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1. Extreme Hyperferritinemia: Causes and Prognosis

Author

Maxime Fauter, Sabine Mainbourg, Thomas El Jammal, Arthur Guerber, Sabine Zaepfel, Thomas Henry, Mathieu Gerfaud-Valentin, Pascal Sève, and Yvan Jamilloux

Subjects
hyperferritinemia, hemophagocytic lymphohistiocytosis, septic shock, hyperferritinemic syndrome, ferritin, General Medicine
Abstract

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.

Published
2022
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2. Low glycosylated ferritin is a sensitive biomarker of severe COVID-19

Author

Pascal Sève, Maxime Fauter, Sébastien Viel, Yvan Jamilloux, Pierre Pradat, Marine Villard, Lorna Garnier, Sabine Zaepfel, Thomas Henry, Thierry Walzer, and Julie Fiscus

Subjects
Adult, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Immunology, Betacoronavirus, Prognostic markers, Internal medicine, Correspondence, medicine, Humans, Immunology and Allergy, Prospective Studies, Pandemics, Aged, Aged, 80 and over, biology, business.industry, SARS-CoV-2, Disease progression, COVID-19, Diagnostic markers, Middle Aged, Ferritin, Hospitalization, Endocrinology, Infectious Diseases, Ferritins, biology.protein, Disease Progression, Biomarker (medicine), Female, business, Coronavirus Infections, Biomarkers
Published
2020
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3. Reference percentiles for paired arterial and venous umbilical cord blood gases: An indirect nonparametric approach

Author

Laurent Desmurs, Sabine Zaepfel, Régine Cartier, Muriel Doret-Dion, Denis Monneret, Laurence Chardon, Maison des Sciences de l'Homme et de la Société Sud-Est (MSHS Sud-Est), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Male, 030213 general clinical medicine, medicine.medical_specialty, Percentile, Umbilical Veins, [SDV]Life Sciences [q-bio], Clinical Biochemistry, 030204 cardiovascular system & hematology, Umbilical cord, pCO2, Umbilical Arteries, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Oxygen saturation (medicine), Skewed data, business.industry, Nonparametric statistics, General Medicine, Carbon Dioxide, Hydrogen-Ion Concentration, Fetal Blood, Oxygen, % total haemoglobin, medicine.anatomical_structure, Concomitant, Cardiology, Female, business
Abstract

BACKGROUND Reference intervals for arterial and venous umbilical cord blood gas (UCBG) parameters are scarce, are mainly focused on pH, pO2, pCO2 and base deficit, and are usually assessed using parametric tests, despite a generally skewed data distribution. Here, the purpose is to determine reference percentiles for nine parameters of concomitant arterial and venous UCBG (CAV-UCBG) from neonates at birth, using nonparametric tests. METHODS Results of CAV-UCBG, assayed over a 4.5-year period, were extracted from a hospital laboratory database for pH, pCO2, pO2, oxygen saturation, concentration of total oxygen, total carbon dioxide, hydrogen carbonate, total haemoglobin, and acid-base excess. Exclusion criteria were: a venous-arterial pH difference

Published
2019
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4. Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial

Author

Bohé, Julien, Abidi, Hassane, Brunot, Vincent, Klich, Amna, Klouche, Kada, Sedillot, Nicholas, Tchenio, Xavier, Quenot, Jean-Pierre, Roudaut, Jean-Baptiste, Mottard, Nicolas, Thiollière, Fabrice, Dellamonica, Jean, Wallet, Florent, Souweine, Bertrand, Lautrette, Alexandre, Preiser, Jean-Charles, Timsit, Jean-François, Vacheron, Charles-Hervé, Ait Hssain, Ali, Maucort-Boulch, Delphine, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation de Coopération Scientifique Bourgogne Franche-Comté (FCS Bourgogne Franche-Comté), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital l'Archet, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université libre de Bruxelles (ULB), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), CONTROLe INdividualisé de la Glycémie (CONTROLING) Study Group: Aurèle Buzancais, Anne Marie Dupuy, Rémi Bruyère, Henri de Montclos, Marion Provent, Jocelyne Drai, Joëlle Goudable, Anne Mialon, Bernard Allaouchiche, Arnaud Friggeri, Véréna Landel, Hélène Boyer, Hervé Hyvernat, Céline Caruba-Bafghi, Edouard Soum, Christophe Leroy, Laurence Roszyk, Pierre Eric Danin, Julio Badie, Stefan Georgiev, Martine Laplace, Richard Jospe, Jérôme Morel, Ali Mofredj, Abdelbaki Azaouzi, Jean-Paul Aubry, Abdelhamid Fatah, Stanislas Ledochowski, Sabine Zaepfel, Eric Fontaine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Service de Biostatistiques [Lyon], and MORNET, Dominique

Subjects
[SDV] Life Sciences [q-bio], Glycated haemoglobin A1c, [SDV]Life Sciences [q-bio], Glucose control, Individualised glucose control, Hyperglycaemia, Insulin
Abstract

International audience; Purpose: Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient's pre-admission usual glycaemia, could improve outcome.Methods: In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.Results: Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018).Conclusion: Targeting an ICU patient's pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

Published
2021
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5. Atteintes myocardiques au cours de la maladie à coronavirus 19 (Covid-19) : principaux mécanismes physiopathologiques et utilité clinique des biomarqueurs cardiaques

Author

Kamel, Saïd, Raynor, Alexandre, Zozor, Samuel, Lacape, Geneviève, Brunel, Valéry, Nivet-Antoine, Valérie, Collin-Chavagnac, Delphine, Peoc’h, Katell, Cohen, Ariel, Lassoued, Amin Ben, Chévrier, Marc, Alemann, Mathieu, Lessinger, Jean-Marc, Bérard, Annie, Sapin, Vincent, Beauvieux, Marie-Christine, Levy, Pacifique, Lehmann, Sylvain, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), CHU Necker - Enfants Malades [AP-HP], 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), CHU Saint-Antoine [AP-HP], Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Hôpital de la Timone [CHU - APHM] (TIMONE), Hospices Civils de Lyon (HCL), Nouvel Hôpital Civil de Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Pour le Groupe de Travail de la SFBC « Marqueurs Biochimiques de la pathologie Covid-19 »: Isabelle Aimone-Gastin, Stéphanie Alcaraz, Stéphane Allouche, Malika Balduyck, Françoise Barbé, Yann Barguil, Jean-Philippe Bastard, Jean-Louis Beaudeux, Marie-Christine Beauvieux, Amin Ben Lassoued, Isabelle Benz de Bretagne, Annie Bérard, Laurent Bermont, Edith Bigot-Corbel, Muriel Bost, Valery Bourbonneux, Valery Brunel, Jean-Luc Carré, Camille Chenevier-Gobeaux, Marc Chevrier, Giulia Chinetti, Delphine Collin-Chavagnac, Hervé Delacour, Delphine Delevallée, François Desroys du Roure, Patrice Faure, Jean-Philippe Galhaud, Anne Galinier, Thierry Hauet, Carine Helj, Emilie Jolly, Said Kamel, Sylvain Lehmann, Aline Leroy, Jean-Marc Lessenger, Pacifique Levy, Anne-Marie Lorec-Penet, Samir Mesli, Dagui Monnet, Caroline Moreau, Laurence Mouly, Valérie Nivet-Antoine, Nathalie Oueidat, Mathieu Pecquet, Katell Peoc’h, Laurence Piéroni, Carole Poupon, Martine Roubille, Benoit Rucheton, Medhi Sakka, Vincent Sapin, Vincent Saunier, Florian Scherrer, François Schmitt, Sabine Zaepfel, Samuel Zozor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, 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), VIAUD, Karine, Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
Adult, Male, medicine.medical_specialty, Myocarditis, [SDV]Life Sciences [q-bio], Myocardial Infarction, troponine, Disease, Systemic inflammation, Predictive Value of Tests, Internal medicine, myocarde, Coagulopathy, medicine, myocardium, Humans, Hospital Mortality, Myocardial infarction, Pandemics, Aged, Aged, 80 and over, Endocarditis, biology, business.industry, SARS-CoV-2, troponin, Heart, General Medicine, Middle Aged, Prognosis, medicine.disease, Troponin, Pathophysiology, 3. Good health, myocardite, [SDV] Life Sciences [q-bio], peptides natriurétiques, biology.protein, Cardiology, Female, France, Myocardial infarction diagnosis, medicine.symptom, myocarditis, business, Covid-19, natriuretic peptides, Biomarkers
Abstract

International audience; Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.

Published
2021
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