combined therapy previously reported. Whereas the findings reported remain hypothesis generating, more conclusive prospective research is needed for confirming the findings of this preliminary analysis.
Abstract T MP19: Intreped Registry: Association of Procedure Time With Complications
Authors: Lopes Demetrius , Kallmes David ,   IntrePED Investigators
Published: July 2021

Purpose:
To assess the association of procedure time with neurologic adverse events post Pipeline Embolization Device (PED) placement for intracranial aneurysm treatment.

Methods:
In the IntrePED Registry, a retrospective review was performed at 17 centers to identify consecutive intracranial aneurysms treated with the PED following regulatory approval in the given country. All patients in whom at least one PED was placed and follow-up was available prior to IRB approval were enrolled. “Primary adverse events” included major stroke, major hemorrhage, and neurological mortality.

Results:
793 patients with 906 aneurysms, including 311 large ICA, 536 other anterior and 59 posterior circulation aneurysms were enrolled and followed for a mean duration of 19.3 months. 689 (77%) of 906 aneurysms were saccular and 116(13%) were fusiform. 824 (91%) were unruptured. 308 (34%) treated with multiple PEDs. Incidence of major hemorrhage, stroke and neurological mortality was 2.4%, 4.7% and 3.8% respectively. Heparin was administered in 89% of the patients during the procedure. An average of 1.5 PEDs were utilized per case. The mean procedure time was 101.5 ± 50.5 mins. Patients with a major complication (major stroke, major hemorrhage, neurological mortality) had procedure time of 138.2 + 81.5 min, and those without a major complication had procedure time of 98.3 + 45.5 min (p< 0.001). A logistic regression incorporating aneurysm size and number of PEDs used still showed a highly significant relationship between major complications and procedure time (p<0.001) and also found aneurysm size to be an independent predictor of longer procedures (p=0.007).

Conclusions:
The present analysis of IntrePED Registry subjects demonstrates a strong association of procedure time with complication rates. Further analyses of factors leading to longer procedure times is needed.
Abstract T MP20: A Rapid Clot Lysis Assay to Predict Response to IV rt-PA in Stroke
Authors: Sazonova Irina Y , Janes Francesco , Waller Jennifer L , Brittain Julia E , Gigli Gian Luigi , Giacomello Roberta , Hess David C , Switzer Jeffrey A
Published: July 2021

Background:
The cornerstone of acute stroke therapy is intravenous rt-PA, with the goal of rapid thrombolysis and restoration of blood flow. Unfortunately, less than half of patients treated have a favorable outcome. Since recanalization is closely correlated with the clinical response, endogenous resistance to rt-PA may inhibit thrombolysis and neurologic improvement. The primary objective of this research study was to evaluate whether an in vitro clot lysis assay and thrombolytic biomarkers could predict response to IV rt-PA in acute ischemic stroke patients

Methods:
Ischemic stroke patients who received IV rt-PA were recruited from two sites (Augusta, GA and Udine, Italy). Blood samples were collected prior to rt-PA administration and a favorable clinical response to rt-PA was specified as an NIHSS score of two or less at 24 hours. The time required for 50% platelet-poor clot lysis (C50%) was measured by an in vitro turbidimetric assay. The endogenous major fibrinolytic inhibitors (tissue plasminogen inhibitor, PAI-1; and α2-antiplasmin, α2-AP), D-dimer, fibrinogen and pro-thrombin time (PT), were assessed and correlated with clinical outcome.

Results:
We enrolled 54 rt-PA recipients (63±15 years; 72% male, and 85% white). The mean NIHSS was 11.2±5.1 at admission and 8.2±8.1 at 24 hours; 36% of patients had a favorable clinical response. There was a moderate reduction in C50% among patients with a favorable clinical outcome compared to those with an unfavorable outcome (669.5±46.3 vs. 704.7±91.6; p=0.075). There was no significant difference in PT (13.6±0.8 sec vs. 13.8±1.2 sec; p=0.444), PAI-1(28.2±34.1 pg/mL vs. 19.8±25.9 pg/mL; p=0.321), α2-AP (85.1±7.2 % vs. 88.8±10.1 %; p=0.153), D-dimer (269.5±232.2 ng/mL vs. 368.2±444.6 ng/mL; p=0.303) or fibrinogen (318.1±71.4 mg/dL vs. 343.0±173.1 mg/dL; p=0.465) levels between subjects with favorable and unfavorable response to rt-PA. Summary: Lack of response to IV rt-PA in stroke patients may reflect endogenous resistance to fibrinolysis reflected by prolonged clot lysis in vitro. The utility of clot lysis to predict rt-PA unresponsiveness should be tested in a larger clinical study.