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1. Myocardial infarction in women under 50: Possible implication of clonal haematopoiesis of indetermined potential

Author

Simon Soudet, Guillaume Jedraszak, Ludovic Drouet, Marie Antoinette Sevestre-Pietri, Loic Garcon, Ophélie Evrard, Estelle Vautrin, Stéphanie Marlière, Anne Bellemain-Appaix, Anne Gompel, Claire Bal dit Sollier, Tessa Bergot, Francis Couturaud, and Stéphane Manzo-Silberman

Subjects
General Medicine, Cardiology and Cardiovascular Medicine
Published
2023
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2. Audit of urgent pacing therapy in nonagenarian patients and their follow up over one year

Author

V Saint-Joy, Y Dagher-Hayeck, A Bellemain-Appaix, F Frattini, and L Jacq

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: None. Introduction and objectives The aging of the population in the world and particularly in developed countries is changing the panorama of patients who are treated both on the socio-demographic level and on the indications for the care of elderly subjects. Antibes is the sixth region in France with the most nonagenarians. A study had already been carried out in our center on the management of coronary emergencies in people over 90 years old and this time we are interested in the management of rhythmic emergencies in the latter with a focus on permanent cardiac stimulation in emergency. Methods This 5-year retrospective descriptive study runs from 2016 to 2020 and analyzes the records of 156 nonagenarians hospitalized in the intensive care unit and 1322 planned visits of patients over 90 years old to the electrophysiology unit. Results Nonagenarians represent 16.6% of patients admitted for cardiac arrhythmias requiring intensive and / or invasive management. 65% of patients hospitalized in cardiac critical care unit (CCU) benefited from the implantation of a pacemaker, with 13% of them presenting non-severe complications related to the procedure. 2% died in the CCU. After their hospital stay 60% came for follow-up at 3 months and only 19.6% at 1 year. Conclusion This study highlights the need to make invasive cardiology practitioners aware of the growing proportion of this geriatric subgroup of very old patients (>90). There were no serious complications limiting the eligibility of nonagenarians. It seems necessary to develop a close collaboration of cardio-geriatricians and telecardiology in this subset of frail patients.

Published
2023
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5. SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion

Author

Giuseppe De Luca, Magdy Algowhary, Berat Uguz, Dinaldo C Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Gerard Roura i Ferrer, Alexandre Quadros, Marek Milewski, Fortunato Scotto Di Uccio, Clemens von Birgelen, Francesco Versaci, Jurrien Ten Berg, Gianni Casella, Aaron Wong Sung Lung, Petr Kala, José Luis Díez Gil, Xavier Carrillo, Maurits Dirksen, Victor M. Becerra-Munoz, Michael Kang-yin Lee, Dafsah Arifa Juzar, Rodrigo de Moura Joaquim, Ciro De Simone, Davor Milicic, Periklis Davlouros, Nikola Bakraceski, Filippo Zilio, Luca Donazzan, Adriaan Kraaijeveld, Gennaro Galasso, Lux Arpad, Lucia Marinucci, Vincenzo Guiducci, Maurizio Menichelli, Alessandra Scoccia, Aylin Hatice Yamac, Kadir Ugur Mert, Xacobe Flores Rios, Tomas Kovarnik, Michal Kidawa, Josè Moreu, Vincent Flavien, Enrico Fabris, Iñigo Lozano Martínez-Luengas, Marco Boccalatte, Francisco Bosa Ojeda, Carlos Arellano-Serrano, Gianluca Caiazzo, Giuseppe Cirrincione, Hsien-Li Kao, Juan Sanchis Forés, Luigi Vignali, Helder Pereira, Stephane Manzo-Silbermann, Santiago Ordoñez, Alev Arat Özkan, Bruno Scheller, Heidi Lehtola, Rui Teles, Christos Mantis, Ylitalo Antti, João António Brum Silveira, Ivan Bessonov, Rodrigo Zoni, Stefano Savonitto, George Kochiadakis, Dimitrios Alexopoulos, Carlos E Uribe, John Kanakakis, Benjamin Faurie, Gabriele Gabrielli, Alejandro Gutierrez Barrios, Juan Pablo Bachini, Alex Rocha, Frankie Chor-Cheung Tam, Alfredo Rodriguez, Antonia Anna Lukito, Anne Bellemain-Appaix, Gustavo Pessah, Giuliana Cortese, Guido Parodi, Mohammed Abed Burgadha, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Matteo Nardin, Monica Verdoia, TechMed Centre, Health Technology & Services Research, YAMAÇ, AYLİN HATİCE, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H01 Clinical atrial fibrillation

Subjects
IMPACT, ELEVATION MYOCARDIAL-INFARCTION, PRIMARY ANGIOPLASTY, COVID-19, STEMI, outcome, thrombosis, ASPIRATION, Thrombosis, n/a OA procedure, De Luca G., Algowhary M., Uguz B., Oliveira D. C. , Ganyukov V., Zimbakov Z., Cercek M., Jensen L. O. , Loh P. H. , Calmac L., et al., -SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion-, ANGIOLOGY, 2022, Cardiology and Cardiovascular Medicine, METAANALYSIS, Outcome
Abstract

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

Published
2022
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6. Characteristics of young women presenting with acute myocardial infarction: the prospective, multicentre, observational WAMIF study

Author

S Manzo-Silberman, F Couturaud, A Bellemain-Appaix, E Vautrin, A Gompel, L Drouet, S Marliere, C Bal Dit Solier, S Uhry, H Eltchaninoff, T Bergot, P Motreff, Y Cottin, C Mounier-Vehier, and M Gilard

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background Cardiovascular diseases are the leading cause of death in women, killing sevenfold more women than breast cancer. Rates of hospital death for myocardial infarction in women, although decreasing, remains significantly higher than in men (more than double), especially among women under the age of 50. The occurrence of myocardial infarction in non-menopausal women is not unusual, and the incidence continues to rise. While women under the age of 60 accounted for less than 12% of patients with myocardial infarction admitted in 1995, they accounted for more than 25% in 2015. In addition to the traditional cardiovascular risk factors, women present specific ones linked to hormonal modifications, inflammatory high-risk profiles, and thrombophilia. Purpose We comprehensively and systematically collected all clinical and biological data and the results of morphological explorations in all women admitted for myocardial infarction under the age of 50 in high-volume French centres. To date, no systematic descriptive analysis has been carried out incorporating not only clinical, morphological, and extraordinary characteristics, but biological characteristics, in particular hormonal and immunological parameters. Methods This prospective, observational study included all women admitted for myocardial infarction under the age of 50 years at 30 centres in France from May 2017 to June 2019. Results The population comprised 314 women (mean age 44.9 years): 192 presented with ST-segment elevation myocardial infarction and 122 with non-ST-segment elevation myocardial infarction, 75% were current smokers, 35 had a family history of cardiovascular disease, 33% had a complication of pregnancy, and 55% reported recent emotional stress. Ten had a normal coronary angiogram. Independent predictors of premature MI, Conclusion The WAMIF study showed that most young women with acute myocardial infarction reported typical symptoms of chest pain, and modifiable cardiovascular risk factors, most commonly tobacco use. Gynaecological status, history of pregnancy complications, and non-compliance with non-indication of combined contraception were overrepresented, emphasizing the urge for a better cardiological and gynaecological network. The overall prognosis for these women was better than previously reported despite the high rate of emergency consultations in the year following the index myocardial infarction, highlighting the need for more comprehensive follow-up following the myocardial infarction. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): French Society of CardiologyGrants from Indusctries Biosensors Europe SA, AstraZeneca, Boston Scientific Corporation, Abbott Medical Devices, Terumo Corporation, Daiichi Sankyo, Inc., Hexacath, France, Biotronik SE & Co. KG.

Published
2022
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7. Anomalous Left Coronary Artery Connected to the Pulmonary Artery in a 15-Year-Old Girl: Case Report and Discussion on Secondary Prevention of Sudden Death

Author

Philippe De Swardt, Virginie Fouilloux, Jérôme Hourdain, François Bernasconi, Jérémy Laïk, Laurent Jacq, Philippe Aldebert, Linda Koutbi, Anne Bellemain-Appaix, and Fabrice Tiger

Subjects
medicine.medical_specialty, Heart disease, business.industry, Case Report, Fainting, medicine.disease, Ventricular tachycardia, Sudden death, Left coronary artery, medicine.anatomical_structure, Fibrosis, RC666-701, medicine.artery, Internal medicine, Pulmonary artery, cardiovascular system, medicine, Cardiology, Diseases of the circulatory (Cardiovascular) system, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Papillary muscle
Abstract

Background. Anomalous left coronary artery connected to the pulmonary artery (ALCAPA) is a rare congenital heart disease. Adaptive development of sufficient heterocoronary collaterality in the newborn may allow survival to a later age. In older children or adults, malignant ventricular arrhythmias can reveal the disease. Case Report. A 15-year-old girl was referred to the local hospital after a resuscitated out-of-hospital cardiac arrest. CT scan and coronary angiography revealed an ALCAPA. Direct aortic reimplantation of the left coronary artery was performed. Postoperative ECG monitoring showed short episodes of nonsustained ventricular tachycardia. Transthoracic echocardiography and cardiac MRI revealed subendocardial fibrosis of the anterolateral papillary muscle. Beta-blockade therapy was initiated at first intention. After hospital discharge, the patient reported several fainting without loss of consciousness. Considering sudden death nonrelated to effort, episodes of nonsustained ventricular tachycardia, and areas of myocardial fibrosis, the patient underwent subcutaneous cardioverter-defibrillator implantation. 6-month follow-up is satisfactory without clinical or rhythmic abnormalities. Discussion. Indication for surgical correction of ALCAPA is well defined, but rhythmic secondary prevention after resuscitated cardiac arrest is less consensual. Cardiac MRI is an essential tool in the identification of a potential rhythmic substrate and should be taken into account in the discussion of a preventive cardioverter-defibrillator implantation.

Published
2021
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8. Post-discharge and long-term follow-up after an acute coronary syndrome: International Collaborative Group of CNCF position paper

Author

Pierre Sabouret, Gilles Lemesle, Anne Bellemain-Appaix, Pierre Aubry, Pier-Paolo Bocchino, Erik Raffenbeul, Loïc Belle, Jim Nolan, Marco Bernardi, Giuseppe Biondi-Zoccai, Michael Savage, Maciej Banach, and Guillaume Cayla

Subjects
General Medicine
Abstract

IntroductionLong-term follow-up after an acute coronary syndrome (ACS) presents a crucial challenge due to the high residual cardiovascular risk and the potential for major bleeding events. Although several treatment strategies are available, this article focuses on patients who have undergone percutaneous coronary intervention (PCI) for ACS, which represent a frequent clinical situation. This position paper aims to support physicians in daily practice to improve the management of ACS patients.Material and methodsA group of recognized international and French experts in the field, provides an overview of current evidence-based recommendations − supplemented by expert opinion where such evidence is lacking − and a practical guide for the management of patients with ACS after hospital discharge.ResultsThe International Collaborative Group underlines the need of a shared collaborative approach, and a care plan individualized to the patient’s risk profile for both ischemia and bleeding. Each follow-up appointment should be viewed as an opportunity to optimize the personalized approach, to reduce adverse clinical outcomes and improve quality of life. As risks – both ischaemic and haemorrhagic – evolve over time, the risk–benefit balance should be assessed in an ongoing dynamic process to ensure that patients are given the most suitable treatment at each time point.ConclusionsThis Expert Opinion aims to help clinicians with a practical guide underlying the proven strategies and the remaining gaps of evidence to optimize the management of coronary patients.

Published
2022
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10. Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients

Author

Jennifer Cautela, Anne Bellemain-Appaix, Thierry Tibi, Nicolas Girerd, Alain Cohen-Solal, Alexis Theron, Jean-Michel Tartière, François Roubille, James L. Januzzi, Heart Failure and Valvular Heart Diseases Unit, Department of Cardiology, Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Hôpital Nord, Aix-Marseille I University, Marseille, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cardiology Department, Hôpital Sainte Musse, Toulon, Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cardiology Department, Centre Hospitalier d'Antibes Juan les Pins, Antibes, Centre Hospitalier Antibes - Juan-les-Pins, Aix Marseille Université (AMU), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Cardiology Department, Centre Hospitalier de Cannes, Cannes, Centre Hospitalier de Cannes, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MORNET, Dominique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Reviews, Heart failure, Review, 030204 cardiovascular system & hematology, Asymptomatic, Angiotensin‐converting enzyme inhibitor, 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Internal medicine, medicine, Beta-blocker, Angiotensin receptor blocker, Diuretics, Beta blocker, Angiotensin receptor–neprilysin inhibitor, Ejection fraction, Mineralocorticoid receptor antagonist, business.industry, Loop diuretic, medicine.disease, Angiotensin receptor-neprilysin inhibitor, 3. Good health, [SDV] Life Sciences [q-bio], Blood pressure, Angiotensin-converting enzyme inhibitor, Beta‐blocker, Shock (circulatory), Cardiology, Hypotension, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non-severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.

Published
2020
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11. Intérêts et limites de l’angioplastie coronaire chez les patients nonagénaires : expérience monocentrique

Author

L. Jacq, N. Kourireche, H. Sanoussi, Anne Bellemain-Appaix, F. Bernasconi, N. Bitton, and A. Tounsi

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, business, Mace
Abstract

Resume Objectifs Exposer les resultats de notre centre dans l’angioplastie des nonagenaires pour en evaluer l’utilite mais aussi les risques, les MACE et la mortalite a court et a long terme. Methodes Etude retrospective de 98 patients realisee au centre hospitalier d’Antibes de novembre 2013 a septembre 2018. Resultats La mediane d’âge etait de 91,8 [90,8–93,4]. Au total, 52,6 % etait de sexe masculin. Parmi les malades, 9,7 % avaient un terrain polyvasculaire. De plus, 50,6 % des patients avaient une insuffisance renale moderee. La voie radiale etait la voie la plus utilisee avec un desilet 6 French dans 88,4 % des cas. Parmi les patients, 21,6 % presentaient des lesions tritronculaires, alors que 46,4 % etaient monotronculaires, l’IVA etait l’artere coupable dans 67 % des cas. En moyenne on a utilise un stent par lesion chez nos patients. Notre taux de succes etait de 90 %. Apres angioplastie 96 % des malades etaient sous double anti-agregation plaquettaire, dont 74,4 % sous clopidogrel. La presence de troubles du rythme avant angioplastie, la voie d’abord femorale, la dissection coronaire et le choc cardiogenique en post-angioplastie etaient des facteurs predictifs de mortalite a court et a long termes. Le diabete, l’antecedent d’infarctus du myocarde, la fraction d’ejection du ventricule gauche alteree, les lesions calcifiees coronaires, la survenue de troubles du rythme ou d’insuffisance cardiaque en post-procedure etaient des facteurs predictifs de survenue de MACE. Conclusions Cette etude demontre que l’angioplastie chez une population selectionnee de nonagenaires est parfaitement realisable avec un bon rapport benefices/risques et precise les differents facteurs predictifs de MACE, mortalite a court et a long termes.

Published
2020
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12. Supplemental Material - SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion

Author

De Luca, Giuseppe, Algowhary, Magdy, Uguz, Berat, Oliveira, Dinaldo C, Ganyukov, Vladimir, Zimbakov, Zan, Cercek, Miha, Okkels Jensen, Lisette, Loh, Poay Huan, Calmac, Lucian, Roura i Ferrer, Gerard, Quadros, Alexandre, Milewski, Marek, Scotto Di Uccio, Fortunato, von Birgelen, Clemens, Versaci, Francesco, Ten Berg, Jurrien, Casella, Gianni, Wong Sung Lung, Aaron, Kala, Petr, Díez Gil, José Luis, Carrillo, Xavier, Dirksen, Maurits, Becerra-Munoz, Victor M., Kang-yin Lee, Michael, Juzar, Dafsah Arifa, de Moura Joaquim, Rodrigo, De Simone, Ciro, Milicic, Davor, Davlouros, Periklis, Bakraceski, Nikola, Zilio, Filippo, Donazzan, Luca, Kraaijeveld, Adriaan, Galasso, Gennaro, Arpad, Lux, Marinucci, Lucia, Guiducci, Vincenzo, Menichelli, Maurizio, Scoccia, Alessandra, Yamac, Aylin Hatice, Ugur Mert, Kadir, Flores Rios, Xacobe, Kovarnik, Tomas, Kidawa, Michal, Moreu, Josè, Flavien, Vincent, Fabris, Enrico, Lozano Martínez-Luengas, Iñigo, Boccalatte, Marco, Bosa Ojeda, Francisco, Arellano-Serrano, Carlos, Caiazzo, Gianluca, Cirrincione, Giuseppe, Kao, Hsien-Li, Sanchis Forés, Juan, Vignali, Luigi, Pereira, Helder, Manzo-Silbermann, Stephane, Ordoñez, Santiago, Arat Özkan, Alev, Scheller, Bruno, Lehtola, Heidi, Teles, Rui, Mantis, Christos, Antti, Ylitalo, Brum Silveira, João António, Bessonov, Ivan, Zoni, Rodrigo, Savonitto, Stefano, Kochiadakis, George, Alexopoulos, Dimitrios, Uribe, Carlos E, Kanakakis, John, Faurie, Benjamin, Gabrielli, Gabriele, Gutierrez Barrios, Alejandro, Bachini, Juan Pablo, Rocha, Alex, Tam, Frankie Chor-Cheung, Rodriguez, Alfredo, Lukito, Antonia Anna, Bellemain-Appaix, Anne, Pessah, Gustavo, Cortese, Giuliana, Parodi, Guido, Burgadha, Mohammed Abed, Kedhi, Elvin, Lamelas, Pablo, Suryapranata, Harry, Nardin, Matteo, and Verdoia, Monica

Subjects
Cardiology
Abstract

Supplemental Material for SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion by Giuseppe De Luca, MD, PhD, Magdy Algowhary, Berat Uguz, Dinaldo C Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Gerard Roura i Ferrer, Alexandre Quadros, Marek Milewski, Fortunato Scotto Di Uccio, Clemens von Birgelen, Francesco Versaci, Jurrien Ten Berg, Gianni Casella, Aaron Wong Sung Lung, Petr Kala, José Luis Díez Gil, Xavier Carrillo, Maurits Dirksen, Victor M. Becerra-Munoz, Michael Kang-yin Lee, Dafsah Arifa Juzar, Rodrigo de Moura Joaquim, Ciro De Simone, Davor Milicic, Periklis Davlouros, Nikola Bakraceski, Filippo Zilio, Luca Donazzan, Adriaan Kraaijeveld, Gennaro Galasso, Lux Arpad, Marinucci Lucia, Guiducci Vincenzo, Maurizio Menichelli, Alessandra Scoccia, Aylin Hatice Yamac, Kadir Ugur Mert, Xacobe Flores Rios, Tomas Kovarnik, Michal Kidawa, Josè Moreu, Vincent Flavien, Enrico Fabris, Iñigo Lozano Martínez-Luengas, Marco Boccalatte, Francisco Bosa Ojeda, Carlos Arellano-Serrano, Gianluca Caiazzo, Giuseppe Cirrincione, Hsien-Li Kao, Juan Sanchis Forés, Luigi Vignali, Helder Pereira, Stephane Manzo-Silbermann, Santiago Ordoñez, Alev Arat Özkan, Bruno Scheller, Heidi Lehtola, Rui Teles, Christos Mantis, Ylitalo Antti, João António Brum Silveira, Rodrigo Zoni, Ivan Bessonov, Stefano Savonitto, George Kochiadakis, Dimitrios Alexopoulos, Carlos E Uribe, John Kanakakis, Benjamin Faurie, Gabriele Gabrielli, Alejandro Gutierrez Barrios, Juan Pablo Bachini, Alex Rocha, Frankie Chor-Cheung Tam, Alfredo Rodriguez, Antonia Anna Lukito, Anne Bellemain-Appaix, Gustavo Pessah, Giuliana Cortese, Guido Parodi, MD, Mohammed Abed Burgadha, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Matteo Nardin, Monica Verdoia in Angiology

Published
2022
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13. CRMP4-mediated fornix development involves Semaphorin-3E signaling pathway

Author

Amandine Peyrel, Jean-Christophe Deloulme, Charlotte Ravanello, Christian Delphin, Alyson E. Fournier, Florence Appaix, Christophe Bosc, Muriel Jaquier-Sarlin, Alexandra Kraut, Sylvie Gory-Fauré, Eric Denarier, Benoit Boulan, Annie Andrieux, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), McGill University = Université McGill [Montréal, Canada], and Bruley, Christophe

Subjects
Male, Receptor complex, Collapsin-Response-Mediator-Proteins, detergent-resistant membrane domains, QH301-705.5, [SDV]Life Sciences [q-bio], Science, Fornix, Brain, Nerve Tissue Proteins, Semaphorins, fornix, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, Mediator, Semaphorin, Animals, MAP6, Biology (General), Growth cone, Protein kinase B, axonal guidance, lipid rafts, General Immunology and Microbiology, General Neuroscience, Fornix, General Medicine, [SDV] Life Sciences [q-bio], nervous system, Semaphorin-3E, Detergent-Resistant-Membrane-Domains, Medicine, Female, Signal transduction, Neuroscience, CRMP4, Research Article, Developmental Biology, Signal Transduction
Abstract

Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-associated protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the collapsin response mediator protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within detergent-resistant membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E’s growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

Published
2021
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15. Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Author

François Jourda, Christophe Saint-Etienne, Luc Christiaens, Grégoire Rangé, Benoit Lattuca, Philippe Brunel, Paul Guedeney, Hervé Le Breton, Marie Hauguel-Moreau, Eric Vicaut, Anne Bellemain-Appaix, Jean-Louis Georges, Guillaume Cayla, Christophe Pouillot, Christophe Caussin, Gregory Ducrocq, Ziad Boueri, Farzin Beygui, Johanne Silvain, Thibault Lhermusier, Gilles Montalescot, Jean-Noël Labèque, Jean-Philippe Collet, Zuzana Motovska, Franck Boccara, Mohamad El Kasty, Raphaelle Dumaine, Jean-Guillaume Dillinger, Mikael Laredo, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de cardiologie [Chartres], Les hôpitaux de Chartres [Chartres], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital de Bastia, Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Clinique Sainte Clotilde, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de cardiologie [Centre Hospitalier de la Côte Basque, Bayonne], Centre Hospitalier de la Côte Basque, CHU Toulouse [Toulouse], Centre Hospitalier de Versailles André Mignot (CHV), Cardiology Department, Centre Hospitalier d'Antibes Juan les Pins, Antibes, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Institut Mutualiste de Montsouris (IMM), Hôpital d'Auxerre, Partenaires INRAE, Grand Hôpital de l'Est Francilien (GHEF), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, AstraZeneca France Novartis Daiichi-Sankyo Bristol-Myers Squibb, BMS Eli Lilly and Company Bayer AstraZeneca France Boston Scientific Corporation, BSC Abbott Laboratories Medtronic Biotronik Fédération Française de Cardiologie, FFC, The ALPHEUS and the Bio-ALPHEUS studies are funded by the Fond de dotation ACTION ( www.action-fonds.org ) and a grant from AstraZeneca . The Bio-ALPHEUS study is also funded by the Institute of Cardiometabolism and Nutrition . The first draft of the paper was developed by Dr Silvain and Dr Montalescot, and all authors subsequently contributed to its development and final content and are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. AstraZeneca reviewed the manuscript and was allowed to make suggestions, but final content was determined by the authors., Dr Silvain reports receiving consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, BPI France, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, Abbott Medical France SAS, and Zoll and is a stockholder of Pharmaseeds. Dr Cayla reports speaker or congress fees and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Beygui reports receiving consulting and lecture fees from Astrazeneca, Bristol-Myers Squibb, Medtronic, Biosensors, Boston Scientific Institutional and research grants from Medtronic, Biosensors, Acist, and Boston scientific. Dr Rangé reports receiving speaker’s and/or consulting fees from Abbott. Dr Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi-Sankyo, Fédération Française de Cardiologie, and Institute of CardioMetabolism and Nutrition, consultant fees from Daiichi-Sankyo and Eli Lilly, and lecture fees from AstraZeneca, Medtronic, and Novartis. Dr Collet reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. Dr Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, and Sanofi and grants from Bayer, Bristol-Myers Squibb/Pfizer, and Biosensors. Dr Boueri reports receiving consulting and lecture fees from Novartis and Astra Zeneca. Dr Boccara reports consulting or speaker fees from Amgen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. Dr Christiaens reports consulting or speaker fees from Astra Zeneca. Dr Lhermusier reports consulting or speaker fees from Astra Zeneca, Boston Scientifics, and Abbott and a research grant from Astra Zeneca. Dr Georges reports consulting or speaker fees from AstraZeneca France, Sanofi-Aventis, Amgen, and Merck Sharpe and Dohme. Dr Bellemain-Appaix reports consulting or speaker fees from Astra Zeneca, Novartis, and Pfizer. Dr Saint-Etienne reports consulting or speaker fees from Abbott, Medtronic, Edwards, and Biotronik. Dr Motovska reports consulting or speaker fees from Astrazeneca. Dr Laredo reports fellowship grants from Medtronic, Biotronik, and Boston Scientific. Dr Ducrocq reports consulting or speaker fees from Amgen, Astra Zeneca, Bayer, BMS, Janssen, Sanofi, and Terumo, proctoring: Boston scientific, CEC: Novo Nordisk, and travel fees: Astra Zeneca, Bayer, and BMS. Dr Vicaut reports consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi, and Novartis. Dr Montalescot reports consulting or speaker fees from Abbott, AIM group, Amgen, Actelion, American College of Cardiology Foundation, Astrazeneca, Axis-Santé, Bayer, Boston-Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Fréquence Médicale, ICOM, Idorsia, Elsevier, Fédération Française de Cardiologie, Fréquence Médicale, Institute of Cardiometabolism and Nutrition, Lead-Up, Menarini, Medtronic, MSD, Novo-Nordisk, Pfizer, Quantum Genomics, Sanofi-Aventis, SCOR global life, Servier, and WebMD. Other authors have no conflict of interest to report., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier d'Auxerre (CHA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
medicine.medical_specialty, Ticlopidine, medicine.medical_treatment, Myocardial Infarction, Coronary Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Loading dose, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Aged, Aspirin, business.industry, Percutaneous coronary intervention, medicine.disease, Clopidogrel, 3. Good health, Conventional PCI, Cardiology, Purinergic P2Y Receptor Antagonists, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, Ticagrelor, Platelet Aggregation Inhibitors, medicine.drug
Abstract

International audience; Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Methods: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Published
2020
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16. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial

Author

Johanne Silvain, Benoit Lattuca, Farzin Beygui, Grégoire Rangé, Zuzana Motovska, Jean-Guillaume Dillinger, Ziad Boueri, Philippe Brunel, Thibault Lhermusier, Christophe Pouillot, Elisa Larrieu-Ardilouze, Franck Boccara, Jean-Noël Labeque, Paul Guedeney, Mohamad El Kasty, Mikael Laredo, Raphaëlle Dumaine, Grégory Ducrocq, Jean-Philippe Collet, Guillaume Cayla, Katrien Blanchart, Petr Kala, Eric Vicaut, Gilles Montalescot, Johanne SILVAIN, Jean-Philippe COLLET, Gilles MONTALESCOT, Mathieu KERNEIS, Nassim BRAIK, Olivier BARTHELEMY, Gérard HELFT, Claude LEFEUVRE, Rémi CHOUSSAT, Marie HAUGUEL, Michel ZEITOUNI, Thomas CUISSET, Jean-Louis BONNET, Pierre DEHARO, Benoit LATTUCA, Guillaume CAYLA, Luc CORNILLET, Bertrand LEDERMANN, Clément LONJON, Laurent SCHMUTZ, Grégoire RANGE, Franck ALBERT, Thibault DEMICHELI, Laurent ROUSSEL, Reda BENSAID, Christophe THUAIRE, Jean-Guillaume DILLINGER, Patrick HENRY, Stéphane MANZO-SILBERMAN, Georgios SIDERIS, Damien LOGEART, Vincent SPAGNOLI, Léa CACOUB, Christophe POUILLOT, Jean Richard VI-FANE, Jens GLASENAPP, Karim BOUGRINI, Nicolas COMBARET, Pascal MOTREFF, Géraud SOUTEYRAND, Aimé AMONCHOT, Thomas MOUYEN, Thibault LHERMUSIER, Didier CARRIE, Frédéric BOUISSET, Thomas CHOLLET, Francisco CAMPELO-PARADA, Nicolas DELARCHE, François SCHIELE, Mathieu BESUTTI, Marie HAUGUEL-MOREAU, Rami EL MAHMOUD, Christophe CAUSSIN, Mami ZOHEIR, Aurelie VEUGEOIS, Alain DIBIE, Olivier VARENNE, Fabien PICARD, Alexandre LAFONT, Julien ADJEDJ, Philippe DEGRELL, Farzin BEYGUI, Rémi SABATIER, Vincent ROULE, Mathieux BIGNON, Katrien BLANCHART, Pierre ARDOUIN, Adrien LEMAITRE, Clément BRIET, Ziad BOUERI, Pascal GOUBE, Pierre COSTE, Laura CETRAN, Jérôme CLERC, Hervé LE BRETON, Dominique BOULMIER, Vincent AUFFRET, Jean-Noël LABEQUE, Jean-Luc BONAS, Jean-Louis GEORGES, Bernard LIVAREK, Elodie BLICQ, Nicolas BARON, Géraldine GIBAULT-GENTY, Yves COTTIN, Isabelle LHUILLIER, Carole RICHARD, Luc LORGIS, Philippe BUFFET, Christian SPAULDING, Nicole KARAM, Etienne PUYMIRAT, Marco MENNUNI, Emmanuel POULIDAKIS, Lionel BONNEVIE, Franck BOCCARA, Marion CHAUVET, Laurie DUFOUR, Yann ANCEDY, Stéphane EDERHY, Arnaud ETIENNEY, Anne BELLEMAIN-APPAIX, Nathaniel BITTON, Laurent JACQ, Christophe SAINT-ETIENNE, Florence LECLERCQ, François ROUBILLE, Gilles RIOUFOL, François DERIMAY, Marc GORALSKI, Wael YAFI, Emmanuelle FILIPPI, Alain KERMARREC, Christophe LE RAY, Antoine MERLET, Aurelie LOIRAT, Philippe BRUNEL, Damien BRUNET, Jack RAVISY, Laurent MOCK, Guillaume MOLINS, Max CARRE, Erwan BRESSOLLETTE, Luc CHRISTIAENS, Elisa LARRIEU-ARDILOUZE, Romain CADOR CADOR, Eric VAN BELLE, Gilles LEMESLE, Cédric DELHAYE, Flavien VINCENT, Sina POROUCHANI, Hugues SPILLEMAEKER, Katy PETIT, Olivier RESSENCOURT, Vincent HUMEAU, François JOURDA, Marc-Antoine ARNOULD, Stephen CHASSAING, Karl ISAAZ, Laurent PAYOT, Jacques MONTSEGU, Benjamin FAURIE, Michel PANSIERI, Marc METGE, Karim MOUSSA, Mathieu PANKERT, Olivier MOREL, Sébastien HESS, Luc MAILLARD, Thibault MANIGOLD, Vincent LETOCART, Julien PLESSIS, Pauline BERTHOME, Mickael BONIN, François HUCHET, Emmanuel TEIGER, Romain GALLET, Gauthier MOUILLET, Madjid BOUKANTAR, Mohammed NEJJARI, David ATTIAS, Mathieu STEINECKER, Zuzana MOTOVSKA, Martin KOZEL, Zdenko STELMACH, Ota HLINOMAZ, Michal REZEK, Martin NOVAK, Jan SITAR, Jiri SEMENKA, Petr KALA, Otakar BOCEK, Roman ŠTIPAL, Martin POLOCZEK, Jan KANOVSKÝ, Petr JERABEK, Jiří KARASEK, Sylvie HRUSKOVA, Marian BRANNY, Jan MROZEK, Tomas GREZL, Leos PLEVA, Pavel KUKLA, Martin PORZER, Lesnik, Philippe, Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Louis Pasteur [Chartres], Charles University [Prague] (CU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Bastia (G2HC), Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Clinique Sainte Clotilde, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Le CHCB, Centre Hospitalier de la Côte Basque, Grand Hôpital de l'Est Francilien (GHEF), Centre de Réadaptation Cardiaque Les Grands Prés [Villeneuve Saint Denis] (CRCLGP), Service de cardiologie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot, Sorbonne Paris Cité, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), University Hospital Brno, Masaryk University [Brno] (MUNI), Hopital Saint-Louis [AP-HP] (AP-HP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), ALPHEUS investigators: Johanne Silvain, Jean-Philippe Collet, Gilles Montalescot, Mathieu Kerneis, Nassim Braik, Olivier Barthelemy, Gérard Helft, Claude Lefeuvre, Rémi Choussat, Marie Hauguel, Michel Zeitouni, Thomas Cuisset, Jean-Louis Bonnet, Pierre Deharo, Benoit Lattuca, Guillaume Cayla, Luc Cornillet, Bertrand Ledermann, Clément Lonjon, Laurent Schmutz, Grégoire Range, Franck Albert, Thibault Demicheli, Laurent Roussel, Reda Bensaid, Christophe Thuaire, Jean-Guillaume Dillinger, Patrick Henry, Stéphane Manzo-Silberman, Georgios Sideris, Damien Logeart, Vincent Spagnoli, Léa Cacoub, Christophe Pouillot, Jean Richard Vi-Fane, Jens Glasenapp, Karim Bougrini, Nicolas Combaret, Pascal Motreff, Géraud Souteyrand, Aimé Amonchot, Thomas Mouyen, Thibault Lhermusier, Didier Carrie, Frédéric Bouisset, Thomas Chollet, Francisco Campelo-Parada, Nicolas Delarche, François Schiele, Mathieu Besutti, Marie Hauguel-Moreau, Rami El Mahmoud, Christophe Caussin, Mami Zoheir, Aurelie Veugeois, Alain Dibie, Olivier Varenne, Fabien Picard, Alexandre Lafont, Julien Adjedj, Philippe Degrell, Farzin Beygui, Rémi Sabatier, Vincent Roule, Mathieux Bignon, Katrien Blanchart, Pierre Ardouin, Adrien Lemaitre, Clément Briet, Ziad Boueri, Pascal Goube, Pierre Coste, Laura Cetran, Jérôme Clerc, Hervé LE Breton, Dominique Boulmier, Vincent Auffret, Jean-Noël Labeque, Jean-Luc Bonas, Jean-Louis Georges, Bernard Livarek, Elodie Blicq, Nicolas Baron, Géraldine Gibault-Genty, Yves Cottin, Isabelle Lhuillier, Carole Richard, Luc Lorgis, Philippe Buffet, Christian Spaulding, Nicole Karam, Etienne Puymirat, Marco Mennuni, Emmanuel Poulidakis, Lionel Bonnevie, Franck Boccara, Marion Chauvet, Laurie Dufour, Yann Ancedy, Stéphane Ederhy, Arnaud Etienney, Anne Bellemain-Appaix, Nathaniel Bitton, Laurent Jacq, Christophe Saint-Etienne, Florence Leclercq, François Roubille, Gilles Rioufol, François Derimay, Marc Goralski, Wael Yafi, Emmanuelle Filippi, Alain Kermarrec, Christophe LE Ray, Antoine Merlet, Aurelie Loirat, Philippe Brunel, Damien Brunet, Jack Ravisy, Laurent Mock, Guillaume Molins, Max Carre, Erwan Bressollette, Luc Christiaens, Elisa Larrieu-Ardilouze, Romain Cador Cador, Eric VAN Belle, Gilles Lemesle, Cédric Delhaye, Flavien Vincent, Sina Porouchani, Hugues Spillemaeker, Katy Petit, Olivier Ressencourt, Max Carre, Vincent Humeau, François Jourda, Marc-Antoine Arnould, Stephen Chassaing, Karl Isaaz, Laurent Payot, Jacques Montsegu, Benjamin Faurie, Michel Pansieri, Marc Metge, Karim Moussa, Mathieu Pankert, Olivier Morel, Sébastien Hess, Luc Maillard, Thibault Manigold, Vincent Letocart, Julien Plessis, Pauline Berthome, Mickael Bonin, François Huchet, Emmanuel Teiger, Romain Gallet, Gauthier Mouillet, Madjid Boukantar, Rami El Mahmoud, Mohammed Nejjari, David Attias, Léa Cacoub, Mathieu Steinecker, François Huchet, Zuzana Motovska, Martin Kozel, Zdenko Stelmach, Ota Hlinomaz, Michal Rezek, Martin Novak, Jan Sitar, Jiri Semenka, Petr Kala, Otakar Bocek, Roman Štipal, Martin Poloczek, Jan KanovskÝ, Petr Jerabek, Jiří Karasek, Sylvie Hruskova, Marian Branny, Jan Mrozek, Tomas Grezl, Leos Pleva, Pavel Kukla, Martin Porzer., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, Ticagrelor, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Percutaneous coronary intervention, General Medicine, Middle Aged, medicine.disease, Clopidogrel, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Action study, Elective Surgical Procedures, Anesthesia, Conventional PCI, Purinergic P2Y Receptor Antagonists, Female, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

International audience; Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070).Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.Funding: ACTION Study Group and AstraZeneca.

Published
2020
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17. Spatiotemporal reorganization of corticostriatal networks encodes motor skill learning

Author

Nagham Badreddine, Gisela Zalcman, Florence Appaix, Guillaume Becq, Nicolas Tremblay, Frédéric Saudou, Sophie Achard, Elodie Fino, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto Boliviano de Biologia de Altura (IBBA), Universidad Mayor de San Andrés (UMSA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), GIPSA-Services (GIPSA-Services), Grenoble Images Parole Signal Automatique (GIPSA-lab), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), GIPSA Pôle Géométrie, Apprentissage, Information et Algorithmes (GIPSA-GAIA), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), ANR-18-CE16-0009,AXYON,Transport axonal et maturation neuronale: conséquences pour la fonction synaptique et les connexions neuronales en situation normale et dans la maladie de Huntington.(2018), ANR-19-CE37-0026,ProMeSS,La mémoire procédurale et la dynamique des réseaux neuronaux striataux(2019), Modèles statistiques bayésiens et des valeurs extrêmes pour données structurées et de grande dimension (STATIFY), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), and Fino, Elodie

Subjects
Neurons, [STAT.AP]Statistics [stat]/Applications [stat.AP], [SCCO.NEUR]Cognitive science/Neuroscience, dorsolateral striatum, motor skill learning, striatum, spatiotemporal dynamics, General Biochemistry, Genetics and Molecular Biology, Corpus Striatum, Neostriatum, Motor Skills, CP: Neuroscience, plasticity, Learning, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], neuronal populations, dorsomedial striatum, [STAT.ME]Statistics [stat]/Methodology [stat.ME]
Abstract

International audience; Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report that highly active (HA) striatal populations arise from distinct spatiotemporal reorganization in the dorsomedial (DMS) and dorsolateral (DLS) striatum networks and are correlated with learning performance. The DMS overall activity decreases in early training, with few and sparsely distributed HA cells, while the DLS shows a progressive and long-lasting formation of HA cell clusters. These reorganizations result from reinforcement of synaptic connections to the DMS and anatomical rearrangements to the DLS. Targeted silencing of DMS or DLS HA cells with the cFos-TRAP strategy strongly impairs individual performance. Our data reveal that discrete domains of striatal populations encode acquisition and long-lasting retention of a motor skill.

Published
2021
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18. Anomalous Left Coronary Artery Connected to the Pulmonary Artery in a 15-Year-Old Girl: Case Report and Discussion on Secondary Prevention of Sudden Death

Author

Laïk, Jérémy, Fouilloux, Virginie, Aldebert, Philippe, Koutbi, Linda, Hourdain, Jérôme, De Swardt, Philippe, Tiger, Fabrice, Bellemain-Appaix, Anne, Bernasconi, François, and Jacq, Laurent

Subjects
Article Subject, cardiovascular system
Abstract

Background. Anomalous left coronary artery connected to the pulmonary artery (ALCAPA) is a rare congenital heart disease. Adaptive development of sufficient heterocoronary collaterality in the newborn may allow survival to a later age. In older children or adults, malignant ventricular arrhythmias can reveal the disease. Case Report. A 15-year-old girl was referred to the local hospital after a resuscitated out-of-hospital cardiac arrest. CT scan and coronary angiography revealed an ALCAPA. Direct aortic reimplantation of the left coronary artery was performed. Postoperative ECG monitoring showed short episodes of nonsustained ventricular tachycardia. Transthoracic echocardiography and cardiac MRI revealed subendocardial fibrosis of the anterolateral papillary muscle. Beta-blockade therapy was initiated at first intention. After hospital discharge, the patient reported several fainting without loss of consciousness. Considering sudden death nonrelated to effort, episodes of nonsustained ventricular tachycardia, and areas of myocardial fibrosis, the patient underwent subcutaneous cardioverter-defibrillator implantation. 6-month follow-up is satisfactory without clinical or rhythmic abnormalities. Discussion. Indication for surgical correction of ALCAPA is well defined, but rhythmic secondary prevention after resuscitated cardiac arrest is less consensual. Cardiac MRI is an essential tool in the identification of a potential rhythmic substrate and should be taken into account in the discussion of a preventive cardioverter-defibrillator implantation.

Published
2021
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19. Life-threatening and major cardiac events during long-distance races: updates from the prospective RACE PARIS registry with a systematic review and meta-analysis

Author

Hazrije Mustafic, Jacques Monsegu, Anne Bellemain-Appaix, Thomas Levasseur, Jean-Philippe Collet, Lionel Lamhaut, Paul Guedeney, Benoît Gerardin, Hakim Benamer, Gilles Montalescot, Pierre Aubry, Centre Chirurgical Marie Lannelongue (CCML), Centre chirurgical Marie Lannelongue, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Foch [Suresnes], Groupe Hospitalier Mutualiste [Grenoble] (GHM), SAMU 75 [Paris], CIC - CHU Bichat, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], air pollution, Long distance running, 030204 cardiovascular system & hematology, Sudden cardiac death, Running, 03 medical and health sciences, Race (biology), 0302 clinical medicine, sudden cardiac arrest, Case fatality rate, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Registries, Intensive care medicine, Stroke, business.industry, Medical record, Incidence (epidemiology), Sudden cardiac arrest, medicine.disease, 3. Good health, Heart Arrest, Death, Sudden, Cardiac, Meta-analysis, medicine.symptom, Cardiology and Cardiovascular Medicine, business, sport
Abstract

Aims Limited data exist regarding the incidence and aetiology of life-threatening events such as major cardiac events or exertional heat stroke during long-distance races. We aimed to provide an updated incidence, etiology and prognosis of life-threatening events during long-distance races. Methods The prospective RACE PARIS registry recorded all life-threatening events/fatal events occurring during 46 marathons, half-marathons and other long-distance races in the Paris area between 2006 and 2016, comprising 1,073,722 runners. Event characteristics were determined by review of medical records and interviews with survivors. Results The incidence of life-threatening events, exertional heat stroke and major cardiac events was 3.35 per 100,000, 1.02 per 100,000 and 2.33 per 100,000, respectively, including 18 sudden cardiac arrests (1.67 per 100,000). The main aetiology of sudden cardiac arrest was myocardial ischaemia (11/18), due to acute coronary thrombosis (6/11), stable atherosclerotic coronary artery disease (2/11), coronary dissection (1/11), anomalous connection (1/11) or myocardial bridging (1/11). A third of participants with ischaemia-related major cardiac events presented with pre-race clinical symptoms. Major cardiac events were more frequent in the case of a high pollution index (6.78 per 100,000 vs. 2.07 per 100,000, odds ratio 3.27, 95% confidence interval 1.12–9.54). Case fatality was low (0.19 per 100,000). Similarly, we report in a meta-analysis of eight long-distance race registries comprising 16,223,866 runners a low incidence of long-distance race-related sudden cardiac arrest (0.82 per 100,000) and fatality (0.39 per 100,000). Death following sudden cardiac arrest was strongly associated with initial asystole or pulseless rhythm. Conclusion Long-distance race-related life-threatening events remain rare although serious events. Better information for runners on the risk of pre-race clinical symptoms, outside air pollution and temperature may reduce their incidence.

Published
2020
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20. Classification of neuron types from calcium imaging

Author

Becq, Guillaume, Badreddine, Nagham, Tremblay, Nicolas, Appaix, Florence, Zalcman, Gisela, Fino, Elodie, Achard, Sophie, GIPSA-Services (GIPSA-Services), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Communication Information and Complex Systems (GIPSA-CICS), Département Images et Signal (GIPSA-DIS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS ), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA-Services (GIPSA-Services [2016-2019]), Grenoble Images Parole Signal Automatique [2016-2019] (GIPSA-lab [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Centre National de la Recherche Scientifique (CNRS), GIPSA Pôle Géométrie, Apprentissage, Information et Algorithmes [2020-....] (GIPSA-GAIA [2020-....]), Grenoble Images Parole Signal Automatique [2020-....] (GIPSA-lab [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2020-....] (Grenoble INP [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2020-....] (UGA [2020-....])-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2020-....] (Grenoble INP [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU), Modelling and Inference of Complex and Structured Stochastic Systems [2016-2019] (MISTIS [2016-2019]), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Laboratoire Jean Kuntzmann [2016-2019] (LJK [2016-2019]), and Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing
Abstract

International audience; Videos of calcium activities of mice striatum slices are recorded under stimulations by two-photon fluorescence microscopy. Neurons are selected by regions of interests (ROI) on the images and labelled into two classes: medium spiny neuron (MSN); interneurons (IN). Each ROI enables to obtain a neural signal. Features are extracted on these ROI and signals. A subset feature selection is performed with a quadratic discriminant analysis, to solve the supervised learning of the two classes of neuron of the striatum. It is shown, that a realistic evaluation of the database leads to a classification with an accuracy of 75 % for IN and 90% for MSN.; Les activités calciques de neurones dans des tranches de striatum de souris sont enregistrées en réponse à des stimulations sous forme de films par microscopie de fluorescence biphoton. Les neurones sont répérés sur les images sous forme de régions d'intérêt (ROI) et étiquetés suivant deux classes: neurone épineux moyen (medium spiny neuron, MSN) ; interneurone (interneuron, IN). L'analyse des ROI permet de calculer les signaux calciques neuronaux. Des caractéristiques sont extraites sur ces ROI et sur ces signaux calciques. Une recherche des caractéristiques pertinentes est proposée en utilisant une analyse discriminante quadratique sur la base d'un apprentissage supervisé des deux classes de neurones du striatum. On montre qu'une évaluation réaliste de la base de données permet d'obtenir un taux de bonne classification de l'ordre de 75 % pour les IN, tout en obtenant un taux de bonne classification de l'ordre de 90 % pour les MSN.

Published
2019

21. [Interests and limitations of percutaneous coronary intervention strategy in nonagenarian patients: A single center experience]

Author

H, Sanoussi, N, Bitton, N, Kourireche, F, Bernasconi, A, Tounsi, A, Bellemain-Appaix, and L, Jacq

Subjects
Aged, 80 and over, Male, Percutaneous Coronary Intervention, Time Factors, Treatment Outcome, Humans, Female, Coronary Artery Disease, Retrospective Studies
Abstract

To expose our center results in the angioplasty in nonagenarians and to evaluate its effectiveness but also the MACEs and the mortality in the short and long term.A retrospective study of 98 patients admitted to the Antibes hospital center from November 2013 to September 2018.The median age was 91.8 [90.8-93.4]. 52.6% was male. 9.7% of the patients had a polyvascular site. 50.6% of patients had moderate renal failure. The radial approach was used in 88.4% of cases. 21.6% of patients had tri-truncal lesions, while 46.4% were monotruncular, LAD artery was the culprit artery in 67% of cases. One stent per lesion was used in the majority of cases. Our successful rate was 90%. After angioplasty, 96% of the patients underwent double antiaggregation platelet therapy, 74.4% under clopidogrel. The presence of arrhythmias before angioplasty, the femoral approach, the coronary dissection and cardiogenic shock after angioplasty were predictors of short- and long-term mortality. Diabetes, history of myocardial infarction, impaired left ventricular ejection fraction, calcified coronary lesions, occurrence of arrhythmias or signs of heart failure on post-procedure were predictors of MACE occurrence.This study demonstrates that angioplasty in selected population of nonagenarians is perfectly feasible with a good risk/benefit ratio and specifies the different predictors of MACE, both short- and long-term mortality.

Published
2019

22. Classification of neuron types from calcium imaging

Author

Becq, Guillaume, Badreddine, Nagham, Tremblay, Nicolas, Appaix, Florence, Zalcman, Gisela, Fino, Elodie, Achard, Sophie, Becq, Guillaume, GIPSA-Services (GIPSA-Services), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Communication Information and Complex Systems (GIPSA-CICS), Département Images et Signal (GIPSA-DIS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS ), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA-Services (GIPSA-Services [2016-2019]), Grenoble Images Parole Signal Automatique [2016-2019] (GIPSA-lab [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Centre National de la Recherche Scientifique (CNRS), GIPSA Pôle Géométrie, Apprentissage, Information et Algorithmes [2020-....] (GIPSA-GAIA [2020-....]), Grenoble Images Parole Signal Automatique [2020-....] (GIPSA-lab [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2020-....] (Grenoble INP [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2020-....] (UGA [2020-....])-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2020-....] (Grenoble INP [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....])-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU), Modelling and Inference of Complex and Structured Stochastic Systems [2016-2019] (MISTIS [2016-2019]), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Laboratoire Jean Kuntzmann [2016-2019] (LJK [2016-2019]), and Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing
Abstract

Videos of calcium activities of mice striatum slices are recorded under stimulations by two-photon fluorescence microscopy. Neurons are selected by regions of interests (ROI) on the images and labelled into two classes: medium spiny neuron (MSN); interneurons (IN). Each ROI enables to obtain a neural signal. Features are extracted on these ROI and signals. A subset feature selection is performed with a quadratic discriminant analysis, to solve the supervised learning of the two classes of neuron of the striatum. It is shown, that a realistic evaluation of the database leads to a classification with an accuracy of 75 % for IN and 90% for MSN., Les activités calciques de neurones dans des tranches de striatum de souris sont enregistrées en réponse à des stimulations sous forme de films par microscopie de fluorescence biphoton. Les neurones sont répérés sur les images sous forme de régions d'intérêt (ROI) et étiquetés suivant deux classes: neurone épineux moyen (medium spiny neuron, MSN) ; interneurone (interneuron, IN). L'analyse des ROI permet de calculer les signaux calciques neuronaux. Des caractéristiques sont extraites sur ces ROI et sur ces signaux calciques. Une recherche des caractéristiques pertinentes est proposée en utilisant une analyse discriminante quadratique sur la base d'un apprentissage supervisé des deux classes de neurones du striatum. On montre qu'une évaluation réaliste de la base de données permet d'obtenir un taux de bonne classification de l'ordre de 75 % pour les IN, tout en obtenant un taux de bonne classification de l'ordre de 90 % pour les MSN.

Published
2019

23. Prospective study in young women presenting acute MYOCARDIAL infarction in France: Clinical, morphological and biological descriptive analysis: WAMIF Study

Author

Stéphanie Marlière, Ludovic Drouet, Claire Mounier-Vehier, T. Bergot, Francis Couturaud, Yves Cottin, Stéphane Manzo-Silberman, C. Bal Dit Sollier, Anne Bellemain-Appaix, Martine Gilard, Hélène Eltchaninoff, Pascal Motreff, A. Gompel, E. Vautrin, and S. Uhry

Subjects
medicine.medical_specialty, Nausea, business.industry, ST elevation, Incidence (epidemiology), medicine.disease, Chest pain, Internal medicine, medicine, Vomiting, Myocardial infarction, Family history, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Prospective cohort study
Abstract

Background However, women younger than 50 years accounted for 11% of MI admitted in hospital and their incidence is increasing. Purpose The main objective of this study is to systematically collect and describe clinical, morphological and biological characteristics, in hospital mortality and 12 months outcomes. Methods and Results We performed a clinical prospective observational multicenter study including all female patients admitted for MI under the age of 50. Three hundred and fourteen patients were included in twenty-eight participating centers. Mean age was 42.9 (±5.7) years old. One hundred and ninety two presented with ST elevation MI and One hundred and twenty two with non ST elevation MI. A total of 75% were active smokers, 14.6% had diabetes, 26.4% high blood pressure but only 15.3% with antihypertensive therapy, 35% had a family history of cardiovascular disease. Their specific risk factor included 33% of prior complication of pregnancy, 45.5% were under hormonal contraception 15.6% were already menopaused. Among STEMI patient 90.6% presented with typical chest pain and 58.9% reported also associated symptoms (nausea, vomiting, asthenia, sweats, dizziness or palpitation). A total of 10.4% reported prior symptoms for more than 1 week before. At admission, 13% presented with cardiac arrest. Interestingly, for STEMI patients, pre-hospital antiplatelet drugs were not systematically administered. At angiography, normal coronary angiogram was found in 6.8% of STEMI and 10.7% of NSTEMI. 29.6% of the patients included had significant multivessel disease despite their young age. Spontaneous coronary artery dissection was reported in 14.6% of STEMI and 20.5% of NSTEMI. No death, but 3 strokes, 3 recurrences of MI and 1 serious bleeding occurred during the hospitalization. Conclusion A comprehensive and systematized analysis of MI in young woman would improve our understanding and enable physician to offer patients a more appropriate therapeutic and monitoring.

Published
2021
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24. Microscopic DTI accurately identifies early glioma cell migration: correlation with multimodal imaging in a new glioma stem cell model

Author

Michele El-Atifi, Boudewijn van der Sanden, François Berger, Karin Pernet-Gallay, Hana Lahrech, Florence Appaix, Ulysse Gimenez, Adriana-T. Perles-Barbacaru, and Arnaud Millet

Subjects
Pathology, medicine.medical_specialty, Chemistry, Brain tumor, Cell migration, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, In vivo, Glioma, Fractional anisotropy, medicine, Molecular Medicine, Radiology, Nuclear Medicine and imaging, Stem cell, 030217 neurology & neurosurgery, Spectroscopy, Ex vivo, Diffusion MRI
Abstract

Monitoring glioma cell infiltration in the brain is critical for diagnosis and therapy. Using a new glioma Glio6 mouse model derived from human stem cells we show how diffusion tensor imaging (DTI) may predict glioma cell migration/invasion. In vivo multiparametric MRI was performed at one, two and three months of Glio6 glioma growth (Glio6 (n = 6), sham (n = 3)). This longitudinal study reveals the existence of a time window to study glioma cell/migration/invasion selectively. Indeed, at two months only Glio6 cell invasion was detected, while tumor mass formation, edema, blood-brain barrier leakage and tumor angiogenesis were detected later, at three months. To robustly confirm the potential of DTI for detecting glioma cell migration/invasion, a microscopic 3D-DTI (80 μm isotropic spatial resolution) technique was developed and applied to fixed mouse brains (Glio6 (n = 6), sham (n = 3)). DTI changes were predominant in the corpus callosum (CC), a known path of cell migration. Fractional anisotropy (FA) and perpendicular diffusivity (D⊥ ) changes derived from ex vivo microscopic 3D-DTI were significant at two months of tumor growth. In the caudate putamen an FA increase of +38% (p < 0.001) was observed, while in the CC a - 28% decrease in FA (p < 0.005) and a + 95% increase in D⊥ (p < 0.005) were observed. In the CC, DTI changes and fluorescent Glio6 cell density obtained by two-photon microscopy in the same brains were correlated (p < 0.001, r = 0.69), validating FA and D⊥ as early quantitative biomarkers to detect glioma cell migration/invasion. The origin of DTI changes was assessed by electron microscopy of the same tract, showing axon bundle disorganization. During the first two months, Glio6 cells display a migratory phenotype without being associated with the constitution of a brain tumor mass. This offers a unique opportunity to apply microscopic 3D-DTI and to validate DTI parameters FA and D⊥ as biomarkers for glioma cell invasion.

Published
2016
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25. Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial

Author

Marie Plissonneau, Alexandre Detappe, Florence Appaix, Vu-Long Tran, Shady Kotb, Claire Rodriguez-Lafrasse, François Lux, Ross Berbeco, Florence Lefranc, Lucie Sancey, Emmanuel L. Barbier, Olivier Tillement, Hélène Gehan, Camille Verry, Rayet, Béatrice, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Radiation Oncology, Department of RBrigham and Women’s Hospital, Dana-Farber Cancer Institute, and Harvard Medical School, Nano-H SAS, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurosurgery, Erasmus University Hospital, Erasmus University Hospital, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de Physique Nucléaire de Lyon (IPNL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)

Subjects
Pathology, Gadolinium, medicine.medical_treatment, Contrast Media, Medicine (miscellaneous), Nanoparticle, Phases of clinical research, 02 engineering and technology, radiation therapy, 0302 clinical medicine, brain metastases, Melanoma, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), medicine.diagnostic_test, Brain Neoplasms, personalized medicine, Sciences bio-médicales et agricoles, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, 3. Good health, Radiation therapy, AGuIX, Imaged-guided therapy, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], 0210 nano-technology, Research Paper, medicine.medical_specialty, Radiosensitizer, chemistry.chemical_element, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, radiosensitizer, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], business.industry, Brain metastases, Magnetic resonance imaging, medicine.disease, Personalized medicine, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Cancer research, Nanoparticles, nanoparticles, Sciences pharmaceutiques, imaged-guided therapy, Positive Contrast Agent, business, Radiotherapy, Image-Guided
Abstract

Nanoparticles containing high-Z elements are known to boost the efficacy of radiation therapy. Gadolinium (Gd) is particularly attractive because this element is also a positive contrast agent for MRI, which allows for the simultaneous use of imaging to guide the irradiation and to delineate the tumor. In this study, we used the Gd-based nanoparticles, AGuIX®. After intravenous injection into animals bearing B16F10 tumors, some nanoparticles remained inside the tumor cells for more than 24 hours, indicating that a single administration of nanoparticles might be sufficient for several irradiations. Combining AGuIX® with radiation therapy increases tumor cell death, and improves the life spans of animals bearing multiple brain melanoma metastases. These results provide preclinical proof-of-concept for a phase I clinical trial., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016
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26. P1722Platelet function monitoring for the prediction of clinical outcomes: a pooled analysis of the randomized ARCTIC and ANTARCTIC trials

Author

Simon Elhadad, G Montalescot, J. Silvain, Thomas Cuisset, Yan Yan, Eric Vicaut, B Lattuca, Anne Bellemain-Appaix, Stéphane Manzo-Silberman, J P Collet, Grégoire Rangé, Florence Leclercq, Christophe Pouillot, Guillaume Cayla, and M. Kerneis

Subjects
medicine.medical_specialty, Pooled analysis, Arctic, business.industry, Internal medicine, medicine, Function (mathematics), Cardiology and Cardiovascular Medicine, business
Published
2018
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27. The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary intervention for ST-elevation myocardial infarction: a systematic review and meta-analysis

Author

Kenneth Ducci, Stephen D. Wiviott, Johanne Silvain, Céline Bégué, Deepak L. Bhatt, Anne Bellemain-Appaix, Jean-Philippe Collet, Robert A. Harrington, Michel Cucherat, Gilles Montalescot, François Bernasconi, Matthew T. Roe, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), VA Boston Healthcare System, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]

Subjects
medicine.medical_specialty, medicine.medical_treatment, Myocardial Infarction, Platelet Glycoprotein GPIIb-IIIa Complex, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, Internal medicine, medicine, Clinical endpoint, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, ComputingMilieux_MISCELLANEOUS, business.industry, Percutaneous coronary intervention, Thrombolysis, medicine.disease, 3. Good health, Meta-analysis, Conventional PCI, Cardiology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Purinergic P2Y Receptor Antagonists, ST Elevation Myocardial Infarction, Cardiology and Cardiovascular Medicine, business, TIMI, Mace, Platelet Aggregation Inhibitors
Abstract

Aims The aim of this meta-analysis was to compare the benefit of "early" vs. "delayed" P2Y12 inhibition in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Methods and results We conducted a meta-analysis including seven randomised controlled trials (RCTs) which compared early vs. delayed P2Y12inhibition in STEMI patients scheduled for PCI, providing data on major adverse cardiac events (MACE), all-cause death, and major bleeding. The primary endpoint was MACE. Secondary endpoints included stent thrombosis and the use of GP IIb/IIIa inhibitors (GPI). All endpoints were analysed at the shortest follow-up available. A total of 9,648 patients were included ("early"=4,792, "delayed"=4,856). "Early" P2Y12 inhibition was associated with a significant reduction in MACE rate (OR 0.73, 95% CI: 0.61-0.88, p=0.0008), myocardial infarction (OR 0.71, 95% CI: 0.57-0.90, p=0.004), bail-out GPI use (OR 0.87, 95% CI: 0.75-1.00, p=0.04) and improved coronary reperfusion before PCI (OR for Thrombolysis In Myocardial Infarction [TIMI] flow grade 2-3=1.12, 95% CI: 1.00-1.26, p=0.04). Major bleeding was not increased (OR 0.87, 95% CI: 0.62-1.21, p=0.41). Conclusions A strategy of early effective P2Y12 inhibition in PCI of STEMI appears to improve coronary reperfusion before PCI, and reduce MACE, MI and bail-out GPI use without increase of major bleeding.

Published
2018
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28. Registry on acute cardiovascular events during endurance running races: the prospective RACE Paris registry

Author

Benoît Gerardin, Catherine Fleischel, Hakim Benamer, Hazrije Mustafic, Anne Bellemain-Appaix, Lionel Lamhaut, Jean-Philippe Collet, Jacques Monsegu, Bernard Livarek, Emmanuel Teiger, Pierre Aubry, and M. Jaffry

Subjects
Adult, Male, Paris, Pediatrics, medicine.medical_specialty, Acute coronary syndrome, 030204 cardiovascular system & hematology, Sudden death, Running, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Case fatality rate, Humans, Medicine, Prospective Studies, Registries, 030212 general & internal medicine, Treadmill, business.industry, Incidence (epidemiology), Medical record, Hypertrophic cardiomyopathy, medicine.disease, Surgery, Death, Sudden, Cardiac, Etiology, Cardiology and Cardiovascular Medicine, business
Abstract

Aim Long distance running races are associated with a low risk of life-threatening events much often attributed to hypertrophic cardiomyopathy. However, retrospective analyses of aetiology lack consistency. Methods and results Incidence and aetiology of life-threatening/fatal events were assessed in long distance races in the prospective Registre des Accidents Cardiaques lors des courses d'Endurance (RACE Paris Registry) from October 2006 to September 2012. Characteristics of life-threatening/fatal events were analysed by interviewing survivors and reviewing medical records including post-mortem data of each case. Seventeen life-threatening events were identified of 511 880 runners of which two were fatal. The vast majority were cardiovascular events (13/17) occurring in experienced male runners [mean (±SD) age 43 ± 10 years], with infrequent cardiovascular risk factors, atypical warning symptoms prior to the race or negative treadmill test when performed. Acute myocardial ischaemia was the predominant aetiology (8 of 13) and led to immediate myocardial revascularization. All cases with initial shockable rhythm survived. There was no difference in event rate according to marathons vs. half-marathons and events were clustered at the end of the race. A meta-analysis of all available studies including the RACE Paris registry ( n = 6) demonstrated a low prevalence of life-threatening events (0.75/100 000) and that presentation with non-shockable rhythm [OR = 29.9; 95% CI (4.0–222.5), P = 0.001] or non-ischaemic aetiology [OR = 6.4; 95% CI (1.4–28.8), P = 0.015] were associated with case-fatality. Conclusion Life-threatening/fatal events during long distance races are rare, most often unpredictable and mainly due to acute myocardial ischaemia. Presentation with non-shockable rhythm and non-ischaemic aetiology are the major determinant of case fatality.

Published
2015
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29. Colchicine for postoperative pericardial effusion: a multicentre, double-blind, randomised controlled trial

Author

P, Meurin, S, Lelay-Kubas, B, Pierre, H, Pereira, B, Pavy, M C, Iliou, J L, Bussière, H, Weber, J P, Beugin, T, Farrokhi, A, Bellemain-Appaix, L, Briota, J Y, Tabet, and Delphine Hourton, Keslick

Subjects
Male, medicine.medical_specialty, Placebo, Pericardial effusion, Pericardial Effusion, law.invention, Postoperative Complications, Acute pericarditis, Double-Blind Method, Randomized controlled trial, law, Cardiac tamponade, medicine, Humans, Cardiac Surgical Procedures, Aged, business.industry, Middle Aged, medicine.disease, Tubulin Modulators, Cardiac Tamponade, Surgery, Cardiac surgery, Treatment Outcome, Effusion, Echocardiography, Female, Tamponade, Drug Monitoring, Colchicine, Cardiology and Cardiovascular Medicine, business
Abstract

Objectives Pericardial effusion is common after cardiac surgery. Growing evidence suggests that colchicine may be useful for acute pericarditis, but its efficacy in reducing pericardial effusion volume postoperatively has not been assessed. Methods This randomised, double-blind, placebo-controlled study conducted in 10 centres in France included 197 patients at high risk of tamponade (ie, with moderate to large-sized persistent effusion (echocardiography grades 2, 3 or 4 on a scale of 0–4)) at 7–30 days after cardiac surgery. Patients were randomly assigned to receive colchicine, 1 mg daily (n=98), or a matching placebo (n=99). The main end point was change in pericardial effusion grade after 14-day treatment. Secondary end points included frequency of late cardiac tamponade. Results The placebo and the colchicine groups showed a similar mean baseline pericardial effusion grade (2.9±0.8 vs 3.0±0.8) and similar mean decrease from baseline after treatment (−1.1±1.3 vs −1.3±1.3 grades). The mean difference in grade decrease between groups was −0.19 (95% CI −0.55 to 0.16, p=0.23). In total, 13 cases of cardiac tamponade occurred during the 14-day treatment (7 and 6 in the placebo and colchicine groups, respectively; p=0.80). At 6-month follow-up, all patients were alive and had undergone a total of 22 (11%) drainages: 14 in the placebo group and 8 in the colchicine group (p=0.20). Conclusions In patients with pericardial effusion after cardiac surgery, colchicine administration does not reduce the effusion volume or prevent late cardiac tamponade. Clinical trial reg No NCT01266694.

Published
2015
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30. Keto-polymethines: a versatile class of dyes with outstanding spectroscopic properties for in cellulo and in vivo two-photon microscopy imaging

Author

San-Hui Chi, Boudewijn van der Sanden, Olivier Maury, Denis Jacquemin, Chantal Andraud, Joseph W. Perry, Alexei Grichine, Cyrille Monnereau, Alain Duperray, Boris Le Guennic, Jérôme Cuny, Simon Pascal, Florence Appaix, Sandrine Denis-Quanquin, Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPHY-DYFCOM, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), INSERM U823, équipe 8 (Immunologie Analytique des Pathologies Chroniques), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Modélisation, Agrégats, Dynamique (LCPQ) (MAD), Laboratoire de Chimie et Physique Quantiques (LCPQ), Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), School of Chemistry and Biochemistry, and Center for Organic Electronics and Photonics, Georgia Institute of Technology [Atlanta], D. J. acknowledges the ERC for financial support in the framework of a Starting Grant (Marches – 278845). J. W. P. and S.-H. C. acknowledge the support from the DARPA ZOE Program (W31P4Q-09-1-0012), and the AFOSR MURI (FA9550-10-1-0558)., Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), DYnamique des Fluides COmplexes et Morphogénèse [Grenoble] (DYFCOM-LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Elefantis, Nicolas, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Chemistry, Stereochemistry, Hydrogen bond, Quantum yield, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, Photochemistry, 01 natural sciences, Fluorescence, 0104 chemical sciences, Molecular engineering, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Molecular dynamics, Membrane, Two-photon excitation microscopy, Molecule, 0210 nano-technology
Abstract

International audience; The synthesis of keto-heptamethine derivatives has been expanded to various new symmetrical and asymmetrical structures, including an unprecedented di-anionic keto-polymethine. The spectroscopic behavior of these new dyes has been systematically and thoroughly investigated, revealing that the formation of hydrogen bond interactions with protic solvents is responsible for a dramatic enhancement of the fluorescence quantum yield in the far-red spectral region. The existence of these strong hydrogen-bond interactions was further confirmed by molecular dynamics simulations. These bis-dipolar polymethines exhibit large two-photon absorption (TPA) cross-sections (σ2 in GM) in the near-infrared, making them ideal candidates for NIR-to-NIR two-photon microscopy imaging applications. We demonstrate that the molecular engineering of the hydrophilic/hydrophobic balance enables targeting of different cellular components, such as cytoplasm or cell membranes. Addition of appropriate substituents provides the molecule with high-water-solubility, affording efficient two-photon probes for angiography.

Published
2017
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31. Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages

Author

Boudewijn van der Sanden, Florence Appaix, Talitha Fernandes Stefanello, Celso Vataru Nakamura, Rachel Auzély-Velty, Lauriane Hamard, Anna Szarpak-Jankowska, Bruno G. De Geest, and Benoit Louage

Subjects
Materials science, Proton Magnetic Resonance Spectroscopy, Biomedical Engineering, Nanogels, Spleen, Biochemistry, Fluorescence, Cell Line, Polyethylene Glycols, Biomaterials, Mice, chemistry.chemical_compound, In vivo, Hyaluronic acid, medicine, Animals, Polyethyleneimine, Hyaluronic Acid, Particle Size, Molecular Biology, Drug Carriers, Photons, Macrophages, Temperature, General Medicine, Endocytosis, In vitro, medicine.anatomical_structure, chemistry, Drug delivery, Drug carrier, Hydrophobic and Hydrophilic Interactions, Ethylene glycol, Intracellular, Biotechnology
Abstract

Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases.

Published
2014
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32. Platelet function testing predicts bleeding complications in elderly patients admitted for an acute coronary syndrome: insights from the ANTARCTIC trial

Author

Pierre Sabouret, Pascal Motreff, Guillaume Cayla, Gilles Montalescot, Thomas Cuisset, Abdourahmane Diallo, Olivier Varenne, J P Collet, J. Silvain, Jean-Louis Bonnet, Eric Vicaut, Ziad Boueri, B Lattuca, Farzin Beygui, Anne Bellemain-Appaix, ProdInra, Migration, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Sorbonne Universités (COMUE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Antibes - Juan-les-Pins, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Bastia, Partenaires INRAE, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Invasive strategy, Acute coronary syndrome, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Prasugrel, Randomization, business.industry, Significant difference, Coronary stenting, 030204 cardiovascular system & hematology, medicine.disease, Clopidogrel, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Platelet, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Background Elderly patients are at high-risk of bleedings, particularly in the setting of acute coronary syndrome treated with an invasive strategy. Treatment adjustment by platelet function testing (PFT) failed to improve clinical outcomes in the randomized ANTARCTIC trial. Purpose This prespecified substudy aims at determining the predictive value of PFT on occurrence of bleedings. Methods We analyzed the 877 patients over the age of 75 years included in the ANTARCTIC trial and randomized to a strategy of dose or drug antiplatelet therapy adjustment or a conventional “one size fits all” strategy without PFT. In the monitoring group, patients received prasugrel 5 mg daily after coronary stenting and PFT was done 14 days after randomization and repeated 14 days after treatment adjustment. Occurrence of bleedings was collected up to one year and correlated with PFT. Results Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n = 181 patients) with one third occurring in the first month. Cutaneous and gastro-intestinal bleedings were the two predominant complications. There was no significant difference in the final treatment between patients with or without clinically relevant bleedings (respectively, clopidogrel 75 mg: 19.9% and 19.6%, prasugrel 5 mg: 77.3% and 77.9%, prasugrel 10 mg: 2.6% and 2.8%; P = 0.91) The main predictive factors of major bleedings in multivariate model were age > 85 years [adj.HR(95% CI): 2.48(1.25;4.91); P = 0.0093] and hemoglobin level (per gram of decrease) [adj.HR(95% CI): 1.45(1.18;1.79); P = 0.0004]. The last PFT was an independent predictive factor of clinically relevant bleedings (adj.HR(95% CI): 0.95(0.90;0.99); P = 0.017). Conclusion Clinically relevant bleedings were frequent in elderly patients in the setting of acute coronary syndrome. PFT did not improve clinical outcomes but identified the bleeding risk of these patients when the chronic treatment was installed.

Published
2019
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33. Platelet function monitoring for the prediction of clinical outcomes: A pooled analysis of the randomized ARCTIC and ANTARCTIC trials

Author

Thomas Cuisset, Simon Elhadad, Grégoire Rangé, Florence Leclercq, J. Silvain, B Lattuca, Christophe Pouillot, Guillaume Cayla, Yan Yan, Stéphane Manzo-Silberman, Eric Vicaut, M. Kerneis, Gilles Montalescot, J P Collet, and Anne Bellemain-Appaix

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Population, medicine.disease, law.invention, Coronary artery disease, Pooled analysis, P2Y12, Randomized controlled trial, law, Internal medicine, Clinical endpoint, Medicine, Platelet, Risk factor, Cardiology and Cardiovascular Medicine, business, education
Abstract

Background Platelet function testing offers the possibility to individualize antiplatelet therapy in coronary artery disease patients but failed to improve clinical outcomes in randomized trials. However, high-on-treatment platelet reactivity (HPR) remains a risk factor for recurrent ischemic events and low-on-treatment platelet reactivity (LPR) is a risk factor for bleedings. Methods We collected data of patients assigned to the monitoring arm of the randomized ARCTIC and ANTARCTIC trials that evaluated the platelet reactivity by the VerifyNow P2Y12 test two weeks after coronary stenting. HPR was defined by PRU ≥ 208, LPR by PRU ≤ 85 and optimal platelet reactivity (OPR) by 85. Results Among the 1418 patients included, HPR was present in 269 patients (18.9%), OPR was reached in 681 patients (48.0%) and LPR in 468 patients (33.0%). The primary composite endpoint occurred in 9.7%, 11.5% and 14.3% respectively. There was no significant difference in the net clinical benefit between HPR and OPR patients (adjusted HR: 0.91(0.48–1.72); P = 0.77) and between LPR and OPR patients (adjusted HR: 1.13 (0.67–1.90); P = 0.64). There were no difference in the individual clinical endpoints between the three groups. ROC curve analysis demonstrated that PRU when used for treatment adjustment has a limited ability to discriminate net clinical benefit, ischemic or bleeding complications (curve–c index = 0.55, 0.51 or 0.59, respectively). Conclusion Two weeks after stenting, an optimal platelet reactivity was obtained in less than half of the population. The net clinical benefit of these patients was not different from that of patients with HPR and LPR who had treatment adjustment.

Published
2019
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34. Optimal time for catheterization in NSTE-ACS patients with impaired renal function

Author

O. Barthelemy, Gilles Montalescot, J P Collet, Georges Sideris, Eric Vicaut, Guillaume Cayla, Johanne Silvain, Anne Bellemain-Appaix, Olivier Varenne, Farzin Beygui, and Stephen A. O’Connor

Subjects
education.field_of_study, medicine.medical_specialty, business.industry, Insulin, medicine.medical_treatment, Population, Renal function, Time optimal, Clopidogrel, Surgery, Impaired renal function, Internal medicine, Conventional PCI, Cardiology, Medicine, Cardiology and Cardiovascular Medicine, business, education, Nste acs, medicine.drug
Abstract

Background To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. Methods We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance Results Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p =0.043) and non-CABG MB (9.3% vs. 2.2%, p =0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p =0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. Conclusion IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.

Published
2013
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35. Translation of the ecological trap concept to glioma therapy: the cancer cell trap concept

Author

Didier Wion, Jean-Paul Issartel, Boudewijn van der Sanden, François Berger, Laurent Selek, and Florence Appaix

Subjects
Cancer Research, Cancer therapy, Biology, Article, Trap (computing), 03 medical and health sciences, 0302 clinical medicine, Glioma, Tumor Microenvironment, medicine, Animals, Humans, Local population, 030304 developmental biology, 0303 health sciences, Ecology, fungi, food and beverages, General Medicine, medicine.disease, Data science, Oncology, 030220 oncology & carcinogenesis, Neoplasm Recurrence, Local, Ecological trap
Abstract

Viewing tumors as ecosystems offers the opportunity to consider how ecological concepts can be translated to novel therapeutic perspectives. The ecological trap concept emerged approximately half a century ago when it was observed that animals can prefer an environment of low quality for survival over other available environments of higher quality. The presence of such a trap can drive a local population to extinction. The cancer cell trap concept is the translation of the ecological trap into glioma therapy. It exploits and diverts the invasive potential of glioma cells by guiding their migration towards specific locations where a local therapy can be delivered efficiently. This illustrates how an ecological concept can change therapeutic obstacles into therapeutic tools.

Published
2013
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36. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo

Author

Valentin-Adrian Maraloiu, Florence Appaix, Alexis Broisat, Dominique Le Guellec, Valentin Serban Teodorescu, Catherine Ghezzi, Boudewijn van der Sanden, and Marie Genevieve Blanchin

Subjects
0303 health sciences, 03 medical and health sciences, 02 engineering and technology, 021001 nanoscience & nanotechnology, 0210 nano-technology, 030304 developmental biology
Published
2016
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37. Women in interventional cardiology: The French experience

Author

A Bellemain-Appaix, E. Vautrin, Stéphanie Marlière, Martine Gilard, and Stéphane Manzo-Silberman

Subjects
Adult, medicine.medical_specialty, Cardiac Catheterization, medicine.medical_treatment, education, Population, Cardiology, Coronary Disease, 030204 cardiovascular system & hematology, Career plan, Health Services Accessibility, 03 medical and health sciences, Physicians, Women, 0302 clinical medicine, Child Rearing, Sex Factors, Epidemiology, medicine, Humans, Medical physics, 030212 general & internal medicine, Child, Radiometry, Gender equality, education.field_of_study, Child rearing, Interventional cardiology, Career Choice, business.industry, Percutaneous coronary intervention, Mean age, Middle Aged, Family medicine, Female, France, Cardiology and Cardiovascular Medicine, business, Specialization
Abstract

Objectives Exploring the discrepancy in sex-ratio among interventional cardiologists by analysing the population of the female interventionalist. Background Despite an increase number of women who graduate from medical school in France during the last generation today, women represent only 24% of all cardiologists and 3% are interventional cardiologists. To face this international gender-based issue of interventional cardiology, committees were established in US (WIN) and recently within the EAPCI: the Women EAPCI chaired by Drs Mehilli and Mauri. In France, the Intervention’Elles committee emerged in order to participate in this concern. Methods As a first initiative, the Intervention’Elles group launched an e-survey to obtain information on the population of French female interventional cardiologists, focused on demography, work patterns, maternity and radiation exposure. Results Mean age is 40 years old (±7,4), 68% are working in large volume center, 28% have also structural interventional activity. Only 40% have left arm coverage. Despite 80% of French female interventional cardiologists wear personal dosimeters only 45% of them have a dosimetry feedback. Interestingly, even if 54% of women have children (mean: 1.9 ± 1) 28% of them report that childbearing had interfered with their career plan. Conclusion This questionnaire identifies for the first time the women population in interventional cardiology in France and highlights some of the issues encountered in more detail. This first descriptive step would help to develop strategies for attaining gender equality in interventional cardiology.

Published
2016

38. [Antiplatelet therapy in women: A gender-specificity?]

Author

A, Bellemain-Appaix

Subjects
Male, Clinical Trials as Topic, Sex Factors, Coronary Thrombosis, Humans, Female, Hemorrhage, Platelet Activation, Platelet Aggregation Inhibitors
Abstract

Women is a fragile and complex substet of patients, under-represented in clinical trials, but experiencing growing cardiovascular events, with higher mortality, delayed presentation, higher bleeding complications and undertreatment with antithrombotic therapies, compared to their male counterparts. Female gender has been associated with enhanced basal platelet reactivity, high residual on-treatment platelet reactivity and various responses to antiplatelet agents. Growing concern on gender-specificity has emerged, including potential difference in women compared with men on the benefits and risks of antiplatelet therapy in primary or secondary prevention and according the antiplatelet agent used. We provide here a review of available data on antiplatelet therapy in women.

Published
2016

39. A carbazole-substituted iridium complex as a solid state emitter for two-photon intravital imaging

Author

Jérôme Marrot, Cyrille Monnereau, Florence Appaix, Frédéric Dumur, Marc Lepeltier, Tangui Le Bahers, Yuan-Yuan Liao, Chantal Andraud, Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC)

Subjects
Intravital Microscopy, Infrared Rays, Carbazoles, Solid-state, chemistry.chemical_element, 02 engineering and technology, Iridium, 010402 general chemistry, Photochemistry, 01 natural sciences, Fluorescence, Inorganic Chemistry, Mice, chemistry.chemical_compound, Two-photon excitation microscopy, Coordination Complexes, Fluorescence microscope, Animals, Physical and Theoretical Chemistry, Fluorescent Dyes, Common emitter, Photons, Carbazole, Absorption cross section, Brain, [CHIM.MATE]Chemical Sciences/Material chemistry, Intravital Imaging, 021001 nanoscience & nanotechnology, 0104 chemical sciences, 3. Good health, chemistry, 0210 nano-technology
Abstract

A tris-cyclometalated iridium complex that bears two ligands functionalized by peripheral carbazole groups combines an intense solid state emission and a significant two-photon absorption cross section in the near-infrared. After incorporation into a physiological micellar suspension, it can be used for the intravital two-photon fluorescence microscopy of cerebral vasculature.

Published
2016
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40. A Fluorescent Polymer Probe with High Selectivity toward Vascular Endothelial Cells for and beyond Noninvasive Two-Photon Intravital Imaging of Brain Vasculature

Author

Marek Samoc, Bastien Mettra, A. Leung, Florence Appaix, Katarzyna Matczyszyn, T. Le Bahers, B. van der Sanden, Joanna Olesiak-Banska, Cyrille Monnereau, Chantal Andraud, Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Physical and Theoretical Chemistry, Wroclaw University of Science and Technology, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Brain vasculature, Intravital Microscopy, Polymers, Nanotechnology, 02 engineering and technology, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, Two-photon absorption, Two-photon excitation microscopy, Microscopy, General Materials Science, Fluorescent Dyes, Photons, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Brain, Endothelial Cells, [CHIM.CATA]Chemical Sciences/Catalysis, [CHIM.MATE]Chemical Sciences/Material chemistry, Chromophore, 021001 nanoscience & nanotechnology, Fluorescence, 0104 chemical sciences, Staining, Biophysics, 0210 nano-technology, Intravital microscopy
Abstract

International audience; A chromophore-engineering strategy that relies on the introduction of a ground-state distortion in a quadrupolar chromophore was used to obtain a quasi-quadrupolar chromophore with red emission and large two-photon absorption (2PA) cross-section in polar solvents. This molecule was functionalized with water-solubilizing polymer chains. It constitutes not only a remarkable contrast agent for intravital two-photon microscopy of the functional cerebral vasculature in a minimally invasive configuration but presents intriguing endothelial staining ability that makes it a valuable probe for premortem histological staining.

Published
2016
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41. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial

Author

Didier Carrié, Thomas Cuisset, Olivier Varenne, Hélène Rousseau, Christophe Pouillot, Stéphane Manzo-Silberman, Pierre Aubry, Johanne Silvain, Simon Elhadad, Rami El Mahmoud, Jean-Philippe Collet, Loic Belle, Nicolas Delarche, Patrick Henry, Anne Bellemain-Appaix, Florence Leclercq, Grégoire Rangé, Jean-Louis Bonnet, Farzin Beygui, Xavier Halna du Fretay, Jérémie Abtan, Gilles Montalescot, Eric Vicaut, Géraud Souteyrand, Ziad Boueri, Joe-Elie Salem, Eric Van Belle, Pascal Motreff, Guillaume Cayla, Pierre Sabouret, Benoit Lattuca, Christophe Saint-Etienne, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, Fondation Coeur et Recherche, Assistance Publique des Hopitaux de Paris (Paris, France), and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Prasugrel, Platelet Function Tests, medicine.medical_treatment, 030204 cardiovascular system & hematology, Risk Assessment, Drug Administration Schedule, law.invention, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, Randomized controlled trial, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Aged, Monitoring, Physiologic, Aged, 80 and over, Intention-to-treat analysis, Prasugrel Hydrochloride, business.industry, Percutaneous coronary intervention, General Medicine, medicine.disease, 3. Good health, Surgery, Editorial, Platelet aggregation inhibitor, Female, Stents, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Summary Background Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome. Methods We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01538446. Findings Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio [HR], 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups. Interpretation Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Funding Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

Published
2016
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42. Keto-polymethines: a versatile class of dyes with outstanding spectroscopic properties for

Author

Simon, Pascal, Sandrine, Denis-Quanquin, Florence, Appaix, Alain, Duperray, Alexei, Grichine, Boris, Le Guennic, Denis, Jacquemin, Jérôme, Cuny, San-Hui, Chi, Joseph W, Perry, Boudewijn, van der Sanden, Cyrille, Monnereau, Chantal, Andraud, and Olivier, Maury

Subjects
Chemistry, lipids (amino acids, peptides, and proteins)
Abstract

The keto-heptamethine family has been expanded to various symmetrical and asymmetrical structures., The synthesis of keto-heptamethine derivatives has been expanded to various new symmetrical and asymmetrical structures, including an unprecedented di-anionic keto-polymethine. The spectroscopic behavior of these new dyes has been systematically and thoroughly investigated, revealing that the formation of hydrogen bond interactions with protic solvents is responsible for a dramatic enhancement of the fluorescence quantum yield in the far-red spectral region. The existence of these strong hydrogen-bond interactions was further confirmed by molecular dynamics simulations. These bis-dipolar polymethines exhibit large two-photon absorption (TPA) cross-sections (σ 2 in GM) in the near-infrared, making them ideal candidates for NIR-to-NIR two-photon microscopy imaging applications. We demonstrate that the molecular engineering of the hydrophilic/hydrophobic balance enables targeting of different cellular components, such as cytoplasm or cell membranes. Addition of appropriate substituents provides the molecule with high-water-solubility, affording efficient two-photon probes for angiography.

Published
2016

43. [Cardiovascular events during the severe weather affecting the French Riviera on 3 October 2015]

Author

L, Jacq, A, Vallet-Anfosso, T, Tibi, P L, Genillier, B, Petit, D, Desse, F, Franke, A, Bellemain-Appaix, D, Rafidiniaina, and F, Bernasconi

Subjects
Chest Pain, Cross-Sectional Studies, Patient Admission, Cardiovascular Diseases, International Classification of Diseases, Rain, Utilization Review, Humans, Arrhythmias, Cardiac, France, Acute Coronary Syndrome, Emergency Service, Hospital, Floods
Published
2016

44. Fluorescent Tobacco mosaic virus-derived bio-nanoparticles for intravital two-photon imaging

Author

Boudewijn van der Sanden, Annette Niehl, Sonia Boscá, Florence Appaix, Jean-François Nicoud, Frédéric Bolze, Manfred Heinlein, Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Conception et application de molécules bioactives (CAMB), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Systèmes Fonctionnels, Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte

Subjects
0301 basic medicine, Plant virus, 02 engineering and technology, Plant Science, Biology, lcsh:Plant culture, Blood–brain barrier, 03 medical and health sciences, Two-photon excitation microscopy, Tobacco mosaic virus, medicine, Fluorescence microscope, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, lcsh:SB1-1110, two-photon microscopy, Original Research, viral nanoparticles, 021001 nanoscience & nanotechnology, Virology, Fluorescence, 030104 developmental biology, medicine.anatomical_structure, Biophysics, intravital imaging, Nanocarriers, 0210 nano-technology, Preclinical imaging
Abstract

Multi-photon intravital imaging has become a powerful tool to investigate the healthy and diseased brain vasculature in living animals. Although agents for multi-photon fluorescence microscopy of the microvasculature are available, issues related to stability, bioavailability, toxicity, cost or chemical adaptability remain to be solved. In particular, there is a need for highly fluorescent dyes linked to particles that do not cross the blood brain barrier (BBB) in brain diseases like tumor or stroke to estimate the functional blood supply. Plant virus particles possess a number of distinct advantages over other particles, the most important being the multi-valency of chemically addressable sites on the particle surface. This multi-valency, together with biological compatibility and inert nature, makes plant viruses ideal carriers for in vivo imaging agents. Here, we show that the well-known Tobacco mosaic virus is a suitable nanocarrier for two-photon dyes and for intravital imaging of the mouse brain vasculature.

Published
2016

45. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo

Author

Valentin S. Teodorescu, Dominique Le Guellec, Florence Appaix, M.G. Blanchin, Boudewijn van der Sanden, Alexis Broisat, Valentin-Adrian Maraloiu, Catherine Ghezzi, Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
0301 basic medicine, Biodistribution, Pathology, medicine.medical_specialty, Materials science, Metabolic Clearance Rate, MRI contrast agent, Biomedical Engineering, Iron oxide, Contrast Media, Pharmaceutical Science, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, Mice, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], Microscopy, Electron, Transmission, Two-photon excitation microscopy, In vivo, Materials Testing, medicine, Animals, [CHIM]Chemical Sciences, Tissue Distribution, General Materials Science, Magnetite Nanoparticles, High-resolution transmission electron microscopy, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], biology, Dextrans, 021001 nanoscience & nanotechnology, Plaque, Atherosclerotic, Mice, Inbred C57BL, Ferritin, Metabolism, Microscopy, Fluorescence, Multiphoton, 030104 developmental biology, chemistry, biology.protein, Molecular Medicine, 0210 nano-technology, Ex vivo, Subcellular Fractions, Biomedical engineering
Abstract

The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.

Published
2016
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46. High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study

Author

Olivier Barthelemy, Jonathan Finzi, Farzin Beygui, Mathieu Kerneis, Johanne Silvain, Jean-Sébastien Hulot, Anne Bellemain-Appaix, Stephen A. O’Connor, Guillaume Cayla, Gilles Montalescot, and Jean-Philippe Collet

Subjects
Adult, Male, medicine.medical_specialty, Ticlopidine, Prasugrel, Platelet Aggregation, Thienopyridine, Population, Myocardial Infarction, Thiophenes, Gastroenterology, Piperazines, Platelet reactivity, P2Y12, Internal medicine, medicine, Humans, Platelet, Prospective Studies, cardiovascular diseases, Acute Coronary Syndrome, education, Aged, Aged, 80 and over, Aspirin, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Age Factors, Middle Aged, Clopidogrel, Cross-Sectional Studies, Anesthesia, Multivariate Analysis, Female, Cardiology and Cardiovascular Medicine, business, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Aims The aim of this study was to compare on-thienopyridine platelet reactivity of elderly patients (≥75 years) vs. younger patients (14 days) treated with aspirin and a thienopyridine (clopidogrel 75 mg, n = 1027; clopidogrel 150 mg, n = 139; or prasugrel 10 mg, n = 165). Platelet response to clopidogrel and prasugrel was assessed by the VerifyNow assay and light transmission aggregrometry (LTA). Response to treatment, rate of high platelet reactivity (HPR), and inhibition (HPI) were compared in the two age categories. On-treatment platelet reactivity with clopidogrel 75 mg, 150 mg or prasugrel 10 mg was higher in elderly patients ( n = 205) than in younger patients ( n = 1126) whichever the test used. The difference in P2Y12 reaction units (PRU) between the two populations was +45 in patients treated with clopidogrel 75 mg ( P < 0.0001), +30 in patients treated with clopidogrel 150 mg ( P = 0.17), and +20 with prasugrel 10 mg ( P = 0.10). Differences in residual platelet aggregation were consistent when measured by LTA. Elderly patients treated with clopidogrel 75 mg were more likely to have HPR than younger patients (38.2 vs. 18.2%, OR: 2.58, 95% CI: 1.76–3.79; P < 0.0001) even after adjustment for potential confounders (adj OR: 1.83, 95% CI: 1.16–2.87; P = 0.009). Conclusion Elderly patients present an impaired response to clopidogrel with a high rate of HPR. Clopidogrel 150 mg or prasugrel 10 mg blunt, but do not eliminate the difference in response observed between old and young patients.

Published
2011
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47. Impact of anticoagulation on ionic and nonionic contrast media effect on thrombogenesis and fibrinolysis: The PEPCIT study

Author

Yann Allali, Gilles Montalescot, Guillaume Cayla, Farzin Beygui, Jean-Philippe Collet, C. Lesty, Satya Gupta, Claude Le Feuvre M.D., Johanne Silvain, and Anne Bellemain-Appaix

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Ioxaglic acid, Contrast Media, Coronary Angiography, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Fibrin, Triiodobenzoic Acids, Internal medicine, Fibrinolysis, Ioxaglic Acid, medicine, Humans, Bivalirudin, Drug Interactions, Radiology, Nuclear Medicine and imaging, Angioplasty, Balloon, Coronary, Aged, biology, business.industry, Coronary Thrombosis, Coronary Stenosis, Anticoagulants, General Medicine, Heparin, Middle Aged, medicine.disease, Thrombosis, Iodixanol, Surgery, Conventional PCI, biology.protein, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Objectives: The effect of ionic low osmolar contrast media (ICM) and nonionic iso-osmolar CM (NICM) on acute thrombotic complications of percutaneous coronary intervention (PCI) is subject to controversies possibly related to a potential interaction with anticoagulation regimens. We sought to compare physical and morphological properties of fibrin clots made in the presence of ioxaglate (ICM), iodixanol (NICM) versus control and to evaluate the effect of four anticoagulants used in PCI. Methods and Results: Maximum platelet aggregation (MPA%), maximum elastic modulus (EM, dyne/cm2) fiber density (n/10−5/μm2), and lysis front velocity (nm/sec) of fibrin rich clot (FRC) were measured simultaneously using peripheral blood from 12 patients undergoing elective PCI. We compared the effects of adding iodixanol or ioxaglate or saline (control) to blood with enoxaparin, unfractionated heparin, fondaparinux, and bivalirudin. Iodixanol and ioxaglate led to nonsignificant reduction in MPA compared to control (33.6% ± 16.9%, 28.2% ± 18.9%, and 40.7% ± 13.9%, respectively, P = ns). Fibrin formed with iodixanol was stiffer (42.7 ± 41.9, 18.7 ± 3.7, and 15.9 ± 9 dyne/cm2, P < 0.01) and displayed more fibrin fibers (1089 ± 175, 260 ± 108, and 456 ± 131 n/10−5/μm2, respectively, P < 0.01) than with ioxaglate or control. This resulted in a profound reduction in the lysis front velocity (191 ± 95, 261 ± 112, and 360 ± 153 nm/sec). None of the four anticoagulants displayed any significant interaction on the effect of contrast media. Conclusions: The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities. © 2011 Wiley-Liss, Inc.

Published
2011
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48. High Doses of Clopidogrel to Overcome Genetic Resistance

Author

Jean-Baptiste Vignalou, Farzin Beygui, Claire Caron, Ghalia Anzaha, Jean-Sébastien Hulot, Anne Bellemain-Appaix, Thomas Chastre, Ana Pena, Vanessa Gallois, Jean-Philippe Collet, Olivier Barthelemy, Sophie Galier, Clovis Investigators, Guillaume Cayla, Johanne Silvain, and Gilles Montalescot

Subjects
medicine.medical_specialty, business.industry, Crossover, CYP2C19, Pharmacology, medicine.disease, Clopidogrel, Response Variability, Surgery, Coronary artery disease, Pharmacokinetics, Pharmacodynamics, Conventional PCI, medicine, cardiovascular diseases, business, Cardiology and Cardiovascular Medicine, medicine.drug
Abstract

Objectives: This study sought to determine whether the pharmacokinetic (PK) and pharmacodynamic (PD) responses to high or standard clopidogrel loading doses (LDs) differ according to CYP2C19*2 alle...

Published
2011
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49. Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Author

David Brieger, Nicolas Vignolles, Anne Bellemain-Appaix, Antoine Landivier, Olivier Barthelemy, Dominique Costagliola, Johanne Silvain, Gilles Montalescot, Anne Mercadier, Jean-Philippe Collet, Farzin Beygui, and Rémi Choussat

Subjects
Male, Paris, medicine.medical_specialty, Time Factors, medicine.drug_class, medicine.medical_treatment, Myocardial Infarction, Low molecular weight heparin, Hemorrhage, Risk Assessment, Risk Factors, Internal medicine, Odds Ratio, Secondary Prevention, medicine, Humans, Radiology, Nuclear Medicine and imaging, Hospital Mortality, Prospective Studies, Registries, Myocardial infarction, Angioplasty, Balloon, Coronary, Enoxaparin, Propensity Score, Aged, Analysis of Variance, Chi-Square Distribution, Heparin, business.industry, ST elevation, Anticoagulant, Anticoagulants, Percutaneous coronary intervention, General Medicine, Thrombolysis, Middle Aged, medicine.disease, Logistic Models, Treatment Outcome, Conventional PCI, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, TIMI
Abstract

Objectives: The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background: Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods: Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitie-Salpetriere registry of ischemic coronary syndromes (e-PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity-weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results: Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti-Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions: In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley-Liss, Inc.

Published
2011
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50. FXIII-A Leu34 genetic variant in premature coronary artery disease: A genotype – phenotype case control study

Author

J.P. Collet, Jean-Baptiste Vignalou, John W. Weisel, Ana Pena, Farzin Beygui, Anne Bellemain-Appaix, Jean-Sébastien Hulot, Johanne Silvain, Olivier Barthelemy, Guillaume Cayla, Sophie Galier, Gilles Montalescot, Ludovic Drouet, and Claire Bal-dit-Sollier

Subjects
Pathology, medicine.medical_specialty, biology, Surrogate endpoint, business.industry, medicine.medical_treatment, Case-control study, Hematology, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Thrombosis, Fibrin, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fibrinolysis, medicine, Cardiology, biology.protein, 030212 general & internal medicine, Myocardial infarction, business, Pharmacogenetics
Abstract

SummaryThe FXIII-A Leu34 genetic variant increases and accelerates fibrin stabilisation; however, its association with premature coronary artery disease (CAD) and thrombotic events remains controversial. FXIII Val34Leu genotype was determined in 242 young individuals (

Published
2011
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