bluuebunny/crossref_metadata_2025 huggingface dataset:
Precise Metabolomics Defines Systemic Metabolic Dysregulation Distinct to Acute Myocardial Infarction Associated With Diabetes
Authors: Xia Jing-gang , Li Bowen , Zhang Hao , Li Qin-xue , Lam Sin Man , Yin Chun-lin , Tian He , Shui Guanghou
Published: February 2023

Background:

Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes.

Methods:

In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged.

Results:

In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c (glycosylated hemoglobin, type A1C) specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI.

Conclusions:

As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.
Predictors of Improvement in Exercise Tolerance After Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension
Authors: Daigo Kyohei , Katsumata Yoshinori , Esaki Kosho , Iwasawa Yuji , Ichihara Genki , Miura Kotaro , Shirakawa Kohsuke , Sato Yasunori , Sato Kazuki , Fukuda Keiichi
Published: January 2023

Background

Balloon pulmonary angioplasty (BPA) improves exercise tolerance and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension. However, it is still unclear which patient characteristics contribute to the improvement in exercise tolerance after BPA in chronic thromboembolic pulmonary hypertension.

Methods and Results

We retrospectively analyzed 126 patients with chronic thromboembolic pulmonary hypertension (aged 63±14 years; female, 65%) who underwent BPA without concomitant programmed exercise rehabilitation at Keio University between November 2012 and April 2018. Hemodynamic data and 6‐minute walk distance (6MWD), as a measure of exercise tolerance, were evaluated before and 1 year after BPA. The clinical characteristics that contributed to improvement in exercise tolerance were elucidated. The 6MWD significantly increased from 372.0 m (256.5–431.3) to 462.0 m (378.8–537.0) 1 year after BPA (
P
<0.001). The improvement rate in the 6MWD after BPA exhibited a good correlation with age, height, mean pulmonary artery pressure, and 6MWD at baseline (Spearman rank correlation coefficients=−0.28, 0.24, −0.40, and 0.44, respectively). Additional multivariable linear regression analysis revealed that young age, tall height, high mean pulmonary artery pressure, short 6MWD at baseline, and high lung capacity at baseline were significant predictors of the improvement in 6MWD by BPA (standardized partial regression coefficient −0.39, 0.22, 0.19, −0.62, and 0.25,
P
<0.001, 0.007, 0.011, <0.001, and <0.001, respectively).

Conclusions

BPA without concomitant programmed exercise rehabilitation significantly improves exercise tolerance. This was particularly true in young patients with high stature, high mean pulmonary artery pressure, short 6MWD, and lung capacity at the time of diagnosis.
Health Status Outcomes in Older Adults Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Nguyen Dan D. , Gosch Kensey L. , El‐Zein Rayan , Chan Paul S. , Lombardi William L. , Karmpaliotis Dimitri , Spertus John A. , Wyman R. Michael , Nicholson William J. , Moses Jeffrey W. , Grantham J. Aaron , Salisbury Adam C. , Grantham J. Aaron , Cook Stephen L. , Doshi Parag , Federici Robert , Karmpaliotis Dmitri , Lombardi William L. , Moses Jeffrey W. , Nicholson William J. , Pershad Ashish , Spaedy Anthony J. , Wyman R. Michael
Published: January 2023

Background

Although chronic total occlusions (CTOs) are common in older adults, they are less likely to be offered CTO percutaneous coronary intervention for angina relief than younger adults. The health status impact of CTO percutaneous coronary intervention in adults aged ≥75 years has not been studied. We sought to compare technical success rates and angina‐related health status outcomes at 12 months between adults aged ≥75 and <75 years in the OPEN‐CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion) registry.

Methods and Results

Angina‐related health status was assessed with the Seattle Angina Questionnaire (score range 0–100, higher scores denote less angina). Technical success rates were compared using hierarchical modified Poisson regression, and 12‐month health status was compared using hierarchical multivariable linear regression between adults aged ≥75 and <75 years. Among 1000 participants, 19.8% were ≥75 years with a mean age of 79.5±4.1 years. Age ≥75 years was associated with a lower likelihood of technical success (adjusted risk ratio=0.92 [95% CI, 0.86–0.99;
P
=0.02]) and numerically higher rates of in‐hospital major adverse cardiovascular events (9.1% versus 5.9%,
P
=0.10). There was no difference in Seattle Angina Questionnaire Summary Score at 12 months between adults aged ≥75 and <75 years (adjusted difference=0.9 [95% CI, −1.4 to 3.1;
P
=0.44]).

Conclusions

Despite modestly lower success rates and higher complication rates, adults aged ≥75 years experienced angina‐related health status benefits after CTO‐percutaneous coronary intervention that were similar in magnitude to adults aged <75 years. CTO percutaneous coronary intervention should not be withheld based on age alone in otherwise appropriate candidates.
Derivation and Validation of an Algorithm to Detect Stroke Using Arm Accelerometry Data
Authors: Messé Steven R. , Kasner Scott E. , Cucchiara Brett L. , McGarvey Michael L. , Cummings Stephanie , Acker Michael A. , Desai Nimesh , Atluri Pavan , Wang Grace J. , Jackson Benjamin M. , Weimer James
Published: January 2023

Background

Early diagnosis is essential for effective stroke therapy. Strokes in hospitalized patients are associated with worse outcomes compared with strokes in the community. We derived and validated an algorithm to identify strokes by monitoring upper limb movements in hospitalized patients.

Methods and Results

A prospective case–control study in hospitalized patients evaluated bilateral arm accelerometry from patients with acute stroke with lateralized weakness and controls without stroke. We derived a stroke classifier algorithm from 123 controls and 77 acute stroke cases and then validated the performance in a separate cohort of 167 controls and 33 acute strokes, measuring false alarm rates in nonstroke controls and time to detection in stroke cases. Faster detection time was associated with more false alarms. With a median false alarm rate among nonstroke controls of 3.6 (interquartile range [IQR], 2.1–5.0) alarms per patient per day, the median time to detection was 15.0 (IQR, 8.0–73.5) minutes. A median false alarm rate of 1.1 (IQR. 0–2.2) per patient per day was associated with a median time to stroke detection of 29.0 (IQR, 11.0–58.0) minutes. There were no differences in algorithm performance for subgroups dichotomized by age, sex, race, handedness, nondominant hemisphere involvement, intensive care unit versus ward, or daytime versus nighttime.

Conclusions

Arm movement data can be used to detect asymmetry indicative of stroke in hospitalized patients with a low false alarm rate. Additional studies are needed to demonstrate clinical usefulness.
Abstract 106: Novel Imaging-based Morphological Markers For Improved Prediction Of Stroke Outcomes: A Machine Learning Approach
Authors: Laksari Kaveh , Deshpande Aditi , Wintermark Max , Jiang Bin , Tahsili-Fahadan Pouya , Kidwell Chelsea S , Elliot Jordan
Published: February 2023

Patient selection for acute reperfusion therapies of acute ischemic stroke is based on assessment of the core and tissue-at-risk and the time from stroke onset. Response to treatment and clinical outcomes, however, vary significantly since patient-specific cerebrovascular anatomy plays a vital role in governing flow and reperfusion. We developed an end-to-end automated machine learning approach to extract advanced cerebrovascular morphological features, including tortuosity and collateral index, to improve outcome prediction, and patient selection.

Methods:
Using our validated automatic cerebrovascular segmentation and feature extraction algorithm, we obtained the morphological properties of the brain vasculature, including vessel tortuosity, length, diameter, and bifurcation patterns, in MR angiography scans of 100 anonymized stroke patients. Each patient’s collateral index was also automatically graded using a previously established probabilistic atlas of healthy cerebrovasculature. To predict 90-day functional outcomes (mRS), a statistical model was trained using patients' clinical features (demographics, comorbidities, and baseline NIHSS), imaging features (initial ASPECTS, perfusion mismatch volume, and collateral index), and the extracted morphologic features (length, diameter, number of branches, vessel tortuosity, fractal dimension, and total volume). The predictions were compared against ground truth mRS to assess model accuracy. We also compared the model’s performance against conventional outcome predictors with only the clinical and imaging features.

Results:
The conventional model including the common clinical and imaging features excluding the collateral index gave an area under the curve (AUC) of 0.63, which is comparable to previously published results. Including the automatically scored collateral index improved the accuracy to 0.74. We found that further including the morphological features to the predictor model significantly improved AUC accuracy to 0.83.

Conclusion:
Including automatically extracted cerebrovascular morphologic features in traditional clinical and imaging markers significantly improves outcome prediction and response to treatment in stroke patients.
Abstract 112: Cerebral Venous Sinus Thrombosis Due To Vaccine-induced Immune Thrombotic Thrombocytopenia In Middle-Income Countries
Authors: van de Munckhof Anita , Borhani-Haghighi Afshin , Aaron Sanjith , Krzywicka Katarzyna , Poli Sven , Cordonnier Charlotte , Kleinig Timothy J , Lemmens Robin , Sanchez van Kammen Mayte , Scutelnic Adrian , Lindgren Erik , Mbroh Joshua , Ciccone Alfonso , Wittstock Matthias , Zimmermann Julian , Bode Felix J , Skjelland Mona , Devroye Annemie , Duan Jiangang , Hiltunen Sini , Petruzzellis Marco , Kremer Hovinga Johanna A. , Günther Albrecht , Jood Katarina , Tatlisumak Turgut , Putaala Jukka , Heldner Mirjam , Arnold Marcel , Aguiar De Sousa Diana , Wasay Muhammad , Arauz Antonio , Conforto Adriana B , Ferro Jose M , Coutinho Jonathan M ,   Cerebral Venous Sinus Thrombosis with Thrombocytopenia Syndrome Study Group
Published: February 2023

Introduction:
Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). In India alone, 1.67 billion ChAdOx1 nCoV-19 vaccines have been administered by August 23, 2022. Surprisingly however, there are only few reports of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) from LMICs. We aimed to gain insight into the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs.

Methods:
We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared characteristics of CVST-VITT cases from LMICs to cases from high-income countries (HICs).

Results:
By August 15, 2022, 228 CVST cases after vaccination were reported, of which 63 cases from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, and Turkiye). Of these, 32/63 (51%) met the criteria for definite, probable or possible VITT. Only 5/32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-PF4 antibodies were not tested in 21/32 (66%) cases. Patients from MICs were diagnosed in a later time period than patients from HICs (1/32 [3%] vs 65/103 [63%] cases diagnosed before May 2021, respectively). Median age was 26 (IQR 20-37) vs 47 (IQR 32-58) years, and proportion of women was 25/32 (78%) vs 77/103 (75%) in MICs vs HICs, respectively. Clinical manifestations, such as focal neurologic deficits, coma, seizures, and intracranial hemorrhages, were similar. Concomitant venous thromboembolism was less frequent in MICs (3/31 [10%] vs 26/97 [27%]). Median platelet count nadir was higher in the MICs than the HICs group (65 x10
9
/L [IQR 36-115] vs 33 x10
9
/L [IQR 18-55],
p
=0.001). Intravenous immunoglobulin use was similar (19/30 [63%] vs 63/99 [64%]). In-hospital mortality was lower in the MICs than the HICs group (7/32 [22%, 95%CI 11-39] vs 44/102 [43%, 95%CI 34-53],
p
=0.031).

Conclusions:
The absolute number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines in these countries. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
Abstract 13: Aptamer-Based Plasma Proteomics Nominates Biomarkers Of Neurological Severity, Stroke Diagnosis And Age
Authors: Natu Aditya , Kumar Prateek , Frankel Michael R , RANGARAJU Srikant
Published: February 2023

Background:
Plasma protein biomarkers measured in the hyperacute setting that are associated with stroke diagnosis or with clinical neurological severity, can be diagnostically and prognostically meaningful in patient care. We hypothesized that high-throughput proteomics can identify panels of plasma proteins that can differentiate stroke mimics from ischemic and hemorrhagic stroke, and are associated with neurological severity.

Methods:
From a clinically-characterized biorepository of 320 plasma samples collected at time of patient presentation to the Emergency Room at Grady Memorial Hospital (Atlanta), 40 samples (10 stroke mimics, 10 intracerebral hemorrhage [ICH], 20 acute ischemic stroke [AIS]) were included (Fig A). 7,000 proteins were measured per sample using aptamer-based proteomics (SomaLogic). A combination of differential-expression and variance partitioning analyses (VPA) identified proteins associated with diagnosis (mimic vs ICH vs AIS), neurological severity (NIHSS), age and sex.

Results:
Cohort characteristics are shown (Fig B). VPA identified top proteins that accounted for majority of variance in several traits (Fig C). One-way ANOVA identified >400 proteins showing group-wise differences, of which a panel of 56 proteins collectively distinguished mimics from both AIS and ICH, ICH from both mimics and AIS, as well as distinguished between AIS based on NIHSS (Fig D). The pattern of expression of these 56 plasma proteins across diagnostic groups is shown in Fig E. We also identified plasma biomarkers associated with increasing age, indicative of age-related vascular dysfunction.

Conclusions:
This pilot study of AIS, ICH and stroke mimics demonstrates the applicability of aptamer-based proteomics as a promising approach for plasma protein biomarker discovery in stroke. We identified acute plasma protein biomarkers of neurological severity, diagnostic group and age-related vascular dysfunction that need further validation.
Abstract 131: Brain Mri Biomarkers Of Impaired Balance And Slow Walk Speed: Atherosclerosis Risk In Communities And UK Biobank Studies
Authors: Sharma Richa , De Havenon Adam H , Rivier Cyprien , Payabvash Sam , Forman Rachel , Krumholz Harlan M , Falcone Guido J , Sheth Kevin N , Kernan Walter N
Published: February 2023

Background and Objectives:
Vascular brain injury (VBI) may contribute to imbalance and slow walk speed, but this is uncertain. We hypothesize that MRI biomarkers of VBI associate with impaired balance and slow walk speed.

Methods:
We performed separate, cross-sectional analyses in the Atherosclerosis Risk in Communities (ARIC) and UK Biobank (UKB) studies. Eligible participants had no prior clinical stroke and underwent a brain MRI and balance and walk speed ascertainment. MRI biomarkers of VBI analyzed were: ventricular volume, white matter hyperintensity volume (WMH), non-lacunar infarction, lacunar infarction, microhemorrhage in ARIC; ventricular volume, brain volume, WMH, fractional anisotropy (FA), mean diffusivity (MD), intra-cellular volume fraction, isotropic free water volume fraction in UKB. Quantitative biomarker levels were classified into tertiles, the unhealthiest tertile designated as the exposure. Our outcomes were poor balance and slow walk speed. We constructed multivariable logistic regression models to examine the associations between each MRI biomarker and the outcomes, adjusting for demographics and clinical history.

Results:
We included 1,626 ARIC participants (mean age 76.2 years; 23.4% impaired balance, 25.0% slow walk speed) and 40,098 UKB participants (mean age 55 years; 15.8% impaired balance, 2.8% slow walk speed). In ARIC, impaired balance was associated with 4 of 5 MRI measures of VBI in adjusted analysis (all p-values <0.05). The strongest association was with WMH (OR 1.36; 95% C.I. 1.04-1.76). Slow walk speed in ARIC was significantly associated with 4 of 5 MRI measures; the strongest association was with silent lacunar infarcts (OR 2.17; 95% C.I. 1.61-2.93). In UKB, poor balance was associated with all MRI biomarkers except WMH. The strongest association was with FA (OR 1.16; 95% C.I. 1.08-1.24). Slow walking speed was associated with WMH, FA, and MD. The strongest association was with FA (OR 1.42; 95% C.I. 1.21-1.67).

Conclusions:
We demonstrate that MRI measures of VBI are independently associated with impaired balance and slow walk speed in two studies of community-dwelling adults with no history of clinical stroke. Consequences of VBI may extend beyond clinically apparent stroke to also include mobility.
Abstract 136: Canonical Correlation Analysis Of Histomic And Transcriptomic Data From Ischemic Stroke Thrombi Identifies Complex Traits Associated With Etiology
Authors: Santo Briana , Poppenberg Kerry , Monteiro Andre , Siddiqui Adnan H , Tutino Vincent
Published: February 2023

Background:
Determination of ischemic stroke etiology is essential for guiding post-operative stroke treatment and secondary prevention.

Hypothesis:
Canonical correlation analysis (CCA) of paired clot histomic and transcriptomic features can identify etiology-specific white blood cell (WBC) image-omic correlates.

Methods:
We analyzed paired H&E histology and transcriptome data from 31 clots (large artery atherosclerosis, LAA=5; cardio embolism, CE=18; stroke of other cause, OTH=3; cryptogenic, CR=5). A published computational pipeline for WBC segmentation and characterization was used to quantify 46 image features (e.g., textures representative of heterochromatin-euchromatin ratio) from >100,000 WBC instances. Features were used to classify WBCs into 1 of 10 validated classes and calculate clot class frequency distributions. SparseCCA was used to test associations among image features and expression signatures. Gene ontology (GO) enrichment analysis was used to identify biological process (BP) ontologies that were associated with positively correlated genes for each etiology.

Results:
Canonical covariates (e.g., histology canonical variable [CV] 1 and transcriptome CV1) were strongly and significantly correlated (
R
>0.9,
p
<0.001). Pairwise correlation of CVs and original feature sets (e.g., to identify WBC features captured in histology CVs) showed the most enriched CVs in LAA (CV6, top row of Figure), CE (CV14, middle row of Figure), and OTH (CV17, bottom row of Figure). These represented distinct WBC subtypes on histology and unique GO signatures. LAA clots had enrichment of leukocytes (and greater T-cell regulation and cytokine production), while CE clots had granulocyte enrichment, and OTH clots had many WBCs embedded in RBC-rich regions with greater heme biosynthesis.

Conclusion:
We found significant structure-expression covariates representing biologically-interpretable traits that are different among stroke etiologies.
Abstract 141: Contemporary Trends In Oral Anticoagulation Utilization After Acute Ischemic Stroke With Atrial Fibrillation: The Treatment Disparities In Stroke And Atrial Fibrillation Study
Authors: Sur Nicole B , Ying Hao , Asdaghi Negar , Gardener Hannah , Zhou Lili , Gutierrez Carolina M , Sacco Ralph L , Romano Jose G , Rundek Tatjana
Published: February 2023

Background:
Acute ischemic stroke (AIS) is a devastating consequence of atrial fibrillation (AF), which is preventable with oral anticoagulants (OACs). The goal of this study was to evaluate contemporary trends and disparities in OAC use at hospital discharge in patients with AIS and AF in the era of direct oral anticoagulants (DOACs).

Methods:
Data on 34,715 cases admitted to hospital for AIS with AF were obtained from the Florida Stroke Registry, 2017-2021. Baseline sociodemographics, medical history, stroke and hospital characteristics and anticoagulant status were compared by OAC use at discharge. Multivariable logistic regression was used to identify predictors of OAC non-use after AIS with AF after adjusting for confounders. Temporal trends in the frequency of OAC use at hospital discharge was assessed from 2010-2021.

Results:
From 2017-2021, a total of 21,011 (61%) patients with AIS and AF were discharged on OAC (median age 77 years; 49% female; 74% white, 13% black, 13% Hispanic). The rate of DOAC use increased from 43% to 59%, and the rate of warfarin use declined from 13% to 6% from 2017-2021. The overall use of OAC at hospital discharge increased by 9% from 2017-2021, and by 13% from 2010-2021. After adjustment, stroke hospital designation was the strongest predictor of OAC non-use with 4-fold higher odds of OAC non-use at discharge from an Acute Stroke Ready Hospital compared with a Comprehensive Stroke Center (P=0.012). Increasing age, male sex, renal insufficiency, lower CHA2DS2-VASc, NIHSS ≥5, mRS 3-5, ambulation status, and discharge destination were significant predictors of OAC non-use after AIS with AF.

Conclusion:
OAC use increased by 13% over the last decade in patients with AIS and AF in Florida. Previously identified race/ethnic disparities did not persist in 2017-2021; however, sex, stroke hospital designation, stroke severity, medical comorbidities, functional disability, and ambulation status had a significant impact on OAC use after AIS with AF.
Abstract 147: First-in-human Phase 1/2a Study Of Intracerebral Transplantation Using Embryonic-derived Neural Stem Cells (NR1) For Chronic Ischemic Stroke
Authors: Steinberg Gary K , Bet Anthony , Williams Jennifer , McDonald Kathy , Diaz Robert , Samos Cindy , Trisler Kirk , Weissinger Judy , Coburn Maria L , Tong Elizabeth , Schwartz Neil E
Published: February 2023

Introduction:
Currently, no treatment exists to restore function in chronic stroke patients. Several prior intracerebral stem cell trials showed safety, but are not being further developed.

Objective:
NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models, and was expanded to produce GMP cryopreserved Cell Lots (P18). The aim is to assess the safety, tolerability and efficacy using intracerebral transplantation of NR1 cells in chronic stroke patients (NCT04631406).

Methods:
Inclusion Criteria: 18-75 yo; 6-60 months post-ischemic subcortical MCA stroke; mRS 3-4. Subjects are transplanted with NR1 (2.5M, 5M, 10M or 20M). Primary Outcomes: Adverse events 0-6 mos; Change in Fugl-Meyer (FM) motor score (maximum FM 100) compared to baseline at 6 months (≥10 points improvement considered “clinically meaningful”). Other outcomes: Barthel Index, NIHSS, Gait Speed test, mRS, MRI DTI, FLAIR, Resting State fMRI and
[18F]
FDG PET.

Results:
Six patients have been transplanted. Adverse events included headache and worsened speech, all resolving spontaneously. At 6 mos post-transplant: FM improved 15, 13 and 9 points in patients 1, 2 and 3 (all with faster gait); Barthel Index improved 5, 10 and 15 points. At 3 months FM improved 15 points (with faster gait) in patient 4. NIHSS improved 2 points in 2 patients and worsened 1 point in 1 patient. There was no change in mRS. All 6 patients demonstrated a new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which in prior studies was highly correlated with sustained neurologic recovery. An increase in regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs) was observed in the sensorimotor network ipsilateral to the chronic infarction in patients with clinical improvement. Six additional patients are scheduled in the next 6 months.

Conclusions:
Intraparenchymal transplantation with NR1 cells in chronic stroke patients appears safe and well tolerated. Early results suggest improved motor function at 1-6 months post-implant.
Abstract 150: Vagus Nerve Stimulation (VNS) Paired With Upper Extremity Rehabilitation In Chronic Stroke: Improvements In Wrist And Hand Impairment And Function
Authors: Kimberley Teresa J , Engineer Navzer , Cramer Steven C , Dawson Jesse , Pierce David , Tarver W B , Prudente Cecilia , Vora Isha
Published: February 2023

Introduction:
In the VNS-REHAB trial, vagus nerve stimulation (VNS) paired with task-specific arm and hand rehabilitation (Paired VNS) led to clinically meaningful improvements in both impairment and function of the upper extremity in people with chronic ischemic stroke. In this post hoc analysis of trial data, we assessed whether improvements were driven by proximal (shoulder and elbow) and/or distal (wrist and hand) components of the Upper Extremity Fugl-Meyer Assessment (FMA-UE). We also wanted to determine whether FMA-UE improvements correlated with improvements in functional outcome.

Methods:
Chronic stroke participants (n=108) with moderate-severe UE impairment (FMA-UE 35.1±8) were implanted with the VNS device and randomized to Paired VNS (n=53) or Controls (n=55). Participants underwent 6 weeks of in-clinic therapy followed by 90 days of a home exercise program. Outcomes, including the FMA-UE and Wolf Motor Function Test (WMFT), were collected after in-clinic therapy (Post-1) and 90 days of home therapy (Post-90).

Results:
Distal FMA-UE change was significantly greater after Paired VNS compared to Controls, both at Post-1 (2.43±2.52 vs. 0.64±2.33; 95% CI 0.87-2.72, p<0.001, Cohen’s d=0.74) and Post-90 (2.58±2.88 vs. 0.93±3.16; 95% CI 0.5-2.81, p=0.005, Cohen’s d=0.55). Proximal FMA-UE change was also greater after Paired VNS compared to Controls but did not reach statistical significance at either timepoint. At Post-90, both proximal (r=0.50, p<0.0001) and distal (r=0.42, p=0.001) FMA-UE change significantly correlated with WMFT change after Paired VNS, but not in Controls (proximal: r=0.24, p=0.06; distal: r=0.14, p=0.24).

Conclusions:
The data suggest that Paired VNS leads to greater improvement in the distal upper extremity compared to rehabilitation alone and that improvements in FMA-UE scores are correlated with improvements in function. These findings suggest that the improvements seen with Paired VNS are of functional importance. A greater understanding of region-specific arm and hand recovery after Paired VNS therapy will facilitate planning and implementation of a personalized neurorehabilitation approach based on patient-specific impairments.
Abstract 159: Impact Of Health Inequities On Outcomes Of Stroke In Children
Authors: Pai Akshat M , Nichol Daniel , Musaphir Scherazad , Parthasarathy Sujatha , To Teresa , Kassner Andrea , Ertl-Wagner Birgit , Moharir Mahendranath D , Bhathal Ishvinder , MacGregor Daune , Domi Trish , deVeber Gabrielle A , Dlamini Nomazulu
Published: February 2023

Introduction:
Recent studies have reported access to initial imaging and underlying chronic disorders to be associated with post-stroke outcome in children. However, the influence of sociodemographic factors is yet to be investigated within the Canadian context. Our study explored the role of health inequities while considering the influence of clinical and radiological factors on post-stroke outcomes.

Methods:
A consecutive cohort of children >28 days-18 years of age diagnosed with arterial ischemic stroke between 2004 and 2019 at a comprehensive stroke centre in Ontario were included. Patient residential postal codes were linked to the Ontario Marginalization Index including area-level data on income, education, single-parent families, and housing quality. Post-stroke outcomes were assessed using the validated Pediatric Stroke Outcome Measure - Severity Classification System (PSOM-SCS). Poor outcome was defined as moderate-to-severe deficit at discharge or at 18 months from the onset of stroke. Univariable and multivariable logistic regression models were developed to examine the influence of material deprivation on neurological outcomes while controlling for demographic, clinical, and radiological factors.

Results:
Amongst 234 children, predictors of poor outcome at discharge included moderate-to-severe stroke at presentation (OR = 4.00,
p
< 0.05) while the presence of a single infarct may protect the patient from poor outcome at discharge (OR = 0.32,
p
< 0.05). Predictors of poor outcome at 18 months post-stroke included patients from moderately deprived neighborhoods (OR = 5.36,
p
< 0.05), stroke onset between 2014 and 2019 (OR = 7.44,
p
< 0.05), or presence of a left cerebral hemispheric infarction (OR = 8.20,
p
< 0.05).

Conclusion:
Our study demonstrated that stroke severity and the number of infarcts were important in determining outcome at discharge whereas neighbourhood-level material deprivation, year of onset, and infarct location predicted outcome at 18 months from the onset of stroke. Further research is needed to explore the role of broader social determinants of health in predicting stroke outcomes longitudinally over time.
Abstract 28: First Pass Outcomes And Associated Clot Characteristics: Secondary Analysis Of The Excellent Registry
Authors: Andersson Tommy , Nogueira Raul G , Yoo Albert J , Hanel Ricardo , Zaidat Osama O , Hacke Werner , Jovin Tudor , Fiehler Jens , De Meyer Simon F , Brinjikji Waleed , Doyle Karen , Liebeskind David S , Haussen Diogo C , Inoa Violiza , Humphries William E , Woodward Keith B , Jabbour Pascal M , Francois Olivier , Bozorgchami Hormozd , Levy Elad I , Boor Stephan , Cohen Jose , Dashti Shervin R , Taqi Muhammad A , Budzik Ronald F , Schirmer Clemens M , Hussain M. Shazam , Estrade Laurent , De Leacy Reade A , Puri Ajit S , Chitale Rohan V , Brekenfeld Caspar , Siddiqui Adnan H
Published: February 2023

Introduction:
EXCELLENT (NCT03685578) is a global prospective, multicenter, real-world registry of mechanical thrombectomy for stroke with the EmboTrap device as first line treatment which includes clot collection and analysis.

Aim of the study:
To report the rates of clinical outcomes and clot characteristics associated with first pass reperfusion in EXCELLENT.

Methods:
Per pass angiographic outcomes assessed by an independent core lab were available in 984 subjects Analysis of clot from 538 cases was performed by independent central labs blinded to clinical data. 90-day mRS assessment was blinded to subject data.

Results:
First pass reperfusion of mTICI 2b-3 (63.2%) and 2c-3 (38.3%) was significantly predictive of mRS 0-2 or ≤pre-stroke (p=0.011 and p=0.016) but not all-cause mortality at 90 days (p=0.080 and p=0.123, respectively). Further, mTICI 2c-3 in one pass was associated with a higher rate of mRS 0-2 or ≤pre-stroke vs. mTICI 2c-3 reperfusion in >1 pass, (55.5% and 45.1%, respectively, p=0.013) and a rate of all-cause mortality at 90 days of 14.6% vs. 19.8% (p=0.097). Full patient characteristics and clinical outcomes are shown in Table 1. Notable clot composition findings included: RBC (%, mean±SD): mTICI 2c-3, 1 pass 47.69±22.25, mTICI 2c-3, >1 pass 43.86±19.05, (p=0.088); fibrin: mTICI 2c-3, 1 pass 23.20±13.80, mTICI 2c-3 >1 pass 25.40 ± 13.52 (p=0.131); von Willebrand factor (VWF): mTICI2c-3, 1 pass 16.09±14.62, mTICI 2c-3, >1 pass 19.42±17.15 (p=0.038).

Conclusions:
First pass reperfusion in the EXCELLENT registry was associated with better clinical outcomes at 90 days. Clots retrieved with first pass reperfusion had higher RBC and lower fibrin and VWF content compared to those who achieved reperfusion at greater than one pass.
Abstract 3: Cerebral Small Vessel Disease Burden For Bleeding Risk During Antithrombotic Therapy -BAT2-
Authors: Tanaka Kanta , Miwa Kaori , Yoshimura Sohei , Kamiyama Kenji , Yagita Yoshiki , Nagakane Yoshinari , Hoshino Haruhiko , Terasaki Tadashi , Okada Yasushi , Yakushiji Yusuke , Takahashi Shinichi , Ueda Toshihiro , Hasegawa Yasuhiro , Shiozawa Masayuki , Sasaki Makoto , Kudo Kohsuke , Tanaka Jun , Nishihara Masashi , Yamaguchi Yoshitaka , Fujita Kyohei , Honda Yuko , Kawano Hiroyuki , Ide Toshihiro , Yoshimoto Takeshi , Ihara Masafumi , Koga Masatoshi , Hirano Teruyuki , Toyoda Kazunori
Published: February 2023

Background:
Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs.

Purpose:
To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden.

Methods:
Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models.

Results:
Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P<0.001 for each). A unit increase of SVD score was associated with a higher risk of major bleeding (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.29-1.85) and intracranial hemorrhage (adjusted HR 1.61, 95% CI 1.28-2.03). With SVD score 4 compared to score 0, extracranial major bleeding (adjusted HR 3.37, 95% CI 1.12-10.15) and gastrointestinal bleeding (adjusted HR 2.54, 95% CI 1.02-6.35) were also significantly increased. A higher SVD score was associated with a mild but significant elevation of ischemic event risk (adjusted HR per unit increase 1.17, 95% CI 1.06-1.29).

Conclusions:
The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.
Abstract 33: Risk Scores And Brain Mri Markers In Distinguishing Ischemic Stroke And Intracerebral Hemorrhage Risk Among Atrial Fibrillation Patients: The Neuro-Afib Study
Authors: Gurol Edip M , Das Alvin S , Daoud Nader , Abramovitz Avia , Gokcal Elif , Rotschild Ofer , Yaghi Shadi , Smith Eric E ,   The Neuro-AFib Study Investigators
Published: February 2023

Background:
Recent studies cast doubt on the accuracy of the most-commonly used risk scores (CHA
2
DS
2
-VASC and HAS-BLED) in differentiating the risk of acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) among patients with fibrillation (AF). Because of the importance of AIS/ICH risk determination for choice of proper preventive approaches, we aimed to compare the value of these risk scores and brain MRI markers to differentiate the occurrence of AIS and ICH in a large cohort of AF-related strokes.

Methods:
The Neuro-AFib study is a multicenter effort to elucidate the causes and consequences of AIS and ICH in AF patients. Demographics, CHA
2
DS
2
-VASC and HAS-BLED scores, and ischemic/hemorrhagic brain MRI markers were compared between AF patients admitted with AIS and ICH to 15 academic stroke centers in the US between 1/2018-12/2019.

Results:
Of 5694 stroke admissions with AF, 4826 (84.8%) had AIS and 868 (15.2%) ICH. Mean age was similar between groups (75.9±11.5 vs 76.6±11.9, p=0.1), more ICH patients were male (57% vs 50%). Pre-index event CHA
2
DS
2
-VASC (4.14±1.6 vs 4.22±1.6) and HAS-BLED (2.71±1.09 vs 2.68±1.13) were similar between groups [both p>0.2]. Cerebral microbleeds (CMB, 56% vs 33.5%), cortical superficial siderosis (cSS, 15% vs 9.4%), and moderate-to-severe leukoaraiosis (41% vs 33.4%) were more commonly found among ICH patients compared to AIS (all p<0.001). Chronic lacunar infarcts (43.5% vs 39.5%, p=0.03) and chronic non-lacunar infarcts (29% vs 18%, p<0.001) were more commonly found in AIS. In a multivariable logistic regression model that included all variables above, male sex, presence of CMBs, cSS, moderate-to-severe leukoaraiosis were associated with ICH, chronic non-lacunar infarcts with AIS (all p<0.005), while CHA
2
DS
2
-VASC (p=0.9) and HAS-BLED (p=0.9) were not related to the stroke type.

Conclusions:
Data from our multicenter study confirm the lack of specificity of CHA
2
DS
2
-VASC and HAS-BLED to categorize the risk of AIS vs ICH in AF patients. The chronic MRI findings (CMB, cSS, moderate-to-severe leukoaraiosis, chronic infarcts) should be incorporated into risk scores, and their predictive value for AIS and ICH should be investigated in prospective studies to select optimal stroke prevention methods in AF patients.
Abstract 35: Changes In Sickle Cell Vasculopathy After Hematopoietic Stem Cell Transplantation
Authors: Lightfoot Nathan , Pinna Pranusha , Bicher Nathan , Hsieh Matthew , Norato Gina , Tisdale John F , Lynch John K
Published: February 2023

Introduction:
Cerebral vasculopathies (stenoses and aneurysms) are a major cause of stroke and disability in adults and children with sickle cell disease (SCD). HSCT has been shown to prevent or improve large vessel intracranial stenosis in children when compared to standard care (Verlhac 2020). We sought to determine the impact of HSCT on the development and progression of cerebral vasculopathies in adults with SCD.

Methods:
The study population included patients with SCD (HbSS, HbSC, and HbS/beta-thalassemia) that were enrolled in NIH studies (14-H-0077, 09-H-0225, 03-H-0170) and underwent HSCT from 2004-19 and received pre- and post-transplant MRI/MRA studies. MRA images were reviewed by two independent readers and scored for stenoses in eight intracranial arteries, Moyamoya collateralization, and presence and progression of intracranial aneurysms. Changes in vasculopathy were compared before and after transplantation.

Results:
Eighty-seven patients were included in the study, mean age 32.2 yrs. and 58% male. Median follow-up period was 3.3 yrs. (range: 0.5-17 yrs.), and 28% had evidence of vasculopathy at transplant; 17% with stenotic vasculopathy and 13% with aneurysm(s). None of the patients without vasculopathy developed stenoses or aneurysms after HSCT. MRA stenoses scores improved after HSCT in 62% of patients with vasculopathy, with a median change of 1.0 (range: 1-6; p=0.01). All intracranial aneurysms identified at transplant remained unchanged in follow-up.

Conclusions:
Hematopoietic stem cell transplantation improved or prevented the development of vasculopathy in adults with sickle cell disease.
Abstract 44: Impact Of Novel Oral Anticoagulant Use On Secular Trend Of Vascular Events Or Death After Atrial Fibrillation-related Acute Ischemic Stroke
Authors: Lee Minwoo , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Kim Beom J , Kim Jun Y , Kang Jihoon , Park Jong-moo , Kang Kyusik , Park Tai H , Lee Kyung Bok , Hong Keun-sik , Park Hong-kyun , Cho Yong-Jin , Kim Dong-Eog E , Lee Soo Joo , Kim Jae G , Lee Jun , Cha Jae-kwan , Kim Dae Hyun , Kim Joon-Tae , Choi Kangho , Choi Jay Chol , Sohn Sung-il , Hong Jeong-Ho , Lee Sanghwa , Chul Ho Kim , Shin Dong Ick I , Yum Kyu Sun , LEE JUNEYOUNG , Lee Ji Sung , BAE Hee-joon
Published: February 2023

Introduction:
Now novel oral anticoagulants (NOAC) are strongly recommended for secondary stroke prevention in patients with atrial fibrillation (AF). However, it remains unclear to what extent the introduction of NOACs improved clinical outcomes in real-world practice.

Methods:
Using a nationwide prospective multi-center stroke registry database, we identified consecutive AIS patients with AF enrolled between Jan 2011 and Dec 2019, and analyzed one-year clinical events and NOAC prescription at discharge. The primary outcome was the composite of stroke, myocardial infarction, and all-cause death. To assess the mediation effect of NOAC on the outcomes, we performed natural effect models according to the calendar year. The exposure-mediator analysis, exposure-outcome analysis, and mediator-outcome analysis were performed using multivariate regression analysis according to the characteristics of the variables.

Results:
We analyzed 12,500 patients (mean age, 74.4 years; 51.3% male; median NIHSS at presentation, 8). From 2011 to 2019, the cumulative one-year incidence of the primary composite outcome (28.3% to 22.1%), all-cause mortality (23.8% to 17.9%), and stroke recurrence (8.3% to 5.1%) significantly decreased, while the NOAC prescription rate at discharge increased (0% to 75.6%). One-year increase in the calendar year was independently associated with a delayed occurrence of primary composite outcomes (Step 1: adjusted Time Ratio (aTR), 1.10; 95% confidence interval, 1.07-1.14) and with an increased NOAC prescription rate (Step 2: adjusted odds ratio, 2.20; 2.14-2.27). Increase in the NOAC prescription rate was significantly associated with the delayed occurrence of primary composite outcome (Step 3: aTR, 3.80; 3.15-4.58). However, after controlling for the NOAC prescription rate (mediator), the calendar year was no longer associated with the primary composite outcomes. (Step 4: aTR, 0.78; 95% CI 0.60-1.03). Thus, our results indicate full mediation of NOAC prescription in the association between the calendar year and primary composite outcomes.

Conclusion:
The reduced risk of major vascular events or death over time in AIS patients with AF was fully mediated by the increase in NOAC use.
Abstract 47: Outcomes In Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy Before And After 2015: An Analysis Of The National Inpatient Sample
Authors: Hardigan Trevor , Yaeger Kurt , Philbrick Brandon , Fifi Johanna T , Kellner Christopher P , Mocco J D , Majidi Shahram
Published: February 2023

Background:
Endovascular thrombectomy (EVT) demonstrated superiority to medical management in the 2015 trials. We sought to compare outcomes in acute ischemic stroke (AIS) treated with EVT before and after 2015.

Methods:
A query of the 2000-2019 National Inpatient Sample was performed for patients admitted with AIS (ICD9 433, 43401, 43411, 43491, ICD-10 I63). Demographics, comorbidities, and outcomes were identified. Univariate analysis with t-tests or chi-square performed as appropriate. A 1:1 nearest neighbor propensity score matched cohort was generated. Variables with standardized mean differences >0.1 used in multivariate regression to generate adjusted odds ratios (AOR)/β-coefficients for EVT on outcomes. Significance set at an alpha level of <0.001. All analysis performed in R version 4.1.3.

Results:
A total of 10,415,286 patients with AIS were identified; 149,367 (1.4%) underwent EVT. Among the EVT cohort, 35,562 patients were treated before 2015 (23.8%) vs. 113,805 (76.2%) after. EVT patients after 2015 were more likely to be younger, on private insurance, treated at large urban nonteaching hospitals, had lower Elixhauser Comorbidity Scores (14.71 ± 9.15 vs. 16.21 ± 9.17; p<0.001) but increased markers of stroke severity such as higher rates of ventilator use, paresis, seizures, craniotomy and tracheostomy placement (all p<0.001). After propensity matching, EVT patients after 2015 were more likely to be discharged home (AOR 1.35, 95%CI:1.24-1.47), have increased hospital charges ($40828.79; 95%CI: $36391.76-45265.81), had shorter hospital stay (-0.74 days, 95%CI: -0.99 - -0.48)(all p<0.001), with no difference in In-hospital mortality.

Conclusions:
This 20-year nationally representative propensity matched analysis of AIS patients shows that outcomes after EVT continue to improve following the landmark 2015 publications, with a higher chance of favorable outcome, lower hospital charge and shorter hospital stay compared to before 2015.
Abstract 50: Rescue Stenting For Failed Mechanical Thrombectomy In Acute Ischemic Stroke: Systematic Review And Meta-analysis
Authors: Rodriguez-Calienes Aaron , Galecio-Castillo Milagros , Vivanco Suarez Juan , Zevallos Mau Cynthia , Siddiqui Fazeel , Samaniego Edgar A , Farooqui Mudassir , Ortega-Gutierrez Santiago
Published: February 2023

Introduction:
When mechanical thrombectomy (MT) fails to achieve successful recanalization, rescue stenting (RS) has proven to be a feasible rescue therapy. However, the available evidence remains underpowered to assess its safety and efficacy.

Objective:
To compare the safety and efficacy of RS versus routine medical treatment in patients who failed MT using an aggregated metanalysis.

Methods:
A systematic review was performed in Scopus, Embase, Medline, and Web of Science from inception to July 2022 for all studies that tested the safety and efficacy of RS after failed MT. Outcomes of interest included an mRS score of 0-2 at 90 days, successful recanalization (mTICI 2b-3) after RS, symptomatic intracranial hemorrhage (sICH), and all-cause mortality at 90 days. A random-effects meta-analysis was performed between the RS and medical treatment arm to calculate pooled odds ratios (OR) for each outcome. Statistical heterogeneity across studies was assessed with I
2
statistics.

Results:
In total 12 studies involved 1855 participants, 729 in the RS arm and 1126 in the medical treatment arm. The pooled results indicated that RS was associated with a higher proportion of patients with an mRS score of 0-2 at 90 days (RS: 41% vs. 21%; OR = 3.27; 95% CI 2.08 - 5.16; I
2
= 64%) and a decreased risk of mortality at 90 days (RS: 22.5% vs. 33.8%; OR = 0.47; 95% CI 0.32 - 0.69; I
2
= 45%), compared with medical treatment after failed MT. The pooled rate of successful recanalization after RS was 87% (95% CI 82 - 91; I
2
= 57%). The rate of sICH did not differ between groups (RS: 8.5% vs. 11.7%; OR = 0.85; 95% CI 0.59 - 1.20; I
2
= 7%)

Conclusion:
RS represents a promising strategy that for maximizing recovery in acute stroke patients after first line MT fails to achieve meaningful reperfusion. However, a randomized trial using a standardized approach/technique and independently adjudicated outcomes is needed to confirm this observation.