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1. Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study

Author: Jolan Malherbe, Pierre Godard, Jean-Claude Lacherade, Valentin Coirier, Laurent Argaud, Hervé Hyvernat, Francis Schneider, Julien Charpentier, Florent Wallet, Juliette Pocquet, Gaëtan Plantefeve, Jean-Pierre Quenot, Pierre Bay, Agathe Delbove, Hugues Georges, Tomas Urbina, David Schnell, Charlène Le Moal, Matthieu Stanowski, Corentin Muris, Maud Jonas, Bertrand Sauneuf, Olivier Lesieur, Amaury Lhermitte, Laure Calvet, Ines Gueguen, and Damien du Cheyron
Subjects: Varicella-Zoster virus, Intensive care units, Encephalitis, Pneumonia, Immunocompromised host, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. Results One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p
Published: 2024
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2. Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study

Author: Nicolas Deye, MD, PhD, Amelie Le Gouge, MSc, Bruno François, MD, Camille Chenevier-Gobeaux, MD, PhD, Thomas Daix, MD, Hamid Merdji, MD, PhD, Alain Cariou, MD, PhD, Pierre-François Dequin, MD, PhD, Christophe Guitton, MD, Bruno Mégarbane, MD, PhD, Jacques Callebert, PharmD, PhD, Bruno Giraudeau, PhD, Alexandre Mebazaa, MD, PhD, Nicolas Vodovar, PhD, for the Clinical Research in Intensive Care and Sepsis-TRIal Group for Global Evaluation and Research in SEPsis (TRIGGERSEP) Network and the ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) Study Group, Arnaud Desachy, Christophe Cracco, Laurence Robin, Marie Anne Fally, David Schnell, Olivier Baudin, Charles Lafon, Philippe Petua, Stéphane Rouleau, Cyrille Nowak, Gaétan Plantefeve, Hervé Mentec, Olivier Pajot, Damien Contou, Jo-Anna Tirolien, Constance Vuillard, Cécile Zylberfajn, Nadile Ali, Dieudonne Kilendo, Olivia Chauvel, Elias Karam, Pascal Chevallier, Dorothée Ducoux, Fabrice Raymond, Christophe Gellis, Jean-Pierre Quenot, Thérèse Devaux, Audrey Large, Sébastien Mortreux, Pierre-Emmanuel Charles, Sébastien Prin, Jean-Baptiste Roudaut, Pascal Andreu, Auguste Dargent, Nora Perrot, Audrey Massard, Solenne Villot, Corinne Pernot, Bruno Francois, Thomas Daix, Philippe Vignon, Nicolas Pichon, Celine Gonzalez, Nicolas Rodier, Jean François Mary, Ludmila Baudrillart, Christine Vallejo, Emmanuelle Begot, Claire Mancia, Michelle Nouaille, Cécile Duchiron, Sandrine Naturel, Marie-Anne De Vinzellles, Hélène Beacco, Thierry Boulain, Chantal Brossard, Armelle Mathonnet, Dalila Benzekri-Lefevre, Anne Bretagnol, Isabelle Runge, François Barbier, Grégoire Muller, Mai-Anh Nay, Julie Rossi, Lucie Muller, Sophie Tollec, Alain Cariou, Nathalie Marin, Camille Chenevier-Gobeaux, Michel Arnaout, Omar Ben Hadj Salem, Wulfran Bougouin, Simon Bourcier, Benoit Champigneulle, Matthieu Jamme, Alexis Ferre, Guillaume Geri, Frédéric Pene, Julien Charpentier, Jean-Daniel Chiche, Lucie Guillemet, Jean-Paul Mira, Marine Paul, Nicolas Deye, Bruno Megarbane, Alexandre Mebazaa, Isabelle Malissin, Sebastian Voicu, Nicolas Vodovar, Jacques Callebert, Claire Pernin, Lydia Suarez, Philippe Manivet, Dominique Vodovar, Anthony Checinski, Lamia Kerdjana, Pierre Garcon, Antoine Goury, Catherine Fauvaux, Salamata Agne, Nahima Gueblaoui, Aude Jacob, Loic Chimot, Catherine Huchet, Nadège Lacoste, Pierre-Henri Dessalles, Mélanie Saint-Leger, Yannick Monseau, Marie Heil, Ferhat Meziani, Hamid Merdji, DrKhoury, Samir Chenaf, Christine Kummerlen, Yannick Rabouel, Hayat Allam, Anne Hutt-Clauss, Alexandra Monnier, Pierre-François Dequin, Christine Mabilat, Emmanuelle Rouve, Charlotte Salmon-Gandonnière, Denis Garot, Youen Jouan, Stephan Ehrmann, Antoine Guillon, Laetitia Bodet–Contentin, Emmanuelle Mercier, Julie Mankikian, Stéphane Legriel, MrSébastien Cavelot, Christophe Guitton, Charlotte Garret, Cédric Bretonniere, Laurent Nicolat, Noëlle Brule, and Olivier Zambon
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.
Published: 2024
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3. Critically ill severe hypothyroidism: a retrospective multicenter cohort study

Author: Simon Bourcier, Maxime Coutrot, Alexis Ferré, Nicolas Van Grunderbeeck, Julien Charpentier, Sami Hraiech, Elie Azoulay, Saad Nseir, Nadia Aissaoui, Jonathan Messika, Pierre Fillatre, Romain Persichini, Serge Carreira, Alexandre Lautrette, Clément Delmas, Nicolas Terzi, Bruno Mégarbane, Jean-Baptiste Lascarrou, Keyvan Razazi, Xavier Repessé, Claire Pichereau, Damien Contou, Aurélien Frérou, François Barbier, Stephan Ehrmann, Etienne de Montmollin, Benjamin Sztrymf, Elise Morawiec, Naïke Bigé, Danielle Reuter, David Schnell, Olivier Ellrodt, Jean Dellamonica, Alain Combes, and Matthieu Schmidt
Subjects: Hypothyroidism, Myxedema, Coma, Cardiogenic shock, Critical care, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. Methods We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. Results Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality. Conclusions SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.
Published: 2023
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4. Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic

Author: Alexandra Laurent, Alicia Fournier, Florent Lheureux, Guillaume Louis, Saad Nseir, Gwenaelle Jacq, Cyril Goulenok, Grégoire Muller, Julio Badie, Bélaïd Bouhemad, Marjolaine Georges, Paul-Michel Mertes, Hamid Merdji, Vincent Castelain, Caroline Abdulmalak, Olivier Lesieur, Gaëtan Plantefeve, Jean-Claude Lacherade, Jean-Philippe Rigaud, Nicholas Sedillot, Damien Roux, Nicolas Terzi, Pascal Beuret, Antoine Monsel, Anne-Laure Poujol, Khaldoun Kuteifan, Thierry Vanderlinden, Anne Renault, Bérengère Vivet, Christophe Vinsonneau, Saber Davide Barbar, Gilles Capellier, Jean Dellamonica, Stephan Ehrmann, Thomas Rimmelé, Julien Bohé, Pierre Bouju, Sébastien Gibot, Bruno Lévy, Johanna Temime, Cyrille Pichot, David Schnell, Diane Friedman, Pierre Asfar, Eddy Lebas, Philippe Mateu, Kada Klouche, Juliette Audibert, Fiona Ecarnot, Nicolas Meunier-Beillard, Mélanie Loiseau, Irène François-Pursell, Christine Binquet, Jean-Pierre Quenot, and PsyCOVID-ICU Trial Investigators and the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis)
Subjects: Mental health, Stress factors, ICU, Healthcare professionals, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. Methods This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. Results In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p
Published: 2021
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5. Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study

Author: Cyrille Delpierre, Pierre-louis Declercq, Vanessa Bironneau, Nicolas Terzi, Jean Dellamonica, Jean-Pierre Quenot, Saad Nseir, Christine Binquet, Laura Federici, Elise Artaud-Macari, Gaetan Beduneau, Agathe Delbove, Nicholas Sedillot, Jean-Philippe Rigaud, Isabelle Fournel, Nicolas Meunier-Beillard, Julio Badie, Julien Maizel, Gaetan Plantefeve, Thierry Vanderlinden, Marjolaine Georges, Paul Abraham, David Schnell, Bertrand Sauneuf, Matthieu Demeyere, Eléa Ksiazek, Antoine Rivière, Caroline Clarot, Alexandre Ampere, Cédric Daubin, Pierre Kalfon, Élise Redureau, Mehdi Bousta, Laurie Lagache, Béatrice La Combe, Gaël Bourdin, Mehran Monchi, Martine Nyunga, Michel Ramakers, Walid Oulehri, Hugues Georges, Charlotte Salmon Gandonniere, Xavier Monnet, Nicolas Delberghe, Gurvan Le Bouar, Arnaud-Felix Miailhe, Sami Hraiech, Marie-Anne Hoppe, Saber Davide Barbar, George-Daniel Calcaianu, Stéphanie Gélinotte, and Marie Labruyère
Subjects: Medicine
Published: 2022
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6. Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME)

Author: Thomas Kerforne, Christiane Mousson, Karim Asehnoune, Fanny Feuillet, Olivier Huet, Bertrand Rozec, Aude Garin, Alexandre Hertig, Jeremy Bourenne, Nassim Kamar, Emmanuel Morelon, Denis Glotz, Morgane Péré, Thierry Boulain, Jean Reignier, René Robert, Dominique Bertrand, Pierre-Yves Egreteau, Thierry Benard, Raphaëlle Larmet, Luc Frimat, Sophie Girerd, Mathias Büchler, Anne Renault, Patrice Tirot, Cécile Vigneau, Eric Delpierre, David Schnell, Olivier Lesieur, Lionel Rostaing, Mathieu Lesouhaitier, Laurent Martin-Lefevre, Antoine Durrbach, Noëlle Brulé, Emmanuel Canet, Maryvonne Hourmant, Agnes Duveau, Laurent Dube, Marc Pierrot, Stanislas Humbert, Jean-Marc Boyer, François Labadie, Antoine Thierry, Jean-François Vincent, Angelique Goepp, Pierre Bouju, Charlotte Quentin, Yannick Le Meur, Jean-Christophe Venhard, Olivier Michel, Marie-Hélène Voellmy, Fabien Herve, Anne Courte, Lucile Amrouche, Marc Hazzan, Valerie Moal, Moglie Le Quintrec-Donnette, Philippe Grimbert, Anne Elisabeth Heng, Pierre Merville, Christian Hiesse, Brice Fermier, Charlotte Guyot-Colosio, Nicolas Bouvier, Jean-Philippe Rerolle, Sarah Drouin, Sophie Caillard, Laetitia Albano, Pierre-Francois Westeel, Florent Montini, Dider Dorez, Eric Alamartine, Carole Ouisse, and Veronique Sebille
Subjects: Medicine
Abstract: Introduction Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysis HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and dissemination The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration number NCT03098706.
Published: 2022
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7. Multicentre observational status-epilepticus registry: protocol for ICTAL

Author: Cédric Bruel, Nicolas Mongardon, Jean-Pierre Quenot, Didier Ledoux, Pierre Bailly, Jean-Baptiste Lascarrou, Gaetan Plantefeve, Jean Philippe Rigaud, Arnaud Galbois, David Schnell, Annabelle Stoclin, Gwenaelle Jacq, Jonathan Chelly, Pauline Soulier, Olivier Lesieur, Pascal Beuret, Mathilde Holleville, Bertrand Sauneuf, Caroline Sejourne, Marine Arrayago, Candice Fontaine, François Perier, Wulfran Bougouin, Nicolas Pichon, and Stephane Legriel
Subjects: Medicine
Published: 2022
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8. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol

Author: Sigismond Lasocki, Claire Dahyot-fizelier, Benoit Veber, Damien Roux, Stephan Ehrmann, Jean-Pierre Quenot, Thierry Boulain, Mai-Anh Nay, Elsa Tavernier, Gaetan Beduneau, Philippe Seguin, Jean-Claude Lacherade, Grégoire Muller, Maria Cabrera, Gaetan Plantefeve, Mickael Landais, Nicolas Grégoire, Francois Barbier, Ferhat Meziani, Jean-Etienne Herbrecht, David Schnell, Anne Veinstein, Qin Lu, Martine Ferrandiere, Hamid Merdji, Pascal Andreu, Laurent Vecellio, Deborah Le Pennec, Renaud Respaud, Philippe Lanotte, Marie Leclerc, and Julie Helms
Subjects: Medicine
Published: 2021
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9. In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human

Author: Yunhai Cui, Stephanie Claus, David Schnell, Frank Runge, and Caroline MacLean
Subjects: Caco-2, EpiIntestinal, first-pass, P-gp, BCRP, drug transporter, Pharmacy and materia medica, RS1-441
Abstract: The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.
Published: 2020
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10. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival.

Author: Emmanuel Canet, Lara Zafrani, Jerome Lambert, Catherine Thieblemont, Lionel Galicier, David Schnell, Emmanuel Raffoux, Etienne Lengline, Sylvie Chevret, Michael Darmon, and Elie Azoulay
Subjects: Medicine, Science
Abstract: BackgroundOptimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient's ability to receive optimal chemotherapy.Design and methodsTo compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).ResultsAccording to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, PConclusionAKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.
Published: 2013
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11. Luciferase reporter gene assay on human, murine and rat histamine H4 receptor orthologs: correlations and discrepancies between distal and proximal readouts.

Author: Uwe Nordemann, David Wifling, David Schnell, Günther Bernhardt, Holger Stark, Roland Seifert, and Armin Buschauer
Subjects: Medicine, Science
Abstract: The investigation of the (patho)physiological role of the histamine H4 receptor (H4R) and its validation as a possible drug target in translational animal models are compromised by distinct species-dependent discrepancies regarding potencies and receptor subtype selectivities of the pharmacological tools. Such differences were extremely pronounced in case of proximal readouts, e. g. [(32)P]GTPase or [(35)S]GTPγS binding assays. To improve the predictability of in vitro investigations, the aim of this study was to establish a reporter gene assay for human, murine and rat H4Rs, using bioluminescence as a more distal readout. For this purpose a cAMP responsive element (CRE) controlled luciferase reporter gene assay was established in HEK293T cells, stably expressing the human (h), the mouse (m) or the rat (r) H4R. The potencies and efficacies of 23 selected ligands (agonists, inverse agonists and antagonists) were determined and compared with the results obtained from proximal readouts. The potencies of the examined ligands at the human H4R were consistent with reported data from [(32)P]GTPase or [(35)S]GTPγS binding assays, despite a tendency toward increased intrinsic efficacies of partial agonists. The differences in potencies of individual agonists at the three H4R orthologs were generally less pronounced compared to more proximal readouts. In conclusion, the established reporter gene assay is highly sensitive and reliable. Regarding discrepancies compared to data from functional assays such as [(32)P]GTPase and [(35)S]GTPγS binding, the readout may reflect multifactorial causes downstream from G-protein activation, e.g. activation/amplification of or cross-talk between different signaling pathways.
Published: 2013
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12. Correction: Determinants of Recovery from Severe Posterior Reversible Encephalopathy Syndrome.

Author: Stephane Legriel, Olivier Schraub, Elie Azoulay, Philippe Hantson, Eric Magalhaes, Isaline Coquet, Cedric Bretonniere, Olivier Gilhodes, Nadia Anguel, Bruno Megarbane, Laurent Benayoun, David Schnell, Gaetan Plantefeve, Julien Charpentier, Laurent Argaud, Bruno Mourvillier, Arnaud Galbois, Ludivine Chalumeau-Lemoine, Michel Rivoal, François Durand, Arnaud Geffroy, Marc Simon, Annabelle Stoclin, Jean-Louis Pallot, Charlotte Arbelot, Martine Nyunga, Olivier Lesieur, Gilles Troché, Fabrice Bruneel, Yves-Sébastien Cordoliani, Jean-Pierre Bedos, and Fernando Pico
Subjects: Medicine, Science
Published: 2013
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13. Determinants of recovery from severe posterior reversible encephalopathy syndrome.

Author: Stephane Legriel, Olivier Schraub, Elie Azoulay, Philippe Hantson, Eric Magalhaes, Isaline Coquet, Cedric Bretonniere, Olivier Gilhodes, Nadia Anguel, Bruno Megarbane, Laurent Benayoun, David Schnell, Gaetan Plantefeve, Julien Charpentier, Laurent Argaud, Bruno Mourvillier, Arnaud Galbois, Ludivine Chalumeau-Lemoine, Michel Rivoal, François Durand, Arnaud Geffroy, Marc Simon, Annabelle Stoclin, Jean-Louis Pallot, Charlotte Arbelot, Martine Nyunga, Olivier Lesieur, Gilles Troché, Fabrice Bruneel, Yves-Sébastien Cordoliani, Jean-Pierre Bedos, Fernando Pico, and Critically III Posterior Reversible Encephalopathy Syndrome Study Group (CYPRESS)
Subjects: Medicine, Science
Abstract: ObjectiveFew outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES.Design70 patients with severe PRES admitted to 24 ICUs in 2001-2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90.Main resultsConsciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105-143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3-5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOSConclusionsBy day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.
Published: 2012
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14. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

Author: David Hajage, Alain Combes, Christophe Guervilly, Guillaume Lebreton, Alain Mercat, Arthur Pavot, Saad Nseir, Armand Mekontso-Dessap, Nicolas Mongardon, Jean Paul Mira, Jean-Damien Ricard, Alexandra Beurton, Guillaume Tachon, Loay Kontar, Christophe Le Terrier, Jean Christophe Richard, Bruno Mégarbane, Ruth H. Keogh, Aurélien Belot, Camille Maringe, Clémence Leyrat, Matthieu Schmidt, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W. Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, Sébastian Voicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Meriam Lamraoui, Claire Alessandri, Quentin de Roux, Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien Pili Floury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris-Saclay, CHU Lille, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS [Créteil] (UPEC/Faculté de Médecine de Créteil), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Foch [Suresnes], CHU Amiens-Picardie, Geneva University Hospital (HUG), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], London School of Hygiene and Tropical Medicine (LSHTM), RICHARD, Jean-Christophe, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, Adult, Respiratory Distress Syndrome, SARS-CoV-2, [SDV]Life Sciences [q-bio], acute respiratory distress syndrome (ARDS), COVID-19, extracorporeal membrane oxygenation, Critical Care and Intensive Care Medicine, Cohort Studies, [SDV] Life Sciences [q-bio], emulated target trial, acute respiratory distress syndrome, Treatment Outcome, surgical procedures, operative, Humans, Retrospective Studies
Abstract: International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2
Published: 2022

15. Multicentre observational status-epilepticus registry: Protocol for ICTAL

Author: Gwenaelle Jacq, Jonathan Chelly, Jean-Pierre Quenot, Pauline Soulier, Olivier Lesieur, Pascal Beuret, Mathilde Holleville, Cedric Bruel, Pierre Bailly, Bertrand Sauneuf, Caroline Sejourne, Jean Philippe Rigaud, Arnaud Galbois, Marine Arrayago, Gaetan Plantefeve, Annabelle Stoclin, David Schnell, Candice Fontaine, François Perier, Wulfran Bougouin, Nicolas Pichon, Nicolas Mongardon, Didier Ledoux, Jean-Baptiste Lascarrou, Stephane Legriel, Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe Hospitalier Sud, Groupe hospitalier de La Rochelle, Centre Hospitalier de Roanne, Hôpitaux Universitaires Paris Nord Val de Seine (HUPNVS), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Saint-Joseph [Paris], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Réanimation Polyvalente [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Centre hospitalier de Dieppe, Centre Hospitalier Privé Claude Galien - Ramsay Santé, Centre Hospitalier de Cannes, Centre hospitalier Argenteuil (CH Argenteuil), Institut Gustave Roussy (IGR), Département de soins aigus [Gustave Roussy] (DSA), Centre Hospitalier d'Angoulême (CH Angoulême), Hôpital Privé Jacques Cartier [Massy], Hôpital de Brive, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Acknowledgements We thank A Wolfe MD (Chaumont, France) for helping to prepare the manuscript. The study was supported by the French public funding agency Délégation à la Recherche Clinique et à l’Innovation (DRCI), Versailles, France., and HAL UVSQ, Équipe
Subjects: Critical Care, adult neurology, General Medicine, Cross-Sectional Studies, Status Epilepticus, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, Multicenter Studies as Topic, Medicine, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Registries, adult intensive & critical care, Retrospective Studies
Abstract: IntroductionStatus epilepticus (SE) is a common life-threatening neurological emergency that can cause long-term impairments. Overall outcomes remain poor. Major efforts are required to clarify the epidemiology of SE and the determinants of outcomes, thereby identifying targets for improved management.Methods and analysisICTAL Registry is a multicentre open cohort of critically ill patients with convulsive, non-convulsive or psychogenic non-epileptic SE. Observational methods are applied to collect uniform data. The goal of the ICTAL Registry is to collect high-quality information on a large number of patients, thereby allowing elucidation of the pathophysiological mechanisms involved in mortality and morbidity. The registry structure is modular, with a large core data set and the opportunity for research teams to create satellite data sets for observational or interventional studies (eg, cohort multiple randomised controlled trials, cross-sectional studies and short-term and long-term longitudinal outcome studies). The availability of core data will hasten patient recruitment to studies, while also decreasing costs. Importantly, the vast amount of data from a large number of patients will allow valid subgroup analyses, which are expected to identify patient populations requiring specific treatment strategies. The results of the studies will have a broad spectrum of application, particularly given the multidisciplinary approach used by the IctalGroup research network.Ethics and disseminationThe ICTAL Registry protocol was approved by the ethics committee of the French Intensive Care Society (#CE_SRLF 19-68 and 19-68a). Patients or their relatives/proxies received written information to the use of the retrospectively collected and pseudonymised data, in compliance with French law. Prospectively included patients receive written consent form as soon as they recover decision-making competency; if they refuse consent, they are excluded from the registry. Data from the registry will be disseminated via conference presentations and peer-reviewed publications.Trial registration numberNCT03457831.
Published: 2022

16. Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic

Author: Gaëtan Plantefève, Pascal Beuret, Khaldoun Kuteifan, Olivier Lesieur, Saad Nseir, Nicholas Sedillot, Kada Klouche, Vincent Castelain, Cyrille Pichot, Jean-Claude Lacherade, Jean Dellamonica, Nicolas Meunier-Beillard, Florent Lheureux, Fiona Ecarnot, Bérengère Vivet, Pierre Bouju, Gilles Capellier, Grégoire Muller, Paul Michel Mertes, Nicolas Terzi, Eddy Lebas, Sébastien Gibot, PsyCOVID-ICU Trial Investigators, Jean-Philippe Rigaud, Diane Friedman, Julio Badie, Jean-Pierre Quenot, Pierre Asfar, Cyril Goulenok, Anne Renault, Anne-Laure Poujol, Irène François-Pursell, Philippe Mateu, David Schnell, Marjolaine Georges, Antoine Monsel, Belaid Bouhemad, Johanna Temime, Hamid Merdji, Christophe Vinsonneau, Thierry Vanderlinden, Alexandra Laurent, Mélanie Loiseau, Juliette Audibert, Alicia Fournier, Caroline Abdulmalak, Christine Binquet, Gwenaëlle Jacq, Stephan Ehrmann, Damien Roux, Bruno Levy, Saber Barbar, Julien Bohé, Guillaume Louis, Thomas Rimmelé, Laboratoire de psychologie : dynamiques relationnelles et processus identitaires [Dijon] (PSY-DREPI), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Lille, Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Ramsay Générale de Santé - Hôpital Privé La Louvière, Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Service d'anesthésie - réanimation chirurgicale [CHU de Dijon], Service de Pneumologie Soins Intensifs, Appareillage Respiratoire [CHU de Dijon], Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Hôpital de Hautepierre [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Centre Hospitalier Chalon-sur-Saône William Morey, Centre Hospitalier de La Rochelle (CHR), Service de réanimation (CH d'Argenteuil), Centre Hospitalier Victor Dupouy, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Service de Médecine Intensive Réanimation (CH Dieppe), Centre hospitalier de Dieppe, Espace régional de réflexion éthique de Normandie (EREN), Centre hospitalier de Bourg-en-Bresse / Fleyriat (CHBBF), Service des soins intensifs [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de Réanimation Médicale [Grenoble], CHU Grenoble-Hôpital Michallon, Centre Hospitalier de Roanne, Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), École de Psychologues Praticiens (EPP), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), CHRU Brest - Département d'Anesthésie Réanimation (CHU - BREST - DAR), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe Hospitalier de La Haute-Saône, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Unité de réanimation médicale [CHU de Carémeau, Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier de Lens, Centre Hospitalier Louis Pasteur [Dole], Centre Hospitalier d'Angoulême (CH Angoulême), Hôpital Raymond Poincaré [AP-HP], CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier de Charleville-Mezières, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation polyvalente [Chartres], Hôpital Louis Pasteur [Chartres], Service de cardiologie [CHRU de Besançon], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Délégation à la recherche clinique et à l'innovation [CHU Dijon] (DRCI), Service de médecine légale (Institut médico-légal et Unité médico-judiciaire) (CHU de Dijon), Cellule d'urgence médico-psychologique (CUMP), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Espace de Réflexion Éthique Bourgogne Franche-Comté (EREBFC) (EREBFC)
Subjects: Mediation (statistics), [SDV]Life Sciences [q-bio], Context (language use), Critical Care and Intensive Care Medicine, law.invention, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Environmental health, Intensive care, Healthcare professionals, Health care, Medicine, 030212 general & internal medicine, business.industry, RC86-88.9, Research, Stressor, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Mental health, 3. Good health, ICU, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Health Questionnaire, business, Stress factors, 030217 neurology & neurosurgery
Abstract: Background We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. Methods This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. Results In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p p B = 0.13; 95% confidence interval [CI] = 0.08–0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09–0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02–0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = − 0.32, 95% CI = − 0.54, − 0.11. Conclusion COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).
Published: 2021

17. A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3)

Author: Pilar Garrido, Yvonne Summers, Ute von Wangenheim, Michael Flynn, Allan Hackshaw, Manuel Cobo, Siow Ming Lee, Anne-Marie C. Dingemans, Arsene Bienvenu Loembe, David Schnell, Rolf Kaiser, Martin Forster, Tommaso De Pas, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, and MUMC+: MA Med Staf Spec Longziekten (9)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, PHARMACOKINETICS, Indoles, Lung Neoplasms, PACLITAXEL, Deoxycytidine, ANGIOGENESIS, Squamous, chemistry.chemical_compound, 0302 clinical medicine, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, BIBF 1120, Aged, 80 and over, Middle Aged, Prognosis, Treatment Outcome, Paclitaxel, LABEL DOSE-ESCALATION, 030220 oncology & carcinogenesis, Nintedanib, Female, CLINICAL-PRACTICE GUIDELINES, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Bevacizumab, Maximum Tolerated Dose, BEVACIZUMAB, CONTROLLED-TRIAL, Disease-Free Survival, 03 medical and health sciences, Pharmacokinetics, Internal medicine, medicine, Humans, Adverse effect, Aged, Neoplasm Staging, TRIPLE ANGIOKINASE INHIBITOR, Cisplatin, CARBOPLATIN, business.industry, Gemcitabine, Carboplatin, 030104 developmental biology, chemistry, business
Abstract: Background There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. Materials and methods A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2–7, 9–21) were given for 4–6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (Grade ≥3) or hematologic (Grade 4) AEs. Results Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17–35 months). Conclusions The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.
Published: 2018

18. Phase I open-label study of afatinib plus vinorelbine in patients with solid tumours overexpressing EGFR and/or HER2

Author: Jean-Charles Soria, Yann Berge, Martina Uttenreuther-Fischer, David Schnell, I. Tschoepe, Rastislav Bahleda, Andrea Varga, and Jean-Pierre Delord
Subjects: 0301 basic medicine, Oncology, Adult, Diarrhea, Male, Cancer Research, medicine.medical_specialty, phase Ib, Maximum Tolerated Dose, Nausea, Receptor, ErbB-2, Vomiting, Afatinib, afatinib, Administration, Oral, Neutropenia, Vinorelbine, 03 medical and health sciences, ErbB family blocker, 0302 clinical medicine, Internal medicine, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Adverse effect, Infusions, Intravenous, Aged, Febrile Neutropenia, business.industry, Middle Aged, medicine.disease, Progression-Free Survival, 030104 developmental biology, 030220 oncology & carcinogenesis, Asthenia, Clinical Study, Female, medicine.symptom, business, Febrile neutropenia, medicine.drug
Abstract: Background: This phase Ib study evaluated afatinib plus vinorelbine in patients with advanced solid tumours overexpressing epidermal growth factor receptor (EGFR) and/or human EGFR 2 (HER2). Methods: Maximum tolerated doses (MTDs) were determined for afatinib (20, 40 or 50 mg, once daily) combined with standard intravenous vinorelbine (part A; 25 mg m−2 per week) or oral vinorelbine (part B; 60 mg m−2 per week, increased to 80 mg m−2 per week at week 3). Secondary end points for expanded MTD cohorts included assessments of safety, pharmacokinetics, tumour response and progression-free survival (PFS). Results: The afatinib MTD was 40 mg with intravenous (MTDA) and oral (MTDB) vinorelbine. The most frequent cycle 1 dose-limiting toxicities were febrile neutropenia and diarrhoea, consistent with individual safety profiles of vinorelbine and afatinib. Common treatment-related adverse events included: diarrhoea (92.7%), asthenia (76.4%), nausea (63.6%), neutropenia (56.4%) and vomiting (54.5%). No notable pharmacokinetic interactions were observed. Best overall tumour response was stable disease in part A (16 out of 28 patients), and partial response in part B (3 out of 27 patients). Median PFS was 14.6 and 15.9 weeks for patients treated at the MTDA and MTDB, including dose-escalation and expansion cohorts. Conclusions: Afatinib in combination with intravenous or oral vinorelbine demonstrated a manageable safety profile and antitumour activity at the MTD of 40 mg per day.
Published: 2018

19. Early Recognition of Persistent Acute Kidney Injury

Author: Michael Darmon, David Schnell, Anne-Sophie Truche, Moustapha Abdel-Nabey, Bertrand Souweine, Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Department of Pharmacology and Toxicology, Universität Regensburg (UR), Centre Hospitalier d'Angoulême (CH Angoulême), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier d'Angoulême, CHU Gabriel Montpied (CHU), CCSD, Accord Elsevier, 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: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Renal function, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, urologic and male genital diseases, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, 0302 clinical medicine, medicine, Failure risk, Humans, Renal replacement therapy, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Models, Statistical, business.industry, Acute kidney injury, Ultrasonography, Doppler, Recovery of Function, Acute Kidney Injury, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, female genital diseases and pregnancy complications, Resistive index, 3. Good health, 030104 developmental biology, Early Diagnosis, Nephrology, Critical illness, Risk of death, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite the vast amount of literature dedicated to acute kidney injury (AKI) and its clinical consequences, short-term renal recovery has been relatively neglected. Recent studies have suggested that timing of renal recovery is associated with longer-term risk of death, residual renal function, and end-stage renal failure risk. In addition, longer AKI duration is associated with an increased requirement for renal replacement therapy. Comorbidities, especially renal and cardiovascular, severity of AKI, criteria to reach AKI diagnosis, as well as severity of critical illness have been associated with longer AKI duration, and, more specifically, risk of persistent renal dysfunction. Because predicting short-term renal recovery is clinically relevant, several tests, imaging, and biomarkers have been tested in a way to predict the course of AKI and chances for early renal recovery. In this review, the definition of recovery, consequences of persistent AKI, and tools proposed to predict recovery are described. The performance of these tools and their limits are discussed.
Published: 2019

20. Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies

Author: Lillian L. Siu, David Schnell, Remy B. Verheijen, Albiruni Ryan Abdul Razak, Martijn P. Lolkema, Linda C Pronk, Diane A.J. van der Biessen, Filip de Vos, Monique Jansen, Hal W. Hirte, Maja J.A. de Jonge, Sebastien J. Hotte, and Neeltje Steeghs
Subjects: 0301 basic medicine, Male, Cancer Research, Peripheral edema, Gastroenterology, 0302 clinical medicine, Neoplasms, 80 and over, Tissue Distribution, Pharmacology (medical), Original Research Article, Neoplasm Metastasis, Non-U.S. Gov't, Aged, 80 and over, Proteinuria, Research Support, Non-U.S. Gov't, Protein Kinase Inhibitors/pharmacokinetics, Middle Aged, Prognosis, Clinical Trial, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Vomiting, Female, medicine.symptom, Focal Adhesion Kinase 1/antagonists & inhibitors, Adult, medicine.medical_specialty, Maximum Tolerated Dose, Nausea, Research Support, Clinical Trial, Phase I, 03 medical and health sciences, Young Adult, Phase I, Pharmacokinetics, Internal medicine, medicine, Journal Article, Humans, Adverse effect, Protein Kinase Inhibitors, Aged, business.industry, medicine.disease, Neoplasms/drug therapy, 030104 developmental biology, Focal Adhesion Kinase 1, Pharmacodynamics, business, Progressive disease, Follow-Up Studies
Abstract: Background Overexpression/activation of focal adhesion kinase (FAK) in human malignancies has led to its evaluation as a therapeutic target. We report the first-in-human phase I study of BI 853520, a novel, potent, highly selective FAK inhibitor. Objective Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity. Patients and Methods The study comprised a standard 3 + 3 dose-escalation phase followed by an expansion phase in patients with selected advanced, nonhematologic malignancies. Results Thirty-three patients received BI 853520 in the dose-escalation phase; the MTD was 200 mg once daily (QD). Dose-limiting toxicities included proteinuria and fatigue, both of which were grade 3. Preliminary PK data supported QD dosing. In the expansion cohort, 63 patients received BI 853520 200 mg QD. Drug-related adverse events (AEs) in > 10% of patients included proteinuria (57%), nausea (57%), fatigue (51%), diarrhea (48%), vomiting (40%), decreased appetite (19%), and peripheral edema (16%). Most AEs were grade 1–2; grade 3 proteinuria, reported in 13 patients (21%), was generally reversible upon treatment interruption. Nineteen patients underwent dose reduction due to AEs, and three drug-related serious AEs were reported, none of which were fatal. Preliminary PD analysis indicated target engagement. Of 63 patients, 49 were evaluable; 17 (27%) achieved a best response of stable disease (4 with 150 + days), and 32 (51%) patients had progressive disease. Conclusions BI 853520 has a manageable and acceptable safety profile, favorable PK, and modest antitumor activity at an MTD of 200 mg QD in patients with selected advanced nonhematologic malignancies. ClinicalTrials.gov identifier NCT01335269. Electronic supplementary material The online version of this article (10.1007/s11523-018-00617-1) contains supplementary material, which is available to authorized users.
Published: 2019

21. Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors

Author: Jaafar Bennouna, Jean Fan, Nicolas Isambert, Sandrine Hiret, David Schnell, Hélène de Mont-Serrat, Mouna Sassi, Carlos Gomez-Roca, Jean-Pierre Delord, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Boehringer Ingelheim France S.A.S., Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Oncology, Afatinib, medicine.medical_treatment, Docetaxel, Deoxycytidine, Cohort Studies, 0302 clinical medicine, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Solid tumors, Pharmacology (medical), Middle Aged, Rash, Progression-Free Survival, 3. Good health, ErbB Receptors, Treatment Outcome, Tolerability, Area Under Curve, 030220 oncology & carcinogenesis, Combination, Female, medicine.symptom, medicine.drug, medicine.medical_specialty, Maximum Tolerated Dose, Antineoplastic Agents, 03 medical and health sciences, Phase I, Internal medicine, medicine, Humans, neoplasms, Pharmacology, Chemotherapy, Dose-Response Relationship, Drug, business.industry, medicine.disease, Gemcitabine, Regimen, 030104 developmental biology, business, Febrile neutropenia, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Afatinib, an irreversible ErbB family blocker, has shown synergistic antitumor activity and manageable tolerability in combination with chemotherapy. This phase I study assessed oral afatinib plus intravenous gemcitabine or docetaxel in patients with relapsed/refractory solid tumors. Methods Patients received afatinib (30, 40, or 50 mg) plus gemcitabine (1000 or 1250 mg/m2) or docetaxel (60 or 75 mg/m2). Dose escalation proceeded via a 3 + 3 design until the maximum tolerated dose (MTD) was reached. Adverse events (AEs), pharmacokinetics and antitumor activity were also assessed. Results Dose-limiting toxicities during Cycle 1 were reported in 6/39 patients receiving afatinib/gemcitabine (most commonly diarrhea, thrombocytopenia and vomiting) and 16/54 patients receiving afatinib/docetaxel (most commonly febrile neutropenia and stomatitis). The MTDs were established as afatinib 40 mg/gemcitabine 1000 mg/m2 and afatinib 30 mg/docetaxel 60 mg/m2. The most common drug-related AEs were diarrhea, asthenia and rash with afatinib/gemcitabine, and diarrhea, asthenia and stomatitis with afatinib/docetaxel. No relevant pharmacokinetic interactions were observed for either combination. Both combinations demonstrated clinical activity and durable disease control at the MTDs. Compared with the MTD, higher response rates were achieved with afatinib 30 mg/docetaxel 75 mg/m2 (28% vs 6%); however, this regimen was associated with problematic febrile neutropenia, an expected AE with docetaxel, that is often managed with growth factor support. Conclusions Afatinib/gemcitabine and afatinib/docetaxel demonstrated manageable safety profiles, with evidence of clinical efficacy at the MTDs. For afatinib/docetaxel, a dose level of afatinib 30 mg/docetaxel 75 mg/m2 produced higher response rates. Trial registration: NCT01251653 ( ClinicalTrials.gov ).
Published: 2018

22. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study

Author: David Schnell, Dietmar Gansser, Raimund Külzer, Anne Weber, Gudrun Wallenstein, Sven Wind, Sabrina Wiebe, Atef Halabi, and Anja Conrad
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Lung Neoplasms, Clinical chemistry, Afatinib, Coefficient of variation, Urology, Renal function, Urine, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Carcinoma, Non-Small-Cell Lung, medicine, Humans, Pharmacology (medical), Dosing, Original Research Article, Renal Insufficiency, Aged, business.industry, Case-control study, Middle Aged, 030104 developmental biology, 030220 oncology & carcinogenesis, Area Under Curve, Case-Control Studies, Quinazolines, Female, business, medicine.drug
Abstract: Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30–59 mL/min/1.73 m2 and 15–29 mL/min/1.73 m2, respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUClast) and maximum plasma concentration (C max) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUClast and C max, was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUClast for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3–213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28–39 % for moderate impairment, 34–42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.
Published: 2016

23. A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

Author: Markus Peck-Radosavljevic, Arsene-Bienvenu Loembe, Yuk Ting Ma, Laetitia Fartoux, David Schnell, Janet Graham, Julia Hocke, Paul Ross, Daniel H. Palmer, Andrzej Deptała, Matus Studeny, and Tim Meyer
Subjects: Sorafenib, Adult, Male, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Indoles, Maximum Tolerated Dose, Phases of clinical research, Gastroenterology, Disease-Free Survival, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Adverse effect, neoplasms, Aged, Aged, 80 and over, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Europe, Treatment Outcome, Oncology, chemistry, Tolerability, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, 030211 gastroenterology & hepatology, Nintedanib, Female, business, medicine.drug
Abstract: Background: \ud This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC).\ud \ud Methods: \ud Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression. Time-to-progression (TTP, primary endpoint), overall survival (OS) and progression-free survival (PFS) were determined.\ud \ud Results: \ud Phase-I: no DLTs observed; nintedanib MTD in both groups was 200 mg bid. Phase-II: patients (N = 93) were randomised to nintedanib (n = 62) or sorafenib (n = 31); TTP was 5.5 vs. 4.6 months (HR = 1.44 [95% CI, 0.81–2.57]), OS was 11.9 vs. 11.4 months (HR = 0.88 [95% CI, 0.52–1.47]), PFS was 5.3 vs. 3.9 months (HR = 1.35 [95% CI, 0.78–2.34]), respectively (all medians). Dose intensity and tolerability favoured nintedanib. Fewer patients on nintedanib (87.1%) vs. sorafenib (96.8%) had drug-related adverse events (AEs) or grade ≥ 3 AEs (67.7% vs. 90.3%), but more patients on nintedanib (28 [45.2%]) had AEs leading to drug discontinuation than did those on sorafenib (7 [22.6%]).\ud \ud Conclusions: \ud Nintedanib may have similar efficacy to sorafenib in aHCC.
Published: 2018

24. A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors

Author: Sheeba Irshad, Deborah Enting, Martina Uttenreuther-Fischer, Joo Ern Ang, James Spicer, David Schnell, Karine Pemberton, Rebecca Kristeleit, K Pelling, and Johann S. de Bono
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Cancer Research, Paclitaxel, Maximum Tolerated Dose, Bevacizumab, Nausea, Afatinib, Toxicology, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Phase I, 0302 clinical medicine, Pharmacokinetics, Neoplasms, Internal medicine, Solid tumors, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Adverse effect, Aged, Pharmacology, business.industry, Middle Aged, Rash, Phase i study, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Quinazolines, Original Article, Female, medicine.symptom, business, medicine.drug
Abstract: Purpose The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors. Methods This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed. The starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel (fixed dose 80 mg/m2, Days 1, 8, and 15 of a 4-week cycle) and intravenous bevacizumab 5 mg/kg every 2 weeks. Results Twenty-nine patients were enroled. The afatinib dose was de-escalated to 30 mg and then 20 mg after 2/6 and 2/5 evaluable patients developed dose-limiting toxicities at 40 and 30 mg, respectively, when combined with paclitaxel and bevacizumab 5 mg/kg. The bevacizumab dose was subsequently escalated to 10 mg/kg, and MTD was defined as afatinib 20 mg plus paclitaxel 80 mg/m2 and bevacizumab 10 mg/kg. Frequent (any grade) treatment-related adverse events (AEs) included diarrhea (83%), rash/acne (83%), fatigue (79%), mucosal inflammation (59%), and nausea (59%). Based on overall safety, bevacizumab was amended to 7.5 mg/kg for the recommended phase II dose. Pharmacokinetic analyses suggested no relevant drug–drug interactions. Three (10%) confirmed partial responses were observed; 15 (52%) patients had stable disease. Conclusions The recommended phase II dose schedule was afatinib 20 mg/day with paclitaxel 80 mg/m2 (Days 1, 8, and 15 every 4 weeks) and bevacizumab 7.5 mg/kg every 2 weeks. At this dose schedule, AEs were manageable, and anti-tumor activity was observed. Electronic supplementary material The online version of this article (doi:10.1007/s00280-016-3189-1) contains supplementary material, which is available to authorized users.
Published: 2017

25. Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520

Author: Neeltje Steeghs, Hal W. Hirte, Lillian L. Siu, Linda C Pronk, David Schnell, Sebastien J. Hotte, Martijn P. Lolkema, Maja J.A. de Jonge, Diane A.J. van der Biessen, Anna Spreafico, Filip de Vos, and Remy B. Verheijen
Subjects: 0301 basic medicine, Male, Cancer Research, Analytical chemistry, Administration, Oral, Food-Drug Interactions, 0302 clinical medicine, Treatment compliance, Neoplasms, 80 and over, Medicine, Tissue Distribution, Pharmacology (medical), Original Research Article, Neoplasm Metastasis, Non-U.S. Gov't, Aged, 80 and over, Cross-Over Studies, Research Support, Non-U.S. Gov't, Protein Kinase Inhibitors/pharmacokinetics, Middle Aged, Prognosis, Clinical Trial, Oncology, 030220 oncology & carcinogenesis, Area Under Curve, Administration, Randomized Controlled Trial, Female, Open label, Focal Adhesion Kinase 1/antagonists & inhibitors, Tablets, Oral, Adult, Maximum Tolerated Dose, Cmax, Capsules, Bioequivalence, Research Support, Clinical Trial, Phase I, 03 medical and health sciences, Phase I, Pharmacokinetics, Journal Article, Humans, Protein Kinase Inhibitors, Aged, business.industry, Order (ring theory), Crossover study, Neoplasms/drug therapy, 030104 developmental biology, Therapeutic Equivalency, Focal Adhesion Kinase 1, Tablets/administration & dosage, Geometric mean, business
Abstract: Background BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies. Objective The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies. Patients and Methods Sixteen patients with advanced solid tumors were enrolled in each substudy. The order of administration was randomized, and pharmacokinetic samples were collected for 48 h after administration of a 200 mg dose of BI 853520. Lack of effect would be demonstrated if the 90% confidence interval (CI) of the ratio of the adjusted geometric mean (GMR) of the area under the plasma curve (area under the plasma concentration–time curve from time zero to the last quantifiable concentration at tz [\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{AUC}}_{{0{-}t_{\text{z}} }}$$\end{document}AUC0-tz] and observed area under the plasma concentration–time curve extrapolated from time zero to infinity [AUC0–∞,obs]) and maximum plasma concentration (Cmax) did not cross the 80–125% (bioequivalence) boundaries. Results Adjusted GMRs (90% CIs) for the fed versus fasted state were 92.46% (74.24–115.16), 98.17% (78.53–122.74), and 87.34% (71.04–107.38) for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{AUC}}_{{0{-}t_{\text{z}} }}$$\end{document}AUC0-tz, AUC0–∞,obs, and Cmax, respectively. Although the 90% CIs were not within bioequivalence limits for the food-effect study, the limited reductions in these pharmacokinetic parameters after administration with a high-fat meal are unlikely to be clinically relevant. Compared with a tablet, administration of BI 853520 as a liquid dispersion did not strongly affect \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{AUC}}_{{0{-}t_{\text{z}} }}$$\end{document}AUC0-tz, AUC0–∞,obs, or Cmax, resulting in adjusted GMRs (90% CIs) of 1.00 (0.92–1.09), 0.98 (0.90–1.07), and 0.93 (0.86–1.01), respectively. Conclusions These studies demonstrate that BI 853520 can be given with no food restrictions, and as a liquid dispersion, without strongly impacting pharmacokinetics. These pharmacokinetic properties may help make BI 853520 dosing more convenient and flexible, improving treatment compliance. Clinical trials registration ClinicalTrials.gov identifier: NCT01335269. Electronic supplementary material The online version of this article (10.1007/s11523-018-00618-0) contains supplementary material, which is available to authorized users.
Published: 2019

26. Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes

Author: Elie Azoulay, Maité Garrouste-Orgeas, Samir Jamali, Yves Cohen, Christophe Adrie, Lila Soufir, Michael Darmon, Anne-Sylvie Dumenil, Bertrand Souweine, Aurélien Vesin, Benjamin Planquette, Jean-François Timsit, Dany Goldgran-Toledano, Lila Bouadma, Carole Schwebel, David Schnell, Department of Pharmacology and Toxicology, Universität Regensburg (UR), Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-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), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Medical-Surgical ICU, Hôpital de Gonesse, Service de réanimation chirurgicale [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Saint Joseph, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie, soins intensifs (Pneumo - HEGP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de Réanimation Médicale [Grenoble], CHU Grenoble-Hôpital Michallon, Hôpital de Dourdan, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), BRICHEUX, Genevieve, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Saint Joseph, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris 13 (UP13)-Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), and Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Databases, Factual, medicine.medical_treatment, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Critical Care and Intensive Care Medicine, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anesthesiology, Medicine, Intubation, Humans, Treatment Failure, Risk factor, ComputingMilieux_MISCELLANEOUS, Aged, Mechanical ventilation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Hazard ratio, Middle Aged, Respiration, Artificial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Confidence interval, 3. Good health, Clinical trial, Treatment Outcome, Respiratory failure, Anesthesia, Acute Disease, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Respiratory Insufficiency, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Noninvasive ventilation (NIV) had proven benefits in clinical trials that included selected patients admitted to highly skilled centers. Whether these benefits apply to every patient and in everyday practice deserves appraisal. The aim of the study was to assess the use and outcomes of NIV over the last 15 years. Multicenter database study of critically ill patients who required ventilatory support for acute respiratory failure between 1997 and 2011. The impact of first-line NIV on 60-day mortality was evaluated using a marginal structural model. Follow-up was censored on day 60. Of 3,163 patients, 1,232 (39 %) received NIV. Over the study period, first-line NIV increased from 29 to 42 %, and NIV success rates increased from 69 to 84 %. NIV decreased 60-day mortality [adjusted hazard ratio (aHR), 0.75; 95 % confidence interval (95 % CI), 0.68–0.83; P
Published: 2014

27. Predictors of Functional Outcome after Intraoperative Cardiac Arrest

Author: David Schnell, Emmanuelle Begot, Jean-François Loriferne, Pierrick Cronier, Jean-Pierre Bedos, Alexis Soummer, Gilles Dhonneur, Matthieu Resche-Rigon, Claire Montlahuc, Benoit Vandenbunder, Bertrand Sauneuf, David Grimaldi, Anne-Laure Constant, Nicolas Pichon, Jennifer Brunet, Belaid Bouhemad, Sylvie Ricome, Benoit Misset, Philippe Jullien, Lauriane Bordenave, Etienne Dubuisson, Nicolas Mongardon, Sigismond Lasocki, Stéphane Legriel, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Return of spontaneous circulation, Ventricular tachycardia, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, law, Intensive care, Internal medicine, medicine, Humans, Cardiopulmonary resuscitation, Asystole, Coma, Intraoperative Complications, Aged, Retrospective Studies, business.industry, 030208 emergency & critical care medicine, Length of Stay, Middle Aged, medicine.disease, Intensive care unit, Cardiopulmonary Resuscitation, 3. Good health, Heart Arrest, Intensive Care Units, Anesthesiology and Pain Medicine, Pulseless electrical activity, Ventricular fibrillation, Cardiology, Female, business
Abstract: Background: Few outcome data are available about intraoperative cardiac arrest (IOCA). The authors studied 90-day functional outcomes and their determinants in patients admitted to the intensive care unit after IOCA. Methods: Patients admitted to 11 intensive care units in a period of 2000–2013 were studied retrospectively. The main outcome measure was a day-90 Cerebral Performance Category score of 1 or 2. Results: Of the 140 patients (61 women and 79 men; median age, 60 yr [interquartile range, 46 to 70]), 131 patients (93.6%) had general anesthesia, 80 patients (57.1%) had emergent surgery, and 73 patients (52.1%) had IOCA during surgery. First recorded rhythms were asystole in 73 patients (52.1%), pulseless electrical activity in 44 patients (31.4%), and ventricular fibrillation/ventricular tachycardia in 23 patients (16.4%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation were 0 min (0 to 0) and 10 min (5 to 20), respectively. Postcardiac arrest shock was identified in 114 patients (81.4%). Main causes of IOCA were preoperative complications (n = 46, 32.9%), complications of anesthesia (n = 39, 27.9%), and complications of surgical procedures (n = 36, 25.7%). On day 90, 63 patients (45.3%) were alive with Cerebral Performance Category score 1/2. Independent predictors of day-90 Cerebral Performance Category score 1/2 were day-1 Logistic Organ Dysfunction score (odds ratio, 0.78 per point; 95% CI, 0.71 to 0.87; P = 0.0001), ventricular fibrillation/tachycardia as first recorded rhythm (odds ratio, 4.78; 95% CI, 1.38 to 16.53; P = 0.013), and no epinephrine therapy during postcardiac arrest syndrome (odds ratio, 3.14; 95% CI, 1.29 to 7.65; P = 0.012). Conclusions: By day 90, 45% of IOCA survivors had good functional outcomes. The main outcome predictors were directly related to IOCA occurrence and postcardiac arrest syndrome; they suggest that the intensive care unit management of postcardiac arrest syndrome may be amenable to improvement.
Published: 2014

28. Outcomes in critically ill chronic lymphocytic leukemia patients

Author: François Vincent, Michael Darmon, Aliénor Xhaard, Vincent Levy, David Schnell, Loïc Epelboin, Elie Azoulay, Marion Malphettes, Service de greffe de moelle osseuse [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-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), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), Department of Pharmacology and Toxicology, Universität Regensburg (UR), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, medicine.medical_specialty, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Hospital mortality, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, MESH: Leukemia, Lymphocytic, Chronic, B-Cell/therapy, Humans, Medicine, Hospital Mortality, Intensive care medicine, Alemtuzumab, Aged, Retrospective Studies, business.industry, Critically ill, Cancer, Middle Aged, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, Intensive Care Units, Leukemia, Logistic Models, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Rituximab, business, Vidarabine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: International audience; BACKGROUND:Although recent studies have demonstrated an improvement in the prognosis of critically ill cancer patients, little is known regarding the prognosis of patients with non-aggressive underlying malignancies. The aims of this study were to assess the prognosis of critically ill patients with chronic lymphocytic leukemia (CLL) and to evaluate risk factors for hospital mortality.METHODS:In retrospective mono-center cohort study, consecutive adult patients with CLL requiring ICU admission from 1997 to 2008 were included.RESULTS:Sixty-two patients of 67 years (62-75) were included. Median time interval between CLL diagnosis and ICU admission was 6.7 years (2.6-10.8). Nine patients (15 %) had stage C disease at the time of ICU admission, and seven patients (11 %) had Richter syndrome. Most ICU admissions were related to bacterial or fungal pulmonary infections (n = 47; 76 %). ICU, in-hospital, and 90-day mortality were 35 % (n = 22), 42 % (n = 26), and 58 % (n = 36), respectively. Only three factors were independently associated with in-hospital mortality: oxygen saturation lower than 95 % when breathing room air (odds ratio (OR) 5.80; 95 % confidence interval (CI) 1.23-27.33), need for vasopressors (OR 27.94; 95 % CI 5.37-145.4), and past history of infection (OR 6.62; 95 % CI 1.34-32.68). The final model did not change when disease-related variables (Binet classification, Richter syndrome, long-term steroids) or treatment-related variables (fludarabine, rituximab, or alemtuzumab) were included.CONCLUSION:Acute pulmonary infections remain the leading cause of ICU admission in patients with CLL. The severity at ICU admission and past history of infection were the only factors associated with hospital mortality. Neither disease characteristics nor previous cancer treatments were associated with outcome.
Published: 2013

29. Acylguanidines as Bioisosteres of Guanidines: NG-Acylated Imidazolylpropylguanidines, a New Class of Histamine H2Receptor Agonists.

Author: Prasanta Ghorai, Anja Kraus, Max Keller, Carsten Götte, Patrick Igel, Erich Schneider, David Schnell, Günther Bernhardt, Stefan Dove, Manfred Zabel, Sigurd Elz, Roland Seifert, and Armin Buschauer
Published: 2008
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30. Pharmacokinetics of afatinib in subjects with mild or moderate hepatic impairment

Author: Martina Uttenreuther-Fischer, Susanne Buschke, Peter Stopfer, Rüdiger Koenen, Atef Halabi, Marc Petersen-Sylla, Rainer-Georg Goeldner, Holger Fuchs, Dietmar Gansser, David Schnell, and Sven Wind
Subjects: Adult, Male, medicine.medical_specialty, Cancer Research, Adolescent, Maximum Tolerated Dose, Receptor, ErbB-2, medicine.drug_class, Afatinib, Tyrosine kinase inhibitor, Urine, Pharmacology, Biology, Toxicology, Gastroenterology, Tyrosine-kinase inhibitor, Young Adult, Pharmacokinetics, Internal medicine, medicine, Humans, Tissue Distribution, Pharmacology (medical), Dosing, Adverse effect, Aged, Liver Diseases, Case-control study, Middle Aged, Prognosis, Epidermal growth factor receptor (EGFR), Hepatic impairment, Oncology, Area Under Curve, Case-Control Studies, Toxicity, Quinazolines, Female, Original Article, Follow-Up Studies, Human, medicine.drug
Abstract: Afatinib, an oral irreversible ErbB family blocker, undergoes minimal metabolism by non-enzyme-catalysed adduct formation with proteins or nucleophilic small molecules and is predominantly non-renally excreted via the entero-hepatic system. This trial assessed whether mild or moderate hepatic impairment influences the pharmacokinetics of afatinib. This was an open-label single-dose study. Pharmacokinetic parameters after afatinib 50 mg were investigated in subjects with mild (n = 8) or moderate (n = 8) hepatic impairment (Child-Pugh A and B) and healthy controls (n = 16) matched for age, weight and gender. Plasma and urine samples for pharmacokinetic assessment were collected before and up to 10 days after dosing. Additional blood samples were drawn to determine ex vivo plasma protein binding of afatinib. Primary endpoints were comparisons of afatinib C max and AUC0–∞ between subjects with hepatic impairment and healthy matched controls. Study progression was based on drug-related toxicity (CTCAE v. 3.0) and C max of afatinib. Afatinib pharmacokinetic profiles and plasma protein binding were similar in subjects with impaired liver function and healthy controls. Compared with matched controls, the afatinib-adjusted geometric mean ratio for AUC0–∞ was 92.6 % (90 % CI 68.0–126.3 %) and C max was 109.5 % (90 % CI 82.7–144.9 %) for subjects with mild hepatic impairment, and 94.9 % (90 % CI 72.3–124.5 %) and 126.9 % (90 % CI 86.0–187.2 %), respectively, for subjects with moderate hepatic impairment. For all parameters, the 90 % CI included 100 %. Afatinib was generally well tolerated with no serious adverse events reported. Mild to moderate hepatic impairment had no clinically relevant effect on the pharmacokinetics of a single 50 mg dose of afatinib, implying that adjustments to the starting dose of afatinib are not considered necessary in this patient population.
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31. Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

Author: Dres, Martin, Hajage, David, Lebbah, Said, Kimmoun, Antoine, Pham, Tai, Béduneau, Gaëtan, Combes, Alain, Mercat, Alain, Guidet, Bertrand, Demoule, Alexandre, Schmidt, Matthieu, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), 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], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Saint-Antoine [AP-HP], COVID-ICU investigators: Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Reignier Jean, Seguin Amélie, Garret Charlotte, Canet Emmanuel, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-AhnNay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Marie Anne Melone, Maxime Gauzi, Arnaud Guilbert, Geoffrey Kouadri, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clémet Hoffmann, Nicolas Donat, Violaine Muller, Thibault Martinez, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan L E Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, SqébastianVoicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Nicolas Mongardon, Olivier Langeron, Eric Levesque, Arié Attias, Charles de Roquetaillade, Benjamin G Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, ThiMy Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, RostaneGaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien PiliFloury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Florent Bavozet, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, and dres, martin
Subjects: [SDV] Life Sciences [q-bio], Acute respiratory distress syndrome, Frailty, [SDV]Life Sciences [q-bio], Old patients, COVID-19, Intensive care unit, Mortality, Intubation
Abstract: International audience; Abstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO 2 /FiO 2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO 2 /FiO 2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p
Published: 2021

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31 results on '"David Schnell"'

1. Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study

2. Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study

3. Critically ill severe hypothyroidism: a retrospective multicenter cohort study

4. Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic

5. Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study

6. Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME)

7. Multicentre observational status-epilepticus registry: protocol for ICTAL

8. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol

9. In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human

10. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival.

11. Luciferase reporter gene assay on human, murine and rat histamine H4 receptor orthologs: correlations and discrepancies between distal and proximal readouts.

12. Correction: Determinants of Recovery from Severe Posterior Reversible Encephalopathy Syndrome.

13. Determinants of recovery from severe posterior reversible encephalopathy syndrome.

14. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

15. Multicentre observational status-epilepticus registry: Protocol for ICTAL

16. Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic

17. A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3)

18. Phase I open-label study of afatinib plus vinorelbine in patients with solid tumours overexpressing EGFR and/or HER2

19. Early Recognition of Persistent Acute Kidney Injury

20. Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies

21. Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors

22. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study

23. A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

24. A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors

25. Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520

26. Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes

27. Predictors of Functional Outcome after Intraoperative Cardiac Arrest

28. Outcomes in critically ill chronic lymphocytic leukemia patients

29. Acylguanidines as Bioisosteres of Guanidines: NG-Acylated Imidazolylpropylguanidines, a New Class of Histamine H2Receptor Agonists.

30. Pharmacokinetics of afatinib in subjects with mild or moderate hepatic impairment

31. Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

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31 results on '"David Schnell"'

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