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1. Hemostasis testing in patients with liver dysfunction: Advantages and caveats

Author

B. Crichi, Manon Lejeune, Guillaume Nguyen, Corinne Frere, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Thrombin generation, medicine.medical_specialty, Hemostatic agents, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Bleeding risk, Internal medicine, medicine, Humans, In patient, Conventional tests, Hemostasis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Viscoelastic tests, business.industry, Liver Diseases, Minireviews, General Medicine, Blood Coagulation Disorders, Thrombelastography, 3. Good health, 030211 gastroenterology & hepatology, Blood Coagulation Tests, Liver dysfunction, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a “rebalanced hemostasis”, which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.

Published
2021

2. Performance evaluation of the fully automated random‐access multiparameter Sysmex CN‐6000 hemostasis analyzer at a core laboratory with a high sample throughput

Author

Isabelle Martin-Toutain, Corinne Frere, Yasmine Bourti, Mayssa Gaaloul, Manon Lejeune, Jean-Pierre Delorme, and Guillaume Nguyen

Subjects
Prothrombin time, Hemostasis, Spectrum analyzer, Materials science, medicine.diagnostic_test, Sample (material), Coefficient of variation, Biochemistry (medical), Clinical Biochemistry, Hematology, General Medicine, Fibrinogen, Turnaround time, Prothrombin Time, medicine, Humans, Partial Thromboplastin Time, Blood Coagulation Tests, Laboratories, Throughput (business), medicine.drug, Biomedical engineering
Abstract

INTRODUCTION We aimed to evaluate the performance of the fully automated multiparameter CN-6000 hemostasis analyzer. METHODS Performance evaluation of the CN-6000 analyzer was conducted for 10 tests including prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen level, anti-Xa activity, and antithrombin activity using a unique portfolio of liquid ready-to-use reagents. Precision, sample and reagent carryovers, throughput, and sample turnaround time (STAT) function were prospectively assessed. Results from 343 samples (normal subjects, critically ill patients, patients receiving anticoagulants, subjects with high or low fibrinogen levels, and patients with decreased levels of factor II, V, VII, and X) were compared to those obtained on the STA-R Max 2® analyzer using dedicated reagents. RESULTS Total precision (coefficient of variation) was below 7% for all parameters in both normal and pathological ranges. For all analyzed parameters, results obtained on the CN-6000 were strongly correlated with those obtained on the STA-R Max 2®analyzer. Agreement between both instruments was excellent for all assays. The CN-6000 demonstrated a 30% higher throughput compared to the STA-R Max 2® (258 vs 185 tests per hour for a panel of tests including PT, aPTT, fibrinogen, factor V, anti-Xa, and D-Dimer). STAT turnaround time for critical care samples testing was

Published
2021

3. Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome

Author

Guillaume Lebreton, Ania Nieszkowska, Corinne Frere, Marc Pineton de Chambrun, Isabelle Martin-Toutain, Guillaume Hékimian, Manon Lejeune, Paul Masi, Juliette Chommeloux, Matthieu Schmidt, Charles-Edouard Luyt, Alain Combes, Nicolas Bréchot, Cyrielle Desnos, and Pascal Leprince

Subjects
Adult, Male, ARDS, medicine.medical_specialty, medicine.medical_treatment, Hemorrhage, 030204 cardiovascular system & hematology, Fibrinogen, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Von Willebrand factor, law, Internal medicine, von Willebrand Factor, Fibrinolysis, medicine, Extracorporeal membrane oxygenation, Humans, Prospective Studies, Blood Coagulation, Respiratory Distress Syndrome, biology, business.industry, COVID-19, 030208 emergency & critical care medicine, Hematology, Middle Aged, medicine.disease, Intensive care unit, Coagulation, biology.protein, Cardiology, Female, Median body, business, medicine.drug
Abstract

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p

Published
2021

4. Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia

Author

Jean-Sébastien Casalegno, Céline Monnard, Hanaa Benmansour, Stéphane Bonacorsi, Chloé Plouzeau, Agathe Becker, Guillaume Geslain, Camille d’Humières, Paul Duquaire, Catherine Neuwirth, Lauranne Broutin, Emmanuel Lecorche, Claude-Alexandre Gustave, Carole Lemarié, Laurence Armand-Lefevre, Emmanuelle Vigier, Adel Maamar, Jean-Philippe Lavigne, Jean-Pierre Quenot, Christophe Burucoa, Olivier Dauwalder, Gabriel Auger, Julie Cremniter, Alexy Tran-Dinh, Marion Baldeyrou, Hervé Jacquier, Maxime Pichon, Rafael Mahieu, Claire Poyart, Julien Loubinoux, Solen Kernéis, Manon Lejeune, Jean-François Timsit, Nabil Gastli, Bruno Lina, François Vandenesch, Achille Kouatchet, Vincent Cattoir, Pierre Saint-Sardos, Emmanuelle Cambau, Anthony Michaud, Sophie Alviset, André Boibieux, Aurélie Cointe, Gauthier Péan de Ponfilly, Grégory Destras, Robin Stéphan, Matthieu Daragon, Philippe Montravers, Michael Levy, Vincent Rzepecki, Hélène Pailhoriès, Service de Bactériologie [CHU Cochin, AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de bactériologie (CHU Dijon), Plateau technique de Biologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Bactériologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Laboratoire de Bactériologie et Hygiène Hospitalière [Rennes], CHU Pontchaillou [Rennes], Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), Hôpital Cochin [AP-HP], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Meso Scale Diagnostics, The French FA-PP study group includes the following investigators: Sophie Alviset (Paris Cochin), Laurence Armand-Lefèvre (Paris Bichat), Marion Baldeyrou (Rennes), Agathe Becker (Hospices Civils de Lyon), André Boibieux (Hospices Civils de Lyon), Stéphane Bonacorsi (Paris, Robert-Debré), Christophe Burucoa (Poitiers), Emmanuelle Cambau (Paris Lariboisière), Jean-Sébastien Casalegno (Hospices Civils de Lyon), Aurélie Cointe (Paris, Robert-Debré), Julie Cremniter (Poitiers), Grégory Destras (Hospices Civils de Lyon), Paul Duquaire (Hospices Civils de Lyon), Guillaume Geslain (Paris, Robert-Debré), Claude-Alexandre Gustave (Hospices Civils de Lyon), Hervé Jacquier (Paris Lariboisière), Achille Kouatchet (Angers), Emmanuel Lecorche (Paris Lariboisière), Manon Lejeune (Paris Bichat), Bruno Lina (Hospices Civils de Lyon), Rafaël Mahieu (Angers), Adel Maamar (Rennes), Anthony Michaud (Poitiers), Céline Monnard (Hospices Civils de Lyon), Philippe Montravers (Paris Bichat), Catherine Neuwirth (Dijon), Gauthier Péan de Ponfilly (Paris, Lariboisière), Maxime Pichon (Poitiers), Chloé Plouzeau (Poitiers), Claire Poyart (Paris Cochin), Jean-Pierre Quenot (Dijon), Vincent Rzepecki (Nîmes), Robin Stéphan (Nîmes), Jean-François Timsit (Paris Bichat), Alexy Tran-Dinh (Paris Bichat), François Vandenesch (Hospices Civils de Lyon) and Emmanuelle Vigier (Paris Bichat)., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Atypical bacteria, Concordance, [SDV]Life Sciences [q-bio], FilmArray pneumonia panel, 030106 microbiology, Gastroenterology, Lower respiratory tract infection, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Multiplex polymerase chain reaction, Diagnosis, medicine, Pneumonia, Bacterial, Humans, 030212 general & internal medicine, medicine.diagnostic_test, biology, Bacteria, business.industry, General Medicine, Syndromic panel, Multiplex PCR, medicine.disease, biology.organism_classification, 3. Good health, Pneumonia, Infectious Diseases, Bronchoalveolar lavage, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Diagnostic Techniques, Sputum, medicine.symptom, business, Multiplex Polymerase Chain Reaction
Abstract

International audience; OBJECTIVES: To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. METHODS: This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. RESULTS: A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%-96.5%) and 96.0% (95% CI 95.5%-96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log(10) in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥10(6) DNA copies/mL grew significantly in culture. CONCLUSIONS: FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia.

Published
2021

5. Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19–Associated Coagulopathy

Author

Isabelle Martin-Toutain, Juliette Chommeloux, Alain Combes, Nicolas Bréchot, Charles Edouard Luyt, Ania Nieszkowska, Corinne Frere, Matthieu Schmidt, Guillaume Hékimian, Guillaume Lebreton, Marc Pineton de Chambrun, Cyrielle Desnos, Manon Lejeune, and Paul Masi

Subjects
medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), business.industry, 030204 cardiovascular system & hematology, biology.organism_classification, Single Center, medicine.disease, Systemic inflammatory response syndrome, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Pandemic, medicine, Coagulopathy, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Prospective cohort study, business, Betacoronavirus, Cohort study
Published
2020

6. Are Patients with Active Cancer and Those with History of Cancer Carrying the Same Risks of Recurrent VTE and Bleeding While on Anticoagulants?

Author

Manon Lejeune, Corinne Frere, Jean-Philippe Spano, B. Crichi, Nicolas Janus, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Cancer Research, medicine.medical_specialty, medicine.drug_class, Population, MEDLINE, Subgroup analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, active cancer, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, history of cancer, cancer-associated-thrombosis, education, Prospective cohort study, education.field_of_study, business.industry, Anticoagulant, anticoagulant, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Thrombosis, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Cohort, Perspective, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract

International audience; Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of "cancer patient" differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.

Published
2020

7. Beta-1,4-galactosyltransferase 2 c.909C>T gene variant is predictive of on-clopidogrel platelet reactivity

Author

Sébastien Bertil, Manon Lejeune, Nicolas Pallet, Anne Savalle, Tiphaine Belleville-Rolland, Laetitia Mauge, Pascale Gaussem, and Marie-Anne Loriot

Subjects
Male, 0301 basic medicine, Platelet Aggregation, CYP2C19, 030204 cardiovascular system & hematology, Beta-1 adrenergic receptor, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Genetics, medicine, Humans, cardiovascular diseases, Exome sequencing, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Galactosyltransferase, business.industry, Genetic Variation, Retrospective cohort study, Middle Aged, Galactosyltransferases, Platelet Activation, Clopidogrel, 030104 developmental biology, Phosphoprotein, Pharmacogenomics, Immunology, Molecular Medicine, Female, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

CYP2C19 genotype influences clopidogrel response but only accounts for a small part of the variability in platelet reactivity. Recently, exome sequencing identified a variant of the gene encoding B4GALT2 as a potential candidate implicated in on-treatment platelet reactivity. Carriers of the B4GALT2 c.909C>T variant have lower platelet reactivity indicating that B4GALT2 could influence clopidogrel sensitivity and could expose to the risk of bleeding events. We undertook this observational retrospective study to determine if B4GALT2 c.909C>T influences P2RY12-specific vasodilator-stimulated phosphoprotein phosphorylation and agonist-induced platelet aggregation in a nonselected cohort of 174 patients under clopidogrel-based antiplatelet therapy. Our results indicate that in individuals under dual antiplatelet therapy, B4GALT2 c.909C>T might be an independent genetic predictor of on-treatment platelet reactivity.

Published
2018

8. Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies

Author

Corinne Frere, Manon Lejeune, Pierre Kubicek, Dorothée Faille, Zora Marjanovic, the Groupe Francophone Thrombose et Cancer, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Chemoprotective agent, Cancer Research, medicine.medical_specialty, Colorectal cancer, aspirin, [SDV]Life Sciences [q-bio], colorectal cancer, Review, antiplatelet drugs, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, medicine, chemoprevention, cancer, 030212 general & internal medicine, Intensive care medicine, Aspirin, Cancer prevention, business.industry, Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Lynch syndrome, 3. Good health, Clinical research, Oncology, 030220 oncology & carcinogenesis, thienopyridines, Chemoprotective, cancer-related mortality, adenoma, business, medicine.drug
Abstract

International audience; Over the past two decades, aspirin has emerged as a promising chemoprotective agent to prevent colorectal cancer (CRC). In 2016, the mounting evidence supporting its chemoprotective effect, from both basic science and clinical research, led the US Preventive Services Task Force to recommend regular use of low-dose aspirin in some subgroups of patients for whom the benefits are deemed to outweigh the risks. In contrast, data on the chemoprotective effect of aspirin against other cancers are less clear and remain controversial. Most data come from secondary analyses of cardiovascular prevention trials, with only a limited number reporting cancer outcomes as a prespecified endpoint, and overall unclear findings. Moreover, the potential chemoprotective effect of aspirin against other cancers has been recently questioned with the publication of 3 long-awaited trials of aspirin in the primary prevention of cardiovascular diseases reporting no benefit of aspirin on overall cancer incidence and cancer-related mortality. Data on the chemoprotective effects of other antiplatelet agents remain scarce and inconclusive, and further research to examine their benefit are warranted. In this narrative review, we summarize current clinical evidence and continuing controversies on the potential chemoprotective properties of antiplatelet agents against cancer.

Published
2019

9. Utility of a mainstreamed genetic testing pathway in breast and ovarian cancer patients during the COVID-19 pandemic

Author

Charlotte Paul, Patrick R. Benusiglio, Jean Pierre Lotz, Erell Guillerm, Florence Coulet, Sophie Geoffron, Roseline Vibert, Sandrine Richard, Joël Ezenfis, Nathalie Chabbert-Buffet, Veronique Byrde, Noémie Basset, Joseph Gligorov, Manon Lejeune, Clément Korenbaum, CCSD, Accord Elsevier, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Site de recherche intégrée en cancérologie (SiRIC CURAMUS), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Sud Francilien, Grand Hôpital de l'Est Francilien (GHEF), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Genetic testing, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Breast cancer, 0302 clinical medicine, Pandemic, Young adult, Mastectomy, Genetics (clinical), Neoadjuvant therapy, Aged, 80 and over, Ovarian Neoplasms, 0303 health sciences, medicine.diagnostic_test, BRCA1 Protein, 030305 genetics & heredity, High-Throughput Nucleotide Sequencing, General Medicine, Middle Aged, Neoadjuvant Therapy, 3. Good health, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, 030220 oncology & carcinogenesis, Hereditary Breast and Ovarian Cancer Syndrome, Female, Fanconi Anemia Complementation Group N Protein, Adult, Paris, medicine.medical_specialty, Genetic counseling, Salpingo-oophorectomy, Breast Neoplasms, Genetic Counseling, Article, Young Adult, 03 medical and health sciences, Ovarian cancer, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Pandemics, Aged, BRCA2 Protein, business.industry, COVID-19, medicine.disease, business
Abstract

International audience; Introduction: Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation, since trained oncologists (O) and gynaecologists (G) provide counseling, prescribe testing and deliver results. We report results from our MGT program and emphasize its utility during the COVID-19 lockdown, when cancer genetics clinics had suspended their activity.Methods: An MGT pathway for breast and ovarian cancer (BC/OC) patients was established in Jan-2018 between the Assistance Publique - Hôpitaux de Paris.Sorbonne Université Cancer Genetics team and the Oncology/Gynecology departments at one teaching and two regional hospitals. Trained O + G evaluated patients with the Manchester Scoring System. A 12-point threshold was recommended for testing. Next-generation sequencing of BRCA1, BRCA2, PALB2, RAD51C and RAD51D was performed. Results were delivered to the patient by O/G. Pathogenic variants (PV) carriers were referred to the genetics clinic. Results are reported for the 2nd-Jan-2018 to 1st-June-2020 period. That includes the eight-week COVID-19 lockdown and three-week de-confinement phase 1.Results: Results were available for 231/234 patients. Twenty-eight (12.1%) carried a PV. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The clinical impact was immediate for the two BRCA1 BC cases undergoing neo-adjuvant chemotherapy, since double mastectomy and salpingo-oophorectomy will now be performed using two-step strategies.Conclusions: MGT guaranteed care continuity in BC/OC patients during the critical phases of the COVID-19 pandemic, with immediate implications for PV carriers. More broadly, we report for the first time the successful implementation of MGT in France.

Published
2020

10. Utilisation de la méthodologie du mind mapping pour initier un projet cpom

Author

Manon Lejeune, Dorothée Metta, Marie Odile Mariée, Fara Ralison, Bao Le Thai, and Sandrine Grynberg

Subjects
Public Health, Environmental and Occupational Health
Abstract

Nous avons utilise la methodologie de projet Mind Mapping (MM), appelee aussi carte heuristique, pour la gestion de notre projet CPOM prevention des accidents de travail (PAT). Celle-ci a ete adaptee a nos besoins car le domaine de la PAT est vaste et complexe, recouvrant l’ensemble de la prevention en entreprise. Methodes Le MM est une methodologie reconnue pour la gestion de projet. Nous avons utilise un des nombreux logiciels de Mind Mapping disponibles sur internet. Trois reunions du groupe de travail ont ete necessaires pour finaliser le MM : consultation de la bibliographie disponible sur le sujet, identification des pistes d’actions, et enfin confection du MM sous la forme d’une arborescence claire et detaillee. Resultats Cette methode a permis de faire participer tous les membres de l’equipe projet de facon creative pour poser les problematiques du projet et les solutions envisageables. Cette representation graphique a aussi l’avantage de faciliter la memorisation des idees et les classer entre elles par thematiques d’actions. Il a ete ainsi distingue 9 branches principales et 53 ramifications secondaires a partir du noyau central (voir Fig. 1). Ainsi, une branche principale nouvelle technologie de l’information et de la communication (NTIC) a ete cree afin d’integrer ces nouveaux outils dans notre offre d’accompagnement de PAT. Conclusion La methodologie MM peut etre facilement maitrisable pour la gestion de projet par les medecins du travail pour les assister dans leur role d’animateur et de coordinateur de l’equipe pluridisciplinaire. En effet, elle est proche de la demarche d’etude clinique que les medecins maitrisent par leur formation. Elle a aussi l’avantage d’illustrer tres rapidement les fiches actions a entreprendre en priorite en fonction de l’agenda du projet.

Published
2018

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