bluuebunny/crossref_metadata_2025 huggingface dataset:
Implication of Different ECG Left Ventricular Hypertrophy in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Yang Yujin , Ahn Jung‐Min , Kang Do‐Yoon , Ko Euihong , Kim Seonok , Kim Tae Oh , Kim Ju Hyeon , Lee Junghoon , Lee Seung‐Ah , Kim Dae‐Hee , Kim Ho Jin , Kim Joon Bum , Choo Suk Jung , Park Seung‐Jung , Park Duk‐Woo
Published: February 2022

Background

Various ECG criteria for left ventricular hypertrophy (LVH) have been proposed, but their association with clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement is unknown. We investigated the prevalence of ECG LVH according to different criteria and its prognostic impact on clinical outcomes after transcatheter aortic valve replacement.

Methods and Results

In this prospective observational cohort, we evaluated 700 patients who underwent transcatheter aortic valve replacement between March 2010 and December 2019. Baseline preprocedural LVH was defined by 3 ECG criteria—Sokolow‐Lyon, Romhilt‐Estes, and Cornell voltage criteria. The primary outcome was major adverse cardiac or cerebrovascular event (MACCE; composite of death, myocardial infarction, stroke, or rehospitalization from cardiovascular cause); the key secondary outcome was all‐cause and cardiovascular mortality. Among 596 eligible patients, the prevalence of LVH was determined as 56.3% by Sokolow‐Lyon, 31.1% by Romhilt‐Estes, and 48.1% by Cornell criteria. Regardless of the criteria, patients with ECG LVH had more severe aortic stenosis hemodynamics and higher left ventricular mass index. After multivariate adjustment, the presence of LVH by the Cornell criteria was significantly associated with lower risks of MACCE (adjusted hazard ratio [HR], 0.68; 95% CI, 0.51–0.91;
P
=0.009), all‐cause mortality (adjusted HR, 0.55; 95% CI, 0.34–0.90 [
P
=0.017]), and cardiovascular mortality (adjusted HR, 0.40; 95% CI, 0.20–0.79 [
P
=0.008]). However, this association was absent with the Sokolow‐Lyon and Romhilt‐Estes criteria.

Conclusions

ECG LVH by Cornell criteria only was significantly associated with lower risks of MACCE and all‐cause or cardiovascular mortality.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03298178.
Abstract 100: Meningeal Lymphatic System Modulates Intra-parenchymal Hematoma Clearance And Brain Recovery In Experimental Intracerebral Hemorrhage
Authors: Hsieh Yung , Tsai Hsin-hsi C , Lin Jhih Syuan , Kuo Zi Ting , Ho Chi Ying , Chen Chih Hung , CHANG Che-feng
Published: February 2022

Background:
Intracerebral hemorrhage (ICH) brain injury is induced by toxic blood components and subsequent neurologic deficits can be alleviated by promoting hematoma resolution. The meningeal lymphatic system has been shown to mediate substances clearance from the central nervous system, including macromolecules and pathogenic metabolites. However, it remains unclear whether this system plays a role in hematoma clearance and ICH outcomes. In this study, we investigated the correlation between meningeal lymphatic function and ICH pathologies. Pharmacological promotion of meningeal lymphatic function was also used to determine whether targeting meningeal lymphatic system can facilitate ICH recovery.

Methods:
Whole-mount meninges were used to evaluate the complexity and coverage rate of meningeal lymphatic vessels. Meningeal lymphatic drainage was evaluated by injecting fluorescent microbeads and PKH26-labeled erythrocytes into the cisterna magna and brain parenchyma, respectively. Hematoma volume was measured in fresh coronal brain sections. Neurobehavioral performance was evaluated by cylinder test. Pathological outcomes including iron deposition, residual erythrocytes, neuronal loss, and astrogliosis were detected by immunohistochemistry or immunofluorescence.

Results:
Meningeal lymphangiogenesis and increased lymphatic drainage occur during the late phase of ICH. Depriving the function of meningeal lymphatic vessels impeded hematoma clearance, whereas boosting meningeal lymphatic drainage and lymphangiogenesis improved hematoma clearance rate and behavioral function as well as reduced iron deposition, neuronal loss, and astrogliosis in the ICH brain.

Conclusion:
Early enhancement of meningeal lymphatic function is beneficial for ICH recovery, implicating the meningeal lymphatic system as a potential therapeutic target for treating ICH.
Abstract 129: Electromagnetic Portable Brain Imaging For Stroke
Authors: Dos Santos Angela , Balabanski Anna , Cook David , Crozier Stuart , Bialkowski Konstanty , Langenberg Francesca , Bivard Andrew , Bishop Lara , Easton Damien , Donnan Geoffrey A , Davis Stephen
Published: February 2022

Background:
Electromagnetic imaging (EMI) is an emerging technology that transmits low energy electromagnetic waves from a ring of transceivers around the head, modified as they pass through abnormal tissue, providing unique signatures for brain pathology. It promises to provide portable, non-ionizing, rapid neuroimaging for prehospital and bedside evaluation of stroke, based on the dielectric properties of the tissue. We aimed to assess the clinical utility of EMI in stroke diagnosis in a pilot study.

Methods:
In a prospective, observational, open, non-interventional pilot study, patients with imaging-proven ischemic (IS) or haemorrhagic stroke (ICH) within the preceding 48 hours were recruited. Using the EMVision scanner, EMI was performed within 1-24 hours of diagnostic CT or MRI. Images were obtained by processing signals from encircling transceiver antennae contained in an instrumented 18 kg helmet which emit and detect low energy non-ionising signals in the microwave frequency spectrum (0.5-2.0 GHz). Localisation was assessed by determining whether fusion images resulted in target detection in the same quadrant as comparable CT or MRI. Electromagnetic (EM) images were reconstructed by creating maps of the EM wave scattering arising from contrast in electrical parameters between IS or ICH lesions and normal brain. A blinded clinician assessed agreement between regional abnormalities on EMI and CT or MRI scans. Algorithms for distinction between IS and ICH were based on differences in EM transmission, reflection and scattering through brain tissue.

Results:
Thirty patients were studied, 21 IS and 9 ICH. Mean age was 66.7 years (range 37-87), 57% were female. Mean NIHSS at presentation was 5. Mean time to routine imaging was 5.5 hrs (range 1-48) and to EMI 24 hrs (range 6-60). Nineteen patients (63%) had only CT performed; 11 (37%) had both CT and MRI. EMI differentiated ICH from IS with 93% accuracy and localised the stroke to the correct brain quadrant with 87% accuracy.

Conclusion:
In this early validation pilot study we show the ability to distinguish between IS and ICH and stroke location within a given brain quadrant. Further developments may produce a valuable imaging tool to assist in prehospital and bedside stroke diagnosis and management.
Abstract 135: Number-needed-to-review: A Novel Metric To Assess Triage Efficiency Of Large Vessel Occlusion Detection Systems
Authors: Catapano Joshua , Lee Katriel , Desai Shashvat , Ducruet Andrew F , Albuquerque Felipe C , Jadhav Ashutosh P
Published: February 2022

Background:
Endovascular thrombectomy is the gold standard treatment for acute ischemic strokes with large vessel occlusions (LVO). Manual image analysis is often time consuming and requires clinicians to be skilled in reading perfusion scans, as well as vessel images. RapidAI software has an automated processor to detect LVO of the middle cerebral artery and is analyzed in this study. A novel metric, number-needed-to-review (NNR), is introduced to assess the clinical efficiency of this software.

Methods:
This is a retrospective review of patients with a suspected ischemic stroke and an image processed by RapidAI software from 11/1/2020 to 4/30/2021 at a regional hospital system. Only M1 LVOs were included. Sensitivities, specificities, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the following: Rapid LVO detection, gaze deviation (GD), hyperdense sign (HDS), Tmax >6 seconds, and NIHSS at presentation. The NNR was calculated for an M1 occlusion.

Results:
559 patients were included in this study. M1 occlusion was detected in 42 (7.5%) cases. Rapid LVO detection software was found to have a sensitivity of 71%, specificity of 94%, PPV of 49%, and NPV of 92% for a M1 occlusion. When both GD and HDS were combined with Rapid LVO, the specificity and PPV increased to 100% for a M1 occlusion. A negative LVO software combined with either a low (<15 mL on Tmax >6s) or high (<50 mL on Tmax >6s) Tmax threshold were found to have a specificity and PPV of 100% for no M1 occlusion. The combination of GD, HDS, Rapid LVO+ (for M1 occlusion) and Rapid LVO- with a low Tmax threshold (for no M1 occlusion) yielded 24 images NNR per 100 cases. When the combination of GD, HDS, Rapid LVO+ was combined with Rapid LVO- and a high Tmax threshold, the NNR per 100 cases was 16. With the addition of NIHSS<7 for the remaining cases in the high Tmax group, the NNR per 100 cases decreased to 9.

Conclusion:
The addition of GD and HDS to the Rapid LVO increases the specificity and PPV for a M1 occlusion. When combined with a negative Rapid LVO detection and either a low or high Tmax >6s threshold, the NNR is significantly decreased. As few as 9 images per 100 would be needed to be manually reviewed by a clinician during stroke triage.
Abstract 138: Thrombus Composition Is Associated With First Pass Recanalization
Authors: Juega Jesus , Palacio Carlos , Piñana Carlos , Rodriguez Maite , deck matias , Moline Teresa , Camacho Jessica , Cardona Pedro , QUESADA HELENA , Hernandez-Perez Maria , Dorado Laura , Requena Manuel , Alvaro Garcia-Tornel , Rodriguez-villatoro Noelia , Olive Marta , boned sandra , Muchada Marian , Lozano Prudencio , Li Jiahui , Rubiera Marta , tomasello alejandro , Hernandez David , DE Dios Marta , Ramon y Cajal Santiago , Ribo Marc , Sabin Jose A , Molina Carlos A , PAGOLA JORGE
Published: February 2022

Introduction:
Our objective is to identify thrombus composition associated with first pass recanalization (FPR) in mechanical thrombectomy (MT).

Methods:
Intracranial thrombi obtained in MT were divided in two equal parts. One part was analyzed with anatomopathological studies to quantify fibrin, red-blood cell( Hematoxilin & Eosin) and platelets( cd61 Immunohistochemical
staining
) , the other part was analyzed by flow cytometry to quantify leukocyte populations (granulocytes, lymphocytes and monocytes) and their relative proportions . FPR were defined as ≥ mTICI 2b after first pass in MT. Thrombi composition, baseline variables (demographics, previos use of antiplatelets or anticoagulants, blood pressure and blood glucose at hospital arrival ) etiology, intravenous fibrinolysis, ASPECTS score and first attempt thrombectomy devices: direct aspiration, stent retriever or combinations were compared between FPR and Non-FPR groups.

Results:
Fifty percent (38/76) of the cases analyzed obtained FPR. There were no differences in baseline variables , etiology, Aspects score, previous use of fibrinolysis or type of device used for MT. The thrombi obtained with FPR presented higher proportion of red blood cells (33.64% vs 18.16% p = 0.048) and lymphocytes (10.07% vs 4.43% p = 0.042) and lower proportion of platelets (61, 48% vs 67.26% p = 0.042) in comparison to non-FPR group. The proportion of platelets was an independent marker of FPR (OR 0.97; CI 0.95-0.99). There was an inverse correlation between the proportion of platelets and lymphocytes (rho -0.44, p <0.001).

Conclusion:
Platelets proportion in intracranial thrombus is an independent marker of first pass recanalization. Inverse relationship between lymphocytes and platelets may be a target for future reperfusion treatments
Abstract 142: Lives Lost Due To Disparities Quantified:
Black-White And Rural-Urban Disparities In Cerebrovascular Mortality
Among Middle-Aged Adults
Authors: Cierny Marek , Man Shumei , Uchino Ken
Published: February 2022

Introduction:
We aimed to quantify and trend excess cerebrovascular deaths among middle-aged adults that could be attributed to Black-white and rural-urban disparity in the US.

Methods:
Annual age-adjusted mortality rates (AAMR) for ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) among middle aged adults (ages 35-64) were obtained from Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research database from 1999 to 2019. AAMR difference between African-Americans and whites (Black-white disparity), as well as residents of Non-Metro and Large Metro counties (Rural-Urban disparity) was used to estimate excess event- and gender- specific annual deaths attributable to each disparity. Linear AAMR epochs and parallelism were assessed with Joinpoint.

Results:
Lives lost to Black-white disparity decreased from 3850 in 1999 to 2750 in 2013 and stagnated since. The finding was driven by decline in SAH and ICH mortality between 1999 and 2019, and recent increase in excess deaths due to IS (105 in 2014, 240 in 2019). Lives lost to Rural-urban disparity increased from 360 in 1999 to 740 in 2019, driven by excess deaths due to ICH (-30 in 1999, 100 in 2019) and recently IS (50 in 2013, 130 in 2019).

Conclusion:
Black-white disparity accounting for ~2750 excess deaths among blacks per year remains the leading inequity in cerebrovascular mortality. This is 3.7 times more deaths than Rural-Urban disparity in 2019.
Abstract 148: Impact Of Performing Vascular Imaging At Local Stroke Centers On Functional Outcome In The Drip And Ship Model. A Racecat Sub-study
Authors: Flores Alan , García-Tornel Alvaro , Seró Laia , Ustrell Xavier , Pellise Anna , Castilho Gislaine , Abilleira Sonia , Perez De La Ossa Natalia , Ribo Marc
Published: February 2022

Background:
Although recommended, impact of vascular imaging performed to determine a large vessel occlusion (LVO) at local stroke centers on functional outcome in the drip and ship model is uncertain. Our aim was to compare functional outcomes in patients with (VI+) and without (VI-) vascular imaging at local stroke center using data from the RACECAT trial.

Methods:
RACECAT study was a multicenter, cluster-randomized trial that compared drip-n-ship vs. mother-ship models in acute stroke patients with LVO suspicion based on the prehospital RACE scale, performed in the period of March 2017 to Juny 2020. Patients allocated to Local-center arm, were included in this substudy to evaluate the impact of performing VI (CT-Angiography) at Local-center on functional outcome at 3 months assessed by modified Rankin scale (mRS)

Results:
From 690 patients, ischemic stroke or transient ischemic attack was diagnosed in 467. Among these, a vascular imaging was performed at the Local-center in 55.6% (n:260), of which an LVO was confirmed in 76.1% (n:198). No differences in baseline characteristics were observed between VI+ and VI- groups. The rate iv-tPA treatment at Local-centers was higher in VI+ (67.8% vs. 54.2%; p=0.004) with shorter door-to-needle times time (VI+: 31 (24-44) Vs VI-: 39 (27-56) minutes, p=0.003). The rate of patients receiving endovascular treatment at the comprehensive center was similar (VI+: 41.9% Vs VI-:39.4%; p=0.602), however VI+ patients presented shorter time from EVT-center arrival to groin-puncture (VI+: 37 (26-48) Vs VI-:52 (42-70) minutes; p<0.001). Overall, the time from symptom onset to groin puncture was not significantly different between both groups (VI+:279 (228-355) Vs VI-: 233 (214-327) minutes; p=0.068). The common odds ratio for a better distribution of scores on the mRS at 3 months was 1.48 (95% confidence interval [CI], 1.059 to 2.068; P=0.022), favoring the VI+ group.

Conclusion:
Initial evaluation in a local stroke center capable to efficiently perform vascular imaging might be associated with better long term functional outcome in stroke patients with high suspicion of LVO. Whether this association is related to vascular imaging acquisition or a better performance of centers in which it is acquired should be further evaluated.
Abstract 15: The Novel Complement C3ar Antagonist Jr14a Is Neuroprotective In Stroke
Authors: Ahmad Saif , Kindelin Adam , Wang Kendra , Lambay Ateeq , Karra Sakshi , Miller Karis , Bhatia Kanchan , Fairlie David P , Ahmad Abdullah S , Waters Michael F , Ducruet Andrew F
Published: February 2022

Background:
Stroke is the third leading cause of disability and mortality in the world. The
c
omplement C3a receptor plays a prominent role in post stroke brain inflammation. We and others have reported that either genetic deficiency of complement C3a receptor (C3aR) or its pharmacological inhibition in rodents protect against cerebral ischemia. The existing C3aR antagonist (SB290157) is limited by its reported agonist effect in different model systems.

Hypothesis:
The novel highly-selective C3aR antagonist JR14a confers robust neuroprotection in stroke

Methods:
Mouse primary brain endothelial cells (cell biologics Inc. IL, USA) were seeded at a density of 5000 cells/well in 96-well plates and cultured until 80-90% confluency. Endothelial cytotoxicity was tested using an LDH assay following 24 hours of exposure to JR14a. Oxygen-glucose deprivation (OGD) was followed by reperfusion to compare the in-vitro effects of JR14a and SB290157, using ELISA performed for TNF-α and IL-6 and immunofluorescence for ICAM-1 expression. We also compared JR14a and SB290157 in the middle cerebral artery occlusion (MCAO, C57BL/6) stroke model, evaluating infarct volume.

Results:
JR14a treated endothelial cells exhibited reduced LDH release (Fig.1) and more potent anti-inflammatory response following OGD/R compared to SB290157. We found that JR14a treatment significantly reduced endothelial TNF-α, IL-6 and ICAM-1 expression. JR14a also significantly reduced brain infarction and microglial activation relative to SB290157 following MCAO in C57BL/6 mice (Fig 2).

Conclusion:
We conclude that the novel C3aR inhibitor JR14a attenuates inflammation and endothelial dysfunction in stroke and may confer a more potent neuroprotective effect than SB290157. Further work is warranted to explore the mechanisms underlying JR14a-mediated neuroprotection
Abstract 153: Long-Term Risk Of Stroke After Posterior Reversible Encephalopathy Syndrome
Authors: Parauda Sarah C , Zhang Cenai , Schweitzer Andrew D , Murthy Santosh B , Merkler Alexander E , Navi Babak B , Kamel Hooman , Parikh Neal S
Published: February 2022

Introduction:
Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke.

Methods:
We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using
ICD-10-CM
codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded.

Results:
We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period.

Conclusions:
PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.
Abstract 156: Main Results Of The Take Off Pounds After Stroke Trial
Authors: Dearborn-Tomazos Jennifer L , viscoli catherine , Rivera Jessica , Gull Anum , Lovelett Laurel , Amin Hardik , Kernan Walter N
Published: February 2022

Objective:
To test the effectiveness of a 12-week partial meal replacement (PMR) intervention for achieving meaningful weight loss in overweight or obese patients with a recent ischemic stroke.

Methods:
Take Off Pounds After Stroke (TOPS) was a prospective randomized open blinded endpoint trial. Eligible patients had an ischemic stroke within the past 90 days, were ≥18 years of age, with BMI 27 to 49.9 kg/m
2
, maximum weight ≤350 pounds (limit of home scale we provided), and were able to stand on a scale unassisted, meet all nutritional needs by oral intake, and ready to undergo behavioral change. Patients were excluded if they required dialysis, had a contra-indication to a weight loss diet, had lost ≥12 lbs in the prior 3 months, were allergic to soy, did not speak English or were pregnant, breast feeding, or desired to become pregnant. Patients were randomized to a PMR (OPTAVIA® Optimal Weight 4&2&1 Plan™) or enhanced standard care (SC). The PMR program is commercially available and consists of daily intake of four meal replacements, two “lean and green” meals and one healthy snack (1,100 to 1,300 calories per day). Enhanced standard care consisted of one instructional session on a healthy diet advocated by the US Department of Agriculture (and provision of a manual). The primary outcome was achievement of at least 5% weight loss at 12 weeks.

Results:
From 1 2/2019 to 2/2021, a total of 38 patients were enrolled from two sites. Two patients in each arm did not complete the study. At 12 weeks, 9 of 17 patients in the PMR group and 2 of 17 patients in the SC group achieved at least 5% weight loss (52.9% v. 11.9%; Fisher’s exact p=.02). Mean percent weight loss in the PMR group was 3.0% (SD 13.7) compared with 2.6% (SD 3.4) in the SC group (Wilcoxon rank sum p=.17). Patients in the PMR group had a mean change in waist circumference of -5.0 cms (SD 9.8) compared to -4.7 cms (SD 6.3) in the standard advice group (ANOVA p=.94). Changes in blood pressure and modified Rankin Scale did not differ between groups. No adverse outcomes were associated with the study intervention.

Conclusion:
A dietary intervention for weight loss implemented soon after ischemic stroke is feasible, safe and effective for weight loss.
Abstract 161: Aberrant B Cell Responses Promote Neuroinflammation In Mice With Cerebral Amyloid Angiopathy
Authors: Honarpisheh Parisa , Banerjee Anik , Lee Juneyoung , McCullough Louise
Published: February 2022

Cerebral amyloid angiopathy (CAA) is a small vessel disease, characterized by amyloid beta deposition in the cerebral vasculature. CAA increases the incidence of hemorrhagic stroke and dementia in the elderly. Evidence has revealed that aging alone induces disruption in B cell differentiation and immunosenescence by promoting the presence of age-associated B cells (ABCs) characterized by an upregulation of CD11b
high
. However, little is known on how these ABCs influence the neuroimmune landscape of vascular dementia, an immune-mediated age-associated disease.

Hypothesis:
CAA induces the differentiation of B cells in the brain resulting in neuroinflammation characterized by an exacerbated presence of microglia and lymphocytic infiltration. Pre-symptomatic (2mo) and symptomatic (18mo) Tg-SwDI (harboring Swedish, Dutch, and Iowa) mutations of human amyloid precursor protein male mice were used as a model of CAA. Through flow cytometry, we investigated the role of CD11b
high
B cells in promoting neuroinflammation in CAA. Age-matched C57BL/6 wild-type (WT) male mice were included to determine CAA-specific effects.

Results:
A remarkably heterogeneous CD19
+
B cell population was identified in symptomatic CAA mice. Interestingly, CD19
+
CD11b
high
B cells were significantly increased in the symptomatic CAA brain (n=4-6/gp,
P
=<0.0001) as compared to pre-symptomatic and age-matched WT mice. Protein expression of CD73, CD80, and CD138 was assessed to determine memory formation, antibody production, and inflammatory properties of these CD19
+
CD11b
high
B cells. Notably, CD19
+
CD11b
high
B cells from CAA symptomatic mice had significantly lower expression of CD73 (n=4-6/gp,
P
=0.0004), CD80 (n=4-6/gp,
P
=0.0007), and CD138 (n=4-6/gp,
P
=0.0154) compared with those CD19
+
CD11b
high
B cells from age-matched WT brain. Finally, CAA mice had significantly higher microglial counts (n=4-6/gp,
P
=0.0013) and lymphocytic infiltration (n=4-6/gp,
P
=0.0071) in the brain as compared to pre-symptomatic and WT aged mice. Here, we highlight the diversity of B cells in age-associated vascular dementia. Our data give us further perception into the influence of humoral immunity mediated by ABCs and their immune crosstalk in CAA.
Abstract 162: Arterial Aspirate Derived Exosomes From Patients With Large Vessel Occlusion Are Associated With Increased Blood-brain Barrier Permeability, Decreased Endothelial Integrity As Well Poor Clinical And Radiographic Outcomes Following Mechanical Thrombectomy
Authors: Khadem Alsrouji Owais , Li Chao , Kole Max , Marin Horia , Chopp Michael , Zhang Zheng Gang , Chebl Alex
Published: February 2022

Introduction:
Exosomes (~30-150nm microvessicles [MVs]), are important mediators of cell-cell communication and have been associated with injurious and neuroprotective processes in experimental stroke models. Since many patients treated with mechanical thrombectomy (MT) do not improve despite successful recanalization we hypothesized that these exosomes may mediate injurious processes leading to worse outcomes.

Methods:
As part of an IRB approved protocol we analyzed arterial blood and retrieved clots aspirated during MT from patients with anterior circulation LVO. MVs were isolated and their effects on BBB permeability and endothelial monolayer integrity measured by transepithelial/endothelial electrical resistance (TEER) in cultured human endothelial cells were measured. Following adjustment for age, DM, NIHSS this effect was also correlated (Pearson R) with NIHSS, RAPID™ CTP parameters, TICI score, BP post MT, 24hr ASPECTS, ICH incidence and mRS.

Results:
Forty-eight patients were enrolled; mean age was 71±14yrs, 56% were female and 20% were African-American. Mean NIHSS was 16±6.6 with a median baseline ASPECTS score of 9 (range 3-10). Baseline CTP parameters (N=21) were: infarct core 25.8±38.5cc, mismatch volume 103±72.2cc and hypoperfusion index (Tmax>10s/Tmax>6s) 0.34±0.25. Recanalization (TICI 2b/c/3) was achieved in 93.8%. The median 24hr ASPECTS was 7 (range 0-10). At last follow-up 43.5% of patients achieved a good outcome (mRS<=2). BBB permeability was associated with NIHSS change (r=-0.31, p=0.0093), TICI (r=-0.31, p=0.031), SBP post MT (r=0.41, p=0.0036) and 24hr ASPECTS (r=-0.31, p=0.015). TEER correlated most strongly with NIHSS change (r=0.36, p=0.0041), TICI (r=0.35, p=0.02), 24hr ASPECTS (r=0.37, p=0.027) and hypoperfusion index (r=-0.4, p=0.041).

Conclusions:
Arterial aspirate derived MVs can be isolated from LVO stroke patients. Their effects on BBB permeability and endothelial integrity significantly correlated with clinical and radiographical markers of poor outcomes. It is therefore plausible that clot derived exosomes may impact neurological outcomes following MT through endothelial and BBB injury. In addition, these in vitro BBB measures may serve as biomarkers for post-stroke outcomes.
Abstract 164: Bet Protein Degradation With The Proteolysis-targeting Chimera, Dbet1, Ameliorates Brain Damage And Neurological Deficits After Transient Cerebral Ischemia
Authors: Liu Lei , Yang Changjun , Lavayen Bianca P , Larochelle Jonathan , Candelario-jalil Eduardo
Published: February 2022

Introduction:
Accumulating evidence indicates that
b
romodomain and
e
xtra-
t
erminal domain (BET) proteins play a pivotal role in the transcriptional regulation of the inflammatory response, and consequently, BET inhibition has emerged as a promising novel therapeutic strategy to reduce inflammation linked to many diseases, including ischemic brain injury. dBET1 is the first BET-targeted proteolysis-targeting chimera (PROTAC) that induces a rapid and efficient deletion of BET proteins
in vivo
.

Hypothesis:
In this study, we hypothesized that dBET1 protects against brain damage and neurological deficits in a transient cerebral ischemia mouse model through the regulation of the inflammatory process.

Methods:
Adult C57BL/6 WT mice were subjected to transient cerebral ischemia surgery (tMCAO) and were administered intraperitoneally with dBET1 (30 mg/kg) or vehicle at 4 and 24 hours after the stroke onset. Infarct volume, neurological deficits, blood-brain barrier integrity, and several inflammatory mediators were examined 48h after tMCAO.

Results:
The expression level of the BET protein, BRD4, in the cerebral cortex was remarkably lower in the dBET1-treated animals compared to the controls. dBET1 significantly reduced infarct volume (56.2±7.9%, P≤0.01, n=13-14) and improved the neurological performance in the open field test, vertical grid test, and neurological deficit scoring (P≤0.05, n=19-20). In dBET1-treated mice, in both ischemic striatum and cerebral cortex, the inflammation-associated reactive gliosis in astrocytes and microglia was significantly attenuated (P≤0.05, n=6), along with a reduction in stroke-mediated blood-brain barrier damage and neutrophil infiltration. Mechanistically, dBET1 produced a dramatic decrease in the expression levels of pro-inflammatory mediators, while it enhanced levels of anti-inflammatory mediators (P≤0.05, n=6).

Conclusion:
Overall, this study provides direct
in vivo
evidence that BET protein degradation with dBET1 suppresses neuroinflammation and leads to anatomical and functional protection against ischemic brain damage. Blocking BET proteins is a promising new strategy to reduce neuroinflammation and eventually improve functional outcomes in stroke.
Abstract 23: Population Access To Acute Stroke Expertise In The United States
Authors: Zachrison Kori S , Cash Rebecca , Adeoye Opeolu , Boggs Krislyn M , Schwamm Lee H , Mehrotra Ateev , Camargo Carlos A
Published: February 2022

Backgound:
In 2011, nearly 20% of Americans lacked timely access to alteplase-capable hospitals. We update this work by assessing access to stroke centers and emergency departments (EDs) with telestroke capacity. Our objectives are to identify all US EDs with acute stroke capabilities (i.e., in a confirmed stroke center or with telestroke capacity), and to characterize the proportion of the US population with access to an ED with either capacity.

Methods:
We used the 2019 National ED Inventory-USA to identify all US EDs and characterize stroke capabilities by hospital stroke center status (none, acute stroke ready hospital [ASRH], primary stroke center [PSC], thrombectomy-capable or comprehensive stroke center [TSC/CSC]) and telestroke capacity. We used 2020 US Census data for census block group population and centroid. For each block group, we used ArcGIS to assess whether an ED with stroke expertise was within a 60 minute (min) response and transport time by ground emergency medical services (EMS). To determine the transport time, we used data from actual EMS stroke transports using the 2019 National EMS Information System with median EMS dispatch, response, and scene times in access calculations.

Results:
Of 5,587 US EDs, 2,563 (46%) were in a stroke center (691 ASRH, 1,505 PSC, 367 TSC/CSC); of these, 55% also had telestroke capacity. Of the 3,024 (54%) that were not a confirmed stroke center, 36% had telestroke. We estimate that 91% of the US population is within 60 min of a confirmed stroke center by ground EMS and 96% is within 60 min of a confirmed stroke center or telestroke ED (Figure). The percentage of the population without access to a confirmed stroke center or telestroke ED varied by region, from 1% in the Middle Atlantic to 9% in the West Mountain.

Conclusion:
Relative to previous reports, an increasing proportion of the US population has access to acute stroke expertise. While geographic disparities in access remain, telestroke plays an important role in filling this gap.
Abstract 24: Mobile Stroke Units Associated With Favorable Clinical Outcome In Large Vessel Occlusion Stroke Patients: BEST-MSU Substudy
Authors: Czap Alexandra L , Nour May , Alexandrov Anne W , Wang Mengxi , Singh Noopur , Yamal Jose-Miguel , Parker Stephanie , Bowry Ritvij , Grotta James C
Published: February 2022

Introduction:
Mobile Stroke Units (MSUs) improve clinical outcome in patients treated with tPA compared to standard management by Emergency Medical Services (EMS), but the impact of MSUs on outcomes in patients with large vessel occlusions (LVOs) having endovascular thrombectomy (EVT) has yet to be determined.

Methods:
A pre-specified substudy of tPA-eligible stroke patients with LVOs on CT and/or CTA who were enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management, was conducted. The primary outcome was the score on the 90-day utility-weighted modified Rankin Scale (uw-mRS). Secondary outcomes were rate of early neurologic recovery (30% improvement in NIHSS score) at 24 hours and functional independence (mRS 0-1) at 90 days.

Results:
A total of 295 patients were included, 169 in the MSU group and 126 in the EMS group. Baseline characteristics were comparable between the groups, with the exception of baseline NIHSS (MSU median 19.0 [IQR 13.0, 23.0] vs EMS 16.0 [11.0, 20.0], p=0.003). 92% MSU vs 87% EMS LVO patients received tPA, and 78% vs 85% went on to have EVT. MSU LVO patients had faster tPA bolus from symptom onset (65.0 min [50.5, 92.0] vs 96.0 [79.3, 130.0], p<0.001), however the two groups had similar onset to groin puncture (169.0 min [133.8, 212.3] vs 162.0 [135.3, 207.0], p=0.77). The mean (±SD) score on the uw-mRS at 90 days was 0.64±0.39 in the MSU group and 0.50±0.40 in the EMS group (mean difference 0.16, 95% CI [0.07, 0.25] after adjustment for age, baseline NIHSS, premorbid functional status, prior stroke/TIA and site; p<0.001). Early neurologic recovery (68% vs 52%; adjusted OR 1.89 95% CI [1.14,3.17]) and functional independence (Figure 1, 42% vs 29%; 2.48 [1.38,4.55]) also favored the MSU group.

Conclusions:
In tPA-eligible LVO stroke patients, MSU management was associated with better clinical outcomes compared with standard EMS management.
Abstract 31: One-year Mortality And Stroke Readmissions After Ischemic Stroke In Critical Access Hospitals
Authors: Lichtman Judith H , Leifheit Erica C , Wang Yun , Goldstein Larry B
Published: February 2022

Background:
Critical access hospitals (CAHs) provide emergency and inpatient care in rural communities. CAHs have higher 30-day mortality after stroke, but little is known about long-term outcomes. We compared 1-year outcomes after ischemic stroke for patients treated at CAHs versus other hospitals.

Methods:
We identified all Medicare fee-for-service beneficiaries aged ≥65 years discharged alive from US hospitals with a principal diagnosis of ischemic stroke in 2015. Patients were followed 1 year for death or stroke recurrence, accounting for competing risks. We balanced characteristics between CAH and non-CAH patients using stabilized inverse probability weights (IPW) based on patient demographic and clinical characteristics. We created adjusted Kaplan-Meier curves based on the IPW and fit Cox models to assess differences in 1-year mortality and recurrent stroke weighted by the IPW.

Results:
There were 4,487 patients discharged with stroke from CAHs and 202,502 from non-CAHs. CAH vs non-CAH patients were older (mean age 82.8y vs 78.6y) and more often women (61.8% vs 53.9%), white (94.3% vs 83.7%), and dual Medicare-Medicaid eligible (21.6% vs 17.1%). Discharge to home (29.6% vs 36.8%) and inpatient rehabilitation (4.2% vs 18.9%) was less common for CAH patients, whereas discharge to an intermediate care/skilled nursing facility was more common (26.7% vs 23.9%). For CAHs and non-CAHs, respectively, 1-year mortality rates were 27.8% (95% CI 26.5-29.0) and 22.2% (22.0-22.4), and 1-year recurrence rates were 4.3% (3.6-4.9) and 4.6% (4.5-4.7) (Figure). In IPW-adjusted analyses, stroke patients treated at CAHs vs non-CAHs had higher risk of 1-year mortality (HR 1.29, 95% CI 1.22-1.37) but not recurrent stroke (0.91, 0.78-1.06).

Conclusions:
Stroke patients discharged from CAHs vs non-CAHs had greater risk of 1-year mortality but not recurrence. Further work is needed to understand the observed disparity, potentially with a focus on post-acute care services.
Abstract 32: Post Stroke Suicide In Georgia, 2011-2018: Identifying High Risk Groups
Authors: Ido Moges S , Blankenship Elizabeth , Bayakly Rana
Published: February 2022

Background:
Disability can impact stroke survivors’ quality of life and mental health and may lead to suicide. Identifying and treating people at risk is one of the strategies listed by the Centers for Disease Control and Prevention to reduce suicide. The objectives of this study were to estimate the burden of suicide among stroke survivors in Georgia, identify predisposing factors, determine when patients are more likely to die of suicide, and examine suicide circumstances.

Methods:
Clinically diagnosed ischemic stroke (IS) patients from the Georgia Coverdell Acute Stroke Registry were linked with the Georgia Violent Death Reporting System (GVDRS) and death data for a retrospective cohort study. We applied survival analysis to estimate the annual suicide rate and cox proportional hazard model to identify high risk groups for suicide among stroke survivors. For those who died by suicide, circumstances were analyzed descriptively.

Results:
A total of 68,122 IS patients, from 2011 to 2018, were included. The median follow-up period was 40 months, and 70 suicide deaths were observed with a suicide rate of 28.3/100,000 person-years. About two-thirds of the suicides happened within 2 years of the stroke incident. Whites (HR=3.4), males (HR=10.8), young adults (HR=2.8), patients with depression (HR=3.8), and those who left hospitals against medical advice (HR=5.6) were more likely to die by suicide compared to blacks, females, older adults, patients without depression, and those who were discharged home respectively. Depression was reported in 36% of deaths, of which 25% had a past medical history of depression at hospital admission for stroke or were discharged with an antidepressant prescription. Firearms were used in 86.4% of the suicides.

Conclusion:
Ischemic stroke survivors have a 30% higher risk of death by suicide compared to the general Georgia population. This increased risk is mainly among males, patients with depression, and those who left hospitals against medical advice. More than four out of five suicides are by firearm; therefore, it is reasonable to make screening for suicide and counseling on firearm safety for patients and caregivers be a part of the discharge process and post discharge follow-up.
Abstract 33: Stroke Severity Mediates The Association Between Socioeconomic Disadvantage And Poor Outcomes Among Patients With Acute Ischemic Stroke
Authors: Pan Alan , Potter Thomas , Bako Abdulaziz , Meeks Jennifer , Tannous Jonika , MCCANE Charles D , Garg Tanu , GADHIA RAJAN R , Misra Vivek , Volpi John J , Chiu David , Vahidy Farhaan S
Published: February 2022

Background:
Impact of socioeconomic disadvantage on outcomes among acute ischemic stroke (AIS) patients has not been well characterized.

Methods:
Clinical data on AIS patients were extracted from electronic medical records and 90-day modified Rankin Scale (mRS) scores were collected as a part of prospective stroke registry. Exact patient addresses were geocoded, and state-level Area Deprivation Index (ADI) ranks were categorized as low, medium, high. Patients with a 90-day mRS score ≥ 4 were categorized as severe disability or death (SDD). Logistic regression models (adjusted for treatment with intravenous tissue plasminogen activator or mechanical thrombectomy, age, sex, race/ethnicity, insurance, prior stroke, vascular risk factors) were fitted to compute odds ratios (OR) and 95% confidence intervals (CI) for total effect of high ADI on SDD. Structural equation modeling was used to assess mediation effects of stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS).

Results:
Between May 2016 and Apr 2021, a total of 2,900 AIS patients (mean age: 68.5 years; 50.1% male; 28.4% non-Hispanic Black; 12.9% Hispanic) with complete outcomes data were included. In an adjusted model, high ADI was significantly associated with SDD (OR, CI: 1.14, 1.02-1.28). In the mediation analysis, patients in higher ADI neighborhoods had a 28% increased likelihood of having higher NIHSS (OR: 1.28, CI: 1.15-1.44). Likewise, higher NIHSS was associated with SDD (OR: 7.10, CI: 5.96-8.51). The effect of neighborhood disadvantage on SDD was fully mediated by NIHSS (average causal mediation effect of ADI on SDD: P=0.002), with 77% of the total effect pathway mediated through NIHSS. The proportions of 90-day mRS by ADI categories are reported (Figure).

Conclusion:
Neighborhood disadvantage leads to poor stroke outcomes mediated via stroke severity. Tracking social determinants of health may identify opportunities for reducing stroke related disability.
Abstract 37: Clopidogrel Bolus Is Inferior To Sustained Clopidogrel Pre-treatment In Patients Undergoing Carotid Artery Stent Placement
Authors: Qureshi Adnan I , Huang Wei , Lobanova Iryna , ISHFAQ Muhammad F , French Brandi R , Siddiq Farhan , Gomez Camilo R
Published: February 2022

Background:
Clopidogrel bolus is an option used prior to carotid artery stent placement (CAS) when sustained clopidogrel pre-treatment is not used.

Objective:
To compare the effect of clopidogrel bolus (450 mg administered ≥4 hours) with sustained clopidogrel pre-treatment (48 hours or greater) prior to CAS in patients prospectively followed over 10 years in Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

Methods:
The rates of primary endpoint (composite of any stroke, myocardial infarction (MI), or death during the periprocedural period or ipsilateral stroke within 4 years after randomization) were compared between patients who received clopidogrel bolus with those who received sustained clopidogrel pre-treatment after adjusting for age, gender, symptomatic status and initial severity of stenosis (≥70% versus <70%) over 4 years using Cox proportional hazards analysis.

Results:
The rate of periprocedural stroke (7.3% versus 3.4%, p=0.03) and primary end point (11.3% versus 5.9%, p=0.02) was significantly higher among patients who received clopidogrel bolus. The risk of primary end point was significantly higher in patients who received clopidogrel bolus (hazards ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.4, p=0.02) after adjusting for potential confounders. The overall mean (± SD) primary end point free survival based on Kaplan-Meier analysis was 7.0±0.2 years for patients who received clopidogrel bolus and 8.9±0.1 years for those who received sustained clopidogrel pre-treatment (log-rank test P=0.011).

Conclusion:
Clopidogrel bolus was associated with higher rates of adverse outcomes compared with sustained clopidogrel pre-treatment in patients who underwent CAS. Therefore, clopidogrel bolus may not be equivalent to sustained clopidogrel pre-treatment.
Abstract 4: Patient-reported And Performance-based Outcomes Separate Independently And Are Associated With Distinct Patterns Of Neuroanatomical Injury After Stroke
Authors: DiCarlo Julie A , Erler Kimberly S , Jaywant Abhishek , Ranford Jessica , Cramer Steven C , Lin David J
Published: February 2022

Introduction:
Patient-reported outcome measures (PROMs) provide valuable insights into health status and function, but their relationships with performance-based outcomes remain incompletely understood. Here we compared these two classes of measures using dimensionality-reduction techniques with longitudinal data and examined their relationships with neuroanatomical injury.

Methods:
Sixty-three adults with hemiparesis were serially assessed (acute, sub-acute, early-chronic, chronic) after stroke using performance-based scales (Upper Extremity Fugl-Meyer, Barthel Index, modified Rankin Scale, Box and Blocks, 9- Hole Peg, Grip Strength) and PROMs (PROMIS-Global Physical, Mental, and General Health, Patient Health Questionnaire-9). Principal component analysis (PCA) was performed at each timepoint to reduce variable dimensionality. Voxel-Based Lesion Symptom Mapping examined the relationship between lesion location and PCA components.

Results:
Two PCA components accounted for more than 70% of the total variance among outcomes. Performance-based variables loaded onto factor 1 while PROMs loaded onto factor 2. Results were consistent at each timepoint. Performance-based measures were related to injury to subcortical brain regions particularly corticospinal tract (figure, top row), while PROMs were related to injury to cortical areas including intraparietal sulcus and parietal operculum (figure, bottom row).

Discussion:
A multidimensional battery of assessments scored across the first year post-stroke separated independently into PCA components related to performance-based measure and PROMs. Each component was associated with injury to brain regions concordant with the content of the assessment. These findings emphasize the distinct behavioral elements and neuroanatomical underpinnings for performance-based measures and PROMs after stroke.
Abstract 66: Prevalence Of Shunting In Patients With Moyamoya
Authors: Xu Lori , Bonnet Wilmot , Dowling Michael M
Published: February 2022

Moyamoya (MMD) is a rare progressive stenosis of anterior cerebral circulation of unknown etiology that occurs at higher prevalence in patients with neurofibromatosis 1, trisomy 21, sickle cell disease (SCD), and East Asians. We hypothesized that vasoactive substances, normally inactivated in the lungs, may escape inactivation through right-to-left shunting and contribute to the development of MMD in at-risk groups. We compared the prevalence of shunting in MMD patients versus controls without MMD. In an IRB-approved, retrospective study we identified 67 MMD patients who had echocardiograms between 1991-2018 and compared the prevalence of potential right-to-left shunting with that of a control group of 123 patients without MMD or stroke from a prior study. In the MMD group, 32 (48%) had potential shunting identified on echocardiogram (23 (34%) intracardiac and 9 (13%) intrapulmonary) versus 29 (24%) potential shunting in our control group (P=0.0006). We also evaluated our MMD patients considering possible bias regarding SCD patients and increased prevalence of pulmonary shunting. In the 43 MMD patients without SCD, 21 (49%) had potential shunting identified on echocardiogram versus 29 (24%) potential shunting in our control group (P=0.0018). In conclusion, these observations support our hypothesis that shunting could contribute to MMD development, possibly through unknown vasoactive substances escaping lung inactivation, subsequently inducing vascular changes in patients with predisposing conditions. This has potential mechanistic and therapeutic implications and will need to be verified in larger prospective studies.