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1. Analysis of capacitive discharges in motor bearings under different operation conditions

Author

Sara Jammoul, Remus Pusca, Raphael Romary, Guillaume Lefevre, Nicolas Voyer, and Guilherme Bueno Mariani

Subjects
ageing, ball bearings, machine bearings, PWM invertors, Applications of electric power, TK4001-4102
Abstract

Abstract Despite being a well‐known problem, bearing faults are still one of the major challenges that the industry face. The growing use of voltage source inverters imposed the alertness of possible bearing damage due to their high‐frequency signals. The aim of this paper is to investigate the effect of capacitive discharges on a rolling element bearing to obtain a series of faulty bearings with different deterioration levels. An ageing test bench is built to generate bearing roughness using Electric Discharge Machining. The purpose is to study the effect of operation conditions, such as frequency of drive, amplitude of shaft voltage, radial load level as well as rotational speed, on the capacitive discharge occurrence within the bearing. Having the desire to further understand this phenomenon, the influence of each parameter on the discharge activity and the discharge waveform is analysed. A worst‐case scenario is conducted and applied to a series of bearings. Finally, the bearing damage is examined, and a quantitative fault detection method is presented based on a microscopic inspection of the bearing's surface.

Published
2024
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2. Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review

Author

Elisa Chapuis, Elodie Bousquet, Jean-François Viallard, Benjamin Terrier, Zahir Amoura, Veronica Batani, Antoine Brézin, Patrice Cacoub, Marco Caminati, Thibaud Chazal, Cloé Comarmond, Isabelle Durieu, Mikael Ebbo, Maximilien Grall, Emmanuel Ledoult, Laura Losappio, Irene Mattioli, Arsène Mékinian, Roberto Padoan, Francesca Regola, Jan Schroeder, Lior Seluk, Ludovic Trefond, Michael E. Wechsler, Guillaume Lefevre, Jean-Emmanuel Kahn, Pascal Sève, and Matthieu Groh

Subjects
eosinophilia, hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, retinal artery occlusion, retinal vein occlusion, retinal vasculitis, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionEosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia.MethodsWe conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. ResultsFifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher’s retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). DiscussionThis study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Published
2024
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5. The PID Odyssey 2030: outlooks, unmet needs, hurdles, and opportunities — proceedings from the IPOPI global multi-stakeholders’ summit (June 2022)

Author

Susan Tadros, Johan Prévot, Isabelle Meyts, Silvia Sánchez-Ramón, Nahla H. Erwa, Alain Fischer, Guillaume Lefevre, Matthew Hotchko, Peter M. Jaworski, Helen Leavis, Cornelis Boersma, Jose Drabwell, Martin van Hagen, Samya Van Coillie, Martine Pergent, Siobhan O. Burns, and Nizar Mahlaoui

Subjects
primary immunodeficiencies/inborn errors of immunity, immunoglobulin replacement therapy/plasma derived medicinal products, hematopoietic stem cell transplantation, gene therapy, newborn screening, next generation sequencing, Immunologic diseases. Allergy, RC581-607
Abstract

IPOPI held its first Global Multi-Stakeholders’ Summit on 23-24 June 2022 in Cascais, Portugal. This IPOPI initiative was designed to set the stage for a stimulating forward-thinking meeting and brainstorming discussion among stakeholders on the future priorities of the PID community. All participants were actively engaged in the entire Summit, bringing provocative questions to ensure a high level of discussion and engagement, and partnered in identifying the outlooks, unmet needs, hurdles and opportunities of PIDs for 2030. The topics that were covered include diagnosis (e.g., newborn screening [NBS], genomic sequencing— including ethical aspects on the application of genomics on NBS, the role of more accurate and timely diagnostics in impacting personalized management), treatment (e.g., the therapeutic evolution of immunoglobulins in a global environment, new therapies such as targeted therapies, new approaches in curative therapies), the interactions of Primary ID with Secondary ID, Autoinflammatory Diseases and other diseases as the field experiences an incessant evolution, and also the avenues for research in the field of humanities and human sciences such as Patient-Reported Outcome Measures (PROMs), Patient-Reported Experience Measures (PREMs), and Health-Related Quality Of Life (HRQoL). During this meeting, all participants contributed to the drafting of recommendations based on our common understanding of the future opportunities, challenges, and scenarios. As a collection of materials, perspectives and summaries, they are succinct and impactful and may help determine some of the next key steps for the PID community.

Published
2023
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6. Successful Introduction of Benralizumab for Eosinophilic Ascites

Author

Nabil Belfeki, Nouha Ghriss, Souheil Zayet, Faten El Hedhili, Cyrus Moini, and Guillaume Lefevre

Subjects
benralizumab, eosinophilic ascites, eosinophilic gastroenteritis, steroids, Biology (General), QH301-705.5
Abstract

Eosinophilic ascites is a rare disorder, reported in both adult and pediatric patients, characterized by high eosinophil counts in the peritoneal fluid. Eosinophilic ascites appears as a manifestation of various diseases such as parasitic and fungal infections, malignancy, and hypereosinophilic syndrome. It also represents an uncommon manifestation of eosinophilic gastroenteritis, usually treated with corticosteroids. We present the case of a 16-year-old woman with abdominal distention related to abundant ascites. Further work-up concluded that it was eosinophilic gastroenteritis complicated with eosinophilic ascites. The patient was on oral steroids for three weeks, but various abdominal relapses were observed, leading to the introduction of benralizumab, as a steroid-sparing therapy with a favorable outcome.

Published
2024
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7. Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome

Author

Fabrizio Pane, Guillaume Lefevre, Namhee Kwon, Jane H. Bentley, Steven W. Yancey, and Jonathan Steinfeld

Subjects
antibody, anti-interleukin-5 therapy, hypereosinophilic syndrome, mepolizumab, uncontrolled disease, Immunologic diseases. Allergy, RC581-607
Abstract

In patients with hypereosinophilic syndrome (HES), mepolizumab reduces the incidence of HES-related clinical signs and symptoms (flares). However, reports characterizing flare manifestations are limited. The double-blind, parallel-group 200622 trial (NCT02836496) enrolled patients ≥12 years old with HES for ≥6 months, ≥2 flares in the previous year, and screening blood eosinophil count ≥1000 cells/μL. Patients maintained ≥4 weeks stable HES therapy, before randomization (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. This post hoc analysis investigated flare manifestations and duration by re-examining the Core Assessments form and narrative recorded for each flare during the study. Flare symptoms were retrospectively categorized into constitutional, dermatological, respiratory, nasal, gastrointestinal, neurologic and other. The most frequently reported flare symptoms were constitutional (94% of flares), dermatological (82% of flares) and respiratory (72% of flares); flares reported in patients receiving mepolizumab compared with placebo were generally similar in terms of the frequency of symptoms reported. Mepolizumab was associated with a shorter median (range) duration of flares (10.0 [4, 126] days) versus placebo (26.0 [1, 154] days). In patients with HES, flares were associated with symptoms linked to multiple organ systems highlighting the challenges faced for treating flares.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02836496, identifier NCT02836496.

Published
2022
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8. Venous thrombosis and predictors of relapse in eosinophil-related diseases

Author

Valériane Réau, Alexandre Vallée, Benjamin Terrier, Aurélie Plessier, Noémie Abisror, Félix Ackermann, Ruben Benainous, Gérôme Bohelay, Marie-Laure Chabi-Charvillat, Divi Cornec, Anne-Claire Desbois, Stanislas Faguer, Nathalie Freymond, Antoine Gaillet, Mohamed Hamidou, Martin Killian, Sylvain Le Jeune, Anne Marchetti, Guy Meyer, Francisco Osorio-Perez, Kewin Panel, Pierre-Emmanuel Rautou, Julien Rohmer, Nicolas Simon, Colas Tcherakian, Marc Vasse, Elina Zuelgaray, Guillaume Lefevre, Jean-Emmanuel Kahn, and Matthieu Groh

Subjects
Medicine, Science
Abstract

Abstract Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Published
2021
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9. Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome

Author

Andreas Reiter, Guillaume Lefevre, Maria C. Cid, Namhee Kwon, Eleni Mavropolou, Steven W. Yancey, and Jonathan Steinfeld

Subjects
hypereosinophilic syndrome, eosinophils, clinical immunology, mepolizumab, oral corticosteroids, immunosuppressive therapy, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundCurrent standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496).MethodsIn the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks’ stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This post hoc, descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo.ResultsMepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32–96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3–31.4%) than placebo (35.7–74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22–0.68 vs 1.14–1.62). The proportion of patients who experienced ≥1 flare during Weeks 20–32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55–85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group.ConclusionsPatients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy.Clinical Trial Registration(https://clinicaltrials.gov/ct2/show/NCT02836496).

Published
2022
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10. Relevance of partitioning DLCO to detect pulmonary hypertension in systemic sclerosis.

Author

Nadia Sivova, David Launay, Lidwine Wémeau-Stervinou, Pascal De Groote, Martine Remy-Jardin, Guillaume Denis, Marc Lambert, Nicolas Lamblin, Sandrine Morell-Dubois, Marie Fertin, Guillaume Lefevre, Vincent Sobanski, Olivier Le Rouzic, Pierre-Yves Hatron, Benoit Wallaert, Eric Hachulla, and Thierry Perez

Subjects
Medicine, Science
Abstract

We investigated whether partitioning DLCO into membrane conductance for CO (DmCO) and pulmonary capillary blood volume (Vcap) was helpful in suspecting precapillary pulmonary (arterial) hypertension (P(A)H) in systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD). We included 63 SSc patients with isolated PAH (n=6), isolated ILD (n=19), association of both (n=12) or without PAH and ILD (n=26). Partitioning of DLCO was performed by the combined DLNO/DLCO method. DLCO, DmCO and Vcap were equally reduced in patients with isolated PAH and patients with isolated ILD but Vcap/alveolar volume (VA) ratio was significantly lower in the isolated PAH group. In patients without ILD, DLCO, DmCO, Vcap and Vcap/VA ratio were reduced in patients with isolated PAH when compared to patients without PAH and both Vcap/VA and DLCO had the highest AUC to detect PAH. In patients with ILD, Vcap had the highest AUC and performed better than DLCO to detect PH in this subgroup. In conclusion, Vcap/VA was lower in PAH than in ILD in SSC whereas DLCO was not different. Vcap/VA ratio and DLCO had similar high performance to detect PAH in patients without ILD. Vcap had better AUC than DLCO, DmCO and FVC/DLCO ratio to detect PH in SSC patients with ILD. These results suggest that partitioning of DLCO might be of interest to detect P(A)H in SSC patients with or without ILD.

Published
2013
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11. Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria

Author

Nahid Tabibzadeh, Emmanuelle Vidal-Petiot, Lynda Cheddani, Jean-Philippe Haymann, Guillaume Lefevre, Bruno Etain, Frank Bellivier, Emeline Marlinge, Marine Delavest, François Vrtovsnik, and Martin Flamant

Subjects
Nephrology
Abstract

Lithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output.Prospective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement inOf the individuals, 21% displayed polyuria (3 l/d), but 55% displayed elevated fasting vasopressin level (5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for10 years. MaxUosm was600 mOsm/KgHHigher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.

Published
2022

12. Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser

Author

Bernardino González de la Presa, Valerie Chicha-Cattoir, Jose Luis Bedini, Luigi Vecchia, Guillaume Lefevre, Aurea Mira, Pilar Fernández Calle, Efrem Bonelli, Tiphaine Robert, Nayra Rico, Maria Sanz de Pedro, Simone Canovi, Antonio Buño Soto, Katell Peoc’h, Tommaso Fasano, and Jorge Diaz-Garzon

Subjects
Europe, Troponin I, Biochemistry (medical), Clinical Biochemistry, Humans, Biological Assay, Blood Coagulation Tests, Laboratories, analytical techniques and equipment, high-sensitive troponin I, immunoassay, performance evaluation
Abstract

The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer’s cut-offs. Sample turnaround time (TAT) was examined. Imprecision repeatability CVs were 1.1–4.7% and within-lab imprecision were 1.8–7.6% (10.0–25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer’s values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Published
2022

13. Prognostic performance of GRACE and TIMI risk scores in critically ill patients with sepsis and a concomitant myocardial infarction

Author

Cyrielle Desnos, Stéphane Ederhy, Pierre Belnou, Nathanaël Lapidus, Guillaume Lefevre, Guillaume Voiriot, Ariel Cohen, Muriel Fartoukh, Vincent Labbé, Gestionnaire, Hal Sorbonne Université, Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire APPROCHES, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Groupe de REcherche en Cardio Oncologie [CHU Saint-Antoine] (GRC 27 GRECO), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), 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 Henri Mondor, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Aspirin, [SDV]Life Sciences [q-bio], Critical Illness, Myocardial Infarction, General Medicine, Prognosis, Risk Assessment, Brain Ischemia, [SDV] Life Sciences [q-bio], Stroke, Risk Factors, Sepsis, Humans, Female, Registries, Cardiology and Cardiovascular Medicine, Aged, Retrospective Studies
Abstract

Identifying which patients with acute myocardial infarction (AMI) during sepsis are at risk of poor outcome is a clinical challenge.To evaluate Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores to predict in-hospital mortality and severe ischaemic events in this setting.In this single-centre retrospective study conducted from 2012 to 2016, all consecutive adults hospitalized in the intensive care unit for sepsis who had a concomitant AMI (within 72hours of admission) were enrolled. AMI was defined by an elevated cardiac troponin I value associated with at least one sign (clinical, electrocardiographic or echocardiographic) suggestive of myocardial ischaemia. The primary outcome was in-hospital mortality from any cause. Secondary outcomes were in-hospital occurrence of severe ischaemic events (cardiac arrest with resuscitation, ischaemic stroke and myocardial reinfarction) and major bleeding events.Among 856 patients hospitalized for sepsis, 120 (14.5%) had a concomitant AMI (37.5% women; median age 65 years; median Sequential Organ Failure Assessment [SOFA] score 8). Severe ischaemic events occurred in 15 patients (12.5%), and 39 (33%) died in hospital. Neither the GRACE score (median 192, interquartile range 154-223) nor the TIMI score (median 3, interquartile range 2-4) was associated with occurrence of severe ischaemic events. Only the GRACE score was associated with in-hospital mortality (odds ratio 1.01, 95% confidence interval 1.00-1.02 per 1 point increase). Multivariable analysis identified previous aspirin use and SOFA score as independent factors associated with in-hospital mortality.GRACE and TIMI scores did not predict in-hospital severe ischaemic events and mortality in patients with AMI during sepsis. Among individual components of both scores, previous aspirin use was associated with poor prognosis. However, because of lack of statistical power, we cannot formally rule out the usefulness of these scores in this setting.

Published
2021

14. Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome

Author

Andreas Reiter, Guillaume Lefevre, Maria C. Cid, Namhee Kwon, Eleni Mavropolou, Steven W. Yancey, and Jonathan Steinfeld

Subjects
Eosinophils, Adrenal Cortex Hormones, Immunology, Hypereosinophilic Syndrome, Immunology and Allergy, Humans, Antibodies, Monoclonal, Humanized, Child, Immunosuppressive Agents
Abstract

BackgroundCurrent standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496).MethodsIn the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks’ stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This post hoc, descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo.ResultsMepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32–96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3–31.4%) than placebo (35.7–74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22–0.68 vs 1.14–1.62). The proportion of patients who experienced ≥1 flare during Weeks 20–32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55–85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group.ConclusionsPatients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy.Clinical Trial Registration(https://clinicaltrials.gov/ct2/show/NCT02836496).

Published
2021

16. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
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17. From Pregnancy to Preeclampsia: A Key Role for Estrogens

Author

Nadia Berkane, Michael Schumacher, Jean-Paul Oudinet, Alexandre Hertig, Philippe Liere, Guillaume Lefevre, Nicola Pluchino, Nathalie Chabbert-Buffet, Petites Molécules de neuroprotection, neurorégénération et remyélinisation, and Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Placenta Diseases/metabolism/physiopathology, medicine.medical_specialty, Placenta Diseases, MESH: Pre-Eclampsia, Angiogenesis, medicine.drug_class, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Pre-Eclampsia/metabolism/physiopathology, MESH: Estrogens, Preeclampsia, MESH: Placenta Diseases, 03 medical and health sciences, MESH: Pregnancy, 0302 clinical medicine, Endocrinology, Pre-Eclampsia, Pregnancy, Internal medicine, Placenta, Animals, Humans, Medicine, MESH: Animals, Fetus, ddc:618, MESH: Humans, 030219 obstetrics & reproductive medicine, business.industry, Estrogens, medicine.disease, Androgen, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Estrogen, Biomarker (medicine), Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Estrogens/biosynthesis, business, MESH: Female
Abstract

International audience; Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation. Previous assessments of estrogen synthesis during PE yielded conflicting results, possibly because of the lack of specificity of the assays. However, with the introduction of reliable analytical protocols using liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry, more recent studies suggest a marked decrease in estradiol levels in PE. The aim of this review is to summarize current knowledge of estrogen synthesis, regulation in the placenta, and biological effects during pregnancy and PE. Moreover, this review highlights the links among the occurrence of PE, estrogen biosynthesis, angiogenic factors, and cardiovascular risk factors. A close link between estrogen dysregulation and PE occurrence might validate estrogen levels as a biomarker but could also reveal a potential approach for prevention or cure of PE.

Published
2017

19. Chemical discrimination of the particulate and gas phases of miniCAST exhausts using a two-filter collection method

Author

Linh Dan Ngo, Dumitru Duca, Yvain Carpentier, Jennifer A. Noble, Raouf Ikhenazene, Marin Vojkovic, Cornelia Irimiea, Ismael K. Ortega, Guillaume Lefevre, Jérôme Yon, Alessandro Faccinetto, Eric Therssen, Michael Ziskind, Bertrand Chazallon, Claire Pirim, Cristian Focsa, Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0005/11-LABX-0005,Cappa,Physiques et Chimie de l’Environnement Atmosphérique(2011), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Physique Moléculaire aux Interfaces (PMI), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), DMPE, ONERA, Université Paris Saclay [Palaiseau], ONERA-Université Paris-Saclay, Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM], Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 [PC2A], DMPE, ONERA, Université Paris Saclay (COmUE) [Palaiseau], and Complexe de recherche interprofessionnel en aérothermochimie [CORIA]

Subjects
[PHYS.PHYS.PHYS-AO-PH]Physics [physics]/Physics [physics]/Atmospheric and Oceanic Physics [physics.ao-ph], [SPI]Engineering Sciences [physics], 13. Climate action, combustion, soot, particles, CAST, gas phase, [SPI.FLUID]Engineering Sciences [physics]/Reactive fluid environment, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 0210 nano-technology, [SDE.ES]Environmental Sciences/Environmental and Society, 01 natural sciences, ComputingMilieux_MISCELLANEOUS, 0104 chemical sciences
Abstract

Combustion of hydrocarbons produces both particulate and gas phase emissions responsible for major impacts on atmospheric chemistry and human health. Ascertaining the impact of these emissions, especially on human health, is not straightforward because of our relatively poor knowledge of how chemical compounds are partitioned between the particle and gas phases. Accordingly, we propose to couple a two-filter sampling method with a multi-technique analytical approach to fully characterize the particulate and gas phase compositions of combustion by-products. The two-filter sampling method is designed to retain particulate matter (elemental carbon possibly covered in a surface layer of adsorbed molecules) on a first quartz fiber filter while letting the gas phase pass through, and then trap the most volatile components on a second black carbon-covered filter. All samples thus collected are subsequently subjected to a multi-technique analytical protocol involving two-step laser mass spectrometry (L2MS), secondary ion mass spectrometry (SIMS), and micro-Raman spectroscopy. Using the combination of this two-filter sampling/multi-technique approach in conjunction with advanced statistical methods we are able to unravel distinct surface chemical compositions of aerosols generated with different set points of a miniCAST burner. Specifically, we successfully discriminate samples by their volatile, semi-volatile and non-volatile polycyclic aromatic hydrocarbon (PAH) contents and reveal how subtle changes in combustion parameters affect particle surface chemistry.

Published
2019

20. Educational Recommendations on Selected Analytical and Clinical Aspects of Natriuretic Peptides with a Focus on Heart Failure: A Report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers

Author

Amy K. Saenger, Carolyn S.P. Lam, Tobjørn Omland, Paul Collinson, Allan S. Jaffe, Jordi Ordóñez-Llanos, Fred S. Apple, Guillaume Lefevre, Kari Pulkki, Richard Body, and Peter A. Kavsak

Subjects
medicine.medical_specialty, Cardiac troponin, Cardiac biomarkers, medicine.drug_class, Clinical Biochemistry, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Intensive care medicine, Heart Failure, Immunoassay, Task force, business.industry, Biochemistry (medical), medicine.disease, Peptide Fragments, Clinical Practice, Heart failure, Educational resources, business, Research setting, Biomarkers
Abstract

The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), with a focus on heart failure.

Published
2019

21. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

Author

Nizar Mahlaoui, Capucine Picard, Perrine Bach, Laurence Costes, Virginie Courteille, Anja Ranohavimparany, Alexandre Alcaïs, Jean-Philippe Jais, Alain Fischer, Christine Bellanné-Chantelot, Jacinta Bustamante, Sylvie Chollet-Martin, Christian Drouet, Véronique Fremeaux-Bacchi, Caroline Kannengiesser, Virginie Girardin, Nathalie Lambert, Valérie Proulle, Jérémie Rosain, Marie José Stasia, Dominique Stoppa Lyonnet, Ioannis Theodorou, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Emilie Catherinot, Nathalie Cheikh, Sarah Cohen-Beaussant, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Geneviève de Saint Basile, Catherine Devoldere, Anne Deville, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, David Launay, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Dalila Nouar, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Service de Biostatistique et Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], 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), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), the Study Center of Primary Immunodeficiencies, CHU Necker - Enfants Malades [AP-HP], Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Tronche, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hématogoie pédiatrique, hôpital Sud, SIGNAL-IMAGE-COMMUNICATION (SIC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Foch [Suresnes], Service de pédiatrie (CHU de Dijon), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Claude Huriez [Lille], CHU Lille, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, cellules dendritiques et greffes (JE 2448), Université de Tours (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne, maladies infectieuses, immunologie clinique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Hémato-Oncologie Pédiatrique, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Internal Medicine, Paris, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Clermont-Ferrand, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], American Memorial Hospital, American Memory Hospital, Department of Clinical Immunology, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Hématologie Infantile, CHU Amiens-Picardie, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Clinical Haematology, CHU Hôtel-Dieu, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], French Ministry of Health, LFB, GlaxoSmithKlineGlaxoSmithKline, CSL BehringCSL Behring, ShireShire, Octapharma, Binding Site, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Chaire Médecine expérimentale (A. Fischer), Service de Génétique Cytogénétique et Embryologie [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), GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Toulouse [Toulouse]-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), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie pédiatrique, CHU Toulouse [Toulouse], CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de médecine de l'enfant et de l'adolescent, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Service de médecine interne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], McGill University, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Amiens (CHU), centre hospitalier universitaire amiens, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)

Subjects
0301 basic medicine, Primary Immunodeficiency Diseases, medicine.medical_treatment, Genetic counseling, Immunology, Genomics, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Genotype, Humans, Immunology and Allergy, Medicine, Genetic Testing, Registries, Retrospective Studies, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Common variable immunodeficiency, Retrospective cohort study, medicine.disease, Phenotype, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Identification (biology), France, business, 030215 immunology
Abstract

International audience; To the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...]

Published
2019

22. Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin : educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB)

Author

Torbjørn Omland, Amy K. Saenger, Allan S. Jaffe, Jordi Ordóñez-Llanos, Guillaume Lefevre, Kari Pulkki, Fred S. Apple, Richard Body, Paul Collinson, Peter A. Kavsak, and Carolyn S.P. Lam

Subjects
030213 general clinical medicine, medicine.medical_specialty, Cardiac troponin, medicine.drug_class, Cardiac biomarkers, Clinical Biochemistry, Biotin, 030204 cardiovascular system & hematology, Hemolysis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medisinske Fag: 700 [VDP], Internal medicine, Natriuretic peptide, medicine, Artikkel, VDP::Medisinske Fag: 700, health care economics and organizations, natriuretic peptide, biology, business.industry, Biochemistry (medical), General Medicine, medicine.disease, Troponin, chemistry, Interferences, Peptide, biology.protein, Biomarker (medicine), Natriuretic, business
Abstract

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation. Keywords: biotin; hemolysis; interferences; natriuretic peptide; troponin Cardiac troponin I and T (cTnI, cTnT) and the natriuretic peptides (NP; B-type natriuretic peptide, BNP; N Terminal-proBNP; NT-proBNP) are the primary cardiac biomarkers utilized in the diagnosis of myocardial injury and infarction (MI) and heart failure (HF), respectively. As with any clinical laboratory test, there are exogenous and endogenous factors that adversely interfere with the analytical performance of the cTn and NP assays, potentially resulting in inappropriate clinical interpretation of the results if the interferences are not identified. Analytical interferences are particularly concerning when dealing with cardiac biomarker assays, which are utilized to make time sensitive critical clinical decisions. Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7, vitamin H, coenzyme R). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays (Table 1) [1], and NP assays (Table 2) [2] interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation.

Published
2019

23. French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes

Author

Matthieu Groh, Julien Rohmer, Nicolas Etienne, Wadih Abou Chahla, Antoine Baudet, Aurélie Chan Hew Wai, Cécile Chenivesse, Irena Clisson Rusek, Vincent Cottin, Matthieu Decamp, Pascal De Groote, Fanny Delahousse, Nicolas Duployez, Stanislas Faguer, Frédéric Gottrand, Florent Huang, Thierry Leblanc, Antoine Magnan, Thierry Martin, Geoffrey Mortuaire, Antoine Néel, Luc Paris, Arnaud Petit, Julien Rossignol, Nicolas Schleinitz, Juliette Soret-Dulphy, Delphine Staumont-Salle, Benjamin Terrier, Louis Terriou, Jean-François Viallard, Guillaume Lefèvre, and Jean-Emmanuel Kahn

Subjects
Hypereosinophilia, Hypereosinophilic syndromes, Recommendation, Management, Medicine
Abstract

Abstract Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients’ association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

Published
2023
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24. Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

Author

Eric Gayon, Guillaume Lefèvre, Olivier Guerret, Adrien Tintar, and Pablo Chourreu

Subjects
catalysis, cross-coupling, insect pheromones, iron, Science, Organic chemistry, QD241-441
Abstract

In the current ecological context, use of insect sex pheromones as an alternative to conventional pesticides is in constant growth. In this report, we discuss the recent contributions brought by our groups in the field of iron-catalyzed cross-couplings applied to the synthesis of insect pheromones. The pivotal question of the development of sustainable synthetic procedures involving cheap, non-toxic and efficient additives is also discussed, as well as the mechanistic features guiding the reactivity of such catalytic systems.

Published
2023
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25. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

Author

David E. Newby, Alec Vahanian, Calvin W. L. Chin, Scott Ian Kay Semple, Nicholas L. Mills, Marc R. Dweck, David Messika-Zeitoun, Guillaume Lefevre, Emily Yeung, Maria Koo, Anoop S V Shah, Saeed Mirsadraee, Sophie Bailleul, and Tiffany Mathieu

Subjects
Male, Cardiac & Cardiovascular Systems, medicine.medical_treatment, 030204 cardiovascular system & hematology, RECOMMENDATIONS, DISEASE, 0302 clinical medicine, Valve replacement, PROGNOSTIC-SIGNIFICANCE, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, Prognosis, 3. Good health, Aortic valve stenosis, Cohort, Cardiology, HEART, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, AMERICAN-COLLEGE, Asymptomatic, Risk Assessment, 03 medical and health sciences, LEFT-VENTRICULAR HYPERTROPHY, Clinical Research, Internal medicine, medicine, Humans, Decompensation, Aged, Cardiovascular magnetic resonance imaging, High-sensitivity troponin I concentrations, Science & Technology, business.industry, Aortic stenosis, Myocardium, 1103 Clinical Sciences, Aortic Valve Stenosis, medicine.disease, Midwall myocardial fibrosis, Fibrosis, Survival Analysis, Confidence interval, VALVE STENOSIS, Stenosis, Cardiovascular System & Hematology, Electrocardiogram strain, MARKER, Heart failure, Valvular Heart Disease, Cardiovascular System & Cardiology, business, Magnetic Resonance Angiography
Abstract

Aims: Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis.Methods and results: One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score 57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001).Conclusion: We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement.

Published
2016

26. Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In Vivo

Author

Sandrine Placier, Chantal Jouanneau, David Legouis, Alexandre Hertig, Guillaume Lefevre, David Buob, Sophie Vandermeersch, Morgane Wetzstein, Naïke Bigé, Yi-Chun Xu-Dubois, Aurélien Bataille, Caroline Martin, Eric Rondeau, Juan L. Iovanna, Pierre Galichon, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de néphrologie et de transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie et hormonologie [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), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Cyclosporine/toxicity, Biology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephrotoxicity, 03 medical and health sciences, Mice, Neoplasm Proteins/genetics, Downregulation and upregulation, In vivo, Stress, Physiological, Cyclosporin a, Gene expression, medicine, Animals, Humans, ATF4, Kidney Diseases/chemically induced/genetics, General Medicine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Neoplasm Proteins, DNA-Binding Proteins, 030104 developmental biology, Basic Research, Nephrology, Apoptosis, Cancer research, Cyclosporine, Kidney Diseases, Cell activation, DNA-Binding Proteins/genetics
Abstract

International audience; Acute tubular damage is a major cause of renal failure, especially at the early phase of kidney transplant when ischemia-reperfusion injury and cyclosporin A toxicity may coexist. The mechanisms of the latter are largely unknown. Using an mRNA microarray on microdissected tubules from a rat model of cyclosporin A toxicity to describe the related epithelial-specific transcriptional signature in vivo, we found that cyclosporin A induces pathways dependent on the transcription factor ATF4 and identified nuclear protein transcriptional regulator 1 (Nupr1), a stress response gene induced by ATF4, as the gene most strongly upregulated. Upon cyclosporin A treatment, Nupr1-deficient mice exhibited worse renal tubular lesions than wild-type mice. In primary cultures treated with cyclosporin A, renal tubular cells isolated from Nupr1-deficient mice exhibited more apoptosis and ATP depletion than cells from wild-type mice. Furthermore, cyclosporin A decreased protein synthesis and abolished proliferation in wild-type tubular cells, but only reduced proliferation in Nupr1-deficient cells. Compared with controls, mouse models of ischemia-reperfusion injury, urinary obstruction, and hypertension exhibited upregulated expression of renal NUPR1, and cyclosporin A induced Nupr1 expression in cultured human tubular epithelial cells. Finally, immunohistochemical analysis revealed strong expression of NUPR1 in the nuclei of renal proximal tubules of injured human kidney allografts, but not in those of stable allografts. Taken together, these results suggest that epithelial expression of NUPR1 has a protective role in response to injury after renal transplant and, presumably, in other forms of acute tubular damage.

Published
2016

27. Prognostic value of PCT in septic emergency patients

Author

Guillaume Lefevre, Camille Chenevier-Gobeaux, Vianney Aquilina, Siham Ouahabi, Nicolas Peschanski, Patrick Ray, Lynda Mzabi, Valéry Brunel, Rémy Lucas, Department of Emergency Medicine, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Department of Automated Biological Diagnosis, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Laboratoire de biochimie générale [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Département Hospitalo-Universitaire Fight Ageing and STress (DHU FAST ), Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Normandie Université (NU)

Subjects
medicine.medical_specialty, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Prognostic, Procalcitonin, Sepsis, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Daily practice, Internal medicine, Anesthesiology, medicine, Elevated value, business.industry, Emergency department, Research, 030208 emergency & critical care medicine, Retrospective cohort study, medicine.disease, Predictive value, 3. Good health, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; Background: An accurate assessment of septic patients at risk for poor clinical outcomes is challenging for clinicians in the emergency department (ED).Objectives: We aimed to evaluate the prognostic value of procalcitonin (PCT) in septic patients in the ED for predicting death.Results: In a retrospective study, 188 septic patients (median age 63 [IQR 51–80]) of two French university hospitals were included. Patients who deceased within 30 days (20 %, n = 37) presented higher PCT value at admission (median 34.0 µg/L [5.0–71.9]) in comparison with the survivals (median 6.4 µg/L [4.1–13.1], p = 0.0005). ROC curve analysis indicated a moderate AUC of 0.686 [95 % CI 0.613–0.752] and an optimal PCT threshold value at 32.5 [95 % CI 21.8–43.3] µg/L that was associated with a 51 % [34–67] sensitivity, a 96 % [90–98] specificity, a 73 % [52–88] positive predictive value, and a 89 % [83–93] negative predictive value for death. Only 26 patients (14 %) had PCT values above this threshold (19 in the deceased group vs 7 in survival group, p < 0.0001). By multivariate analysis, only three variables remained significantly predictive of the death: personal history of cardiovascular disease (OR 3.1 [1.0–9.4], p = 0.046), the presence of severe sepsis/septic shock in the ER (OR 4.4 [1.3–12.3], p = 0.013), and a PCT level >32.5 µg/L (OR 36.0 [10.0–128.4], p < 0.0001). Similar results were obtained when considering the combined outcome death and/or admission in ICU.Conclusion: Elevated value of PCT at admission has moderate accuracy to identify poor outcome in ED septic patients in daily practice.

Published
2016

28. Angiogenic factors in preeclampsia: so complex, so simple?

Author

Nadia Berkane, Guillaume Lefevre, and Alexandre Hertig

Subjects
Vascular Endothelial Growth Factor A, HELLP Syndrome, medicine.medical_specialty, Pregnancy Proteins, chemistry.chemical_compound, Immune system, Pre-Eclampsia, Pregnancy, Transforming Growth Factor beta, Internal medicine, medicine, Humans, Placenta Growth Factor, Clinical Trials as Topic, Transplantation, Kidney, Vascular Endothelial Growth Factor Receptor-1, biology, business.industry, Chinese hamster ovary cell, Immunogenicity, Molecular biology, Sialic acid, Continuous erythropoietin receptor activator, Pregnancy Complications, medicine.anatomical_structure, Endocrinology, chemistry, Nephrology, Erythropoietin, biology.protein, Angiogenesis Inducing Agents, Female, Kidney Diseases, Antibody, business, medicine.drug
Abstract

Hoechst.htm 23. Cointe D, Beliard R, Jorieux S et al. Unusual N-glycosylation of a recombinant human erythropoietin expressed in a human lymphoblastoid cell line does not alter its biological properties. Glycobiology 2000; 10: 511–519 24. Shahrokh Z, Flatman S, Davies M, Baycroft A, Heartlein M. Erythropoietin produced by a human cell line has only trace levels of potentially immunogenic N-glycolylneuraminic acid residues. Haematologica 2006; 91 [S1]: 208 (Abstract) 25. Noguchi A, Mukuria CJ, Suzuki E et al. Immunogenicity of N-glycolylneuraminic acid-containing carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells. J Biochem (Tokyo) 1995; 117: 59–62 26. Tangvoranuntakul P, Gagneux P, Diaz S et al. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA 2003; 100: 12045–12050 27. Nguyen DH, Tangvoranuntakul P, Varki A. Effects of natural human antibodies against a nonhuman sialic acid that metabolically incorporates into activated and malignant immune cells. J Immunol 2005; 175: 228–236 28. Kwan JT, Pratt RD. Epoetin-d, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients. Curr Med Res Opin 2007; 23: 307–311 29. Spinowitz BS, Pratt RD. Epoetin-d is effective for the management of anaemia associated with chronic kidney disease. Curr Med Res Opin 2006; 22: 2507–2513 30. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 2001; 84: 3–10 31. Elliott S, Lorenzini T, Asher S et al. Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 2003; 21: 414–421 32. Jelkmann W. The enigma of the metabolic fate of circulating erythropoietin (Epo) in view of the pharmacokinetics of the recombinant drugs rhEpo and NESP. Eur J Haematol 2002; 69: 265–274 33. MacDougall IC. Novel erythropoiesis stimulating protein. Semin Nephrol 2000; 20: 375–381 34. Wish JB. The economic realities of erythropoiesis-stimulating agent therapy in kidney disease. Kidney Int 2006; 70: S21–S25 35. MacDougall IC. CERA (Continuous Erythropoietin Receptor Activator): a new erythropoiesis-stimulating agent for the treatment of anemia. Curr Hematol Rep 2005; 4: 436–440 36. SteadRB, Lambert J,WesselsD et al.Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers. Blood 2006; 108: 1830–1834 37. Kochendoerfer GG. Site-specific polymer modification of therapeutic proteins. Curr Opin Chem Biol 2005; 9: 555–560

Published
2007

29. Severe chronic primary neutropenia in adults: report on a series of 108 patients

Author

Sylvain P Chantepie, Despina Moshous, Norbert IFRAH, Didier Bouscary, Nicolas Cagnard, Catherine Paillard, Raphael Borie, Marlene Rio, Mohamad Mohty, HERVE CHAMBOST, Jean-Marie Michot, Nizar MAHLAOUI, Philippe Moreau, Eric Jeziorski, Sarah BEAUSSANT COHEN, Eric DECONINCK, Nicolas Schleinitz, Louis Terriou, Aurore Perrot, Mathilde Hunault, Elizabeth Anne Macintyre-Davi, Jean-Francois Schved, Olivier Hermine, Jean-francois BRASME, Guillaume LEFEVRE, Pierre S Rohrlich, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine] (Cnr-mat), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie clinique, Département d'Immunologie Clinique, Hopital Saint-Louis [AP-HP] (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire d'Immunologie, Service de Génétique Cytogénétique et Embryologie [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), Registre français des neutropénies chroniques sévères, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de référence des microangiopathies thrombotiques Paris, Service d'hématologie, CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), AP-HP Groupe Hospitalier Saint-Louis, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)

Subjects
Adult, Male, medicine.medical_specialty, Neutropenia, [SDV]Life Sciences [q-bio], Immunology, Clone (cell biology), Granulocyte, Biochemistry, Internal medicine, Granulocyte Colony-Stimulating Factor, medicine, Humans, Congenital Neutropenia, Autoantibodies, [ SDV ] Life Sciences [q-bio], business.industry, Autoantibody, Cell Biology, Hematology, medicine.disease, 3. Good health, Surgery, Granulocyte colony-stimulating factor, medicine.anatomical_structure, Absolute neutrophil count, Female, business, Primary neutropenia, Immunosuppressive Agents
Abstract

International audience; Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 109/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 109/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 109/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients

Published
2015

30. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies

Author

Alain Fischer, Johan Provot, Jean-Philippe Jais, Alexandre Alcais, Nizar Mahlaoui, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Philippe Arlet, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Beatrice Beaurain, Yves Bertrand, Boris Bienvenu, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Carolina Brito, Jacques Brouard, Emilie Catherinot, Olivia Chandesris, Sarah Cohen-Beaussant, Hélène Coignard-Biehler, Laurence Costes, Louis-Jean Couderc, Gérard Couillault, Virginie Courteille, Elodie Curlier, Geneviève de Saint Basile, François Demeocq, Nathalie de Vergnes, Catherine Devoldere, Anne Deville, Jean Donadieu, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Christine Edan, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sébastien Héritier, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Philippe Labrune, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Philippe Le Moine, Valérie Li Thiao Te, Olivier Lortholary, Patrick Lutz, Aude Magerus-Chatinet, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Odile Minckes, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Jean-Louis Pasquali, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Capucine Picard, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Marie Roger, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France (CdF), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Médecine expérimentale (A. Fischer), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Risk, 0301 basic medicine, Primary immunodeficiencies, Adolescent, T-Lymphocytes, Immunology, Population, Context (language use), medicine.disease_cause, Inflammatory bowel disease, Autoimmunity, Young Adult, 03 medical and health sciences, Prevalence, medicine, Humans, Immunology and Allergy, Age of Onset, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, education, Aged, Retrospective Studies, Aged, 80 and over, Autoimmune disease, Purpura, Thrombocytopenic, Idiopathic, education.field_of_study, business.industry, Common variable immunodeficiency, Autoimmune Cytopenia, autoimmunity, Immunologic Deficiency Syndromes, Infant, Middle Aged, Inflammatory Bowel Diseases, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030104 developmental biology, inflammation, Child, Preschool, Primary immunodeficiency, Female, France, business
Abstract

International audience; BACKGROUND:Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerable increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and immune diseases, including allergy, autoimmunity, and inflammation.OBJECTIVE:We aimed at determining the incidence of autoimmunity and inflammation in patients with PIDs.METHODS:We have retrospectively screened 2183 consecutive cases of PID in the Centre de Référence Déficits Immunitaires Héréditaires registry (CEREDIH; the French national PID registry) for the occurrence of autoimmunity and inflammation.RESULTS:One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient's lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children was 80 times higher, and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PIDs were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T-cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival.CONCLUSIONS:Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.

Published
2017

31. Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide

Author

Jérôme, Avouac, Christophe, Meune, Camille, Chenevier-Gobeaux, Didier, Borderie, Guillaume, Lefevre, André, Kahan, and Yannick, Allanore

Subjects
Adult, Aged, 80 and over, Male, Scleroderma, Systemic, Middle Aged, Peptide Fragments, Young Adult, Cross-Sectional Studies, Troponin T, Cardiovascular Diseases, Risk Factors, Natriuretic Peptide, Brain, Humans, Female, Biomarkers, Aged
Abstract

To measure plasma concentrations of high-sensitivity cardiac troponin T (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with systemic sclerosis (SSc; scleroderma) and age- and sex-matched healthy control subjects, and to examine the contribution of traditional cardiovascular risk factors and SSc features to the concentrations of these 2 cardiac biomarkers.Plasma HS-cTnT and NT-proBNP concentrations were measured using the electrochemiluminescence method and sandwich immunoassay, respectively.The study group comprised 161 unrelated patients with SSc and 213 matched control subjects. HS-cTnT and NT-proBNP plasma levels were significantly increased in SSc patients compared with controls (both P 0.001). Similar results were observed in the subgroup of patients with SSc who had no cardiovascular risk factors (n = 72). Multivariate logistic regression analysis confirmed diabetes mellitus (P = 0.006), high blood pressure (P = 0.021), precapillary pulmonary hypertension (P = 0.039), and the diffuse cutaneous SSc (P = 0.004) as factors independently associated with an HS-cTnT level of14 ng/liter. Increased NT-proBNP concentrations were associated only with the presence of precapillary pulmonary hypertension (P 0.001). Normal concentrations of both HS-cTnT and NT-proBNP had a high negative predictive value for precapillary pulmonary hypertension (92%), and the combination of increased values of these 2 markers had the highest strength of association with precapillary pulmonary hypertension in logistic regression analysis.HS-cTnT and NT-proBNP concentrations are increased in patients with SSc, even in those who are free of cardiovascular risk factors. These easily obtained biomarkers may be useful for systematic evaluation and stratification of SSc patients, especially to identify those at risk of pulmonary hypertension.

Published
2014

32. Activities of Clinical Expertise and Research in a Rare Disease Referral Centre: A Place for Telemedicine beyond the COVID-19 Pandemic?

Author

Quentin Ducrocq, Laurence Guédon-Moreau, David Launay, Louis Terriou, Sandrine Morell-Dubois, Hélène Maillard, Guillaume Lefèvre, Vincent Sobanski, Marc Lambert, Cécile Yelnik, Meryem-Maud Farhat, Maria José Garcia Fernandez, Eric Hachulla, and Sébastien Sanges

Subjects
telemedicine, telehealth, teleconsultation, tele-expertise, tele-trial, rare diseases, Medicine
Abstract

Introduction: Rare disease referral centres are entrusted with missions of clinical expertise and research, two activities that have to contend with numerous obstacles. Providing specialist opinions is time-consuming, uncompensated and limited by difficulties in exchanging medical data. Clinical research is constrained by the need for frequent research protocol visits. Our objective was to determine whether telemedicine (TLM) can overcome these difficulties. Methods: To better characterise the activity of clinical expertise provided by our French centre, each opinion delivered by our team was reported on a standardised form. To investigate our clinical research activity, investigators and patients were asked to complete a questionnaire on the acceptability of research protocol teleconsultations. Results: Regarding clinical expertise, our team delivered 120 opinions per week (representing a total of 21 h), of which 29% were delivered to patients and 69% to medical practitioners. If these were delivered using TLM, it would represent a potential weekly income of EUR 500 (tele-expertise) and EUR 775 (teleconsultations). Regarding the research activity, 70% of investigators considered the frequency of visits to be a limiting factor for patient inclusions; nearly half of the patients surveyed would be in favour of having teleconsultations in place of (40%) or in addition to (56%) in-person visits. Conclusion: Whereas TLM has become widely used as a back-up procedure to in-person consultations during the COVID-19 pandemic, the solutions it provides to the problems encountered in performing expertise and research activities have made it a new conventional follow-up modality for patients with rare diseases.

Published
2023
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33. [Value of biological markers in cardiovascular disease]

Author

Rémy, Couderc, Guillaume, Lefevre, and Jean-Noël, Fiessinger

Subjects
C-Reactive Protein, Cardiovascular Diseases, Natriuretic Peptide, Brain, Humans, Biomarkers, Peptide Fragments, Troponin, Apolipoproteins B
Published
2012

34. Analytical evaluation of a high-sensitivity troponin T assay and its clinical assessment in acute coronary syndrome

Author

Marie-Céline Blanc, Guillaume Lefevre, Patrick Jaffray, Christophe Meune, Camille Chenevier-Gobeaux, and Luc Cynober

Subjects
Adult, Male, medicine.medical_specialty, Acute coronary syndrome, Pathology, Cardiac troponin, Clinical Biochemistry, Young Adult, Troponin T, Limit of Detection, Reference Values, Internal medicine, medicine, Humans, cardiovascular diseases, Myocardial infarction, Acute Coronary Syndrome, Diagnostic Techniques and Procedures, Aged, Aged, 80 and over, Immunoassay, medicine.diagnostic_test, business.industry, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, Highly sensitive, Reference values, Luminescent Measurements, cardiovascular system, Cardiology, Female, business, Troponin T Assay
Abstract

Background The recently developed, highly sensitive cardiac troponin T (hs-cTnT) immunoassay improves the detection of acute myocardial infarction (AMI). However, this assay requires further analytical and clinical evaluation. Methods Imprecision, linearity, limits of quantification and interferences were evaluated; hs-cTnT was compared with a conventional cardiac troponin I assay (cTnI), performed on an X-pand®HM, in a population of patients with suspected AMI. Finally, the 99th percentile cut-off point for a reference population was explored in 213 healthy control subjects. Results Imprecision analysis demonstrated coefficients of variation (CVs) below 4%, linearity showed a 0.999 coefficient of correlation, with excellent recovery (99.9%) and a limit of quantification (10%CV) was found at 9.2 ng/L. A negative interference (>20%) with haemolysis was observed when supplemental haemoglobin was above 0.25 g/dL. Patients with suspected AMI more frequently displayed an increased hs-cTnT (83%) than an increased cTnI (55%, P < 0.01). Unstable angina was present in 63% of patients with an increased hs-cTnT associated with no increase in cTnI. The 99th percentile value for our reference population was 16.9 ng/L. In 213 healthy blood donors, hs-cTnT levels were significantly correlated with age ( P < 0.0001), and were higher in men than in women ( P < 0.0001). Conclusions The analytical performance of hs-cTnT complied with the international guidelines for AMI detection. Determining the degree of haemolysis in a sample is of paramount importance to the interpretation of hs-cTnT results. The 99th percentile value of our reference population was established.

Published
2011

35. Case report: Changes in the levels of stress hormones during Takotsubo syndrome

Author

Pablo Ruiz, Paul Gabarre, Camille Chenevier-Gobeaux, Hélène François, Mathieu Kerneis, John A. Cidlowski, Robert H. Oakley, Guillaume Lefèvre, and Mathieu Boissan

Subjects
cortisol, copeptin, cardiac biomarkers, Takotsubo syndrome, case report, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundTakotsubo syndrome is an acute cardiac condition usually involving abnormal regional left ventricular wall motion and impaired left ventricular contractility. It is due mainly to hyper-stimulation of the sympathetic nerve system, inducing an excess of catecholamines, usually triggered by intense psychological or physiological stress. The relationship between Takotsubo syndrome and the circulating stress hormones cortisol and copeptin (a surrogate marker of arginine vasopressin) has not been well documented.Case summaryHere, we describe the dynamic changes in circulating cortisol and copeptin during an entire episode of Takotsubo syndrome in a post-partum woman after spontaneous vaginal delivery. The patient was diagnosed with inverted Takotsubo syndrome accompanied by HELLP syndrome. We found qualitative and quantitative changes in cortisol: a loss of circadian rhythm and a three-fold elevation in the plasma concentration of the hormone with a peak appearing several hours before circulating cardiac biomarkers began to rise. By contrast, levels of copeptin remained normal during the entire episode.DiscussionOur findings indicate that the levels of cortisol change during Takotsubo syndrome whereas those of copeptin do not. This association between elevated cortisol and Takotsubo syndrome suggests that aberrant levels of this stress hormone may contribute to the observed cardiac pathology. We conclude that biochemical assays of circulating cortisol and cardiac biomarkers may be a useful complement to the diagnosis of Takotsubo syndrome by non-invasive cardiac imaging.

Published
2022
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36. Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension

Author

Sébastien Sanges, Thomas Guerrier, Alain Duhamel, Lucile Guilbert, Carine Hauspie, Alexis Largy, Maïté Balden, Céline Podevin, Guillaume Lefèvre, Manel Jendoubi, Silvia Speca, Éric Hachulla, Vincent Sobanski, Sylvain Dubucquoi, and David Launay

Subjects
systemic sclerosis, pulmonary arterial hypertension, B cell, humoral immunity, angiogenesis, pro-angiogenic factors, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionSoluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.Methods1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.ResultsIn a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.ConclusionSoluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.

Published
2022
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37. Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years

Author

Enagnon Kazali Alidjinou, Julie Demaret, Bénédicte Corroyer-Simovic, Julien Labreuche, Anne Goffard, Jacques Trauet, Daniela Lupau, Sophie Miczek, Fanny Vuotto, Arnaud Dendooven, Dominique Huvent-Grelle, Juliette Podvin, Daniel Dreuil, Karine Faure, Dominique Deplanque, Laurence Bocket, Alain Duhamel, Annie Sobaszek, Didier Hober, Michael Hisbergues, Francois Puisieux, Brigitte Autran, Yazdan Yazdanpanah, Myriam Labalette, and Guillaume Lefèvre

Subjects
BNT162b2 vaccine, Boost, SARS-CoV-2, Delta, Omicron, Older people, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents. Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered). Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p

Published
2022
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38. Diagnostic value of procalcitonin in acutely hospitalized elderly patients

Author

Olivier Steichen, Jacqueline Capeau, Eric Bouvard, Guillaume Lefevre, Gilles Grateau, Sophie Bailleul, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie et hormonologie [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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Calcitonin, Male, Microbiology (medical), medicine.medical_specialty, Calcitonin Gene-Related Peptide, Diagnostic accuracy, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Procalcitonin, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Older patients, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Protein Precursors, Prospective cohort study, Intensive care medicine, Aged, Aged, 80 and over, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Bacterial Infections, General Medicine, 3. Good health, Hospitalization, Infectious Diseases, Female, business, Biomarkers
Abstract

International audience; The aim of this study was to evaluate procalcitonin as an adjunct to diagnose bacterial infections in older patients. One hundred seventy-two patients admitted to an acute-care geriatric unit during a 6-month period were prospectively included, 39 of them with an invasive bacterial infection. The best cut-off value to rule in a bacterial infection was 0.51 µg/l with sensitivity 64% and specificity 94%. The best cut-off value to rule out a bacterial infection was 0.08 µg/l with sensitivity 97% and specificity 20%. Procalcitonin was inconclusive (between 0.08 and 0.51 µg/l) for 112 admissions. Procalcitonin over 0.51 µg/l was useless 22 times out of 33 (infection already ruled in on clinical grounds) and misleading in eight of the 11 remaining cases (no infection). Procalcitonin below 0.08 µg/l was useless 23 times out of 27 (infection already ruled out on clinical grounds) and misleading in one of the four remaining cases (infection). Despite a good overall diagnostic accuracy, the clinical usefulness of PCT to diagnose invasive bacterial infections in elderly patients hospitalized in an acute geriatric ward appears to be very limited.

Published
2009

39. Inverted Takotsubo Syndrome With HELLP Syndrome: A Case Report

Author

Paul Gabarre, Pablo Ruiz, Camille Chenevier-Gobeaux, Etienne Charpentier, Laurie Soulat-Dufour, Ariel Cohen, Laurence Monnier-Cholley, Lotfi Chemali, Hélène François, Mathieu Kerneis, Guillaume Lefèvre, and Mathieu Boissan

Subjects
troponin T, troponin I, NT-proBNP, Takotsubo, HELLP syndrome, pregnancy, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundTakotsubo syndrome is an acute cardiac condition involving sudden, transient apical ballooning of the left ventricle of the heart that may be triggered by emotional stress and some non-cardiac conditions. Its diagnosis is based on clinical presentation, electrocardiogram, cardiac imaging and biomarkers.Case SummaryHere, we present a novel and original case report of a patient presenting very soon in the post-partum period with an unusual form of Takotsubo syndrome without clinical symptoms of cardiac disease and accompanied by HELLP syndrome. The overall dynamics of the changes in troponin I, troponin T and NT-proBNP levels after delivery were generally similar, but the amount of troponin I was much greater than that of troponin T and troponin I was already elevated before delivery. NT-proBNP levels peaked around the same time as the troponins and the peak concentration was within the same range as that of troponin I.DiscussionOur findings indicate that assaying circulating cardiac biomarkers, especially troponin I and NT-proBNP, may be a useful complement to non-invasive cardiac imaging including transthoracic echocardiography and cardiovascular magnetic resonance imaging, in the diagnosis of Takotsubo syndrome. They illustrate the importance of cardiac biomarkers in assisting diagnosis of this disease.

Published
2022
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40. Multicenter evaluation of analytical performance of the Liaison troponin I assay

Author

Jean-Paul Chapelle, Jutta Engelmayer, Franca Pagani, Mauro Panteghini, Hilmar Luthe, Francesca Stefini, Guillaume Lefevre, and Hanafi Graine

Subjects
Adult, Male, 030213 general clinical medicine, Clinical Biochemistry, Analytical chemistry, macromolecular substances, 030204 cardiovascular system & hematology, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, 99th percentile, Troponin I, medicine, Humans, Aged, Detection limit, Aged, 80 and over, Immunoassay, Chromatography, Liaison, medicine.diagnostic_test, business.industry, Healthy subjects, General Medicine, Middle Aged, musculoskeletal system, Sample stability, 3. Good health, Reference values, cardiovascular system, Linear Models, Female, business
Abstract

Objectives: This study evaluated the analytical characteristics of the LiaisonR immunoassay for cardiac troponin I (cTnI). Design and methods: The protocol consisted of eight sections: evaluation of antibody specificity, linearity, detection limit and imprecision, method comparison, evaluation of endogenous interferents, anticoagulant interference, sample stability, and reference values. Results: The assay equally measured free and complexed cTnI. The minimum detectable cTnI concentration was 0.021 Ag/l. The cTnI concentration corresponding to a total CVof 10% was 0.056 Ag/l. Linearity of response was demonstrated along the entire dynamic range of the assay. Assay interferences were minimal. cTnI concentrations in serum and heparinized plasma were significantly different. Values in EDTA plasma were on average approximately 5% higher than in matched serum, but this difference was not significant. The 99th percentile cTnI value in healthy subjects was 0.036 Ag/l. Conclusions: Being sensitive, specific, and precise, the LiaisonR cTnI assay meets current requirements to aid in the diagnosis of myocardial necrosis. D 2004 The Canadian Society of Clinical Chemists. All rights reserved.

Published
2004

41. Evaluation of kryptor cardiac troponin I immunoassay

Author

Ginette Marlin, Hanafi Graine, Guillaume Lefevre, Eric Garbarz, Pierre Louis Michel, Jacqueline Capeau, and Karim Bakkouch

Subjects
Adult, Male, medicine.medical_specialty, Digoxin, Adolescent, medicine.drug_class, Clinical Biochemistry, Myocardial Infarction, macromolecular substances, Sensitivity and Specificity, Internal medicine, Troponin I, medicine, Rheumatoid factor, Humans, cardiovascular diseases, Myocardial infarction, Aged, Aged, 80 and over, Immunoassay, Aspirin, medicine.diagnostic_test, business.industry, Myocardium, Anticoagulant, General Medicine, Middle Aged, musculoskeletal system, medicine.disease, Endocrinology, cardiovascular system, Cardiology, Female, Myocardial infarction diagnosis, business, Biomarkers, medicine.drug
Abstract

Background and Methods: Cardiac troponin I (cTnI) is well recognized as a specific marker for myocardial infarction. A fully automated, random access, fluorescent immunoassay for cTnI was evaluated in comparison with an established assay (Stratus cTnI) using samples from healthy subjects and from patients with cardiac disease. Results: The detection and precision were acceptable, and no interference was observed from bilirubin, triglycerides, haemoglobin, rheumatoid factor, drugs (aspirin, dopamine, digoxin) or heparin. Results on the Kryptor cTnI assay correlated with those on the Stratus II cTnI assay. The optimum Kryptor cTnI concentration for acute myocardial infarction was 0.63 µg/L, with a sensitivity of 89% [95% confidence interval (CI): 75.9-96.3] and specificity of 98.9% (95% CI: 93.9-99.8). Conclusion: Kryptor cTnI immunoassay is suitable for use in the diagnosis of myocardial infarction.

Published
2002

42. Influence of protein composition on total urinary protein determined by pyrocatechol-violet (UPRO vitros) and pyrogallol red dye binding methods

Author

Sylvie Bloch, Sylvain Arien, Thierry Le Bricon, Guillaume Lefevre, Sylviane Billier, and Jacqueline Capeau

Subjects
Microbiology (medical), Globulin, Pyrogallol red, Clinical Biochemistry, Pyrogallol, Sensitivity and Specificity, chemistry.chemical_compound, medicine, Immunology and Allergy, Humans, Sodium dodecyl sulfate, Coloring Agents, Serum Albumin, Molybdenum, Chromatography, Proteinuria, biology, Biochemistry (medical), Benzenesulfonates, Public Health, Environmental and Occupational Health, Albumin, Sodium Dodecyl Sulfate, Serum Albumin, Bovine, Hematology, Protein composition, Original Articles, Bence Jones protein, Solutions, Medical Laboratory Technology, chemistry, biology.protein, gamma-Globulins, medicine.symptom, Multiple Myeloma, Bence Jones Protein
Abstract

Influence of protein composition on total urinary protein assays was evaluated for pyrogallol red‐molybdate both with and without sodium dodecyl sulfate (SDS) and pyrocatechol violet‐molybdate complex (UPRO) techniques. Using mixtures of albumin and γ‐globulins (n = 8; albumin/globulin ratio, 0 to 10), mean recoveries were 79, 77, and 81% for pyrogallol red, pyrogallol red‐SDS, and UPRO, respectively. Using diluted myeloma sera (n = 26; A/G ratio, 0.39 to 2.35), mean recovery by the UPRO method was 115% (vs. 63% for pyrogallol red and 83% pyrogallol red‐SDS). Results positively correlated with A/G ratio for UPRO (r = 0.69; P < 0.001), pyrogallol red (r = 0.48; P < 0.05), but not pyrogallol red‐SDS (r = 0.191; NS). The difference between UPRO and pyrogallol red assays correlated with the A/G ratio (r = 0.82; P < 0.001). In light chain proteinuria (n = 10), no significant difference (< 15%) was observed between techniques, whereas in glomerular selective proteinuria (n = 10), values were significantly higher with the UPRO assay (2.20 ± 1.61 vs. 1.43 ± 1.10 g/L; P < 0.02). Our results support the idea that screening for renal diseases can be performed with UPRO or pyrogallol red assays. However, since A/G ratios may vary with renal disease evolution, follow‐up of patients with positive proteinuria should be performed using the same assay, preferably the pyrogallol red‐SDS. J. Clin. Lab. Anal. 15:40–42, 2001. © 2001 Wiley‐Liss, Inc.

Published
2001

43. Exercise does not induce oxidative stress in trained heart transplant recipients

Author

Michel Rieu, Ruddy Richard, Liliana Jimenez, Guillaume Lefevre, and Alain Duvallet

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Physical Therapy, Sports Therapy and Rehabilitation, Physical exercise, Incremental exercise, Lipid peroxidation, chemistry.chemical_compound, Oxygen Consumption, Internal medicine, Malondialdehyde, medicine, Humans, Vitamin E, Orthopedics and Sports Medicine, Exercise physiology, Exercise, chemistry.chemical_classification, business.industry, Glutathione peroxidase, Middle Aged, Transplantation, Oxidative Stress, Endocrinology, chemistry, Exercise Test, Heart Transplantation, Lipid Peroxidation, business
Abstract

PURPOSE: The objectives of this study were twofold: 1) to determine the effect of incremental exercise to volitional fatigue on plasma levels of lipid peroxidation (malondialdehyde) in heart transplant recipients (HRT) and 2) to examine blood antioxidant capacity in HTR by assessment of antioxidant enzyme activities and vitamin E levels. METHODS: Seven endurance-trained HTR (mean +/- SD; age 39.7 +/- 12.8 yr) and seven endurance-trained healthy, age-matched control subjects (HC) (mean age 40.6 +/- 10.7 yr) performed a symptom-limited incremental exercise test on a cycle ergometer. Venous blood samples were obtained at rest, exercise, and during recovery and analyzed for plasma levels of malondialdehyde (MDA) as well as markers of blood antioxidant capacity. After exercise and during recovery, all dependent measures were corrected for plasma volume changes induced by exercise. Significance was established at (P < 0.05). RESULTS: No group differences existed in plasma levels of MDA at rest. Further, graded exercise did not alter plasma levels of MDA in either group. Resting erythrocyte glutathione peroxidase (GPX) activity was significantly lower and erythrocyte superoxide dismutase (SOD) activity was higher in HTR compared with HC. Finally, at rest, no group differences existed in plasma GPX activity or vitamin E levels. CONCLUSIONS: Graded exercise to fatigue does not promote an increase in oxidative stress in blood of exercise trained HTR. Therefore, physical exercise does not appear to pose an oxidative-stress risk for these patients.

Published
2000

44. Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People

Author

Julie Demaret, Bénédicte Corroyer-Simovic, Enagnon Kazali Alidjinou, Anne Goffard, Jacques Trauet, Sophie Miczek, Fanny Vuotto, Arnaud Dendooven, Dominique Huvent-Grelle, Juliette Podvin, Daniel Dreuil, Karine Faure, Dominique Deplanque, Laurence Bocket, Alain Duhamel, Julien Labreuche, Annie Sobaszek, Michael Hisbergues, Francois Puisieux, Myriam Labalette, and Guillaume Lefèvre

Subjects
SARS – CoV – 2, vaccine, older people and ageing, T cells response, mRNA vaccination, Immunologic diseases. Allergy, RC581-607
Abstract

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p

Published
2021
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45. Maternal Serum sFlt1 Concentration Is an Early and Reliable Predictive Marker of Preeclampsia

Author

Alexandre Hertig, Nadia Berkane, Eric Rondeau, Serge Uzan, Hans-Peter Marti, Jacqueline Capeau, Guillaume Lefevre, and Karine Toumi

Subjects
Placental growth factor, medicine.medical_specialty, Pregnancy Complications, Cardiovascular, Clinical Biochemistry, Sensitivity and Specificity, Preeclampsia, chemistry.chemical_compound, Pre-Eclampsia, Predictive Value of Tests, Pregnancy, Internal medicine, Placenta, medicine, Humans, Extracellular Matrix Proteins, Fetus, Predictive marker, business.industry, Biochemistry (medical), medicine.disease, Pathophysiology, Vascular endothelial growth factor, medicine.anatomical_structure, Endocrinology, chemistry, Hypertension, Female, business
Abstract

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. It occurs in two phases: abnormal implantation of the placenta leads to impaired placental blood flow, which in turn induces the release of a critical placental substance into the maternal circulation (1). Clinical onset usually occurs in the third trimester of pregnancy, long after initiation of the underlying process. Recently, Maynard et al. (2) compared the gene expression profile in placental tissue from women with and without preeclampsia and identified soluble Flt1 (sFlt1), a vascular endothelial growth factor receptor, as a molecule of particular pathophysiologic interest. It is now suspected that trophoblastic injury markedly enhances placental sFlt1 production, antagonizing the endothelial protective role of vascular endothelial growth factor and/or placental growth factor and eventually leading to clinical preeclampsia (2)(3). A recent study pointed out that, compared with women with a retrospective diagnosis of normal pregnancy (i.e., without hypertension), preeclamptic women had increased serum sFlt1 several weeks before the onset of clinical disease, …

Published
2004

46. Cardiac troponin I release after dobutamine stress echocardiography in patients with coronary artery disease

Author

Antoine Flahaut, Guillaume Lefevre, Eric Garbarz, David Messika-Zeitoun, Mathieu Poupineau, Bernard Iung, and Michel Pl

Subjects
Coronary artery disease, medicine.medical_specialty, Cardiac troponin, business.industry, Dobutamine stress echocardiography, Internal medicine, medicine, Cardiology, In patient, Cardiology and Cardiovascular Medicine, medicine.disease, business
Published
2003

47. Severe SARS‐CoV‐2 patients develop a higher specific T‐cell response

Author

Julie Demaret, Guillaume Lefèvre, Fanny Vuotto, Jacques Trauet, Alain Duhamel, Julien Labreuche, Pauline Varlet, Arnaud Dendooven, Sarah Stabler, Benoit Gachet, Jules Bauer, Brigitte Prevost, Laurence Bocket, Enagnon Kazali Alidjinou, Marc Lambert, Cécile Yelnik, Bertrand Meresse, Laurent Dubuquoy, David Launay, Sylvain Dubucquoi, David Montaigne, Eloise Woitrain, François Maggiotto, Mohamed Bou Saleh, Isabelle Top, Vincent Elsermans, Emmanuelle Jeanpierre, Annabelle Dupont, Sophie Susen, Thierry Brousseau, Julien Poissy, Karine Faure, Myriam Labalette, and the Lille Covid Research Network (LICORNE)

Subjects
ELISpot, SARS‐CoV‐2, T cells, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response.

Published
2020
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48. An updated evaluation of serum sHER2, CA15.3, and CEA levels as biomarkers for the response of patients with metastatic breast cancer to trastuzumab-based therapies.

Author

Alexandre Perrier, Pierre-Yves Boelle, Yves Chrétien, Joseph Gligorov, Jean-Pierre Lotz, Didier Brault, Eva Comperat, Guillaume Lefèvre, and Mathieu Boissan

Subjects
Medicine, Science
Abstract

BACKGROUND:The transmembrane receptor tyrosine kinase HER2 is overexpressed in approximately 15% of breast tumors and correlates with poor clinical prognosis. Several treatments that target HER2 are approved for treatment of HER2-positive metastatic breast cancer. The serum biomarkers most widely used to monitor anti-HER2 therapies in patients with HER2-positive metastatic breast cancer currently are CA15.3 and CEA. Nevertheless, their clinical utility in patients with breast cancer remains a subject of discussion and controversy; thus, additional markers may prove useful in monitoring the therapeutic responses of these patients. The extracellular domain of HER2 can be shed by proteolytic cleavage into the circulation and this shed form, sHER2, is reported to be augmented during metastasis of HER2-positive breast tumors. Here, we studied the clinical usefulness of sHER2, CA15.3, and CEA for monitoring treatment for breast cancer. METHODS:We measured prospectively pretreatment and post-treatment serum levels (day 1, 30, 60 and 90) of these three biomarkers in 47 HER2-positive, metastatic breast cancer patients treated with trastuzumab in combination with paclitaxel. Evaluation of the disease was performed according to the Response Evaluation Criteria in Solid Tumor (RECIST) at day 90. RESULTS:Patients with progressive disease at day 90 had smaller relative changes between day 1 and day 30 than those with complete, partial or stable responses at day 90: -9% versus -38% for sHER2 (P = 0.02), +23% versus -17% for CA15.3 (P = 0.005) and +29% versus -26% for CEA (P = 0.02). Patients with progressive disease at day 90 were less likely than the other patients to have a relative decrease of > 20% in their biomarker levels at day 30: 6% vs 33% for sHER2 (P = 0.03), 0% vs 27% for CA15.3 (P = 0.03), 4% vs 29% for CEA (P = 0.04). No patient with progressive disease at day 90 had > 20% reduction of the average combined biomarker levels at day 30 whereas 63% of the other patients had (P = 0.003). Moreover, when we analyzed a > 10% reduction of the average biomarker levels no patient with progressive disease at day 90 had a decrease > 10% at day 30 whereas 78% of other patients had (P 10% appears to be the best parameter to distinguish patients who go on to have progressive disease from those who will have a complete, partial or stable response.

Published
2020
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49. Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database

Author

Quentin Scanvion, Johana Béné, Sophie Gautier, Aurélie Grandvuillemin, Christine Le Beller, Chouki Chenaf, Nicolas Etienne, Solenn Brousseau, Alexis B. Cortot, Laurent Mortier, Delphine Staumont-Sallé, Franck Morschhauser, Alexandra Forestier, Matthieu Groh, David Launay, Eric Hachulla, Myriam Labalette, Jean-Emmanuel Kahn, and Guillaume Lefèvre

Subjects
eosinophilia, immune-related adverse events, emergent adverse event, immune checkpoint inhibitors, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median [range] time to the absolute eosinophil count (AEC) peak was 15 [4─139] weeks. The median AEC was 2.7 [0.8─90.9] G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.

Published
2020
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50. Multi-centre evaluation of recent troponin assays for the diagnosis of NSTEMI

Author

Camille Chenevier-Gobeaux, Louis Deweerdt, Anne-Valérie Cantero, Bertrand Renaud, Bruno Desmaizières, Sandrine Charpentier, Aline Leroy, Emmanuelle Adelaïde, Delphine Collin-Chavagnac, Eric Bonnefoy-Cudraz, Laurence Estepa, Akli Chekroune, Sylvie Basco, Stéphane Andrieu, Stéphane Bourgeois, Marie-Agnès Costa, Christine Vallejo, Tiphaine Robert, Siham Ouahabi, Bruno Baudin, Benedicte Beneteau-Burnat, Anne-Marie Gorce-Dupuy, Patrick Ray, Claire Gast, Monique Dehoux, and Guillaume Lefèvre

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

Objectives: We aimed to compare the use of nine different cardiac troponin (cTn) assays (2 cTnT and 7 cTnI) for the diagnosis of NSTEMI in a single multi-centre population. Design and methods: One hundred and fifty-eight patients were included (mean age 60 years, SD 17 years), including 23 patients (14%) with NSTEMI. Results: The analytical comparison highlighted a large heterogeneity of cTn assays, as reflected by percentages of patients with detectable cTn, correlation coefficients, Passing-Bablok comparisons and concordance coefficients. Correlations within cTnI assays were good and correlation within cTnT assays was excellent. Diagnostic performances demonstrated that each cTn assay has specific threshold values. Furthermore, some assays (HS-cTnI and T, cTnI-Pathfast and cTnI-Centaur) indicated high sensitivity and negative predictive value using the limit of detection (LoD) diagnostic strategy. For the latter assays, a significant increase in specificity was found when using the 99th percentile or the H0-H3 strategies, in comparison to the LoD strategy. When applying the European Society of Cardiology H0-H3 algorithm, comparable diagnostic performances were obtained. Conclusion: All 9 cTn assays indicated overall good diagnostic performances for the diagnosis of NSTEMI in emergency departments when the recommended algorithm based on the variation of cTn value between two measurements at admission and 3 h later was used. Keywords: Cardiac troponin, High-sensitivity assay, Chest pain, Emergency department, NSTEMI, Analytical evaluation

Published
2018
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