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1. Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors

Author

Alice Blet, Joel B. McNeil, Julie Josse, Bernard Cholley, Raphaël Cinotti, Gad Cotter, Agnès Dauvergne, Beth Davison, Kévin Duarte, Jacques Duranteau, Marie-Céline Fournier, Etienne Gayat, Samir Jaber, Sigismond Lasocki, Thomas Merkling, Katell Peoc’h, Imke Mayer, Malha Sadoune, Pierre-François Laterre, Romain Sonneville, Lorraine Ware, Alexandre Mebazaa, and Antoine Kimmoun

Subjects
Transfusion, Mortality, Critical care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. Methods FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. Results Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45–2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06–1.46). Conclusions Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration ( NCT01367093 ; Registered 6 June 2011). Graphic Abstract

Published
2022
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2. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study

Author

Alice Blet, Benjamin Deniau, Karine Santos, Dirk P. T. van Lier, Feriel Azibani, Xavier Wittebole, Benjamin G. Chousterman, Etienne Gayat, Oliver Hartmann, Joachim Struck, Andreas Bergmann, Massimo Antonelli, Albertus Beishuizen, Jean-Michel Constantin, Charles Damoisel, Nicolas Deye, Salvatore Di Somma, Thierry Dugernier, Bruno François, Stephane Gaudry, Vincent Huberlant, Jean-Baptiste Lascarrou, Gernot Marx, Emmanuelle Mercier, Haikel Oueslati, Peter Pickkers, Romain Sonneville, Matthieu Legrand, Pierre-François Laterre, Alexandre Mebazaa, and AdrenOSS-1 Study Investigators

Subjects
DPP3, Biomarker, Outcome, Sepsis, Septic shock, Organ dysfunction, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients. Methods The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later. Results Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2–40.4] ng/mL. Initial SOFA score was 7 [5–10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6–2.1]; adjusted HR 1.5 [CI 1.3–1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality. Conclusions Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

Published
2021
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3. Positive effects of lumbar puncture simulation training for medical students in clinical practice

Author

Sinead Gaubert, Alice Blet, Fadia Dib, Pierre-François Ceccaldi, Thomas Brock, Maude Calixte, Léa De Macédo, Tiphaine Dujardin, Ludivine Jean-Louis, Dhihia Leghima, Samuel Mouyal, Dan David Tordjman, Patrick Plaisance, Caroline Roos, Sid-Ahmed Remini, Damien Roux, and Claire Paquet

Subjects
Lumbar puncture, Simulation training, Clinical skills, Medical education, Medical student, Special aspects of education, LC8-6691, Medicine
Abstract

Abstract Background Lumbar puncture (LP) is an invasive medical procedure that can be done by any doctor. Several simulation-based trainings have been built however the evaluations of the theoretical knowledge and the impact of the simulation-based training have never been performed in real life. The objective was to evaluate the impact of a LP training on the theoretical knowledge improvement and the performance of a LP in clinical practice. Methods Before and after medical students’ training, theoretical knowledge and confidence level were assessed. Over a 6 months period, the impact of simulation training was evaluated by the success rate of students’ first LP carried out in hospitalized patients and compared to the results of a no-training control. Results Students’ theoretical knowledge and confidence level showed significant improvement after simulation training on 115 students (p

Published
2021
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6. A novel urinary biomarker predicts 1-year mortality after discharge from intensive care

Author

Esther Nkuipou-Kenfack, Agnieszka Latosinska, Wen-Yi Yang, Marie-Céline Fournier, Alice Blet, Blerim Mujaj, Lutgarde Thijs, Elodie Feliot, Etienne Gayat, Harald Mischak, Jan A. Staessen, Alexandre Mebazaa, Zhen-Yu Zhang, and The French and European Outcome Registry in Intensive Care Unit Investigators

Subjects
Biomarker, Intensive care medicine, Heart failure, Mortality, Urinary proteomics, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Rationale The urinary proteome reflects molecular drivers of disease. Objectives To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality. Methods In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses. Measurements and main results In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708–0.798) and 0.688 (0.656–0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00–2.91) for ACM128 (+ 1 SD), 1.24 (1.16–1.32) for the Charlson Comorbidity Index (+ 1 point), and ≥ 1.19 (P ≤ 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P ≤ 0.0001) IDI (≥ + 0.50), NRI (≥ + 53.7), and AUC (≥ + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis. Conclusions The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.

Published
2020
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7. Adrecizumab, a non-neutralizing anti-adrenomedullin antibody, improves haemodynamics and attenuates myocardial oxidative stress in septic rats

Author

Alice Blet, Benjamin Deniau, Christopher Geven, Malha Sadoune, Anaïs Caillard, Paul-Robert Kounde, Evelyne Polidano, Peter Pickkers, Jane-Lise Samuel, and Alexandre Mebazaa

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Sepsis still represents a major health issue, with persistent high morbidity and mortality rates. Cardiovascular dysfunction occurs frequently during sepsis. Adrenomedullin has been identified as a key mediator in vascular tone regulation. A non-neutralizing anti-adrenomedullin antibody, Adrecizumab, may improve haemodynamic dysfunction during caecal ligation and puncture-induced septic shock in a murine model. Our objective was to determine the role of Adrecizumab on haemodynamics in a rat model of sepsis. Methods For the induction of sepsis, caecal ligation and puncture were performed in Wistar male rats. Single blinded administration of Adrecizumab (2 mg/kg) or placebo was injected i.v. 24 h after the surgery, and norepinephrine was infused as the standard of care. There were > 7 animals per group. Invasive blood pressure and cardiac function (by echocardiography) were assessed until 3 h after Adrecizumab injection. Results A single therapeutic injection of Adrecizumab in septic rats induced rapid haemodynamic benefits with an increase in systolic blood pressure in septic-Adrecizumab rats versus untreated-septic rats (p = 0.049). The shortening fraction did not differ between the untreated-septic and septic-Adrecizumab groups. However, cardiac output increased during the 3 h after a single dose of Adrecizumab compared to untreated septic rats (p = 0.006). A single dose of Adrecizumab resulted in similar haemodynamics to the continuous administration of norepinephrine. Three hours after a single injection of Adrecizumab, there was no change in the inflammatory phenotype (TNFα, IL-10) in the hearts of the septic rats. By contrast, 3 h after a single Adrecizumab injection, free-radical production decreased in the hearts of septic-Adrecizumab vs untreated septic rats (p

Published
2019
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8. Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Author

Alexandre Mebazaa, Christopher Geven, Alexa Hollinger, Xavier Wittebole, Benjamin Glen Chousterman, Alice Blet, Etienne Gayat, Oliver Hartmann, Paul Scigalla, Joachim Struck, Andreas Bergmann, Massimo Antonelli, Albertus Beishuizen, Jean-Michel Constantin, Charles Damoisel, Nicolas Deye, Salvatore Di Somma, Thierry Dugernier, Bruno François, Stephane Gaudry, Vincent Huberlant, Jean-Baptiste Lascarrou, Gernot Marx, Emmanuelle Mercier, Haikel Oueslati, Peter Pickkers, Romain Sonneville, Matthieu Legrand, Pierre-François Laterre, and AdrenOSS-1 study investigators

Subjects
Biomarker, Outcome, Sepsis-2, Sepsis-3, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5–148.1 pg/ml]. Initial SOFA score was 7 [IQR 5–10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9–2.9]; adjusted HR 1.6 [CI 1.1–2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5–9.8). Conclusions AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

Published
2018
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9. Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study.

Author

Benjamin Deniau, Alice Blet, Karine Santos, Prabakar Vaittinada Ayar, Magali Genest, Mandy Kästorf, Malha Sadoune, Andreia de Sousa Jorge, Jane Lise Samuel, Nicolas Vodovar, Andreas Bergmann, Alexandre Mebazaa, and Feriel Azibani

Subjects
Medicine, Science
Abstract

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p

Published
2020
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10. Free-style puzzle flap as a cross-leg pedicled flap: the concept of re-using a flap in acute burns, a case report

Author

Kevin Serror, Marc Chaouat, Golda Romano, Magali Schmidt, Alice Blet, Maurice Mimoun, and David Boccara

Subjects
Burns, Free flap, Pedicled flap, Puzzle flap, Cross-leg, Medicine
Abstract

Abstract Background In well-selected cases, flaps can play a pivotal role in optimizing outcomes in the acute phase of burns. A previous redundant flap could be reused or recycled as a donor site from which a new flap could be raised. Case presentation We report the case of a patient with full thickness burns on both legs, leading to the exposure of joints of the right ankle and the right foot and left patellar tendon. The right lower extremity was covered with a free musculo-cutaneous latissimus dorsi flap. Then, a musculo-cutaneous cross-leg flap pedicled on the anterior branch and centered on a perforator was harvested from the previous redundant flap to cover the controlateral knee. Conclusion Sequential flap coverage can be considered in cases of extensive soft tissue defects and particularly in burns. This case illustrates that re-using a redundant part of a previous flap to cover another defect is a safe and interesting alternative in the event of a lack of donor sites or to save donor sites for later reconstruction of contracted burn scars.

Published
2018
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12. Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure

Author

Liyong Zhang, David Smyth, Mohammad Al-Khalaf, Alice Blet, Qiujiang Du, Jordan Bernick, Michael Gong, Xu Chi, Yena Oh, Malaika Roba-Oshin, Elizabeth Coletta, Michel Feletou, Anthony O. Gramolini, Kyoung-Han Kim, Thais Coutinho, James L. Januzzi, Benoit Tyl, Andre Ziegler, and Peter P. Liu

Abstract

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF.

Published
2022

13. Current and future trial design in refractory cardiogenic shock

Author

Mattia Arrigo, Alice Blet, Andrew Morley‐Smith, Nadia Aissaoui, David A. Baran, Antoni Bayes‐Genis, Ovidiu Chioncel, Steffen Desch, Mahir Karakas, Jacob Eifer Moller, Janine Poess, Susanna Price, Uwe Zeymer, and Alexandre Mebazaa

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

15. The association of biological sex and long-term outcomes in patients with acute dyspnea at the emergency department

Author

Prabakar Vaittinada Ayar, Justina Motiejūnaitė, Kamilė Čerlinskaitė, Benjamin Deniau, Alice Blet, Aušra Kavoliūnienė, Alexandre Mebazaa, Jelena Čelutkienė, and Feriel Azibani

Subjects
Adult, Hospitalization, Male, Dyspnea, Acute Disease, Emergency Medicine, Humans, Female, Registries, Emergency Service, Hospital, Aged
Abstract

Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission.The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED.Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries.The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin.A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65-80) vs. 68 (59-77) years, P0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1-14) vs. 7(2-14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac).Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.

Published
2021

16. La revue Anesthésie & Réanimation (ANREA) : des nouveautés et une nouvelle impulsion

Author

Jean-Yves Lefrant, Marc-Olivier Fischer, Romain Pirracchio, Dan Benhamou, Rosanna Njeim, Sylvain Ausset, Sophie Bastide, Matthieu Biais, Lionel Bouvet, Olivier Brissaud, Xavier Capdevila, Philippe Cuvillon, Christophe Dadure, Jean-Stéphane David, Patrice Forget, Anne Godier, Sophie Hamada, Olivier Joannes-Boyau, Sébastien Kerever, Éric Kipnis, Ruth Landau, Arthur Le Gall, Morgan Le Guen, Matthieu Legrand, Emmanuel Lorne, Frédéric Mercier, Nicolas Mongardon, Armelle Nicolas-Robin, Hervé Quintard, Philippe Richebé, Antoine Rocquilly, Antoine Schneider, Francis Veyckemans, Paul Zetlaoui, Laurent Zieleskiewicz, Osama Abou Arab, Alice Blet, Fanny Bounes, Matthieu Boisson, Anaïs Caillard, Aude Carillon, Thomas Clavier, Denis Frasca, Arthur James, Stéphanie Sigaut, Sacha Rozencwajg, and Hervé Bouaziz

Subjects
Anesthesiology and Pain Medicine
Published
2022

17. Intravenous fluids for vascular loading

Author

Stéphanie Sigaut, Anaïs Caillard, and Alice Blet

Subjects
Anesthesiology and Pain Medicine, Fluid Therapy, Humans, General Medicine, Critical Care and Intensive Care Medicine, Infusions, Intravenous
Published
2022

18. Quel impact de la présence sur les réseaux sociaux pour un journal médical ? L’exemple de l’équipe dédiée d’Anaesthesia Critical Care and Pain Medicine

Author

Aude Carillion, Sacha Rozencwajg, Denis Frasca, Osama Abou-Arab, Arthur James, Alice Blet, Rosanna Njeim, Marc-Olivier Fischer, Anaïs Caillard, Stéphanie Sigaut, Fanny Vardon Bounes, Matthieu Boisson, and Thomas Clavier

Subjects
03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 020205 medical informatics, 0202 electrical engineering, electronic engineering, information engineering, 030212 general & internal medicine, 02 engineering and technology
Abstract

Resume Pour une revue medicale, la diffusion a grande echelle de chacun de ses articles est aujourd’hui indispensable pour toucher un large public scientifique. Dans ce contexte, l’utilisation du reseau social Twitter permet a chaque nouvelle publication d’etre diffusee tres rapidement, a faible cout, pour des lecteurs precis et partout dans le monde. C’est de loin le reseau social le plus utilise pour partager les publications en 2021. Les reflexions autour de ce sujet ont ainsi abouti a la creation en novembre 2020 de la Social Media Team (SoMe Team) d’Anaesthesia Critical Care and Pain Medicine, le journal anglophone international de la Societe francaise d’anesthesie et de reanimation (SFAR). Cette equipe est coordonnee par un editeur en charge des reseaux sociaux, en lien direct avec le redacteur en chef du journal. Il elabore le planning des tweets en fonction du programme de publication du journal, il fleche le type de contenu qui y sera associe et sollicite les auteurs pour l’obtention d’images ou de courtes videos de presentation de leur publication. Le contenu graphique et la diffusion sur Twitter sont assures par les membres de l’equipe dediee aux reseaux sociaux.

Published
2021

19. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study

Author

Etienne Gayat, Nicolas Deye, Xavier Wittebole, AdrenOSS study investigators, Pierre-François Laterre, Bruno François, Oliver Hartmann, Gernot Marx, Charles Damoisel, Vincent Huberlant, Emmanuelle Mercier, Thierry Dugernier, Alice Blet, Jean-Michel Constantin, Dirk van Lier, Karine Santos, Stéphane Gaudry, Benjamin G. Chousterman, Peter Pickkers, Jean-Baptiste Lascarrou, Salvatore Di Somma, Matthieu Legrand, Romain Sonneville, Feriel Azibani, Albertus Beishuizen, Andreas Bergmann, Alexandre Mebazaa, Benjamin Deniau, Joachim Struck, Massimo Antonelli, Haikel Oueslati, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
Male, Kidney Disease, Organ Dysfunction Scores, medicine.medical_treatment, Organ dysfunction, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Medical and Health Sciences, law.invention, 0302 clinical medicine, law, Septic shock, Prospective Studies, Outcome, Cardiogenic shock, Statistics, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Hematology, Middle Aged, Intensive care unit, Intensive Care Units, Infectious Diseases, AdrenOSS-1 Study Investigators, Female, SOFA score, medicine.symptom, Infection, medicine.medical_specialty, Multiple Organ Failure, DPP3, Statistics, Nonparametric, Sepsis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Internal medicine, medicine, Humans, Nonparametric, Renal replacement therapy, Mortality, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Aged, Proportional Hazards Models, Mechanical ventilation, Chi-Square Distribution, business.industry, Inflammatory and immune system, Research, 030208 emergency & critical care medicine, Biomarker, lcsh:RC86-88.9, medicine.disease, Emergency & Critical Care Medicine, Good Health and Well Being, business, Biomarkers
Abstract

Critical care 25(1), 61 (2021). doi:10.1186/s13054-021-03471-2, Published by BioMed Centra, London

Published
2021

22. Peace, not war in Ukraine or anywhere else, please

Author

Jean-Yves Lefrant, Romain Pirracchio, Dan Benhamou, Marc-Olivier Fischer, Rosanna Njeim, Bernard Allaouchiche, Sophie Bastide, Matthieu Biais, Lionel Bouvet, Olivier Brissaud, Sorin J. Brull, Xavier Capdevila, Nicola Clausen, Philippe Cuvillon, Christophe Dadure, Jean-Stéphane David, Bin Du, Sharon Einav, Victoria Eley, Patrice Forget, Tomoko Fujii, Anne Godier, Dean P. Gopalan, Sophie Hamada, Ahmed Hasanin, Olivier Joannes-boyau, Sébastien Kerever, Éric Kipnis, Kerstin Kolodzie, Ruth Landau, Arthur Le Gall, Morgan Le Guen, Matthieu Legrand, Emmanuel Lorne, Frédéric J. Mercier, Nicolas Mongardon, Sheila Myatra, Armelle Nicolas-Robin, Mark John Peters, Hervé Quintard, Jordi Rello, Philippe Richebé, Jason Alexander Roberts, Antoine Rocquilly, Filippo Sanfilippo, Antoine Schneider, Mircea T. Sofonea, Francis Veyckemans, Paul Zetlaoui, Ahed Zeidan, Laurent Zieleskiewicz, Marzena Zielinska, Britta Von Ungern-Sternberg, Osama Abou Arab, Alice Blet, Fanny Bounes, Matthieu Boisson, Anaïs Caillard, Aude Carillion, Thomas Clavier, Denis Frasca, Arthur James, Stéphanie Sigaut, Sacha Rozencwajg, Pierre Albaladejo, Hervé Bouaziz, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Société française d'anesthésie et de réanimation (SFAR), SFAR, University of California [San Francisco] (UC San Francisco), University of California (UC), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département d'anesthésiologie [CHU 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), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Mayo Clinic [Jacksonville], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Odense University Hospital (OUH), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Peking Union Medical College Hospital [Beijing] (PUMCH), The Hebrew University of Jerusalem (HUJ), University of Queensland [Brisbane], University of Aberdeen, The Jikei University School of Medicine, 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), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Cairo University - Faculty of Medicine, Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Lille, Columbia University Medical Center (CUMC), Columbia University [New York], CHU Pontchaillou [Rennes], Hôpital Foch [Suresnes], Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Homi Bhabha National Institute (HBNI), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Centre Hospitalier Universitaire de Nice (CHU Nice), Universitat Internacional de Catalunya [Barcelona] (UIC), Hôpital Maisonneuve-Rosemont, Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Wrocław Medical University, The University of Western Australia (UWA), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service SAMU-SMUR [CHU Toulouse], Pôle Médecine d'urgences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des urgences [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Beaujon [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Service de Réanimation Médicale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Warfare, Anesthesiology and Pain Medicine, MESH: Humans, MESH: Warfare, MESH: Ukraine, ARTICLE CLINIQUE, Humans, General Medicine, Critical Care and Intensive Care Medicine, Ukraine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; War is back in Europe. With all its horrific pictures and live videos.In its report issued on the 24th of March 2022, the World Health Organization (WHO) [1] states that the Ukrainian conflict has involved 18 million persons so far, with 3.4 million refugees in bordering countries and 6.4 million persons internally displaced (Fig. 1). In this report, 1,035 deaths and 1,650 civilian injuries were reported in Ukraine without any reported data from Russia.

Published
2022

23. The Science Underlying COVID-19

Author

David Smyth, Peter P. Liu, Alice Blet, and Hongliang Li

Subjects
0303 health sciences, education.field_of_study, Myocarditis, business.industry, Population, Organ dysfunction, 030204 cardiovascular system & hematology, medicine.disease, Sudden death, Angiotensin II, 03 medical and health sciences, 0302 clinical medicine, Immune system, Physiology (medical), Heart failure, Immunology, Angiotensin-converting enzyme 2, medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, education, business, 030304 developmental biology
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.

Published
2020

24. Guidelines: Anaesthesia in the context of COVID-19 pandemic

Author

Lionel Velly, Etienne Gayat, Hervé Quintard, Emmanuel Weiss, Audrey De Jong, Philippe Cuvillon, Gérard Audibert, Julien Amour, Marc Beaussier, Matthieu Biais, Sébastien Bloc, Marie Pierre Bonnet, Pierre Bouzat, Gilles Brezac, Claire Dahyot-Fizelier, Souhayl Dahmani, Mathilde de Queiroz, Sophie Di Maria, Claude Ecoffey, Emmanuel Futier, Thomas Geeraerts, Haithem Jaber, Laurent Heyer, Rim Hoteit, Olivier Joannes-Boyau, Delphine Kern, Olivier Langeron, Sigismond Lasocki, Yoan Launey, Frederic le Saché, Anne Claire Lukaszewicz, Axel Maurice-Szamburski, Nicolas Mayeur, Fabrice Michel, Vincent Minville, Sébastien Mirek, Philippe Montravers, Estelle Morau, Laurent Muller, Jane Muret, Karine Nouette-Gaulain, Jean Christophe Orban, Gilles Orliaguet, Pierre François Perrigault, Florence Plantet, Julien Pottecher, Christophe Quesnel, Vanessa Reubrecht, Bertrand Rozec, Benoit Tavernier, Benoit Veber, Francis Veyckmans, Hélène Charbonneau, Isabelle Constant, Denis Frasca, Marc-Olivier Fischer, Catherine Huraux, Alice Blet, Marc Garnier, Assistance Publique - Hôpitaux de Marseille (APHM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Anesthésie et Réanimation [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mutualiste de Montsouris (IMM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anesthésie réanimation chirurgicale [Rennes], Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, CHU Toulouse [Toulouse], Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie et Pharmacologie Clinique de la Douleur, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Juge - Clinique du sport [Marseille], Pôle d'Anesthésie-Réanimation [CHU Rangueil], CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'anesthésie - réanimation chirurgicale [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'Anesthésie Réanimation, 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), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Institut Curie [Paris], Réanimation Médico-Chirurgicale, Service d'Anesthésie Réanimation, CHU Necker - Enfants Malades [AP-HP], Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Mitochondries, stress oxydant et protection musculaire (Strasbourg), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe d’Anesthésie-Réanimation Chirurgie cardio-thoracique et vasculaire [Toulouse], Clinique Pasteur [Toulouse], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Département d'anesthésiologie [CHU 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), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Hôpital Pontchaillou, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Pôle Anesthésie Réanimation [CHU de Toulouse], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Histoire et Cultures de l'Antiquité et du Moyen Âge (HISCANT-MA), Université de Lorraine (UL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Emergency Department, Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin - Bordeaux, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Anaesthesiology, Robert Debré Hospital, Service d'anesthésie réanimation chirurgicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie mitochondriale, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Anesthésiologie, Université Pierre et Marie Curie - Paris 6 (UPMC), and Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France.

Subjects
Infection prevention and control, [SDV]Life Sciences [q-bio], Psychological intervention, Airway management, Context (language use), Critical Care and Intensive Care Medicine, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030202 anesthesiology, Informed consent, Personal protective equipment, Pandemic, Health care, Medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Modalities, SARS-CoV-2, business.industry, COVID-19, 030208 emergency & critical care medicine, General Medicine, Guideline, 3. Good health, Anesthesiology and Pain Medicine, Universal precautions, Anesthesia, Viruses, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Objectives The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. Methods The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. Results The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. Conclusion We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.

Published
2020

25. Management of severe thermal burns in the acute phase in adults and children

Author

Isabelle Constant, Sabri Soussi, Nicolas Louvet, Damien Barraud, Sandrine Wiramus, Clément Hoffmann, Matthieu Legrand, Jeanne Jonqueres, Mathieu Fontaine, Laetitia Goffinet, Hugues Lefort, Thomas Leclerc, Etienne Gayat, Mathieu Jeanne, Pauline Devauchelle, Anne-Françoise Rousseau, Antoine Roquilly, Célia Lucas, Olivier Pantet, Alice Blet, Marie-Reine Losser, and N. Donat

Subjects
education.field_of_study, Telemedicine, Burn wound, business.industry, Industry funding, medicine.medical_treatment, Population, 030208 emergency & critical care medicine, General Medicine, Critical Care and Intensive Care Medicine, medicine.disease, Phase (combat), 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Intervention (counseling), Intensive care, Medicine, Airway management, Medical emergency, business, education
Abstract

Objectives To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. Design A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. Results The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. Conclusion Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

Published
2020

26. Features of inflammatory heart reactions following mRNA COVID-19 vaccination at a global level

Author

James A. Robblee, Jean-Marc Treluyer, Milou-Daniel Drici, Joëlle Micallef, Mohammad Al-Khalaf, Girish M. Nair, Francesco Salvo, Alice Blet, Tahir S Kafil, Laurent Chouchana, Peter P. Liu, Marie-Blanche Valnet-Rabier, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], University of Ottawa [Ottawa], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Genome Canada, University of Ottawa, and Admin, Oskar

Subjects
Adult, Male, medicine.medical_specialty, Myocarditis, COVID-19 Vaccines, Adolescent, 030204 cardiovascular system & hematology, 03 medical and health sciences, Pericarditis, Young Adult, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Pharmacovigilance, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Young adult, Child, Aged, Retrospective Studies, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pharmacology, Vaccines, Synthetic, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Vaccination, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Relative risk, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, mRNA Vaccines, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Published
2021

27. The <scp>CLIP</scp> ‐based mortality score in cardiogenic shock: suitable only for cardiogenic shock?

Author

Benjamin Deniau, Adrien Picod, Alice Blet, Etienne Gayat, Feriel Azibani, and Alexandre Mebazaa

Subjects
Heart Failure, medicine.medical_specialty, business.industry, Cardiogenic shock, Shock, Cardiogenic, medicine.disease, Intensive care unit, law.invention, Risk Factors, law, Internal medicine, Heart failure, medicine, Cardiology, Humans, Hospital Mortality, Cardiology and Cardiovascular Medicine, business
Published
2021

28. High plasma dipeptidyl peptidase 3 levels are associated with mortality and organ failure in shock: results from the international, prospective and observational FROG-ICU cohort

Author

Benjamin Deniau, Adrien Picod, Dirk Van Lier, Prabakar Vaittinada Ayar, Karine Santos, Oliver Hartmann, Etienne Gayat, Alexandre Mebazaa, Alice Blet, and Feriel Azibani

Subjects
Cohort Studies, Anesthesiology and Pain Medicine, Multiple Organ Failure, Humans, Shock, Prospective Studies, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Published
2021

29. Elevated Plasma Bioactive Adrenomedullin and Mortality in Cardiogenic Shock: Results from the OptimaCC Trial

Author

Beth A Davison, Janin Schulte, Etienne Gayat, Oliver Hartmann, Alice Blet, Alexandre Mebazaa, Bruno Levy, Ayu Asakage, Gad Cotter, Koji Takagi, Antoine Kimmoun, Kevin Duarte, Òscar Miró, Benjamin Deniau, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Momentum Research Inc., Durham, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Barcelona, Emergency Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Department of Emergency and Critical Care Medicine, Yokohama City Minato Red Cross Hospital, Department of Anesthesiology, Critical Care and Burn Center, Lariboisière-Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, SphingoTec, and BOZEC, Erwan

Subjects
medicine.medical_specialty, medicine.drug_class, Renal function, Gastroenterology, Article, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Refractory, Interquartile range, Internal medicine, medicine, Clinical endpoint, Natriuretic peptide, business.industry, Cardiogenic shock, cardiogenic shock, biomarkers, General Medicine, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adrenomedullin, adrenomedullin, outcome, Medicine, business
Abstract

Aims: Bioactive adrenomedullin (bio-ADM) was recently shown to be a prognostic marker in patients with acute circulatory failure. We investigate the association of bio-ADM with organ injury, functional impairment, and survival in cardiogenic shock (CS). Methods: OptimaCC was a multicenter and randomized trial in 57 patients with CS. In this post-hoc analysis, the primary endpoint was to assess the association between bio-ADM and 30-day all-cause mortality. Secondary endpoints included adverse events and parameters of organ injury or functional impairment. Results: Bio-ADM values were higher in 30-day non-survivors than 30-day survivors at inclusion (median (interquartile range) 67.0 (54.6–142.9) pg/mL vs. 38.7 (23.8–63.6) pg/mL, p = 0.010), at 24 h (p = 0.012), and up to 48 h (p = 0.027). Using a bio-ADM cutoff of 53.8 pg/mL, patients with increased bio-ADM had a HR of 3.90 (95% confidence interval 1.43–10.68, p = 0.008) for 30-day all-cause mortality, and similar results were observed even after adjustment for severity scores. Patients with the occurrence of refractory CS had higher bio-ADM value at inclusion (90.7 (59.9–147.7) pg/mL vs. 40.7 (23.0–64.7) pg/mL p = 0.005). Bio-ADM values at inclusion were correlated with pulmonary vascular resistance index, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide (r = 0.49, r = –0.47, and r = 0.64, respectively, p &lt, 0.001). Conclusions: In CS patients, the values of bio-ADM are associated with some parameters of organ injury and functional impairment and are prognostic for the occurrence of refractory CS and 30-day mortality.

Published
2021

30. Cardiac Inflammation after COVID-19 mRNA Vaccines: A Global Pharmacovigilance Analysis

Author

Marie-Blanche Valnet-Rabier, Tahir S Kafil, Milou-Daniel Drici, Girish M. Nair, Francesco Salvo, Peter Liu, Joëlle Micallef, Mohammad Al-Khalaf, Alice Blet, James A. Robblee, Jean-Marc Treluyer, and Laurent Chouchana

Subjects
Pediatrics, medicine.medical_specialty, Myocarditis, business.industry, medicine.disease, Vaccination, Pericarditis, Adverse Event Reporting System, Relative risk, Pharmacovigilance, medicine, Observational study, Young adult, business
Abstract

BackgroundTo counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis cases following vaccination have been reported. This safety signal has been recently confirmed by the European Medicine Agency and the U.S. Food and Drug Administration.This study aimed to investigate and analyze this safety signal using a dual pharmacovigilance database analysis.MethodsThis is as an observational study of reports of inflammatory heart reactions associated with mRNA COVID-19 vaccines reported in the World Health Organization’s global individual case safety report database (up to June 30th 2021), and in the U.S. Vaccine Adverse Event Reporting System (VAERS, up to May 21st 2021). Cases were described, and disproportionality analyses using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI) were performed to assess relative risk of reporting according to patient sex and age.ResultsAt a global scale, the inflammatory heart reactions most frequently reported were myocarditis (1241, 55%) and pericarditis (851, 37%), the majority requiring hospitalization (n=796 (64%)). Overall, patients were young (median age 33 [21-54] years). The main age group was 18-29 years old (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting in males (ROR, 9.4 [8.3-10.6]) as well as in adolescents (ROR, 22.3 [19.2-25.9]) and 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients were observed.ConclusionsThe inflammatory heart reactions, namely myocarditis and pericarditis, have been reported world-wide shortly following COVID-19 mRNA vaccination. An important disproportionate reporting among adolescents and young adults, particularly in males, was observed especially for myocarditis. Guidelines must take this specific risk into account and to optimize vaccination protocols according to sex and age. While the substantial benefits of COVID-19 vaccination still prevail over risks, clinicians and the public should be aware of these reactions and seek appropriate medical attention.

Published
2021

31. Clothing in the operating theatre

Author

Stéphanie Sigaut, Anaïs Caillard, Matthieu Boisson, Aude Carillion, and Alice Blet

Subjects
Operating Rooms, Anesthesiology and Pain Medicine, Humans, General Medicine, Critical Care and Intensive Care Medicine, Clothing
Published
2022

32. 2021 adaptation of the editorial policy of Anaesthesia Critical Care and Pain Medicine (ACCPM)

Author

Arthur James, Sylvain Ausset, Antoine G. Schneider, Emmanuel Lorne, Matthieu Boisson, Anaïs Caillard, Ruth Landau, Patrice Forget, Sorin J. Brull, Eric Kipnis, O. Brissaud, Morgan Le Guen, Francis Veyckemans, Antoine Rocquilly, Nicolas Mongardon, Sacha Rozencwajg, Lionel Bouvet, Marc-Olivier Fischer, Jean-Yves Lefrant, Alice Blet, Sophie Hamada, Armelle Nicolas-Robin, Sophie Bastide, Mark J. Peters, Hervé Quintard, Philippe Cuvillon, Jason A. Roberts, Frédéric J. Mercier, Anne Godier, Jean-Stéphane David, Xavier Capdevila, Matthieu Biais, Romain Pirracchio, Du Bin, Philippe Richebé, Arthur Le Gall, Olivier Joannes-Boyau, Kerstin Kolodzie, Jordi Rello, Paul Zetlaoui, Per-Arne Lönnqvist, Denis Frasca, Osama Abou Arab, Aude Carillon, Tomoko Fujii, Hervé Bouaziz, Thomas Clavier, Christophe Dadure, Sébastien Kerever, Stéphanie Sigaut, Matthieu Legrand, Rosanna Njeim, Dean Gopalan, Fanny Vardon Bounes, and Dan Benhamou

Subjects
medicine.medical_specialty, Critical Care, business.industry, Pain medicine, MEDLINE, Pain, General Medicine, Critical Care and Intensive Care Medicine, Anesthesiology and Pain Medicine, Anesthesiology, Medicine, Humans, Anesthesia, Adaptation (computer science), business, Intensive care medicine, Editorial Policies
Published
2021

33. Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure

Author

Zaid Sabti, Christian Mueller, Christian Puelacher, Iain B. Squire, Danielle Menosi Gualandro, Tobias Breidthardt, Pedro Lopez-Ayala, M Belkin, Albina Nowak, Leong L. Ng, Joachim Struck, Jasmin Martin, Samyut Shrestha, Mohamed Eltayeb, Desiree Wussler, Max Rieger, Tobias Zimmermann, Oliver Hartmann, Ivo Strebel, Sabrina Stefanelli, Andreas Bergmann, Alexandre Mebazaa, Alice Blet, Nikola Kozhuharov, and Eleni Michou

Subjects
medicine.medical_specialty, Post discharge, Prohormone, Aftercare, 030204 cardiovascular system & hematology, Adrenomedullin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Diuretics, Heart Failure, Creatinine, business.industry, Hazard ratio, General Medicine, Emergency department, Prognosis, medicine.disease, Diuretic treatment, Patient Discharge, chemistry, Heart failure, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers, medicine.drug
Abstract

Background Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. Methods This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. Results Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values n = 764) (interaction p values p p Conclusions Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

Published
2021
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34. Positive effects of lumbar puncture simulation training for medical students in clinical practice

Author

Claire Paquet, Maude Calixte, Sid-Ahmed Remini, Dhihia Leghima, Fadia Dib, Caroline Roos, Tiphaine Dujardin, Thomas Brock, Ludivine Jean-Louis, Pierre-François Ceccaldi, Patrick Plaisance, Dan David Tordjman, Damien Roux, Léa De Macédo, Samuel Mouyal, Alice Blet, Sinead Gaubert, Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Hôpital Louis Mourier - AP-HP [Colombes], HAL-SU, Gestionnaire, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
Medical education, medicine.medical_specialty, Students, Medical, Medical procedure, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, education, lcsh:Medicine, Educational study, Spinal Puncture, Education, Simulation training, 03 medical and health sciences, 0302 clinical medicine, Physicians, Lumbar puncture, Medicine, Humans, Routine clinical practice, In patient, 030212 general & internal medicine, Clinical skills, Medical student, lcsh:LC8-6691, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, lcsh:Special aspects of education, business.industry, lcsh:R, General Medicine, Confidence interval, 3. Good health, Clinical Practice, Physical therapy, Clinical Competence, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Background Lumbar puncture (LP) is an invasive medical procedure that can be done by any doctor. Several simulation-based trainings have been built however the evaluations of the theoretical knowledge and the impact of the simulation-based training have never been performed in real life. The objective was to evaluate the impact of a LP training on the theoretical knowledge improvement and the performance of a LP in clinical practice. Methods Before and after medical students’ training, theoretical knowledge and confidence level were assessed. Over a 6 months period, the impact of simulation training was evaluated by the success rate of students’ first LP carried out in hospitalized patients and compared to the results of a no-training control. Results Students’ theoretical knowledge and confidence level showed significant improvement after simulation training on 115 students (p p = 0.0025). The technical assistance was also less frequently needed in the LP simulation group (19% vs 57%, respectively, p = 0.017). The rate of students who participated in this educational study was low. Discussion Simulation-based teaching was an effective way to improve students’ theoretical and practical knowledge. Whether this approach translates to other procedural skills in real clinical settings merits further study. The low participation rate in the study is due to the fact that students are not used to be included in educational studies and to the complexity of evaluation in routine clinical practice.

Published
2021

35. A communication strategy based on Twitter improves article citation rate and impact factor of medical journals

Author

Marc-Olivier Fischer, Denis Frasca, Alice Blet, Emmanuel Besnier, Matthieu Boisson, Stéphanie Sigaut, Vincent Compère, Osama Abou Arab, Clément Buléon, Thomas Clavier, Service Anesthésie et soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Ottawa Heart Institute, University of Ottawa [Ottawa], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire de Beaujon (AP/HP), Beaujon, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), CHU Amiens-Picardie, Department of Anesthesiology and Critical Care, Rouen University Hospital, Rouen, France, Université de Caen Normandie (UNICAEN), Département d'anesthésiologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques

Subjects
020205 medical informatics, [SDV]Life Sciences [q-bio], Twitter, MEDLINE, 02 engineering and technology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Citation rate, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Humans, Social media, 030212 general & internal medicine, Impact factor, Citation, ComputingMilieux_MISCELLANEOUS, business.industry, Communication, Advertising, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Anesthesiology and Pain Medicine, Publication, Journal Impact Factor, Periodicals as Topic, business, Social Media
Abstract

International audience

Published
2020

37. Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19

Author

Youqin Yan, Xu Cheng, Ze Chen, Xiaodong Huang, Pengcheng Luo, Jingjing Cai, Ming Ming Chen, Xiaohui Song, Haitao Wang, Juan Juan Qin, Xiao Jing Zhang, Jing Xie, Alice Blet, Da Xiang, Liming Liu, Peng Zhang, Liangjie Bai, Rhian M. Touyz, Chen Gao, Zizhen Huang, Lihua Zhu, Yufeng Yuan, Meng Xia, Hongliang Li, Feng Zhou, Ping Ye, Weiming Mao, Bing Hong Zhang, Ling Ping Zhao, Xingyuan Zhang, Qingbo Xu, Lijin Lin, Gauri Akolkar, Yibin Wang, Manhua Chen, Guohua Chen, Ye Mao Liu, Fang Lei, Zhi-Gang She, Jing Chen, Xin-Liang Ma, and Peter P. Liu

Subjects
Male, Heart disease, Outcome Assessment, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, 0302 clinical medicine, heart injuries, cardiac biomarkers, Troponin I, Natriuretic Peptide, Brain, Outcome Assessment, Health Care, Natriuretic peptide, Medicine, Creatine Kinase, MB Form, heart injury, 030212 general & internal medicine, Viral, Prospective cohort study, Creatine Kinase, screening and diagnosis, Hazard ratio, Brain, Middle Aged, Brain natriuretic peptide, Prognosis, Hospitalization, MB Form, Detection, Heart Disease, Predictive value of tests, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Public Health and Health Services, Biomarker (medicine), Original Article, Female, Coronavirus Infections, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, China, Heart Diseases, medicine.drug_class, Pneumonia, Viral, Clinical Sciences, 03 medical and health sciences, Betacoronavirus, Clinical Research, Natriuretic Peptide, Predictive Value of Tests, Internal medicine, Internal Medicine, Humans, Mortality, Pandemics, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, biomarkers, Pneumonia, medicine.disease, Peptide Fragments, 4.1 Discovery and preclinical testing of markers and technologies, Health Care, Good Health and Well Being, Cardiovascular System & Hematology, myoglobin, business, Biomarkers
Abstract

Supplemental Digital Content is available in the text., The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019, to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for high-sensitivity cardiac troponin I was 7.12 ([95% CI, 4.60–11.03] P

Published
2020

38. Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study

Author

Nicolas Vodovar, Andreia de Sousa Jorge, Magali Genest, Karine Santos, Mandy Kästorf, Andreas Bergmann, Alexandre Mebazaa, Feriel Azibani, Benjamin Deniau, Prabakar Vaittinada Ayar, Malha Sadoune, Alice Blet, and Jane Lise Samuel

Subjects
Male, Cardiac output, Physiology, Hemodynamics, Blood Pressure, 030204 cardiovascular system & hematology, Cardiovascular Physiology, Vascular Medicine, 0302 clinical medicine, Blood plasma, Medicine and Health Sciences, Enzyme Inhibitors, Mammals, Multidisciplinary, Eukaryota, Heart, Stroke volume, Hematology, Animal Models, Body Fluids, Blood, Experimental Organism Systems, Vertebrates, Medicine, Anatomy, Research Article, Cardiac function curve, medicine.medical_specialty, Systole, Science, Research and Analysis Methods, Rodents, Proof of Concept Study, Dipeptidyl peptidase, Blood Plasma, Sepsis, 03 medical and health sciences, Signs and Symptoms, Model Organisms, Internal medicine, medicine, Animals, Rats, Wistar, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Septic shock, business.industry, Organisms, Biology and Life Sciences, 030208 emergency & critical care medicine, Cell Biology, medicine.disease, Rats, Oxidative Stress, Disease Models, Animal, Endocrinology, Amniotes, Cardiovascular Anatomy, Animal Studies, Clinical Medicine, business, Zoology
Abstract

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p

Published
2020

39. Analysis of blood culture in a rat model of cecal ligation and puncture induced sepsis

Author

Feriel Azibani, Alexandre Mebazaa, Benjamin Deniau, Prabakar Vaittinada Ayar, Hervé Jacquier, and Alice Blet

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Rat model, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Cecal ligation, lcsh:RC86-88.9, Critical Care and Intensive Care Medicine, medicine.disease, Sepsis, Text mining, medicine, Blood culture, business, Letter to the Editor
Published
2020

40. Inotropes and vasopressors are associated with increased short-term mortality but not long-term survival in critically ill patients

Author

Justina Motiejunaite, Benjamin Deniau, Alice Blet, Etienne Gayat, and Alexandre Mebazaa

Subjects
Adult, Cohort Studies, Intensive Care Units, Cardiotonic Agents, Anesthesiology and Pain Medicine, Critical Illness, Humans, Vasoconstrictor Agents, Hospital Mortality, Prospective Studies, General Medicine, Prognosis, Critical Care and Intensive Care Medicine
Abstract

Limited information is currently available on the impact of vasoactive medications in intensive care (ICU) and long-term outcomes. The main objective of our study was to describe the association between the use of inotropes and/or vasopressors and ICU mortality. Secondary objectives were to evaluate the association between the use of vasoactive drugs and in-hospital as well as 1-year all-cause mortality in ICU survivors.FROG-ICU was a prospective, observational, multi-centre cohort designed to investigate long-term mortality of critically ill adult patients. Cox proportional hazards models were used to evaluate the association between the use of inotropes and/or vasopressors and ICU mortality, as well as in-hospital and 1-year all-cause mortality in a propensity-score matched cohort.The study included 2087 patients, 939 of whom received inotropes and/or vasopressors during the initial ICU stay. Patients treated with vasoactive medications were older and had a more severe clinical presentation. In a propensity score-matched cohort of 1201 patients, ICU mortality was higher in patients who received vasoactive medications (HR of 1.40 [1.10-1.78], p = 0.007). One thousand six hundred thirty-five patients survived the index ICU hospitalisation. There was no significant difference according to the use of inotropes and/or vasopressors in the propensity-score matched cohort on in-hospital mortality (HR of 0.94 [0.60-1.49], p = 0.808) as well as one-year all-cause mortality (HR 0.94 [0.71-1.24], p = 0.643).Inotropic and/or vasopressor therapy is a strong predictor of in-ICU death. However, the use of inotropes and/or vasopressors during ICU admission was not associated with a worse prognosis after ICU discharge.

Published
2022

41. Methods used to assess the performance of biomarkers for the diagnosis of acute kidney injury: a systematic review and meta-analysis

Author

Léa Lemasle, Matthieu Legrand, Alice Blet, Etienne Gayat, Anaïs Codorniu, and Alexandre Mebazaa

Subjects
Oncology, medicine.medical_specialty, Health, Toxicology and Mutagenesis, Clinical Biochemistry, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Lipocalin-2, Internal medicine, Data accuracy, Methods, medicine, Animals, Humans, 030212 general & internal medicine, urogenital system, business.industry, Acute kidney injury, Publication bias, Acute Kidney Injury, medicine.disease, Data Accuracy, ROC Curve, Meta-analysis, business, Publication Bias, Biomarkers
Abstract

Methods used to explore biomarkers for acute kidney injury (AKI) might have a major impact on the results and the use of these biomarkers. We evaluated the methods used to investigate biomarkers of AKI.A systematic review and meta-analysis were performed using a computerized search of the MEDLINE and the EMBASE databases (PROSPERO CRD42017059618). Articles reporting biomarker's performance to diagnose AKI were included. The outcome included a description of the methods used to assess the performance of biomarkers to diagnose AKI.Among the 295 included studies, assessment of biomarkers was the primary endpoint in 284 with sample size calculation in only 8% of cases. Eighty-five percent of the studies summarized the performance of biomarkers with receiver operating characteristic (ROC) curves; however, 74 studies (25%) did not provide the threshold, sensibility or specificity. A total of 176 studies evaluated more than one biomarker, and only 25% combined biomarkers to increase diagnostic performance. We determined that the definition of AKI and study design impacted the diagnostic performance using uNGAL (urinary neutrophil gelatinase-associated lipocalin) as an example. Major publication bias was identified.Most articles that reported biomarkers of AKI performance present methodological weaknesses. Basic rules should be provided to increase the quality of reporting in this area.

Published
2018

42. Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects

Author

Roel V Peelen, Christopher Geven, Bas ten Elzen, Matthijs Kox, Alice Blet, Peter Pickkers, Dirk van Lier, and Alexandre Mebazaa

Subjects
Pharmacology, business.industry, medicine.medical_treatment, 030208 emergency & critical care medicine, 030204 cardiovascular system & hematology, medicine.disease, Systemic inflammation, Sepsis, Adrenomedullin, 03 medical and health sciences, 0302 clinical medicine, Cytokine, Bolus (medicine), Tolerability, Pharmacokinetics, Pharmacodynamics, medicine, Pharmacology (medical), medicine.symptom, business
Abstract

Aims Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis. The non-neutralizing ADM antibody adrecizumab has shown promising results in preclinical sepsis models. In the present study, we investigated the safety, tolerability and pharmacokinetics (PK)/pharmacodynamics of adrecizumab in a first-in-man study and in a second study during experimental human endotoxaemia. Methods Forty-eight healthy male volunteers were enrolled in two randomized, double-blind, placebo-controlled phase I studies. In both studies, subjects received placebo or one of three doses of adrecizumab (n = 6 per group). In the second study, a bolus of 1 ng kg-1 endotoxin was followed by infusion of 1 ng kg-1 h-1 endotoxin for 3 h to induce systemic inflammation, and the study medication infusion started 1 h after endotoxin bolus administration. Results Adrecizumab showed an excellent safety profile in both studies. PK analyses showed proportional increases in the maximum plasma concentration of adrecizumab with increasing doses, a small volume of distribution, a low clearance rate and a terminal half-life of ~14 days. adrecizumab elicited a pronounced increase in plasma ADM levels, whereas levels of mid-regional pro-adrenomedullin remained unchanged, indicating that de novo synthesis of ADM was not influenced. In the second study, no effects of adrecizumab on cytokine clearance were observed, whereas endotoxin-induced flu-like symptoms resolved more rapidly. Conclusions Administration of adrecizumab is safe and well tolerated in humans, both in the absence and presence of systemic inflammation. These findings pave the way for further investigation of adrecizumab in sepsis patients.

Published
2018

43. The Physiological Deep Learner: First application of multitask deep learning to predict hypotension in critically ill patients

Author

Romain Pirracchio, Matthieu Resche-Rigon, Ményssa Cherifa, Yannet Interian, and Alice Blet

Subjects
medicine.medical_specialty, Mean arterial pressure, Critical Care, Critical Illness, education, Medicine (miscellaneous), Multi-task learning, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Artificial Intelligence, Internal medicine, Heart rate, medicine, Humans, Arterial Pressure, 030304 developmental biology, 0303 health sciences, business.industry, Critically ill, Deep learning, External validation, Confidence interval, Cardiology, Artificial intelligence, Hypotension, business, Very high risk, 030217 neurology & neurosurgery
Abstract

Critical care clinicians are trained to analyze simultaneously multiple physiological parameters to predict critical conditions such as hemodynamic instability. We developed the Multi-task Learning Physiological Deep Learner (MTL-PDL), a deep learning algorithm that predicts simultaneously the mean arterial pressure (MAP) and the heart rate (HR). In an external validation dataset, our model exhibited very good calibration: R2 of 0.747 (95% confidence interval, 0.692 to 0.794) and 0.850 (0.815 to 0.879) for respectively, MAP and HR prediction 60-minutes ahead of time. For acute hypotensive episodes defined as a MAP below 65 mmHg for 5 min, our MTL-PDL reached a predictive value of 90% for patients at very high risk (predicted MAP ≤ 60 mmHg) and 2‰ for patients at low risk (predicted MAP >70 mmHg). Based on its excellent prediction performance, the Physiological Deep Learner has the potential to help the clinician proactively adjust the treatment in order to avoid hypotensive episodes and end-organ hypoperfusion.

Published
2021

45. Bioactive Adrenomedullin, Organ Support Therapies, and Survival in the Critically Ill: Results from the French and European Outcome Registry in ICU Study

Author

Benjamin Deniau, Andreas Bergmann, Pierre-François Laterre, Alexandre Mebazaa, Alice Blet, Xavier Monnet, Marie-Céline Fournier, Oliver Hartmann, Léa Lemasle, Christopher Geven, Michael Darmon, Alexa Hollinger, Etienne Gayat, Isabelle Rennuit, Ményssa Cherifa, Joachim Struck, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
Male, Icu patients, medicine.medical_specialty, medicine.medical_treatment, Critical Illness, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Sepsis, Cohort Studies, 03 medical and health sciences, Adrenomedullin, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Outcome Assessment, Health Care, medicine, Humans, Vasoconstrictor Agents, Renal replacement therapy, Prospective Studies, Registries, Prospective cohort study, Intensive care medicine, Survival rate, Aged, business.industry, Critically ill, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Europe, Renal Replacement Therapy, Survival Rate, Intensive Care Units, 030228 respiratory system, Female, France, business, hormones, hormone substitutes, and hormone antagonists, Cohort study
Abstract

OBJECTIVES: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin. DESIGN: Prospective multicenter observational cohort study. SETTING: Data from the French and euRopean Outcome reGistry in ICUs study. PATIENTS: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included. INTERVENTIONS: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality. MEASUREMENTS AND MAIN RESULTS: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92). CONCLUSIONS: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients

Published
2019

46. Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics

Author

Malha Sadoune, Nicolas Vodovar, Linda Rehfeld, Feriel Azibani, Benjamin Deniau, Karine Santos, Oliver Hartmann, Paul R Kounde, Heli Tolpannen, Andreas Bergmann, Alexandre Mebazaa, Anke Dienelt, Alice Blet, Veli-Pekka Harjola, Jane Lise Samuel, and Johan Lassus

Subjects
Cardiac function curve, medicine.medical_specialty, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Dipeptidyl peptidase, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Heart Failure, Kidney, business.industry, Cardiogenic shock, Organ dysfunction, Hemodynamics, Myocardial depressant factor, medicine.disease, Angiotensin II, 3. Good health, medicine.anatomical_structure, Heart failure, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Anti-Arrhythmia Agents, Biomarkers
Abstract

Aims Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice. Methods and results cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling. Conclusion Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF.

Published
2019

47. A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2)

Author

Matthijs Kox, Paul Scigalla, Christopher Geven, Pierre-François Laterre, Oliver Hartmann, Gernot Marx, Alexandre Mebazaa, Peter Pickkers, Alice Blet, Jens Zimmermann, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
medicine.medical_specialty, Adrecizumab, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Phase Ii clinical trial, Vascular integrity, adrecizumab, Placebo, Proof of Concept Study, Antibodies, sepsis, Sepsis, Adrenomedullin, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Septic shock, Internal medicine, Protocol, Clinical endpoint, Humans, media_common.cataloged_instance, Medicine, 030212 general & internal medicine, European union, media_common, business.industry, Organ dysfunction, Intensive Care, vascular integrity, General Medicine, medicine.disease, Shock, Septic, 3. Good health, Clinical trial, Tolerability, septic shock, medicine.symptom, business, 030217 neurology & neurosurgery, phase Ii clinical trial
Abstract

BMJ open 9(2), e024475 (2019). doi:10.1136/bmjopen-2018-024475, Published by BMJ Publishing Group, London

Published
2019

48. Adrecizumab, a non-neutralizing anti-adrenomedullin antibody, improves haemodynamics and attenuates myocardial oxidative stress in septic rats

Author

Benjamin Deniau, Jane-Lise Samuel, Paul-Robert Kounde, Christopher Geven, Alexandre Mebazaa, Evelyne Polidano, Anaïs Caillard, Peter Pickkers, Alice Blet, and Malha Sadoune

Subjects
Cardiac function curve, Cardiac output, medicine.medical_specialty, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Hemodynamics, Critical Care and Intensive Care Medicine, Norepinephrine (medication), Sepsis, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Septic shock, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Adrenomedullin, Blood pressure, 030228 respiratory system, Cardiology, business, medicine.drug
Abstract

Background Sepsis still represents a major health issue, with persistent high morbidity and mortality rates. Cardiovascular dysfunction occurs frequently during sepsis. Adrenomedullin has been identified as a key mediator in vascular tone regulation. A non-neutralizing anti-adrenomedullin antibody, Adrecizumab, may improve haemodynamic dysfunction during caecal ligation and puncture-induced septic shock in a murine model. Our objective was to determine the role of Adrecizumab on haemodynamics in a rat model of sepsis. Methods For the induction of sepsis, caecal ligation and puncture were performed in Wistar male rats. Single blinded administration of Adrecizumab (2 mg/kg) or placebo was injected i.v. 24 h after the surgery, and norepinephrine was infused as the standard of care. There were > 7 animals per group. Invasive blood pressure and cardiac function (by echocardiography) were assessed until 3 h after Adrecizumab injection. Results A single therapeutic injection of Adrecizumab in septic rats induced rapid haemodynamic benefits with an increase in systolic blood pressure in septic-Adrecizumab rats versus untreated-septic rats (p = 0.049). The shortening fraction did not differ between the untreated-septic and septic-Adrecizumab groups. However, cardiac output increased during the 3 h after a single dose of Adrecizumab compared to untreated septic rats (p = 0.006). A single dose of Adrecizumab resulted in similar haemodynamics to the continuous administration of norepinephrine. Three hours after a single injection of Adrecizumab, there was no change in the inflammatory phenotype (TNFα, IL-10) in the hearts of the septic rats. By contrast, 3 h after a single Adrecizumab injection, free-radical production decreased in the hearts of septic-Adrecizumab vs untreated septic rats (p

Published
2019

49. Preclinical safety evaluation of the adrenomedullin-binding antibody Adrecizumab in rodents, dogs and non-human primates

Author

Peter Pickkers, Alice Blet, Mathias Schroedter, Andreas Bergmann, Matthijs Kox, Alexandre Mebazaa, Christopher Geven, and Joachim Struck

Subjects
Male, 0301 basic medicine, Vasoactive peptide, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Adrenomedullin binding, Hemodynamics, Pharmacology, Antibodies, Monoclonal, Humanized, Toxicology, Risk Assessment, Beagle, Sepsis, Adrenomedullin, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Dogs, 0302 clinical medicine, Species Specificity, Animals, Toxicokinetics, Medicine, Rats, Wistar, biology, business.industry, medicine.disease, Macaca fascicularis, 030104 developmental biology, 030220 oncology & carcinogenesis, Injections, Intravenous, biology.protein, Female, Antibody, business
Abstract

Adrenomedullin (ADM) is a vasoactive peptide in sepsis. The non-neutralizing ADM-binding antibody Adrecizumab improved outcome in animal models of systemic inflammation and sepsis. Herein, we evaluated the preclinical safety of Adrecizumab in various animal species. First, Wistar rats received vehicle, 100, 200 or 400 mg/kg/day of Adrecizumab intravenously (n = 20 each) on days 1, 4, 8 and 14. An additional set of rats received vehicle or 400 mg/kg/day (n = 10 each) on the same days and were followed for 42 days. For toxicokinetics, satellite animals received vehicle (n = 6), 100, 200, or 400 mg/kg/day Adrecizumab intravenously (n = 18 each). A hemodynamic study was performed in Beagle dogs (n = 3) receiving vehicle (day 1), 2 mg/kg (day 3), 10 mg/kg (day 5), 50 mg/kg (day 8) and 10 mg/kg Adrecizumab intravenously (day 29). In final experiments, cynomolgus monkeys received vehicle, 25, 50 or 100 mg/kg/day Adrecizumab intravenously (n = 6 each) on days 1, 4, 8 and 14. Additional groups of monkeys received vehicle or 100 mg/kg/day Adrecizumab intravenously (n = 4 each) on the same days and were followed for 42 days. No mortality or moribund conditions occurred and no toxicologically relevant effects were attributed to Adrecizumab. Adrecizumab significantly increased circulating concentrations of its target peptide ADM, consistent with previous studies and mechanistically relevant. Toxicokinetic analyses showed immediate and dose-dependent peak concentrations, slow elimination and no gender differences. In conclusion, intravenous, repeated administration of high doses of Adrecizumab appeared well-tolerated across species. These results pave the way for further investigation of Adrecizumab in humans (intended dose of 2 mg/kg).

Published
2019

50. Prediction of an acute hypotensive episode during an ICU hospitalization with a super learner machine learning algorithm

Author

Etienne Gayat, Romain Pirracchio, Matthieu Resche-Rigon, Ményssa Cherifa, Antoine Chambaz, Alice Blet, Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Anesthésie-Réanimation, Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-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 de Paris (UP), Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France., Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France, Department of Anesthesia and Peri-operative Care, University of California, San Francisco, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint Louis [APHP]-Institut national du cancer [Boulogne] (INCA), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
Male, Sedation, medicine.medical_treatment, law.invention, Cohort Studies, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, law, Predictive Value of Tests, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Intensive care, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Mechanical ventilation, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Middle Aged, Intensive care unit, Confidence interval, Hospitalization, Pulse oximetry, Intensive Care Units, Anesthesiology and Pain Medicine, Brier score, Acute Disease, Female, medicine.symptom, Hypotension, business, Algorithm, 030217 neurology & neurosurgery, Algorithms
Abstract

International audience; Background: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP)

Published
2019

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