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1. Semi-supervised Bladder Tissue Classification in Multi-Domain Endoscopic Images

Author: Lazo, Jorge F., Rosa, Benoit, Catellani, Michele, Fontana, Matteo, Mistretta, Francesco A., Musi, Gennaro, Cobelli, Ottavio de, Mathelin, Michel de, Momi, Elena De, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), European Institute of Oncology [Milan] (ESMO), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Università degli Studi di Milano = University of Milan (UNIMI), European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (Grant Number: 813782), ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), and European Project: 813782,ATLAS
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Informatique [cs]/Imagerie médicale, Computer Vision and Pattern Recognition (cs.CV), Image and Video Processing (eess.IV), Computer Science - Computer Vision and Pattern Recognition, FOS: Electrical engineering, electronic engineering, information engineering, Biomedical Engineering, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Electrical Engineering and Systems Science - Image and Video Processing, Machine Learning (cs.LG)
Abstract: Objective: Accurate visual classification of bladder tissue during Trans-Urethral Resection of Bladder Tumor (TURBT) procedures is essential to improve early cancer diagnosis and treatment. During TURBT interventions, White Light Imaging (WLI) and Narrow Band Imaging (NBI) techniques are used for lesion detection. Each imaging technique provides diverse visual information that allows clinicians to identify and classify cancerous lesions. Computer vision methods that use both imaging techniques could improve endoscopic diagnosis. We address the challenge of tissue classification when annotations are available only in one domain, in our case WLI, and the endoscopic images correspond to an unpaired dataset, i.e. there is no exact equivalent for every image in both NBI and WLI domains. Method: We propose a semi-surprised Generative Adversarial Network (GAN)-based method composed of three main components: a teacher network trained on the labeled WLI data; a cycle-consistency GAN to perform unpaired image-to-image translation, and a multi-input student network. To ensure the quality of the synthetic images generated by the proposed GAN we perform a detailed quantitative, and qualitative analysis with the help of specialists. Conclusion: The overall average classification accuracy, precision, and recall obtained with the proposed method for tissue classification are 0.90, 0.88, and 0.89 respectively, while the same metrics obtained in the unlabeled domain (NBI) are 0.92, 0.64, and 0.94 respectively. The quality of the generated images is reliable enough to deceive specialists. Significance: This study shows the potential of using semi-supervised GAN-based bladder tissue classification when annotations are limited in multi-domain data. The dataset is available at https://zenodo.org/record/7741476#.ZBQUK7TMJ6k, Comment: Title and abstract updated. Typos corrected
Published: 2023
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2. Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction

Author: Javed Butler, Gerasimos Filippatos, Tariq Jamal Siddiqi, João Pedro Ferreira, Martina Brueckmann, Edimar Bocchi, Michael Böhm, Vijay K. Chopra, Nadia Giannetti, Tomoko Iwata, James L. Januzzi, Sanjay Kaul, Ileana L. Piña, Piotr Ponikowski, Ursula Rauch-Kröhnert, Sanjiv J. Shah, Michele Senni, Mikhail Sumin, Subodh Verma, Jian Zhang, Stuart J. Pocock, Faiez Zannad, Milton Packer, Stefan D. Anker, Baylor Scott and White Research Institute, University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Attikon University Hospital, 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 ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Boehringer Ingelheim International GmbH, Medizinische Fakultät Mannheim, Universidade de São Paulo = University of São Paulo (USP), Universität des Saarlandes [Saarbrücken], Saarland University Hospital (UKS), Max Superspeciality Hospital, Saket, McGill University Health Center [Montreal] (MUHC), Boehringer Ingelheim Pharma GmbH & Co. KG, Massachusetts General Hospital [Boston, MA, USA], Harvard Medical School [Boston] (HMS), Baim Institute for Clinical Research Boston MA, Cedars-Sinai Medical Center, Central Michigan University (CMU), Wrocław Medical University, Department of Cardiology, Charité University Medicine Berlin, Campus Benjamin-Franklin, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Northwestern University Feinberg School of Medicine, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), St. Michael's Hospital, Fuwai Hospital Chinese Academic of Medical Science, London School of Hygiene and Tropical Medicine (LSHTM), Baylor Heart and Vascular Institute, Baylor University Medical Center, Imperial College London, Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], The EMPEROR-Preserved trial was supported by the Boehringer Ingelheim andEli Lilly and Company Diabetes Alliance, and BOZEC, Erwan
Subjects: Heart Failure, Male, Stroke Volume, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Uric Acid, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucosides, Physiology (medical), Humans, Female, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine, Cardiomyopathies
Abstract: Background: Women and men with heart failure (HF) and preserved ejection fraction may differ in their clinical characteristics and their response to therapy. The aim of this study was to evaluate the influence of sex on the effects of empagliflozin in patients with HF and preserved ejection fraction enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction). Methods: The effects of empagliflozin on the primary outcome of cardiovascular death or hospitalization for HF and on secondary outcomes (including total HF hospitalization, cardiovascular and all-cause mortality, and Kansas City Cardiomyopathy Questionnaire scores) were compared in women and men in the overall cohort and in subgroups defined by left ventricular ejection fraction (41%–49%, 50%–59%, and ≥60%). The effects of empagliflozin on physiological measures, including changes in systolic blood pressure, uric acid, hemoglobin, body weight, and natriuretic peptide levels, were also assessed. Results: Of the 5988 patients randomized, 2676 (44.7%) were women. In the placebo arm, women tended to have lower risk for adverse outcomes, including a lower risk of all-cause mortality (hazard ratio, 0.69 [95% CI, 0.56, 0.84]). Compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for HF to a similar degree in both sexes (hazard ratio, 0.81 [95% CI, 0.69, 0.96] for men; and hazard ratio, 0.75 [95% CI, 0.61, 0.92] for women; P interaction =0.54). Sex did not modify the relationship between empagliflozin and outcomes across ejection fraction groups. Similar results were seen for secondary outcomes and physiological measures. Compared with placebo, empagliflozin improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score to a similar extent in both sexes (1.38 for men versus 1.63 for women at 52 weeks; P interaction =0.77); the results were similar for Kansas City Cardiomyopathy Questionnaire overall summary score and total summary score. Conclusions: Empagliflozin produced similar benefits on outcomes and health status in women and men with HF and preserved ejection fraction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03057951.
Published: 2022
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3. Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial

Author: Michele Senni, Jose Lopez‐Sendon, Alain Cohen‐Solal, Piotr Ponikowski, Richard Nkulikiyinka, Cecilia Freitas, Vanja Miodrag Vlajnic, Lothar Roessig, Burkert Pieske, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Universidad Autónoma de Madrid (UAM), 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 de cardiologie (APHP-Hôpital Lariboisière), Hôpital Lariboisière-APHP, University of Wrocław [Poland] (UWr), Bayer AG [Wuppertal, Germany], Bayer Pharma AG [Berlin], Bayer HealthCare Pharmaceuticals Inc [Whippany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Heart Institute Berlin [Berlin, Germany] (GHIB), and leboeuf, Christophe
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, NT-proBNP, Heart failure, Cardiology and Cardiovascular Medicine, Heart failure with reduced ejection fraction, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Aims Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4]. Methods and results VICTORIA participants with available baseline NT-proBNP levels (n = 4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556 pg/mL; Q2, >1556-2816 pg/mL; and Q3, >2816-5314 pg/mL), patients in Q4 (NT-proBNP: >5314 pg/mL) were older (69.2 ± 12.0 vs. 66.6 ± 12.1 years), had lower mean ejection fraction (27.2 ± 8.3% vs. 29.5 ± 8.2%; P < 0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3 ± 6.6 vs. 23.5 ± 6.4; P < 0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5 ± 25.5 vs. 65.0 ± 26.8 mL/min/1.73 m 2 ; P < 0.0001) and haemoglobin (12.8 ± 2.0 vs. 13.6 ± 1.9 g/dL; P < 0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P = 0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P < 0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P < 0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P < 0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P = 0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P = 0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P < 0.0001). Conclusions Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.
Published: 2022
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4. Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Author: Aidin Foroutan, Sadegheh Haghshenas, Pratibha Bhai, Michael A. Levy, Jennifer Kerkhof, Haley McConkey, Marcello Niceta, Andrea Ciolfi, Lucia Pedace, Evelina Miele, David Genevieve, Solveig Heide, Mariëlle Alders, Giuseppe Zampino, Giuseppe Merla, Mélanie Fradin, Eric Bieth, Dominique Bonneau, Klaus Dieterich, Patricia Fergelot, Elise Schaefer, Laurence Faivre, Antonio Vitobello, Silvia Maitz, Rita Fischetto, Cristina Gervasini, Maria Piccione, Ingrid van de Laar, Marco Tartaglia, Bekim Sadikovic, Anne-Sophie Lebre, Foroutan A., Haghshenas S., Bhai P., Levy M.A., Kerkhof J., McConkey H., Niceta M., Ciolfi A., Pedace L., Miele E., Genevieve D., Heide S., Alders M., Zampino G., Merla G., Fradin M., Bieth E., Bonneau D., Dieterich K., Fergelot P., Schaefer E., Faivre L., Vitobello A., Maitz S., Fischetto R., Gervasini C., Piccione M., van de Laar I., Tartaglia M., Sadikovic B., Lebre A.-S., Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, University of Western Ontario (UWO), London Health Sciences Center (LHSC), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Amsterdam UMC - Amsterdam University Medical Center, University of Amsterdam [Amsterdam] (UvA), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University of Naples Federico II = Università degli studi di Napoli Federico II, Fondazione Casa Sollievo della Sofferenza [San Giovanni Rotondo, Italy] (FC2S), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), San Gerardo Hospital [Monza, Italy] (SGH), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Palermo - University of Palermo, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Foroutan, A., Haghshenas, S., Bhai, P., Levy, M. A., Kerkhof, J., Mcconkey, H., Niceta, M., Ciolfi, A., Pedace, L., Miele, E., Genevieve, D., Heide, S., Alders, M., Zampino, G., Merla, G., Fradin, M., Bieth, E., Bonneau, D., Dieterich, K., Fergelot, P., Schaefer, E., Faivre, L., Vitobello, A., Maitz, S., Fischetto, R., Gervasini, C., Piccione, M., van de Laar, I., Tartaglia, M., Sadikovic, B., Lebre, A. -S., Martinez Rico, Clara, and Clinical Genetics
Subjects: Wiedemann–Steiner syndrome, QH301-705.5, Intellectual disability, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Catalysis, Inorganic Chemistry, KMT2A gene, Neurodevelopmental disorder, Growth Disorder, Abnormalities, Multiple, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology (General), Physical and Theoretical Chemistry, Episignature, QD1-999, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Spectroscopy, DNA methylation, Organic Chemistry, Neurodevelopmental disorders, Craniofacial Abnormalitie, Epigenetic, Hypertrichosi, General Medicine, Facie, Computer Science Applications, Chemistry, epigenetics, episignature, intellectual disability, neurodevelopmental disorders, Phenotype, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Epigenetics, Human
Abstract: Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.
Published: 2022
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5. Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis

Author: Enrico Ammirati, Laura Lupi, Matteo Palazzini, Nicholas S. Hendren, Justin L. Grodin, Carlo V. Cannistraci, Matthieu Schmidt, Guillaume Hekimian, Giovanni Peretto, Thomas Bochaton, Ahmad Hayek, Nicolas Piriou, Sergio Leonardi, Stefania Guida, Annalisa Turco, Simone Sala, Aitor Uribarri, Caroline M. Van de Heyning, Massimo Mapelli, Jeness Campodonico, Patrizia Pedrotti, Maria Isabel Barrionuevo Sánchez, Albert Ariza Sole, Marco Marini, Maria Vittoria Matassini, Mickael Vourc’h, Antonio Cannatà, Daniel I. Bromage, Daniele Briguglia, Jorge Salamanca, Pablo Diez-Villanueva, Jukka Lehtonen, Florent Huang, Stéphanie Russel, Francesco Soriano, Fabrizio Turrini, Manlio Cipriani, Manuela Bramerio, Mattia Di Pasquale, Aurelia Grosu, Michele Senni, Davide Farina, Piergiuseppe Agostoni, Stefania Rizzo, Monica De Gaspari, Francesca Marzo, Jason M. Duran, Eric D. Adler, Cristina Giannattasio, Cristina Basso, Theresa McDonagh, Mathieu Kerneis, Alain Combes, Paolo G. Camici, James A. de Lemos, Marco Metra, Ammirati, E, Lupi, L, Palazzini, M, Hendren, N, Grodin, J, Cannistraci, C, Schmidt, M, Hekimian, G, Peretto, G, Bochaton, T, Hayek, A, Piriou, N, Leonardi, S, Guida, S, Turco, A, Sala, S, Uribarri, A, Van De Heyning, C, Mapelli, M, Campodonico, J, Pedrotti, P, Barrionuevo Sanchez, M, Ariza Sole, A, Marini, M, Matassini, M, Vourc'H, M, Cannata, A, Bromage, D, Briguglia, D, Salamanca, J, Diez-Villanueva, P, Lehtonen, J, Huang, F, Russel, S, Soriano, F, Turrini, F, Cipriani, M, Bramerio, M, Di Pasquale, M, Grosu, A, Senni, M, Farina, D, Agostoni, P, Rizzo, S, De Gaspari, M, Marzo, F, Duran, J, Adler, E, Giannattasio, C, Basso, C, Mcdonagh, T, Kerneis, M, Combes, A, Camici, P, De Lemos, J, Metra, M, CarMeN, laboratoire, Niguarda Hospital [Milan, Italy], University of Brescia, University of Texas Southwestern Medical Center [Dallas], Tsinghua University [Beijing] (THU), Center for Systems Biology Dresden [Dresden, Germany] (CSBD), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Université de Lyon, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Università degli Studi di Pavia = University of Pavia (UNIPV), Fondazione IRCCS Policlinico San Matteo [Pavia], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Instituto de Salud Carlos III [Madrid] (ISC), University of Antwerp (UA), Università degli Studi di Milano = University of Milan (UNIMI), IRCCS Istituto Nazionale dei Tumori [Milano], Bellvitge University Hospital [Barcelona, Spain], Presidio Ospedaliero 'G. Salesi' AN = Ancona Hospital Salesi [Ancona, Italy] (POGSA-AHS), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), King‘s College London, King's College Hospital (KCH), Mater Domini Humanitas Hospital [Castellanza, Italy] (MD2H), Hospital Universitario de La Princesa, Helsinki University Hospital [Finland] (HUS), Hôpital Foch [Suresnes], Ospedale Civile di Baggiovara [Modena, Italy] (OCB), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Ospedale 'Infermi' di Rimini [Rimini, Italy] (OIR), University of California [San Diego] (UC San Diego), University of California (UC), and Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB)
Subjects: Adult, Male, outcome, SARS-CoV-2, cardiac, [SDV]Life Sciences [q-bio], Left, COVID-2019, MRI, myocarditis, Female, Humans, Prevalence, Retrospective Studies, Stroke Volume, Ventricular Function, Left, COVID-19, Myocarditis, [SDV] Life Sciences [q-bio], myocarditi, Physiology (medical), Ventricular Function, Human medicine, Cardiology and Cardiovascular Medicine
Abstract: Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.
Published: 2022
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6. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author: Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital la Tronche, Universidad Austral de Chile, Ghent University Hospital, Arcispedale S Maria Nuova, Universidade Estadual de Campinas = University of Campinas (UNICAMP), CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Strasbourg, Universidad de Chile = University of Chile [Santiago] (UCHILE), Hôpital Universitaire de Rangueil, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Instituto Universitario del Hospital Italiano [Buenos Aires, Argentina], Hôpital JeanMinjoz, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Hôpital Paul Brousse, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), None, French-Italian-Belgium and Latin American collaborative group for HCC and liver transplantation: Karim Boudjema, Philippe Bachellier, Filomena Conti, Olivier Scatton, Fabrice Muscari, Ephrem Salame, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-Lorraine Woehl, Claire Vanlemmens, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Daniel Cherqui, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J Gugenheim, M Altieri, Marie Noelle Hilleret, Thomas Decaens, Christophe Duvoux, Federico Piñero, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sergio Hoyos Duque, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Jaime Poniachik, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G Podestá, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka Sf Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Marcelo Silva, Andrea Notarpaolo, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D'Ambrosio, Giuseppe Maria Ettorre, Alessandro Vitale, Patrizia Burra, Stefano Fagiuoli, Umberto Cillo, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Quirino Lai, Helena Degroote, Hans Van Vlierberghe, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Henri Mondor [Créteil]
Subjects: TTR= time to recurrence, [SDV.CAN]Life Sciences [q-bio]/Cancer, Explants pathology, Liver cancer, Liver transplantation, Prediction, Recurrence, MVI= microvascular invasion, VC= validation cohort, VALIDATION, LT= liver transplantation, RETREAT SCORE, SHR= sub-distribution of hazard ratio, R3= recurrence risk reassessment, HBV= hepatitis B virus, SIROLIMUS-BASED IMMUNOSUPPRESSION, Internal Medicine, HCV= hepatitis C virus, Medicine and Health Sciences, IMPROVES, Immunology and Allergy, Hepatology, TC= test cohort, Gastroenterology, DEATH, COMPETING RISKS, MODEL, AFP= alpha-foetoprotein, SORAFENIB, SURVIVAL, HCC= hepatocellular carcinoma, RETREAT= Risk Estimation of Tumour Recurrence After Transplant
Abstract: Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging +/- alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management.Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085).Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of -4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83,1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria.Clinical Trials Registration: NCT03775863.Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables inde-pendently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
Published: 2022
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7. Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey

Author: Antonella Lezo, Antonella Diamanti, Evelyne M. Marinier, Merit Tabbers, Anat Guz-Mark, Paolo Gandullia, Maria I. Spagnuolo, Sue Protheroe, Noel Peretti, Laura Merras-Salmio, Jessie M. Hulst, Sanja Kolaček, Looi C. Ee, Joanna Lawrence, Jonathan Hind, Lorenzo D’Antiga, Giovanna Verlato, Ieva Pukite, Grazia Di Leo, Tim Vanuytsel, Maryana K. Doitchinova-Simeonova, Lars Ellegard, Luisa Masconale, María Maíz-Jiménez, Sheldon C. Cooper, Giorgia Brillanti, Elena Nardi, Anna S. Sasdelli, Simon Lal, Loris Pironi, Regione Piemonte Azienda Ospedaliera - S. Anna [Turin, Italy] (OIRM-S), Ospedale Bambin Gesù [Rome, Italy] (OBG), Centre de Référence des Maladies Digestives Rares [AP-HP Hôpital Robert-Debré] (CRMDR), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Emma Children’s Hospital, Amsterdam UMC - Amsterdam University Medical Center, Schneider Children’s Medical Center [Petah Tikva, Israel] (SCMC), Tel Aviv University (TAU), IRCCS Istituto Giannina Gaslini [Genoa, Italy], University of Naples Federico II = Università degli studi di Napoli Federico II, Birmingham Women's and Children's NHS Foundation Trust, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Helsinki University Hospital [Finland] (HUS), Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, Children’s Hospital Srebrnjak [Zagreb, Croatia], Children’s Health Queensland [Brisbane] (CHQ), Royal Children’s Hospital & Department of Paediatrics [Parkville, VIC, Australia], King‘s College London, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Children's Clinical University Hospital [Riga, Latvia] (CCUH), Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo' [Trieste], Leuven Intestinal Failure and Transplantation [Leuven, Belgium] (LIFT), University Hospitals Leuven [Leuven], Bulgarian Association of Patients with Malnutrition [Sofia, Bulgaria] (BAPM), Sahlgrenska University Hospital [Gothenburg], Ospedale Orlandi [Bussolengo, Italy] (2O), Hospital Universitario 12 de Octubre [Madrid], Alma Mater Studiorum University of Bologna (UNIBO), University of Bologna/Università di Bologna, Azienda Ospedaliero-Universitaria di Bologna [Bolohna, Italy] (AOUB), Salford Royal NHS Foundation Trust [Salford, UK], CarMeN, laboratoire, Pediatrics, Pediatric surgery, Clinicum, HUS Children and Adolescents, Children's Hospital, University of Helsinki, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Lezo A., Diamanti A., Marinier E.M., Tabbers M., Guz-Mark A., Gandullia P., Spagnuolo M.I., Protheroe S., Peretti N., Merras-Salmio L., Hulst J.M., Kolacek S., Ee L.C., Lawrence J., Hind J., D'antiga L., Verlato G., Pukite I., Di Leo G., Vanuytsel T., Doitchinova-Simeonova M.K., Ellegard L., Masconale L., Maiz-Jimenez M., Cooper S.C., Brillanti G., Nardi E., Sasdelli A.S., Lal S., Pironi L., Lezo, Antonella, Diamanti, Antonella, Marinier, Evelyne M., Tabbers, Merit, Guz-Mark, Anat, Gandullia, Paolo, Spagnuolo, Maria I., Protheroe, Sue, Peretti, Noel, Merras-Salmio, Laura, Hulst, Jessie M., Kola( (c))ek, Sanja, Ee, Looi C., Lawrence, Joanna, Hind, Jonathan, D'Antiga, Lorenzo, Verlato, Giovanna, Pukite, Ieva, Di Leo, Grazia, Vanuytsel, Tim, Doitchinova-Simeonova, Maryana K., Ellegard, Lar, Masconale, Luisa, Ma('(i))z-Jim('(e))nez, Mar('(i))a, Cooper, Sheldon C., Brillanti, Giorgia, Nardi, Elena, Sasdelli, Anna S., Lal, Simon, and Pironi, Loris
Subjects: Adult, Male, Short Bowel Syndrome, [SDV]Life Sciences [q-bio], YOUNG-PEOPLE, ENTERAL NUTRITION, CLASSIFICATION, home parenteral nutrition, Intestinal Failure, children, body growth, Humans, chronic intestinal failure, intravenous supplementation, intestinal transplantation, transition, ADULT PATIENTS, HEPATOLOGY, Child, Cross-Sectional Studie, Nutrition and Dietetics, Science & Technology, Intestinal Disease, Nutrition & Dietetics, GASTROENTEROLOGY, PREVALENCE, [SDV] Life Sciences [q-bio], Intestinal Diseases, Cross-Sectional Studies, ITALIAN SOCIETY, Chronic Disease, HOME PARENTERAL-NUTRITION, Female, REHABILITATION PROGRAMS, 3143 Nutrition, Parenteral Nutrition, Home, Life Sciences & Biomedicine, Food Science, Human
Abstract: Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children. ispartof: NUTRIENTS vol:14 issue:9 ispartof: location:Switzerland status: published
Published: 2022
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8. DNA methylation episignature in Gabriele-de Vries syndrome

Author: Florian Cherik, Jack Reilly, Jennifer Kerkhof, Michael Levy, Haley McConkey, Mouna Barat-Houari, Kameryn M. Butler, Christine Coubes, Jennifer A. Lee, Gwenael Le Guyader, Raymond J. Louie, Wesley G. Patterson, Matthew L. Tedder, Mads Bak, Trine Bjørg Hammer, William Craigen, Florence Démurger, Christèle Dubourg, Mélanie Fradin, Rachel Franciskovich, Eirik Frengen, Jennifer Friedman, Nathalie Ruiz Palares, Maria Iascone, Doriana Misceo, Pauline Monin, Sylvie Odent, Christophe Philippe, Flavien Rouxel, Veronica Saletti, Petter Strømme, Perla Cassayre Thulin, Bekim Sadikovic, David Genevieve, CHU Clermont-Ferrand, University of Western Ontario (UWO), London Health Sciences Center (LHSC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The Greenwood Genetic Center, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Baylor College of Medicine (BCM), Baylor University, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], Oslo University Hospital [Oslo], University of California [San Diego] (UC San Diego), University of California (UC), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', and University of Utah
Subjects: Male, Gabriele-de Vries syndrome, Genome, Phenotype, Neurodevelopmental Disorders, [SDV]Life Sciences [q-bio], Intellectual Disability, Humans, Epigenetics, Syndrome, DNA Methylation, YY1, Genetics (clinical)
Abstract: International audience; PURPOSE: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant. METHODS: Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS. RESULTS: Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants. CONCLUSION: We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance.
Published: 2021
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9. Surgical Treatment of Postinfarction Ventricular Septal Rupture

Author: Massimiliano Carrozzini, Nikolaos Bonaros, Bart Meyns, Roberto Scrofani, Giosuè Falcetta, Matteo Pozzi, Antonio Fiore, Stefano D'Alessandro, Salman Almobayedh, Giuseppe Filiberto Serraino, Matteo Matteucci, Vittoria Lodo, Matthias Thielmann, Piotr Suwalski, Carlo Fino, Nikolaos Kalampokas, Shabir Hussain Shah, Marek A. Deja, Dario Fina, Roberto Lorusso, Nawwar Al-Attar, Theodor Fischlein, Udo Boeken, Guglielmo Maria Actis Dato, Francesco Formica, Sandro Sponga, Adam Kowalówka, Fareed A Khouqeer, Carlo De Vincentiis, Giulio Massimi, Igor Vendramin, Jean-François Obadia, Thierry Folliguet, Daniele Ronco, Giovanni Troise, Federica Jiritano, Michele De Bonis, Cesare Beghi, Caterina Simon, Emmanuel Villa, Mariusz Kowalewski, Jurij M. Kalisnik, Shiho Naito, Marco Ranucci, Claudio Russo, CTC, RS: Carim - V04 Surgical intervention, MUMC+: MA Med Staf Spec CTC (9), CarMeN, laboratoire, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Central Clinical Hospital of the Ministry of the Interior & Administration [Warsaw, Poland] (2CHMIA), Ministry of the Interior and Administration [Warsaw, Poland] (MIA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Università degli studi di Parma = University of Parma (UNIPR), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Università degli Studi di Milano, IRCCS Policlinico San Donato, CHU Henri Mondor, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Niguarda Hospital [Milan, Italy], Università degli Studi di Udine - University of Udine [Italie], University of Pisa - Università di Pisa, Klinikum Nürnberg Nord, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione Poliambulanza, Mauriziano Umberto Hospital [Turin, Italy] (MUH), King Fahad Medical City [Riyadh, Saudi Arabia], Luigi Sacco University Hospital [Milan], Medical University of Silesia (SUM), Upper Silesian Medical Centre [Katowice, Poland] (USMC), West German Heart Center, Universität Duisburg-Essen [Essen], University Hospitals Leuven [Leuven], King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Golden Jubilee National Hospital, Glasgow, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital Düsseldorf, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), University Heart Center [Hamburg], Cardiovascular Research Institute Maastricht (CARIM), Università degli Studi di Brescia = University of Brescia (UniBs), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Ronco, D., Matteucci, M., Kowalewski, M., De Bonis, M., Formica, F., Jiritano, F., Fina, D., Folliguet, T., Bonaros, N., Russo, C. F., Sponga, S., Vendramin, I., De Vincentiis, C., Ranucci, M., Suwalski, P., Falcetta, G., Fischlein, T., Troise, G., Villa, E., Dato, G. A., Carrozzini, M., Serraino, G. F., Shah, S. H., Scrofani, R., Fiore, A., Kalisnik, J. M., D'Alessandro, S., Lodo, V., Kowalowka, A. R., Deja, M. A., Almobayedh, S., Massimi, G., Thielmann, M., Meyns, B., Khouqeer, F. A., Al-Attar, N., Pozzi, M., Obadia, J. -F., Boeken, U., Kalampokas, N., Fino, C., Simon, C., Naito, S., Beghi, C., and Lorusso, R.
Subjects: Male, MORTALITY-RATES, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, Myocardial Infarction, Cohort Studies, Odds Ratio, Myocardial infarction, Prospective Studies, Coronary Artery Bypass, Prospective cohort study, Original Investigation, Ventricular Septal Rupture, OUTCOMES, Cardiogenic shock, Mortality rate, CARDIAC RUPTURE, General Medicine, MECHANICAL CIRCULATORY SUPPORT, Middle Aged, [SDV] Life Sciences [q-bio], Online Only, Female, Life Sciences & Biomedicine, Cohort study, medicine.medical_specialty, Preoperative care, EXTRACORPOREAL MEMBRANE-OXYGENATION, Medicine, General & Internal, General & Internal Medicine, medicine, Extracorporeal membrane oxygenation, Humans, cardiovascular diseases, Aged, Retrospective Studies, REPAIR, Science & Technology, business.industry, Research, ELEVATION MYOCARDIAL-INFARCTION, Perioperative, medicine.disease, Surgery, DEFECT, RISK-FACTORS, business, TASK-FORCE
Abstract: Key Points Question What are the early outcomes of surgical treatment of postinfarction ventricular septal rupture? Findings In this cohort study of 475 patients from 26 different centers worldwide, the early mortality rate for surgically treated ventricular septal rupture was 40.4%, mostly due to low cardiac output, and it did not improve in the last 2 decades. Meaning The findings of this study suggest that patient-tailored preoperative and perioperative management of postinfarction ventricular septal rupture should be addressed to improve the current suboptimal survival rates., This cohort study assesses the clinical characteristics and early outcomes for patients who received surgery for postinfarction ventricular septal rupture and identifies factors independently associated with mortality., Importance Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic. Objectives To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality. Design, Setting, and Participants The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR. Exposures Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting). Main Outcomes and Measures The primary outcome was early mortality; secondary outcomes were postoperative complications. Results Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P
Published: 2021
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10. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author: Luca S. Belli, Christophe Duvoux, Thierry Artzner, William Bernal, Sara Conti, Paolo A. Cortesi, Sophie-Caroline Sacleux, George-Philippe Pageaux, Sylvie Radenne, Jonel Trebicka, Javier Fernandez, Giovanni Perricone, Salvatore Piano, Silvio Nadalin, Maria C. Morelli, Silvia Martini, Wojciech G. Polak, Krzysztof Zieniewicz, Christian Toso, Marina Berenguer, Claudia Iegri, Federica Invernizzi, Riccardo Volpes, Vincent Karam, René Adam, François Faitot, Liane Rabinovich, Faouzi Saliba, Lucy Meunier, Mickael Lesurtel, Frank E. Uschner, Costantino Fondevila, Baptiste Michard, Audrey Coilly, Magdalena Meszaros, Domitille Poinsot, Andreas Schnitzbauer, Luciano G. De Carlis, Roberto Fumagalli, Paolo Angeli, Vincente Arroyo, Rajiv Jalan, Raffaella Viganò, Chiara Mazzarelli, Andrea Lauterio, Alessandro Giacomoni, Francesca Donato, Pietro Lampertico, Luisa Pasulo, Stefano Fagiuoli, Michele Colledan, Maria Cristina Morelli, Giovanni Vitale, Damiano Patrono, Renato Romagnoli, Antonio Ottobrelli, Ioannis Petridis, Umberto Cillo, Giacomo Germani, Patrizia Burra, Philippe Bachellier, Pietro Addeo, Camille Besch, Francoise Faitot, Sophie Caroline Sacleux, Saliba Faouzi, Rene Adam, Didier Samuel, Celine Guichon, Stéfanie Faure, Josè Ursic-Bedoya, Jorde Colmenero, David Toapanta, María Hernández-Tejero, Carmen Vinaixa, Caroline den Hoed, Jubi E. de Haan, Andrea Della Penna, Frank Erhard Uschner, Martin Welker, Stefan Zeuzem, Wolf Bechstein, Nicolas Goossens, Joanna Raszeja-Wyszomirska, Dev Katarey, Banwari Agarwal, Surgery, Internal Medicine, Gastroenterology & Hepatology, Intensive Care, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de Hautepierre [Strasbourg], King‘s College London, Ospedale Multimedica Sesto San Giovanni, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Goethe-University Frankfurt am Main, European Foundation for Study of Chronic Liver Failure [Barcelona] (EF CLIF), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, Geneva University Hospitals and Geneva University, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Department of Physiopatology and Transplantation, University of Milan (DEPT), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale S. Giovanni Battista-Molinette, Azienda Ospedaliera di Padova, Università degli Studi di Padova = University of Padua (Unipd), Hospital Clinic i Provincial de Barcelona (SCReN), University College London Hospitals (UCLH), Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Goossens, Nicolas, and Salvy-Córdoba, Nathalie
Subjects: Male, 0301 basic medicine, Multi-drug resistant organisms, medicine.medical_treatment, Waiting list, Salvage therapy, Liver transplantation, Severity of Illness Index, MESH: Proportional Hazards Models, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Medicine, MESH: Cohort Studies, Acute-on-Chronic Liver Failure, MESH: Aged, High rate, MESH: Middle Aged, ddc:617, Hazard ratio, MESH: Acute-On-Chronic Liver Failure, Middle Aged, Prognosis, Predictive factors, Italy, Female, 030211 gastroenterology & hepatology, Adult, MESH: Liver Transplantation, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH: Severity of Illness Index, Internal medicine, Humans, Acute on chronic liver failure, Renal replacement therapy, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Hepatology, business.industry, MESH: Italy, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Multi-drug resistant organism, MESH: Male, 030104 developmental biology, Predictive factor, business, MESH: Female
Abstract: Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.
Published: 2021
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11. Management of Cancer-Associated Thrombosis: Unmet Needs and Future Perspectives

Author: Ismail Elalamy, Hikmat Abdel-Razeq, Giancarlo Agnelli, Ana Thereza Rocha, Benjamin Brenner, Andrés J Muñoz Martin, Anna Falanga, Cihan Ay, Marc Carrier, Grégoire Le Gal, Department of Immunohematology and Transfusion Medicine (Dep Immuno Hematol - BERGAMO), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Ottawa Hospital Research Institute [Ottawa] (OHRI), Medizinische Universität Wien = Medical University of Vienna, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universidade Federal da Bahia (UFBA), Università degli Studi di Perugia (UNIPG), Service d'Hématologie biologique [CHU Tenon], CHU Tenon [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), Technion - Israel Institute of Technology [Haifa], and Sechenov First Moscow State Medical University
Subjects: medicine.medical_specialty, Gastrointestinal bleeding, thrombocytopenia, 030204 cardiovascular system & hematology, law.invention, Unmet needs, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Randomized controlled trial, law, medicine, Cancer associated thrombosis, Diseases of the circulatory (Cardiovascular) system, cancer, Primary Brain Tumors, Intensive care medicine, thrombosis, business.industry, Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, DOACs, Thrombosis, LMWH, 3. Good health, 030220 oncology & carcinogenesis, RC666-701, Original Article, VTE, PE, business, DVT
Abstract: Patients with cancer are at a high risk of symptomatic venous thromboembolism (VTE), which is a common cause of morbidity and mortality in this patient population. Increased risk of recurrent VTE and bleeding complications are two major challenges associated with therapeutic anticoagulation in these patients. Long-term therapy with low-molecular-weight heparins (LMWHs) has been the standard of care for the treatment of cancer-associated VTE given its favorable risk–benefit ratio in comparison with vitamin K antagonists. Direct oral anticoagulants (DOACs), which offer the convenience of oral administration and have a rapid onset of action, have recently emerged as a new treatment option for patients with cancer-associated thrombosis (CT). Randomized clinical trial data with head-to-head comparisons between DOACs and LMWHs showed that overall, DOACs have a similar efficacy profile but a higher risk of bleeding was observed in some of these studies. This review aims to identify unmet needs in the treatment of CT. We discuss important considerations for clinicians tailoring anticoagulation (1) drug–drug interactions, (2) risk of bleeding (e.g., gastrointestinal bleeding), (3) thrombocytopenia, hematological malignancies, (4) metastatic or primary brain tumors, and (5) renal impairment. Additional research is warranted in several clinical scenarios to help clinicians on the best therapeutic approach.
Published: 2021
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12. International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Author: Helena Degroote, Federico Piñero, Charlotte Costentin, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Aline Lopes Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrio Di Benedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Adrián Gadano, Claire Vanlemmens, Stefano Fagiuoli, Fernando Rubinstein, Patrizia Burra, Daniel Cherqui, Marcelo Silva, Hans Van Vlierberghe, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, M. Fauda, A. Gonzalez Campaña, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Ghent University Hospital, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Arcispedale S Maria Nuova, University of Campinas [Campinas] (UNICAMP), CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Strasbourg, Hôpital de Rangueil, CHU Toulouse [Toulouse], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Degroote, H, Piñero, F, Costentin, C, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Di Benedetto, F, Duque, S, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Cherqui, D, Silva, M, Van Vlierberghe, H, Duvoux, C, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Rennes (UR), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: RFA, LRT, Hepatocellular carcinoma, ITT, University of California San Francisco downstaging, medicine.medical_treatment, RC799-869, Liver transplantation, Gastroenterology, United Network for Organ Sharing, SHR, hazard ratio, 0302 clinical medicine, HR, UCSF-DS, HCC, 10. No inequality, All-comer, Milan criteria, AC, all-comers, Hazard ratio, intention to treat, Diseases of the digestive system. Gastroenterology, 3. Good health, MVI, MVI, microvascular invasion, 030220 oncology & carcinogenesis, liver resection, 030211 gastroenterology & hepatology, radiofrequency ablation, Cohort study, UNOS, medicine.medical_specialty, education, AFP, LT, liver transplantation, 03 medical and health sciences, alpha-foetoprotein, Downstaging, UNOS, United Network for Organ Sharing, TACE, medicine.disease, HR, hazard ratio, UCSF downstaging protocol, AC, ITT, intention to treat, PEI, Clinical trial, DS, downstaging, SHR, subdistribution hazard ratio, locoregional therapies, percutaneous ethanol ablation, AFP, alpha-foetoprotein, EASL, European Association for the Study of the Liver, [SDV]Life Sciences [q-bio], microvascular invasion, LR, LT, Medicine and Health Sciences, UCSF-DS, University of California San Francisco downstaging, Immunology and Allergy, MC, DS, PEI, percutaneous ethanol ablation, all-comers, liver transplantation, waiting list, COMPETING RISKS, CANCER, Research Article, European Association for the Study of the Liver, ALPHA-FETOPROTEIN, MC, Milan criteria, WL, waiting list, EASL, VALIDATION, Internal medicine, Internal Medicine, medicine, subdistribution hazard ratio, WL, LRT, locoregional therapies, RFA, radiofrequency ablation, transarterial chemoembolisation, Intention-to-treat analysis, Hepatology, business.industry, TACE, transarterial chemoembolisation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, All-comers, Alpha-foetoprotein, HCC, hepatocellular carcinoma, LR, liver resection, MODEL, Transplantation, business
Abstract: Background & Aims Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p, Graphical abstract, Highlights • Successful downstaging from UCSF criteria resulted in a similar outcome compared with the group initially within Milan criteria. • Patients within UCSF-DS criteria and with AFP values below or equal to 20 ng/ml at listing have excellent survival and recurrence rates. • All-comers have a higher recurrence after downstaging to Milan criteria, with frequent microvascular invasion in the explant.
Published: 2021
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13. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR‐Preserved trial

Author: Stefan Janssens, Investigators, Dong-Ju Choi, Juan Esteban Gomez-Mesa, Marie-France Seronde, Ileana L. Piña, James L. Januzzi, Dragos Vinereanu, Janet Schnee, Javed Butler, Stephen J. Nicholls, Subodh Verma, Edimar Alcides Bocchi, Stefano Taddei, Gerasimos Filippatos, Nadia Giannetti, David Sim, Martina Brueckmann, Béla Merkely, Jindrich Spinar, Piotr Ponikowski, Milton Packer, João Pedro Ferreira, Stefan D. Anker, Stuart J. Pocock, Michele Senni, Muhammad Shahzeb Khan, Vijay K. Chopra, EMPEROR-Preserved Trial Committees, José Ramón González-Juanatey, Waheed Jamal, Eduardo Chuquiure, Sergio V. Perrone, Michael Böhm, Iain B. Squire, Faiez Zannad, Sven Schnaidt, Jian Zhang, Hiroyuki Tsutsui, Hans Pieter Brunner-La Rocca, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Anker, S, Butler, J, Filippatos, G, Shahzeb Khan, M, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Seronde, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial Committees and, I, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Universidade de São Paulo = University of São Paulo (USP), Saarland University [Saarbrücken], Saarland University Hospital (UKS), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Seoul National University Bundang Hospital (SNUBH), Max Superspeciality Hospital, Saket, Instituto Nacional de Cardiologia Ignacio Chavez, McGill University Health Center [Montreal] (MUHC), Fundacion Vallee del Lili, University Hospitals Leuven [Leuven], Massachusetts General Hospital [Boston], Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Semmelweis University of Medicine [Budapest], Monash university, Department of Cardiology, FLENI Institute, Wayne State University [Detroit], Wrocław Medical University, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), National Heart Centre Singapore (NHCS), Masaryk University Hospital, Glenfield Hospital, University of Pisa - Università di Pisa, Kyushu University, St. Michael's Hospital, University of Toronto, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Fuwai Hospital Chinese Academic of Medical Science, Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Universität Heidelberg [Heidelberg], London School of Hygiene and Tropical Medicine (LSHTM), Baylor University Medical Center, Baylor College of Medecine, Imperial College London, The EMPEROR-Preserved trial was funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance., and BOZEC, Erwan
Subjects: Male, Cardiac & Cardiovascular Systems, Empagliflozin, 030204 cardiovascular system & hematology, 0302 clinical medicine, Glucosides, glucose co&#8208, Natriuretic Peptide, Brain, Sodium&#8211, Aged, 80 and over, OUTCOMES, Ejection fraction, Sodium–glucose co-transporter 2 inhibitor, Atrial fibrillation, Middle Aged, SPIRONOLACTONE, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Heart failure with preserved ejection fraction, Cohort, Cardiology, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, transporter 2 inhibitors, Sodium-glucose co-transporter 2 inhibitors, medicine.medical_specialty, sodium&#8211, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Double-Blind Method, Internal medicine, Diabetes mellitus, medicine, Humans, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, Heart Failure, Science & Technology, business.industry, Cardiovascular Agents, Stroke Volume, medicine.disease, Peptide Fragments, Diabetes Mellitus, Type 2, Heart failure, Cardiovascular System & Cardiology, Sodium–glucose co-transporter 2 inhibitors, business, Biomarkers, Kidney disease
Abstract: AIMS: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. METHODS AND RESULTS: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. CONCLUSION: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:22 issue:12 pages:2383-2392 ispartof: location:England status: published
Published: 2020
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14. Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis

Author: E. Hulegardh, Samantha Pasca, Y. W. Cheung, V. Rigamonti, Thomas L. Ortel, Walter Ageno, Pieter Willem Kamphuisen, Alexander Gallus, G. Le Gal, Agnes Y.Y. Lee, Philippe Debourdeau, Susanna Ranta, Sam Schulman, Anna Falanga, S. Molnar, Michelle Zondag, Lori-Ann Linkins, Ramón Lecumberri, M. De Sancho, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Karolinska Institutet [Stockholm], Center for Hemorrhagic and Thrombotic Disease (CHTD - UDINE), University of Udine and University Hospital of Udine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Weill Medical College of Cornell University [New York], Department of Haematology (ADELAIDE - Dep Haemato), Flinders Medical Centre-Flinders University, Department of Haematology (DH - Pamplona), Clinica Universitaria de Navarra, Oncology and Hematology Department (Oncol Hemato Dep - CORDOBA), Sanatorio Allende (Sanatorio Allende - CORDOBA), Department of Clinical and Experimental Medicine (VARESE - Thrombosis Center), Universitá degli Studi dell’Insubria, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Ottawa Hospital Research Institute [Ottawa] (OHRI), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Immunohematology and Transfusion Medicine (Dep Immuno Hematol - BERGAMO), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Department of Hematology and Coagulation (Dep Hematol Coag - GOTHENBURG), Sahlgrenska University Hospital [Gothenburg], Department of Vascular Medicine (DVM - Groningen), University Medical Center Groningen [Groningen] (UMCG), Département d'Oncologie (Dep Oncol - AVIGNON), Institut Ste Catherine, Praxis Bubenberg (Praxis Bubenberg - BERN), Praxis Bubenberg, Division of Hematology (Div Hematol - DURHAM), Duke University Medical Center, Columbia University [New York], Diamond Health Care Centre (DHCC - VANCOUVER), University of British Columbia (UBC), Schulman, S, Zondag, M, Linkins, L, Pasca, S, Cheung, Y, de Sancho, M, Gallus, A, Lecumberri, R, Molnar, S, Ageno, W, Le Gal, G, Falanga, A, Hulegårdh, E, Ranta, S, Kamphuisen, P, Debourdeau, P, Rigamonti, V, Ortel, T, Lee, A, 01 Internal and external specialisms, and Other departments
Subjects: Male, Time Factors, Vitamin K, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, PROPHYLAXIS, 0302 clinical medicine, Recurrence, Risk Factors, Neoplasms, Prospective Studies, Registries, low-molecular-weight heparin, PREDICTORS, Drug Substitution, Anticoagulant, Hazard ratio, Low-Molecular-Weight, MOLECULAR-WEIGHT HEPARIN, Hematology, Heparin, Middle Aged, Vitamin K antagonist, Thrombosis, 3. Good health, ACTIVE CANCER, Treatment Outcome, 030220 oncology & carcinogenesis, POPULATION-BASED-COHORT, Female, medicine.drug, medicine.medical_specialty, medicine.drug_class, venous thromboembolism, Bleeding, Cancer, Low-molecular-weight heparin, Venous thromboembolism, Warfarin, Aged, Anticoagulants, Chi-Square Distribution, Hemorrhage, Heparin, Low-Molecular-Weight, Humans, Proportional Hazards Models, Retrospective Studies, Venous Thromboembolism, WARFARIN, 03 medical and health sciences, Internal medicine, medicine, cancer, DOSE-ESCALATION, cardiovascular diseases, MALIGNANCY, business.industry, bleeding, medicine.disease, BLEEDING COMPLICATIONS, Confidence interval, Surgery, THROMBOSIS, Regimen, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BackgroundRecommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies.MethodsPatients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression.ResultsWe registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation.ConclusionMorbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
Published: 2015
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15. The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Author: Federico Coccolini, Leonel Lagunes, André Ricardo Araujo da Silva, Massimo Sartelli, Sara Al-Dahir, Young R. Lee, Mario Tumbarello, Faryal Khamis, Natalia Santos, Jean Carlet, Fausto Catena, Agron Dogjani, Jan Ulrych, Isidro Martinez Casas, András Vereczkei, Salomone Di Saverio, Sydney Malama, Harry van Goor, Garima Kapoor, Hong Bin Kim, Norio Sato, Gustavo M. Machain, Chinmay Gandhi, Iryna Kozlovska, Ramiro Manzano-Nunez, Katia Iskandar, Fikri M. Abu-Zidan, Sujith J Chandy, Rosio Isabel Guerra Gronerth, Therese M. Duane, Lena M. Napolitano, Carlos A. Ordoñez, Yonghong Xiao, Michael McFarlane, Cristian Mesina, Sanjay Marwah, Goran Augustin, Tatjana Goranovic, Bruno M. Pereira, Ivan Kerschaever, Timothy Craig Hardcastle, Marcelo A. Beltrán, Stephen Y. Liang, Julio C. Haidamus Monteiro, Vishalkumar G Shelat, Kuo Ching Yuan, Sandro Scarpelini, Narayan Dutt Pant, Martha Quiodettis, Carlos Alves, Mutasim M. Elmangory, Céline Pulcini, Addison K. May, Guntars Pupelis, Selman Uranues, Pamela Barbadoro, Sandro Rizoli, Ernest E. Moore, Rifat Latifi, Ashish Khanna, Hossein Samadi Kafil, Richard R. Watkins, Boonying Siribumrungwong, Abdelkarim H. Omari, Agnes Wechsler-Fördös, Lewis J. Kaplan, Nusrat Shafiq, Jason A. Roberts, Warren Lowman, Laurent Dortet, Stephen M. Brecher, Luca Ansaloni, Rodolfo Soto, Tanya L. Zakrison, Sameer Dhingra, Jacobus Preller, Eleftherios Mylonakis, Wagih Ghnnam, Asri Che Jusoh, Pierluigi Viale, Costi D. Sifri, Miklosh Bala, José Gustavo Parreira, Alfredo Ponce-de-León, Jae G. Lee, Jakub Kenig, Kjetil Søreide, Halil Alis, Lilian M. Abbo, Mahir Gachabayov, Marco Catani, Ronald Kiguba, Jean-Ralph Zahar, Wietse P. Zuidema, Robert G. Sawyer, Loredana Scoccia, Nuno Pereira, Vladimir Khokha, Ionut Negoi, Aneel Bhangu, Michał Pędziwiatr, Helen Giamarellou, Garyphallia Poulakou, Shyam Kumar Mishra, Francesco Di Marzo, Jeffrey M. Tessier, Boris Sakakushev, Milica D. Nestorovic, Hamilton Petry de Souza, Tarcisio Reis, Yousheng Li, Dominik Mertz, Andreas Hecker, Ngo Tat Trung, Anand Kumar, Belefquih Bouchra, Leonardo Pagani, James M. Sanders, AA Munyika, Brian S. Zuckerbraun, Souha S. Kanj, Arda Isik, Luigia Scudeller, Adrien Hodonou, Philip S. Barie, Marc Maegele, Jill R. Cherry-Bukowiec, Peep Talving, Orestis Ioannidis, Miran Rems, Oliver A. Cornely, Harumi Gomi, Ewen A. Griffiths, Mushira Enani, Zaza Demetrashvili, Gereltuya Dorj, Piotr Major, Miguel Caínzos, Ari Leppäniemi, Jesús Rodríguez-Baño, Wen Chien Ko, Ziad A. Memish, Osvaldo Chiara, Elif Colak, José Artur Paiva, A R K Adesunkanmi, Timothy M. Rawson, Georgios Gkiokas, Paula Ferrada, Francesco M. Labricciosa, Alain Chichom-Mefire, Jan J. De Waele, Yunfeng Cui, Adrián Camacho-Ortiz, J. Esteban Foianini, Majdi N. Al-Hasan, Belinda De Simone, David P. Nicolau, Kaoru Koike, Athanasios Marinis, Florian M.E. Wagenlehner, Aleksandar Karamarkovic, Adrian Brink, Emilio Maseda, II kirurgian klinikka, Department of Surgery, Clinicum, HUS Abdominal Center, Surgery, Other Research, Università degli Studi di Macerata = University of Macerata (UNIMC), Università Politecnica delle Marche [Ancona] (UNIVPM), Central Hospital [Bolzano, Italy], Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Milpark Hospital (Milpark Hospital), Milpark Hospital, University of Cape Town, World Alliance against Antibiotics Resistance, Cleveland Clinic, Regional Hospital, Limbe, Rimini Infermi Hospital, Maggiore Hospital, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], University of Bologna, Northeastern Ohio Medical University (NEOMED), Foundation IRCCS Policlinico San Matteo, University of Miami Leonard M. Miller School of Medicine (UMMSM), United Arab Emirates University (UAEU), Obafemi Awolowo University (OAU), Xavier University of Louisiana, University of South Carolina School of Medicine, Columbia, South Carolina, Training Hospital Istanbul, Hospital de São João [Porto], Centro de Investigação em Estudos da Criança (CIEC), Universidade do Minho, University Hospital Center Zagreb, Hadassah Hebrew University Medical Center [Jerusalem], Weill Cornell Medicine [New York], Universidad de La Serena (USERENA), Queens Elizabeth Hospital [Birmingham], Université Internationale de Casablanca (UIC), VA Boston Healthcare System, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, University Hospital of Cologne [Cologne], 4th Department of Internal Medicine, University of Athens Medical School [Athens], Center for Visual Information Technology [Hyderabad] (CVIT), International Institute of Information Technology, Hyderabad [Hyderabad] (IIIT-H), Chonnam National University [Gwangju], Shanghai Jiaotong University, University of Houston, Centro Hospitalar Universitário São João - Faculty of Medicine - University of Porto - Grupo de Infecção e Sepsis, Porto, Unité de biostatistiques, CHU Clermont-Ferrand, ATTIKON University General Hospital, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Duke University Marine Laboratory, University Hospital Virgen Macarena, Service de bactériologie, virologie, parasitologie et hygiène, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sartelli, M, Labricciosa, FM, Barbadoro, P, Pagani, L, Dorj, G, Catena, Fausto, Sartelli, Massimo, Labricciosa, Francesco M., Barbadoro, Pamela, Pagani, Leonardo, Ansaloni, Luca, Brink, Adrian J., Carlet, Jean, Khanna, Ashish, Chichom-Mefire, Alain, Coccolini, Federico, Di Saverio, Salomone, May, Addison K., Viale, Pierluigi, Watkins, Richard R., Scudeller, Luigia, Abbo, Lilian M., Abu-Zidan, Fikri M., Adesunkanmi, Abdulrashid K., Al-Dahir, Sara, Al-Hasan, Majdi N., Alis, Halil, Alves, Carlo, Araujo da Silva, André R., Augustin, Goran, Bala, Miklosh, Barie, Philip S., Beltrán, Marcelo A., Bhangu, Aneel, Bouchra, Belefquih, Brecher, Stephen M., Caínzos, Miguel A., Camacho-Ortiz, Adrian, Catani, Marco, Chandy, Sujith J., Jusoh, Asri Che, Cherry-Bukowiec, Jill R., Chiara, Osvaldo, Colak, Elif, Cornely, Oliver A., Cui, Yunfeng, Demetrashvili, Zaza, De Simone, Belinda, De Waele, Jan J., Dhingra, Sameer, Di Marzo, Francesco, Dogjani, Agron, Dorj, Gereltuya, Dortet, Laurent, Duane, Therese M., Elmangory, Mutasim M., Enani, Mushira A., Ferrada, Paula, Esteban Foianini, J., Gachabayov, Mahir, Gandhi, Chinmay, Ghnnam, Wagih Mommtaz, Giamarellou, Helen, Gkiokas, Georgio, Gomi, Harumi, Goranovic, Tatjana, Griffiths, Ewen A., Guerra Gronerth, Rosio I., Haidamus Monteiro, Julio C., Hardcastle, Timothy C., Hecker, Andrea, Hodonou, Adrien M., Ioannidis, Oresti, Isik, Arda, Iskandar, Katia A., Kafil, Hossein S., Kanj, Souha S., Kaplan, Lewis J., Kapoor, Garima, Karamarkovic, Aleksandar R., Kenig, Jakub, Kerschaever, Ivan, Khamis, Faryal, Khokha, Vladimir, Kiguba, Ronald, Kim, Hong B., Ko, Wen-Chien, Koike, Kaoru, Kozlovska, Iryna, Kumar, Anand, Lagunes, Leonel, Latifi, Rifat, Lee, Jae G., Lee, Young R., Leppäniemi, Ari, Li, Yousheng, Liang, Stephen Y., Lowman, Warren, Machain, Gustavo M., Maegele, Marc, Major, Piotr, Malama, Sydney, Manzano-Nunez, Ramiro, Marinis, Athanasio, Martinez Casas, Isidro, Marwah, Sanjay, Maseda, Emilio, McFarlane, Michael E., Memish, Ziad, Mertz, Dominik, Mesina, Cristian, Mishra, Shyam K., Moore, Ernest E., Munyika, Akutu, Mylonakis, Eleftherio, Napolitano, Lena, Negoi, Ionut, Nestorovic, Milica D., Nicolau, David P., Omari, Abdelkarim H., Ordonez, Carlos A., Paiva, José-Artur, Pant, Narayan D., Parreira, Jose G., Pedziwiatr, Michal, Pereira, Bruno M., Ponce-de-Leon, Alfredo, Poulakou, Garyphallia, Preller, Jacobu, Pulcini, Céline, Pupelis, Guntar, Quiodettis, Martha, Rawson, Timothy M., Reis, Tarcisio, Rems, Miran, Rizoli, Sandro, Roberts, Jason, Pereira, Nuno Rocha, Rodríguez-Baño, Jesú, Sakakushev, Bori, Sanders, Jame, Santos, Natalia, Sato, Norio, Sawyer, Robert G., Scarpelini, Sandro, Scoccia, Loredana, Shafiq, Nusrat, Shelat, Vishalkumar, Sifri, Costi D., Siribumrungwong, Boonying, Søreide, Kjetil, Soto, Rodolfo, de Souza, Hamilton P., Talving, Peep, Trung, Ngo Tat, Tessier, Jeffrey M., Tumbarello, Mario, Ulrych, Jan, Uranues, Selman, Van Goor, Harry, Vereczkei, Andra, Wagenlehner, Florian, Xiao, Yonghong, Yuan, Kuo-Ching, Wechsler-Fördös, Agne, Zahar, Jean-Ralph, Zakrison, Tanya L., Zuckerbraun, Brian, and Zuidema, Wietse P.
Subjects: 0301 basic medicine, Cross-sectional study, Psychological intervention, Antibiotics, Antimicrobial stewardship, Infections, Surgery, Anti-Infective Agents, Antimicrobial Stewardship, Cross-Sectional Studies, Global Health, Humans, Intraabdominal Infections, Postoperative Complications, Surveys and Questionnaires, GUIDELINES, HEALTH-CARE EPIDEMIOLOGY, 0302 clinical medicine, Global health, Medicine and Health Sciences, PROGRAM, Infection control, Medicine, 030212 general & internal medicine, Response rate (survey), DISEASES SOCIETY, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 3. Good health, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], CIRURGIA, Emergency Medicine, Infection, Life Sciences & Biomedicine, medicine.medical_specialty, 030106 microbiology, lcsh:Surgery, MEDLINE, 03 medical and health sciences, Antibiotic resistance, AMERICA, Science & Technology, business.industry, Antibiotic, lcsh:RD1-811, lcsh:RC86-88.9, 3126 Surgery, anesthesiology, intensive care, radiology, HOSPITALS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Contains fulltext : 177987.pdf (Publisher’s version ) (Open Access) BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. RESULTS: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). CONCLUSION: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.
Published: 2017
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16. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study

Author: Stewardson, Andrew J., Allignol, A., Beyersmann, J., Graves, N., Schumacher, M., Meyer, R., Tacconelli, E., De Angelis, G., Farina, C., Pezzoli, F., Bertrand, X., Gbaguidi-Haore, H., Edgeworth, J., Tosas, O., Martinez, J. A., Ayala-Blanco, M. P., Pan, A., Zoncada, A., Marwick, C. A., Nathwani, D., Seifert, H., Hos, N., Hagel, S., Pletz, M., Harbarth, S., Masuet-Aumatell, Cristina, Navarro, Marta Banqué, Falcone, Chiara, Freiburg Center for Data Analysis and Modeling (FDM), Albert-Ludwigs-Universität Freiburg, Laboratoire de Biologie Moléculaire et Cellulaire du Cancer [Luxembourg] (LBMCC), Hôpital Kirchberg [Luxembourg], Department of Infectious Diseases, Università cattolica del Sacro Cuore [Milano] (Unicatt), INFN Laboratori Nazionali di Legnaro, Unità di Microbiologia, AO 'Ospedale San Carlo Borromeo', Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Groupe d'histoire et diffusion des sciences d'Orsay (GHDSO), Université Paris-Sud - Paris 11 (UP11), Divisione di Malattie Infettive, Istituti Ospitalieri di Cremona, Feinberg School of Medicine, Northwestern University, Department of Pulmonary Medicine, Hannover Medical School [Hannover] (MHH), and Infection Control Programme and WHO Collaborating Centre on Patient Safety
Subjects: 0301 basic medicine, Male, Epidemiology, medicine.disease_cause, Antimicrobial resistance, MESH: Length of Stay, MESH: Proportional Hazards Models, 0302 clinical medicine, MESH: Staphylococcus aureus, 030212 general & internal medicine, Hospital Mortality, MESH: Enterobacteriaceae Infections, MESH: Treatment Outcome, ddc:616, MESH: Aged, MESH: Middle Aged, Cephalosporin Resistance, Hazard ratio, Enterobacteriaceae Infections, Health Care Costs, Middle Aged, Staphylococcal Infections, Antimicrobial, MESH: Hospitals, Hospitals, 3. Good health, Anti-Bacterial Agents, Europe, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Escherichia coli, Meticillin-resistant Staphylococcus aureus (MRSA) in humans, Staphylococcus aureus, bacterial infections, bloodstream infection, multidrug resistance, Aged, Enterobacteriaceae, Female, Humans, Length of Stay, Methicillin-Resistant Staphylococcus aureus, Proportional Hazards Models, Retrospective Studies, Research Article, medicine.medical_specialty, 030106 microbiology, MESH: Cephalosporin Resistance, MESH: Staphylococcal Infections, MESH: Health Care Costs, MESH: Methicillin-Resistant Staphylococcus aureus, Staphylococcal infections, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, 03 medical and health sciences, MESH: Enterobacteriaceae, Antibiotic resistance, Virology, Internal medicine, MESH: Anti-Bacterial Agents, medicine, MESH: Hospital Mortality, MESH: Humans, Proportional hazards model, business.industry, Public Health, Environmental and Occupational Health, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, Methicillin-resistant Staphylococcus aureus, Confidence interval, MESH: Male, Surgery, MESH: Europe, business, MESH: Female
Abstract: We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34–2.42, HR = 1.81; 95% CI: 1.49–2.20 and HR = 2.42; 95% CI: 1.66–3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2–9.4, 11.5 days; 95% CI: 11.5–11.6 and 13.3 days; 95% CI: 13.2–13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8–5.9) but not hazard of death (1.16; 95% CI: 0.98–1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13–2.35), excess LOS (4.9 days; 95% CI: 1.1–8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.
Published: 2016
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17. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study

Author: Hos , Andrew J, Allignol , Arthur, Beyersmann , Jan, Graves , Nicholas, Schumacher , Martin, Hos , Rodolphe, Hos , Evelina, Hos , Giulia, Hos , Claudio, Hos , Fabio, Bertrand , Xavier, Gbaguidi-Haore , Houssein, Edgeworth , Jonathan, Tosas , Olga, Hos , Jose A, Hos , M Pilar, Pan , Angelo, Zoncada , Alessia, Hos , Charis A, Hos , Dilip, Seifert , Harald, Hos , Nina, Hagel , Stefan, Pletz , Mathias, Harbarth , Stephan, Meyer , Rodolphe, Tacconelli , Evelina, De Angelis , Giulia, Farina , Claudio, Pezzoli , Fabio, Martinez , Jose A, Ayala-Blanco , M Pilar, Marwick , Charis A, Nathwani , Dilip, Freiburg Center for Data Analysis and Modeling, University of Freiburg [Freiburg], Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Fondation de Recherche Cancer et Sang - Hôpital Kirchberg, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Divisione di Malattie Infettive, Istituti Ospitalieri di Cremona, Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Feinberg School of Medicine, Northwestern University, Department of Pulmonary Medicine, Hannover Medical School [Hannover] ( MHH ), Infection Control Programme and WHO Collaborating Centre on Patient Safety, Department of Infectious Diseases, Università Cattolica del Sacro Cuore, INFN Laboratori Nazionali di Legnaro, Unità di Microbiologia, AO 'Ospedale San Carlo Borromeo', Hospital Papa Giovanni XXIII ( Hosp P Giovanni XXIII ), Groupe d'histoire et diffusion des sciences d'Orsay ( GHDSO ), Université Paris-Sud - Paris 11 ( UP11 ), Laboratoire Interdisciplinaire de Recherche en Didactique, Éducation et Formation ( LIRDEF ), and Université Paul-Valéry - Montpellier 3 ( UM3 ) -Université de Montpellier ( UM )
Subjects: Staphylococcus aureus, MESH : Retrospective Studies, MESH : Male, MESH : Europe, MESH : Aged, bloodstream infection, MESH : Treatment Outcome, Antimicrobial resistance, MESH : Hospital Mortality, multidrug resistance, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Enterobacteriaceae Infections, Escherichia coli, MESH : Methicillin-Resistant Staphylococcus aureus, MESH : Female, MESH : Middle Aged, MESH : Anti-Bacterial Agents, MESH : Cephalosporin Resistance, MESH : Staphylococcus aureus, MESH : Humans, MESH : Enterobacteriaceae, MESH : Proportional Hazards Models, MESH : Hospitals, MESH : Length of Stay, bacterial infections, MESH : Staphylococcal Infections, Meticillin-resistant Staphylococcus aureus (MRSA) in humans, MESH : Health Care Costs
Abstract: International audience; We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.
Published: 2016

18. Cobimetinib combined with vemurafenib in advanced BRAF V600 -mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial

Author: Ascierto, Paolo, Mcarthur, Grant, Dréno, Brigitte, Atkinson, Victoria, Liszkay, Gabrielle, Di Giacomo, Anna Maria, Mandalà, Mario, Demidov, Lev, Stroyakovskiy, Daniil, Thomas, Luc, De La Cruz-Merino, Luis, Dutriaux, Caroline, Garbe, Claus, Yan, Yibing, Wongchenko, Matthew, Chang, Ilsung, Hsu, Jessie, Koralek, Daniel, Rooney, Isabelle, Ribas, Antoni, Larkin, James, Bernardo, Elizabeth, Istituto Nazionale Tumori, Molecular Oncology Laboratory [East Melbourne, Australia], Peter MacCallum Cancer Centre [East Melbourne, Australia], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Princess Alexandra Hospital, Brisbane, Institute of Oncology, Azienda Ospedaliera Universitaria Senese, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Russian Cancer Research Centre, Moscow City Oncology Hospital, CHU Lyon, Hospital Universitario Virgen del Rocío [Sevilla], Hôpital Saint-André, University of Tübingen, Genentech, Inc., Genentech, Inc. [San Francisco], and Comprehensive Cancer Center
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Background The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF V600-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated effi cacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies.
Published: 2016

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16. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study

17. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study

18. Cobimetinib combined with vemurafenib in advanced BRAF V600 -mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial

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