bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 189: Intensive Versus Guideline Antiplatelet Therapy For Preventing Recurrence In Patients With Acute Ischaemic Stroke Or TIA: Results In Minor Stroke And TIA From The Triple Antiplatelets For Reducing Dependency In Ischaemic Stroke (TARDIS) Trial
Authors: Bath Philip M , Woodhouse Lisa J , Flaherty Katie , Havard Diane , England Timothy J , Sprigg Nikola
Published: June 2021

Background:
The risk of recurrence following an ischaemic stroke (IS) or transient ischaemic attack (TIA) is high, especially immediately after the event. Since one antiplatelet agent is more effective than none, and two are are superior to one, even more intensive treatment might be more effective in preventing recurrence.

Methods:
TARDIS was an international prospective randomised open-label blinded-endpoint controlled trial. Patients with acute (<48 hours) non-cardioembolic IS or TIA were randomised to intensive antiplatelet therapy (combined aspirin, clopidogrel and dipyridamole) or guideline antiplatelets (clopidogrel alone, or combined aspirin and dipyridamole) given for one month. The primary outcome was stroke and TIA recurrence, and their severity (based on modified Rankin Scale), at 3 months. Patients or relatives gave written informed (proxy) consent and all sites had research ethics approval. The trial was funded by the British Heart Foundation and NIHR Health Technology Assessment programme.

Results:
The Independent Data Monitoring Committee recommended stopping the trial in March 2016 since a definitive result had been reached. Of 3,096 patients, 2213 (71%) were enrolled with minor stroke (NIHSS <=3) or TIA. At baseline: mean age 69 (SD 10); male 62%; prior stroke 10%; diabetes 18%; index event IS 57%, TIA 43%; severity in IS (National Institutes of Health Stroke Scale) 1.8 (1.0); ABCD2 in TIA 5.1 (0.9); onset to randomisation <12 hours 11%, <24 hours 35%.

Summary:
The results will be available for presentation in quarter 4 2016. TARDIS is large enough to influence clinical practice.
Abstract 19: Machine Learning Approach Identifies a Pattern of Gene Expression in Peripheral Blood Which Can Accurately Detect Ischemic Stroke
Authors: O’Connell Grant C , Petrone Ashley B , Treadway Madison B , Tennant Connie S , Lucke-Wold Noelle , Chantler Paul D , Barr Taura L
Published: June 2021

Objective:
The identification of stroke-associated biomarkers represents a means by which prehospital triage could be expedited to increase the probability of successful intervention. Thus, the objective of this work was to use high-throughput transcriptomics in combination with basic machine learning techniques to identify a pattern of gene expression in peripheral whole blood which could be used to identify acute ischemic stroke (AIS) in the acute care setting.

Methods:
A two-stage study design was used which included a discovery cohort and an independent validation cohort. In the discovery cohort, peripheral whole blood samples were obtained from 39 AIS patients upon emergency department admission, and from 24 neurologically asymptomatic controls. Microarray was used to measure the expression of over 22,000 genes and a pattern recognition technique known as genetic algorithm k-nearest neighbors (GA/kNN) identified a pattern of gene expression that optimally discriminated between AIS and controls. In an independent validation cohort, the gene expression pattern was tested for its ability to discriminate between 39 AIS patients and each of two different control groups, one consisting of 30 neurologically asymptomatic controls, and the other consisting of 15 stroke mimics, with gene expression levels being assessed by qRT-PCR.

Results:
In the discovery cohort, GA/kNN identified ten transcripts (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B, and PLXDC2) whose coordinate pattern of expression correctly identified 98.4% of subjects (97.4% sensitive, 100% specific). In the validation cohort, the same 10 transcripts correctly identified 95.6% of subjects when comparing AIS patients to asymptomatic controls (92.3% sensitive, 100% specific), and 96.3% of subjects when comparing AIS patients to stroke mimics (97.4% specific, 93.3% sensitive).

Conclusion:
These results demonstrate that a highly accurate RNA-based companion diagnostic for AIS is plausible using a relatively small number of markers. The pattern of gene expression identified in this study shows strong diagnostic potential, and warrants further evaluation to determine true clinical efficacy.
Abstract 193: Real-time Quantitative Changes in Cerebral Blood Flow From Intra-arterial Vasodilator Treatment in Cerebral Vasospasm
Authors: Sheth Sunil A , Scalzo Fabien , Quachtran Benjamin , Liebeskind David S , Saver Jeffrey L , Duckwiler Gary , Gonzalez Nestor R
Published: June 2021

Introduction:
Intra-arterial (IA) vasodilators are key components in the treatment of cerebral vasospasm (CV) resulting from subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI). Angiographic assessments of vessel caliber immediately after infusion, however, are unreliable metrics of treatment effect, and as a result there does not currently exist a clear biomarker against which to titrate treatment. Quantitative cerebral blood flow (CBF) measurements from angiographic images may better characterize treatment effect and provide real-time feedback to guide infusion protocols.

Methods:
From our prospectively maintained institutional registry, we identified patients treated with IA vasodilators in the anterior circulation for CV between July 2014 and June 2016. Angiograms were reviewed by an experienced neuro angiographer blinded to clinical data and subsequent imaging. Regions of interest (ROIs) were drawn by two experienced neuroimagers over the MCA territory. CBF maps were calculated automatically from immediate pre- and immediate post-infusion angiograms using perfusion angiography and averaged over the ROIs.

Results:
A total of 65 angiograms were evaluated from 22 patients treated with vasodilators for CV. Average age was 48 and 60% were female. Etiology of vasospasm included SAH in 83% (54/65), TBI in 14% (9/65) and stroke/vasculopathy in 3% (2/65) Degree of vasospasm varied from mild (20% (13/65)) to moderate ((62% (40/65)) and severe (18% (12/65)). All patients were treated with IA verapamil ranging from 5 mg to 30 mg over the course of 10-60 minutes. Immediate post-infusion angiograms demonstrated improved vascular caliber in 23% (15/65) cases. In comparison, CBF increased on average 11% (SD 49) after verapamil infusion. Verapamil dosage correlated with percent change in CBF (p<0.05, Spearman’s correlation).

Conclusions:
Verapamil infusion resulted in increased CBF in patients with CV from SAH and TBI. Quantitative angiographic CBF may serve as an effective real-time biomarker of treatment efficacy.
Abstract 199: A Predicting Model of Aneurysm Rupture Status Based on High-resolution Magnetic Resonance Imaging
Authors: Liang Feng , Li Fanying , Ou Siqi , Yang Yibing , Qi Tiewei , Huang Zhengsong
Published: June 2021

Objective:
Aneurysm wall enhancement on high-resolution magnetic resonance imaging (HR-MRI) is seen in ruptured aneurysms. However, site, size and other morphology features also contribute to aneurysm rupture. We introduce a model combining aneurysm wall enhancement and these factors to predict rupture status of aneurysm.

Methods:
We prospectively collected data of patients with intracranial aneurysms who received HR-MRI scan before surgical treatment. Aneurysms were divided into ruptured group (n=25) and unruptured group (n=116). Clinical features, imaging features including size, site, width of neck, aspect ratio(AR), daughter sac, and aneurysm wall enhancement scale(AWES) in both groups were analyzed. AWES was categorized on HR-MRI contrast-enhanced T1WI images: grade 0, no enhancement; grade 1, enhancement greater than grade 0 but less than that of the pituitary infundibulum or choroidal plexus; grade 2, enhancement greater than or equal to that of the pituitary infundibulum or choroidal plexus. Univariate and multivariate logistic regression were performed to evaluate the risk factors of aneurysm rupture status.

Results:
AWES(P<0.001),AR(P=0.0001),daughter sac(P=0.001) and non-ICA location(P=0.002) were higher in ruptured aneurysms. Multivariate logistic regression showed that AWES(OR 5.99,95%CI 2.51-14.29,P<0.001),daughter sac(OR6.22,95%CI 1.68-23.16,P=0.006),and non-ICA location(OR6.25,95%CI 1.35-28.30,P=0.019) were associated with aneurysm rupture status. A simplified predicting model (SAD model) using site(non-ICA,1; ICA,0), AWES(2,1,0), daughter sac(yes,1; no,0) predicted 0, 2%, 12%, 44% and 100% of ruptured aneurysms from scale 0 to 4(Area under curve 0.8920, 95%CI 0.8241-0.9404).

Conclusion:
SAD model is helpful to predict rupture stutus of aneurysm and may provide a new tool to screen high-risk aneurysms.
Abstract 20: Specific Point-of-care Testing of Coagulation in Patients Treated with Non-vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)
Authors: Härtig Florian J , Peter Andreas , Spencer Charlotte , Ebner Matthias , Meyer-Zuern Christine , Peveto Theresa , Pearman David , Spencer Jeffrey , Blumenstock Gunnar , Kuhn Joachim , Birschmann Ingvild , Ziemann Ulf , Poli Sven
Published: June 2021

Introduction:
Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF). Despite treatment, stroke rate in NOAC-treated AF-patients remains 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis or reversal therapy, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT.

Hypothesis:
Ecarin clotting time (ECT)- and anti-Xa activity (ENOX)-POCT predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban.

Methods:
80 patients receiving first NOAC-dose and 80 already on NOAC-treatment are enrolled in the SPOCT-NOAC I trial (N=40 for each NOAC). Subjects receiving other anticoagulants are excluded. Six blood samples are collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations are measured by mass spectrometry.

Results:
240 blood samples of 40 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-274ng/mL. ECT-POCT ranged from 20-196s. Pearson’s correlation coefficient showed strong correlation between ECT-POCT and dabigatran-concentrations (r=0.87). Performance was improved through the use of citrated in place of non-citrated whole blood (r=0.93). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT >50s with 98% sensitivity and 79% specificity. Baseline-samples not containing any dabigatran yielded normal ECT values.

Conclusions:
This is the first study evaluating NOAC-specific POCT. Final results in the dabigatran group of SPOCT-NOAC show excellent correlation between ECT-POCT and dabigatran plasma concentrations; performance of ECT-POCT is even increased through the use of citrated whole blood. Relevant dabigatran-concentrations are detected with excellent sensitivity and specificity. In addition to ECT-POCT, we will present data on ENOX-POCT from apixaban-, edoxaban- and rivaroxaban-treated patients.
Abstract 201: Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-necked, Bifurcation Aneurysms
Authors: Spiotta Alex M
Published: June 2021

Background:
The safety and probable benefit of the PulseRider
®
(Pulsar Vascular, San Jose, CA) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, non-randomized, single arm clinical trial - the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction Trial (ANSWER).

Objective:
We present the results of the United States cases employing the PulseRider

®

device as part of the ANSWER clinical trial.

Methods:
Aneurysms treated with the PulseRider

®

device among U.S. sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study.

Results:
34 patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3 - 11.6 mm). In all patients the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at six month follow up.
A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months.

Conclusions:
The results from the U.S. cases of the ANSWER trial demonstrate that the Pulse Rider® device is safe and effective as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.
Abstract 202: Vision Outcomes for Paraclinoid Aneurysms Treated with Clipping, Coiling, or Flow Diversion: A Meta-analysis
Authors: Silva Michael A , See Alfred P , Dasenbrock Hormuzdiyar H , Aziz-Sultan Mohammad A
Published: June 2021

Introduction:
Paraclinoid aneurysms commonly present with visual impairment. They were traditionally treated with clipping or coiling, but flow diversion has recently been introduced as an alternative treatment modality. Although there is still initial aneurysm thrombosis, flow diversion is hypothesized to reduce mass effect, which may decompress the optic nerve when treating visually symptomatic paraclinoid aneurysms. We performed a meta-analysis to compare vision outcomes following clipping, coiling, or flow diversion of paraclinoid aneurysms in patients presenting with visual impairment.

Methods:
A systematic literature review was performed using the PubMed and Web of Science databases. Studies written in English between 1980-2016 were included if they reported preoperative and postoperative visual function in at least 5 patients with visually symptomatic paraclinoid aneurysms (cavernous segment through ophthalmic segment) treated with clipping, coiling, or flow diversion. Neuro-ophthalmologic assessment was used when reported.

Results:
Thirty-nine studies totaling 2458 patients (20%, 510 of whom presented with visual symptoms) met our inclusion criteria, including 309 visually symptomatic cases treated with clipping (mean follow-up, 25.9 mo), 138 treated with coiling (17.1 mo), and 63 treated with flow diversion (11 mo). Postoperative vision in these patients was classified as improved, unchanged, or declined compared to preoperative vision. We found that vision improved in 57% (95% CI 47-67) of patients after clipping, 45% (34-57) after coiling, and 73% (56-88) after flow diversion. Vision worsened in 11% (7-17) of patients after clipping, 8% (2-17) after coiling, and 7% (0-27) after flow diversion. New visual deficits were found in patients with intact baseline vision at a rate of 0.69% (0-2) for clipping, 0.53% (0-3) for coiling, and 0.80% (0-3) for flow diversion.

Conclusion:
Our data demonstrates a high rate of visual improvement and a low rate of iatrogenic vision impairment for patients with paraclinoid aneurysms treated with flow diversion. Further analysis is needed to compare flow diversion to clipping and coiling and inform clinical management of visually symptomatic paraclinoid aneurysms.
Abstract 205: Longitudinal Study of Intracranial Atherosclerosis Using 3D High Resolution MRI Imaging
Authors: Zhang Xuefeng , Yang Huan , Shahriari Mona , Liu Li , Zhang Yiyi , Guallar Eliseo , Wasserman Bruce , Qiao Ye
Published: June 2021

Hypothesis:
The progression of asymptomatic intracranial atherosclerotic disease (ICAD) remains relatively unknown. We sought to determine whether the progression of ICAD over 24 months can be quantitatively detected using 3D high-resolution vessel wall MRI.

Methods:
28 participants with identified ICAD (14 male; mean age, 80.1±4.94 years, ranges, 71 to 89) were enrolled from Atherosclerosis Risk in Communities Study. The baseline MRI exams were performed on a 3T Siemens scanner that included 3D time-of-flight MRA and 3D black blood MRI (BBMRI) (e.g., acquired resolution: TOF, 0.55 x 0.5 x 0.5 mm
3
; BBMRI, 0.5 mm
3
) for identifying atherosclerosis in major intracranial arteries. The follow-up MRI exams were repeated to determine the progression of ICAD. The mean time interval between two scans was 2.65±1.48 years. Three trained readers independently measured the degree of stenosis, plaque thickness, and normalized wall index for both normal wall and identified plaques in both visits. Plaque progression was defined by plaque showing > 2 measurement error of increase in plaque thickness. Reliability was assessed by intraclass correlations (ICC).

Results:
Inter- and intra-reader reliability for MRI measurements ranged from fair to excellent (ICC, 0.58-0.82). The mean coefficient of variation was 10% for mean wall thickness, 13% for maximum wall thickness and 12% for normalized wall index. Of the 28 participants with ICAD identified at baseline, 18 of 28 participants (64%) had either new plaques or evidence of plaque progression. A total of 152 and 163 plaques were identified at baseline and follow-up, respectively. Among 152 plaques, 45 (30%) progressed, and mean, maximum wall thickness, stenosis and normalized wall index increased 36%, 28%, 27% and 14%, respectively (Table 1).

Conclusion:
3D High-resolution vessel wall MRI is reliable tool for measuring changes in ICAD plaque and provides insight into the natural history of ICAD progression in general population.
Abstract 208: Periprocedural Stroke and Myocardial Infarction as Risks for Long-term Mortality in CREST
Authors: Jones Michael R. , Roubin Gary S. , Clark Wayne M. , Mackey Ariane , Blackshear Joseph , Hill Michael D. , Cohen David J. , Hughes Susan E. , Voeks Jenifer H. , Meschia James F. , Brott Thomas G.
Published: June 2021

Introduction:
Occurrence of stroke and myocardial infarction (MI) after carotid endarterectomy or stenting have each been associated with increased later mortality.

Methods:
In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) 69 strokes, 37 protocol MIs, and 19 biomarker + only events occurred within 30 days among 2272 patients followed up to 10 years. Mortality was determined and compared for patients with stroke, MI, or biomarker + only to those without. Cox proportional hazard models adjusting for age, sex, symptomatic status and treatment were calculated to assess the relationship between mortality and stroke and mortality and MI status. Kaplan-Meier survival curves were plotted.

Results:
Patients with peri-procedural stroke had a 67% greater likelihood of long-term mortality compared to those without stroke (HR=1.67, 95% CI 1.15,2.43; p<0.007)(Figure A). Patients with a protocol MI had a 249% greater likelihood of mortality, and biomarker+ only patients had a 104% greater likelihood of mortality, compared to those without MI (HR=3.49; 95%CI 2.20,5.53, p<0.0001; and HR=2.04; 95% CI 1.09,3.83, p=0.03)(Figure B).

Discussion:
Stroke, MI, and biomarker + only events following CEA or CAS are associated with increased long-term mortality. The higher risk for MI may be a marker for patients with serious underlying heart disease, rather than causal, providing an opportunity to decrease long-term mortality through aggressive diagnostic evaluation and preventive treatment.
Abstract 211: The Role of Vascular Amyloid β in the Formation of Microhemorrhages in Cerebral Amyloid Angiopathy
Authors: van Veluw Susanne J , Charidimou Andreas , Viswanathan Anand , Frosch Matthew , Bacskai Brian , Greenberg Steven
Published: June 2021

Introduction:
Cerebral microhemorrhages are a key diagnostic feature of advanced cerebral amyloid angiopathy (CAA), but the underlying mechanisms remain poorly understood. We investigate the role of vascular Amyloid β (Aβ) in the formation of microhemorrhages in CAA, examining both human tissue and mouse models.

Methods:
First, we examined the histopathology of microhemorrhages, targeted with post-mortem MRI in humans. Brain slabs from nine cases with moderate/severe CAA were subjected to 7 T MRI. Samples were taken from representative MRI-observed microhemorrhages. On the corresponding histopathological sections we assessed the presence of Aβ in the walls of involved vessels, as well as number of Aβ-positive cortical vessels in areas (<2 mm) surrounding the rupture site. Second, to evaluate microhemorrhage formation in real-time in 3D, we performed in vivo two-photon microscopy in aged APP/PS1 mice with advanced CAA. Mice with previously installed cranial windows were injected with fluorescently labeled anti-fibrin, dextran, and methoxy-XO4 to study clot formation (i.e. microhemorrhages) and their spatial localization in relation to Aβ-positive vessels.

Results:
Human data: in 7/19 microhemorrhages the involved vessels were preserved. Only one of these vessels was positive for Aβ. Moreover, the density of Aβ-positive cortical vessels was lower close to the site of microhemorrhage (~1 positive vessel/mm
2
), compared to control areas (~2 positive vessels/mm
2
). Mouse data: we studied six transgenic ~21 month old APP/PS1 mice and two age-matched wild-type littermates. Mean number of in vivo observed microhemorrhages did not differ between groups (Tg: 1.3 / WT: 1), but the transgenic mice tended to have bigger microhemorrhages (mean size 4706 μm
3
) than their wild-type controls (2505 μm
3
). Interestingly, in the transgenic animals only one microhemorrhage was found in close proximity to vascular Aβ deposits.

Conclusions:
These findings question the widely held assumption that microhemorrhages in CAA are a direct consequence of Aβ deposition in the walls of responsible vessels. Our observations suggest that microhemorrhage formation may not be a direct consequence of more severe CAA locally, but may occur preferentially in areas of relatively low CAA.
Abstract 212: Cortical Superficial Siderosis and Risk of Recurrent Intracerebral Haemorrhage in Cerebral Amyloid Angiopathy: A Meta-analysis
Authors: Charidimou Andreas , Boulouis Gregoire , Moulin Solene , Roongpiboonsopit Duangnapa , Raposo Nicolas , Hernandez-Guillamon Mar , Olivot Jean Marc , Ayres Alison , Schwab Kristin M , Wollenweber Frank A , Rosand Jonathan , Linn Jennifer , Gurol M. E , Cordonnier Charlotte , Greenberg Steven M , Viswanathan Anand
Published: June 2021

Background:
Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre.

Methods:
We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis.

Results:
Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (>3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I
2
: 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p<0.0001, I
2
: 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p<0.0001, I
2
: 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age.

Conclusions:
Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.
Abstract 217: Trends and Outcomes of Intracranial Hemorrhage in HIV Positive Population (2002-2012)
Authors: Patel Achint , Limaye Kaustubh , Shah Harshil , Dave Mihir , Chauhan Kinsuk , Nadkarni Girish , Jani Vishal , Patel Urvish , Lunagariya Abhishek , Onteddu Sanjeeva
Published: June 2021

Background:
The incidence of Intracranial Hemorrhage (ICrH) in HIV patients is on the rise in the United States, especially after the development of newer antiretroviral drugs. This study determines the trends of ICrH in HIV patients in the United States.

Design/Methods:
Data from the Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project (HCUP) were analyzed for years 2002-2012.Hospitalizations with HIV positive status were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 042, V08 and ICrH by 430.xx-432.xx. Cochrane Armitage trend test and multivariate regression were used to analyze temporal trends and the potential reasons for temporal changes over the years.

Results:
A total of 2,584,548 hospitalizations with HIV status were made from 2002 to 2012. Of these, 10,292 (0.40%) admissions were due to ICrH or developed ICrH during hospitalization. Concurrent trend of ICrH and HIV increased from 0.34% to 0.45% in 2012 (p
trend
<0.001). This trend increased annually by 3.5% (OR 1.035; 95% CI 1.01-1.05;p<0.001). The temporal rise was explained by changes in demographics and co-morbidities. Amongst HIV-related hospitalizations, Age (10 year increase) (OR 1.23; 95% CI 1.09-1.43; p<0.001), African-American race (OR 1.25; 95% CI 1.09-1.43; p<0.001), Hispanic race (OR 1.29; 95% CI 1.07-1.55; p<0.001) and history of Hypertension (OR 1.97; 95% CI 1.76-2.22; p<0.001) were significantly associated with the development of ICrH, However females had lower odds of developing ICrH(OR 0.80; 95% CI 0.71-089; p<0.001).

Conclusions:
These data suggest that the incidence of ICrH among hospitalized adults with HIV infection continue to increase. This increasing ICrH was explained by an aging HIV population, changing demographics and chronic comorbidities, but questions still remain regarding unexplained factors which merit in-depth study.
Abstract 224: Angiogenic Imbalance Causes Cerebrovascular Pathological Neovascularization in Diabetes: Role of Pericytes.
Authors: Abdelsaid Mohammed , Valenzuel John Paul , Ergul Adviye
Published: June 2021

Diabetes increases cerebrovascular complications such as stroke and cognitive impairment. We have previously showed that diabetes causes dysfunctional cerebral neovascularization. Pericytes have a pivotal role in modulating microvascular physiology and pathology, yet its role in diabetes dysfunctional cerebral neovascularization is unknown. In the present study we testedthe hypothesis that pericytes play a crucial role in diabetes-mediated dysfunctional pathological cerebral neovascularization via dysregulation of antiangiogenic Slit-2/ROBO4 and the proangiogenic EphrinB2/EphB4 signaling.

Methods:
Diabetes was induced in Wistar rats using low dose of streptozotocin and high fat diet (STZ/HFD). Immunohistochemistry and immunoblotting were used to assess ROBO4 and EphrinB2 expression in the brain and human brain microvascular pericytes (HBMVP). HBMVP was exposed to glucose (25 mM) /palmitate (200 uM) to mimic diabetic conditions. Scratch migration assay was used to assess the effect of high glucose/palmitate (HG/Pal) on pericytes migration. Adenovirus was used to overexpress ROBO4 in the brain in vivo.

Results:
STZ/HFD caused a significant increase in HbA1C (10.8*). Diabetic brains and HBMVP exposed to HG/Pal showed reduced ROBO4 expression (66%* and 48%*) and increased EphrinB2 expression (1.9* and 1.6* folds). HG/Pal increased pericyte migration by 2* fold. Pericyte migration was increased by 2.5* fold with silencing ROBO4 but significantly reduced with silencing EphrinB2 (35%*) or ROBO4 overexpression (47%*) under HG/Pal. In vivo ROBO4 overexpression decreased pathological neovascularization indices and increased pericyte coverage. (n= 3-5, *P<0.05).

Conclusion:
Our findings emphasize the importance of balanced anti- and proangiogenic signaling for proper pericyte function in diabetes. Our results suggest that pericytes are involved in proangiogenic and barrier functions of endothelial cells and pericyte dysfunction may contribute to pathological neovascularization in diabetes. Thus, pericyte ROBO4 and EphrinB2 signaling are promising therapeutic targets to improve cerebrovascular integrity in diabetes.
Abstract 36: Acute Stroke Evolution is in the Eye of the Beholder: Effects of Interrater Variability on Patient Selection and Outcomes in the Mr Witness (nct01282242) Multicenter Thrombolysis Trial
Authors: Wu Ona , Latour Lawrence L , Song Shlee S , Copen William A , Yoo Albert J , Lev Michael H , Ford Andria L , Hsia Amie , Betensky Rebecca , Muzikansky Alona , Boulouis Gregoire , Lauer Arne , Cougo Pedro , Harris Gordon J , Warach Steven , Schwamm Lee H
Published: June 2021

Background:
MR WITNESS was a safety trial giving tPA to acute ischemic stroke (AIS) patients with unwitnessed onset with MRI findings of early stroke. A DWI-positive, FLAIR negative pattern has been shown to identify strokes <4.5 hr duration, but visual inspection alone may be unreliable and insensitive. Signal intensity ratios (SIR) of manual outlines (lesion/contralateral side) increase sensitivity but can lead to variability in patient selection. We investigated the influence of interrater variability on clinical and safety outcomes.

Methods:
Core readers blinded to enrollment status and clinical presentation reviewed MRI of screened patients. The MR WITNESS algorithm enrolled subjects with no visible FLAIR or a pre-specified SIR <1.15. Good outcome was defined as 90 Day modified Rankin Scale (mRS)
<
2. SIR consistency was measured with intraclass coefficient (ICC) and reader agreement assessed with Fleiss’ Kappa. Statistical analysis included 2-sided Fisher’s Exact test or Wilcoxon Exact test as appropriate.

Results:
201 subjects were screened. 153 baseline MRIs with DWI lesions were reviewed. ICC was 71% (P<.001) and kappa was 67% (P<.0001). Among the 80 subjects enrolled using SIR <1.15 by site reading, 15 (18.8%) subjects would have been excluded based on Core readings. These 15 subjects were younger with worse NIHSS and 90-day mRS (Table). Subset analyses of subjects with pre-stroke mRS<2 showed no statistical difference (P=0.19) between subjects deemed eligible and not eligible by core readers. No difference in hemorrhagic transformation (HT) or good outcome rates was found. Using SIR <1.25 would have only excluded 3 subjects by Core readings, all of whom had HT, and poor 90 day outcomes.

Discussion:
Although SIR reads between Core and sites showed good agreement, there was still variability in the absolute values. This demonstrates the potential limitation of subjective lesion volume delineation. Automated approaches should be investigated.
Abstract 38: Brain CT Perfusion is Superior to Non-contrast CT Aspects in the Evaluation of Hyperacute Infarct Volume
Authors: Demeestere Jelle , Garcia-Esperon Carlos , Garcia-Bermejo Pablo , Ombelet Fouke , McElduff Patrick , Bivard Andrew , Parsons Mark , Levi Christopher
Published: June 2021

Objective:
To compare the predictive capacity to detect established infarct in acute anterior circulation stroke between the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on non-contrast computed tomography (CT) and CT perfusion.

Methods:
Fifty-nine acute anterior circulation ischemic stroke patients received brain non-contrast CT, CT perfusion and hyperacute magnetic resonance imaging (MRI) within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 independent vascular neurologists, blinded from CT perfusion and MRI data. CT perfusion infarct core volumes were calculated by MIStar software. The accuracy of commonly used ASPECTS cut-off scores and a CT perfusion core volume of ≥ 70 mL to detect a hyperacute MRI diffusion lesion of ≥ 70 ml was evaluated.

Results:
Median ASPECTS score was 9 (IQR 7-10). Median CT perfusion core volume was 22 ml (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24,5 ml (IQR 10-63.9). ASPECTS score of < 6 had a sensitivity of 0.37, specificity of 0.95 and c-statistic of 0.66 to predict an acute MRI lesion ≥ 70 ml. In comparison, a CT perfusion core lesion of ≥ 70 ml had a sensitivity of 0.76, specificity of 0.98 and c-statistic of 0.92. The CT perfusion core lesion covered a median of 100% of the acute MRI lesion volume (IQR 86-100%).

Conclusions:
CT perfusion is superior to ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.
Abstract 39: CT Perfusion Selection May Lead to Better Clinical Outcomes Following Endovascular Therapy in Large Vessel Occlusion Stroke
Authors: Bouslama Mehdi , Haussen Diogo C , Grossberg Jonathan A , Dehkharghani Seena , Bowen Meredith , Rebello Leticia C , Bianchi Nicolas , Bianchi Nicolas , Frankel Michael R , Nogueira Raul G
Published: June 2021

Background and Purpose:
Different imaging paradigms have been used to select patients for endovascular therapy (ET) in large vessel occlusion stroke (LVOS). We sought to determine whether CT perfusion (CTP) selection improves ET outcomes as compared to non-contrast CT (NCCT) alone.

Methods:
Review of a prospective single-center interventional database of consecutive patients between September 2010 and March 2016. Patients with anterior circulation strokes undergoing stent-retriever thrombectomy were categorized according to imaging selection: (1) CTP and (2) NCCT alone. Two separate analyses were performed: (1) Uni- and Multivariate analyses of the overall cohort and (2) Matched analysis based on age, baseline NIHSS, and glucose levels.

Results:
A total of 602 patients were included. CTP-selected patients (n=365; 61%) were younger (p=0.02) and had less comorbidities. On univariate analysis, CTP-selection was associated with higher rates of full reperfusion (mTICI-3, p<0.001), good outcomes (90-day mRS 0-2, p=0.005), lower mortality rates (p=0.005), and a favorable shift in the overall distribution of 90-day mRS (p<0.001) as compared with NCCT alone. The rates of any parenchymal hematoma were comparable between groups (p=0.671). Multivariate logistic regression showed that CTP was independently associated with mTICI-3 (OR=1.79 95%CI [1.27-2.53], p=0.001) and good outcomes (aOR=1.72 95%CI [1.10-2.67], p=0.017). In the matched case-control analysis (n=424 patients), CTP-selection was associated with a favorable shift in the distribution of 90-day mRS (p=0.016), lower 90-day mortality (p=0.02), higher rates of mTICI-3 reperfusion (p<0.001), and a trend towards higher rates of 90-day independence (p=0.06). There was an advantage in the ability of CTP to determine functional outcomes in patients presenting later than 6h (Akaike information criterion (AIC) 199.35 vs. 287.49 and Bayesian information criterion (BIC) 196.71 vs 283.27) and with an ASPECTS ≤7 (AIC 216.69 vs 334.96 and BIC 213.6 vs 329.94).

Conclusion:
CTP-based selection is associated with a favorable shift in functional outcomes in patients undergoing stent-retriever thrombectomy. Future prospective studies are warranted.
Abstract 42: Blood Biomarkers Refect Tissue Viability in Acute Ischemic Stroke
Authors: Bustamante Alejandro , Terceño Mikel , Giralt Dolors , van Eendenburg Cecile , López-Cancio Elena , Cardona Pere , García-Berrocoso Teresa , Canovas David , Garces Moises , Rubiera Marta , Baldrich Eva , Castellanos Mar , Serena Joaquín , Dávalos Antoni , Montaner Joan
Published: June 2021

Introduction:
Assessment of tissue viability, usually performed by multimodal neuroimaging, allows the use of reperfusion therapies in selected patients, even out of the therapeutic time-window. However, multimodal imaging is still a scarce and expensive tool. The availability of blood biomarkers reflecting tissue viability could be a useful tool to manage reperfusion therapies. We aimed to test whether selected candidate biomarkers may reflect tissue viability in relation to Alberta Stroke Program Early CT score (ASPECTS) and multimodal imaging.

Methods:
The StrokeChip was a prospective, observational study, conducted at six Hospitals in Catalonia. Patients with suspected stroke were enrolled at Emergency Departments. Blood samples were obtained within the first six hours after symptoms onset to measure a 21-biomarker panel. Acute brain neuroimaging was dichotomized into normal (ASPECTS=10) or pathological (ASPECTS<10). For those patients with perfusion imaging, comparison was performed between patients with and without significant mismatch (>20%).

Results:
From August-2012 to December-2013, 941 out of 1308 patients were ischemic strokes. ASPECTS was obtained in admission neuroimaging in 927 patients. Among them, 25% displayed pathological neuroimaging. Levels of Apo-CIII disclosed a positive correlation with ASPECTS, while negative correlations were found for D-dimer, IL-6, GroA, NT-proBNP and IGFBP-3. In logistic regression analysis, Apo-CIII [OR=0.52(0.36-0.75)], D-dimer [OR=2.47(1.39-4.39)] and IGFBP-3 [OR=2.28(1.51-3.43)] were independently associated with ASPECTS <10, after adjustment by age, sex and NIHSS. Moreover, in 103 patients with baseline perfusion imaging (70% with mismatch >20%), Apo-CIII was an independent predictor of the presence of mismatch after adjustment by age, sex and NIHSS [OR=0.27(0.10-0.75)].

Conclusions:
Assessment of tissue viability with blood biomarkers seems feasible. Apo-CIII might represent a surrogate marker for tissue viability assessment.
Abstract 43: Neuroprotective Effects of Inhibition of α5β1 Integrin Following Experimental Stroke: A Dual Center Pre-Clinical Study
Authors: Edwards Danielle , Reber Kittani Biav , Grohs Gillian , Macrae Mhairi , Fraser Justin F , McCabe Chris , Bix Gregory J
Published: June 2021

Blood-brain barrier (BBB) dysfunction after ischemic stroke exacerbates brain damage by contributing to edema and inflammation. The β1 integrin receptor family may contribute to this dysfunction via alteration of BBB-forming tight junction proteins. We hypothesize that inhibition of the β1 integrin receptor subtype α5β1, which is acutely expressed in infarct and peri-infarct vasculature after experimental stroke, reduces BBB permeability, reduces infarct volume, and improves functional recovery. A randomized and blinded trial was conducted using transient middle cerebral artery occlusion (MCAO) in mice (60 min; n=8) and rats (90 min; n=15) in two independent laboratories. ATN-161 (α5β1 inhibitor; 1 mg/kg) was administered IV immediately upon reperfusion and on post-stroke day 1 and 2. Infarct volume was determined by cresyl violet (mice) and T
2
weighted MRI (rat) at day 3 post MCAO. Steady state contrast enhanced MRI was used to assess BBB breakdown in rats at day 3. ATN-161 resulted in a significant reduction in infarct volume in both mice and rats when measured at post-stroke day 3 (p<0.001). BBB permeability was decreased upon ATN-161 treatment
in vivo
as determined by reduced IgG and claudin-5 immunostaining in mice and reduced extent of Gadolinium enhanced MRI signal change in rats. Behavioral tests (open field, rotorod, sticky label and 28 point neuroscore), demonstrated significantly improved functional recovery in both mice and rats following treatment with ATN-161. Finally,
in vitro
studies where stroke was simulated using oxygen and glucose deprivation or TNF-α, ATN-161 (10 μM) treatment demonstrated decreased barrier permeability as measured by trans-endothelial cell electrical resistance, FITC-dextran permeability, and claudin-5 immunocytochemistry. Collectively, our results demonstrate that post-stroke inhibition of α5β1 integrin with the small peptide ATN-161 profoundly reduces infarct volume, improves functional outcome and decreases BBB permeability in both mice and rats using two different ischemic stroke models. Therefore, inhibition of α5β1 by ATN-161 could represent a novel stroke therapeutic target worthy of further investigation.
Abstract 47: Age of Donor of Human Mesenchymal Stem Cells Drastically Affects Structural and Functional Recovery After Cell Therapy Following Ischemic Stroke
Authors: Yamaguchi Susumu , Horie Nobutaka , Satoh Katsuya , Morofuji Yoichi , Izumo Tsuyoshi , Nishida Noriyuki , Suyama Kazuhiko , Matsuo Takayuki
Published: June 2021

Background and purpose:
Cell transplantation therapy holds great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is uncertain. We investigate regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischemic stroke.

Methods:
The value of platelet-derived growth factor (PDGF)-BB secreted from human mesenchymal stem cells (hMSC) was analyzed regarding in two age groups; young (20-30 years) and old (57-65 years) in vitro. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion, and received young or old hMSC trans-arterially at 24 h after stroke. Functional recovery was assessed with modified neurological severity score (mNSS). Structural recovery was assessed on neovascularization and endogenous cell migration as well as trophic factor secretion.

Results:
The value of PDGF-BB was significantly higher in young hMSC (40.47±4.29 pg/ml/10
4
cells) than that in old hMSC (25.35±3.16 pg/ml/10
4
cells;
P
=0.02) and negatively correlated with age (
P
=0.048, r=-0.79, Spearman). Rats treated with young hMSC (3.7±0.6) showed better behavior recovery in mNSS with prevention of brain atrophy than that with control (6.1±0.5) or old (5.2±0.7) at D21 (
P
<0.01). The number of RECA-1 and PDGFR-β double positive vessels in rat with young hMSC (113±48.6/mm
2
) was higher than that in control (61.5±35.9/mm
2
) or old (76.9±36.9/mm
2
) suggesting vessel maturation (
P
<0.01). Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment (
P
<0.01, r=0.27; Spearman), which was more pronounced in young hMSC (
P
<0.05).

Conclusions:
Aging of hMSC may be the critical factor which affects outcome of cell therapy, and transplantation of young hMSC could provide better functional recovery by vessel maturation and endogenous cell migration potentially due to dominance of trophic factor secretion.
Abstract 53: Changes in Physical Activity and Risk of Stroke in the California Teachers Study
Authors: Willey Joshua Z , Voutsinas Jenna , Sherzai Ayesha , Wang Sophia S , Bernstein Leslie , Elkind Mitchell S , Cheung Ying K
Published: June 2021

Introduction:
Leisure time physical activity (LTPA) has been consistently associated with a lower risk of stroke across several populations. Less is known however about how changes over the life-time in physical activity may influence the risk of stroke. We examined the association of changes in engaging in moderate and strenuous physical activity with risk of stroke in the California Teachers Study.

Methods:
The California Teachers Study is a prospective cohort study established in 1995. Baseline LTPA was obtained using a questionnaire outlining time spent in moderate (brisk walking for example) and strenuous (swimming and running for example); the same questionnaire was repeated in 2005-6. We defined the exposure as engaging in any activity for at least 15 minutes per week (any) in the second questionnaire when not engaging in any on the first questionnaire, with the reference being no change or a decline in activity between both. Multi-variable Cox models were constructed to examine the association of the change in LTPA with risk of stroke. Separate models were created for moderate and strenuous activity.

Results:
There were a total of 61,256 participants with two LTPA questionnaires available separated by 10 years. A total of 3,111 participants increased their level of moderate activity, 11,744 remained active in both, 2,760 declined from the first to the second questionnaire, while 2,508 reported no activity in both. There were 987 (709 ischemic, 221 hemorrhagic, 247 deaths) strokes after the second questionnaires (mean follow up 6.5 years). In multi-variable models increasing any moderate intensity from none from the two questionnaires, versus no change or decline in activity, was associated with a lower risk of all stroke (adjusted HR 0.83, 95% CI 0.72-0.95). We found no associations of changes in strenuous LTPA with risk of stroke (adjusted HR 0.99, 95% CI 0.83-1.17). The associations were statistically significant for ischemic stroke (adjusted HR 0.75, 95% CI 0.64-0.89) but not hemorrhagic stroke (adjusted HR 0.94, 95% CI 0.72-1.25).

Conclusion:
Improving or maintaining moderate intensity physical activity is associated with a lower risk of stroke, while changes in strenuous activity is not.
Abstract 60: Inter-alpha Inhibitor Proteins Reduce the Quantity of Microglia in the Hippocampus After Hypoxic-ischemic Brain Injury in the Neonate
Authors: Barrios-Anderson Adriel , Chen Xiaodi , Naqvi Syed S , Lim Yow-Pin , Stonestreet Barbara S
Published: June 2021

Background:
Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory proteins that act as anti-inflammatory agents in hypoxic-ischemic (HI) injury. We have recently shown that administering IAIP after HI improves histopathological brain injury, and behavioral outcomes in neonatal rats. Microglia are glial cells that act as macrophages in the brain and are important constituents in the neuroinflammatory response.

Objective:
To determine the effect of IAIP treatment on microglial expression in specific brain regions of neonatal rats after HI brain related injury.

Methods:
The Vannucci model was used to induce neonatal HI brain injury. Postnatal day 7 rats were assigned to a non-ischemic sham-control group (Sham, n=11), a right carotid ligation and hypoxia exposed (8% oxygen for 90 min) placebo-treated group (IschPL, n=12), or a right carotid ligation and hypoxia IAIP-treated group (Isch-IAIP, n=12). The sex of the rats was recorded. IAIP (30 mg/kg) or PL was given intraperitoneally at 0, 24 and 48 h after HI. 72 h after HI, brains were collected, sectioned, and prepared for slides. We performed immunohistochemistry by staining with Iba-1 (selective for microglia) and DAPI. Stereological analyses were then performed with the StereoInvestigator 10.0 Fractionator probe without knowledge of group assignment to quantify microglia present in the whole hemisphere, cortex, corpus callosum, and hippocampus.

Results:
The number of Iba-1 positive microglial cells per area of tissue was lower in Sham than in the Isch-PL animals in the cortex, hippocampus, and hemisphere of female and in the hippocampus and corpus callosum of male rats (P <0.05). IAIP treatment appears to reduce the number of Iba-1 positive cells across all brain regions compared with the PL treated HI in the male but not female neonatal rats. Post hoc analysis showed that IAIP treatment significantly reduced the number of positive Iba-1 cells in the hippocampus of the male rats (P<0.01).