المؤلفون: Martins, Raphael P, Hamel-Bougault, Mathilde, Bessière, Francis, Pozzi, Matteo, Extramiana, Fabrice, Brouk, Zohra, Guenancia, Charles, Sagnard, Audrey, Ninni, Sandro, Goemine, Céline, Defaye, Pascal, Boignard, Aude, Maille, Baptiste, Gariboldi, Vlad, Baudinaud, Pierre, Martin, Anne-Céline, Champ-Rigot, Laure, Blanchart, Katrien, Sellal, Jean-Marc, De Chillou, Christian, Dyrda, Katia, Jesel-Morel, Laurence, Kindo, Michel, Chaumont, Corentin, Anselme, Frédéric, Delmas, Clément, Maury, Philippe, Arnaud, Marine, Flecher, Erwan, Benali, Karim

المصدر: European Heart Journal Acute Cardiovascular Care; September 2023, Vol. 12 Issue: 9 p571-581, 11p

مستخلص: Graphical Abstract

المؤلفون: Anselmi, Amedeo, Tomasi, Jacques, Aymami, Marie, Mancini, Julien, Nesseler, Nicolas, Langanay, Thierry, Flecher, Erwan, Verhoye, Jean-Philippe

المصدر: Journal of Cardiovascular Medicine; August 2023, Vol. 24 Issue: 8 p514-521, 8p

المؤلفون: Charbonneau, Etienne, Donal, Erwan, Nessler, Nicolas, Flecher, Erwan, Paven, Elise

المصدر: Acta Cardiologica; Jun2023, Vol. 78 Issue 4, p468-471, 4p

المؤلفون: Charbonneau, Etienne, Donal, Erwan, Nessler, Nicolas, Flecher, Erwan, Paven, Elise

المصدر: Acta cardiologica; May 2023, Vol. 78 Issue: 4 p468-471, 4p

المؤلفون: Lesouhaitier, Mathieu, Uhel, Fabrice, Gregoire, Murielle, Gacouin, Arnaud, Frerou, Aurélien, Gaudriot, Baptiste, Bendavid, Claude, Boukthir, Sarrah, Le Tulzo, Yves, Verhoye, Jean-Philippe, Flecher, Erwan, Roussel, Mikael, Tarte, Karin, Tadié, Jean-Marc

المصدر: Shock; December 2022, Vol. 58 Issue: 6 p476-483, 8p

مستخلص: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an immune paresis that predisposes to the development of postoperative infections and sepsis. Among factors responsible for CPB-induced immunosuppression, circulating myeloid-derived suppressor cells (MDSCs) have been found to induce early lymphocyte apoptosis and lymphocyte proliferation inhibition. However, the mechanisms involved are not fully understood. In this study, we found that the main lymphocyte subsets decreased significantly 24 h after cardiac surgery with CBP. As expected, cardiac surgery with CPB induced a monocytic MDSC expansion associated with an increased T-cell apoptosis and decreased proliferation capacity. Noteworthy, granulocytic MDSCs remain stable. Myeloid-derived suppressor cell depletion restored the ability of T-cell to proliferate ex vivo. After CPB, indoleamine 2,3-dioxygenase activity and IL-10 plasma level were increased such as programmed death-ligand 1 monocytic expression, whereas plasma level of arginine significantly decreased. Neither the inhibition of indoleamine 2,3-dioxygenase activity nor the use of anti–programmed death-ligand 1 or anti–IL-10 blocking antibody restored the ability of T-cell to proliferate ex vivo. Only arginine supplementation restored partially the ability of T-cell to proliferate.

المؤلفون: Lesouhaitier, Mathieu, Gregoire, Murielle, Gacouin, Arnaud, Coirier, Valentin, Frerou, Aurélien, Piau, Caroline, Cattoir, Vincent, Dumontet, Erwan, Revest, Matthieu, Tattevin, Pierre, Roisne, Antoine, Verhoye, Jean‐Philippe, Flecher, Erwan, Le Tulzo, Yves, Tarte, Karin, Tadié, Jean‐Marc

المصدر: Journal of Leukocyte Biology; April 2022, Vol. 111 Issue: 4 p867-876, 10p

مستخلص: Staphylococcus aureusis the main bacterial pathogen encountered in mediastinitis after cardiac surgical procedures; it remains a devastating complication with a high mortality rate. As neutrophils have a primordial role in the defense against staphylococcus infection and cardiopulmonary bypass (CPB) is known to induce immunosuppression, the aim of this study was to investigate CPB impact on neutrophil functions. Patients without known immunosuppression scheduled for cardiac surgery with CPB were included. Bone marrow and blood samples were harvested before, during, and after surgery. Neutrophil phenotypic maturation and functions (migration, adhesion, neutrophil extracellular trap [NET] release, reactive oxygen species (ROS) production, phagocytosis, and bacteria killing) were investigated. Two types of Staphylococcus aureusstrains (one from asymptomatic nasal carriage and another from mediastinitis infected tissues) were used to assess in vitro bacterial direct impact on neutrophils. We found that CPB induced a systemic inflammation with an increase in circulating mature neutrophils after surgery. Bone marrow sample analysis did not reveal any modification of neutrophil maturation during CPB. Neutrophil lifespan was significantly increased and functions such as NET release and ROS production were enhanced after CPB whereas bacteria killing and phagocytosis were not impacted. Results were similar with the two different isolates of Staphylococcus aureus. These data suggest that CPB induces a recruitment of mature neutrophils via a demargination process rather than impacting their maturation in the bone marrow. In addition, neutrophils are fully efficient after CPB and do not contribute to postoperative immunosuppression. Cardiopulmonary bypass does not immediately affect neutrophils functions.

المؤلفون: Nader, Joseph, Anselmi, Amedeo, Tomasi, Jacques, Martin, Amandine, Aymami, Marie, Rouze, Simon, Corbineau, Hervé, Langanay, Thierry, Flecher, Erwan, Nesseler, Nicolas, Verhoye, Jean-Philippe

المصدر: Archives of Cardiovascular Diseases; May2021, Vol. 114 Issue 5, p364-370, 7p

الملخص (بالإنجليزية): Central illustration. Impact of coronavirus disease 2019 (COVID-19) on adult cardiac surgery activity. ▪ • COVID-19 outbreak and lockdown seriously affected adult cardiac surgery activity. • A drop in activity of 60–100% was observed in French cardiac surgical centres. • Patients operated on during the first French lockdown were at higher operative risk. • Operative mortality was higher during the first French lockdown. • The rate of nosocomial SARS-CoV-2 infection remains very low. • Postponing cardiac interventions may be harmful for patients on the waiting list. The coronavirus disease 2019 (COVID-19) outbreak had a direct impact on adult cardiac surgery activity, which systematically necessitates a postoperative stay in intensive care. To study the effect of the COVID-19 lockdown on cardiac surgery activity and outcomes, by making a comparison with the corresponding period in 2019. This prospective observational cohort study compared adult cardiac surgery activity in our high-volume referral university hospital from 9 March to 10 May 2020 versus 9 March to 10 May 2019. Data were collected in our local certified database and a national database sponsored by the French society of thoracic and cardiovascular surgery. The primary study endpoints were operative mortality and postoperative complications. With 105 interventions in 2020, our activity dropped by 57% compared with the same period in 2019. Patients were at higher risk, with a significantly higher EuroSCORE II score (3.8 ± 4.5% vs. 2.0 ± 1.8%; P < 0.001) and higher rates of active endocarditis (7.6% vs. 2.9%; P = 0.047) and recent myocardial infarction (9.5% vs. 0%; P < 0.001). The weight and priority of the interventions were significantly different in 2020 (P = 0.019 and P < 0.001, respectively). The rate of acute aortic syndromes was also significantly higher in 2020 (P < 0.001). Operative mortality was higher during the lockdown period (5.7% vs. 1.7%; P = 0.038). The postoperative course was more complicated in 2020, with more postoperative bleeding (P = 0.003), mechanical circulatory support (P = 0.032) and prolonged mechanical ventilation (P = 0.005). Only two patients (1.8%) developed a positive status for severe acute respiratory syndrome coronavirus 2 after discharge. Adult cardiac surgery was heavily affected by the COVID-19 lockdown. A further modulation plan is necessary to improve outcomes and reduce postponed operations to decrease operative mortality and morbidity. [ABSTRACT FROM AUTHOR]

Abstract (French): L'épidémie de la COVID-19 a impacté sérieusement l'activité de chirurgie cardiaque adulte. Pour étudier l'impact et les résultats de cette crise sur notre activité chirurgicale pendant la durée du confinement en France, par rapport à l'année précédente. Étude prospective observationnelle monocentrique, comparant l'activité de chirurgie cardiaque adulte du 09/03 au 10/05/2020 à la même période en 2019, dans une région épargnée lors de la première vague de la pandémie. Les données ont été saisies dans notre base de données locale, ainsi que dans la base de données nationale EPICARD, de la Société française de chirurgie thoracique et cardiovasculaire. Le critère de jugement principal était la mortalité opératoire. Avec 105 interventions, notre activité a chuté de 57 % par rapport à l'année précédente. Les patients étaient à plus haut risque opératoire, estimé par l'EuroSCORE II (3,8 ± 4,5 % vs 2,0 ± 1,8 % ; p < 0,001), avec un plus haut taux d'endocardites actives opérées (7,6 % vs 2,9 % ; p = 0,047) et significativement plus d'infarctus du myocardes récents (p < 0,001). Le type des interventions, ainsi que leur degré d'urgence, étaient significativement différents cette année (p = 0,019 et p < 0,001, respectivement). Le taux de syndromes aortiques aigus était plus important (p < 0,001) pour cette même période. La mortalité opératoire a été plus importante (5,7 % vs 1,7 % ; p = 0,038). Les patients ont saigné davantage en postopératoire (p = 0,003), ont nécessité davantage une ventilation invasive (p = 0,032) et pour une plus longue durée (p = 0,005). Seulement deux patients ont contracté la COVID-19 (1,8 %) après la sortie de l'hôpital. La réduction de la morbi-mortalité de la chirurgie cardiaque adulte en période de pandémie nécessite un plan de modulation propre à cette activité chirurgicale spécialisée. [ABSTRACT FROM AUTHOR]

: Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Delmas, Clément, Aissaoui, Nadia, Meneveau, Nicolas, Bouvaist, Helene, Rousseau, Hervé, Puymirat, Etienne, Sapoval, Marc, Flecher, Erwan, Meyer, Guy, Sanchez, Olivier, Del Giudice, Costantino, Roubille, François, Bonello, Laurent

المصدر: Archives of Cardiovascular Diseases; Nov2020, Vol. 113 Issue 11, p749-759, 11p

الملخص (بالإنجليزية): Acute pulmonary embolism is a frequent cardiovascular emergency with an increasing incidence. The prognosis of patients with high-risk and intermediate-high-risk pulmonary embolism has not improved over the last decade. The current treatment strategies are mainly based on anticoagulation to prevent recurrence and reduce pulmonary vasculature obstruction. However, the slow rate of thrombus lysis under anticoagulation is unable to acutely decrease right ventricle overload and pulmonary vasculature resistance in patients with severe obstruction and right ventricle dysfunction. Therefore, patients with high-risk and intermediate-high-risk pulmonary embolism remain a therapeutic challenge. Reperfusion therapies may be discussed for these patients, and include systemic thrombolysis, catheter-directed therapies and surgical thrombectomy. High-risk patients require systemic thrombolysis, but may have contraindications as a result of the high risk of bleeding. In addition, intermediate-high-risk patients should not receive systemic thrombolysis, despite its high efficacy, because of prohibitive bleeding complications. Recently, percutaneous reperfusion techniques have been developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially higher safety than systemic thrombolysis. Some of these techniques improve key haemodynamic variables. Cardiac surgical techniques and venoarterial extracorporeal membrane oxygenation as temporary circulatory support may be useful in selected cases. The development of pulmonary embolism centres with multidisciplinary pulmonary embolism teams is mandatory to enable adequate use of reperfusion and improve outcomes. We aim to present the state of the art regarding reperfusion therapies in pulmonary embolism, but also to provide guidance on their indications and patient selection. [ABSTRACT FROM AUTHOR]

Abstract (French): L'embolie pulmonaire aiguë est une urgence cardiovasculaire fréquente. Son incidence augmente rapidement tandis que sa mortalité reste stable. Le pronostic des patients à haut risque et à risque intermédiaire élevé reste médiocre sans amélioration au cours de la dernière décennie. Les stratégies de traitement actuelles reposent sur l'anticoagulation pour prévenir les récidives et réduire l'obstruction vasculaire pulmonaire. Cependant, la lyse du thrombus sous anticoagulant est lente et ne permet pas une diminution rapide de la surcharge du ventricule droit et des résistances vasculaires pulmonaires chez les patients présentant une obstruction sévère et une dysfonction ventriculaire droite. La prise en charge de ces patients reste un défi thérapeutique et peut amener à discuter des thérapies de reperfusion comme la thrombolyse systémique, les techniques percutanées par cathéter et la thrombectomie chirurgicale. La thrombolyse systémique est indiquée chez les patients à haut risque en l'absence de contre-indication formelle en raison du risque hémorragique. Mais elle ne devrait pas être utilisée chez les patients à risque intermédiaire élevé malgré son efficacité élevée en raison de complications hémorragiques rédhibitoires. Récemment, les techniques de reperfusion percutanées ont été développées visant à diminuer de manière aiguë l'obstruction vasculaire pulmonaire avec un dose réduite ou sans thrombolytique et en conséquence un profil de sécurité amélioré. Certaines de ces techniques ont démontré une grande efficacité sur les paramètres hémodynamiques clés. Enfin, les techniques de chirurgie cardiaque et le support circulatoire temporaire par ECMO veno-artérielle se sont améliorées et peuvent être utiles dans certains cas. Le développement de centres spécialisés avec une équipe multidisciplinaire est obligatoire afin de permettre une utilisation adéquate de la reperfusion pour améliorer le pronostic des patients. Ce document vise à faire un état de l'art concernant les thérapies de reperfusion de l'embolie pulmonaire tout en discutant leurs indications et la sélection des patients. [ABSTRACT FROM AUTHOR]

: Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Dumontet, Erwan, Pangault, Céline, Roulois, David, Desoteux, Matthis, Léonard, Simon, Marchand, Tony, Latour, Maelle, Legoix, Patricia, Loew, Damarys, Dingli, Florent, Dulong, Joelle, Flecher, Erwan, Coulouarn, Cédric, Cartron, Guillaume, Fest, Thierry, Tarte, Karin

المصدر: Blood; July 2021, Vol. 138 Issue: 1 p57-70, 14p

مستخلص: Follicular lymphoma (FL) originates in the lymph nodes (LNs) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSCs) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been identified. In the current work, we demonstrate that FL B cells produce extracellular vesicles (EVs) that can be internalized by BM-MSCs, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activate transforming growth factor β–dependent and independent pathways in BM-MSCs and modify their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 and angiopoietin-1. Moreover, we provide the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSCs. This work identifies FL-derived EVs as putative mediators of BM stroma polarization and supports further investigation of their clinical interest for targeting the crosstalk between BM-MSCs and malignant B cells.

المؤلفون: Dumontet, Erwan, Pangault, Céline, Roulois, David, Desoteux, Matthis, Léonard, Simon, Marchand, Tony, Latour, Maelle, Legoix, Patricia, Loew, Damarys, Dingli, Florent, Dulong, Joelle, Flecher, Erwan, Coulouarn, Cédric, Cartron, Guillaume, Fest, Thierry, Tarte, Karin

المصدر: Blood; July 2021, Vol. 138 Issue: 1 p57-70, 14p

مستخلص: Follicular lymphoma (FL) originates in the lymph nodes (LNs) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSCs) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been identified. In the current work, we demonstrate that FL B cells produce extracellular vesicles (EVs) that can be internalized by BM-MSCs, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activate transforming growth factor β–dependent and independent pathways in BM-MSCs and modify their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 and angiopoietin-1. Moreover, we provide the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSCs. This work identifies FL-derived EVs as putative mediators of BM stroma polarization and supports further investigation of their clinical interest for targeting the crosstalk between BM-MSCs and malignant B cells.