Author: "David Schnell" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"David Schnell"' showing total 127 results

Start Over Author "David Schnell"

127 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

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

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
Full Text: View/download PDF

14. Suivi thérapeutique pharmacologique de la cyamémazine : comment interpréter une concentration ? Une revue de la littérature

Author: Hugo Alarcan, David Schnell, Stéphane Rouleau, Anissa Chachia, Franck Saint-Marcoux, Olivier Mathieu, and Sylvain Couderc
Subjects: Pharmacology (medical)
Published: 2022

15. Data from Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer

Author: David Schnell, Katy Pelling, Graham Temple, Martina Uttenreuther-Fischer, Ruth Plummer, Robert Laing, Helen Hatcher, Duncan Wheatley, and Alistair Ring
Abstract: Purpose: The HER2 mAb, trastuzumab, is a standard therapy for patients with HER2-positive breast cancer before acquired resistance. Afatinib, an irreversible, oral, small-molecule ErbB family blocker, shows clinical activity in trastuzumab-refractory HER2-positive breast cancer.Experimental Design: This phase I study used a 3+3 dose escalation to determine the MTD of oral once-daily afatinib in combination with the recommended dose of intravenous trastuzumab (4 mg/kg week 1; 2 mg/kg/wk thereafter). Adult women with confirmed advanced/metastatic HER2-positive breast cancer were eligible.Results: Of 18 patients treated, 16 received daily afatinib 20 mg and two 30 mg. Overall, 4 of 13 and 2 of 2 patients receiving afatinib 20 mg and 30 mg, respectively, experienced dose-limiting toxicity (DLT; all CTCAE grade 3 diarrhea). Most frequent treatment-related adverse events were diarrhea (94%), rash (56%), and fatigue (56%). Overall, pharmacokinetic profiles of afatinib and trastuzumab in combination were consistent with the known characteristics of each alone. Overall, objective response and disease control rates were 11% and 39%, respectively, with median progression-free survival 111.0 days (95% confidence interval, 56.0–274.0).Conclusions: The MTD of afatinib was 20 mg daily combined with the recommended weekly dose of trastuzumab, with 1 of 6 patients showing DLTs in the dose escalation. However, additional DLTs occurred in the dose-expansion phase meaning that this MTD cannot be recommended for phase II development without strict diarrhea management. There was no evidence suggesting relevant pharmacokinetic drug–drug interactions. Signs of clinical activity were seen in trastuzumab-resistant HER2-positive breast cancer, suggesting further investigation with optimal diarrhea management is warranted. Clin Cancer Res; 21(12); 2737–44. ©2014 AACR.See related commentary by Sledge and Pegram, p. 2663
Published: 2023

16. Data from RelB Expression Determines the Differential Effects of Ascorbic Acid in Normal and Cancer Cells

Author: William H. St. Clair, Daret K. St. Clair, Jinfei Chen, Chi Wang, Teresa Noel, David Schnell, Luksana Chaiswing, Fang Fang Xu, Yong Xu, and Xiaowei Wei
Abstract: Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced injury. We found that the NF-κB transcription factor RelB is a pivotal determinant in the differential radiosensitization effects of ascorbic acid in prostate cancer cells and normal prostate epithelial cells. Mechanistically, high reactive oxygen species concentrations suppress RelB in cancer cells. RelB suppression decreases expression of the sirtuin SIRT3 and the powerful antioxidant MnSOD, which in turn increases oxidative and metabolic stresses in prostate cancer cells. In contrast, ascorbic acid enhances RelB expression in normal cells, improving antioxidant and metabolic defenses against radiation injury. In addition to showing how RelB mediates the differential effects of ascorbic acid on cancer and normal tissue radiosensitivities, our work also provides a proof of concept for the existence of redox modulators that can improve the efficacy of radiotherapy while protecting against normal tissue injury in cancer settings. Cancer Res; 77(6); 1345–56. ©2017 AACR.
Published: 2023

17. Supplementary Table S1 from Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer

Author: David Schnell, Katy Pelling, Graham Temple, Martina Uttenreuther-Fischer, Ruth Plummer, Robert Laing, Helen Hatcher, Duncan Wheatley, and Alistair Ring
Abstract: Supplementary Table S1. Best overall response (RECIST version 1.1)
Published: 2023

18. Supplemental Figure S2 from RelB Expression Determines the Differential Effects of Ascorbic Acid in Normal and Cancer Cells

Author: William H. St. Clair, Daret K. St. Clair, Jinfei Chen, Chi Wang, Teresa Noel, David Schnell, Luksana Chaiswing, Fang Fang Xu, Yong Xu, and Xiaowei Wei
Abstract: After treatment with AA, the expression of RelB, Bcl-xL, and Bax in PC3 and PZ cells was quantified by western blots by RT-PCR.
Published: 2023

19. Supplemental Table and Figure Legend from RelB Expression Determines the Differential Effects of Ascorbic Acid in Normal and Cancer Cells

Author: William H. St. Clair, Daret K. St. Clair, Jinfei Chen, Chi Wang, Teresa Noel, David Schnell, Luksana Chaiswing, Fang Fang Xu, Yong Xu, and Xiaowei Wei
Abstract: Legends for Supplemental Table S1 and Supplemental Figures S1-S3.
Published: 2023

20. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Author: Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, 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 Dijon - Hôpital François Mitterrand (CHU Dijon), 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-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-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)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio]
Abstract: Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
Published: 2023

21. Monitoring of renal perfusion

Author: David Schnell, Antoine Guillaume Schneider, and Michael Darmon
Subjects: Perfusion, Extracorporeal Circulation, Humans, Kidney, Critical Care and Intensive Care Medicine, Renal Circulation
Published: 2022

22. A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial

Author: Nancy, Kentish-Barnes, Sylvie, Chevret, Sandrine, Valade, Samir, Jaber, Lionel, Kerhuel, Olivier, Guisset, Maëlle, Martin, Amélie, Mazaud, Laurent, Papazian, Laurent, Argaud, Alexandre, Demoule, David, Schnell, Eddy, Lebas, Frédéric, Ethuin, Emmanuelle, Hammad, Sybille, Merceron, Juliette, Audibert, Clarisse, Blayau, Pierre-Yves, Delannoy, Alexandre, Lautrette, Olivier, Lesieur, Anne, Renault, Danielle, Reuter, Nicolas, Terzi, Bénédicte, Philippon-Jouve, Maud, Fiancette, Michel, Ramakers, Jean-Philippe, Rigaud, Virginie, Souppart, Karim, Asehnoune, Benoît, Champigneulle, Dany, Goldgran-Toledano, Jean-Louis, Dubost, Pierre-Edouard, Bollaert, Renaud, Chouquer, Frédéric, Pochard, Alain, Cariou, and Elie, Azoulay
Subjects: Adult, Male, Patient Care Team, Terminal Care, Attitude to Death, Communication, Standard of Care, General Medicine, Middle Aged, Intensive Care Units, Professional-Family Relations, Humans, Family, Female, Grief, Empathy, Aged, Bereavement
Abstract: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes.We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992.Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95).Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms.French Ministry of Health.
Published: 2022

23. Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry

Author: Paul Chinardet, Floriane Gilles, Helene Cochet, Jonathan Chelly, Jean-Pierre Quenot, Gwenaelle Jacq, Pauline Soulier, Olivier Lesieur, Pascal Beuret, Mathilde Holleville, Cedric Bruel, Pierre Bailly, Bertrand Sauneuf, Caroline Sejourne, Arnaud Galbois, Candice Fontaine, François Perier, Nicolas Pichon, Marine Arrayago, Nicolas Mongardon, David Schnell, Jean-Baptiste Lascarrou, Raphaële Convers, and Stephane Legriel
Subjects: Critical Care and Intensive Care Medicine
Abstract: To describe early electrocardiogram (ECG) abnormalities after status epilepticus (SE) and evaluate their association with 90-day neurological outcomes.Retrospective analysis of a multicenter, national prospective registry between February 2018 and June 2020.Sixteen ICUs in France, IctalGroup Research Network.Adults with available ECG performed less than or equal to 24 hours after the onset of SE and less than or equal to 12 hours after its resolution.Double-blinded review of all ECGs was performed by two independent cardiologists. ECGs were categorized as normal/abnormal and then with minor/major early ECG abnormalities according to the Novacode ECG Classification system.Among 155 critically ill patients with SE, early ECG abnormalities were encountered in 145 (93.5%), categorized as major in 91 of 145 (62.8%). In addition to sinus tachycardia, the main abnormalities were in the ST segment (elevation [16.6%] or depression [17.9%]) or negative T waves (42.1%). Major early ECG abnormalities were significantly associated with respiratory distress and sinus tachycardia at the scene and hyperlactatemia at ICU admission. By multivariable analysis, three variables were significantly associated with 90-day poor outcome: age, preexisting ultimately fatal comorbidity, and cerebral insult as the cause of SE. Early major ECG abnormalities were not independently associated with 90-day functional outcome.In our study, early ECG abnormalities in the acute phase of SE were frequent, often unrecognized and were associated with clinical and biological stigma of hypoxemia. Although they were not independently associated with 90-day functional outcome, ECG changes at the early stage of SE should be systematically evaluated.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03457831.
Published: 2022

24. Performance of Doppler-Based Resistive Index and Semiquantitative Renal Perfusion in Predicting Persistent Acute Kidney Injury According to Operator Experience: Post Hoc Analysis of a Prospective Multicenter Study*

Author: Anastasia, Saade, Aurelie, Bourmaud, David, Schnell, Michael, Darmon, and Jeremy, Terreaux
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Kidney, Critical Care and Intensive Care Medicine, Logistic regression, Cohort Studies, symbols.namesake, Internal medicine, Post-hoc analysis, medicine, Humans, Prospective Studies, Receiver operating characteristic, business.industry, Acute kidney injury, Odds ratio, Acute Kidney Injury, medicine.disease, Perfusion, Cardiology, symbols, Female, Vascular Resistance, business, Doppler effect, Cohort study
Abstract: OBJECTIVES The Doppler-based resistive index and semiquantitative evaluation of renal perfusion using color Doppler failed to discriminate renal recovery patterns in a recent study. The influence of operator experience on resistive index and semiquantitative evaluation of renal perfusion performances is however unknown. This study aimed at evaluating the performance of resistive index and semiquantitative evaluation of renal perfusion according to the operator experience to predict short-term renal prognosis in critically ill patients. DESIGN Preplanned ancillary analysis of a prospective multicenter cohort study. SETTING Seven ICUs. PATIENTS Unselected ICU patients. INTERVENTION Renal Doppler was performed at admission to the ICU. The diagnostic performance of resistive index and semiquantitative evaluation of renal perfusion to predict persistent acute kidney injury at day 3 was evaluated. MAIN RESULTS Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had acute kidney injury (n = 233; 66.3%), of whom 136 had persistent acute kidney injury (58.4%). Overall performance in discriminating persistent acute kidney injury was however null with an area under the receiver operating characteristic curve less than 0.6 for both resistive index and semiquantitative evaluation of renal perfusion, and no difference across operator experience. A multivariate analysis using logistic regression with the center as a random effect adjusted on the operator experience showed no association between resistive index (odds ratio, 0.02 per international units (95% CI, 0.00-18.60 international units]) or semiquantitative evaluation of renal perfusion (odds ratio, 0.96 per international units [95% CI, 0.43-2.11 international units]) and persistent acute kidney injury. Similar results were obtained within subgroups of expert and nonexpert operators. CONCLUSIONS Doppler-based measurements performed by an expert or a nonexpert operator did not discriminate renal recovery patterns and neither modified the risk stratification of acute kidney injury persistence.
Published: 2021

25. 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

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

Author: Pierre-Louis Declercq, Isabelle Fournel, Matthieu Demeyere, Eléa Ksiazek, Nicolas Meunier-Beillard, Antoine Rivière, Caroline Clarot, Julien Maizel, David Schnell, Gaetan Plantefeve, Alexandre Ampere, Cédric Daubin, Bertrand Sauneuf, Pierre Kalfon, Laura Federici, Élise Redureau, Mehdi Bousta, Laurie Lagache, Thierry Vanderlinden, Saad Nseir, Béatrice La Combe, Gaël Bourdin, Mehran Monchi, Martine Nyunga, Michel Ramakers, Walid Oulehri, Hugues Georges, Charlotte Salmon Gandonniere, Julio Badie, Agathe Delbove, Xavier Monnet, Gaetan Beduneau, Élise Artaud-Macari, Paul Abraham, Nicolas Delberghe, Gurvan Le Bouar, Arnaud-Felix Miailhe, Sami Hraiech, Vanessa Bironneau, Nicholas Sedillot, Marie-Anne Hoppe, Saber Davide Barbar, George-Daniel Calcaianu, Jean Dellamonica, Nicolas Terzi, Cyrille Delpierre, Stéphanie Gélinotte, Jean-Philippe Rigaud, Marie Labruyère, Marjolaine Georges, Christine Binquet, and Jean-Pierre Quenot
Subjects: Cohort Studies, Oxygen, Respiratory Distress Syndrome, Treatment Outcome, Social Class, SARS-CoV-2, Quality of Life, COVID-19, Humans, General Medicine, Prospective Studies
Abstract: IntroductionPrognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients’ health practices and identify social representations of health, disease and care.Methods and analysisThe "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d’Examen de Santé" (EPICES) score ≥30.17 at inclusion.Ethics and disseminationThe study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses.Trial registration numberNCT04556513
Published: 2022

27. 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

28. [Therapeutic drug monitoring of cyamemazine: How to interpret a concentration? A review of literature]

Author: Hugo, Alarcan, David, Schnell, Stéphane, Rouleau, Anissa, Chachia, Franck, Saint-Marcoux, Olivier, Mathieu, and Sylvain, Couderc
Subjects: Anti-Anxiety Agents, Phenothiazines, Humans, Hypnotics and Sedatives, Drug Monitoring, Antipsychotic Agents
Abstract: Cyamemazine is the most prescribed antipsychotic drug in France, often in combination with another antipsychotic, for its sedative and anxiolytic component. Providing to physicians serum concentrations of cyamemazine in different contexts (compliance checking, ineffectiveness, adverse effects, intoxication, modification of pharmacokinetic parameters…) requires to interpret them correctly. This article presents an update on how to interpret a concentration of cyamemazine, wich remains poorly documented. The anxiolysis occurs at steady-state serum trough concentrations of 4 to 5μg/L; the antipsychotic effect from 18-20μg/L. Cyamemazine is not a drug with a narrow therapeutic window and concentrations up to 400μg/L may be sought in cases of partial efficacy; concentrations of 1800μg/L might be fatal; lower concentrations might be fatal if association with high others concentrations of drugs.
Published: 2021

29. Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening.

Author: Birgit Schlegel, Christian Laggner, René Meier, Thierry Langer, David Schnell, Roland Seifert, Holger Stark, Hans-Dieter Höltje, and Wolfgang Sippl
Published: 2007
Full Text: View/download PDF

30. Performance of renal Doppler to predict the occurrence of acute kidney injury in patients without acute kidney injury at admission

Author: David Schnell, Aurélie Bourmaud, Marie Reynaud, Stéphane Rouleau, Hamid Merdji, Alexandra Boivin, Mourad Benyamina, François Vincent, Alexandre Lautrette, Christophe Leroy, Yves Cohen, Matthieu Legrand, Jérôme Morel, Jeremy Terreaux, and Michael Darmon
Subjects: Cohort Studies, Male, Critical Illness, Humans, Female, Ultrasonography, Doppler, Prospective Studies, Acute Kidney Injury, Critical Care and Intensive Care Medicine, Kidney
Abstract: This study aimed at evaluating the performance of Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color-Doppler (SQP) to predict de novo AKI in the subgroup of critically ill patients without AKI at admission.This study is an ancillary analysis of a prospective multicenter cohort study. Consecutive ICU patients requiring mechanical ventilation were included. Renal Doppler was performed at ICU admission. The diagnostic performance of RI and SQP to predict de novo AKI at day 3 was evaluated.Among the 371 patients of the prospective cohort, 118 without AKI at study inclusion were included. Thirty-four patients (29%) developed an AKI. Neither RI (0.64 UI [0.57-0.70] vs 0.67 [0.62-0.70] in no AKI and de novo AKI group respectively, p = 0.177) nor SQP (2 [2, 3] vs 2 [1-3] in no AKI and de novo AKI group respectively, p = 0.061) were associated with AKI occurrence. Overall performance in predicting de novo AKI was null to poor with area under ROC curve of respectively 0.60 (95% CI 0.49-0.65) and 0.58 (95% CI 0.47-0.60) for RI and SQP. Similar results were obtained after adjustment for confounders.These results confirm the poor performance of Doppler-based indices in predicting renal prognosis of ICU patients.
Published: 2021

31. 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

32. Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study

Author: Damien Contou, Gwenhaël Colin, Brendan Travert, Sébastien Jochmans, Marie Conrad, Jean-Baptiste Lascarrou, Benoit Painvin, Alexis Ferré, David Schnell, Béatrice La Combe, Rémi Coudroy, Stephan Ehrmann, Jérôme Rambaud, Arnaud Wiedemann, Pierre Asfar, Pierre Kalfon, Emmanuel Guérot, Sébastien Préau, Laurent Argaud, Florence Daviet, Jean Dellamonica, Audrey Dupont, Muriel Fartoukh, Toufik Kamel, Gaetan Beduneau, Florence Canouï-Poitrine, Emmanuelle Boutin, Gérard Lina, Armand Mekontso Dessap, Anne Tristan, Nicolas de Prost, French m-TSS Study Group, Centre Hospitalier Victor Dupouy, CH Départemental Vendée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Melun (CHM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Laboratoire Lasers, Plasmas et Procédés photoniques (LP3), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Angoulême (CH Angoulême), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation polyvalente [Chartres], Hôpital Louis Pasteur [Chartres], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation (ORLEANS - Réa), Centre Hospitalier Régional d'Orléans (CHRO), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, CarMeN, laboratoire, Centre Hospitalier de Melun, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Staphylococcus aureus, medicine.medical_specialty, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Disease, law.invention, Sepsis, Menstruation, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Intensive care, medicine, Humans, 030212 general & internal medicine, Child, menstrual toxic shock syndrome, Retrospective Studies, Superantigens, Critically ill, business.industry, Medical record, Tracheal intubation, Toxic shock syndrome, Retrospective cohort study, Staphylococcal Infections, tampon, bacterial infections and mycoses, Institutional review board, medicine.disease, Shock, Septic, Intensive care unit, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Infectious Diseases, Icu, Female, Observational study, menstruation, business
Abstract: Background Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. Methods This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. Results In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. Conclusions In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.
Published: 2021

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

Author: Noëlle Brulé, Emmanuel Canet, Morgane Péré, Fanny Feuillet, Maryvonne Hourmant, Karim Asehnoune, Bertrand Rozec, Agnes Duveau, Laurent Dube, Marc Pierrot, Stanislas Humbert, Patrice Tirot, Jean-Marc Boyer, Laurent Martin-Lefevre, François Labadie, René Robert, Thierry Benard, Thomas Kerforne, Antoine Thierry, Olivier Lesieur, Jean-François Vincent, Mathieu Lesouhaitier, Raphaelle Larmet, Cecile Vigneau, Angelique Goepp, Pierre Bouju, Charlotte Quentin, Pierre-Yves Egreteau, Olivier Huet, Anne Renault, Yannick Le Meur, Jean-Christophe Venhard, Mathias Buchler, Olivier Michel, Marie-Hélène Voellmy, Fabien Herve, David Schnell, Anne Courte, Denis Glotz, Lucile Amrouche, Marc Hazzan, Nassim Kamar, Valerie Moal, Jeremy Bourenne, Moglie Le Quintrec-Donnette, Emmanuel Morelon, Thierry Boulain, Philippe Grimbert, Anne Elisabeth Heng, Pierre Merville, Aude Garin, Christian Hiesse, Brice Fermier, Christiane Mousson, Charlotte Guyot-Colosio, Nicolas Bouvier, Jean-Philippe Rerolle, Antoine Durrbach, Sarah Drouin, Sophie Caillard, Luc Frimat, Sophie Girerd, Laetitia Albano, Lionel Rostaing, Dominique Bertrand, Alexandre Hertig, Pierre-Francois Westeel, Florent Montini, Eric Delpierre, Dider Dorez, Eric Alamartine, Carole Ouisse, Veronique Sebille, and Jean Reignier
Subjects: Graft Survival, Humans, Multicenter Studies as Topic, Transplants, Hypothermia, General Medicine, Kidney, Kidney Transplantation, Tissue Donors, Randomized Controlled Trials as Topic
Abstract: IntroductionExpanded-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 analysisHYPOREME 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 disseminationThe 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 numberNCT03098706.
Published: 2022

34. Performance of Doppler-based resistive index and semi-quantitative renal perfusion in predicting persistent AKI: results of a prospective multicenter study

Author: Alexandra Boivin, Jeremy Terreaux, Stéphane Rouleau, Yves Cohen, Marie Reynaud, Aurélie Bourmaud, Mourad Benyamina, Michael Darmon, Ferhat Meziani, Alexandre Lautrette, David Schnell, Matthieu Legrand, Jérôme Morel, François Vincent, and Christophe Leroy
Subjects: Adult, Male, medicine.medical_specialty, Critical Care, Critical Illness, 030204 cardiovascular system & hematology, urologic and male genital diseases, Critical Care and Intensive Care Medicine, Renal Circulation, law.invention, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Predictive Value of Tests, law, Internal medicine, Humans, Medicine, Prospective Studies, Ultrasonography, Doppler, Color, Renal perfusion, Aged, business.industry, Acute kidney injury, 030208 emergency & critical care medicine, Acute Kidney Injury, Middle Aged, medicine.disease, Intensive care unit, Resistive index, Renal Replacement Therapy, ROC Curve, Multicenter study, Cardiology, symbols, Female, Vascular Resistance, business, Doppler effect, Semi quantitative, Cohort study
Abstract: The Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color Doppler (SQP) have shown promising results for predicting persistent acute kidney injury (AKI) in preliminary studies. This study aimed at evaluating the performance of RI and SQP to predict short-term renal prognosis in critically ill patients.Prospective multicenter cohort study including unselected critically ill patients. Renal Doppler was performed at admission to the intensive care unit. The diagnostic performance of RI and SQP to predict persistent AKI at day 3 was evaluated.Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had AKI (n = 233; 66.3%), of whom 136 had persistent AKI (58.4%). Doppler-based RI was higher and SQP lower in AKI patients and according to AKI recovery. Overall performance in predicting persistent AKI was however poor with area under ROC curve of respectively 0.58 (95% CI 0.52-0.64) and 0.59 (95% CI 0.54-0.65) for RI and SQP. Optimal cutoff was respectively 0.71 and 2 for RI and SQP. At optimal cutoff, sensitivity and specificity were 50% (95% CI 41-58%) and 68% (62-74%) for RI and 39% (32-45%) and 75% (66-82%) for SQP.Although statistically associated with AKI occurrence, RI and SQP perform poorly in predicting persistent AKI at day 3. Further studies are needed to adequately describe factors influencing Doppler-based assessment of renal perfusion and to delineate whether these indicators may be useful at the bedside. CLINICALTRIAL.GOV: NCT02355314.
Published: 2018

35. Comparison of etomidate and sodium thiopental for induction during rapid sequence intubation in convulsive status epilepticus: A retrospective single-center study

Author: Gwenaëlle Jacq, Sybille Merceron, Sébastien Cavelot, Olivier Richard, Mathilde Holleville, Stéphane Legriel, François Perier, Anne-Laure Chateauneuf, and David Schnell
Subjects: Male, medicine.medical_treatment, Status epilepticus, law.invention, 03 medical and health sciences, Epilepsy, Status Epilepticus, 0302 clinical medicine, Risk Factors, Etomidate, law, Intensive care, Humans, Hypnotics and Sedatives, Medicine, Intubation, Glasgow Coma Scale, Longitudinal Studies, 030212 general & internal medicine, Thiopental, Critical Care Outcomes, Aged, Retrospective Studies, Coma, business.industry, Hemodynamics, General Medicine, Middle Aged, medicine.disease, Intensive care unit, Treatment Outcome, Sodium thiopental, Neurology, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Purpose Few outcome data are available about morbidity associated with endotracheal intubation modalities in critically ill patients with convulsive status epilepticus. We compared etomidate versus sodium thiopental for emergency rapid sequence intubation in patients with out-of-hospital convulsive status epilepticus. Methods Patients admitted to our intensive care unit in 2006–2015 were studied retrospectively. The main outcome measure was seizure and/or status epilepticus recurrence within 12 h after rapid sequence intubation. Results We included 97 patients (60% male; median age, 59 years [IQR, 48–70]). Median time from seizure onset to first antiepileptic drug was 60 min [IQR, 35–90]. Reasons for intubation were coma in 95 (98%), acute respiratory distress in 18 (19%), refractory convulsive status epilepticus in 9 (9%), and shock in 6 (6%) patients; 50 (52%) patients had more than one reason. The hypnotic drugs used were etomidate in 54 (56%) and sodium thiopental in 43 (44%) patients. Seizure and/or status epilepticus recurred in 13 (56%) patients in the etomidate group and 11 patients (44%) in the sodium thiopental group (adjusted common odds ratio [aOR], 0.98; 95%CI, 0.36–2.63; P = 0.97). The two groups were not significantly different for proportions of patients with hemodynamic instability after intubation (aOR, 0.60; 95%CI, 0.23–1.58; P = 0.30) or with difficult endotracheal intubation (OR, 1.28; 95% CI 0.23 to 7.21; P=0.77). Conclusions Our findings argue against a difference in seizure and/or status epilepticus recurrences rates between critically ill patients with convulsive status epilepticus given etomidate vs. sodium thiopental as the induction agent for emergency intubation.
Published: 2018

36. Thyroid Storm in the ICU: A Retrospective Multicenter Study

Author: Pierre Fillatre, Serge Carreira, Romain Sonneville, Nadia Aissaoui, Julien Charpentier, Yoann Zerbib, David Schnell, Claire Pichereau, Xavier Repessé, Yacine Tandjaoui-Lambiotte, Alexandre Lautrette, Aurélien Frérou, Etienne de Montmollin, Sami Hraiech, Romain Persichini, Matthieu Schmidt, Antoine Kimmoun, Alain Combes, Olivier Ellrodt, Maxime Coutrot, Bruno Mégarbane, Nicolas Terzi, Cecile Aubron, Keyvan Razazi, Elie Azoulay, Alexis Ferré, François Barbier, Vincent Peigne, Elise Morawiec, Danielle Reuter, Guillaume Voiriot, Clément Delmas, Saad Nseir, Naïke Bigé, Simon Bourcier, and Jean-Baptiste Lascarrou
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, medicine, Thyroid storm, Humans, Renal replacement therapy, 10. No inequality, Survival rate, Aged, Retrospective Studies, business.industry, Mortality rate, Cardiogenic shock, Thyroid, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Survival Rate, Intensive Care Units, medicine.anatomical_structure, Emergency medicine, Female, Thyroid Crisis, business
Abstract: Objectives Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome 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 patients with those most severe thyroid storm forms requiring ICU admission. Design Retrospective, multicenter, national study over an 18-year period (2000-2017). Setting Thirty-one French ICUs. Patients The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. Measurements and main results Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. Conclusions Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.
Published: 2019

37. 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

38. 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

39. De-escalation of antimicrobial therapy in critically ill hematology patients: a prospective cohort study

Author: Antoine Rabbat, Michael Darmon, Achille Kouatchet, Matthieu Resche-Rigon, Jean-Ralph Zahar, Djamel Mokart, Claire Montlahuc, Fabrice Bruneel, François Vincent, Frédéric Pène, David Schnell, Elie Azoulay, and Virginie Lemiale
Subjects: Male, medicine.medical_specialty, Hematology, business.industry, Critical Illness, Pain medicine, MEDLINE, Middle Aged, Critical Care and Intensive Care Medicine, Antimicrobial, Hematologic Diseases, Anti-Bacterial Agents, Cohort Studies, Anesthesiology, Internal medicine, Humans, Medicine, Female, Prospective Studies, business, Intensive care medicine, Prospective cohort study, De-escalation, Aged, Cohort study
Published: 2019

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

Author: Jean-Pierre Quenot, Nicolas Grégoire, Stephan Ehrmann, Mai-Anh Nay, Benoit Veber, François Barbier, Jean-Claude Lacherade, Qin Lu, Grégoire Muller, Thierry Boulain, Julie Helms, Marie Leclerc, Pascal Andreu, Gaëtan Plantefève, Deborah Le Pennec, Renaud Respaud, Claire Dahyot-Fizelier, Elsa Tavernier, Martine Ferrandière, Gaetan Beduneau, Laurent Vecellio, Anne Veinstein, Philippe Seguin, Maria Cabrera, Hamid Merdji, David Schnell, Jean-Etienne Herbrecht, Damien Roux, Sigismond Lasocki, Ferhat Meziani, Philippe Lanotte, Mickael Landais, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Les Hôpitaux Universitaires de Strasbourg (HUS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Le Mans (CH Le Mans), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre Hospitalier d'Angoulême (CH Angoulême), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Victor Dupouy, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Départemental Vendée (CHDV), University Hospital of Tours, France, Programme Hospitalier de Recherche Clinique National 2015 of the French Ministry of Health (PHRC-15-260), Association pour la promotion à Tours de la Réanimation Médicale, HAL-SU, Gestionnaire, 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), 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, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, medicine.medical_treatment, infectious diseases, Placebo, law.invention, respiratory infections, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Informed consent, law, Administration, Inhalation, medicine, Humans, Multicenter Studies as Topic, Amikacin, adult intensive & critical care, Randomized Controlled Trials as Topic, Mechanical ventilation, clinical trials, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Intensive Care, Ventilator-associated pneumonia, Pneumonia, Ventilator-Associated, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Respiration, Artificial, 3. Good health, Clinical trial, Pneumonia, Treatment Outcome, 030228 respiratory system, Emergency medicine, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: IntroductionPre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia.Methods and analysisAcademic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee.Ethics and disseminationThe protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals.Trial registration numbersEudraCT 2016-001054-17 and NCT03149640.
Published: 2021

41. Cuff Leak Test for the Diagnosis of Post-Extubation Stridor: A Multicenter Evaluation Study

Author: Sandrine Valade, Lucas Strasbach, Sybille Merceron, Asael Berger, Julien Mayaux, Stéphane Legriel, Ferhat Meziani, Michael Darmon, Benjamin Planquette, and David Schnell
Subjects: Adult, Male, Leak, medicine.medical_specialty, Time Factors, Stridor, Endotracheal intubation, Critical Care and Intensive Care Medicine, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Prospective Studies, Aged, Diagnostic Equipment, Respiratory Sounds, business.industry, Critically ill, Reproducibility of Results, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, Respiratory Function Tests, Surgery, Test (assessment), Intensive Care Units, 030228 respiratory system, Anesthesia, Cuff, Airway Extubation, Female, medicine.symptom, business
Abstract: Background: Cuff leak test was developed to predict the occurrence of post-extubation stridor (PES). This study evaluated the diagnostic performance of this test in unselected critically ill patients. Methods: Multicenter prospective study including unselected ventilated patients at the time of their first planned extubation. The diagnostic performance of 4 different cuff leak tests was assessed. Results: Post-extubation stridor occurred in 34 (9.4%) of 362 included patients. Compared to patients without PES, patients with PES required more frequently reintubation (6 [17.6%] vs 26 [7.9%], P = .041), prolonged duration of ventilation (6 [3-13] vs 5 [2-9] days, P = .029), and longer intensive care unit (ICU) stay (12 [6-17.5] vs 7.5 [4-13] days, P = .018). However, ICU mortality was similar in both groups (1 [2.9%] vs 23 [7.0%], P = .61). The 4 cuff leak tests display poor diagnostic accuracy: sensitivities ranging from 27% to 46%, specificities from 70% to 88%, positive predictive values from 14% to 19%, and negative predictive values from 92% to 93%. Conclusion: Post-extubation stridor occurs in less than 10% of unselected critically ill patients. The several cuff leak tests display limited diagnostic performance for the detection of PES. Given the high rate of false positives, routine cuff leak test may expose to undue prolonged mechanical ventilation.
Published: 2017

42. Notre revue Médecine Intensive Réanimation

Author: David Schnell and Thomas Ritzenthaler
Subjects: Political science, Emergency Medicine, Emergency Nursing, Humanities
Abstract: Chères lectrices, chers lecteurs,Au fil des années, la revue Médecine Intensive Réanimation a évolué avec notre spécialité en gardant pour principal objectif la formation continue des médecins intensivistes réanimateurs francophones. Cette année, elle franchit une nouvelle étape en devenant entièrement produite par notre société. Dès janvier 2020, Mme Juliette Berthoin, Responsable des Publications de la SRLF, assurera le secrétariat et le processus éditorial de la revue sous la houlette de M. Martin Lavillonnière, Directeur Administratif de la SRLF, fort de son expérience dans le domaine.
Published: 2020

43. 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

44. NMDA receptor antagonists traxoprodil and lanicemine improve hippocampal-prefrontal coupling and reward-related networks in rats

Author: Robert Becker, Cornelia Dorner-Ciossek, David Schnell, Wolfgang Weber-Fahr, Alexander Sartorius, Lothar Kußmaul, Stefan Scheuerer, Natalia Gass, and Bernhard Schmid
Subjects: Male, Pyridines, Traxoprodil, Prefrontal Cortex, Hippocampal formation, Hippocampus, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Piperidines, Reward, Phenethylamines, medicine, Animals, Ketamine, Pharmacology, Chemistry, Antagonist, Magnetic Resonance Imaging, Antidepressive Agents, 030227 psychiatry, Rats, Mechanism of action, Lanicemine, Antidepressant, NMDA receptor, medicine.symptom, Neuroscience, Excitatory Amino Acid Antagonists, 030217 neurology & neurosurgery, medicine.drug
Abstract: The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine is known to have not only a rapid antidepressant effect but also dissociative side effects. Traxoprodil and lanicemine, also NMDA antagonists, are candidate antidepressant drugs with fewer side effects. In order to understand their mechanism of action, we investigated the acute effects of traxoprodil and lanicemine on brain connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Functional connectivity (FC) alterations were examined using interregional correlation networks. Graph theoretical methods were used for whole brain network analysis. As interest in NMDAR antagonists as potential antidepressants was triggered by the antidepressant effect of ketamine, results were compared to previous findings from our ketamine studies. Similar to ketamine but to a smaller extent, traxoprodil increased hippocampal-prefrontal (Hc-PFC) coupling. Unlike ketamine, traxoprodil decreased connectivity within the PFC. Lanicemine had no effect on these properties. The improvement of Hc-PFC coupling corresponds well to clinical result, showing ketamine to have a greater antidepressant effect than traxoprodil, while lanicemine has a weak and transient effect. Connectivity changes overlapping between the drugs as well as alterations of local network properties occurred mostly in reward-related regions. The antidepressant effect of NMDA antagonists appears to be associated with enhanced Hc-PFC coupling. The effects on local network properties and regional connectivity suggest that improvement of reward processing might also be important for understanding the mechanisms underlying the antidepressant effects of these drugs.
Published: 2019

45. 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

46. 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

47. 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

48. 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

49. Changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries

Author: Béatrice Eon, Sylvie Chevret, David Schnell, Benjamin Zuber, Ferhat Meziani, Elie Azoulay, Antoine Rabbat, Matthieu Schmidt, Jerome Aboab, Joel Cousson, Didier Perez, Celine Clergue, Samir Jaber, Vincent Das, Alexandre Demoule, Achille Kouatchet, Claude Guérin, Laurent Brochard, Hugues Georges, Annalisa Carlucci, Jean Dellamonica, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituti Clinici Scientifici Maugeri [Pavia] (IRCCS Pavia - ICS Maugeri), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology and Toxicology, Universität Regensburg (UR), Centre Hospitalier Sud Francilien, Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Raymond Poincaré [AP-HP], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Livet [Hôpital de la Croix Rousse, Hospices Civils de Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Réanimation polyvalente et des Maladies infectieuses, Centre Hospitalier Gustave Dron, Centre Hospitalier Tourcoing, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de l’Archet, Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Service de réanimation médicale, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Robert Debré, Centre Hospitalier Louis Pasteur [Dole], University of Toronto, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Critical Illness, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Acute respiratory failure, Critical Care and Intensive Care Medicine, 03 medical and health sciences, Mechanical ventilation, 0302 clinical medicine, Belgium, Anesthesiology, Non-invasive ventilation, Outcome, medicine, Humans, Prospective Studies, Intensive care medicine, Aged, Noninvasive Ventilation, Critically ill, business.industry, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, 3. Good health, Survival Rate, Intensive Care Units, 030228 respiratory system, Acute Disease, Critical illness, Female, Noninvasive ventilation, France, Respiratory Insufficiency, business
Abstract: PURPOSE: Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown. METHODS: Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries. RESULTS: Among the 4132 patients enrolled, 2094 (51%) required ventilatory support for ARF and 2038 (49 %) for non-respiratory conditions. Overall NIV use was markedly increased in 2010/11 compared to 1997 and 2002 (37% of mechanically ventilated patients vs. 16% and 28%, P < 0.05). In 2010/11, the use of first-line NIV for ARF had reached a plateau (24% vs. 16% and 23%, P < 0.05) whereas pre-ICU and post-extubation NIV had substantially increased (11% vs. 4% and 11% vs. 7%, respectively, P < 0.05). First-line NIV remained stable in acute-on-chronic RF, continued to increase in cardiogenic pulmonary edema, but decreased in de novo ARF (16% in 2010/11 vs. 23% in 2002, P < 0.05). The NIV success rate increased from 56% in 2002 to 70% in 2010/11 and remained the lowest in de novo ARF. NIV failure in de novo ARF was associated with increased mortality in 2002 but not in 2010/11. Mortality decreased over time, and overall, NIV use was associated with a lower mortality. CONCLUSION: Increases in NIV use and success rate, an overall decrease in mortality, and a decrease of the adverse impact NIV failure has in de novo ARF suggest better patient selection and greater proficiency of staff in administering NIV. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01449331.
Published: 2015

50. Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer

Author: Alistair Ring, Ruth Plummer, Helen Hatcher, Martina Uttenreuther-Fischer, Robert W. Laing, Duncan Wheatley, Graham Temple, David Schnell, and K Pelling
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Receptor, ErbB-2, Afatinib, Breast Neoplasms, Pharmacology, Breast cancer, Pharmacokinetics, Trastuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Neoplasm Metastasis, skin and connective tissue diseases, Adverse effect, neoplasms, Aged, Aged, 80 and over, business.industry, Cancer, Middle Aged, medicine.disease, Combined Modality Therapy, Rash, Clinical trial, Retreatment, Quinazolines, Female, medicine.symptom, business, medicine.drug
Abstract: Purpose: The HER2 mAb, trastuzumab, is a standard therapy for patients with HER2-positive breast cancer before acquired resistance. Afatinib, an irreversible, oral, small-molecule ErbB family blocker, shows clinical activity in trastuzumab-refractory HER2-positive breast cancer. Experimental Design: This phase I study used a 3+3 dose escalation to determine the MTD of oral once-daily afatinib in combination with the recommended dose of intravenous trastuzumab (4 mg/kg week 1; 2 mg/kg/wk thereafter). Adult women with confirmed advanced/metastatic HER2-positive breast cancer were eligible. Results: Of 18 patients treated, 16 received daily afatinib 20 mg and two 30 mg. Overall, 4 of 13 and 2 of 2 patients receiving afatinib 20 mg and 30 mg, respectively, experienced dose-limiting toxicity (DLT; all CTCAE grade 3 diarrhea). Most frequent treatment-related adverse events were diarrhea (94%), rash (56%), and fatigue (56%). Overall, pharmacokinetic profiles of afatinib and trastuzumab in combination were consistent with the known characteristics of each alone. Overall, objective response and disease control rates were 11% and 39%, respectively, with median progression-free survival 111.0 days (95% confidence interval, 56.0–274.0). Conclusions: The MTD of afatinib was 20 mg daily combined with the recommended weekly dose of trastuzumab, with 1 of 6 patients showing DLTs in the dose escalation. However, additional DLTs occurred in the dose-expansion phase meaning that this MTD cannot be recommended for phase II development without strict diarrhea management. There was no evidence suggesting relevant pharmacokinetic drug–drug interactions. Signs of clinical activity were seen in trastuzumab-resistant HER2-positive breast cancer, suggesting further investigation with optimal diarrhea management is warranted. Clin Cancer Res; 21(12); 2737–44. ©2014 AACR. See related commentary by Sledge and Pegram, p. 2663
Published: 2015

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

127 results on '"David Schnell"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources