Dataset Information

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

ABSTRACT: We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10^-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10^-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10^-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10^-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

SUBMITTER: Llucia-Carol L

PROVIDER: S-EPMC10487930 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

Llucià-Carol Laia L Muiño Elena E Cullell Natalia N Cárcel-Márquez Jara J Lledós Miquel M Gallego-Fabrega Cristina C Martin-Campos Jesús J Martí-Fàbregas Joan J Aguilera-Simón Ana A Planas Anna M AM DeDiego Marta L ML de Felipe Mimbrera Alicia A Masjuan Jaime J García-Madrona Sebastián S Segura Tomás T González-Villar Esther E Serrano-Heras Gemma G Domínguez Mayoral Ana A Menéndez-Valladares Paloma P Montaner Joan J Migeotte Isabelle I Rahmouni Souad S Darcis Gilles G Bernardo David D Rojo Silvia S Schulte Eva C EC Protzer Ulrike U Fricke Lisa L Winter Christof C Niemi Mari E K MEK Cordioli Mattia M Delgado Pilar P Fernández-Cadenas Israel I

International journal of molecular sciences 20230830 17

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both ...[more]

PMID: 37686257

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Project description:Background and purposeHigh revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy.MethodsWe analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization.ResultsTwo hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence.ConclusionsOne half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.

Project description:In many systems, patients with large vessel occlusion (LVO) strokes experience delays in transport to thrombectomy-capable centers. This pilot study examined use of a novel emergency medical services (EMS) protocol to expedite transfer of patients with LVOs to a comprehensive stroke center (CSC). From October 1, 2020 to February 22, 2021, Indianapolis EMS piloted a protocol, in which paramedics, after transporting a patient with a possible stroke remained at the patient's bedside until released by the emergency department or neurology physician. In patients with possible LVO, EMS providers remained at the bedside until the clinical assessment and CT angiography (CTA) were complete. If indicated, the paramedics at bedside transferred the patient, via the same ambulance, to a nearby thrombectomy-capable CSC with which an automatic transfer agreement had been arranged. This five-month mixed methods study included case-control assessment of use of the protocol, number of transfers, safety during transport, and time saved in transfer compared to emergent transfers via conventional interfacility transfer agencies. In qualitative analysis EMS providers, and ED physicians and neurologists at both sending and receiving institutions, completed e-mail surveys on the process, and offered suggestions for process improvement. Responses were coded with an inductive content analysis approach. The protocol was used 42 times during the study period; four patients were found to have LVOs and were transferred to the CSC. There were no adverse events. Median time from decision-to-transfer to arrival at the CSC was 27.5 minutes (IQR 24.5-29.0), compared to 314.5 minutes (IQR 204.0-459.3) for acute non-stroke transfers during the same period. Major themes of provider impressions included: incomplete awareness of the protocol, smooth process, challenges when a stroke alert was activated after EMS left the hospital, greater involvement of EMS in patient care, and comments on communication and efficiency. This pilot study demonstrated the feasibility, safety, and efficiency of a novel approach to expedite endovascular therapy for patients with LVOs.

Dataset Information

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

Publications

Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.

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