Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series

ABSTRACTBackground: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12-receptor antagonist is often used to prevent thrombotic complications after placement of a Pipeline embolization device (PED) for cerebral aneurysm. Although clopidogrel is common in this setting, high rates of nonresponse to this drug have made ticagrelor a potentially attractive alternative. Objective: To describe safety and efficacy outcomes for ticagrelor following PED placement, including measurement of platelet function.Methods: A retrospective analysis of data was completed for patients who underwent PED placement for cerebral aneurysm at a single centre between November 2015 and March 2017, with subsequent prescription of ticagrelor and ASA as dual antiplatelet therapy. The primary end point was any ischemic stroke or death within 1 year after the procedure. Intracranial hemorrhage was a secondary end point. Additionally, measurement of and values for platelet reactivity units (PRUs) during receipt of ticagrelor and ASA were evaluated.Results: A total of 29 patients were included in this retrospective study. One patient experienced ischemic stroke 226 days after placement of the PED. In addition, 3 patients died during the 1-year follow-up period for causes unrelated to stroke or bleeding complications. No cases of intra -cranial hemorrhage were observed. Samples for measurement of P2Y12 levels were drawn at the discretion of the neurointerventionalists, and the PRU value was measured at least once for 28 (97%) of the 29 patients. The mean number of PRU measurements per patient after initiation of ticagrelor was 2.1 (standard deviation [SD] 1). Mean PRU value after initiation of ticagrelor was 65 (SD 57). Conclusions: In this case series describing the use of ticagrelor and ASA as dual antiplatelet therapy after PED placement for cerebral aneurysm, there was just one ischemic stroke, which occurred after the dual antiplatelet therapy had been discontinued. Further prospective trials are needed to describe the utility of ticagrelor use after PED placement, as well as its dosing and monitoring.RÉSUMÉContexte : Une bithérapie antiplaquettaire composée d’acide acétylsali-cylique (AAS) et d’un inhibiteur du récepteur P2Y12 est fréquemment utilisée pour prévenir les complications thrombotiques après la mise en place d’un dispositif d’embolisation Pipeline pour traiter un anévrisme cérébral. Quoique le clopidogrel soit souvent utilisé dans ce contexte, des taux élevés d’absence de réponse à ce médicament ont fait du ticagrélor une solution de rechange potentiellement intéressante. Objectif : Décrire les résultats relatifs à la sécurité et à l’efficacité du ticagrélor après la mise en place d’un dispositif d’embolisation, y compris l’analyse de la fonction plaquettaire.Méthodes : Une analyse rétrospective de données a été réalisée dans un seul centre entre novembre 2015 et mars 2017 à l’aide des dossiers médicaux de patients chez qui a été posé un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral et à qui a ensuite été prescrite une bithérapie antiplaquettaire de ticagrélor et d’AAS. Le critère d’évaluation principal était les cas d’infarctus cérébral ou de décès durant l’année suivant l’opération. Les cas d’hémorragie intracrânienne ont servi de critère d’évaluation secondaire. De plus, l’analyse a porté sur l’évaluation de la réactivité plaquettaire et sa quantification en unités de réaction au P2Y12 pendant la prise de ticagrélor et d’AAS.Résultats : Au total, 29 patients ont été admis à la présente étude rétrospective. Un patient a subi un infarctus cérébral 226 jours après la mise en place d’un dispositif d’embolisation Pipeline. De plus, 3 patients sont décédés au cours de la période de suivi d’un an en raison de causes sans lien avec des complications liées à un accident vasculaire cérébral ou à une hémorragie. Aucun cas d’hémorragie intracrânienne n’a été observé. Les échantillons destinés à la mesure des unités de réaction au P2Y12 ont été prélevés selon le jugement des neuro-intervenants et l’évaluation de la réactivité plaquettaire a été réalisée au moins une fois chez 28 (97 %) des 29 patients. Le nombre moyen de mesures des unités de réaction au P2Y12 par patient était de 2,1 (écart-type de 1). Après l’amorce d’un traitement par ticagrélor, le résultat moyen en unités de réaction au P2Y12 était de 65 (écart-type de 57).Conclusions : Dans la présente série de cas décrivant l’utilisation d’une bithérapie antiplaquettaire composée de ticagrélor et d’AAS après la mise en place d’un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral, seul un cas d’infarctus cérébral a été observé et il s’est produit après l’arrêt de la bithérapie antiplaquettaire. De plus amples études prospectives sont nécessaires pour décrire l’utilité et la posologie du ticagrélor ainsi que le suivi du traitement après la mise en place d’un dis-positif d’embolisation Pipeline

Towards seamless environmental prediction–development of Pan-Eurasian EXperiment (PEEX) modelling platform

The Pan-Eurasian Experiment Modelling Platform (PEEX-MP) is one of the key blocks of the PEEX Research Programme. The PEEX MP has more than 30 models and is directed towards seamless environmental prediction. The main focus area is the Arctic-boreal regions and China. The models used in PEEX-MP cover several main components of the Earth’s system, such as the atmosphere, hydrosphere, pedosphere and biosphere, and resolve the physical-chemical-biological processes at different spatial and temporal scales and resolutions. This paper introduces and discusses PEEX MP multi-scale modelling concept for the Earth system, online integrated, forward/inverse, and socioeconomical modelling, and other approaches with a particular focus on applications in the PEEX geographical domain. The employed high-performance computing facilities, capabilities, and PEEX dataflow for modelling results are described. Several virtual research platforms (PEEX-View, Virtual Research Environment, Web-based Atlas) for handling PEEX modelling and observational results are introduced. The overall approach allows us to understand better physical-chemical-biological processes, Earth’s system interactions and feedbacks and to provide valuable information for assessment studies on evaluating risks, impact, consequences, etc. for population, environment and climate in the PEEX domain. This work was also one of the last projects of Prof. Sergej Zilitinkevich, who passed away on 15 February 2021. Since the finalization took time, the paper was actually submitted in 2023 and we could not argue that the final paper text was agreed with him

An Unprecedented Arctic Ozone Depletion Event During Spring 2020 and its Impacts Across Europe

International audienceThe response of the ozone column across Europe to the extreme 2020 Arctic ozone depletion was examined by analysing ground-based observations at 38 European stations. The ozone decrease at the northernmost site, Ny-Ålesund (79°N) was about 43% with respect to a climatology of more than 30 years. The magnitude of the decrease declined by about 0.7 % deg-1 moving to south to reach nearly 15% at 40°N. In addition, it was found that the variations of the ozone column at each of the selected stations in March-May were similar to those observed at Ny-Ålesund but with a delay increasing to about 20 days at mid-latitudes with a gradient of approximately 0.5 days deg-1. The distributions of reconstructed ozone column anomalies over a sector covering a large European area show decreasing ozone that started from the north at the beginning of April 2020 and spread south. Such behaviour was shown to be similar to that observed after the Arctic ozone depletion in 2011. Stratospheric dynamical patterns in March to May 2011 and during 2020 suggested that the migration of ozone-poor air masses from polar areas to the south after the vortex breakup caused the observed ozone responses. A brief survey of the ozone mass mixing ratios at three stratospheric levels showed the exceptional strength of the 2020 episode. Despite the stronger and longer-lasting Arctic ozone loss in 2020, the analysis in this work indicates a similar ozone response at latitudes below 50°N to both 2011 and 2020 phenomena

Towards seamless environmental prediction – development of Pan-Eurasian EXperiment (PEEX) modelling platform

The Pan-Eurasian Experiment Modelling Platform (PEEX-MP) is one of the key blocks of the PEEX Research Programme. The PEEX MP has more than 30 models and is directed towards seamless environmental prediction. The main focus area is the Arctic-boreal regions and China. The models used in PEEX-MP cover several main components of the Earth’s system, such as the atmosphere, hydrosphere, pedosphere and biosphere, and resolve the physical-chemical-biological processes at different spatial and temporal scales and resolutions. This paper introduces and discusses PEEX MP multi-scale modelling concept for the Earth system, online integrated, forward/inverse, and socioeconomical modelling, and other approaches with a particular focus on applications in the PEEX geographical domain. The employed high-performance computing facilities, capabilities, and PEEX dataflow for modelling results are described. Several virtual research platforms (PEEX-View, Virtual Research Environment, Web-based Atlas) for handling PEEX modelling and observational results are introduced. The overall approach allows us to understand better physical-chemical-biological processes, Earth’s system interactions and feedbacks and to provide valuable information for assessment studies on evaluating risks, impact, consequences, etc. for population, environment and climate in the PEEX domain. This work was also one of the last projects of Prof. Sergej Zilitinkevich, who passed away on 15 February 2021. Since the finalization took time, the paper was actually submitted in 2023 and we could not argue that the final paper text was agreed with him.</p

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons