Author: "Leboeuf, Christophe" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

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43 results on '"Leboeuf, Christophe"'

1. BCL-2 Inhibition with ABT-737 Prolongs Survival in an NRAS/BCL2-Mediated MOUSE MODEL of Myelodyspastic Syndrome (MDS) Progressing to ACUTE Myelogenous Leukemia (AML) by Targeting Leukemia Initiating CELLS

Author: Pierre Fenaux, Michael Andreeff, Marina Konopleva, Beurlet Stephanie, Anne Janin, West Robert, Pierre de la Grange, Le Pogam Carole, Leboeuf Christophe, Krief Patricia, Rose Ann Padua, Petra Gorombei, Nader Omidvar, Noguera Maria-Elena, Christine Chomienne, and Pla Marika
Subjects: Genetically modified mouse, education.field_of_study, TUNEL assay, Acute myelogenous leukemia (AML), business.industry, Immunology, Population, Cell Biology, Hematology, medicine.disease, Biochemistry, Leukemia, medicine.anatomical_structure, Terminal deoxynucleotidyl transferase, Apoptosis, Cancer research, medicine, Bone marrow, education, business
Abstract: Abstract 678 Background and aims: BCL-2 activation plays a role in the progression of MDS to AML and BCL 2 inhibition may represent a therapeutic target in such patients. Using our double transgenic mouse model MRP8[NRASD12/BCL2], in which the transgenes induce MDS progressing to AML with dysplasia (Omidvar Cancer Res, 2007), we assessed the effect of ABT-737, a small molecule and mimetic inhibitor binding the BH3 domain of the BCL-2 family of proteins, on survival and leukemia initiating cells (LIC) in this mouse model. Methods: In this MRP8[NRASD12/hBCL2] double transgenic mouse model 2-week old mice have MDS with a mean of 6% bone marrow (BM) blasts (compared with 3% in the normal wild type littermates), while adult mice have AML, with a mean of 60% marrow blasts. In the present study, double transgenic mice were treated just after weaning and genotyping at 3 weeks of age with 75 mg/kg dose of ABT-737 (MDA & Abbott) 3 times weekly for 30 days. A cohort of mice (60 untreated and 35 treated) was followed for survival. Mice were sacrificed and BM harvested after treatment and Giemsa stained for BM analysis by microscopy (n=6 in each group), for LICs characterized as part of the lineage negative (Lin-)/Sca1+/cKit+ (LSK) population by flow cytometry (in 8 treated and 12 untreated mice), and for progenitor assays (n=4 in each group). Hematoxylin and eosin stained liver sections were examined and apoptosis assessed by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assays of liver sections (n=4 per group). RNA was extracted from Sca+ enriched spleen cells from untreated and treated mice (n=3 from each group) and assayed for gene expression profiling using exon specific arrays (Affymetrix). Results: Survival from birth of 35 treated mice was significantly longer than for 60 untreated mice (p Conclusions: ABT-737 extends lifespan in NRASD12/BCL2 transgenic mice, a preclinical model of high risk MDS/AML. ABT-737 targets the leukemia initiating cell, and regulates, amongst several, cell cycle (proliferation), differentiation and apoptosis pathways. These data suggest that clinical trials in high risk MDS and AML patients are warranted. Disclosures: Grange: Genosplice Technology: Employment.
Published: 2012

2. Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA)

Author: Javed Butler, Adrian F. Hernandez, Paul W. Armstrong, Justin A. Ezekowitz, Piotr Ponikowski, Cynthia M. Westerhout, Vojtěch Melenovský, Burkert Pieske, Ciaran McMullan, Yinggan Zheng, Adriaan A. Voors, Jorge Escobedo, Christopher DeFilippi, Lothar Roessig, Carolyn S.P. Lam, Christopher M. O'Connor, Alain Cohen-Solal, leboeuf, Christophe, University of Alberta, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Institute of Clinical and Experimental Medicine [Prague, Czech Republic] (ICEM), Mexican Social Security Institute [Mexico City] (M2SI), University of Mississippi Medical Center (UMMC), Duke University Medical Center, Duke-National University of Singapore Graduate Medical School, Inova Heart and Vascular Institute [Falls Church, VA, USA] (IHVI), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Wrocław Medical University, University of Groningen [Groningen], Merck & Co., Inc. [Kenilworth, NJ, États-Unis], Bayer AG [Wuppertal, Germany], and Cardiovascular Centre (CVC)
Subjects: Male, medicine.medical_specialty, Anemia, vericiguat, heart failure, World Health Organization, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, medicine, Humans, In patient, hemoglobins, Aged, Ejection fraction, business.industry, Stroke Volume, medicine.disease, anemia, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Heart failure, Cardiology, Vericiguat, Female, Hemoglobin, Cardiology and Cardiovascular Medicine, business
Abstract: Background: In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin. Methods: Anemia was defined as hemoglobin Results: At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo ( P Conclusions: Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat. Registration: URL: https://www.clinicaltrials.gov : Unique identifier: NCT02861534.
Published: 2021

3. Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials

Author: Olav W. Nielsen, Aldo P. Maggioni, Christopher L. Edwards, Marco Metra, Naoki Sato, Barry H. Greenberg, Faiez Zannad, Gad Cotter, Alexandre Mebazaa, Georg Ertl, Beth A. Davison, Alain Cohen-Solal, Ovidiu Chioncel, Stefanie Senger, John R. Teerlink, Momentum Research Inc. [Durham, NC, USA] (MRI), 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, University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, 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), 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), 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 ), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IT University of Copenhagen (ITU), Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University of California [San Diego] (UC San Diego), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Würzburg = Universität Würzburg, Nippon Medical School [Tokyo, Japon], Hôpital Lariboisière-Fernand-Widal [APHP], and leboeuf, Christophe
Subjects: medicine.medical_specialty, 030204 cardiovascular system & hematology, Glucagon-Like Peptide-1 Receptor, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Heart Failure, Humans, Hypoglycemic Agents, Regression Analysis, Sodium-Glucose Transporter 2 Inhibitors, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes Mellitus, medicine, Treatment effect, 030212 general & internal medicine, business.industry, medicine.disease, Random effects model, Differential effects, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, Cardiology and Cardiovascular Medicine, business, Type 2, Mace
Abstract: International audience; Background In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. Methods We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. Results The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83-1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). Conclusion The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.
Published: 2021

4. Iron deficiency in pulmonary arterial hypertension: perspectives

Author: Marceau Quatredeniers, Frédéric Perros, Alain Cohen-Solal, David Montani, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, 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), and leboeuf, Christophe
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Anemia, Diseases of the respiratory system, Right heart failure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Hepcidin, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, RC705-779, Ventricular function, biology, business.industry, right heart failure, iron supplementation, Treatment options, Iron deficiency, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Editorial, RC666-701, Cardiology, biology.protein, Iron supplementation, hepcidin, business, Rare disease
Abstract: International audience; In left heart failure, iron supplementation (IS) is a first-line treatment option, regardless of anemia. Pulmonary arterial hypertension (PAH), a rare disease leading to right heart failure, is also associated with iron deficiency. While it is a much debated topic, recent evidence demonstrate that restoration of iron stores results in improved right ventricular function and exercise tolerance. Hence, IS may also be considered as an option in the treatment of PAH.
Published: 2021

5. Doxorubicin‐induced and trastuzumab‐induced cardiotoxicity in mice is not prevented by metoprolol

Author: Jane Lise Samuel, Evelyne Polidano, Martin Nicol, Alain Cohen-Solal, Feriel Azibani, Jean-Marie Launay, Malha Sadoune, 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), and leboeuf, Christophe
Subjects: Male, Cardiac function curve, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Necrosis, Cardiac fibrosis, 030204 cardiovascular system & hematology, Ventricular Function, Left, Mice, 03 medical and health sciences, 0302 clinical medicine, Atrophy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Original Research Articles, Internal medicine, medicine, Animals, Original Research Article, 030212 general & internal medicine, Metoprolol, Cardiotoxicity, Ejection fraction, business.industry, Stroke Volume, Cardiac atrophy, Trastuzumab, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mice, Inbred C57BL, Endocrinology, lcsh:RC666-701, Doxorubicin, Heart failure, medicine.symptom, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: International audience; Aims Our objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio-protective effect of metoprolol. Methods and results Male C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg). Cardiotoxicity was defined by a decline in left ventricular ejection fraction (LVEF) ≥ 10 points. At Day 42, Dox + Trast-treated mice exhibited a 13-points decline in LVEF (74 ± 2.6% vs. 87 ± 0.8% for control mice, P < 0.001) and a severe cardiac atrophy (heart weight: 105 ± 2.7 mg vs. 119 ± 3.9 mg for control mice, P < 0.01). This cardiac atrophy resulted from an excess of cardiac necrosis (assessed by plasma cardiac troponin I level: 3.2 ± 0.4 ng/L vs. 1.3 ± 0.06 ng/L for control mice, P < 0.01), an increase in apoptosis (caspase 3 activity showing a six-fold increase for Dox + Trast-treated mice vs. controls, P < 0.001), and cardiomyocyte atrophy (myocyte size: 0.67 ± 0.08 μm 2 vs. 1.36 ± 0.10 μm 2 for control mice, P < 0.001). In addition, Dox + Trast-treated mice were shown to have an increased cardiac oxidative stress (164 ± 14 dihydroethidine-marked nuclei per area vs. 56 ± 9.5 for control mice, P < 0.01) and increased cardiac fibrosis (the semi-quantitative fibrosis score was threefold higher for Dox + Trast-treated mice as compared with controls, P < 0.01). Metoprolol was not able to prevent either the decrease in LVEF or the severe cardiac atrophy, the cardiac necrosis, and the cardiac remodelling induced by chemotherapies. Conclusion A murine model of chronic cardiotoxicity induced by Dox and Trast was characterized by a decrease in cardiac function, a cardiac apoptosis and necrosis leading to cardiomyocyte atrophy. Metoprolol did not prevent this cardiotoxicity.
Published: 2021

6. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure

Author: Stefano Savonitto, D Soon, V Tseluyko, J Heymeriks, L Petrescu, Fabio T. M. Costa, P Garcia Pacho, G Chapidze, Michael Motro, M Diez, A Prado, Piotr Ponikowski, Sanjib Kumar Sharma, DL Serban, A. Salvioni, S del Prado, Giuseppe Boriani, Stephan von Haehling, HG Cestari, PR Nierop, LC Iosipescu, Hans Kragten, Má Hominal, Bridget-Anne Kirwan, Andre Keren, D Horvat, J Thierer, D Sim, Rabih R. Azar, Peter van der Meer, G Stanciulescu, F Cosmi, Sy Loh, Jarosław Drożdż, David Sim, K Paposhvili, M Berli, Alain Cohen-Solal, Stefan D. Anker, Arnaout, ML Parody, GO Zapata, T Ben-Gal, J Schaap, Bas L.J.H. Kietselaer, O Raed, G Kiwan, Marco Metra, Shaul Atar, Udo Michael Göhring, Edoardo Gronda, A Ružić, C Beltrano, Dpw Beelen, Davor Milicic, R Ray, JM Weinstein, FI Ga Bosa Ojeda, Y-K Wong, Dalton Bertolim Précoma, Javed Butler, JR Gonzalez Juanatey, V Chumburidze, Gerasimos Filippatos, V Witzling, Y Malynovsky, I Kraiz, A Samodol, J Trevelyan, L Nigro Maia, M Stanislavchuk, Gilmar Reis, I Khintibidze, D Zdrenghea, Beata Wożakowska-Kapłon, BD Molina, C Abdallah, Ham van Kesteren, Tim Friede, Marcin Gruchała, Majdi Halabi, Ewa A. Jankowska, P Van Bergen, Constantin Militaru, O Koval, DA Darabantiu, A Kormann, J Szachniewicz, Maria Dorobantu, M van de Wetering, R Nijmeijer, H Hamdan, Stefano Ghio, Henry J. Dargie, G Azize, Nicolas Danchin, S Chaaban, S Gerward, P Pimentel Filho, M Uguccioni, K Abdelbaki, N Vita, J.F.K. Saraiva, D Almeida, Michael Shochat, M Ohlsson, R Van de Wal, V Zolotaikina, W Kinany, A Tycińska, A Hershson, T Shaburishvili, Vincent Fabien, FR dos Santos, Alfredo Bardají, Rgej Groutars, M Flugelman, J Bono, M Udovicic, M Artuković, K Šutalo, J Drozdz, TJ Yeo, F Ferre Pacora, Z Lominadze, M Emans, S Pettit, HA Luquez, P Terrosu, Marcus Ohlsson, M Gąsior, S Tušek, Enrico Passamonti, Nyy Al-Windy, P Midi, DA Pascual Figal, P van der Meer, V Zvi, Wilco Tanis, Felipe Martinez, RR Borelli, Diana A. Gorog, O Parhomenko, Klaus H Jensen, M Meijs, J Nessler, M Piepoli, DM Toader, Jose C. Nicolau, A Glenny, José Luis Zamorano, L Tilling, T McDonagh, K Pesek, H Fernandez, Davor Miličić, Domingo A. Pascual-Figal, Theresa McDonagh, G Khabeishvili, Josep Comin-Colet, Israel Gotsman, S Rassi, M Dorobantu, E Straburzyńska-Migaj, L Fattore, L Rudenko, D Crisu, S.S. Kabbani, M Gomez Bueno, Basil S. Lewis, S Goland, Y Arbel, M Bronisz, I Vakaliuk, A Fucili, A Mortara, R Zukermann, N Emukhvari, B Hassouna, K Mizia-Stec, F Turrini, R Szelemej, A Rodica Dan, L Lobo Marquez, Hadi Skouri, A Kabir, Frank Ruschitzka, R García Durán, R Gil, Michael Shechter, P Westendorp, Piergiuseppe Agostoni, A Fernandez, Oscar Pereira Dutra, P Ameri, Wolfram Doehner, JG Smith, Irakli Khintibidze, Luciano Moreira Baracioli, J Šikić, Stuart Pocock, Olivier C. Manintveld, MC Tomescu, M Di Biase, Luiz Carlos Bodanese, E Mirek-Bryniarska, Alexander Parkhomenko, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Cardiology, leboeuf, Christophe, Wrocław Medical University, London School of Hygiene and Tropical Medicine (LSHTM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], King's College Hospital (KCH), Universitatea din Bucuresti (UB), University of Lódź, Vifor Pharma Ltd [Glattbrugg, Switzerland], National and Kapodistrian University of Athens (NKUA), Hadassah Hebrew University Medical Center [Jerusalem], Tbilisi State University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Prague University of Economics and Business, Università degli Studi di Brescia = University of Brescia (UniBs), University of Zagreb, Universidade de São Paulo = University of São Paulo (USP), Skane University Hospital [Malmo], Lund University [Lund], National Scientific Center 'M.D. Strazhesko Institute of Cardiology' [Kyiv, Ukraine] (NSC/MDSIC), Universidad de Murcia, University hospital of Zurich [Zurich], National Heart Centre Singapore (NHCS), Saint Joseph Medical Center [Beirut], University Medical Center Groningen [Groningen] (UMCG), Clinical Cardiovascular Research Institute [Haifa, Israel] (2CRI), Bellvitge University Hospital [Barcelona, Spain], University Medical Center Göttingen (UMG), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Charité Campus Virchow-Klinikum (CVK), University of Glasgow, Tel Aviv University (TAU), University of Southern Mississippi (USM), Socar Research S.A. [Nyon, Switzerland] (SR), and AFFIRM-AHF investigators: G Azize, A Fernandez, G O Zapata, P Garcia Pacho, A Glenny, F Ferre Pacora, M L Parody, J Bono, C Beltrano, A Hershson, N Vita, H A Luquez, H G Cestari, H Fernandez, A Prado, M Berli, R García Durán, J Thierer, M Diez, L Lobo Marquez, R R Borelli, M Á Hominal, M Metra, P Ameri, P Agostoni, A Salvioni, L Fattore, E Gronda, S Ghio, F Turrini, M Uguccioni, M Di Biase, M Piepoli, S Savonitto, A Mortara, P Terrosu, A Fucili, G Boriani, P Midi, E Passamonti, F Cosmi, P van der Meer, P Van Bergen, M van de Wetering, Nyy Al-Windy, W Tanis, M Meijs, Rgej Groutars, Hks The, B Kietselaer, Ham van Kesteren, Dpw Beelen, J Heymeriks, R Van de Wal, J Schaap, M Emans, P Westendorp, P R Nierop, R Nijmeijer, O C Manintveld, M Dorobantu, D A Darabantiu, D Zdrenghea, D M Toader, L Petrescu, C Militaru, D Crisu, M C Tomescu, G Stanciulescu, A Rodica Dan, L C Iosipescu, D L Serban, J Drozdz, J Szachniewicz, M Bronisz, A Tycińska, B Wozakowska-Kaplon, E Mirek-Bryniarska, M Gruchała, J Nessler, E Straburzyńska-Migaj, K Mizia-Stec, R Szelemej, R Gil, M Gąsior, I Gotsman, M Halabi, M Shochat, M Shechter, V Witzling, R Zukermann, Y Arbel, M Flugelman, T Ben-Gal, V Zvi, W Kinany, J M Weinstein, S Atar, S Goland, D Milicic, D Horvat, S Tušek, M Udovicic, K Šutalo, A Samodol, K Pesek, M Artuković, A Ružić, J Šikić, T McDonagh, J Trevelyan, Y-K Wong, D Gorog, R Ray, S Pettit, S Sharma, A Kabir, H Hamdan, L Tilling, L Baracioli, L Nigro Maia, O Dutra, G Reis, P Pimentel Filho, J F Saraiva, A Kormann, F R Dos Santos, L Bodanese, D Almeida, D Precoma, S Rassi, F Costa, S Kabbani, K Abdelbaki, C Abdallah, M S Arnaout, R Azar, S Chaaban, O Raed, G Kiwan, B Hassouna, A Bardaji, J Zamorano, S Del Prado, J R Gonzalez Juanatey, F I Ga Bosa Ojeda, M Gomez Bueno, B D Molina, D A Pascual Figal, D Sim, T J Yeo, S Y Loh, D Soon, M Ohlsson, J G Smith, S Gerward, I Khintibidze, Z Lominadze, G Chapidze, N Emukhvari, G Khabeishvili, V Chumburidze, K Paposhvili, T Shaburishvili, G Khabeishvili, O Parhomenko, I Kraiz, O Koval, V Zolotaikina, Y Malynovsky, I Vakaliuk, L Rudenko, V Tseluyko, M Stanislavchuk.
Subjects: Male, medicine.medical_specialty, Anemia, 030204 cardiovascular system & hematology, Rate ratio, Placebo, Ferric Compounds, Ventricular Function, Left, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Maltose, Adverse effect, TOLVAPTAN, Aged, Aged, 80 and over, Heart Failure, RISK, Ejection fraction, Anemia, Iron-Deficiency, business.industry, MORTALITY, Hazard ratio, DEATH, General Medicine, Middle Aged, medicine.disease, Patient Discharge, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, Treatment Outcome, Heart failure, Administration, Intravenous, Female, HOSPITALIZATIONS, business
Abstract: Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin
Published: 2020

7. Measuring physical activity with activity monitors in patients with heart failure: from literature to practice. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology

Author: Anna Wozniak, Ewa Piotrowicz, Andrew J.S. Coats, Ekaterini Lambrinou, Tiny Jaarsma, Barnabas Gellen, Leonie Klompstra, Martha Kyriakou, Maria Simonenko, Maurizio Volterrani, Massimo F Piepoli, Alain Cohen-Solal, Justien Cornelis, Klaus K. Witte, Emeline M. Van Craenenbroeck, David Niederseer, Francesco Orso, Elena Marques-Sule, Linköping University (LIU), Cyprus University of Technology, Limassol General Hospital, Nicosia General Hospital, Piacenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), 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), University of Antwerp (UA), Belgian Health Care Knowledge Centre (KCE), Polyclinique de Poitiers - ELSAN (2PE), Universitat de València (UV), Universität Zürich [Zürich] = University of Zurich (UZH), University hospital of Zurich [Zurich], Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), National Institute of Cardiology [Warsaw, Poland] (NIC), Antwerp University Hospital [Edegem] (UZA), Ministry of Health of the Russian Federation (MHRF), University of Leeds, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust [Doncaster, UK] (DBTH), IRCCS Ospedale San Raffaele [Milan, Italy], University Medical Center [Utrecht], leboeuf, Christophe, University of Zurich, and Klompstra, Leonie
Subjects: medicine.medical_specialty, Cardiology, Physical activity, 610 Medicine & health, Heart failure, Fitness Trackers, 030204 cardiovascular system & hematology, Medical and Health Sciences, 2705 Cardiology and Cardiovascular Medicine, Exercise Capacity, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Cardiac and Cardiovascular Systems, In patient, Exercise physiology, Association (psychology), Set (psychology), Exercise, Monitoring, Physiologic, Heart Failure, Kardiologi, business.industry, Activity monitor, Motion sensor, Accelerometer, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 10209 Clinic for Cardiology, Position paper, Position Paper, Human medicine, Clinical Medicine, Cardiology and Cardiovascular Medicine, Raw data, business
Abstract: The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device. Funding Agencies|European Society of Cardiology Funding Source: Medline
Published: 2020

8. Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis

Author: Damien Logeart, Stephanie Harel, Alessandro Carecci, Mathilde Baudet, Bertrand Arnulf, Remi Neviere, Michele Emdin, Bruno Royer, Giuseppe Vergaro, Jocelyn Inamo, Olivier Lairez, Alain Cohen-Solal, Thibaud Damy, Astrid Montfort, Antoine Deney, Martin Nicol, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Fondazione Toscana Gabriele Monasterio, École supérieure Sainte-Anne de Pise, CHU de la Martinique [Fort de France], CHU Henri Mondor, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and leboeuf, Christophe
Subjects: medicine.medical_specialty, medicine.drug_class, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Troponin T, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Interquartile range, Internal medicine, Natriuretic Peptide, Brain, Amyloidosis, Cardiopulmonary exercise test, Circulatory power, Peak oxygen consumption, Prognosis, medicine, Natriuretic peptide, Humans, Aged, Heart Failure, business.industry, Hazard ratio, Middle Aged, medicine.disease, Peptide Fragments, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Blood pressure, Cardiac amyloidosis, Heart failure, Circulatory system, Exercise Test, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers, Respiratory minute volume
Abstract: International audience; Aims: In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis. We sought to study how the cardiopulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA).Methods and results: We carried out a multicentre study including patients with light chain (AL) or transthyretin (TTR) CA. All patients underwent exhaustive examination including CPET and follow-up. The primary prognostic endpoint was the occurrence of death or heart failure hospitalization. Overall, 150 patients were included (91 AL and 59 TTR CA). Median age, systolic blood pressure, N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin T were 70 (64-78) years, 121 [interquartile range (IQR) 109-139] mmHg, 2806 (IQR 1218-4638) ng/L and 64 (IQR 33-120) ng/L, respectively. New York Heart Association classes were I-II in 64%. Median peak oxygen consumption (VO2 ) and circulatory power were low at 13.0 (10.0-16.9) mL/kg/min and 1730 (1318-2614) mmHg/mL/min, respectively. The minute ventilation/carbon dioxide production slope was increased to 37 (IQR 33-45). A total of 77 patients (51%) had chronotropic insufficiency. After a median follow-up of 20 months, there were 37 deaths and 44 heart failure hospitalizations. At multivariate Cox analysis, peak VO2 ≤13 mL/kg/min [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.6-4.8], circulatory power ≤1730 mmHg/mL/min (HR 2.4, 95% CI 1.2-4.6) and NT-proBNP ≥1800 ng/L (HR 2.2, 95% CI 1.1-4.3) were found to be associated with the primary outcome. No events occurred in patients with both peak VO2 >13 mL/kg/min and NT-proBNP
Published: 2020

9. Mega-trials in heart failure

Author: Peter S. Pang, Barry H. Greenberg, Alexandre Mebazaa, Marco Metra, Koji Takagi, Christopher L. Edwards, John R. Teerlink, Aldo P. Maggioni, Olav W. Nielsen, Gerasimos Filippatos, Piotr Ponikowski, Etienne Gayat, Stefanie Senger, Gad Cotter, Ovidiu Chioncel, Adriaan A. Voors, Alain Cohen-Solal, Georg Ertl, Beth A. Davison, Gary G. Koch, Antoine Kimmoun, Naoki Sato, Cardiovascular Centre (CVC), leboeuf, Christophe, Momentum Research Inc. [Durham, NC, USA] (MRI), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Università degli Studi di Brescia = University of Brescia (UniBs), 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), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], University Medical Center Groningen [Groningen] (UMCG), University of Copenhagen = Københavns Universitet (UCPH), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, University of California [San Diego] (UC San Diego), University of California (UC), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Würzburg = Universität Würzburg, Ludwig-Maximilians University [Munich] (LMU), Nippon Medical School Musashi Kosugi Hospital [Kawasaki, Japan] (NMSMKH), Nippon Medical School [Tokyo, Japon], University of California [San Francisco] (UC San Francisco), Veterans Affairs Medical Center, San Francisco, California, National and Kapodistrian University of Athens (NKUA), Wrocław Medical University, College of Engineering, Mathematics and Physical Sciences [Exeter] (EMPS), and University of Exeter
Subjects: medicine.medical_specialty, CLINICAL-OUTCOMES, 030204 cardiovascular system & hematology, Placebo, Article, PATIENT CHARACTERISTICS, law.invention, 03 medical and health sciences, Ventricular Dysfunction, Left, DOUBLE-BLIND, 0302 clinical medicine, VENTRICULAR SYSTOLIC FUNCTION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Randomized controlled trial, RECEPTOR ANTAGONIST ROLOFYLLINE, law, Internal medicine, Medicine, Humans, Registries, CONVERTING-ENZYME INHIBITORS, Heart Failure, Ejection fraction, business.industry, Acute heart failure, Chronic heart failure, Meta-analysis, MORTALITY, Stroke Volume, Trial Phase, medicine.disease, Prognosis, RANDOMIZED-TRIAL, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trial, PRESERVED EJECTION FRACTION, Sample size determination, Heart failure, Chronic Disease, Cardiology, QUALITY-OF-CARE, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Aims: Over the last 30 years, many medicine development programmes in acute and chronic heart failure (HF) with preserved ejection fraction (HFpEF) have failed, in contrast to those in HF with reduced ejection fraction (HFrEF). We explore how the neutral results in larger HF trials may be attributable to chance and/or the dilution of statistical power.Methods and results: Using simulations, we examined the probability that a positive finding in a Phase 2 trial would result in the study of a truly effective medicine in a Phase 3 trial. We assessed the similarity of clinical trial and registry patient populations. We conducted a meta-analysis of paired Phase 2 and 3 trials in HFrEF and acute HF examining the associations of trial phase and size with placebo event rates and treatment effects for HF events and death. We estimated loss in trial power attributable to dilution with increasing trial size. Appropriately powered Phase 3 trials should have yielded ∼35% positive results. Patient populations in Phase 3 trials are similar to those in Phase 2 trials but both differ substantially from the populations of 'real-life' registries. We observed decreasing placebo event rates and smaller treatment effects with increasing trial size, especially for HF events (and less so for mortality). This was more pronounced in trials in acute HF patients.Conclusions: The selection of more positive Phase 2 trials for further development does not explain the failure of HFpEF and acute HF medicine development. Increasing sample size may lead to reduced event rates and smaller treatment effects, resulting in a high rate of neutral Phase 3 trials.
Published: 2020

10. CCS/CHFS Heart Failure Guidelines: Clinical Trial Update on Functional Mitral Regurgitation, SGLT2 Inhibitors, ARNI in HFpEF, and Tafamidis in Amyloidosis

Author: Abdul Al-Hesayen, Michel D'Astous, Sheri L. Koshman, Karen Harkness, Lisa Mielniczuk, Heather J. Ross, Marie-Hélène Leblanc, David Z.I. Cherney, Elizabeth Swiggum, Adrian F. Hernandez, Haissam Haddad, Simon Kouz, Shelley Zieroth, Eileen O'Meara, Sabe De, Gordon W. Moe, Robert S. McKelvie, Estrellita Estrella-Holder, Nowell M. Fine, Nadia Giannetti, Frederick A. Masoudi, Michael McDonald, Gideon Cohen, Sylvain Matteau, Sean A. Virani, Olivier Desplantie, Howard Abrams, Margot K. Davis, Diego H. Delgado, Alain Cohen-Solal, Jonathan G. Howlett, Subodh Verma, Anique Ducharme, Anita W. Asgar, Adam Grzeslo, Douglas S. Lee, Lee A. Green, Mustafa Toma, Marie-Claude Parent, Justin A. Ezekowitz, Michael Chan, Serge Lepage, Bruce Sussex, George A. Heckman, Miroslaw Rajda, Montreal Heart Institute - Institut de Cardiologie de Montréal, University of Toronto, University of Alberta, McGill University Health Center [Montreal] (MUHC), McMaster University [Hamilton, Ontario], University of Waterloo [Waterloo], University of Calgary, Université de Sherbrooke (UdeS), University of Ottawa [Ottawa], St. Michael's Hospital, University of British Columbia (UBC), University of Manitoba [Winnipeg], University of Western Ontario (UWO), St. Michael’s Hopsital [Toronto, ON, Canada], 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), Dr. Georges-L.-Dumont University Hospital Centre (CHUDGLD), Royal Jubilee Hospital [Victoria, BC, Canada] (RJH), St. Boniface Hospital Albrechtsen Research Centre [Winnipeg], University of Saskatchewan [Saskatoon] (U of S), Hamilton Health Sciences, Duke Clinical Research Institute (DCRI - DURHAM), Duke University [Durham], Centre Hospitalier Régional de Lanaudiere [Joliette, QC, Canada] (CHRDL), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), University of Colorado Anschutz [Aurora], Western University [London, ON, Canada], QEII Health Sciences Centre [Halifax, NS, Canada] (HSC), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), and leboeuf, Christophe
Subjects: Tafamidis, medicine.medical_specialty, Heart Diseases, 030204 cardiovascular system & hematology, Severity of Illness Index, Sacubitril, Angiotensin Receptor Antagonists, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, 030212 general & internal medicine, Sodium-Glucose Transporter 2 Inhibitors, Randomized Controlled Trials as Topic, Heart Failure, Benzoxazoles, Ejection fraction, business.industry, Amyloidosis, Mitral Valve Insufficiency, Stroke Volume, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trial, Valsartan, Cardiac amyloidosis, chemistry, Heart failure, Cardiology, Neprilysin, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: International audience; In this update, we focus on selected topics of high clinical relevance for health care providers who treat patients with heart failure (HF), on the basis of clinical trials published after 2017. Our objective was to review the evidence, and provide recommendations and practical tips regarding the management of candidates for the following HF therapies: (1) transcatheter mitral valve repair in HF with reduced ejection fraction; (2) a novel treatment for transthyretin amyloidosis or transthyretin cardiac amyloidosis; (3) angiotensin receptor-neprilysin inhibition in patients with HF and preserved ejection fraction (HFpEF); and (4) sodium glucose cotransport inhibitors for the prevention and treatment of HF in patients with and without type 2 diabetes. We emphasize the roles of optimal guideline-directed medical therapy and of multidisciplinary teams when considering transcatheter mitral valve repair, to ensure excellent evaluation and care of those patients. In the presence of suggestive clinical indices, health care providers should consider the possibility of cardiac amyloidosis and proceed with proper investigation. Tafamidis is the first agent shown in a prospective study to alter outcomes in patients with transthyretin cardiac amyloidosis. Patient subgroups with HFpEF might benefit from use of sacubitril/valsartan, however, further data are needed to clarify the effect of this therapy in patients with HFpEF. Sodium glucose cotransport inhibitors reduce the risk of incident HF, HF-related hospitalizations, and cardiovascular death in patients with type 2 diabetes and cardiovascular disease. A large clinical trial recently showed that dapagliflozin provides significant outcome benefits in well treated patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤ 40%), with or without type 2 diabetes.
Published: 2020

11. Recent advances in cardio-oncology

Author: Christoph Maack, Stephan von Haehling, Alexander R. Lyon, Y N Belenkov, Sara Hadzibegovic, Hadi Skouri, Alessia Lena, Petar M. Seferovic, Rudolf A. de Boer, Markus S. Anker, Radek Pudil, Andrew J.S. Coats, Carlo G. Tocchetti, Zaza Iakobishvili, Dimitrios Farmakis, Jutta Bergler-Klein, Alain Cohen-Solal, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Sechenov First Moscow State Medical University, Medizinische Universität Wien = Medical University of Vienna, University Medical Center Groningen [Groningen] (UMCG), University of Cyprus [Nicosia] (UCY), National and Kapodistrian University of Athens (NKUA), Georg-August-University = Georg-August-Universität Göttingen, Tel Aviv University (TAU), University Hospital of Würzburg, University of Hradec Králové, American University of Beirut Faculty of Medicine and Medical Center (AUB), 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), University of Naples Federico II = Università degli studi di Napoli Federico II, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), University of Belgrade [Belgrade], Royal Brompton Hospital, Imperial College London, leboeuf, Christophe, Anker, M. S., Hadzibegovic, S., Lena, A., Belenkov, Y., Bergler-Klein, J., de Boer, R. A., Farmakis, D., von Haehling, S., Iakobishvili, Z., Maack, C., Pudil, R., Skouri, H., Cohen-Solal, A., Tocchetti, C., Coats, A. J. S., Seferovic, P. M., Lyon, A. R., and Cardiovascular Centre (CVC)
Subjects: IMMUNE CHECKPOINT INHIBITOR, CHRONIC KIDNEY-DISEASE, CARDIOTOXICITY, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Palliative care, medicine.medical_treatment, Cardiology, Heart failure, Disease, 030204 cardiovascular system & hematology, ESC and HFA Paper, ESC and HFA Papers, Targeted therapy, PALLIATIVE CARE, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, BREAST-CANCER SURVIVORS, Neoplasms, medicine, INDEPENDENT PREDICTOR, CO-MORBIDITIES, Humans, 030212 general & internal medicine, Cardio oncology, Intensive care medicine, Cancer, Cardiotoxicity, business.industry, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PREVALENCE, Radiation therapy, lcsh:RC666-701, Heart Failure Association Cardio-Oncology Study Group of the European Society of Cardiology, Position paper, Cardiology and Cardiovascular Medicine, business, ECHOCARDIOGRAPHY, Cardiotoxicity Heart failure Cancer, POSITION PAPER
Abstract: International audience; While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment.
Published: 2019

12. Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

Author: Eurydice Angeli, Guilhem Bousquet, Université Sorbonne Paris Nord, 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, Service d'Oncologie Médicale [AP-HP Hôpital Avicenne], Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and leboeuf, Christophe
Subjects: business.industry, Melanoma, Pharmaceutical Science, Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, blood-brain barrier, Blood–brain barrier, medicine.disease, blood–brain barrier, RS1-441, medicine.anatomical_structure, Breast cancer, Pharmacy and materia medica, [SDV.CAN] Life Sciences [q-bio]/Cancer, brain metastases, tyrosine kinase inhibitors, Cancer research, Medicine, Efflux, pharmacokinetic, business, Lung cancer, Tyrosine kinase, Brain metastasis
Abstract: International audience; The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood-brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood-brain barrier at relevant concentrations and limit their physiological efflux.
Published: 2021

13. Left Atrioventricular Coupling Index to Predict Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis

Author: Susan R. Heckbert, Théo Pezel, Henrique Doria de Vasconcellos, Wendy S. Post, Patrick Henry, David A. Bluemke, Colin O. Wu, Joao A.C. Lima, Yoko Kato, Alain Cohen-Solal, Bharath Ambale Venkatesh, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Johns Hopkins University School of Medicine [Baltimore], University of Washington [Seattle], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Wisconsin School of Medicine and Public Health, and leboeuf, Christophe
Subjects: medicine.medical_specialty, left ventricle, Population, heart failure, multiethnic study of atherosclerosis, Cardiovascular Medicine, left atria, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Left atrial, Internal medicine, multi-ethnic study of atherosclerosis, medicine, Diseases of the circulatory (Cardiovascular) system, Multivariable model, coupling, education, Original Research, education.field_of_study, Framingham Risk Score, medicine.diagnostic_test, business.industry, Incidence (epidemiology), cardiac magnetic resonance image, Mean age, Magnetic resonance imaging, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, RC666-701, Heart failure, Cardiology, prognosis, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF.Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA).Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000–2002), and 10 years later (Exam 5, 2010–2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI).Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25–1.66] and adjusted HR 1.55, 95% CI [1.30–1.85], respectively; both p < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058).Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.
Published: 2021

14. BCL-2 Inhibitor ABT-737 Effectively Targets Leukemia-Initiating Cells with Differential Regulation of Relevant Genes Leading to Extended Survival in a NRAS/BCL-2 Mouse Model of High Risk-Myelodysplastic Syndrome

Author: Maria Elena Noguera, Satyananda Patel, Niclas Setterblad, Laure Sarda-Mantel, Saravanan Ganesan, Christine Chomienne, Pierre de la Grange, Petra Gorombei, Patricia Krief, Rose Ann Padua, Pascale Merlet, Laure Goursaud, R.R. West, Mathieu Chiquet, Christophe Leboeuf, Jacqueline Boultwood, Nader Omidvar, Nilgun Tekin, Marika Pla, Fabien Guidez, Stephanie Beurlet, Anne Janin, Carole Le Pogam, Michael Andreeff, Lionel Ades, Laura Guerenne, Andrea Pellagatti, Marina Konopleva, Pierre Fenaux, leboeuf, Christophe, Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Radcliffe Department of Medicine [Oxford], University of Oxford, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), GenoSplice [Paris], 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, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Hôpital Lariboisière-Fernand-Widal [APHP], MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Electrical Engineering Institute - EPFL, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Cardiff University
Subjects: Neuroblastoma RAS viral oncogene homolog, Apoptosis, Kaplan-Meier Estimate, Piperazines, Nitrophenols, Mice, Bone Marrow, hemic and lymphatic diseases, Biology (General), Spectroscopy, Regulation of gene expression, Sulfonamides, Stem Cells, General Medicine, Computer Science Applications, Leukemia, Chemistry, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Stem cell, Signal Transduction, QH301-705.5, BCL-2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bone Marrow Cells, Mice, Transgenic, Biology, Catalysis, Article, Inorganic Chemistry, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Epigenetics, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, Cell Proliferation, Monomeric GTP-Binding Proteins, ABT-737, Myelodysplastic syndromes, Gene Expression Profiling, Organic Chemistry, Biphenyl Compounds, medicine.disease, HR-MDS, Gene expression profiling, Disease Models, Animal, Gene Expression Regulation, Myelodysplastic Syndromes, Cancer research, Bone marrow, Transcriptome, gene regulation
Abstract: During transformation, myelodysplastic syndromes (MDS) are characterized by reducing apoptosis of bone marrow (BM) precursors. Mouse models of high risk (HR)-MDS and acute myelogenous leukemia (AML) post-MDS using mutant NRAS and overexpression of human BCL-2, known to be poor prognostic indicators of the human diseases, were created. We have reported the efficacy of the BCL-2 inhibitor, ABT-737, on the AML post-MDS model, here, we report that this BCL-2 inhibitor also significantly extended survival of the HR-MDS mouse model, with reductions of BM blasts and lineage negative/Sca1+/KIT+ (LSK) cells. Secondary transplants showed increased survival in treated compared to untreated mice. Unlike the AML model, BCL-2 expression and RAS activity decreased following treatment and the RAS:BCL-2 complex remained in the plasma membrane. Exon-specific gene expression profiling (GEP) of HR-MDS mice showed 1952 differentially regulated genes upon treatment, including genes important for the regulation of stem cells, differentiation, proliferation, oxidative phosphorylation, mitochondrial function, and apoptosis, relevant in human disease. Spliceosome genes, found to be abnormal in MDS patients and downregulated in our HR-MDS model, such as Rsrc1 and Wbp4, were upregulated by the treatment, as were genes involved in epigenetic regulation, such as DNMT3A and B, upregulated upon disease progression and downregulated upon treatment.
Published: 2021

15. The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: The results of the AFFIRM-AHF study

Author: Marco Metra, Marcus Andreas Ohlsson, Basil S. Lewis, Wolfram Doehner, Peter van der Meer, Irakli Khintibidze, Hans Kragten, Bridget-Anne Kirwan, Jose C. Nicolau, Vincent Fabien, Tim Friede, Nicolas Danchin, Ewa A. Jankowska, Gerasimos Filippatos, Alain Cohen-Solal, Fabio Dorigotti, Hadi Skouri, Davor Miličić, Andre Keren, Alexander Parkhomenko, Jarosław Drożdż, David Sim, Stuart J. Pocock, Michael Motro, Javed Butler, Domingo A. Pascual-Figal, Theresa McDonagh, Henry J. Dargie, Josep Comín-Colet, Maria Dorobantu, Mikhail Kosiborod, Frank Ruschitzka, Stephan von Haehling, Piotr Ponikowski, Stefan D. Anker, Felipe Martinez, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), leboeuf, Christophe, Wrocław Medical University, Socar Research S.A. [Nyon, Switzerland] (SR), London School of Hygiene and Tropical Medicine (LSHTM), Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of Mississippi Medical Center (UMMC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], King‘s College London, Universitatea din Bucuresti (UB), Medical University of Łódź (MUL), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Assuta Hospital in Ramat HaHayal [Tel Aviv-Yafo, Israel] (AHRH), Tbilisi State University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Prague University of Economics and Business, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, University of Zagreb, Skane University Hospital [Malmo], Lund University [Lund], National Scientific Center 'M.D. Strazhesko Institute of Cardiology' [Kyiv, Ukraine] (NSC/MDSIC), Universidad de Murcia, University hospital of Zurich [Zurich], National Heart Centre Singapore (NHCS), American University of Beirut Faculty of Medicine and Medical Center (AUB), University Medical Center Groningen [Groningen] (UMCG), Rappaport faculty of Medicine, Technion - Israel Institute of Technology [Haifa], L’Hospitalet de Llobregat [Barcelona, Spain], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University Medical Center Göttingen (UMG), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Glasgow, Tel Aviv University (TAU), Kfar Saba and Sackler School of Medicine, Vifor Pharma Ltd [Glattbrugg, Switzerland], and University College of London [London] (UCL)
Subjects: medicine.medical_specialty, Randomization, Heart diseases, Iron, Health-related quality of life, Population, Heart failure, 030204 cardiovascular system & hematology, Placebo, law.invention, Malalties del cor, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Clinical Research, Internal medicine, medicine, Humans, Clinical Trials, AcademicSubjects/MED00200, 030212 general & internal medicine, education, education.field_of_study, Ejection fraction, Dèficit de ferro, Anemia, Iron-Deficiency, business.industry, Iron deficiency, Acute heart failure, medicine.disease, Confidence interval, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Dietary Supplements, Intravenous ferric carboxymaltose therapy, Iron deficiency diseases, Randomized clinical trial, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. Methods and results The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. Conclusion In iron-deficient patients with HF and left ventricular ejection fraction, Graphical Abstract
Published: 2021

16. Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy

Author: Dorine de Jong, Laetitia Vercellino, Salim Kanoun, Lawrence H. Schwartz, Roberta Di Blasi, Laurent Dercle, Ran Reshef, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Memorial Sloan Kettering Cancer Center (MSKCC), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Columbia University Irving Medical Center (CUIMC), New York Presbyterian Hospital, and leboeuf, Christophe
Subjects: Oncology, CT scan, medicine.medical_specialty, Cancer Research, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Mini Review, medicine.medical_treatment, lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, CAR T-cell, Refractory, Refractory Non-Hodgkin Lymphoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Medical imaging, prognostic biomarker, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunotherapy, medicine.disease, Chimeric antigen receptor, FDG PET/CT, Lymphoma, Clinical trial, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, CAR T-cell therapy, immunotherapy, business
Abstract: International audience; Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.
Published: 2021

17. Amended STRONG-HF study design

Author: Imad Merai, Koji Takagi, Marco Metra, Hans-Dirk Duengen, Piotr Ponikowski, Albertino Damasceno, Gad Cotter, Karen Sliwa, Ovidiu Chioncel, Eva Goncalvesova, Beth A. Davison, Gerasimos Filippatos, Hadiza Saidu, Mahmoud U Sani, Alexandre Mebazaa, Zaur Shogenov, Alain Cohen Solal, Dmitry Privalov, Adriaan A. Voors, Faouzi Addad, Rafael Diaz, Jelena Celutkiene, Cardiovascular Centre (CVC), Momentum Research Inc. [Durham, NC, USA] (MRI), 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, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, University of Cape Town, University of Groningen [Groningen], Hôpital Abderrahmen Mami, Vilnius University [Vilnius], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto Cardiovascular de Rosario [Argentina] (ICR), Eduardo Mondlane University, Charité Campus Virchow-Klinikum (CVK), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Attikon University Hospital, National Institute of Cardiovascular Diseases [Bratislava, Slovak Republic] (NICD), Moscow City Clinical Hospital [Moscow, Russia] (M2CH), Wrocław Medical University, Bayero University Kano (BUK), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, and leboeuf, Christophe
Subjects: Heart Failure, medicine.medical_specialty, business.industry, MEDLINE, medicine.disease, DIAGNOSIS, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, Humans, medicine, ESC GUIDELINES, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Abstract: International audience; No abstract available
Published: 2021

18. Acute heart failure treatment: a light at the end of the tunnel?

Author: Alain Cohen-Solal, Christopher L. Edwards, Koji Takagi, Gad Cotter, Beth A. Davison, Alexandre Mebazaa, Momentum Research Inc. [Durham, NC, USA] (MRI), 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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and leboeuf, Christophe
Subjects: Heart Failure, medicine.medical_specialty, business.industry, MEDLINE, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Text mining, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, medicine, Humans, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Abstract: International audience; No abstract available
Published: 2021

19. Right ventricular function and iron deficiency in acute heart failure

Author: Alain Cohen-Solal, Vicent Bodí, Enrique Santas, Juan Sanchis, Ernesto Valero, Gema Miñana, Eduardo Núñez, Gonzalo Núñez, Miguel Lorenzo, Francisco J. Chorro, Rafael de la Espriella, Antoni Bayes-Genis, Julio Núñez, Universitat de València (UV), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares [Spain] (CIBERCV), Instituto de Salud Carlos III [Madrid] (ISC), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Universitat Autònoma de Barcelona (UAB), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), and leboeuf, Christophe
Subjects: medicine.medical_specialty, Ventricular Dysfunction, Right, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, Left ventricle ejection fraction, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Interquartile range, Internal medicine, medicine, Humans, 030212 general & internal medicine, Systole, Aged, Aged, 80 and over, Heart Failure, Iron deficiency, Ejection fraction, Anemia, Iron-Deficiency, biology, Transferrin saturation, business.industry, Right ventricle ejection fraction, Stroke Volume, General Medicine, Middle Aged, Prognosis, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Tricuspid annular plane systolic excursion, Ferritin, Blood pressure, Heart failure, Ventricular Function, Right, biology.protein, Cardiology, Female, Cardiology and Cardiovascular Medicine, Heart failure with preserved ejection fraction, business
Abstract: Aims Iron deficiency (ID) is a frequent finding in patients with chronic and acute heart failure (AHF) along the full spectrum of left ventricular ejection fraction (LVEF). Iron deficiency has been related to ventricular systolic dysfunction, but its role in right ventricular function has not been evaluated. We sought to evaluate whether ID identifies patients with greater right ventricular dysfunction in the setting of AHF. Methods and results We prospectively included 903 patients admitted with AHF. Right systolic function was evaluated by tricuspid annular plane systolic excursion (TAPSE) and the ratio TAPSE/pulmonary artery systolic pressure (TAPSE/PASP). Iron deficiency was defined, according to European Society of Cardiology criteria, as serum ferritin Conclusion In AHF, proxies of ID were associated with right ventricular dysfunction. Further studies should confirm these findings and evaluate the pathophysiological facts behind this association.
Published: 2021

20. Colorectal intussusception due to adenocarcinoma presenting as acute bowel obstruction in an adult

Author: Adrien Le Fouler, Nicolas Sellier, Pierre Platevoet, Alexis Roditis, Salma Jendoubi, leboeuf, Christophe, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], 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, and Université Sorbonne Paris Nord
Subjects: lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, lcsh:R895-920, Case Report, [SDV.CAN]Life Sciences [q-bio]/Cancer, Distension, 030218 nuclear medicine & medical imaging, Colorectal adenocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Occlusive syndrome, [SDV.CAN] Life Sciences [q-bio]/Cancer, Intussusception (medical disorder), medicine, Radiology, Nuclear Medicine and imaging, Laparoscopy, medicine.diagnostic_test, business.industry, Invagination, medicine.disease, Endoscopy, Bowel obstruction, Acute abdomen, Adenocarcinoma, Radiology, medicine.symptom, business, Intussusception, 030217 neurology & neurosurgery
Abstract: International audience; Colorectal intussusception is a rare entity in adults presenting an acute abdomen. The authors present a case of a 73-year-old female who presented with an acute large bowel obstruction. Abdominal computed tomography (CT) scan reveals a colorectal intussusception with a colonic distension upstream. Laparoscopy founds out a stenotic tumor on colorectal junction corresponding with an adenocarcinoma on histopathological exam. CT scan is the most specific diagnostic test for intussusception and is superior to ultrasonography and endoscopy and thus should be performed preferentially.
Published: 2021

21. CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction

Author: Frederick A. Masoudi, Kim Anderson, Simon Kouz, Douglas S. Lee, Shelley Zieroth, Michel D'Astous, Sean A. Virani, Sabina L.C. Keen, Stephanie Poon, Mustafa Toma, Brian Clarke, Kate Storm, Eileen O'Meara, Elizabeth Swiggum, Abhinav Sharma, Andrew Grant, Sharon A Bray, Gordon W. Moe, Marie-Claude Parent, Nadia Giannetti, George A. Heckman, Michael Chan, Justin A. Ezekowitz, Jodi Heshka, Bruce Sussex, Harriette G.C. Van Spall, Miroslaw Rajda, Sabe De, Amelia Ming Ching Yip, Adam Grzeslo, Jonathan G. Howlett, Lisa Mielniczuk, Serge Lepage, Sheri L. Koshman, Robert S. McKelvie, Michael McDonald, Margot K. Davis, Alain Cohen-Solal, Anique Ducharme, Kyla Siatecki, leboeuf, Christophe, TGH Peter Munk Cardiac Centre [Toronto, ON, Canada] (PMCC), University of British Columbia (UBC), University of Alberta, Montreal Heart Institute - Institut de Cardiologie de Montréal, McGill University Health Center [Montreal] (MUHC), University of Waterloo [Waterloo], University of Calgary, Université de Sherbrooke (UdeS), University of Ottawa [Ottawa], St. Michael's Hospital, University of Manitoba [Winnipeg], Dalhousie University [Halifax], The Pirbright Institute, Biotechnology and Biological Sciences Research Council (BBSRC), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Dr. Georges-L.-Dumont University Hospital Centre (CHUDGLD), Western University [London, ON, Canada], McMaster University [Hamilton, Ontario], Institut de cardiologie de l'Université d'Ottawa [Ottawa, ON, Canada] (ICUO), Centre Hospitalier Régional de Lanaudiere [Joliette, QC, Canada] (CHRDL), University of Colorado Anschutz [Aurora], Sunnybrook Health Sciences Centre, McGill University = Université McGill [Montréal, Canada], and Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN)
Subjects: Canada, medicine.medical_specialty, Angiotensin receptor, Digoxin, medicine.medical_treatment, Myocardial Infarction, Cardiac resynchronization therapy, Context (language use), 030204 cardiovascular system & hematology, Cardiac Resynchronization Therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Rate, Internal medicine, medicine, Humans, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Heart Failure, Ejection fraction, biology, business.industry, Cardiovascular Agents, Standard of Care, Stroke Volume, Angiotensin-converting enzyme, Canadian Cardiovascular Society, medicine.disease, Defibrillators, Implantable, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Hospitalization, Heart failure, biology.protein, Cardiology, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: International audience; In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a β-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.
Published: 2021

22. COVID-19 vaccination in patients with heart failure: a position paper of the Heart Failure Association of the European Society of Cardiology

Author: Wilfried Mullens, Dimitrios Farmakis, Tuvia Ben Gal, Gerasimos Filippatos, Tiny Jaarsma, Robin Ray, Ekaterini Lambrinou, Gianluigi Savarese, Carlo G. Tocchetti, Alain Cohen-Solal, Yuri N. Belenkov, Maurizio Volterrani, Stamatis Adamopoulos, Arsen D. Ristić, Brenda Moura, Amina Rakisheva, Arantxa González, Michele Senni, Finn Gustafsson, Antoni Bayes-Genis, Thomas Thum, Ovidiu Chioncel, Marco Metra, Magdy Abdelhamid, Fadi Jouhra, Y M Lopatin, Lars Lund, Giuseppe M.C. Rosano, Sophie Van Linthout, Davor Miličić, Petar M. Seferovic, Piotr Ponikowski, Andrew J.S. Coats, Mitja Lainscak, Massimo F Piepoli, Michael Böhm, Loreena Hill, Stefan D. Anker, Ewa A. Jankowska, Rosano, G, Jankowska, E, Ray, R, Metra, M, Abdelhamid, M, Adamopoulos, S, Anker, S, Bayes-Genis, A, Belenkov, Y, Gal, T, Böhm, M, Chioncel, O, Cohen-Solal, A, Farmakis, D, Filippatos, G, González, A, Gustafsson, F, Hill, L, Jaarsma, T, Jouhra, F, Lainscak, M, Lambrinou, E, Lopatin, Y, Lund, L, Milicic, D, Moura, B, Mullens, W, Piepoli, M, Ponikowski, P, Rakisheva, A, Ristic, A, Savarese, G, Seferovic, P, Senni, M, Thum, T, Tocchetti, C, Van Linthout, S, Volterrani, M, Coats, A, IRCCS San Raffaele [Rome, Italy], Wrocław Medical University, University of London [London], St George’s University Hospitals, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, Cairo University, Onassis Cardiac Surgery Center [Athens] (OCSC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Université de Barcelonne, Instituto de Salud Carlos III [Madrid] (ISC), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Sechenov First Moscow State Medical University, Tel Aviv University (TAU), Universität des Saarlandes [Saarbrücken], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), 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), University of Cyprus [Nicosia] (UCY), National and Kapodistrian University of Athens (NKUA), Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), University of Copenhagen = Københavns Universitet (UCPH), Queen's University [Belfast] (QUB), Linköping University (LIU), University of Ljubljana, Cyprus University of Technology, Volgograd State Medical University [Russian Federation] (VSMU), Karolinska University Hospital [Stockholm], University of Zagreb, Universidade do Porto = University of Porto, Hasselt University (UHasselt), Ziekenhuis Oost-Limburg (ZOL), Università degli studi di Parma = University of Parma (UNIPR), Al-Farabi Kazakh National University [Almaty] (KazNU), University of Belgrade [Belgrade], Serbian Academy of Sciences and Arts (SASA), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), University of Naples Federico II = Università degli studi di Napoli Federico II, German Center for Cardiovascular Research (DZHK), University of Warwick [Coventry], leboeuf, Christophe, Publica, Rosano, G., Jankowska, E. A., Ray, R., Metra, M., Abdelhamid, M., Adamopoulos, S., Anker, S. D., Bayes-Genis, A., Belenkov, Y., Gal, T. B., Bohm, M., Chioncel, O., Cohen-Solal, A., Farmakis, D., Filippatos, G., Gonzalez, A., Gustafsson, F., Hill, L., Jaarsma, T., Jouhra, F., Lainscak, M., Lambrinou, E., Lopatin, Y., Lund, L. H., Milicic, D., Moura, B., Mullens, W., Piepoli, M. F., Ponikowski, P., Rakisheva, A., Ristic, A., Savarese, G., Seferovic, P., Senni, M., Thum, T., Tocchetti, C. G., Van Linthout, S., Volterrani, M., and Coats, A. J. S.
Subjects: medicine.medical_specialty, COVID-19 Vaccines, medicine.medical_treatment, media_common.quotation_subject, Frail Elderly, Frailty syndrome, Cardiology, Heart failure, Disease, Medical and Health Sciences, SARS‐CoV‐2, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, SDG 3 - Good Health and Well-being, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, COVID‐19, Hygiene, medicine, Humans, Intensive care medicine, media_common, Aged, Heart transplantation, HFA position paper, business.industry, SARS-CoV-2, Social distance, Vaccination, COVID-19, Iron Deficiencies, medicine.disease, failure, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Failure, Position paper, Position Paper, Clinical Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Cardiology and Cardiovascular Medicine, business
Abstract: Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.]
Published: 2021

23. New treatments for heart failure and exercise capacity

Author: Florence Beauvais, Alain Cohen-Solal, leboeuf, Christophe, 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Heart Failure, medicine.medical_specialty, Exercise Tolerance, business.industry, MEDLINE, Exercise capacity, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Text mining, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, medicine, Humans, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Abstract: International audience; No abstract available
Published: 2021

24. The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model

Author: Charles Kung, Carlo Brugnara, Maria Teresa Valenti, Sebastien Ronseaux, Iana Iatcenko, Tomas Ganz, Anne Janin, Penelope A. Kosinski, Rohini Narayanaswamy, Leonardo Salviati, Achille Iolascon, Francesca Carlomagno, Shaoxia Yu, Giorgia Federico, Enrica Federti, Lucia De Franceschi, Chun-Ling Jung, Alessandro Matte, Roberta Russo, Francesco Michelangelo Turrini, Elisabetta Beneduce, Christophe Leboeuf, Maria Andrea Desbats, Lenny Dang, Università degli studi di Verona = University of Verona (UNIVR), Agios Pharmaceuticals, CEINGE - Biotecnologie Avanzate, University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli Studi di Padova = University of Padua (Unipd), 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, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Torino = University of Turin (UNITO), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), University of California [Los Angeles] (UCLA), University of California (UC), Harvard Medical School [Boston] (HMS), leboeuf, Christophe, Matte, A., Federti, E., Kung, C., Kosinski, P. A., Narayanaswamy, R., Russo, R., Federico, G., Carlomagno, F., Desbats, M. A., Salviati, L., Leboeuf, C., Valenti, M. T., Turrini, F., Janin, A., Yu, S., Beneduce, E., Ronseaux, S., Iatcenko, I., Dang, L., Ganz, T., Jung, C. -L., Iolascon, A., Brugnara, C., and De Franceschi, L.
Subjects: 0301 basic medicine, Ineffective erythropoiesis, thalassemia, Enzyme Activator, Genetic disease, Quinoline, medicine.disease_cause, Mouse models, Transgenic, Piperazines, Mice, 0302 clinical medicine, hemic and lymphatic diseases, Glycolysis, Chemistry, General Medicine, Hematology, Erythroferrone, Hemolysis, 030220 oncology & carcinogenesis, Drug therapy, Genetic diseases, Animals, Disease Models, Animal, Enzyme Activators, Female, Mice, Transgenic, Pyruvate Kinase, Quinolines, beta-Thalassemia, Erythropoiesis, HAMP, medicine.drug, Research Article, medicine.medical_specialty, Hemolysi, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Mouse model, 03 medical and health sciences, Internal medicine, medicine, Piperazine, ineffective erythropoiesis, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], Animal, medicine.disease, 030104 developmental biology, Endocrinology, Erythropoietin, Disease Models, iron homeostasis, Pyruvate kinase
Abstract: International audience; Anemia in β-thalassemia is related to ineffective erythropoiesis and reduced red cell survival. Excess free heme and accumulation of unpaired α-globin chains impose substantial oxidative stress on β-thalassemic erythroblasts and erythrocytes, impacting cell metabolism. We hypothesized that increased pyruvate kinase activity induced by mitapivat (AG-348) in the Hbb th3/+ mouse model for β-thalassemia would reduce chronic hemolysis and ineffective erythropoiesis through stimulation of red cell glycolytic metabolism. Oral mitapivat administration ameliorated ineffective erythropoiesis and anemia in Hbb th3/+ mice. Increased ATP, reduced reactive oxygen species production, and reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance suggested enhanced metabolism following mitapivat administration in β-thalassemia. The amelioration of responsiveness to erythropoietin resulted in reduced soluble erythroferrone, increased liver Hamp expression, and diminished liver iron overload. Mitapivat reduced duodenal Dmt1 expression potentially by activating the pyruvate kinase M2-HIF2α axis, representing a mechanism additional to Hamp in controlling iron absorption and preventing β-thalassemia-related liver iron overload. In ex vivo studies on erythroid precursors from patients with β-thalassemia, mitapivat enhanced erythropoiesis, promoted erythroid maturation, and decreased apoptosis. Overall, pyruvate kinase activation as a treatment modality for β-thalassemia in preclinical model systems had multiple beneficial effects in the erythropoietic compartment and beyond, providing a strong scientific basis for further clinical trials.
Published: 2021

25. Anemia and hemodilution: analysis of a single center cohort based on 2,858 red cell mass measurements

Author: Juliette Soret-Dulphy, Laetitia Vercellino, Anne C. Brignier, Marie-Helene Schlageter, Louis Drevon, Bruno Cassinat, Célia Belkhodja, Christine Chomienne, Nabih Maslah, Christine Dosquet, Nathalie Parquet, Jean-Jacques Kiladjian, Odno Ravdan, Stéphane Giraudier, leboeuf, Christophe, Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), France Intergroupe des Syndromes Myeloproliferatifs (FMI Paris), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Hemodilution, medicine.medical_specialty, Red Cell, Anemia, business.industry, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MEDLINE, Hematology, medicine.disease, Single Center, Cohort Studies, Text mining, Hematocrit, Internal medicine, Cohort, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Letters to the Editor, business, Erythrocyte Volume
Abstract: International audience; No abstract available
Published: 2021

26. G-CSF does not worsen toxicities and efficacy of CAR-T cells in refractory/relapsed B-cell lymphoma

Author: Catherine Thieblemont, Sylvie Chevret, Roberta Di Blasi, Sophie Bernard, Florence Morin, Laetitia Vercellino, Eugenio Galli, Vincent Allain, Hannah Moatti, Sophie Caillat-Zucman, leboeuf, Christophe, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Transplantation, Lymphoma, B-Cell, Receptors, Chimeric Antigen, business.industry, T-Lymphocytes, Antigens, CD19, Receptors, Antigen, T-Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, medicine.disease, Immunotherapy, Adoptive, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, Granulocyte Colony-Stimulating Factor, Cancer research, Medicine, Humans, Car t cells, business, B-cell lymphoma
Abstract: International audience; No abstract available
Published: 2020

27. The Status of Specialized Ambulatory Heart Failure Care in Canada: A Joint Canadian Heart Failure Society and Canadian Cardiovascular Society Heart Failure Guidelines Survey

Author: George A. Heckman, Sean A. Virani, Howard Abrams, Nadia Giannetti, S. Lepage, Eileen O'Meara, Douglas Lee, Marie-Hélène Leblanc, Simon Kouz, Elizabeth Swiggum, Estrellita Estrella-Holder, Heather J. Ross, Adrian F. Hernandez, Frederick A. Masoudi, Sylvain Matteau, Gordon W. Moe, Bruce Sussex, Michel D'Astous, Alain Cohen-Solal, Miroslaw Rajda, Sabe De, Sharon A Bray, Lee A. Green, Sheri L. Koshman, Marie-Claude Parent, Adam Grzeslo, Jonathan G. Howlett, Diego H. Delgado, Secondary Panel, Anique Ducharme, Lisa Mielniczuk, Justin A. Ezekowitz, Michael Chan, Michael McDonald, Karen Harkness, Mustafa Toma, Robert S. McKelvie, Olivier Desplantie, Abdul Al-Hesaye, Shelley Zieroth, Ccs Hf Guidelines Primary, Haissam Haddad, University of British Columbia (UBC), University of Manitoba [Winnipeg], Lived Experience Partner [Toronto, ON, Canada] (LEP), Montreal Heart Institute - Institut de Cardiologie de Montréal, Hamilton Health Sciences, University of Alberta, University Health Network, Royal Alexandra Children's Hospital, McGill University Health Center [Montreal] (MUHC), McMaster University [Hamilton, Ontario], University of Waterloo [Waterloo], University of Calgary, Université de Sherbrooke (UdeS), University of Ottawa [Ottawa], St. Michael's Hospital, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), 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), Dr. Georges-L.-Dumont University Hospital Centre (CHUDGLD), Western University [London, ON, Canada], University of Toronto, Saint Boniface General Hospital [Winnipeg, MA, Canada] (SBGH), University of Saskatchewan [Saskatoon] (U of S), Duke University [Durham], Centre Hospitalier Régional de Lanaudiere [Joliette, QC, Canada] (CHRDL), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), University of Colorado Anschutz [Aurora], Hôpital régional Chaleur [Bathurst, NB, Canada] (HRC), Université de Montréal (UdeM), QEII Health Sciences Centre [Halifax, NS, Canada] (HSC), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Writing Group, Canadian Heart Failure Society and the Canadian Cardiovascular Society Heart Failure Guidelines Panel, CCS HF Guidelines Primary and Secondary Panel., and leboeuf, Christophe
Subjects: lcsh:Diseases of the circulatory (Cardiovascular) system, Shared care, business.industry, MEDLINE, Capacity building, Review, Canadian Cardiovascular Society, Viewpoints, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Nursing, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, lcsh:RC666-701, Heart failure, Health care, Ambulatory, medicine, Cardiology and Cardiovascular Medicine, business
Abstract: This joint Canadian Heart Failure Society and the CCS Heart Failure guidelines report has been developed to provide a pan-Canadian snapshot of the current state of clinic-based ambulatory heart failure (HF) care in Canada with specific reference to elements and processes of care associated with quality and high performing health systems. It includes the viewpoints of persons with lived experience, patient care providers, and administrators. It is imperative to build on the themes identified in this survey, through engaging all health care professionals, to develop integrated and shared care models that will allow better patient outcomes. Several patient and organizational barriers to care were identified in this survey, which must inform the development of regional care models and pragmatic solutions to improve transitions for this patient population. Unfortunately, we were unsuccessful in incorporating the perspectives of primary care providers and internal medicine specialists who provide the majority of HF care in Canada, which in turn limits our ability to comment on strategies for capacity building outside the HF clinic setting. These considerations must be taken into account when interpreting our findings. Engaging all HF care providers, to build on the themes identified in this survey, will be an important next step in developing integrated and shared care models known to improve patient outcomes. Résumé: Ce rapport conjoint des lignes directrices de la Société canadienne d'insuffisance cardiaque et de la Société canadienne de cardiologie (SCC) sur l'insuffisance cardiaque a été élaboré pour fournir un aperçu pancanadien de l'état actuel des soins ambulatoires de l'insuffisance cardiaque (IC) en clinique au Canada, en se référant spécifiquement aux éléments et aux processus de soins associés à des systèmes de santé très performants et de qualité. Il comprend les points de vue de personnes ayant une expérience vécue de l'IC, de prestataires de soins aux patients et d'administrateurs. Il est impératif de s'appuyer sur les thématiques identifiées dans cette enquête, en y engageant tous les professionnels de la santé, pour développer des modèles de soins intégrés et partagés qui permettront de meilleurs pronostics pour les patients. Plusieurs obstacles relatifs aux patients et organisationnels dont il faudra se soucier ont été identifiés dans cette enquête, qui doit servir de base à l'élaboration de modèles de soins régionaux et de solutions pragmatiques pour améliorer les transitions pour cette population de patients. Malheureusement, nous n'avons pas réussi à intégrer les points de vue des prestataires de soins primaires et des spécialistes en médecine interne qui fournissent la majorité des soins en IC au Canada, ce qui limite notre capacité à commenter les stratégies de renforcement des capacités en dehors du cadre des cliniques d’IC. Ces considérations doivent être prises en compte lors de l'interprétation de nos conclusions. L'engagement de tous les prestataires de soins de santé en IC à s'appuyer sur les thématiques identifiées dans cette enquête constituera une prochaine étape importante dans le développement de modèles de soins intégrés et partagés connus pour améliorer le pronostic des patients.
Published: 2020

28. How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

Author: Eurydice Angeli, Anne Janin, Guilhem Bousquet, Thuy T Nguyen, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, National Cancer Hospital [Ha Noi, Viet Nam], Hopital Saint-Louis [AP-HP] (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and leboeuf, Christophe
Subjects: Cell Membrane Permeability, blood-tumor barrier, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, blood–brain barrier, Bioinformatics, Drug penetration, Blood–brain barrier, Catalysis, Inorganic Chemistry, blood–tumor barrier, Drug Delivery Systems, Drug Development, [SDV.CAN] Life Sciences [q-bio]/Cancer, Daily practice, brain metastases, Animals, Humans, Medicine, Molecular Targeted Therapy, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, copy number profiling, Brain Neoplasms, business.industry, Drug Administration Routes, Organic Chemistry, Blood tumor barrier, Cancer, General Medicine, blood-brain barrier, medicine.disease, Anticancer drug, Computer Science Applications, anticancer drugs, medicine.anatomical_structure, mutation, business, pharmacokinetics, Biomarkers
Abstract: International audience; The incidence of brain metastases has increased in the last 10 years. However, the survival of patients with brain metastases remains poor and challenging in daily practice in medical oncology. One of the mechanisms suggested for the persistence of a high incidence of brain metastases is the failure to cross the blood–brain barrier of most chemotherapeutic agents, including the more recent targeted therapies. Therefore, new pharmacological approaches are needed to optimize the efficacy of anticancer drug protocols. In this article, we present recent findings in molecular data on brain metastases. We then discuss published data from pharmacological studies on the crossing of the blood–brain barrier by anticancer agents. We go on to discuss future developments to facilitate drug penetration across the blood–brain barrier for the treatment of brain metastases among cancer patients, using physical methods or physiological transporters.
Published: 2020

29. Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial

Author: Burkert, Pieske, Mahesh J, Patel, Cynthia M, Westerhout, Kevin J, Anstrom, Javed, Butler, Justin, Ezekowitz, Adrian F, Hernandez, Joerg, Koglin, Carolyn S P, Lam, Piotr, Ponikowski, Lothar, Roessig, Adriaan A, Voors, Christopher M, O'Connor, Paul W, Armstrong, Jian, Zhang, leboeuf, Christophe, Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Merck & Co. Inc. [Kenilworth, NJ, USA], University of Alberta, Duke University Medical Center, University of Mississippi Medical Center (UMMC), King‘s College London, University of Wrocław [Poland] (UWr), Bayer Pharma AG [Berlin], University Medical Center Groningen [Groningen] (UMCG), Duke University [Durham], VICTORIA Study Group: Imran Zainal Abidin, Dan Atar, M Cecilia Bahit, Juan Luis Arango Benecke, Edimar A Bocchi, Diana Bonderman, Myeong-Chan Cho, Chern-En Chiang, Alain Cohen-Solal, Martin Cowie, Frank Edelmann, Michele Emdin, Jorge Escobedo, Justin A Ezekowitz, Michael M Givertz, David M Kaye, Fernando Lanas, Johan Lassus, Basil S Lewis, Yury Lopatin, José López-Sendón, Lars H Lund, Kenneth McDonald, Vojtěch Melenovský, Arend Mosterd, Ebrahim Noori, M Ali Oto, Armando Lionel Godoy Palomino, Ileana L Piña, Piotr Ponikowski, Anne-Catherine Pouleur, Jens Refsgaard, Eugene Reyes, Clara Saldarriaga, Michele Senni, David Sim, David Siu, Karen Sliwa-Hähnle, Nancy K Sweitzer, Richard W Troughton, Hiroyuki Tsutsui, Dimitrios N Tziakas, Jose B Vazquez-Tanus, Jian Zhang., and Cardiovascular Centre (CVC)
Subjects: Male, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Interquartile range, Natriuretic Peptide, Brain, Heart Failure/blood, Myocardial infarction, Prospective Studies, education.field_of_study, Framingham Risk Score, Ejection fraction, Atrial fibrillation, Heart failure with reduced ejection fraction, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trial, Treatment Outcome, STIMULATOR, ENALAPRIL, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Population, Heterocyclic Compounds, 2-Ring, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, SOLUBLE GUANYLATE-CYCLASE, Humans, Soluble guanylate cyclase, Cyclic guanosine monophosphate, Protein Precursors, education, Heterocyclic Compounds, 2-Ring/therapeutic use, Aged, Heart Failure, business.industry, Pyrimidines/therapeutic use, Stroke Volume, medicine.disease, Peptide Fragments, Pyrimidines, Stroke Volume/physiology, Heart failure, Natriuretic Peptide, Brain/blood, business, Peptide Fragments/blood, Biomarkers, Biomarkers/blood, Follow-Up Studies
Abstract: International audience; Aim: Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial.Methods and results: Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73 m2 . Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization
Published: 2019

30. Micromolecular methods for diagnosis and therapeutic strategy: a case study

Author: Amélie Benbara, Fatiha Bouhidel, Laurent Zelek, Charlotte Brugière, Iulia Tengher, Morad Elbouchtaoui, Christophe Leboeuf, Marianne Ziol, Anne Janin, Catherine Miquel, Guilhem Bousquet, Service de Pathologie [AP-HP Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Hôpital Avicenne [AP-HP], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Service d'Oncologie Médicale [AP-HP Hôpital Avicenne], Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], and leboeuf, Christophe
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Case Report, micromethods, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Trastuzumab, Internal medicine, medicine, Carcinoma, Copy-number variation, skin and connective tissue diseases, Total Mastectomy, Pathological, business.industry, medicine.disease, HER2 overexpressing breast cancer, 3. Good health, 030104 developmental biology, Estrogen, 030220 oncology & carcinogenesis, Cancer cell, cancer therapy, trastuzumab-based treatment, business, laser-microdissection, Adjuvant, medicine.drug
Abstract: International audience; An intraductal carcinoma, 55 mm across, was diagnosed on a total mastectomy in a 45-year-old woman. The 2 micro-invasive areas found were too small for reliable immunostainings for estrogen, progesterone, and HER2 receptors. In the sentinel lymph-node, a subcapsular tumor embole of about 50 cancer cells was identified on the extemporaneous cryo-cut section, but not on further sections after paraffinembedding of the sample. Considering this tumor metastatic potential, we decided to assess HER2 status on the metastatic embole using pathological and molecular micro-methods. We lasermicrodissected the tumor cells, extracted their DNA, and performed droplet-digital-PCR (ddPCR) for HER2 gene copy number variation. The HER2/RNaseP allele ratio was 5.2 in the laser-microdissected tumor cells, similar to the 5.3 ratio in the HER2overexpressing breast cancer cell line BT-474. We thus optimized the adjuvant treatment of our patient and she received a trastuzumab-based adjuvant chemotherapy.
Published: 2018

31. The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions

Author: Aušra Kavoliūnienė, Carolyn S.P. Lam, Christian Mueller, Òscar Miró, Vera Regitz-Zagrosek, Aldo P. Maggioni, Alexandre Mebazaa, Alain Cohen-Solal, Adriaan A. Voors, Yuya Matsue, Katsuya Kajimoto, Jiri Parenica, Gregg C. Fonarow, W. Frank Peacock, Eiichi Akiyama, Johan Lassus, Dong-Ju Choi, Etienne Gayat, Ali Ahmed, Jelena Čelutkienė, Justina Motiejūnaitė, Justin A. Ezekowitz, Naoki Sato, Cardiovascular Centre (CVC), 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), Lithuanian University of Health Sciences [Kaunas, Lithuania], Yokohama City University (YCU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Basel (Unibas), Seoul National University Bundang Hospital (SNUBH), Lithuanian University of health Sciences [Kaunas], Vilnius University [Vilnius], University Hospital Brno, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Sekikawa Hospital [Tokyo, Japan] (SH), Nippon Medical School [Tokyo, Japan], University of Barcelona, Baylor College of Medicine (BCM), Baylor University, Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), King‘s College London, University of Alberta, Linköping University (LIU), University of California (UC), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], and leboeuf, Christophe
Subjects: Male, medicine.medical_specialty, CONTEMPORARY MANAGEMENT, Asia, Prognosis, 030204 cardiovascular system & hematology, Lower risk, Ventricular Function, Left, EJECTION FRACTION, 03 medical and health sciences, AGE, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, ESC Report, Medicine, Humans, In patient, 030212 general & internal medicine, Prospective Studies, Registries, PREDICTORS, Heart Failure, Ejection fraction, business.industry, GENDER-RELATED DIFFERENCES, MORTALITY, Hazard ratio, Acute heart failure, Gender, Stroke Volume, medicine.disease, Biological sex, Comorbidity, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Clinical trial, Europe, Editorial, Heart failure, Acute Disease, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. Methods and results We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79–0.94), P Conclusion Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF.
Published: 2019

32. Immunotherapy for LELC: Case Report and a Focused Review

Author: Boris Duchemann, Marie Darrason, Laurent Zelek, Guilhem Bousquet, Kader Chouahnia, Pierre-Yves Brillet, Antoine Martin, Hanene Boudabous, Marie-Christine Pailler, Michael Soussan, AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and leboeuf, Christophe
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Respiratory Mucosa, Disease, NSCLC, 03 medical and health sciences, 0302 clinical medicine, Asian People, [SDV.CAN] Life Sciences [q-bio]/Cancer, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Carcinoma, Humans, Stage (cooking), Lung cancer, Cisplatin, Chemotherapy, Lung, business.industry, Rare tumor, Antibodies, Monoclonal, Immunotherapy, medicine.disease, Survival Analysis, Lymphoepithelioma-like carcinoma of the lung, Treatment, [SDV] Life Sciences [q-bio], Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract: International audience; Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare, Epstein-Barr virus-associated tumor. LELC occurs mostly in young, Asian nonsmokers. A few hundred cases have been reported, mostly from retrospective Asian studies. Optimal treatment has not been clearly established. Treatment options are based on surgery for early stage and on cisplatin-based chemotherapy as first-line therapy for metastatic disease. Prognosis may seem better than for other types of nonesmall-cell lung cancer, but it remains poor in advanced disease, with a median survival of 24 months, and new treatments options are still warranted. Immunotherapies are now key players in the treatment of non esmall-cell lung cancer. However, few data are available for this rare histologic subgroup. We have reviewed the available data on LELC with a focus on the first few cases reported with a response to a programmed cell death 1 inhibitor.
Published: 2019

33. Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of beta-thalassemia

Author: Tomas Tomka, Achille Iolascon, Lucia De Franceschi, Christhophe Lebouef, Maria Luisa Di Paolo, Franco Turrini, Annette Koerner, Immacolata Andolfo, Luigia De Falco, Norman A. Mazer, Enrica Federti, Jane-Jane Chen, Alessandro Matte, Anja Harmeier, Alejandra Macias-Garcia, Anne Janin, Carlo Brugnara, Michael Winter, Elisabetta Beneduce, Matte, Alessandro, Federti, Enrica, Winter, Michael, Koerner, Annette, Harmeier, Anja, Mazer, Norman, Tomka, Toma, Di Paolo, Maria Luisa, De Falco, Luigia, Andolfo, Immacolata, Beneduce, Elisabetta, Iolascon, Achille, Macias-Garcia, Alejandra, Chen, Jane-Jane, Janin, Anne, Leboeuf, Christophe, Turrini, Francesco, Brugnara, Carlo, and De Franceschi, Lucia
Subjects: 0301 basic medicine, Ineffective erythropoiesis, Bitopertin, thalassemia, Erythrocytes, Iron Overload, Cell Survival, Anemia, Mice, Transgenic, Pharmacology, medicine.disease_cause, Hemolysis, bitopertin, Piperazines, Mice, 03 medical and health sciences, chemistry.chemical_compound, iron, 0302 clinical medicine, Glycine Plasma Membrane Transport Proteins, Hepcidin, hemic and lymphatic diseases, medicine, Animals, Sulfones, heme, Heme, Glycine transport, biology, Chemistry, beta-Thalassemia, General Medicine, Hematology, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Liver, 030220 oncology & carcinogenesis, biology.protein, Erythropoiesis, Drug therapy, Female, thalassemia, erythropoiesis, iron, heme, bitopertin, erythropoiesis, Research Article
Abstract: Anemia of β-thalassemia is caused by ineffective erythropoiesis and reduced red cell survival. Several lines of evidence indicate that iron/heme restriction is a potential therapeutic strategy for the disease. Glycine is a key initial substrate for heme and globin synthesis. We provide evidence that bitopertin, a glycine transport inhibitor administered orally, improves anemia, reduces hemolysis, diminishes ineffective erythropoiesis, and increases red cell survival in a mouse model of β-thalassemia (Hbb(th3/+) mice). Bitopertin ameliorates erythroid oxidant damage, as indicated by a reduction in membrane-associated free α-globin chain aggregates, in reactive oxygen species cellular content, in membrane-bound hemichromes, and in heme-regulated inhibitor activation and eIF2α phosphorylation. The improvement of β-thalassemic ineffective erythropoiesis is associated with diminished mTOR activation and Rab5, Lamp1, and p62 accumulation, indicating an improved autophagy. Bitopertin also upregulates liver hepcidin and diminishes liver iron overload. The hematologic improvements achieved by bitopertin are blunted by the concomitant administration of the iron chelator deferiprone, suggesting that an excessive restriction of iron availability might negate the beneficial effects of bitopertin. These data provide important and clinically relevant insights into glycine restriction and reduced heme synthesis strategies for the treatment of β-thalassemia.
Published: 2019

34. FADD at the Crossroads between Cancer and Inflammation

Author: Sara Mouasni, Léa Tourneur, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), and leboeuf, Christophe
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Fas-Associated Death Domain Protein, Fas-associated death domain, Immunology, Inflammation, urologic and male genital diseases, 03 medical and health sciences, Death Domain, Neoplasms, post-translational modifications, medicine, cancer, Immunology and Allergy, Animals, Humans, Secretion, FADD, Receptor, innate immunity, Death domain, Innate immune system, biology, Cancer, Inflammasome, medicine.disease, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, biology.protein, signalosomes, biological phenomena, cell phenomena, and immunity, medicine.symptom, medicine.drug
Abstract: International audience; Initially described as an adaptor molecule for death receptor (DR)-mediated apoptosis, Fas-associated death domain (FADD) was later implicated in nonapoptotic cellular processes. During the last decade, FADD has been shown to participate and regulate most of the signalosome complexes, including necrosome, FADDosome, innateosome, and inflammasome. Given the role of these signaling complexes, FADD has emerged as a new actor in innate immunity, inflammation, and cancer development. Concomitant to these new roles, a surprising number of mechanisms deemed to regulate FADD functions have been identified, including post-translational modifications of FADD protein and FADD secretion. This review focuses on recent knowledge of the biological roles of FADD, a pleiotropic molecule having multiple partners, and its impact in cancer, innate immunity, and inflammation.
Published: 2018

35. A novel way to manage trastuzumab cardiotoxicity

Author: Anne Janin, Charles Isorni, Diaddin Hamdan, Guilhem Bousquet, Gilles Paintaud, Laurent Zelek, François Darrouzain, Theodora Bejan-Angoulvant, Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, and leboeuf, Christophe
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Peak concentration, Administration schedule, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Toxicology, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Trastuzumab, Internal medicine, medicine, Humans, Pharmacology (medical), skin and connective tissue diseases, neoplasms, Antibody, Pharmacology, Cardiotoxicity, Ejection fraction, business.industry, Carcinoma, Ductal, Breast, Middle Aged, medicine.disease, Prognosis, Metastatic breast cancer, Carboplatin, Anti-HER2, Regimen, chemistry, 030220 oncology & carcinogenesis, Toxicity, Female, business, medicine.drug
Abstract: International audience; Purpose: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule.Methods: In this paper, we report the case of a patient with metastatic breast cancer responding to trastuzumab, who developed severe cardiac toxicity twice using a 3-weekly regimen. Considering preclinical pharmacological data on trastuzumab cardiotoxicity, we hypothesized that a weekly schedule of trastuzumab with lower peaks of serum concentration could be safe while remaining efficient. With the patient's consent, we started a weekly combination of carboplatin (AUC2) and trastuzumab (2 mg/kg) with close monitoring of trastuzumab concentrations.Results: We successfully controlled the disease for an additional 6 months with relevant trough concentrations of trastuzumab of around 50 mg/L. Another important aspect is that, with this weekly schedule, we observed no cardiac toxicity, and the left ventricular ejection fraction remained stabilized, at over 50%.Conclusions: Trastuzumab is the most widely prescribed anti-HER2 monoclonal antibody for the treatment of HER2 metastatic breast cancer, and it is the only drug that has been approved for the treatment of localized HER2 breast cancer, 1-year treatment being required after surgery. In case of cardiac toxicity, particularly in women over 60 years of age, a weekly regimen with lower peaks of concentration could be an alternative to the standard 3-weekly regimen.
Published: 2018

36. Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas5 cm: Long-Term Results

Author: Valérie Bourcier, Olivier Sutter, Véronique Grando, Nathalie Ganne-Carrié, Jean-Charles Nault, Pierre Nahon, Nicolas Sellier, Emmanuelle Coderc, Abou Diallo, Gisèle N'Kontchou, Olivier Seror, leboeuf, Christophe, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Avicenne [AP-HP]
Subjects: medicine.medical_specialty, Cirrhosis, Hepatocellular carcinoma, Radiofrequency ablation, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Large tumor, Liver transplantation, Gastroenterology, law.invention, Multibipolar technology, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, No touch technique, Internal medicine, medicine, In patient, Original Paper, Hepatology, business.industry, Long term results, medicine.disease, Ablation, Safety profile, Oncology, business
Abstract: Aims and Background: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. Methods: Eighty-three consecutive patients with cirrhosis (median age 70 years [37–93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1–9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. Results: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1–112 months), in naive patients the 3- and 5-year OS was 51% (38–62) and 24% (13–36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33–4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32–6.21], p = 0.008), multinodular form (HR: 2.74 [1.4–5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67–7.01], p = 0.0007) were independent RFS predictors. Conclusions: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.
Published: 2017

37. Peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension

Author: Francesco Manna, Sonia Levi, Angela Siciliano, Enrica Federti, Achille Iolascon, Anne Janin, Lucia De Franceschi, Alessandra Ghigo, Christophe Leboeuf, Elisabetta Beneduce, Alessandro Matte, Dae Won Kim, Immacolata Andolfo, Soo Young Choi, Davide Melisi, Cimino James, Federti, Enrica, Matté, Alessandro, Ghigo, Alessandra, Andolfo, Immacolata, James, Cimino, Siciliano, Angela, Leboeuf, Christophe, Janin, Anne, Manna, Francesco, Choi, Soo Young, Iolascon, Achille, Beneduce, Elisabetta, Melisi, Davide, Kim, Dae Won, Levi, Sonia, and De Franceschi, Lucia
Subjects: 0301 basic medicine, Male, Becaplermin, Gene Expression, Cell-Penetrating Peptides, Biochemistry, Pathogenesis, Mice, 0302 clinical medicine, Peroxiredoxin-2, Hypoxia, Lung, Mice, Knockout, Proto-Oncogene Proteins c-sis, Endoplasmic Reticulum Stress, Extracellular Matrix, 030220 oncology & carcinogenesis, ER stre, medicine.symptom, ER stress, Autophagy, Chronic hypoxia, Hypertension, Pulmonary, Recombinant Fusion Proteins, Physiology (medical), Peroxiredoxin 2, Biology, Pulmonary Artery, 03 medical and health sciences, medicine, Animals, Homeodomain Proteins, Endothelial Cells, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Mice, Inbred C57BL, Oxidative Stress, 030104 developmental biology, Cytoprotection, Immunology, Cancer research, Unfolded protein response, Unfolded Protein Response, Peroxiredoxin, Cytokine storm, Gene Deletion
Abstract: Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homeostasis is yet to be fully defined. Here, we showed that Prx2-/- mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH. We focused on the early phase PAH to dissect the role of Prx2 in generation of PAH. Hypoxic Prx2-/-mice showed (i) amplified inflammatory response combined with cytokine storm; (ii) vascular activation and dysfunction; (iii) increased PDGF-B lung levels, as marker of extracellular-matrix deposition and remodeling; and (iv) ER stress with activation of UPR system and autophagy. Rescue experiments with in vivo the administration of fused-recombinant-PEP-Prx2 show a reduction in pulmonary inflammatory vasculopathy and in ER stress with down-regulation of autophagy. Thus, we propose Prx2 plays a pivotal role in the early stage of PAH as multimodal cytoprotector, targeting oxidation, inflammatory vasculopathy and ER stress with inhibition of autophagy. Collectively, our data indicate that Prx2 is able to interrupt the hypoxia induced vicious cycle involving oxidation-inflammation-autophagy in the pathogenesis of PAH.
Published: 2017

38. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer

Author: Marc Espié, Jean-Paul Feugeas, Philippe Bertheau, Anne Janin, Anne de Roquancourt, Tan Sophie, Laurence Verneuil, Christophe Leboeuf, Philippe Ratajczak, Morad El Bouchtaoui, Guilhem Bousquet, Cédric de Bazelaire, Sylvie Giacchetti, 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 Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Sorbonne Paris Cité (USPC), and leboeuf, Christophe
Subjects: 0301 basic medicine, Oncology, breast cancer stem cells, medicine.medical_treatment, Triple Negative Breast Neoplasms, Mice, 0302 clinical medicine, Medicine, Prospective Studies, Neoadjuvant therapy, Triple-negative breast cancer, chemoresistance, Chloroquine, Middle Aged, Cell Hypoxia, Neoadjuvant Therapy, 3. Good health, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Triple-Negative Breast Carcinoma, Female, TNBC, Research Paper, medicine.medical_specialty, autophagy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer stem cell, Internal medicine, Cell Line, Tumor, Animals, Humans, Cell Proliferation, Neoplasm Staging, Chemotherapy, business.industry, hypoxia, Cancer, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Drug Resistance, Neoplasm, Immunology, Neoplasm Grading, business
Abstract: // Guilhem Bousquet 1, 2, 3, 4 , Morad El Bouchtaoui 2 , Tan Sophie 2 , Christophe Leboeuf 1, 2 , Cedric de Bazelaire 1, 2, 5 , Philippe Ratajczak 1, 2 , Sylvie Giacchetti 6 , Anne de Roquancourt 1, 2, 7 , Philippe Bertheau 1, 2, 7 , Laurence Verneuil 1, 2 , Jean-Paul Feugeas 8 , Marc Espie 1, 6 , Anne Janin 1, 2, 7 1 Universite Paris Diderot, Sorbonne Paris Cite, Laboratoire Pathologie, Paris, France 2 INSERM, Paris, France 3 Universite Paris 13, Villetaneuse, France 4 AP, HP, Avicenne, Service Oncologie, Paris, France 5 AP HP Hopital Saint-Louis, Service Radiologie, Paris, France 6 AP HP Hopital Saint-Louis, Centre Maladies Sein, Paris, France 7 AP HP Hopital Saint-Louis, Service Pathologie, Paris, France 8 INSERM, Paris, France Correspondence to: Guilhem Bousquet, email: guilhem.bousquet@aphp.fr Anne Janin, email: anne.janin1165@gmail.com Keywords: breast cancer stem cells, TNBC, chemoresistance, autophagy, hypoxia Received: March 21, 2017 Accepted: March 29, 2017 Published: April 07, 2017 ABSTRACT There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents. Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage. We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC). We found that chemoresistance was associated with large numbers of breast cancer stem-cells, and that these cancer stem-cells were neither proliferative nor apoptotic, but in an autophagic state related to hypoxia. Using relevant pharmacological models of patient-derived TNBC xenografts, we further investigated the role of autophagy in chemoresistance of breast cancer stem-cells. We demonstrated that hypoxia increased drug resistance of autophagic TNBC stem-cells, and showed that molecular or chemical inhibition of autophagic pathway was able to reverse chemoresistance. Our results support breast cancer stem-cell evaluation in pre-treatment biopsies of TNBC patients, and the need for further research on autophagy inhibition to reverse resistance to chemotherapy.
Published: 2017

39. Pretreatment Liver Injury Predicts Poor Prognosis of DLBCL Patients

Author: Christophe Leboeuf, Qing Shi, Rong Shen, Bin-Shen Ou-Yang, Li Wang, Shu Cheng, Anne Janin, Yan Zhao, Xing Fan, Chao-Fu Wang, Wei-Li Zhao, Ying Qian, leboeuf, Christophe, Shanghai Jiao Tong University School of Medicine, Pennsylvania State University (Penn State), Penn State System, Laboratoire de pathologie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomedical Research Imaging Center [North Carolina] (BRIC), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), 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, Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, Male, Pathology, [SDV]Life Sciences [q-bio], Aggressive lymphoma, Kaplan-Meier Estimate, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Prednisone, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Liver injury, Middle Aged, Prognosis, [SDV] Life Sciences [q-bio], Liver, Vincristine, 030220 oncology & carcinogenesis, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, lcsh:RB1-214, medicine.drug, medicine.medical_specialty, Article Subject, Cyclophosphamide, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Autoimmune Diseases, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, lcsh:Pathology, medicine, Humans, Glucocorticoids, Retrospective Studies, Inflammation, business.industry, Cell Biology, medicine.disease, Lymphoma, 030104 developmental biology, Doxorubicin, Case-Control Studies, Multivariate Analysis, Clinical Study, business
Abstract: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphoma, with different clinical manifestation and prognosis. The International Prognostic Index (IPI), an index designed during the prerituximab era for aggressive lymphoma, showed variable values in the prediction of patient clinical outcomes. The aim of this study was to analyze the prognostic value and causes of pretreatment liver injury in 363 de novo DLBCL patients in our institution. Pretreatment liver impairment, commonly detected in lymphoma patients, showed significant association with poor outcomes and increased serum inflammatory cytokines in DLBCL patients but had no relation to hepatitis B virus replication nor lymphomatous hepatic infiltration. Multivariate analysis revealed that liver dysfunction, advanced Ann Arbor stage, and elevated lactate dehydrogenase (LDH) were independent adverse prognostic factors of both PFS and OS. Accordingly, a new liver-IPI prognostic model was designed by adding liver injury as an important factor in determining IPI score. Based on Kaplan-Meier curves for PFS and OS, the liver-IPI showed better stratification in DLBCL patients than either the IPI or the revised IPI in survival prediction.
Published: 2017

40. Data demonstrating the role of peroxiredoxin 2 as important anti-oxidant system in lung homeostasis

Author: Alessandro Matte, Lucia De Franceschi, Cimino James, Soo Young Choi, Alessandra Ghigo, Elisabetta Beneduce, Dae Won Kim, Christophe Leboeuf, Enrica Federti, Sonia Levi, Achille Iolascon, Angela Siciliano, Francesco Manna, Anne Janin, Davide Melisi, Immacolata Andolfo, Federti, Enrica, Matte, Alessandro, Ghigo, Alessandra, Andolfo, Immacolata, James, Cimino, Siciliano, Angela, Leboeuf, Christophe, Janin, Anne, Manna, Francesco, Choi, Soo Young, Iolascon, Achille, Beneduce, Elisabetta, Melisi, Davide, Kim, Dae Won, Levi, Sonia, and De Franceschi, Lucia
Subjects: 0301 basic medicine, Peroxiredoxin 2, Biology, lcsh:Computer applications to medicine. Medical informatics, peroxiredoxin-2, 03 medical and health sciences, medicine.artery, medicine, Endothelial dysfunction, lcsh:Science (General), Lung, Multidisciplinary, hypoxia, Wild type, Hypoxia (medical), respiratory system, Medicine and Dentistry, medicine.disease, Pulmonary hypertension, 030104 developmental biology, medicine.anatomical_structure, pulmonary artery hypertension, hypoxia, peroxiredoxin-2, Immunology, Pulmonary artery, Cancer research, lcsh:R858-859.7, medicine.symptom, Homeostasis, pulmonary artery hypertension, lcsh:Q1-390
Abstract: The data presented in this article are related to the research paper entitled "peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension" (Federti et al., 2017) [1]. Data show that the absence of peroxiredoxin-2 (Prx2) is associated with increased lung oxidation and pulmonary vascular endothelial dysfunction. Prx2-/- mice displayed activation of the redox-sensitive transcriptional factors, NF-kB and Nrf2, and increased expression of cytoprotective system such as heme-oxygenase-1 (HO-1). We also noted increased expression of both markers of vascular activation and extracellular matrix remodeling. The administration of the recombinant fusion protein PEP Prx2 reduced the activation of NF-kB and Nrf2 and was paralleled by a decrease in HO-1 and in vascular endothelial abnormal activation. Prolonged hypoxia was used to trigger pulmonary artery hypertension (PAH). Prx2-/- precociously developed PAH compared to wildtype animals.
Published: 2017

41. The CRP level and STATE score predict survival in cirrhotic patients with hepatocellular carcinoma treated by transarterial embolization

Author: Véronique Grando, Samia Rekik, Nicolas Sellier, Nathalie Ganne-Carrié, Olivier Seror, Mohannad Bhais, Pierre Nahon, Jean-Charles Nault, Valérie Bourcier, Yves Ajavon, Gisèle N'Kontchou, Erwan Guyot, AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, and leboeuf, Christophe
Subjects: Liver Cirrhosis, Male, Hepatocellular carcinoma, medicine.medical_treatment, Gastroenterology, Severity of Illness Index, Liver disease, 0302 clinical medicine, Embolization, STATE score, biology, Liver Neoplasms, Hepatitis C, Hepatitis B, Middle Aged, Prognosis, Tumor Burden, C-Reactive Protein, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, CRP, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, Chemoembolization, Therapeutic, Serum Albumin, Aged, Proportional Hazards Models, Retrospective Studies, Inflammation, Hepatology, business.industry, Proportional hazards model, C-reactive protein, Transarterial chemo-embolization, medicine.disease, Surgery, Log-rank test, Multivariate Analysis, biology.protein, business
Abstract: International audience; Background: Prognostic biomarkers are needed in a heterogeneous population of patients with intermediate hepatocellular carcinoma (HCC) treated by transarterial (chemo)embolization. We aimed to validate the prognostic value of serum CRP levels and the STATE score, combining CRP, albumin and tumor burden.Methods: All cirrhotic patients with HCC treated by a first transarterial (chemo)embolization (2007-2013) in our institution were included. Overall survival was assessed using the Kaplan-Meier method, log rank, univariate and multivariate Cox analyses.Results: Among 157 patients included, 87% were men, 86% had Child Pugh A. Etiologies of liver disease included alcohol (57%), hepatitis C (32%), hepatitis B (11%) and/or metabolic syndrome (32%); 89% of patients were classified BCLC B. 33% of the patients had a CRP >1mg/dl and 33% a STATE score conferring poor prognosis (1mg/dl (20 vs. 8 months, P=0.00186). Median overall survival was 6.73 months for patients with a STATE score
Published: 2016

42. Real-Time 3D Virtual Target Fluoroscopic Display for Challenging Hepatocellular Carcinoma Ablations Using Cone Beam CT

Author: Olivier Seror, Olivier Sutter, Rafik Ourabia-Belkacem, Nicolas Sellier, Abou Diallo, Amina Fihri, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Hôpital Avicenne [AP-HP], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and leboeuf, Christophe
Subjects: Male, Cancer Research, Cone beam computed tomography, Carcinoma, Hepatocellular, recurrence, Percutaneous, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, ablation, fusion imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, HCV-related HCC, medicine, Humans, Fluoroscopy, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Liver Neoplasms, cone beam CT, Ultrasound, hepatocellular carcinoma, Irreversible electroporation, Cone-Beam Computed Tomography, Middle Aged, Ablation, medicine.disease, metabolomics, fluoroscopy, Treatment Outcome, Liver, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, Female, Original Article, GC-MS, Tomography, X-Ray Computed, metabolic biomarker, business, Nuclear medicine, guidance
Abstract: International audience; Three-dimensional virtual target fluoroscopic display is a new guidance tool that can facilitate challenging percutaneous ablation. The purpose of this study was to assess the feasibility, local efficacy, and safety of liver ablation assisted by three-dimensional virtual target fluoroscopic display. Sixty-seven hepatocellular carcinomas (mean diameter: 31 mm, range: 9-90 mm, 24 ≥ 30 mm, 16 of an infiltrative form) in 53 consecutive patients were ablated using irreversible electroporation (n = 39), multibipolar radiofrequency (n = 25), or microwave (n = 3) under a combination of ultrasound and three-dimensional virtual target fluoroscopic display guidance because the procedures were considered to be unfeasible under ultrasound alone. This guidance technology consisted of real-time fluoroscopic three-dimensional visualization of the tumor previously segmented from cone beam computed tomography images acquired at the start of the procedure. The results were assessed by cross-sectional imaging performed at 1 month and then every 3 months in the event of complete ablation. Factors associated with overall local tumor progression (initial treatment failure and subsequent local tumor progression) were assessed using a logistic regression model. Sixty-one (91%) tumors were completely ablated after 1 (n = 53) or 2 (n = 8) procedures. After a median follow-up of 12.75 months (1-23.2) of the 61 tumors displaying imaging characteristics consistent with complete ablation at 1 month, local tumor progression was observed in 9, so the overall local tumor progression rate was 22.3% (15 of 67). Under multivariate analysis, dome locations and infiltrative forms were associated with local tumor progression. No major complications occurred. Three-dimensional virtual target fluoroscopic display is a feasible and efficient image guidance tool to facilitate challenging ablations that are generally considered as infeasible using ultrasound alone.
Published: 2018

43. The Interplay Between Peroxiredoxin-2 and Nuclear Factor-Erythroid 2 Is Important in Limiting Oxidative Mediated Dysfunction in β-Thalassemic Erythropoiesis

Author: Xiuli An, Luigia De Falco, Dae Won Kim, Lucia De Franceschi, Narla Mohandas, Anne Janin, Mariasole Bruno, Christophe Leboeuf, Alessandro Matte, Soo Young Choi, Angela Siciliano, Achille Iolascon, Matte, Alessandro, DE FALCO, Luigia, Iolascon, Achille, Mohandas, Narla, An, Xiuli, Siciliano, Angela, Leboeuf, Christophe, Janin, Anne, Bruno, Mariasole, Choi, Soo Young, Kim, Dae Won, and De Franceschi, Lucia
Subjects: Erythrocyte Indices, Ineffective erythropoiesis, medicine.medical_specialty, Iron Overload, Erythroblasts, NF-E2-Related Factor 2, Physiology, Recombinant Fusion Proteins, Clinical Biochemistry, Apoptosis, Oxidative phosphorylation, Peroxiredoxin 2, Biology, medicine.disease_cause, Biochemistry, Mice, Bone Marrow, Internal medicine, medicine, Animals, Erythropoiesis, Molecular Biology, General Environmental Science, Erythroid Precursor Cells, Mice, Knockout, chemistry.chemical_classification, Reactive oxygen species, beta-Thalassemia, Beta thalassemia, Peroxiredoxins, Cell Biology, medicine.disease, Original Research Communications, Disease Models, Animal, Oxidative Stress, Phenotype, Endocrinology, Gene Expression Regulation, chemistry, General Earth and Planetary Sciences, Female, Reactive Oxygen Species, Peroxiredoxin, Spleen, Oxidative stress, Protein Binding
Abstract: Aims: β-Thalassemia is a common inherited red cell disorder characterized by ineffective erythropoiesis and severe oxidative stress. Peroxiredoxin-2 (Prx2), a typical 2-cysteine peroxiredoxin, is upregulated during β-thalassemic erythropoiesis, but its contribution to stress erythropoiesis, a common feature of thalassemia, is yet to be fully defined. Results: Here, we showed that Prx2−/− mice displayed reactive oxygen species related abnormalities in erythropoiesis similar to that of Hbbth3/+ mice associated with activation of redox response transcriptional factor nuclear factor-erythroid 2 (Nrf2). We generated β-thalassemic mice genetically lacking Prx2 (Prx2−/−Hbbth3/+) and documented a worsened β-thalassemic hematological phenotype with severe ineffective erythropoiesis. To further validate a key role of Prx2 in stress erythropoiesis, we administrated fused recombinant PEP1Prx2 to Hbbth3/+ mice and documented a decrease in ineffective erythropoiesis. We further show that Prx2 effects are mediated by activation of Nrf2 and upregulation of genes that protect against oxidative damage such as gluthatione S-transferase, heme-oxygenase-1, and NADPH dehydrogenase quinone-1. Innovation: We propose Prx2 as a key antioxidant system and Nrf2 activation is a cellular adaptive process in response to oxidative stress, resulting in upregulation of antioxidant (antioxidant responsive element) genes required to ensure cell survival. Conclusion: Our data shed new light on adaptive mechanisms against oxidative damage through the interplay of Prx2 and Nrf2 during stress erythropoiesis and suggest new therapeutic options to decrease ineffective erythropoiesis by modulation of endogenous antioxidant systems. Antioxid. Redox Signal. 23, 1284–1297.
Published: 2015

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