Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Stroke, Volume 53, Issue Suppl_1, Page AWP28-AWP28, February 1, 2022. Background:Large vessel occlusion (LVO) is the most common stroke subtype for those patient’s presenting with COVID-19. Clot perviousness, or a clot’s permeability to iodinated contrast, provides insight to an individual’s responsiveness of hyperacute revascularization, clot origin and functional post-stroke outcomes. We aimed to calculate LVO perviousness for those with and without COVID-19 and its association with revascularization and outcomes.Methods:This is a retrospective case-control study for individuals presenting with middle cerebral artery (MCA) LVO with and without COVID-19 positivity. Clot perviousness was calculated by a blinded experienced neuroradiologist. Perviousness scores were compared with demographic and comorbidity information as well as revascularization and functional outcomes.Results:18 individuals with a MCA LVO (9 COVID-19 infected) were included. Those with COVID-19 were significantly more likely to have diabetes mellitus [67% (6/9) versus 11% (1/9),p= 0.05] and hypertension [89% (8/9) versus 22% (2/9),p= 0.02]. Clot perviousness trended lower in the COVID-19 group [11.0 (8.2 – 26.4) versus 31.7 (30.4 – 39.2), p = 0.10]. Those with COVID-19 infection tended to have a lower clot pervious score, [22% (2/9) versus 78% (7/9), p =0.057]. The majority of those presenting with COVID-19 died during the hospitalization.Conclusions:Our data suggests for those with COVID-19 and MCA LVO, clots tended to be more impermeable to iodinated contrast. This finding may be due to the underlying coagulopathy of COVID-19, namely alternations in fibrin homeostasis.

Stroke, Volume 53, Issue Suppl_1, Page A21-A21, February 1, 2022. Introduction:Post-stroke cerebral angiogenesis actively participates in tissue repair and plays a vital role in the long-term functional recovery in stroke patients. Accumulating evidence shows that certain microRNAs (miRs) regulate cerebral angiogenesis after CNS disorders. We have demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis by enhancing activity of pro-angiogenic factors and their receptors. Here we further investigate the effects of pericyte-derived miR-15a/16-1 on post-ischemic cerebral angiogenesis and outcomes.Methods:Inducible pericyte-specific miR-15a/16-1 cKO mice and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. Neurobehavioral outcomes were determined by the foot fault, rotarod, adhesive tape removal, and Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density, functional microvessels, and neurons were examined by CD31/BrdU, tomato lectin/BrdU, and NeuN/BrdU double immunostaining, respectively.In vitroangiogenesis assays, including BrdU cell proliferation, scratch assay, and capillary tube formation were analyzed in mBMEC cutures treated with conditional medium from primary mouse vascular pericytes (mBVPs) with lentivirus-mediated miR-15a/16-1 knockdown. Pro-angiogenic factors were detected by qPCR and western blotting.Results:Pericytes-miR-15a/16-1 cKO mice exhibit improved sensorimotor and cognitive outcomes, increased CBF recovery, and reduced brain atrophy compared to WT controls. The number of newly-generated cerebral microvessels, functional microvessels, and neurons in the peri-infarct brain regions of Pericyte-miR-15a/16-1 cKO mice are higher than WT controls. Treatment of conditional medium from miR-15a/16-1 silencing pericytes significantly increases endothelial cell proliferation, migration, and tube formation, respectively. Mechanistically, lentiviral silencing of miR-15a/16-1 in primary mBVPs remarkably enhances the expression of both FGF2 and VEGFA.Conclusions:Our findings suggest that pericytic miR-15a/16-1 negatively regulates post-stroke cerebral angiogenesis.

Stroke, Volume 53, Issue Suppl_1, Page A20-A20, February 1, 2022. Introduction:Identification of key molecules that control conversion of resting microglia/macrophages (Mi/MΦ) to a detrimental or beneficial phenotype may help develop novel therapies to ischemic stroke. The transcription factor STAT1 contributes to acute (< 24h) neuronal death after brain ischemia/reperfusion (I/R), but its role in Mi/MΦ and impact on long term stroke outcome remain unknown.Hypothesis:Activation of STAT1 dictates proinflammatory responses of Mi/MΦ at subacute stage (3-5 d) after I/R. Selective deletion of STAT1 reprograms Mi/MΦ into an inflammation-resolving phenotype and improves long term stroke outcome.Methods:We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1. Brain injury, inflammation and various behavioral deficits were assessed after 1 h MCAO and 1-35 d reperfusion. Mi/MΦ phenotype was examinedin vivo(FACS followed by RNA-seq) andin vitro(primary microglia).Results:STAT1 was activated (phosphorylated) in Mi/MΦ 3 d after I/R in WT but not in STAT1 mKO mice. STAT1 mKO did not alter 24-h infarct size (TTC; p >0.05, n=8), but attenuated Mi/MΦ release of HMGB1 and increased arginase 1-producing Mi/MΦ 3d after I/R (immunostain, n=6), suggesting boosted inflammation-resolving responses of Mi/MΦ. RNA-seq further revealed downregulated proinflammatory genes and a concomitant elevation of phagocytosis-related genes in STAT1 mKO Mi/MΦ 3d after I/R (n=3, FDR

Stroke, Volume 53, Issue Suppl_1, Page ATP10-ATP10, February 1, 2022. Objective:There is a high prevalence of progressive cognitive impairment in intracerebral hemorrhage (ICH) survivors. We sought to identify gene expression changes, in association with long-term neurodegeneration, among patients 12-24 months post-ICH.Methods:TheRecovery and Outcomes from StrokE (ROSE)study prospectively recruits patients with spontaneous, supratentorial ICH, collecting baseline peripheral blood samples and MRI with diffusion tract imaging (DTI). TheRecovery of StrokE-Longitudinal Assessment with Neuroimaging (ROSE-LAWN)study performs long term follow-up at 12-24 months on cases enrolled in ROSE. We report on the first five cases enrolled in the ROSE-LAWN study from December 2020 to March 2021. Controls were matched to an overall ICH population by age, sex, and race. RNA-sequencing, aligned to human genome assembly GRCh38, was tested for differential gene expression. Canonical pathway enrichment and network analyses were computed for differentially expressed genes using Ingenuity Pathway Analysis, STRING and MCODE.Results:RNA-seq analysis of 5 ICH cases [male, 80%; median age, 61 (45 – 73); black, 40%; ICH volume, 14.88cc ± 13.07] and 13 controls [male, 54%; median age, 74 (69 – 79); black, 15%] identified 554 differentially expressed genes (genomic control adjusted p < 0.01), of which 24 met the false discovery rate correction for multiple comparisons (FDR < 0.05). The most significant difference was observed in hypoxia up-regulated 1 (HYOU1),a heat shock protein related gene (p = 2.64E-11). Pathway analysis identified enrichment of dopamine and serotonin receptor signaling (p = 8.74E-03, 2.23E-02), cell cycle regulation (p = 1.75E-02) and agranulocyte adhesion pathways (p = 2.18E-02). Comparison of baseline and follow-up MRI DTI demonstrated extensive cortical tract degeneration, beyond the initial injury.Conclusion:These results provide novel evidence of significant gene expression changes occurring years after the initial ICH. Despite resolution of the ICH, persistent inflammation may correlate with progressive neurodegeneration and subsequent cognitive impairment in ICH survivors. Future studies with greater sample sizes are supported by this work.

Stroke, Volume 53, Issue Suppl_1, Page A136-A136, February 1, 2022. Introduction:The real-world evolution of management and outcomes of patients with unruptured cerebral arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs initial conservative medical therapy.Methods:We analyzed from 2009-2018 the National Inpatient Sample of all AVM admissions in the United States. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013)vs.post-ARUBA (2014-2018). Joinpoint regression models with permutation model selection delineated yearly trends in intervention rate in uAVMs.Results:Among a total of 72,812 uAVMs, 35,420 were in the post-ARUBA and 37,392 in the pre-ARUBA period. Median age was 53.3 in post-ARUBAvs.51.8 in the pre-ARUBA period (p=0.001) with no difference in female sex, 51.1% vs. 51.8% (p=0.44). The intervention rate was lower in the post- vs -pre-ARUBA period, 29.6% vs. 34.0% (p=0.006) (figure). Interventional rate decreased monotonically by -4.32% in the post-ARUBA period (figure). Among the post-ARUBA AVM patients, compared with pre-ARUBA, there were no differences in odds of in-hospital ischemic stroke [OR 1.05 (0.92-1.20), p=0.45] or in-hospital mortality [OR 0.88 (0.62-1.24), p=0.47] but the odds did increase for combined discharge to a facility or in-hospital mortality [OR 1.14 (1.02-1.28), p=0.020]. In addition, the frequency of admissions for ruptured AVMs accelerated in the post-ARUBA period (figure).Conclusion:Nationwide practice in management of unruptured AVMs changed substantially with the publication of the ARUBA trial, in a durable and increasing manner. Fewer admissions with interventional treatment of unruptured AVMs occurred and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event.

Stroke, Volume 53, Issue Suppl_1, Page AWP207-AWP207, February 1, 2022. Introduction:Previous studies have shown that switching antiplatelets after having an ischemic stroke on aspirin may have better outcomes. However, these studies included patients who were switched to dual antiplatelets, which have an established benefit in the immediate post-stroke period. The purpose of this study is to assess outcomes in patients who continue aspirin versus switch to clopidogrel after having a cerebrovascular event on aspirin.Methods:We retrospectively identified patients within 14 Southern California hospitals using ICD-9 and ICD-10 codes who had a diagnosis of ischemic stroke on aspirin from January 2017-December 2019. Outcomes included recurrent hospital admission or emergency room visit for ischemic stroke, TIA, or intracranial hemorrhage up to two years post index event. Patients were grouped by which antiplatelet was prescribed at discharge. Those prescribed dual antiplatelets or an anticoagulant were excluded. Cox regression analysis was used to estimate risk of readmission.Results:Of the 580 patients who met the inclusion criteria, 372 (64%) continued aspirin and 208 (36%) switched to clopidogrel. Those with coronary artery disease (55.0% versus 45.0%, p = 0.015), dyslipidemia (61.4% versus 38.6%, p = 0.001), diabetes (59.5% versus 40.5%, p = 0.007), and a higher NIHSS score (mean 6.06 +/- 6.96 SD versus 4.08 +/- 4.32 SD, p = 0.001) were more likely to be discharged on aspirin. There were no differences in recurrent ischemic stroke {18.8% versus 15.4%, HR 1.12 (95% CI, 0.74-1.72), p = 0.587}, ischemic stroke plus TIA {19.9% versus 18.3%, HR (95% CI, 0.84-1.86), p = 0.253}, systemic embolism {25.5% versus 21.6%, HR 1.16 (95% CI, 0.82-1.66), p = 0.413} or intracranial hemorrhage {3.2% versus 2.4%, HR 0.94 (95% CI, 0.34-2.70), p = 0.919} between those discharged on aspirin versus clopidogrel, respectively.Conclusion:This study suggests that switching antiplatelets after having an ischemic stroke on aspirin may not be warranted.

Stroke, Volume 53, Issue Suppl_1, Page ATP9-ATP9, February 1, 2022. Introduction:Cognitive impairment is common following stroke and is associated with poor functional outcomes. We examined how cognitive domain and depression scores predict long-term functional disability following stroke.Methods:Data were analyzed from 70 participants with chronic ischemic stroke as part of the StrokeCog study. The battery yielded a global composite score and composite scores of memory, processing speed, working memory, language, and spatial ability. The Stroke Impact Scale was used to assess depression (SIS-Depression) and 3 functional disability measures: subjective memory and thinking (SIS-Cognition), activities of daily living (SIS-ADL), and participation in work, social, and leisure activities (SIS-Participation). A correlation network was constructed using a t-SNE algorithm to examine relationships amongst variables. Partial least squares analyses (PLS) were used to determine whether cognitive domains and depression predicted functional disability, with depression, cognitive composites, age, stroke severity (NIHSS), and fatigue (FACIT) as predictor variables.Results:Both the t-SNE plot and PLS indicated that functional disability is more closely related to depression than to cognitive composite scores. PLS analyses demonstrated that depression was the most significant predictor of SIS-Cognition, SIS-Participation, and SIS-ADL, accounting for 37%, 60%, and 47% of the variances, respectively. Processing speed accounted for an additional 11% of variance in SIS-Cognition. Spatial ability accounted for an additional 12% of variance in SIS-Participation and an additional 12% of variance in SIS-ADL. There were no other significant predictors.Conclusions:Depression was significantly associated with all 3 of the long-term functional outcomes we examined. Neuropsychological performance (namely processing speed and spatial ability) was also associated with functional disability, but to a lesser degree than depression, even for self-reported cognition. These findings are of interest given that depression is a common but treatable sequela of stroke.

Stroke, Volume 53, Issue Suppl_1, Page AWP186-AWP186, February 1, 2022. Background:Incidence of gastrointestinal (GI) bleeding after acute ischemic stroke (AIS) was reported as 1.5% during hospitalization, one-thirds of which required blood transfusion. However, it is not known about the long-term incidence and the incidence rates by period after AIS.Methods:AIS patients who were admitted to the 14 participating hospitals between 2011 and 2013 were identified using a nationwide multicenter prospective stroke registry database. GI bleeding was captured with related diagnosis codes by International Classification of Diseases-10th Revision through the linkage between the registry database and the claims data. Bleeding requiring at least 2 packs of blood transfusion was defined as major GI bleeding. Incidence rates were calculated for each period as follow; 0-30 days, 31-90 days, 91-180 days, 181-365 days, 1-2 years, 2-3years, after 3 years.Results:Of 10,818 AIS patients, 59.0% were male and mean age was 67.5 ± 12.9 years. The median follow-up duration was 3.1 (interquartile range 2.3 to 4.0) years. During 31,208 person-years, 947 patients (8.8%) had 1,224 episodes of major GI bleeding. Annual incidence rate was 3.92 per 100 person-years. The incidence rates by periods were the highest at 19.21 per 100 person-years in the first month of AIS, gradually decreased to 9.02 in one to three months, 6.18 in three to six months, and 3.48 in six to twelve months. After three years, it remained at about 2.62 events per 100 person-years. During the observation period, only one major GI bleeding occurred without recurrence in about 80% of patients, about 13% recurred twice, and about 6% of patients had three or more recurrences. In the multivariable recurrent event analysis, anemia at admission, lower eGFR below 60, and mRS at 3 months ≥4 were independently associated with higher risk of major GI bleeding during the most of the observation period above 3 years.Conclusions:Major GI bleeding, requiring transfusion, seems to occur frequently after AIS, and the risk was gradually decreased after stroke. The efforts are needed to prevent it, especially in stroke patients with anemia and decreased renal function.

Stroke, Volume 53, Issue Suppl_1, Page A133-A133, February 1, 2022. Background and Purpose:Angioplasty and stenting is a treatment option for patients with medically refractory symptomatic intracranial atherosclerotic disease (sICAD). Currently the Wingspan Stent System (WSS) is the only FDA approved device for that indication. Nonetheless, our group has shown the Resolute (R) Onyx Stent, a drug-eluting balloon mounted stent (DES), can be feasibly used to treat lesions in this population at lower cost. Herein, we compare the two stents based on our single center experience.Methods:A prospectively maintained neuro-endovascular databased was queried for patients between January 2013 to June 2021. Inclusion criteria for patients included sICAD (≥70% stenosis) with failed medical management, and intracranial stenting with either the R-onyx DES or WSS, including patients treated within 7 days of last stroke. Primary outcomes were assessed via the occurrence of ischemic or hemorrhagic stroke or death within 72 h of the procedure while secondary outcomes consisted of stroke or angiographic reoccurrence (in-stent restenosis) evaluated by a clinical or angiographic follow-up at 6 months.Results:A total of 184 patients, average age 61.26 (SD=12.53) ( 44% women), were eligible for analysis with 58 having R-onyx DES and 126 having WSS. There was no significant difference in age or premorbid risk factors between the two groups. Within 72 h, 1.7% (n=1) of patients had a primary event of ischemic or hemorrhagic stroke or death in the R-onyx DES group while 6.3% (n=8) of patients had those indications in the WSS group (p = 0.089). Among 41 angiographic and clinical follow-ups in the R-onyx DES group, none had a stroke, while among 101 of those follow-ups in the WSS group, 8.9% (n=9) had a stroke (p=0.024). In terms of 6-month angiographic follow-ups, there was a significantly lower rate of symptomatic in-stent restenosis among the R-onyx DES group with 1.7% (n=1) experiencing symptomatic in-stent restenosis, and 21.4% (n=27) in the WSS group having that indication (p=0.0003).Conclusion:Our experience has been that R-onyx DES is more effective at treating sICAD with low rates of periprocedural complications within 72 h, long-term strokes, and symptomatic in-stent restenosis. Future prospective randomized multicenter trials are needed.

Stroke, Volume 53, Issue Suppl_1, Page A140-A140, February 1, 2022. Introduction:There is limited data on real-world efficacy of left atrial appendage closure (LAAC) procedures compared to anticoagulants (AC) for stroke prevention among patients with atrial fibrillation (AF).Methods:We utilized a retrospective cohort of over 63 million patients from 51 healthcare organizations across 6 countries via a harmonized electronic medical record-based research data platform. Utilizing international classification of disease version 10 and current procedural terminology codes, adult (≥ 18 years) patients with AF (I48) were identified and grouped by treatment type (LAAC (33340, 02L73DK) vs AC (1015112, Z79.0, BL110)). Patients with a history of stroke prior to AC initiation or LAAC procedure were excluded. Subjects were followed for 5 years for incident ischemic stroke (I63), intracerebral hemorrhage (I61), and all-cause mortality. Treatment groups were propensity score matched by age, sex, race, ethnicity, and comorbidities. Risk ratio(RR) and 95% confidence intervals(CI) among unmatched and matched populations are reported.Results:Among a total of 1,980,130 AF patients; 1,374,013 were flagged for AC use and 8,004 were treated via LAAC. Treatment cohorts were propensity score matched by age, race, sex, hyperlipidemia, and hypertension resulting in an exact 1:1 matched cohort of 8,004 subjects, across all co-variates. In the matched population the mean (SD) age was 75.2 (8.05) years, 63.2% were male; 86.6% were white, 4.4% black, 0.89% Asian, and 3.5% Hispanic; with 64.4% hyperlipidemic and 79.2% hypertensive. Prior to matching, AC (vs. LAAC) was significantly associated with a higher 5-year risk of ischemic stroke, intracerebral hemorrhage, and all-cause mortality. The protective effect of LAAC (vs. AC) was maintained for 5-year risk of ischemic stroke (RR, CI: 0.68, 0.58 – 0.79) and all-cause mortality (RR, CI: 0.42, 0.39 – 0.45). However, the difference in 5-year risk for intracerebral hemorrhage for LAAC (vs. AC) was not statistically lower (RR, CI: 0.72, 0.50 – 1.05).Conclusion:Notwithstanding the possibility of residual confounding in our analyses, LAAC seems to be associated with a lower long-term risk of ischemic stroke and all-cause mortality as compared to AC treated AF patients in large real-world data.

Stroke, Volume 53, Issue Suppl_1, Page ATP26-ATP26, February 1, 2022. Introduction:The coronavirus disease 2019 (COVID-19) pandemic has changed the medical use of stroke patients. This study evaluated the health-seeking behavior of stroke patients and changes in stroke care services at the time of three domestic COVID-19 outbreaks in Korea using the Korean Stroke Registry (KSR) data.Methods:We reviewed data from patients with acute stroke and transient ischemic attack (TIA) from Jan 2019 to May 2021. There were three domestic COVID-19 outbreaks (1st: Feb to Mar 2020, 2nd Aug to Sep 2020, 3rd Nov 2020 to Jan 2021). Outcomes included patient characteristics, times from stroke onset to hospital arrival, and in-hospital stroke pathways.Results:The study included 34,271 patients who visited hospitals that contribute to the KSR. In the first outbreak, in Daegu city (the main epicenter), the number of patients decreased by two-thirds compared to the pre-COVID period, and the number of TIA patients was particularly decreased (9.97% to 2.91%). Unlike other regions, the median onset-to-door time increased significantly in the epicenter (361 min vs. 526.5 min, p=0.016), and longer times were common for patients with mild symptoms and who were in their 60s or 70s. The median onset-to-door time increased in the epicenter during the second outbreak, but it was not statistically significant. At the third outbreak, the median onset-to-door time was reduced even in the epicenter compared to the previous one. The number of patients decreased with each outbreak compared to the previous one, but the decrease gradually became smaller.Conclusions:Korean stroke patients in a COVID-19 outbreak region showed clear changes in health-seeking behaviors and showed a pattern of adaptation to the COVID-19 environment. There is a need for continued attention to an appropriate triage system and public education on the importance of early treatment during the COVID-19 pandemic.

Stroke, Volume 53, Issue Suppl_1, Page ATP24-ATP24, February 1, 2022. Objectives:Evidence suggests an association of increased cerebrovascular accidents frequency in patients diagnosed with the novel coronavirus disease, COVID-19. Coagulopathy resulting from the 2019 novel coronavirus (SARS-CoV-2) infection is suspected. This study aims at evaluating thrombotic markers in relation to stroke severity and functional outcomes in a patient cohort of acute ischemic stroke (AIS) with concurrent COVID-19.Methods:We performed a retrospective observational cohort study of 28 patients who tested positive for SARS-CoV-2 via polymerase chain reaction and concomitant AIS confirmed by brain imaging. We analyzed data regarding initial stroke presentation, markers of coagulopathy, and 90-day functional outcomes.Results:The patient cohort displayed high rate of comorbidities with 78.6% having at least 1 vascular risk factor. NIHSS had a median of 16 at initial presentation and median stroke volume of 52 mL. Median NIHSS at discharge or prior to death was 19, and median 90-day mRS was 4. Highest fibrinogen level recorded showed a median of 759.54 mg/dL (IQR 653.75-940.75), D-dimer and lactate dehydrogenase (LDH) showed a median highest recorded value 24,106 ng/mL (IQR 6105.00-80165.00) and 442 ng/mL (IQR 277.00-545.50), respectively. LDH (p=0.0008), D-dimer (p=0.001), and maximum fibrinogen levels (p=0.049) near the time of stroke significantly predicted final NIHSS and functional outcome 90-days after discharge.Conclusions:Adult patients with acute ischemic stroke and concurrent COVID-19 disease exhibited abnormally high markers of coagulopathy, and LDH, D-Dimer, and fibrinogen levels were predictors of morbidity and neurological disability at 90-days in this patient population. Further research is necessary to establish a definitive pattern and assess the ability to use these markers as prognostic elements of 90-day functional outcome.

Stroke, Volume 53, Issue Suppl_1, Page AWMP53-AWMP53, February 1, 2022. Introduction:Venous thromboembolism (VTE) is a common medical complication following acute ischemic stroke (AIS). Studies have suggested that VTE rates were higher among patients with a history of COVID-19. We examined the risk of VTE in AIS patients with and without a history of COVID-19 among Medicare beneficiaries.Methods:We identified Medicare fee-for-service (FFS) beneficiaries aged ≥65 years with AIS hospitalizations from 04/01/2020 to 06/30/2021. COVID-19 cases were identified by the first diagnosis of COVID-19 on a claim at any health care setting. We defined AIS with COVID-19 if the dates of COVID-19 diagnoses were earlier than AIS admission dates. To identify VTE for each AIS admission, we used the following secondary diagnoses codes: ICD-CM-10: I80, I81, I82, I26. We compared the prevalence ratio (PR) of VTE between AIS patients with and without a history of COVID-19.Results:Among 178,830 Medicare FFS beneficiaries with AIS admissions, 6.1% had a history of COVID-19 and 2.6% had VTE as a complication. VTE prevalence among AIS patients with a history of COVID-19 was 3.98% (95% confidence interval (CI), 3.62-4.36%) and 2.53% (95% CI, 2.46-2.61%) among patients without a history of COVID-19. The adjusted PR of VTE was 1.55 (95% CI, 1.40-1.70, p50% increased risk of VTE than those without a history of COVID-19 (Adjusted PR, 1.59, 95% CI, 1.42-1.78 for Non-Hispanic White, 1.58, 95% CI, 1.28-1.94 for Non-Hispanic Black, p

Stroke, Volume 53, Issue Suppl_1, Page ATP30-ATP30, February 1, 2022. Introduction:Human subjects research requires the retention of enrolled patients in order to provide accurate data. The COVID-19 pandemic introduced unique challenges for clinical trial coordination. AtRial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) is an NIH StrokeNet national clinical trial designed to test superiority of apixaban over aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. We sought to explore the methods that allowed our site to maintain a high retention rate in our local ARCADIA population.Methods:Prior to COVID-19, our trial coordinator (JP), conducted home visits to enroll and complete study visits every 3 months for the first year. This was approved by our local institution, IRB and study sponsor. During COVID-19 precautions, phone contact was maintained and encouraged. Face-to-face visits were not possible, but our coordinator continued to deliver study drug while maintaining distancing precautions. This was followed by a phone call to remind patients of drug instructions and dosages, and inquiring about any adverse events that may have occurred since the last visit. We evaluated the number of follow up visits before and during the COVID lockdown (March through June 2020).Results:Enrollments decreased during the pandemic, in large part due to a study-wide pause in recruitment efforts. The median monthly follow-up prior to COVID-19 was 3, and increased to 5 during lockdown. Before, during and after COVID, our local retention rate has remained 100%.Conclusions:In conclusion, despite complicating factors of COVID-19, our local coordinator’s retention rate remained 100% during the COVID-19 pandemic and our median number of monthly follow up visits increased, which may be attributable to our coordinator’s efforts of socially distanced home visits and frequent communication.

Stroke, Volume 53, Issue Suppl_1, Page AWP251-AWP251, February 1, 2022. Objective:Prediction of the long-term outcome in Ischemic Stroke (IS) patients can have a significant impact on design of clinical trials and on patients’ care. We studied gene expression (GE) as a novel biomarker to provide an accurate prediction of 90-day outcome in IS patients.Methods:RNA from 72 samples from 2 peripheral blood draws (at ≤3 and 24 hrs post IS onset) was analyzed on Affymetrix U133 Plus 2.0 microarrays. These represented samples from 36 CLEAR trial IS patients that had blood drawn within 3 hrs of stroke onset and were then treated with tPA with or without eptifibatide. The samples were split into derivation (n=25) and validation (n=11) sets. We identified the differential GE in blood at 24 hrs and the difference in GE between 24 hrs and 3 hrs post IS that was associated with 90-day post stroke outcome using the model: GE = μ + NIHSS_24hr+mRS_90day+ ε. Good outcome was defined as mRS 0-2; Poor – as mRS 3-5. Logistic regression was used to derive a biomarker classifier.Results:Using 24 hrs GE, we identified 14 probesets (12 genes) with the highest discriminative power for predicting outcome. The model achieved recall (the probability of correctly identifying the patients with Good outcome) of 0.88 and specificity (the probability of correctly identifying the patients with Poor outcome) of 0.67 in the validation set (The AUC-ROC = 0.88). The biomarker genes were enriched in immune responses such as IL and cytokine signaling. Among the predictors were genes important for stroke and repair after stroke (e.g.,MACC1,GDF11).MACC1has been considered as a potential treatment target for IS with a protective role in hypoxia-induced human brain microvascular endothelial cells.GDF11plays a role in brain repair after IS. We also determined how the change of GE from 3 hrs to 24 hrs would predict the 90-day outcome. A panel of ten genes was able to predict outcome in the validation set (recall= 1, specificity = 0.67, AUC-ROC=0.88). These includedAVPR1A, which mediates platelet aggregation and release of coagulation factors and exacerbates brain inflammatory response to injury.Conclusion:This pilot study suggests gene expression can be used to predict stroke outcome. Some of the genes may serve as potential therapeutic targets.

Stroke, Volume 53, Issue Suppl_1, Page ATP162-ATP162, February 1, 2022. Background and Purpose:Angioplasty and stenting is a therapeutic option for patients with medically refractory intracranial atherosclerotic disease (ICAD). We previously demonstrated the feasibility of using Resolute (R) Onyx Stent, a drug-eluting balloon mounted coronary stent (DES), for ICAD patients. WEAVE (Wingspan Stent System Post Market Surveillance) trial assessed the periprocedural safety of Wingspan Stents in ICAD patients. We present our on-going experience with R-Onyx in ICAD patients integrating WEAVE styled methodology to assess outcomes in our cohort.Methods:A prospectively maintained neuro-endovascular database was queried for intracranial angioplasty and stenting cases from October 2019 to June 2021. Patients with symptomatic ICAD despite maximum medical management with >70% stenosis who were treated with R-Onyx DES were included. Primary outcomes were assessed according to WEAVE trial criteria (ischemic or hemorrhagic stroke or death within 72 h of the procedure). Secondary outcomes were assessed by occurrence of stroke and/or in-stent restenosis evaluated 30 days post-procedure clinically or angiographically.Results:A total of 58 patients were eligible for analysis with a mean age of 63.66 years, and 63.8% (n=37) were males. A total of 42 patients had an indication for treatment consisting of recurrent stroke while 16 had recurrent transient ischemic attacks. A total of 62 R-onyx DES stents were used to treat 58 patients with symptomatic lesions with an average stenosis of 84.7%. All procedures were completed successfully with