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1. Protein-S-100-beta is increased in patients with decompensated cirrhosis admitted to ICU

Author

Nicolas Weiss, Simona Tripon, Maxime Mallet, Françoise Imbert-Bismut, Mehdi Sakka, Dominique Bonnefont-Rousselot, Philippe Sultanik, Sarah Mouri, Marika Rudler, and Dominique Thabut

Subjects
Cirrhosis, Hepatic encephalopathy, Blood–brain barrier, PS100-Beta, Liver disease, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Background: Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood–brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods: We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta – in combination with other factors – to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test. Results: A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P

Published
2024
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2. Burden of grade 3 or 4 liver injury associated with immune checkpoint inhibitors

Author

Lucia Parlati, Mehdi Sakka, Aurelia Retbi, Samir Bouam, Lamia Hassani, Jean-François Meritet, Pierre Rufat, Dominique Bonnefont-Rousselot, Rui Batista, Benoit Terris, Agnès Bellanger, Dominique Thabut, Aurore Vozy, Jean-Philippe Spano, Romain Coriat, François Goldwasser, Selim Aractingi, Philippe Sogni, Stanislas Pol, Vincent Mallet, Jérôme Alexandre, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Sixtine De Percin, Nora Kramkimel, Olivier Huillard, Jeanne Chapron, Benedicte Deau-Fischer, Marie-Laure Brandely-Piat, Diane Damotte, Audrey Lupo, Marco Alifano, Marion Corouge, Clémence Hollande, Hélène Fontaine, Lorianne Lair Mehiri, Anaïs Vallet Pichard, and Patrick Tilleul

Subjects
Cancer treatment protocols, Drug-induced Liver Injury, Hepatitis, Immune checkpoint inhibitors, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes. Results: Among 952 patients (median [IQR] age 66 [57–73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67–6.79]; p

Published
2023
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3. Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression

Author

Walid Khrouf, Dario Saracino, Benoit Rucheton, Marion Houot, Fabienne Clot, Daisy Rinaldi, Joana Vitor, Marie Huynh, Evelyne Heng, Dimitri Schlemmer, Florence Pasquier, Vincent Deramecourt, Sophie Auriacombe, Carole Azuar, Richard Levy, Stéphanie Bombois, Claire Boutoleau-Brétonnière, Jérémie Pariente, Mira Didic, David Wallon, Frédérique Fluchère, Stéphane Auvin, Imen Ben Younes, Yann Nadjar, Alexis Brice, Bruno Dubois, Dominique Bonnefont-Rousselot, Isabelle Le Ber, and Foudil Lamari

Subjects
Frontotemporal dementia (FTD), Neuronal ceroid lipofuscinosis-11 (CLN-11), Progranulin, Lysosphingolipids, Lysosome, Lysosomal storage disease (LSD), Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases.We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation. GRN carriers consisted of 102 heterozygous FTD patients (FTD-GRN), three homozygous patients with neuronal ceroid lipofuscinosis-11 (CLN-11) and 26 presymptomatic carriers (PS-GRN), the latter with longitudinal assessments. Glucosylsphingosin d18:1 (LGL1), lysosphingomyelins d18:1 and isoform 509 (LSM18:1, LSM509) and lysoglobotriaosylceramide (LGB3) were measured by electrospray ionization-tandem mass spectrometry coupled to ultraperformance liquid chromatography.Levels of LGL1, LSM18:1 and LSM509 were increased in GRN carriers compared to non-carriers (p

Published
2023
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4. Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

Author

Olivier Bourron, Franck Phan, Mamadou Hassimiou Diallo, David Hajage, Carole-Elodie Aubert, Aurélie Carlier, Joe-Elie Salem, Christian Funck-Brentano, Salim Kemel, Philippe Cluzel, Alban Redheuil, Jean-Michel Davaine, Ziad Massy, Romuald Mentaverri, Dominique Bonnefont-Rousselot, Philippe Gillery, Stéphane Jaisson, Cees Vermeer, Jean-Marc Lacorte, Nesrine Bouziri, Suzanne Laroche, Chloé Amouyal, and Agnes Hartemann

Subjects
Arterial calcification, Biomarkers, Calcium score, Mediacalcosis, Peripheral artery disease, Type 2 diabetes, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. Results At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p

Published
2020
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5. Disturbances of brain cholesterol metabolism: A new excitotoxic process associated with status epilepticus

Author

Aurélie Hanin, Paul Baudin, Sophie Demeret, Delphine Roussel, Sarah Lecas, Elisa Teyssou, Maria Damiano, David Luis, Virginie Lambrecq, Valerio Frazzini, Maxens Decavèle, Isabelle Plu, Dominique Bonnefont-Rousselot, Randa Bittar, Foudil Lamari, and Vincent Navarro

Subjects
24-hydroxycholesterol, Cholesterol, Status epilepticus, Excitotoxicity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The understanding of the excitotoxic processes associated with a severe status epilepticus (SE) is of major importance.Changes of brain cholesterol homeostasis is an emerging candidate for excitotoxicity. We conducted an overall analysis of the cholesterol homeostasis both (i) in fluids and tissues from patients with SE: blood (n = 63, n = 87 controls), CSF (n = 32, n = 60 controls), and post-mortem brain tissues (n = 8, n = 8 controls) and (ii) in a mouse model of SE induced by an intrahippocampal injection of kainic acid.24-hydroxycholesterol levels were decreased in kainic acid mouse hippocampus and in human plasma and post-mortem brain tissues of patients with SE when compared with controls. The decrease of 24-hydroxycholesterol levels was followed by increased cholesterol levels and by an increase of the cholesterol synthesis. Desmosterol levels were higher in human CSF and in mice and human hippocampus after SE. Lanosterol and dihydrolanosterol levels were higher in plasma from SE patients.Our results suggest that a CYP46A1 inhibition could occur after SE and is followed by a brain cholesterol accumulation. The excess of cholesterol is known to be excitotoxic for neuronal cells and may participate to neurological sequelae observed after SE. This study highlights a new pathophysiological pathway involved in SE excitotoxicity.

Published
2021
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6. Performance of serum apolipoprotein-A1 as a sentinel of Covid-19.

Author

Thierry Poynard, Olivier Deckmyn, Marika Rudler, Valentina Peta, Yen Ngo, Mathieu Vautier, Sepideh Akhavan, Vincent Calvez, Clemence Franc, Jean Marie Castille, Fabienne Drane, Mehdi Sakka, Dominique Bonnefont-Rousselot, Jean Marc Lacorte, David Saadoun, Yves Allenbach, Olivier Benveniste, Frederique Gandjbakhch, Julien Mayaux, Olivier Lucidarme, Bruno Fautrel, Vlad Ratziu, Chantal Housset, Dominique Thabut, and Patrice Cacoub

Subjects
Medicine, Science
Abstract

BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04).ConclusionApolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.

Published
2020
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7. Evaluation of a semi-automatic isoelectric focusing method for apolipoprotein E phenotyping

Author

Randa Bittar, Alain Carrié, Georges Nouadje, Corinne Cherfils, Valérie Fesel-Fouquier, Laurence Barbot-Trystram, Philippe Giral, and Dominique Bonnefont-Rousselot

Subjects
Medicine (General), R5-920, Chemistry, QD1-999
Abstract

A qualitative, semi-automatized method for apolipoprotein E (apoE) phenotyping by isoelectric focusing method has been evaluated on 40 serum samples from patients previously genotyped for apoE, especially as regards concordance with genotyping, but also repeatability and reproducibility of the method, and sample storage. Total concordance with genotyping and good precision criteria, together with its practicability and requirement of a little sample volume, lead to conclude to the usefulness of this method to help clinicians in the diagnosis of dyslipidemic and neurodegenerative diseases. Keywords: Apolipoprotein E, Isoforms, Phenotype, Isoelectric focusing

Published
2020
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8. Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death

Author

Solenn Le Clanche, Tristan Cheminel, François Rannou, Dominique Bonnefont-Rousselot, Didier Borderie, and Christine Charrueau

Subjects
anti-oxidative activity, chondrocyte, osteoarthritis, nano-emulsion, resveratrol, Therapeutics. Pharmacology, RM1-950
Abstract

Osteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavailability, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, and thus decrease resveratrol intrinsic cellular toxicity, allowing the use of higher concentrations, second, to increase resveratrol uptake in membrane and intracellular fractions, and finally, to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments.

Published
2018
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9. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.

Author

Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Yen Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu, Dominique Thabut, Marika Rudler, Vincent Thibault, Ina Schuppe-Koistinen, Dominique Bonnefont-Rousselot, Bernard Hainque, Françoise Imbert-Bismut, Michael Merz, Gerd Kullak-Ublick, Raul Andrade, Florian van Boemmel, Eckart Schott, Thierry Poynard, Drug Induced Liver Injury- Groupe Hospitalier Pitié-Salpêtrière, and Drug Induced Liver Group of the Injury Safer and Faster Evidence-based Translation consortium

Subjects
Medicine, Science
Abstract

There is a clear need for better biomarkers of drug-induced-liver-injury (DILI).We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT

Published
2017
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10. Diaphragmatic function is enhanced in fatty and diabetic fatty rats.

Author

Audrey De Jong, Serge Carreira, Na Na, Aude Carillion, Cheng Jiang, Maud Beuvin, Jean-Marc Lacorte, Dominique Bonnefont-Rousselot, Bruno Riou, and Catherine Coirault

Subjects
Medicine, Science
Abstract

BACKGROUND:Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function. METHODS:Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways. RESULTS:Diaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P

Published
2017
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11. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

Author

Aude Carillion, Sarah Feldman, Na Na, Matthieu Biais, Wassila Carpentier, Aurélie Birenbaum, Nicolas Cagnard, Xavier Loyer, Dominique Bonnefont-Rousselot, Stéphane Hatem, Bruno Riou, and Julien Amour

Subjects
Medicine, Science
Abstract

In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes.β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD.Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response.Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

Published
2017
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12. Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia

Author

Alexina Orsoni, Elise F. Villard, Eric Bruckert, Paul Robillard, Alain Carrie, Dominique Bonnefont-Rousselot, M. John Chapman, Geesje M. Dallinga-Thie, Wilfried Le Goff, and Maryse Guerin

Subjects
cholesteryl ester transfer protein, low density lipoprotein, high density lipoprotein, cellular cholesterol efflux, high density lipoprotein cholesteryl ester uptake, Biochemistry, QD415-436
Abstract

In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis on the efficacy of the RCT pathway in FH patients. LDL apheresis markedly reduced abnormal accelerated cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer from HDL to LDL, thus reducing their CE content. Equally, we observed a major decrease (−53%; P < 0.0001) in pre-β1-HDL levels. The capacity of whole plasma to mediate free cholesterol efflux from human macrophages was reduced (−15%; P < 0.02) following LDL apheresis. Such reduction resulted from a marked decrease in the ABCA1-dependent efflux (−71%; P < 0.0001) in the scavenger receptor class B type I-dependent efflux (−21%; P < 0.0001) and in the ABCG1-dependent pathway (−15%; P < 0.04). However, HDL particles isolated from FH patients before and after LDL apheresis displayed a similar capacity to mediate cellular free cholesterol efflux or to deliver CE to hepatic cells. We demonstrate that rapid removal of circulating lipoprotein particles by LDL apheresis transitorily reduces RCT. However, LDL apheresis is without impact on the intrinsic ability of HDL particles to promote either cellular free cholesterol efflux from macrophages or to deliver CE to hepatic cells.

Published
2012
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13. Modification of LDL with human secretory phospholipase A2 or sphingomyelinase promotes its arachidonic acid-releasing propensity

Author

Janne Oestvang, Dominique Bonnefont-Rousselot, Ewa Ninio, Jukka K. Hakala, Berit Johansen, and Marit W. Anthonsen

Subjects
low density lipoprotein remodeling, inflammation, atherosclerosis, monocytes, oleic acid, Biochemistry, QD415-436
Abstract

Oxidation and lipolytic remodeling of LDL are believed to stimulate LDL entrapment in the arterial wall, expanding the inflammatory response and promoting atherosclerosis. However, the cellular responses and molecular mechanisms underlying the atherogenic effects of lipolytically modified LDL are incompletely understood. Human THP-1 monocytes were prelabeled with [3H]arachidonic acid (AA) before incubation with LDL or LDL lipolytically modified by secretory PLA2 (sPLA2) or bacterial sphingomyelinase (SMase). LDL elicited rapid and dose-dependent extracellular release of AA in monocytes. Interestingly, LDL modified by sPLA2 or SMase displayed a marked increase in AA mobilization relative to native LDL, and this increase correlated with enhanced activity of cytosolic PLA2 (cPLA2) assayed in vitro as well as increased monocyte tumor necrosis factor-α secretion. The AA liberation was attenuated by inhibitors toward cPLA2 and sPLA2, indicating that both PLA2 enzymes participate in LDL-induced AA release.In conclusion, these results demonstrate that LDL lipolytically modified by sPLA2 or SMase potentiates cellular AA release and cPLA2 activation in human monocytes. From our results, we suggest novel atherogenic properties for LDL modified by sPLA2 and SMase in AA release and signaling, which could contribute to the inflammatory gene expression observed in atherosclerosis.

Published
2004
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14. Plasma NOV/CCN3 levels are closely associated with obesity in patients with metabolic disorders.

Author

Jihane Pakradouni, Wilfried Le Goff, Claire Calmel, Bénédicte Antoine, Elise Villard, Eric Frisdal, Marianne Abifadel, Joan Tordjman, Christine Poitou, Dominique Bonnefont-Rousselot, Randa Bittar, Eric Bruckert, Karine Clément, Bruno Fève, Cécile Martinerie, and Maryse Guérin

Subjects
Medicine, Science
Abstract

OBJECTIVE:Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans. METHODS:NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m(2). Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages. RESULTS:After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p

Published
2013
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15. Real time identification of drug-induced liver injury (DILI) through daily screening of ALT results: a prospective pilot cohort study.

Author

Helmi M'Kada, Hugo Perazzo, Mona Munteanu, Yen Ngo, Nittia Ramanujam, Bruno Fautrel, Françoise Imbert-Bismut, Vlad Ratziu, Ina Schuppe-Koistinen, Véronique Leblond, Jean Yves Delattre, Yves Samson, Olivier Lyon Caen, François Bricaire, David Khayat, Charles Pierrot-Deseilligny, Serge Herson, Zahir Amoura, Patrick Tilleul, Olivier Deckmyn, Pierre Coriat, Vincent Nicolas Delpech, Philippe Boulogne, Dominique Bonnefont-Rousselot, Thierry Poynard, Drug Induced Liver Injury Groupe Hospitalier Pitié-Salpêtrière Group, and Safer and Faster Evidence-based Translation Consortium

Subjects
Medicine, Science
Abstract

Identification of drug-induced liver disease (DILI) is difficult, even among hospitalized patients. The aim of this pilot study was to assess the impact of a specific strategy for DILI screening.We prospectively compared the number of acute DILI cases identified in one week of a proactive strategy based on centralized elevated ALT values to those identified with a standard of care strategy for 24-week period based on referral cases to the hepatology unit. In the centralized strategy, a designated study biochemist identified patients with ALT greater than 3 times the upper limit of normal values (ULN) and notified the designated hepatologists, who then went to the patients' wards, analyzed the charts, and if necessary, interviewed the identified patients. During these two periods, patients with possible DILI were included after signing an informed consent in an ongoing European diagnostic study (SAFE-T consortium).During the 24-week period of the standard strategy, 12 (0.04%) patients out of a total of 28,145 were identified as having possible DILI, and 11 of these accepted to be included in the protocol. During the one-week proactive period, 7 patients out of a total of 1407 inpatients (0.498%) [odds ratio vs. standard = 12.1 (95% CI, 3.9-32.3); P3 ULN by designated biochemists and hepatologists identified 12 times more acute cases of drug-induced liver disease than the standard strategy. This pilot cohort is registered on the number AP-HP P110201/1/08-03-2011 and AFSSAPS B110346-70.

Published
2012
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16. An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (FibroTest-ActiTest) and viral load.

Author

Yen Ngo, Yves Benhamou, Vincent Thibault, Patrick Ingiliz, Mona Munteanu, Pascal Lebray, Dominique Thabut, Rachel Morra, Djamila Messous, Frederic Charlotte, Françoise Imbert-Bismut, Dominique Bonnefont-Rousselot, Joseph Moussalli, Vlad Ratziu, and Thierry Poynard

Subjects
Medicine, Science
Abstract

BackgroundThe combination of transaminases (ALT), biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT) and ActiTest (AT), biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status.Methods and findings1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment.Results1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%), 36 deaths occurred (survival 95.0%), including 27 related to HBV (survival 96.1%). The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84-0.93) vs 0.64 (0.55-0.71) vs 0.53 (0.46-0.60) all PConclusionIn patients with chronic hepatitis B, a combination of FibroTest-ActiTest and viral load testing accurately defined the prognosis and the inactive carrier status.

Published
2008
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17. Correction: An Accurate Definition of the Status of Inactive Hepatitis B Virus Carrier by a Combination of Biomarkers (FibroTest-ActiTest) and Viral Load.

Author

Yen Ngo, Yves Benhamou, Vincent Thibault, Patrick Ingiliz, Mona Munteanu, Pascal Lebray, Dominique Thabut, Rachel Morra, Djamila Messous, Frederic Charlotte, Françoise Imbert-Bismut, Dominique Bonnefont-Rousselot, Joseph Moussalli, Vlad Ratziu, and Thierry Poynard

Subjects
Medicine, Science
Published
2008
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18. Non-linearity in lipase assays: A multicentric comparison on different analysers

Author

Denis Monneret, Amélie Moreau, Carole Chirica, Dorra Guergour, Caroline Richet, Laurent Desmurs, Sylvie Colognac, Audrey Frugier, Marc Chévrier, Oriane Marmontel, Dominique Bonnefont-Rousselot, Philippe Gonzalo, Claire Rodriguez-Lafrasse, and Régine Cartier

Subjects
Clinical Biochemistry, General Medicine
Published
2023

22. Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus

Author

Aurélie Hanin, Jérôme Alexandre Denis, Valerio Frazzini, Louis Cousyn, Françoise Imbert-Bismut, Benoit Rucheton, Dominique Bonnefont-Rousselot, Clémence Marois, Virginie Lambrecq, Sophie Demeret, and Vincent Navarro

Subjects
Epilepsy, Progranulins, Status Epilepticus, Neurology, Phosphopyruvate Hydratase, Humans, S100 Calcium Binding Protein beta Subunit, Neurology (clinical), Biomarkers
Abstract

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development of neurological sequels. Several serum and cerebrospinal fluid biomarkers have been proposed to help in the diagnosis of SE. Nevertheless, previous studies were conducted on too small patient cohorts, precluding the utilization of interesting biomarkers for the SE diagnosis. Here, we aimed to assess the ability of Neuron Specific Enolase (NSE), S100-beta protein (S100B) and progranulin to help in the diagnosis of SE in a large cohort of patients (36 control patients, 56 patients with pharmacoresistant epilepsy and 82 SE patients). Blood NSE, S100B and progranulin levels were higher in SE patients when compared with control patients or patients with pharmacoresistant epilepsy. Both NSE and progranulin levels were higher in cerebrospinal fluid from SE patients when compared with control patients. The receiver-operating characteristics curves revealed good accuracy at detecting SE for serum S100B (AUC 0.748) and plasma progranulin (AUC 0.756). The performances were lower for serum NSE (AUC 0.624). Eighty-four percent of patients with serum S100B levels above 0.09 ng/mL presented with a SE, whereas 90% of patients without SE had serum S100B levels lower than 0.09 ng/mL. Serum S100B levels were not significantly different according to SE etiology, SE semiology or SE refractoriness. Our results confirm that NSE, S100B and progranulin levels are increased after SE. We suggest that serum S100B levels might be added to clinical evaluation and electroencephalogram to identify difficult-to-diagnose form of SE.

Published
2022

23. Diagnosis of chylous abdominal effusions: what is the triglyceride threshold value?

Author

Bertrand Lefrère, Emmanuel Curis, Randa Bittar, Antoine Levasseur, Pierre Grès, Zoé Guilbert, Belkacem Zenati, Corinne Cherfils, Mehdi Sakka, and Dominique Bonnefont-Rousselot

Subjects
Biochemistry (medical), Clinical Biochemistry, chylous ascites, lipoprotein gel electrophoresis, triglycerides
Abstract

IntroductionChylous abdominal effusions are serious complications that can be triggered by various aetiologies. The biochemical diagnosis of chyle leakage in ascites or in peritoneal fluid capsules relies on the detection of chylomicrons. Assaying the fluid’s concentration of triglycerides is still the first-line tool. Given that only one comparative study has sought to quantify the value of the triglyceride assay for diagnosing chylous ascites in humans, our objective was to provide practical triglyceride thresholds. Materials and methodsWe conducted a 9-year, retrospective, single-centre study of adult patients and compared a triglyceride assay with lipoprotein gel electrophoresis for the analysis of 90 non-recurring abdominal effusions (ascites and abdominal collections) of which 65 were chylous. ResultsA triglyceride threshold of 0.4 mmol/L was associated with a sensitivity > 95%, and a threshold of 2.4 mmol/L was associated with a specificity > 95%. According to Youden index, the best threshold was 0.65 mmol/L with a sensitivity of 88 (77-95)%, a specificity of 72 (51-88)%, and, in our series, a positive predictive value of 89 (79-95)% and a negative predictive value of 69 (48-86)%. ConclusionsIn our series, cut-off of 0.4 mmol/L could be used for ruling-out diagnosis of chylous effusions, while cut-off of 2.4 mmol/L could be used for reasonably confirming diagnosis.

Published
2023

24. Chylopericardium or contamination by injectable lipid emulsion?

Author

Bertrand, Lefrère, Randa, Bittar, Antoine, Levasseur, Cécile, Lambe, Elie, Abi-Nader, Margaux, Pontailler, Régis, Gaudin, Valérie, Fesel-Fouquier, Mehdi, Sakka, and Dominique, Bonnefont-Rousselot

Subjects
Male, Short Bowel Syndrome, Parenteral Nutrition, Vena Cava, Superior, Humans, Infant, Emulsions, Child, Lipids, Pericardial Effusion
Abstract

Effusions can show some surprises. We document the case of a fourteen-month-old male patient with short-bowel syndrome, hospitalized in a cardiology unit, receiving a chronic parenteral nutrition by a Broviac® catheter. The patient presented several thrombosis following iterative catheter replacements. In parallel with superior vena cava plasty, a right intra-atrial Broviac® catheter was placed in the absence of other peripheral venous accesses. This device has a cutaneous exit site to allow for infusion of a hyperosmolar lipid emulsion. Seven days later, a milky liquid was secreted from pericardial/mediastinal redon. A gel lipoprotein electrophoresis of the fluid suggested a preliminary diagnosis of chylopericardium. However, biochemical testing of certain analytes evoked a parenteral nutrition-related pericardial effusion and a possible pseudochyloperitoneum caused by the shearing of a migrated Broviac® in pericardium. The patient, on a fat-free diet, was admitted to the ICU to drain the effusion and reposition the catheter, with success. In the light of new datas on the interference of parenteral lipid emulsions with the lipoproteins gel electrophoresis, we will try to determine whether the apparent presence of chylomicrons in the gel would be the sign of a lesion of the lymphatic system, or rather the result of a contamination by artificial chylomicron in the lipid emulsion, if not the sign of contaminated blood. In our article, we highlight several considerations in identifying and confirming cases of pericardial effusion, such as chylopericardium and parenteral nutrition-related one, as well as points concerning the use of lipid emulsions for pediatric patients with short-bowel syndrome.Les liquides d'épanchements peuvent renfermer quelques surprises. Nous documentons le cas d'un patient de quatorze mois, hospitalisé en cardiologie, présentant un syndrome de grêle court et recevant une nutrition parentérale au long cours par cathéter Broviac®. Le patient présentait de multiples occlusions veineuses consécutives aux changements itératifs du dispositif. En parallèle d'une plastie de la veine cave supérieure, un Broviac® a été posé en intra-atrial droit devant l'absence d'autres abords veineux périphériques. Ce dispositif comporte un orifice de sortie sous-cutané pour apporter une solution de nutrition hyperosmolaire de type émulsion lipidique. Le liquide recueilli dans les drains péricardiques en post-opératoire est lactescent, particulièrement à partir du septième jour. Le lipidogramme du liquide d'épanchement péricardique semble conclure à la présence de chylomicrons - un chylopéricarde. Cependant, le dosage de certains analytes penche en faveur d'un perfusopéricarde, probablement pseudochyleux, lié au cisaillement du Broviac® dont l'extrémité a migré de l'oreillette droite au péricarde. Le patient, sous régime sans graisses, sans nutrition parentérale, sera réopéré pour drainer l'épanchement et repositionner le cathéter, avec succès. À la lumière de données originales quant à l'interférence des émulsions lipidiques sur le lipidogramme, nous tâcherons de déterminer si l'apparente présence de chylomicrons sur le gel serait le témoin d'une réelle lésion du lymphatique, ou plutôt le fruit d'une contamination par l'émulsion, si ce n'est par le sang. Des considérations au sujet des épanchements péricardiques, dont les chylopéricarde et nutripéricarde, ainsi que sur les émulsions lipidiques pédiatriques dans le contexte du grêle court émailleront ce travail.

Published
2022

26. Abstracts of the BIOMED J Congress, Paris

Author

Mehdi Sakka, Fatma Cheikhrouhou, Frédéric Cotton, C. Cherfils, Fabienne Soudre, Mohamed Lyagoubi, Hanae Lorhlam, Amal Soulef Saadi, Maïlis Lauwers, Gatien Durand, Randa Bittar, Valérie Fesel-Fouquier, Laura Chiaradia, Fabio Silvio Taccone, Tristan Celse, Emna Sghairi, Alexandre Regueme, Charles Marchionini, Marie-Eve Moulies, Biomed J, Yann Barguil, Amira Jomli, Samia Lasri, Olivier Gaillot, Amel Otmane, Sarra Aoufi, Fleur Wolff, David Fage, Julia Masotti, Hichem Assami, Loubna Zerrouki, Rafik Aniba, Amal Frikha, Dominique Bonnefont-Rousselot, and Adnene Otmane

Subjects
General Medicine
Published
2021

27. Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts

Author

Barbara Mátyási, Gábor Petővári, Titanilla Dankó, Henriett Butz, István Likó, Péter Lőw, Isabelle Petit, Randa Bittar, Dominique Bonnefont-Rousselot, Zsolt Farkas, Tamás Szeniczey, Kinga Molnár, Krisztina Pálóczi, Edit I. Buzás, Mathieu Boissan, Anna Sebestyén, and Krisztina Takács-Vellai

Subjects
Cancer Research, Oncology, NME, metastasis suppressor, extracellular vesicles, exosomes, lipid metabolism, fatty acid metabolism
Abstract

Nowadays, extracellular vesicles (EVs) raise a great interest as they are implicated in intercellular communication between cancer and stromal cells. Our aim was to understand how vesicular NME1 and NME2 released by breast cancer cells influence the tumour microenvironment. As a model, we used human invasive breast carcinoma cells overexpressing NME1 or NME2, and first analysed in detail the presence of both isoforms in EV subtypes by capillary Western immunoassay (WES) and immunoelectron microscopy. Data obtained by both methods showed that NME1 was present in medium-sized EVs or microvesicles, whereas NME2 was abundant in both microvesicles and small-sized EVs or exosomes. Next, human skin-derived fibroblasts were treated with NME1 or NME2 containing EVs, and subsequently mRNA expression changes in fibroblasts were examined. RNAseq results showed that the expression of fatty acid and cholesterol metabolism-related genes was decreased significantly in response to NME1 or NME2 containing EV treatment. We found that FASN (fatty acid synthase) and ACSS2 (acyl-coenzyme A synthetase short-chain family member 2), related to fatty acid synthesis and oxidation, were underexpressed in NME1/2-EV-treated fibroblasts. Our data show an emerging link between NME-containing EVs and regulation of tumour metabolism.

Published
2022

28. Usefulness of combined sequencing of the mitochondrial genome and a targeted panel of nuclear genes involved in mitochondrial diseases

Author

Adrien Bloch, Fanny Mochel, Benoit Rucheton, Foudil Lamari, David Goudenège, Sylvie Bannwarth, Réseau MitoDiag, Dominique Bonnefont-Rousselot, Sandrine Filaut, Flavie Ader, Vincent Procaccio, Laura Legrand, Véronique Fressart, and Pascale Richard

Subjects
Mitochondrial DNA, Mitochondrial Diseases, Nuclear gene, Mitochondrial disease, First line, Mutant, Reproducibility of Results, General Medicine, Computational biology, Biology, medicine.disease, DNA, Mitochondrial, Mitochondria, Nuclear DNA, Genome, Mitochondrial, medicine, Humans, Numt, Gene
Abstract

The molecular study of mitochondrial diseases, essential for diagnosis, is special due to the dual genetic origin of these pathologies: mitochondrial DNA and nuclear DNA. Complete mtDNA sequencing still remains the first line diagnostic test followed if negative, by resequencing panels of several hundred mitochondrially-encoded nuclear genes. This strategy, with an initial entire mtDNA sequencing, is currently justified by the presence of nuclear mitochondrial DNA sequences (NUMTs) in the nuclear genome. We designed a resequencing panel combining the mtDNA and 135 nuclear genes which was evaluated compared to the performances of the standard mtDNA sequencing. Method validation was performed on the reading depth and reproducibility of the results. Thirty patients were analyzed by both methods. We were able to demonstrate that NUMTs did not impact the mtDNA sequencing quality, as the identified variants and mutant loads were identical with the reference mtDNA sequencing method. Reading depths were higher than the recommendations of the MitoDiag French diagnostic network, for the entire mtDNA for muscle and for 70% of the mtDNA for blood. These results highlight the usefulness of combining both mtDNA and mitochondrially nuclear-encoded genes and thus obtain more complete results and faster turnaround time for mitochondrial disease patients.

Published
2021

29. Clinico-biological markers for the prognosis of status epilepticus in adults

Author

Aurélie Hanin, Sophie Demeret, Virginie Lambrecq, Benjamin Rohaut, Clémence Marois, Meriem Bouguerra, Alexandre Demoule, Jean-Louis Beaudeux, Randa Bittar, Jérôme Alexandre Denis, Françoise Imbert-Bismut, Foudil Lamari, Benoit Rucheton, Dominique Bonnefont-Rousselot, Mario Chavez, and Vincent Navarro

Subjects
Adult, Progranulins, Status Epilepticus, Neurology, Humans, Neurology (clinical), Prognosis, Lipids, Severity of Illness Index, Biomarkers, Retrospective Studies
Abstract

Prediction of mortality, functional outcome and recovery after status epilepticus (SE) is a challenge. Biological and clinical markers have been proposed to reflect the brain injury or to monitor critical ill patients' severity. The aim of this study was to characterize short-term and long-term prognostic factors for SE patients hospitalized in intensive care unit. Patient's outcome was assessed using the modified Rankin Scale at discharge and after 6-12 months. We first assessed the univariate prognosis significance of 51 clinical, demographic or biochemical markers. Next, we built multivariate clinico-biological models by combining most important factors. Statistical models' performances were compared to those of two previous published scales STESS and mSTESS. Eighty-one patients were enrolled. Thirty-five patients showed a steady state while 46 patients clinically worsened at discharge: 14 died, 14 had persistent disability at 6-12 months and 18 recovered. Logistic regression analysis revealed that clinical markers (SE refractoriness, SE duration, de novo SE) were significant independent predictors of worsening while lipids markers and progranulin better predicted mortality. The association of clinico-biological variables allowed to accurately predict worsening at discharge (AUC 0.72), mortality at discharge (AUC 0.83) and recovery at long-term (AUC 0.89). Previous scales provided lower prediction for worsening (AUC 0.63, STESS; 0.53, mSTESS) and mortality (AUC 0.56, STESS; 0.62, mSTESS) (p 0.001). We proposed new clinico-biological models with a strong discrimination power for prediction of short- and long-term outcome of hospitalized status epilepticus patients. Their implementation in electronic devices may enhance their clinical liability.

Published
2022

30. Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

Author

Romuald Mentaverri, Philippe Cluzel, Cees Vermeer, Aurélie Carlier, Franck Phan, Salim Kemel, N. Bouziri, Carole-Elodie Aubert, Jean-Marc Lacorte, Dominique Bonnefont-Rousselot, Suzanne Laroche, Alban Redheuil, Jean-Michel Davaine, Christian Funck-Brentano, Joe-Elie Salem, Stéphane Jaisson, Ziad A. Massy, Agnes Hartemann, Mamadou Hassimiou Diallo, Chloé Amouyal, David Hajage, Philippe Gillery, Olivier Bourron, Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche Clinique [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CIC Paris Est, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Maastricht University [Maastricht], Cardiovascular Research Institute Maastricht (CARIM), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Institut de cardiologie [CHU Pitié-Salpêtrière], RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Biochemie, Service de diabétologie [CHU Pitié-Salpétrière], and Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Myocardial Ischemia, Type 2 diabetes, 030204 cardiovascular system & hematology, DISEASE, PREDICT, Bone remodeling, Cohort Studies, 0302 clinical medicine, Prospective Studies, Prospective cohort study, Original Investigation, RISK, RANKL, MATRIX GLA PROTEIN, Middle Aged, Calcium score, 3. Good health, Arterial calcification, KAPPA-B LIGAND, Lower Extremity, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, 030209 endocrinology & metabolism, CALCIUM, 03 medical and health sciences, VASCULAR CALCIFICATION, Internal medicine, Diabetes mellitus, medicine, Humans, Mediacalcosis, Triglycerides, Angiology, Aged, Ischemic cardiomyopathy, OSTEOPROTEGERIN, Peripheral artery disease, business.industry, RANK Ligand, medicine.disease, Diabetes Mellitus, Type 2, lcsh:RC666-701, MARKER, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Tomography, X-Ray Computed, Diabetic Angiopathies, Biomarkers, Calcification
Abstract

BackgroundLower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes.MethodsLower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model.ResultsAt baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p ConclusionIn patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.Trial registrationNCT02431234

Published
2020

31. Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

Author

Sandrine Lablanche, Florence Galtier, Pierre Leroy, Vincent Dubée, Dominique Bonnefont-Rousselot, Patrick Saulnier, Matthieu Wargny, Manuel Etienne, Patrice Darmon, Anne-Laure Borel, Jean-Louis LAPLANCHE, Olivier Lesieur, Bertrand Cariou, Malak Taher, Lydia GUITTET, Vincent Minville, BRUNO MOURVILLIER, Jean-Pierre QUENOT, Bernard Bonnotte, Lucien Marchand, Team2 Carmen, Veronique Kerlan, Pascal Reynier, Nadia Sabbah, Matthieu PICHELIN, Jean-Charles Aurégan, Guillaume Martin-Blondel, Olivier Bourron, Blandine Rammaert, Pierre-Edouard Fournier, Coralie Amadou, Giulia Chinetti, Jean-Christophe Lagier, Didier Raoult, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Sud Francilien, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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 Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CH Evry-Corbeil, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de diabétologie [CHU Pitié-Salpétrière], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université

Subjects
Male, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, law.invention, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Diabetes mellitus, Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, education, Pandemics, Case report form, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Glycated Hemoglobin, Advanced and Specialized Nursing, Inpatients, Type 1 diabetes, education.field_of_study, business.industry, e-Letters: Observations, COVID-19, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, Hypertension, Etiology, Female, Observational study, Coronavirus Infections, business
Abstract

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, patients with diabetes were rapidly recognized as a high-risk population for severe disease. Indeed, a high prevalence of diabetes among patients with COVID-19 who required hospitalization has been consistently reported, reaching 33.8% in 5,700 people hospitalized for COVID-19 in the New York City area (1). In addition, diabetes was associated with more than a doubled risk of intensive care unit (ICU) admission and more than a tripled risk of death (2). However, precise data regarding the type of diabetes are scarce. We report here the clinical characteristics and early prognosis of patients with type 1 diabetes (T1D) hospitalized for COVID-19 in the nationwide multicenter observational CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study (3). The aim of the CORONADO study was to describe the phenotypic characteristics and prognosis of patients with diabetes admitted with COVID-19 between 10 March and 10 April 2020 in 68 French hospitals. The protocol (ClinicalTrials.gov reg. no. NCT04324736) obtained all regulatory approvals as recently described (3). Inclusion criteria were 1 ) hospitalization for biologically and/or clinically/radiologically attested COVID-19 and 2 ) personal history of diabetes or newly diagnosed diabetes on admission. The composite primary end point combined tracheal intubation for mechanical ventilation and/or death on day 7 (D7). Secondary outcomes included death, tracheal intubation, and discharge on D7. Classification of diabetes was recorded in the electronic case report form as noted in the medical file by the physician in charge of the patient. In the present subanalysis, patients in whom diabetes was diagnosed on admission were excluded since the etiological diagnosis had not been formally established. All cases noted as T1D were carefully reviewed by local investigators and the steering committee …

Published
2020

32. Les marqueurs de l’oxydation des lipides

Author

Dominique Bonnefont-Rousselot

Subjects
03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract

Resume Les marqueurs de l’oxydation des lipides font partie des marqueurs de desequilibre redox et, a ce titre, certains peuvent etre inclus dans des bilans d’evaluation du stress oxydant, dans un contexte de diagnostic ou de suivi de certaines pathologies humaines, notamment cardiovasculaires ou neurologiques. A ces marqueurs de structures variees (hydroperoxydes, aldehydes, oxysterols, isoprostanes) s’ajoutent des biomarqueurs de l’oxydation des lipoproteines de basse densite. En parallele, le champ de la lipidomique des phospholipides oxydes se developpe et devrait permettre d’avoir acces a ces biomarqueurs phospholipidiques en pratique clinique. A l’heure actuelle, les isoprostanes semblent des marqueurs pertinents d’oxydation des lipides, mais la methode de reference pour leur determination repose sur la spectrometrie de masse, ce qui peut constituer une limitation technologique. Un ecueil majeur est le manque de standardisation actuelle de la plupart des marqueurs d’oxydation lipidique, ayant pour consequence que les valeurs de reference doivent etre etablies par chaque laboratoire. Enfin, il est toujours souhaitable de privilegier un panel de marqueurs de desequilibre redox plutot qu’un marqueur isole, avec une combinaison choisie en fonction de la nature des cibles biologiques oxydees et de la praticabilite des dosages, et associant la quantification de systemes antioxydants.

Published
2020

33. Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis

Author

Pascal Roux, Virginie Escriou, Judith Aron-Wisnewsky, Nour El Houda Djerir, Christine Charrueau, Isabelle Brocheriou, Céline Hoffmann, Anne Danckaert, Karine Clément, Fabienne Foufelle, Anne-Marie Lachagès, Frédéric Charlotte, Vlad Ratziu, Julien Fernandes, Bernard Hainque, Pascal Bigey, Dominique Bonnefont-Rousselot, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Institut Pasteur [Paris], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Université Paris sciences et lettres (PSL), This work was supported by the Agence Nationale de la Recherche (ANR, ANR Fibrother ANR-18-CE18-0005-01 to C.H.). The UtechS PBI (A.D., J.F., and P.R.) is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, 'Investments for the future'). Funding for patient’s recruitment (K.C.) was obtained by the Clinical Research Contrat (CRC-Fibrota)., ANR-18-CE18-0005,FIBROTHER,Nanovecteurs polyvalents pour la thérapie de la fibrose hépatique(2018), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technologie et Service BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Service d’anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de nutrition [CHU Pitié-Salpétrière], École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), ANR-18-CE18-0005,FIBROTHER,MULTIPLEXED NANOVECTORS FOR METABOLIC LIVER FIBROSIS THERAPY(2018), ANR-10-INBS-04-01/10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), École Pratique des Hautes Études (EPHE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bodescot, Myriam, APPEL À PROJETS GÉNÉRIQUE 2018 - Nanovecteurs polyvalents pour la thérapie de la fibrose hépatique - - FIBROTHER2018 - ANR-18-CE18-0005 - AAPG2018 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
0301 basic medicine, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, Liver fibrosis, lcsh:Medicine, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Chronic liver disease, Article, Muscle hypertrophy, 03 medical and health sciences, Liver disease, Mice, 0302 clinical medicine, Fibrosis, Hepatic stellate cells, medicine, Animals, Humans, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Non-alcoholic steatohepatitis, Multidisciplinary, business.industry, Carbon Tetrachloride Poisoning, lcsh:R, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Dietary Fats, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Hepatic stellate cell, lcsh:Q, Steatohepatitis, business, Hepatic fibrosis
Abstract

Hepatic fibrosis is a major consequence of chronic liver disease such as non-alcoholic steatohepatitis which is undergoing a dramatic evolution given the obesity progression worldwide, and has no treatment to date. Hepatic stellate cells (HSCs) play a key role in the fibrosis process, because in chronic liver damage, they transdifferentiate from a “quiescent” to an “activated” phenotype responsible for most the collagen deposition in liver tissue. Here, using a diet-induced liver fibrosis murine model (choline-deficient amino acid-defined, high fat diet), we characterized a specific population of HSCs organized as clusters presenting simultaneously hypertrophy of retinoid droplets, quiescent and activated HSC markers. We showed that hypertrophied HSCs co-localized with fibrosis areas in space and time. Importantly, we reported the existence of this phenotype and its association with collagen deposition in three other mouse fibrosis models, including CCl4-induced fibrosis model. Moreover, we have also shown its relevance in human liver fibrosis associated with different etiologies (obesity, non-alcoholic steatohepatitis, viral hepatitis C and alcoholism). In particular, we have demonstrated a significant positive correlation between the stage of liver fibrosis and HSC hypertrophy in a cohort of obese patients with hepatic fibrosis. These results lead us to conclude that hypertrophied HSCs are closely associated with hepatic fibrosis in a metabolic disease context and may represent a new marker of metabolic liver disease progression.

Published
2020

34. Electrophoresis of serum lipoproteins (lipoproteinogram) with the Hydragel Lipo + Lp(a)® (Sebia) kit: evaluation of Fat Red 7B staining

Author

Nabil Koujah, Laurence Barbot-Trystram, Gautier Pierrat, C. Cherfils, Randa Bittar, Corentin Poignon, Valérie Fesel-Fouquier, and Dominique Bonnefont-Rousselot

Subjects
Electrophoresis, Electrophoresis, Agar Gel, Reproducibility, Chromatography, Staining and Labeling, Chemistry, Lipoproteins, Reproducibility of Results, General Medicine, Repeatability, Chemical Fractionation, Staining, chemistry.chemical_compound, Ascitic Fluid, Humans, Sudan black, Agarose, Reagent Kits, Diagnostic, Azo Compounds, Blood Chemical Analysis, Lipoprotein(a), Lipoprotein, Chylomicron
Abstract

The lipoproteinogram (or lipidogram) consists in an electrophoretic separation of the main classes of serum lipoproteins. Separation was done in agarose gel using the Sebia Hydragel Lipo + Lp(a)® kit. A repeatability study (n=6) was conducted on 3 sera (1 normolipidemic, 1 hypertriglyceridemic and 1 with a high Lp(a) concentration). The reproducibility was studied on these 3 sera and on an ascites liquid containing chylomicrons, upon 6 days (n=6). A quantitative approach was made by studying areas under the curve and percentages of fractions. In both cases (repeatability and reproducibility), the revelation of the lipoproteins in the gel after electrophoretic migration was made either by staining with Sudan Black (procedure recommended by Sebia), or with Fat Red 7B. Regardless of staining, both repeatability and reproducibility studies show that all lipoprotein fractions were correctly detected at their respective positions, leading to satisfactory interpretations of lipoproteinograms. Our reproducibility study also confirmed a good stability of the fractions over 6 days (storage at +5 ± 3̊C). In addition, the Fat Red 7B staining leads to a shorter technical time (about 40 min) for the gel drying and staining/destaining phases, which allows us to respond more quickly to certain urgent requests such as chylothorax diagnosis.

Published
2020

35. Selected plasma oxysterols as a potential multi-marker biosignature panel for Behçet's Disease

Author

Meriam Messedi, Wassim Guidara, Sahar Grayaa, Walid Khrouf, Mouna Snoussi, Zouhir Bahloul, Dominique Bonnefont- Rousselot, Foudil Lamari, and Fatma Ayadi

Subjects
Inflammation, Oxidative Stress, Endocrinology, Endocrinology, Diabetes and Metabolism, Behcet Syndrome, Clinical Biochemistry, Molecular Medicine, Humans, Cell Biology, Oxysterols, Molecular Biology, Biochemistry, Biomarkers
Abstract

Clinical, genetic, and medical evidence has shown the inflammatory vasculitis aspect of Behçet's Disease (BD). Whereas oxysterols are vital factors in inflammation and oxidative stress, it is still unknown whether they are involved in the pathophysiology of BD. The current study aims to explore the profile of oxysterols in plasma of BD patients. Thirty patients diagnosed with BD and forty healthy controls matched for age and gender were included. Results showed that the cholestane-3β,5α,6β-triol, 27-hydroxycholesterol (27-OHC) and cholestanol levels were higher in BD than controls. In addition, plasma levels of 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC) were lower in BD patient. However, levels of 24S-hydroxycholesterol (24-OHC) did not significantly differ. For BD patients, the plasma 7-KC level was negatively correlated with the BD activity index (BDAI) while 27-OHC was positively correlated with high-sensitivity C-reactive protein (hs-CRP) in patients with active course of the disease. According to ROC analysis, a remarkable increase in the area under the curve (AUC) with a higher sensitivity (Se) and specificity (Sp) for 7-KC, 25-OHC and 27-OHC combined markers was observed. The present study indicated that the identification of the predictive value of these three-selected biomarkers related to oxidative stress and inflammation in patients should lead to a better identification of the etiological mechanism of BD.

Published
2022

37. Absolute Versus Relative Changes in Cardiac Troponin T: Corresponding Cutoffs Based on Quantile Generalized Additive Models (QGAM)

Author

Denis Monneret, Dominique Bonnefont-Rousselot, and Matteo Fasiolo

Subjects
Troponin T, Myocardial Infarction, Humans, Biomarkers, General Biochemistry, Genetics and Molecular Biology
Abstract

The diagnosis of myocardial injury/infarction (MI) mainly relies on relative changes in cardiac troponin. However, absolute change cutoffs provide greater diagnostic sensitivity. We determined the absolute changes in high-sensitive cardiac troponin T concentrations (absΔhs-cTnT) corresponding to the main relative cutoffs (relΔhs-cTnT), using a quantile generalized additive model (qgam).Plasma Δhs-cTnT from patients selected with a time variation of 1 to 6 hours were collected over a 6-year period. The absΔhs-cTnT-to-relΔhs-cTnT relationship was fitted using qgam, after ordered quantile-based normalization (OQN) to reduce the influence of extreme values.The qgam regression curve was nonlinear. Classifying patients (n = 9,753) above the recommended relΔhs-cTnT and predicted absΔhs-cTnT cutoffs as positive, the MI diagnosis rates were similar, and more reliable using the OQN-transformed data-based qgam, as compared to the untransformed data-based one.Through an optimized qgam-based approach accounting for heavy-tailed distributions, absolute Δhs-cTnT are provided for the corresponding relative Δhs-cTnT cutoffs.

Published
2022

39. Lipoprotein(a): Pathophysiology, measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Société Francophone d’Athérosclérose (NSFA)

Author

Sybil Charrière, M. John Chapman, Dominique Bonnefont-Rousselot, Eduardo Anglés-Cano, Sophie Béliard-Lasserre, Mathilde Di-Filippo Charcosset, René Valéro, Gilles Lambert, Xavier Collet, Bertrand Cariou, Philippe Gillery, Mathilde Varret, V. Durlach, Jean Ferrières, Alain Carrié, Philippe Moulin, Michel Farnier, Pierre Morange, Franck Boccara, Olivier Meilhac, Eric Bruckert, Université de Reims Champagne-Ardenne (URCA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Angles-Cano, Eduardo, 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 Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140)

Subjects
medicine.medical_specialty, Antifibrinolytic, Consensus, Apolipoprotein B, medicine.drug_class, Context (language use), Atherothrombosis, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Apolipoprotein(a), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, business.industry, Cholesterol, Calcific aortic valve stenosis, Plasminogen, General Medicine, Lipoprotein(a), Atherosclerosis, 3. Good health, Cardiovascular diseases, chemistry, biology.protein, Cardiology, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Lipoprotein
Abstract

International audience; Lipoprotein(a) is an apolipoprotein B100-containing low-density lipoprotein-like particle that is rich in cholesterol, and is associated with a second major protein, apolipoprotein(a). Apolipoprotein(a) possesses structural similarity to plasminogen but lacks fibrinolytic activity. As a consequence of its composite structure, lipoprotein(a) may: (1) elicit a prothrombotic/antifibrinolytic action favouring clot stability; and (2) enhance atherosclerosis progression via its propensity for retention in the arterial intima, with deposition of its cholesterol load at sites of plaque formation. Equally, lipoprotein(a) may induce inflammation and calcification in the aortic leaflet valve interstitium, leading to calcific aortic valve stenosis. Experimental, epidemiological and genetic evidence support the contention that elevated concentrations of lipoprotein(a) are causally related to atherothrombotic risk and equally to calcific aortic valve stenosis. The plasma concentration of lipoprotein(a) is principally determined by genetic factors, is not influenced by dietary habits, remains essentially constant over the lifetime of a given individual and is the most powerful variable for prediction of lipoprotein(a)-associated cardiovascular risk. However, major interindividual variations (up to 1000-fold) are characteristic of lipoprotein(a) concentrations. In this context, lipoprotein(a) assays, although currently insufficiently standardized, are of considerable interest, not only in stratifying cardiovascular risk, but equally in the clinical follow-up of patients treated with novel lipid-lowering therapies targeted at lipoprotein(a) (e.g. antiapolipoprotein(a) antisense oligonucleotides and small interfering ribonucleic acids) that markedly reduce circulating lipoprotein(a) concentrations. We recommend that lipoprotein(a) be measured once in subjects at high cardiovascular risk with premature coronary heart disease, in familial hypercholesterolaemia, in those with a family history of coronary heart disease and in those with recurrent coronary heart disease despite lipid-lowering treatment. Because of its clinical relevance, the cost of lipoprotein(a) testing should be covered by social security and health authorities.

Published
2021

40. Serum Neuron Specific Enolase: a new tool for seizure risk monitoring after status epilepticus

Author

Sophie Demeret, Benjamin Rohaut, Vi-Huong Nguyen-Michel, Aurélie Hanin, Virginie Lambrecq, Dominique Bonnefont-Rousselot, Vincent Navarro, Françoise Imbert-Bismut, Jérôme Alexandre Denis, Clémence Marois, Pierre Levy, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aigüE [CHU Pitié-Salpêtrière] (GRC RESPIRE), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), 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 Paris (UP), Service de Santé Publique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité fonctionnelle d'épilepsie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], HAL-SU, Gestionnaire, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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 Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, endocrine system, Enolase, S100 Calcium Binding Protein beta Subunit, Status epilepticus, Electroencephalography, Risk monitoring, Neuron Specific Enolase, Seizure recurrence, 01 natural sciences, law.invention, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Seizures, law, Internal medicine, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 0101 mathematics, medicine.diagnostic_test, business.industry, Intensive care unit, Neurology, nervous system, continuous EEG, Phosphopyruvate Hydratase, Biomarker (medicine), Seizure prediction, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Background and purpose There is a need for accurate biomarkers to monitor electroencephalography (EEG) activity and assess seizure risk in patients with acute brain injury. Seizure recurrence may lead to cellular alterations and subsequent neurological sequelae. Whether neuron-specific enolase (NSE) and S100-beta (S100B), brain injury biomarkers, can reflect EEG activity and help to evaluate the seizure risk was investigated. Methods Eleven patients, admitted to an intensive care unit for refractory status epilepticus, who underwent a minimum of 3 days of continuous EEG concomitantly with daily serum NSE and S100B assays were included. At 103 days the relationships between serum NSE and S100B levels and two EEG scores able to monitor the seizure risk were investigated. Biochemical biomarker thresholds able to predict seizure recurrence were sought. Results Only NSE levels positively correlated with EEG scores. Similar temporal dynamics were observed for the time courses of EEG scores and NSE levels. NSE levels above 17 ng/ml were associated with seizure in 71% of patients. An increase of more than 15% of NSE levels was associated with seizure recurrence in 80% of patients. Conclusions Our study highlights the potential of NSE as a biomarker of EEG activity and to assess the risk of seizure recurrence.

Published
2021

41. Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus

Author

Vincent Mallet, Lucia Parlati, Alessandro Martinino, Juan Pablo Scarano Pereira, Carmen Navas Jimenez, Mehdi Sakka, Samir Bouam, Aurelia Retbi, Donika Krasteva, Jean-François Meritet, Michaël Schwarzinger, Dominique Thabut, Pierre Rufat, Dominique Bonnefont-Rousselot, Philippe Sogni, Stanislas Pol, Emmanuel Tsochatzis, Hélène Fontaine, Marion Corouge, Anaïs Vallet Pichard, Clémence Hollande, Benoit Terris, Etienne Larger, Jérome Bertherat, Vlad Ratziu, Agnès Hartemann, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Paris, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Hepatocellular carcinoma, Type 2 diabetes, Non-alcoholic liver disease, Cohort Studies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Alcohol use disorders, Cost of Illness, Non-alcoholic Fatty Liver Disease, Risk Factors, Diabetes mellitus, Internal medicine, medicine, Humans, Cumulative incidence, Non-alcoholic steatohepatitis, Aged, Retrospective Studies, 030304 developmental biology, Type-2 diabetes, Aged, 80 and over, 0303 health sciences, Hepatology, business.industry, Incidence, Hazard ratio, Middle Aged, medicine.disease, 3. Good health, Hospitalization, Diabetes Mellitus, Type 2, Disease Progression, Female, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Liver cancer
Abstract

There are uncertainties regarding the burden of liver disease in patients with type 2 diabetes (T2D). Thus, we aimed to quantify the burden of liver disease, identify risk factors, and estimate attributable risks in patients with T2D.We measured adjusted hazard ratios of liver disease progression to hepatocellular carcinoma and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D.Mean age was 64±14 years and 58% were men. Alcohol use disorders accounted for 57% of liver-related complications and were associated with all liver-related risk factors. Non-metabolic liver-related risk factors accounted for 37% of the liver burden. T2D control was not associated with liver disease progression. The incidence (95% CI) of liver-related complications and of competing mortality were 3.9 (3.5-4.3) and 27.8 (26.7-28.9) per 1,000 person-years at risk, respectively. The cumulative incidence of liver disease progression exceeded the cumulative incidence of competing mortality only in the presence of well-identified risk factors of liver disease progression, including alcohol use. The incidence of hepatocellular carcinoma was 0.3 (95% CI 0.1-0.5) per 1,000 person-years in patients with obesity and it increased with age. The adjusted hazard ratios of liver disease progression were 55.7 (40.5-76.6), 3.5 (2.3-5.2), 8.9 (6.9-11.5), and 1.5 (1.1-2.1), for alcohol-related liver disease, alcohol use disorders without alcohol-related liver disease, non-metabolic liver-related risk factors, and obesity, respectively. The attributable fractions of alcohol use disorders, non-metabolic liver-related risk factors, and obesity to the liver burden were 55%, 14%, and 7%, respectively.In this analysis of data from 2 hospital-based cohorts of patients with T2D, alcohol use disorders, rather than obesity, contributed to most of the liver burden. These results suggest that patients with T2D should be advised to drink minimal amounts of alcohol.There is uncertainty on the burden of liver-related complications in patients with type 2 diabetes. We studied the risks of liver cancer and complications of liver disease in over 50,000 patients with type 2 diabetes. We found that alcohol was the main factor associated with complications of liver disease. This finding has major implications on the alcohol advice given to patients with type 2 diabetes.

Published
2021

42. Author response for 'Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study'

Author

null A Diallo, null M Pichelin, null M Wargny, null P Gourdy, null JB Bonnet, null S Hadjadj, null B Cariou, null A Sultan, null F Galtier, null Matthieu Wargny, null Pascale Mahot, null Bertrand Cariou, null Samy Hadjadj, null Matthieu Pichelin, null Anne‐Laure Fournier‐Guilloux, null Nicolas Mauduit, null Edith Bigot‐Corbel, null Anne‐Sophie Boureau, null Laure Dekcer, null Audrey Ernould, null Claire Primot, null Anne Seguin, null Marielle Joliveau, null Sonia Pouvreau, null Chloé FOURNIER, null Jeremy Thureau, null Edith Fonteneau, null Pamela Hublain, null Chu Nantes, null Carole Agasse, null Mathilde DE Kergaradec, null Vincent Minville, null Fanny Vardon‐Bounes, null Guillaume Martin‐Blondel, null Pierre Gourdy, null Blandine Tramunt, null Marie‐Christine Turnin, null Hélène Hanaire, null Jean‐Michel Mansuy, null Didier Fabre, null Marie‐Blanche Arhainx, null Laurent Cazals, null Laure Combes, null Emmanuelle Lami, null Mallory Cianferani, null Bruno Megarbane, null Pierre Leroy, null Jean‐François Gautier, null Tiphaine Vidal‐Trecan, null Jean‐Pierre Riveline, null Jean‐Louis Laplanche, null Stéphane Mouly, null Louis Potier, null Ronan Roussel, null Malak Taher, null Yawa Abouleka, null Fetta Yaker, null Aurelie Carlier, null Anne Boutten, null Marilyne Hallot‐Feron, null Fadila Mourah, null Charles Thivolet, null Emilie Blond, null Muriel Rolland, null Josep Verdecho Mendez, null Marine Alexandre, null Julien Pottecher, null Emilie Richer, null Laurent Meyer, null Florina Luca, null Jean‐Marc Lessinger, null Thibault Bahougne, null Bruno Guerci, null Lisa Ludwig, null Siham Benzirar, null Catherine Malaplate, null Thierry Matton, null Julien Poissy, null Karine Faure, null Pierre Fontaine, null Florence Baudoux, null Anne Vambergue, null Jean David Pekar, null Marc Lambert, null Cécile Yelnik, null Amélie Bruandet, null Laurent Petit, null Didier Neau, null Vincent Rigalleau, null Annie Berard, null Amandine Galioot, null Remy Coudroy, null Arnaud Thille, null René Robert, null France Roblot‐Cazenave, null Blandine Rammaert, null Pierre Jean Saulnier, null Xavier Piguel, null Nesrine Benhenda, null Camille Husson, null Celine Olivier, null Florence Torremocha, null Mathilde Fraty, null Marie Flamen d'assigny, null Aurelie Miot, null Valentin Bossard, null Kada Klouche, null Alain Makinson, null Ariane Sultan, null Jean‐Baptiste Bonnet, null Vincent Foulongne, null Florence Galtier, null Cécile Aubron, null Séverine Ansart, null Véronique Kerlan, null Pascale Quiniou, null Jean‐Luc Carre, null Stéphane Quesnot, null Bruno Laviolle, null Carole Schwebel, null Olivier Epaulard, null Pierre‐Yves Benhamou, null Cécile Betry, null Anne‐Laure Borel, null Sandrine Lablanche, null Dorra Guergour, null Catherine Duclos, null Emmanuel Cosson, null Erwan Guyot, null Aurore Deniau, null Phucthutrang Nguyen, null Yves Reznik, null Michael Joubert, null Stéphane Allouche, null Lydia Guittet, null Steven Grange, null Manuel Etienne, null Gaëtan Prévost, null Valéry Brunel, null Jean‐Christophe Lagier, null Didier Raoult, null Anne Dutour, null Bénédicte Gaborit, null Sandrine Boulllu, null Patrice Darmon, null Adèle Lasbleiz, null Mathieu Cerino, null Fanny Romain, null Marie Houssays, null Jean Pierre Quenot, null Lionel Piroth, null Bruno Vergès, null Laurence Duvillard, null Bernard Bonnotte, null Alain Mercat, null Vincent Dubee, null Ingrid Allix, null Patrice Rodien, null Robin Dhersin, null Maylis Lebeault, null Wojciech Trzepizur, null Jocelyne Loison, null Antoine Brangier, null Pierre Asfar, null Pascal Reynier, null Françoise Larcher, null Françoise Joubaud, null Marie‐Rita Andreu, null Geoffrey Urbanski, null Laurent Hubert, null Cedric Annweiler, null Jean Dellamonica, null Johan Courjon, null Nicolas Chevalier, null Giulia Chinetti, null Magda Chafai, null Bruno Mourvillier, null Firouze Bani‐Sadr, null Sarra Barraud, null Brigitte Delemer, null Philippe Gillery, null Pascale Labedade, null Amélie Chabrol, null Alfred Penfornis, null Catherine Petit, null Coralie Amadou, null Maxime Adler, null Clément Dubost, null Pierre‐Louis Conan, null Lyse Bordier, null Franck Ceppa, null Cyril Garcia, null Mathilde Sollier, null Olivier Dupuy, null Sophie Laplance, null Olivier Billuart, null Marie Joseph Aroulanda, null Frédérique Olivier, null Florence Ayon, null Nathalie Wilhelm, null Loic Epelboin, null Nadia Sabbah, null Aurelie Charpin, null Pierre Squara, null Olivier Belliard, null Claude Dubois, null Michel Marre, null Johann Auchabie, null Roxane Courtois, null Thierry Duriez, null Tiphaine Mergey, null Laura Vallee, null Laetitia Seguin, null Abdallah Al‐Salameh, null Jean‐Philippe Lanoix, null Sandrine Soriot‐Thomas, null Anne‐Marie Bourgeois‐Descouls, null Rachel Desailloud, null Natacha Germain, null Bogdan Galusca, null Gwenaelle Belleton, null Nesrine Marouani, null Delia Palaghiu, null Amira Hammour, null Fernando Berdaguer, null Thimothée Klopfenstein, null Hajer Zayet, null Patrice Winiszewski, null Marie Zanusso, null Pauline Garnier, null Ingrid Julier, null Karim Hamzaoui, null Sophie Marty‐Gres, null Tarik Sadki, null Lucile Cadot, null Jean‐Louis Dubost, null Céline Gonfroy, null Catherine Campinos, null Pascale Martres, null Marie Pierre Coulhon, null Nicolas Allou, null Marwa Bachir, null Stella Hoang, null Candice Kembellec, null Olivia Suply, null Fatima Kharcha, null Anne‐Claire Devouge, null Anna Flaus‐Furmanuk, null Isabelle Madeline, null Vincent Ehinger, null Sophie Bastard, null Loic Raffray, null Frederic Renou, null Aude Bojarski, null Caroline Paul, null Karine Borsu, null Angelique Gorlin, null Servane Bernardo, null Carole Truong Ut, null Stephane Renaud, null Antoine Vignoles, null Emilie Foch, null Laurie Masse, null Hubert Grand, null Helene Ferrand, null Christelle Raffaitin‐Cardin, null Hadjer Zellagui, null Celine Castang‐Brachet, null Frederique Boury, null Ana Alvarez Tena, null Isabelle Moura, null Pierre Kalfon, null Juliana Darasteanu, null Arnaud Monier, null Pascal Foucault, null Alexandra Depuille, null Stéphanie Laugier‐Robiolle, null Patrick Caneiro, null Maud Basso, null Etienne Larger, null Samir Bouam, null Wahiba Benzenati, null Leila Ait Bachir, null Camille Cussac Pillegand, null Marc Vasse, null Christophe Michard, null Nathanaëlle Montanier, null Luc Millot, null Françoise Crepet, null Danielle Ratsimba, null Kevin Bouiller, null Sophie Borot, null Isabelle Bruckert, null Annie Clergeot, null Franck Schillo, null Dorothée Vignes, null Muriel Bourgeon‐Ghittori, null Hamoud Lachgar, null Claire Lambert DE Cursay, null Stéphane Levante, null Jean Charles Auregan, null Antoine Merlet, null Cécile Zaragoza, null Gwénaëlle Arnault, null Anne‐Gaëlle Loupp, null Olivier Lesieur, null Mariam Roncato‐Saberan, null Didier Gouet, null Romain Lemarie, null Hong_an Allano, null Emmanuel Vivier, null Caroline Pariset, null Cédric Luyton, null Lucien Marchand, null Fanny Doroszewski, null Matthieu Pecquet, null Laurent Perard, null Sylvie Vuillermoz‐Blas, null Nicolas Kacki, null Patricia Charrier, null Amélie Ducet‐Boiffard, null Françoise Desroys Roure, null Olivier Bourron, null Dominique Bonnefont‐Rousselot, null Suzanne Laroche, null Franck Phan, null Agnès Hartemann, null Cyrielle Caussy, null Emmanuel Disse, null Claude Guerin, null Thomas Perpoint, null Philippe Moulin, null Régine Cartier, null Geoffroy Hariri, null Dorothée Chopin, null Camille Vatier, null Nathalie Bourcigaux, null Emmanuelle Chaigneau, null Sophie Christin‐Maitre, null Bruno Donadille, null Bruno Feve, null Sophie Lamothe, null Julie Sarfati, null Pascal Pernet, null Anne Chambon, null Delphine Demarsy, null Hugo Campagne, null Françoise Latil‐Plat, null Monica Berne, null Marilyne Grinand, null Marion Touzet, null Aydrey Zabulon, null Jocelyne Craspag, null Catherine Ledoux, null Cedric Contaret, null Blandine Janand‐Delenne, null Anaïs Giraud, null Marie Lou Lacrimini, null Joëlle Arrivie, null Deborah Ancelle, null Carine Guillois, null Bénédicte Fremy, null Amina Chaalal, null Gaëlle Barrande, null Anne Dorange, null Eglantine Rouanet, null Dominique Seret‐Begue, null Audrey Saoud, null Anne‐Marie Guedj, null Nathalie Bedos, null Fritz‐Line Velayoudom, null Marie Dumas, null Benoite Gonda, null Christine Coffin, null Stéphanie Gibiat, null Myriam Lungo, null Chantal Bully, null Pierre Serusclat, null Stella Bully, null Patricia Carre, null Jean‐Philippe Leberre, null Carlos Elkhoury, null Marine Thieux, null Laetitia Paradisi‐Prieur, and null CORONADO investigators

Subjects
Vaccination, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Diabetes mellitus, Medicine, business, medicine.disease
Published
2021

43. Plasma oxysterols: Altered level of plasma 24-hydroxycholesterol in patients with bipolar disorder

Author

Meriam Messedi, Wassim Guidara, Fatma Ayadi, M. Maalej, Sahar Grayaa, Manel Naifar, Mohamed Maalej, Dominique Bonnefont-Rousselot, Foudil Lamari, Walid Khrouf, Université de Sfax, Université de Sfax - University of Sfax, Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), 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 Paris Cité (UPCité), and bigey, pascal

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Tunisia, Oxysterol, 27-hydroxycholesterol, Bipolar disorder, Endocrinology, Diabetes and Metabolism, 24-hydroxycholesterol, Clinical Biochemistry, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Tandem Mass Spectrometry, Internal medicine, medicine, Humans, Decompensation, Prospective Studies, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], business.industry, Cholesterol, Cholestanol, Cell Biology, Biomarker, Oxysterols, medicine.disease, Pathophysiology, Hydroxycholesterols, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Case-Control Studies, 27-Hydroxycholesterol, Molecular Medicine, Biomarker (medicine), lipids (amino acids, peptides, and proteins), sense organs, business, Biomarkers, Chromatography, Liquid
Abstract

International audience; Cholesterol and its oxygenated metabolites, including oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorders. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders. Recent studies have shown that Bipolar disorder (BD) is associated with the disruption of cholesterol metabolism. The present study was aimed at investigating the profile of oxysterols in plasma, their ratio to total cholesterol and their association with clinical parameters in patients with BD. Thirty three men diagnosed with BD and forty healthy controls matched for age and sex were included in the study. Oxysterol levels were measured by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry. Significantly higher levels were observed for cholestane-3β,5α,6β-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol in patients with BD. The concentration of 24-hydroxycholesterol (24-OHC) was significantly lower in patients compared to controls. 24-OHC was also negatively correlated to MAS subscale score (r =-0.343; p = 0.049). In patients, 24-OHC was inversely correlated with age (r = -0.240; p = 0.045). Multivariate analysis found that BD acute decompensation was independently related to the rise in plasma 24-OHC (p = 0.002; OR = 0.966, 95 % CI [0.945 - 0.987]). However, the 24-OHC assay relevance as a biomarker of this disease deserves further investigation in other studies.

Published
2021

44. Non-linearity and gaps in results distribution over successive Roche Lipase method applications: improvement but persistence

Author

Camille Gobeaux-Chenevier, Dominique Bonnefont-Rousselot, Marie-Aude Robert de Rancher, Denis Monneret, Didier Borderie, Hervé Lemaréchal, and Rana Alkouri

Subjects
Materials science, biology, Clinical Biochemistry, Analytical chemistry, Non linearity, Lipase, General Medicine, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Distribution (mathematics), Nonlinear Dynamics, 030220 oncology & carcinogenesis, Linear Models, biology.protein, Humans, Enzyme Assays
Abstract

Non-linearity within the primary measurement range of a lipase assay (® Roche analyzers, causing gaps in results distribution between 300 and 400 U/L. Since, new lipase method applications (LMAs) have been used. The purpose is to retrospectively evaluate their impact on relative frequencies of lipase results (RFLs). Plasma lipase results from two hospital laboratories, assayed over 7.2 years, were collected. Over this period, three successive LMAs, characterized by automated repeat-on-dilution (1/11, 1/2, or 1/10), were applied for lipase results >300 U/L: LMA1 and LMA2 on the Modular®P800, Cobas®c501 and Cobas®C701 analyzers, and LMA3 on the Cobas®C701. RFLs were determined, linearity tests were performed, and inter-agreements between lipase results corrected and uncorrected for nonlinear biases were assessed, using 180 U/L as a decisional cut-off for acute pancreatitis. Overall, RFL gaps narrowed from LMA1 (300 to ∼380 U/L) to LMA3 (300 to ∼330 U/L). For a lipase activity fixed at 300 U/L, non-linearity biases were determined at −11.2% on the Modular®P800 (LMA1), −20.8% on the Cobas®c501 (LMA1), and −3.5% (LMA2) and −2.2% (LM3) on the Cobas®C701. Diagnostically, a maximum of 0.48% lipase results were misclassified as negative (LMA1 on the Cobas®c501), and a minimum of 0.01% misclassified as negative (LMA3 on the Cobas®C701). In conclusion, successive Roche lipase method applications improved linearity within the primary measurement range. While persisting, gaps in lipase results distribution narrowed with the evolution of the methods, with a minor impact in terms of diagnostic of acute pancreatitis.

Published
2019

45. Plasma oxysterols in drug-free patients with schizophrenia

Author

Wassim Guidara, Meriam Messedi, Manel Naifar, Manel Maalej, Walid Khrouf, Sahar Grayaa, Mohamed Maalej, Dominique Bonnefont-Rousselot, Foudil Lamari, and Fatma Ayadi

Subjects
Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Oxysterols, Cell Biology, Biochemistry, Endocrinology, Area Under Curve, Schizophrenia, Humans, Molecular Medicine, Molecular Biology, Biomarkers, Cholestanols
Abstract

Evidence from clinical, genetic, and medical studies has shown the neuronal developmental disorder aspect of schizophrenia (SZ). Whereas oxysterols are vital factors in neurodevelopment, it is still unknown whether they are involved in the pathophysiology of SZ. The current study aims to explore the profile of oxysterols in plasma, ratio to total cholesterol (Tchol) and the association with clinical factors in patients with SZ. Forty men diagnosed with SZ and forty healthy controls matched for age and sex were included in the study. The ratios of cholestane-3β,5α,6β-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol to Tchol increased in the schizophrenic group compared to controls. However, levels of 24S-hydroxycholesterol (24-OHC) were not significantly different between patients and controls. For the SZ patients, the plasma 24-OHC levels were positively correlated with the positive and negative syndrome total scores (PANSS) but negatively correlated with the Montreal Cognitive Assessment scores (MOCA). Moreover, the ratio Cholestanol to Tchol was negatively correlated with MOCA scores and positively correlated with PANSS general. The binary logistic regression analysis revealed that the ratio Cholestane-3β,5α,6β-triol/TChol could be considered as an independent risk factor for SZ. On the other hand, the receiver's operating characteristics analysis corresponding to potential biomarkers on SZ showed Areas Under the Curve (AUCs) of 82.1%; 69.7% and 77.6% for the ratio of Cholestane-3β,5α,6β-triol/TChol, 27-OHC/TChol and Cholestanol/TChol respectively. The relevance of Cholestane-3β,5α,6β-triol, 27-OHC and Cholestanol assays as biomarkers of this disease deserves further investigation.

Published
2022

46. Transportation and handling of blood samples prior to ammonia measurement in the real life of a large university hospital

Author

Thierry Poynard, Mehdi Sakka, Rana Alkouri, Dominique Thabut, Marika Rudler, Jamal Alfaisal, Sylvie Dever, Françoise Imbert-Bismut, Dominique Bonnefont-Rousselot, Shaedah Djavoudine, Mona Munteanu, Philippe Sultanik, Pierre-Emeric Payet, Fouzi Mestari, Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Paris (UP), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), 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 Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Waiting time, Sample (material), [SDV]Life Sciences [q-bio], Clinical Biochemistry, Centrifugation, Transportation, Context (language use), Biochemistry, Specimen Handling, 03 medical and health sciences, Ammonia, chemistry.chemical_compound, 0302 clinical medicine, Freezing, Humans, Ammonia Measurement, Sample handling, Chromatography, Biochemistry (medical), Temperature, General Medicine, University hospital, Hospitals, [SDV] Life Sciences [q-bio], 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Environmental science
Abstract

Background: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results. Aims and methods: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer. In the same routine context, the effects of waiting times of centrifuged samples or after plasma storage at −20 °C and −80 °C were determined. Results: Despite the pneumatic transport, the lead times for sample arrival to the lab were even longer than those recommended for their complete handling until ammonia assay. Ammonia concentration results were not affected by the pneumatic transport of blood samples and by waiting times up to a maximum of 1.75 h before their centrifugation and 1 h after centrifugation. Ammonia stability was superior when plasma was stored at −80 °C. Conclusion: Pneumatic transport and sample handling in the routine practice of our lab do not affect ammonia concentration results provided that waiting times are limited to 1.75 h before and 1 h after centrifugation and samples are kept cold. Otherwise, it is better to freeze plasma at −80 °C.

Published
2020

47. Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

Author

Sepideh Akhavan, Marika Rudler, Dominique Bonnefont-Rousselot, Julien Mayaux, Bruno Fautrel, Clemence Franc, Yves Allenbach, Mehdi Sakka, Chantal Housset, Olivier Lucidarme, Vincent Calvez, Thierry Poynard, Frédérique Gandjbakhch, Jean Marc Lacorte, Olivier Deckmyn, Mathieu Vautier, F. Drane, Patrice Cacoub, Yen Ngo, Dominique Thabut, J.M. Castille, David Saadoun, Valentina Peta, Olivier Benveniste, Vlad Ratziu, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), BioPredictive [Paris], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Service de virologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Viral Diseases, Epidemiology, [SDV]Life Sciences [q-bio], Biochemistry, Geographical locations, law.invention, Medical Conditions, 0302 clinical medicine, law, Medicine and Health Sciences, Virus Testing, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, medicine.diagnostic_test, Liver Diseases, Haptoglobin, Middle Aged, Intensive care unit, Hospitals, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Intensive Care Units, Infectious Diseases, 030220 oncology & carcinogenesis, Medicine, Female, 030211 gastroenterology & hepatology, Apolipoprotein A1, France, Coronavirus Infections, Research Article, Adult, medicine.medical_specialty, Science, Pneumonia, Viral, Population, Gastroenterology and Hepatology, Betacoronavirus, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Humans, European Union, education, Pandemics, Aged, Retrospective Studies, 030304 developmental biology, Plasma Proteins, Haptoglobins, Apolipoprotein A-I, SARS-CoV-2, business.industry, Biology and Life Sciences, Proteins, COVID-19, Covid 19, Retrospective cohort study, medicine.disease, United States, Health Care, Pneumonia, Health Care Facilities, Medical Risk Factors, Relative risk, biology.protein, Observational study, People and places, business, Liver function tests, Biomarkers
Abstract

BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 30 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (183,112 sera) and in France (18,316 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 234,881 and 26,056 sera). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in these populations began decreasing in January 2020, compared to the same 30 weeks in 2019. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 30 weeks, in both France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0;P=0.04).ConclusionApolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population with no new blood sample, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test. NCT01927133, CER-2020-14.Key PointsQuestionDoes serum apolipoprotein-A1 decrease could be a very early biomarker of SARS-CoV-2 pandemic?FindingsDuring the 30 weeks of 2020 we observed in two large cohorts of patients at risk of liver fibrosis a highly significant decrease of serum apolipoprotein-A1, not observed in previous years. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases, including the recovery period.MeaningApolipoprotein-A1 could be used as a sentinel of the pandemic in existing routine surveillance of the general population.

Published
2020

48. Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial

Author

Charles Bouis, Jean Dewailly, Ahlam Azar-Kolakez, Rosa-Maria Guéant-Rodriguez, Isabelle Marey, Oliver Greiner-Mahler, Jean-Louis Guéant, Aude Pichot, Samantha Stora, Silvia Sacco, Dominique Bonnefont-Rousselot, Emilie Schlumberger, Franck Sturtz, Eric Le Galloudec, Nathalie Dorison, Clotilde Mircher, Elodie Blondiaux, Alicia Gambarini, André Baruchel, Sophie Durand, Jennifer Gallard, Aimé Ravel, Didier Borderie, Michel Polak, and Cécile Cieuta

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Down syndrome, Randomization, Population, Leucovorin, 030105 genetics & heredity, Placebo, 03 medical and health sciences, Folinic acid, Double-Blind Method, Thyroid-stimulating hormone, Internal medicine, Clinical endpoint, medicine, Humans, education, Genetics (clinical), education.field_of_study, business.industry, Thyroid, Infant, medicine.disease, Intention to Treat Analysis, Clinical trial, Thyroxine, Treatment Outcome, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Female, Down Syndrome, business, Psychomotor Performance, medicine.drug, Hormone
Abstract

To determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS). The Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6–18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months. Randomization was done by age and sex. The primary endpoint was adjusted change from baseline in Griffiths Mental Development Scale global development quotient (GDQ) after 12 months. Of 175 patients randomized, 143 completed the study. The modified intention-to-treat (mITT) population included all randomized patients who did not prematurely discontinue due to elevated baseline thyroid stimulating hormone (TSH). Baseline characteristics in the mITT were well balanced between groups, with reliable developmental assessment outcomes. Adjusted mean change in GDQ in the mITT showed similar decreases in all groups (placebo: −5.10 [95% confidence interval (CI) −7.84 to −2.37]; FA: −4.69 [95% CI −7.73 to −1.64]; L-thyroxine: −3.89 [95% CI −6.94 to −0.83]; FA+L-thyroxine: −3.86 [95% CI −6.67 to −1.06]), with no significant difference for any active treatment group versus placebo. This trial does not support the hypotheses that thyroxine and/or folinic acid improve development of young children with DS or are synergistic. This trial is registered with ClinicalTrials.gov number, NCT01576705.

Published
2020

49. Homeostasis model assessment of insulin resistance and lobular inflammation in nondiabetic patients with nonalcoholic fatty liver disease: methodological considerations

Author

Denis Monneret and Dominique Bonnefont-Rousselot

Subjects
Inflammation, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, Insulin resistance, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Homeostasis, Humans, medicine.symptom, Insulin Resistance, business
Published
2020

50. Evaluation of a semi-automatic isoelectric focusing method for apolipoprotein E phenotyping

Author

C. Cherfils, Laurence Barbot-Trystram, Georges Nouadje, Philippe Giral, Dominique Bonnefont-Rousselot, Randa Bittar, Valérie Fesel-Fouquier, Alain Carrié, Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Laboratoire de Coprologie Fonctionnelle [Pitié-Salpêtrière], Sorbonne Université (SU), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], and CCSD, Accord Elsevier

Subjects
Apolipoprotein E, 030213 general clinical medicine, HDL, Concordance, [SDV]Life Sciences [q-bio], Clinical Biochemistry, apolipoprotein, IDL, intermediate density lipoprotein, Computational biology, 030204 cardiovascular system & hematology, IDL, Article, LDL, low density lipoprotein, LDL, lcsh:Chemistry, 03 medical and health sciences, Sample volume, VLDL, very low density lipoprotein, 0302 clinical medicine, apo, intermediate density lipoprotein, Medicine, isoelectric focusing, apo, apolipoprotein, Genotyping, Reproducibility, lcsh:R5-920, Radiological and Ultrasound Technology, business.industry, Isoelectric focusing, IEF, Repeatability, HDL, high density lipoprotein, 3. Good health, very low density lipoprotein, [SDV] Life Sciences [q-bio], IEF, isoelectric focusing, Phenotype, lcsh:QD1-999, high density lipoprotein, lipids (amino acids, peptides, and proteins), Semi automatic, business, lcsh:Medicine (General), Isoforms, low density lipoprotein, VLDL
Abstract

A qualitative, semi-automatized method for apolipoprotein E (apoE) phenotyping by isoelectric focusing method has been evaluated on 40 serum samples from patients previously genotyped for apoE, especially as regards concordance with genotyping, but also repeatability and reproducibility of the method, and sample storage. Total concordance with genotyping and good precision criteria, together with its practicability and requirement of a little sample volume, lead to conclude to the usefulness of this method to help clinicians in the diagnosis of dyslipidemic and neurodegenerative diseases., Highlights • Semi-automatic isoelectrofocusing method for apoE phenotyping. • Total concordance with genotyping. • Good repeatability and reproducibility.

Published
2020

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