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55 results on '"MESH: Sepsis"'

1. Liver transplantation for autoimmune hepatitis: Pre‐transplant does not predict the early post‐transplant outcome

Author

Yasmina Chouik, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Olivier Chazouillères, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, Jérôme Dumortier, Hospices Civils de Lyon (HCL), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Edouard Herriot [CHU - HCL], Clinique de la Sauvegarde [Lyon], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Fondation Léon Bouchut

Subjects
early infection, MESH: Liver Transplantation, immunosuppression, MESH: Humans, Hepatology, MESH: Hepatitis, Autoimmune, fulminant hepatitis, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, survival, sepsis, MESH: Massive Hepatic Necrosis, MESH: Female, MESH: Sepsis
Abstract

Background and aims: Autoimmune hepatitis (AIH) is a rare indication (

Published
2023
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2. Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections

Author

François Caméléna, Gauthier Péan de Ponfilly, Hélène Pailhoriès, Lucas Bonzon, Alexandre Alanio, Thibaut Poncin, Matthieu Lafaurie, François Dépret, Emmanuel Cambau, Sylvain Godreuil, Rachel Chenouard, Alban Le Monnier, Hervé Jacquier, Béatrice Berçot, 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, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Groupe Hospitalier Paris Saint-Joseph (hpsj), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris-Saclay, Centre hospitalier Saint-Joseph [Paris], Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, This study was supported by bioMérieux (Marcy L’Etoile, France), which providedconsumables. The funders had no role in study design, data collection and interpretation, ormanuscript preparation.F.C. received lecture fees from bioMérieux. F.D. received lecture fees from bioMérieuxand Sedana and grants from European Society of Intensive Care Medicine, Société Françaised’Anesthésie Reanimation, and the French Ministry of Research. A.A. received lecture feesand travel grants from Gilead Sciences and Pfizer and received grants from AgenceNationale de la Recherche. All other authors report no conflicts of interest., and bioMérieux (Marcy L’Etoile, France)European Society of Intensive Care MedicineSociété Française d’Anesthésie ReanimationFrench Ministry of Research. Gilead SciencesPfizerAgence Nationale de la Recherche

Subjects
Microbiology (medical), BCID2, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, FilmArray, Physiology, [SDV]Life Sciences [q-bio], bloodstream infection, MESH: Blood Culture, BSI, MESH: Gram-Positive Bacteria, sepsis, Biofire, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, resistance gene, MESH: Gram-Negative Bacteria, molecular diagnosis, Genetics, MESH: Bacteremia, MESH: Sepsis, rapid diagnosis, genotypic identification, MESH: Humans, General Immunology and Microbiology, Ecology, Cell Biology, MESH: Bacteria, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Abstract

International audience; The FilmArray Blood Culture Identification 2 panel (BCID2; bioMérieux) is a fully automated PCR-based assay for identifying bacteria, fungi, and bacterial resistance markers in positive blood cultures (BC) in about 1 h. In this multicenter study, we evaluated the performance of the BCID2 panel for pathogen detection in positive BC. Conventional culture and BCID2 were performed in parallel at four tertiary-care hospitals. We included 152 positive BC-130 monomicrobial and 22 polymicrobial cultures-in this analysis. The BCID2 assay correctly identified 90% (88/98) of Gram-negative and 89% (70/79) of Gram-positive bacteria. Five bacterial isolates targeted by the BCID2 panel and recovered from five positive BC, including three polymicrobial cultures, were missed by the BCID2 assay. Fifteen isolates were off-panel organisms, accounting for 8% (15/182) of the isolates obtained from BC. The mean positive percent agreement between the BCID2 assay and standard culture was 97% (95% confidence interval, 95 to 99%), with agreement ranging from 67% for Candida albicans to 100% for 17 targets included in the BCID2 panel. BCID2 also identified the blaCTX-M gene in seven BC, including one for which no extended-spectrum β-lactamase (ESBL)-producing isolate was obtained in culture. However, it failed to detect ESBL-encoding genes in three BC. Two of the 18 mecA/C genes detected by the BCID2 were not confirmed. No carbapenemase, mecA/C, or MREJ targets were detected. The median turnaround time was significantly shorter for BCID2 than for culture. The BCID2 panel may facilitate faster pathogen identification in bloodstream infections. IMPORTANCE Rapid molecular diagnosis combining the identification of pathogens and the detection of antibiotic resistance genes from positive blood cultures (BC) can improve the outcome for patients with bloodstream infections. The FilmArray BCID2 panel, an updated version of the original BCID, can detect 11 Gram-positive bacteria, 15 Gram-negative bacteria, 7 fungal pathogens, and 10 antimicrobial resistance genes directly from a positive BC. Here, we evaluated the real-life microbiological performance of the BCID2 assay in comparison to the results of standard methods used in routine practice at four tertiary care hospitals.

Published
2023
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3. Atrophie diaphragmatique séquellaire du sepsis : étude tomodensitométrique rétrospective

Author

Légère, Simon, Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), and Boris Jung

Subjects
Diaphragmatic atrophy, Diaphragme, MESH: Choc septique, Ventilation mécanique, Amyotrophy, Tomodensitométrique, MESH: Intensive care units, MESH: Shock, septic, MESH: Atrophie, Mechanical ventilation, Volumetry, Segmentation, Volumétrie, MESH: Diaphragm, MESH: Réanimation, MESH: Amyotrophie, Computed tomography, MESH: Sepsis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

In addition of the aftereffects associated with a critical illness and the aggressive intensive care management, diaphragm is affected by sepsis as well as other muscles such as psoas. Its mechanism and duration remain unclear but atrophic sequelae is a major factor of difficulties to ventilator withdrawal in ICU and long term physical rehabilitation. We tried to observe the importance of the diaphragm and psoas atrophy after ICU discharge comparing to anterior data.Methods: we retrospectively included 41 patients admitted in our ICU for a sepsis or a septic shock, and for whom CT-scans have been performed in the course of an oncological follow-up. We used a segmentation software to compare volumetric measurements of the diaphragmatic and the psoas before, and after the ICU stay. The primary endpoint was to the observable atrophy in this period. Results: between 2 CTs, 102±62 days apart, we found a significant loss of volume of 12,1% (that is 26±25 cm³, p59 years (p=0.01), whereas the atrophy of diaphragm was associated with height >166 cm (p=0.023) and absence of metastasis (p=0.031).Conclusion: the diaphragm and psoas are concurrently but independently affected by a loss of muscular mass, in case of severe infection admitted in ICU. We were able to be bring to light differential associated factors, giving reasons to believe that the pathophysiology behind the sepsis-linked atrophy of the diaphragm and psoas is not equivalent and comparable in all points.; En plus des effets néfastes de toute pathologie aiguë grave, et ceux secondaires à la prise en charge agressive de réanimation, le sepsis affecte tout spécifiquement le diaphragme ainsi que les autres muscles tels que le psoas.Mécanismes et évolution de cette agression demeurent obscurs, mais l'atrophie séquellaire est un facteur majeur de retard au sevrage de la ventilation mécanique puis à la rééducation et reprise d'une vie normale. Nous avons voulu observer la survenue de cette atrophie au décours d'un sepsis, en comparaison à des données antérieures au séjour en réanimation.Méthode : chez 41 patients admis réanimation (CHU Lapeyronie, 2015-2019) pour sepsis ou choc septique, nous avons calculé par méthode de segmentation informatique, le volume des psoas et du diaphragme sur des TDM antérieures et postérieures à l'hospitalisation, réalisées dans le cadre du suivi d'un cancer. Le critère principal était l'atrophie observable dans cet intervalle.Résultats : entre 2 TDM espacées de 102 ± 62 jours, nous avons confirmé une atrophie musculaire moyenne après séjour en réanimation pour sepsis, de 12.1 % (soit 26 ± 25 cm³, p < 0.01) pour le psoas et 10,7 % (soit 21 ± 25 cm³, p < 0.01) pour le diaphragme, sans corrélation statistique entre ces deux variations, mais la variation de diaphragme dépendant significativement du volume musculaire de base (p < 0.01). L'atrophie du psoas était associée a un antécédent artériopathique (p < 0.01) et l'âge > 59 ans (p < 0.01) ; alors que celle du diaphragme était associée à la taille > 166 cm (p = 0.023) et l'absence de métastases (p = 0.031).Conclusion : le diaphragme et le psoas semblent souffrir de manière concomitante mais indépendante d'une infection sévère en réanimation. Les facteurs qui s'y associent ne sont pas les mêmes, peut être du fait d'une réponse physiologique différente entre diaphragme et muscles périphériques.

Published
2021

4. Évaluation de la mortalité à 30 jours après passage aux urgences adultes Lapeyronie du CHU de Montpellier pour sepsis ou choc septique : étude avant-après mise en place d’un outil d’aide à la prescription anti-infectieuse

Author

Briquez, Jordan, Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), and Hamza Ghomrani

Subjects
Probabiliste, Before-after, MESH: Mortality, Pratiques professionnelles, MESH: Choc septique, MESH: Antibiothérapie, Probabilistic, Antibiotic therapy, MESH: Sepsie, Professional practice, MESH: Shock, septic, Avant-après, MESH: Mortalité, MESH: Emergencies, MESH: Sepsis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Urgences
Abstract

The anti-infectious strategy within a healthcare establishment is currently at the heart of public health issues. Severe septic states including sepsis and septic shock since 2016 are rapidly life-threatening with high mortality between 30 and 45% at one month. International and national recommendations concerning the comprehensive management of severe septic states and the need for early adapted probabilistic antibiotic therapy introduced within one hour of diagnosis have been issued since 2004 and updated regularly. Despite this, the antibiotic therapy for severe sepsis is still insufficiently adapted to the site of infection and to the patient, with an initiation period exceeding the "Golden Hour".Material and method: this retrospective before-after study carried out over a period of 13 months in the emergency medicine department of the CHU Montpellier took place in two phases. A first phase of six months called "before" of evaluation of professional practices with collection of data concerning each patient with severe sepsis, the antibiotic therapy introduced, the time to initiation and mortality at 30 days. The second six-month phase, called "after", took place 1 month after the implementation of an anti-infectious prescription aid tool depending on the site and the patient's comorbidities. The same data collection was carried out for each patient with severe sepsis. A comparison between the two phases with multivariate analysis is carried out in order to assess the 30-day mortality according to the patient's inclusion phase.Results: from July 12, 2020 to August 12, 2021, 371 patients were included in the study with 186 patients in the "before" phase and 185 patients in the "after" phase. Univariate analyzes comparing the patients included in each phase found two comparable populations with a significant difference in immunosuppression, predominantly in the "after" phase. A significant difference concerning the primary endpoint was demonstrated in multivariate analysis with lower 30-day mortality in the “after” phase (p=0.043). A significant difference was also found concerning the antibiotic therapy initiated with an improvement in the prescription in the “after” phase (p

Published
2021

5. Listeria monocytogenes, a model in infection biology

Author

Marc Lecuit, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Agence Nationale de la RechercheH2020 European Research CouncilInsermInstitut Pasteur, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
Listeria, [SDV]Life Sciences [q-bio], Immunology, Cellular microbiology, Context (language use), Biology, medicine.disease_cause, MESH: Listeria monocytogenes, Microbiology, Mice, 03 medical and health sciences, Infection biology, Listeria monocytogenes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Sepsis, Virology, cell biology, medicine, Animals, Humans, Listeriosis, MESH: Animals, MESH: Food Microbiology, MESH: Mice, MESH: Sepsis, 030304 developmental biology, 0303 health sciences, MESH: Humans, 030306 microbiology, biology, animal model, pathogenesis, MESH: Host-Pathogen Interactions, Outbreak, Meningoencephalitis, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, infection, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Listeriosis, Host-Pathogen Interactions, Food Microbiology, Identification (biology), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Listeria monocytogenes causes listeriosis, a systemic infection which manifests as bacteremia, often complicated by meningoencephalitis in immunocompromised individuals and the elderly, and fetal-placental infection in pregnant women. It has emerged over the past decades as a major foodborne pathogen, responsible for numerous outbreaks in Western countries, and more recently in Africa. L. monocytogenes' pathogenic properties have been studied in detail, thanks to concomitant advances in biological sciences, in particular molecular biology, cell biology and immunology. L. monocytogenes has also been instrumental to basic advances in life sciences. L. monocytogenes therefore stands both a tool to understand biology and a model in infection biology. This review briefly summarises the clinical and some of the pathophysiological features of listeriosis. In the context of this special issue, it highlights some of the major discoveries made by Pascale Cossart in the fields of molecular and cellular microbiology since the mid-eighties regarding the identification and characterisation of multiple bacterial and host factors critical to L. monocytogenes pathogenicity. It also briefly summarises some of the key findings from our laboratory on this topic over the past years.

Published
2020
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6. Using SNOMED-CT to Help the Transition from Microbiological Data to ICD-10 Sepsis Codes

Author

Ternois, Iris, Billard-Pomares, Typhaine, Carbonelle, Etienne, Franchinard, Loriane, Duclos, Catherine, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Fœtale [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and duclos, catherine

Subjects
MESH: Humans, Medical coding, MESH: Systematized Nomenclature of Medicine, [INFO.INFO-CL] Computer Science [cs]/Computation and Language [cs.CL], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, International Classification of Diseases, Sepsis, Humans, Systematized Nomenclature of Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Sepsis, [INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL], MESH: International Classification of Diseases
Abstract

International audience; Assigning ICD-10 code of sepsis in regard of a pathogenic bacterium found in an haemoculture requires knowledge of microbiology because of the difference of granularity. The aim of this paper is to automate this coding thanks to the use of SNOMED-CT. A dichotomous classification of bacteria causing sepsis has been generated in respect of ICD-10. Our algorithm follows this and explores SNOMED-CT to assign the right ICD-10 code of the sepsis. Applied to a list of 164 bacteria, the system has an error rate of 1.22 %.

Published
2019
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7. Management of non-necrotizing cellulitis in France

Author

F. Roblot, B. Castan, X. Lemaire, E. Forestier, Céline Pulcini, Eric Bonnet, F.-X. Lescure, Service maladies infectieuses [CH Douai], Centre Hospitalier [Douai, Nord], Hôpital Joseph Ducuing, Centre hospitalier d'Ajaccio, Service de maladies infectieuses et médecine interne [Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Médecine interne [ Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)

Subjects
0301 basic medicine, Administration, Oral, MESH: Comorbidity, Comorbidity, MESH: Hospitalization, MESH: Health Care Surveys, 0302 clinical medicine, MESH: Practice Guidelines as Topic, Ambulatory Care, 030212 general & internal medicine, Practice Patterns, Physicians', Infusions, Intravenous, Dermo-hypodermites bactériennes non nécrosantes, Prospective cohort study, MESH: Sepsis, Necrotizing cellulitis, Disease Management, Anti-Bacterial Agents, 3. Good health, Hospitalization, Infectious Diseases, Hyperalgesia, Cellulitis, Practice Guidelines as Topic, MESH: Administration, Oral, Disease Progression, MESH: Disease Progression, France, medicine.medical_specialty, MESH: Ambulatory Care, 030106 microbiology, MESH: Drug Administration Schedule, MESH: Disease Management, Drug Administration Schedule, Sepsis, 03 medical and health sciences, Ambulatory care, MESH: Anti-Bacterial Agents, Internal medicine, medicine, Humans, MESH: Infusions, Intravenous, Intensive care medicine, MESH: Cellulitis, Streptocoque, MESH: Humans, Septic shock, business.industry, Streptococcus, medicine.disease, MESH: Hyperalgesia, MESH: France, Infectious disease (medical specialty), Health Care Surveys, MESH: Practice Patterns, Physicians', [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; OBJECTIVE:We aimed to assess medical practices of French infectious disease specialists or any other relevant physicians related to the management of non-necrotizing cellulitis (NNC).METHODS:We sent an online questionnaire to members of the French Infectious Diseases Society (SPILF) mailing list in September 2015.RESULTS:A total of 108 specialists took part in the survey and 10% (11/107) declared to always admit NNC patients to hospital. As for the others, 18% declared to admit patients in more than 80% of cases, 49% in 50-80% of cases, 26% in 20-50% of cases, and 7% in less than 20% of cases. The most frequent criteria for hospital admission were severe sepsis/septic shock (99%), poor social conditions (99%), rapid extension of skin lesions (93%), high level of pain (86%), and failure of first-line antibiotic therapy (84%). Participants mentioned similar criteria for reasons to initiate the intravenous (IV) antibiotic therapy. Fifty-three percent of respondents declared initiating antibiotic therapy using the IV route in more than 80% of cases. Physicians declared that the usual antibiotic therapy duration were 15 days (3%).CONCLUSION:Criteria for hospital admission and use of the IV route for antibiotic therapy as well as optimal treatment duration in patients presenting with NNC need to be detailed in guidelines and evaluated in prospective studies.

Published
2016
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8. Biomarker cruises in sepsis: who is the CAPTAIN? Discussion on 'Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study'

Author

Briassoulis, George, Briassoulis, Panagiotis, Miliaraki, Marianna, Ilia, Stavroula, Parlato, Marianna, Philippart, François, Rouquette, Alexandra, Moucadel, Virginie, Cavaillon, Jean-Marc, Misset, Benoît, Group, Combined Approach, University of Crete [Heraklion] (UOC), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine intensive et réanimation - Hôpital Saint-Joseph, Paris, Groupe Hospitalier Paris Saint-Joseph (hpsj), Endotoxines, Structures et Réponses de l'hôte (ESHR), Département Microbiologie (Dpt Microbio), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département d’Epidémiologie et de Biostatistiques, Hôpitaux Universitaires Paris Centre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), BIOMERIEUX, Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), CHU Rouen, Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Paris Saint-Joseph, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
medicine.medical_specialty, Icu patients, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Cohort Studies, Sepsis, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Anesthesiology, medicine, Humans, Prospective Studies, Prospective cohort study, MESH: Cohort Studies, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, MESH: Humans, business.industry, medicine.disease, MESH: Prospective Studies, 3. Good health, Intensive Care Units, Circulating biomarkers, MESH: Biomarkers, Biomarker (medicine), MESH: Intensive Care Units, Early phase, business, Biomarkers, Cohort study
Abstract

International audience

Published
2019
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9. Facteurs prédictifs des patients cirrhotiques en réanimation pédiatrique, greffés exclus.Étude rétrospective non interventionnelle multicentrique

Author

Claude, Caroline, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Philippe Durand

Subjects
Enfant, INR, CLIF-SOFA, Cirrhose, Intensive Care, MESH: Acute-On-Chronic Liver Failure, MESH: International Normalized Ratio, ACLF, Sepsis, MESH: Bilirubin, MESH: Child, MESH: Fibrosis, MESH: Liver Cirrhosis, MESH: Resuscitation, MESH: Sepsis, Réanimation, Bilirubine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Data on pediatric intensive care unit (PICU)-admitted cirrhotic patients is scarce. We aimed to evaluate the (i)prognosis and (ii) predictive factors for 28-day and 60-day poor outcome (eg mortality, liver transplantation) inchildren admitted in PICU without previous liver transplantation. We performed a multicentric retrospective analysis of pediatric cirrhosis patients admitted into four critical care units between 2011-2016 (ESPNIC research network group). We recorded clinical and biological data at admission then day 7 and followed the patients until discharge. Pediatric index of mortality (PIM2), RIFLE score (acute renal failure), Pediatric End-Stage Liver Disease score (PELD) and pediatric chronic liver failure sequential organ failure assessment score (pCLIF SOFA) were computed during ICU stay. Univariate and multivariate analysis were carried out to identify the best predictors of poor outcome. A total of 130 patients were enrolled (mean age of 21 months) and 51% had a poor outcome at 60-day. Significant risk factors for poor outcome were high international normalized ratio (OR 3.11 IC95% [1.4-6.78] p=0.004), bilirubin (OR 3.5 IC95%[1.54-8.05] p=0.003), acute-on-chronic liver failure (ACLF) (OR 5.8 IC95% [1.86-18.32] p=0.002), renal failure (OR 34 IC95%[4.45-268] p=0.001) and sepsis (OR 2.7 IC95%[1.35-5.62] p=0.005). pCLIF-SOFA showed the best AUC of 0.83 (IC95% [0.74-0.92] p=0.04) and with a score of ≥ 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. Neither the Pediatric Index of Mortality score (PIM2) or the Pediatric End-Stage Liver Disease score (PELD) score were discriminant (AUC of 0.76 (IC95% [0.64-0.86])) whereas the RIFLE score (Risk of renal dysfunction, Injury, Failure, Loss, End-stage) was significantly associated to mortality at day-28 (Failure: OR 18 (IC95% [6.0-55] p=0.000).Fifty one percent of cirrhosis pediatric patients admitted in PICU have a poor outcome. Sepsis and acute-onchronicliver failure are independent predictors of outcome. pCLIF-SOFA is a reliable score in prognostication of 28 mortality or 60- day poor outcome.; Les données disponibles concernant les enfants cirrhotiques admis en réanimation pédiatrique sont rares. Noussouhaitions évaluer (i) le pronostic et (ii) les facteurs prédictifs de mortalité à J28 et J60 chez des enfants admis enréanimation pédiatrique sans antécédent de transplantation hépatique. Nous avons réalisé une étude rétrospective multicentrique chez des patients cirrhotiques admis en réanimation entre 2011 et 2016 (groupe de recherche de l’ESPNIC). Nous avons enregistré les données cliniques et biologiques à l’admission et à J7 ainsi que les évènements notables lors de l’hospitalisation. L’index pédiatrique de mortalité (PIM 2), le score de RIFLE (insuffisance rénale aiguë), le Pediatric End-Stage Liver Disease score (PELD) et le score de défaillances d’organes adapté à la cirrhose (pCLIF SOFA) ont été calculés lors de l’hospitalisation en réanimation. Des analyses univariées et multivariées ont été effectuées afin d’identifier les meilleurs prédicteurs d’évolution défavorable (transplantation hépatique ou décès).130 patients au total ont été inclus (moyenne d’âge de 21 mois) et 51% ont eu une issue défavorable à J60. Desfacteurs de risques significatifs d’évolution défavorable étaient : un international normalized ratio élevé (OR 3.11IC95% [1.4-6.78] p=0.004), un taux élevé de bilirubine (OR 7.34 IC95%[2.83-19.0] p=0.000), unedécompensation hépatique aiguë sur chronique (ACLF) (OR 5.8 IC95% [1.86-18.32] p=0.002), une défaillancerénale (OR 34 IC95%[4.45-268] p=0.001) et un sepsis (OR 2.7 IC95%[1.35-5.62] p=0.005). Dans notre étude, lescore pCLIF-SOFA avait la meilleure AUC de 0.83 (IC95% [0.74-0.92] p=0.04) et un score ≥9 prédisait lamortalité à J28 avec une sensibilité de 87.8% et une spécificité de 77.3%. Ni le Pediatric Index of Mortality score(PIM2) ni le Pediatric End-Stage Liver Disease score (PELD) n’étaient discriminants (AUC de 0.76 (IC95% [0.64-0.86])) alors que le score de défaillance rénale, RIFLE (Risk, Injury, Failure, Loss, End-stage), était associésignificativement à la mortalité à J28 (Failure : OR 18 (IC95% [6.0-55] p=0.000). 51 % de patients cirrhotiques admis en réanimation pédiatrique avaient une issue défavorable.Le sepsis et une défaillance hépatique aiguë sur chronique étaient des facteurs indépendants de mortalité. LepCLIF-SOFA s’avère fiable pour prédire un pronostic défavorable à J28 et J60.

Published
2018

10. Gender and sepsis: first step of personalized medicine?

Author

Calypso Mathieu, Marc Leone, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, medicine.medical_specialty, Critical Care, 030106 microbiology, MESH: Precision Medicine, Sepsis, 03 medical and health sciences, Text mining, Sex Factors, MESH: Critical Care, MESH: Sex Factors, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Precision Medicine, Intensive care medicine, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, business.industry, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Intensive Care Units, Anesthesiology and Pain Medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Intensive Care Units, Personalized medicine, business
Abstract

International audience

Published
2018
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11. A novel paradigm links mitochondrial dysfunction with muscle stem cell impairment in sepsis

Author

Franck Verdonk, Fabrice Chrétien, Miria Ricchetti, Clément Crochemore, Pierre Rocheteau, Laurent Chatre, Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], TRial Group for Global Evaluation and Research in SEPsis (TRIGGERSEP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes, Sorbonne Paris Cité, This work was supported by Institut Pasteur and CNRS funding (UMR 3525 and UMR 3738)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, MESH: Inflammation, Satellite Cells, Skeletal Muscle, [SDV]Life Sciences [q-bio], Inflammation, Mitochondrion, Biology, Mesenchymal Stem Cell Transplantation, DNA, Mitochondrial, Sepsis, 03 medical and health sciences, Muscle stem cells, medicine, Animals, Humans, MESH: Animals, MESH: Mesenchymal Stem Cell Transplantation, Muscle Strength, Myopathy, Molecular Biology, MESH: Sepsis, MESH: Humans, MESH: Muscle Strength, Mesenchymal stem cell, MESH: DNA, Mitochondrial, MESH: Satellite Cells, Skeletal Muscle, Muscle weakness, Skeletal muscle, MESH: Mitochondria, Muscle, medicine.disease, Mitochondrial DNA, Mitochondria, Muscle, 3. Good health, Mitochondria, 030104 developmental biology, medicine.anatomical_structure, MESH: Mesenchymal Stem Cells, Immunology, Molecular Medicine, Mesenchymal stem cells, medicine.symptom, Stem cell
Abstract

International audience; Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life threatening condition associated with multiple organ failure. Survivors may display long-term disability with muscle weakness that remains poorly understood. Recent data suggest that long-term myopathy in sepsis survivors is due to failure of skeletal muscle stem cells (satellite cells) to regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is linked to unusual mitochondrial dysfunctions, characterized by a dramatic reduction of the mitochondrial mass and hyperactivity of residual organelles. Survivors maintain the impairment of satellite cells, including alterations of the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and mitochondrial function in satellite cells, and in fine their regenerative potential. Injection of MSCs in turn increases the force of isolated muscle fibers and of the whole animal, and improves the survival rate. These effects occur in the context of reduced inflammation markers that also raised during sepsis. Targeting muscle stem cells mitochondria, in a context of reduced inflammation, may represent a valuable strategy to reduce morbidity and long-term impairment of the muscle upon sepsis.

Published
2017
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12. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in septic patients

Author

Uhel, Fabrice, Azzaoui, Imane, Grégoire, Murielle, Pangault, Céline, Dulong, Joelle, Tadié, Jean-Marc, Gacouin, Arnaud, Camus, Christophe, Cynober, Luc, Fest, Thierry, Le Tulzo, Yves, Roussel, Mikael, Tarte, Karin, Service des Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme ( PRETRRAM - EA 4466 ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Research grant from the French Intensive Care Society / Société de Réanimation de Langue Française (FICS/SRLF), Research grant from the National Institute of Cancer and Direction Générale de l'Organisation des Soins Ministère de la Santé (Projet Recherche Translationnelle 2010), Research grant from the Comité de la Recherche Translationnelle (CORECT), Rennes University Hospital, UHEL, Fabrice, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM - EA 4466), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
immune tolerance, MESH : monocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, MDSC, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, infections nosocomiales, choc septique, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], sepsis, MESH: immune tolerance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], nosocomial infections, polynucléaires neutrophiles, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : granulocytes, MESH: granulocytes, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Sepsis, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: monocytes, cytométrie en flux, flow cytometry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, granulocytes, myeloid-derived suppressor cells, cross infection, MESH: cross infection, MESH : immune tolerance, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, septic shock, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Sepsis, MESH : cross infection, monocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Rationale - Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined.Objectives - To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis.Methods - Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments.Measurements and main results - Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14HLA-DR monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14CD15 low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P Conclusions - M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

Published
2017
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13. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions

Author

Giulio Superti-Furga, Anna-Dorothea Gorki, Philipp Starkl, Stefan Kubicek, Keiryn L. Bennett, Michael C. Aichinger, Kilian Huber, Branka Radic-Sarikas, Rui Martins, Kari Vaahtomeri, Dontscho Kerjaschki, Ana Korosec, Omar Sharif, Thomas Decker, Stephanie C. Eisenbarth, Michael Sixt, Markus Brown, Harald Esterbauer, Sylvia Knapp, Riem Gawish, Jacques Colinge, Michelle Duggan, Karin Lakovits, Federica Quattrone, Charles-Hugues Lardeau, Simona Saluzzo, Anastasiya Hladik, Julia Maier, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
0301 basic medicine, Phagocyte, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, MESH: Gram-Negative Bacterial Infections, Immunology and Allergy, Guanine Nucleotide Exchange Factors, MESH: RAW 264.7 Cells, MESH: Guanine Nucleotide Exchange Factors, MESH: Animals, MESH: Immune Evasion, Cytoskeleton, cdc42 GTP-Binding Protein, MESH: Phagocytosis, Heme, MESH: Sepsis, Mice, Knockout, Quinine, MESH: Heme Oxygenase-1, MESH: Hemolysis, Hemolysis, 3. Good health, Anti-Bacterial Agents, medicine.anatomical_structure, MESH: Heme, Female, Guanine nucleotide exchange factor, MESH: Membrane Proteins, Dock8, MESH: Quinine, Phagocytosis, Immunology, Microbiology, Sepsis, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Anti-Bacterial Agents, medicine, MESH: Cytoskeleton, Animals, Humans, MESH: Mice, Immune Evasion, MESH: cdc42 GTP-Binding Protein, MESH: Humans, Macrophages, Membrane Proteins, MESH: Macrophages, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, RAW 264.7 Cells, chemistry, Gram-Negative Bacterial Infections, MESH: Female, Heme Oxygenase-1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.

Published
2016
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14. Outcomes in severe sepsis and patients with septic shock: Pathogen species and infection sites are not associated with mortality*

Author

Dany Goldgran-Toledano, Adrien Français, Elie Azoulay, Jean-François Timsit, Yohann Dubois, Aurélien Vesim, Bertrand Souweine, Bernard Allaouchiche, Jean-Ralph Zahar, Adrien Descorps-Declere, Christophe Adrie, Maité Garrouste-Orgeas, Aurélien Vesin, Hakim Haouache, Equipe mobile d'infectiologie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Microbiologie-Hygiène Hospitalière, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation chirurgicale [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, 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), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Service de Réanimation Polyvalente, Centre Hospitalier de Gonesse, Service de Réanimation, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Medical ICU, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de réanimation médicale et chirurgicale, and Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
Male, Databases, Factual, MESH: Drug Resistance, Microbial, Drug resistance, MESH: Risk Assessment, Critical Care and Intensive Care Medicine, Severity of Illness Index, MESH: Gram-Positive Bacteria, MESH: Proportional Hazards Models, MESH: Cause of Death, 0302 clinical medicine, Cause of Death, MESH: Gram-Negative Bacteria, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, MESH: Sepsis, MESH: Treatment Outcome, MESH: Aged, Cross Infection, MESH: Microbial Sensitivity Tests, MESH: Middle Aged, Drug Resistance, Microbial, Middle Aged, Prognosis, Shock, Septic, Anti-Bacterial Agents, 3. Good health, Community-Acquired Infections, Survival Rate, Intensive Care Units, Treatment Outcome, MESH: Community-Acquired Infections, Cohort, Female, medicine.symptom, medicine.medical_specialty, Critical Care, MESH: Survival Rate, MESH: Shock, Septic, Microbial Sensitivity Tests, Gram-Positive Bacteria, Risk Assessment, MESH: Multivariate Analysis, MESH: Prognosis, 03 medical and health sciences, Sepsis, MESH: Anti-Bacterial Agents, MESH: Severity of Illness Index, Intensive care, Gram-Negative Bacteria, Severity of illness, medicine, Humans, MESH: Hospital Mortality, MESH: Intensive Care, Intensive care medicine, Survival rate, Aged, Proportional Hazards Models, MESH: Humans, Septic shock, business.industry, Organ dysfunction, MESH: Cross Infection, 030208 emergency & critical care medicine, medicine.disease, MESH: Databases, Factual, MESH: Male, MESH: Prospective Studies, Bacteremia, Multivariate Analysis, MESH: Intensive Care Units, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; OBJECTIVES: We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections. DESIGN: We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy. SETTING: Twelve intensive care units. PATIENTS: We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups. CONCLUSION: The infectious process may not exert as strong a prognostic effect when severity, organ dysfunction and, above all, appropriateness of early antimicrobials are taken into account. Our findings emphasize the importance of developing valid recommendations for early antimicrobial therapy.

Published
2011
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15. SpdC, a novel virulence factor, controls histidine kinase activity in Staphylococcus aureus

Author

Olivier Poupel, Sarah Dubrac, Caroline Proux, Bernd Jagla, Tarek Msadek, Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, This work was supported by funds from the Institut Pasteur (www.pasteur.fr) and CNRS (www.cnrs.fr)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)

Subjects
MESH: Signal Transduction, 0301 basic medicine, Histidine Kinase, Staphylococcus, [SDV]Life Sciences [q-bio], Gene Expression, MESH: Amino Acid Sequence, MESH: Virulence, Pathology and Laboratory Medicine, medicine.disease_cause, Biochemistry, Virulence factor, Mice, chemistry.chemical_compound, Medicine and Health Sciences, MESH: Animals, Staphylococcus Aureus, Phosphorylation, Amino Acids, lcsh:QH301-705.5, MESH: Sepsis, MESH: Bacterial Proteins, Virulence, Organic Compounds, Staphylococcal Infections, Bacterial Pathogens, Mutant Strains, Chemistry, Medical Microbiology, Staphylococcus aureus, Physical Sciences, MESH: Regulon, MESH: Histidine Kinase, Female, Pathogens, Basic Amino Acids, Cellular Structures and Organelles, Signal Transduction, Research Article, lcsh:Immunologic diseases. Allergy, Virulence Factors, Immunology, MESH: Staphylococcal Infections, MESH: Biofilms, DNA construction, Biology, Regulon, Microbiology, 03 medical and health sciences, Cell Walls, Bacterial Proteins, Protein Domains, Sepsis, Virology, Genetics, medicine, Animals, Histidine, Gene Regulation, Amino Acid Sequence, Microbial Pathogens, MESH: Mice, Molecular Biology, Bacteria, MESH: Phosphorylation, Lysostaphin, Organic Chemistry, Histidine kinase, Autolysin, Organisms, Chemical Compounds, Biology and Life Sciences, Proteins, Gene Expression Regulation, Bacterial, Cell Biology, Research and analysis methods, Molecular biology techniques, 030104 developmental biology, lcsh:Biology (General), chemistry, Biofilms, Mutation, Plasmid Construction, MESH: Virulence factors, Parasitology, Peptidoglycan, lcsh:RC581-607, MESH: Female
Abstract

The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt to a wide spectrum of environmental conditions. Two-component systems (TCSs) play a crucial role in this process. Here, we describe a novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved in signal sensing and/or transduction. We have uncovered a functional link between the WalKR essential TCS and the SpdC Abi membrane protein. Expression of spdC is positively regulated by the WalKR system and, in turn, SpdC negatively controls WalKR regulon genes, effectively constituting a negative feedback loop. The WalKR system is mainly involved in controlling cell wall metabolism through regulation of autolysin production. We have shown that SpdC inhibits the WalKR-dependent synthesis of four peptidoglycan hydrolases, SceD, SsaA, LytM and AtlA, as well as impacting S. aureus resistance towards lysostaphin and cell wall antibiotics such as oxacillin and tunicamycin. We have also shown that SpdC is required for S. aureus biofilm formation and virulence in a murine septicemia model. Using protein-protein interactions in E. coli as well as subcellular localization in S. aureus, we showed that SpdC and the WalK kinase are both localized at the division septum and that the two proteins interact. In addition to WalK, our results indicate that SpdC also interacts with nine other S. aureus histidine kinases, suggesting that this membrane protein may act as a global regulator of TCS activity. Indeed, using RNA-Seq analysis, we showed that SpdC controls the expression of approximately one hundred genes in S. aureus, many of which belong to TCS regulons., Author summary Staphylococcus aureus is a major human pathogen, and has become a significant worldwide health concern due to the rapid emergence of antibiotic resistant strains. Like most bacteria, S. aureus adapts to its environment by adjusting its genetic expression through sensing and regulatory systems. We show here that the SpdC membrane protein is a novel virulence factor of S. aureus, controlling biofilm formation and pathogenesis. We show that SpdC interacts with the WalK histidine kinase to inhibit activity of the WalKR two-component system. SpdC also interacts with nine other histidine kinases of S. aureus, suggesting it acts as a pleiotropic global regulator.

Published
2018
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16. IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

Author

Fernando Q. Cunha, Bernhard Ryffel, Henrique Lemos, Fabiane Sônego, Andressa de Freitas, Tatiana Victoni, Thomas Secher, José C. Alves-Filho, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Signal Transduction, Fever, Neutrophils, Immunology, MESH: Neutrophils, MESH: Receptors, Interleukin-17, MESH: Mice, Knockout, Sepsis, Mice, 03 medical and health sciences, Peritoneal cavity, 0302 clinical medicine, Il 17 receptor, Cell Movement, MESH: Mice, Inbred C57BL, In vivo, MESH: Fever, medicine, Animals, Immunology and Allergy, MESH: Animals, MESH: Cell Movement, MESH: Sepsis, MESH: Mice, 030304 developmental biology, Mice, Knockout, MESH: Cytokines, 0303 health sciences, Receptors, Interleukin-17, business.industry, High mortality, medicine.disease, MESH: Male, In vitro, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, business, Polymicrobial sepsis, Signal Transduction, 030215 immunology
Abstract

Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis.

Published
2009
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17. Host and bacterial determinants of initial severity and outcome of Escherichia coli sepsis

Author

Françoise Jauréguy, C. Clec'h, Edouard Bingen, Philippe Casassus, Xavier Nassif, O. Lortholary, E. Carbonnelle, Bertrand Picard, Stéphane Bonacorsi, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Paris 13 (UP13), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'hématologie clinique [Avicenne], Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vesin, Aurélien, UFR Santé, Médecine et Biologie Humaine ( UFR SMBH ), Université Paris 13 ( UP13 ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Virulence Factors, MESH : Escherichia coli, MESH : Host-Parasite Interactions, Antibiotics, MESH : Prospective Studies, severity, Bacteremia, sepsis, Immunopathology, Prospective Studies, MESH: Bacteremia, Prospective cohort study, MESH: Sepsis, Escherichia coli Infections, MESH : Integration Host Factors, Antibacterial agent, 0303 health sciences, MESH: Escherichia coli, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, host factors, 3. Good health, Infectious Diseases, MESH : Escherichia coli Infections, outcome, MESH : Sepsis, Integration Host Factors, Microbiology (medical), Virulence Factors, medicine.drug_class, Virulence, Biology, MESH: Host-Parasite Interactions, Host-Parasite Interactions, Microbiology, Sepsis, 03 medical and health sciences, Escherichia coli, medicine, Humans, MESH: Escherichia coli Infections, MESH: Virulence Factors, 030304 developmental biology, MESH: Humans, MESH: Integration Host Factors, 030306 microbiology, Septic shock, MESH : Humans, MESH : Bacteremia, medicine.disease, MESH: Prospective Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, virulence determinants
Abstract

International audience; A 1-year prospective cohort study of all episodes of Escherichia coli bacteraemia in two French university hospitals was conducted to assess simultaneously the influence of host and bacterial determinants on the initial severity and outcome of E. coli sepsis. Clinical data (community-acquired/nosocomial infection, immune status, underlying disease, primary source of infection, severity sepsis scoring and outcome), phylogenetic groups (A, B1, D and B2), nine virulence factors (VFs) (papC, papGII, papGIII, sfa/foc, hlyC, cnf1, iucC, fyuA and iroN) and the antibiotic susceptibility of isolates were investigated. All VFs except iucC were significantly more prevalent (p

Published
2007
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18. Effects of dichloroacetate and ubiquinone infusions on glycolysis activity and thermal sensitivity during sepsis

Author

Philippe Sébert, Erwan L'Her, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)

Subjects
Male, MESH: Dichloroacetate, Ubiquinone, Coenzymes, MESH: Rats, Sprague-Dawley, 030204 cardiovascular system & hematology, Rats, Sprague-Dawley, Electron Transport Complex III, chemistry.chemical_compound, 0302 clinical medicine, MESH: Electron Transport Complex III, MESH: Animals, MESH: Ubiquinone, Glycolysis, Infusions, Intravenous, MESH: Sepsis, MESH: Muscle, Skeletal, MESH: Coenzymes, General Medicine, Pyruvate dehydrogenase complex, Mitochondria, 3. Good health, MESH: Body Temperature Regulation, MESH: Glucose, MESH: Glycolysis, Perfusion, Body Temperature Regulation, Hyperthermia, MESH: Enzyme Activation, medicine.medical_specialty, MESH: Rats, MESH: Mitochondria, Pyruvate Dehydrogenase Complex, Biology, Carbohydrate metabolism, Pathology and Forensic Medicine, Sepsis, 03 medical and health sciences, MESH: Pyruvate Dehydrogenase Complex, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Lactic Acid, Muscle, Skeletal, MESH: Infusions, Intravenous, Dichloroacetic Acid, Metabolism, medicine.disease, MESH: Male, Rats, Enzyme Activation, Glucose, Endocrinology, Glucose 6-phosphate, chemistry, MESH: Lactic Acid, 030217 neurology & neurosurgery
Abstract

International audience; Energy-metabolism disturbances during sepsis are characterized by enhanced glycolytic fluxes and reduced mitochondrial respiration. However, it is not known whether these abnormalities are the result of a specific mitochondrial alteration, decreased pyruvate dehydrogenase (PDH) complex activity, depletion of ubiquinone (CoQ(10); electron donor for the mitochondrial complex III), or all 3. In this study we sought to specify metabolism disturbances in a murine model of sepsis, using either a PDH-activator infusion (dichloroacetate, DCA) or CoQ(10) supplementation. After anesthesia, Sprague-Dawley rats received intravenous saline solution (control; n = 5), DCA (n = 5; 20 mg/100 g), or CoQ(10) (n = 5; 1 mg/100 g), before the induction of sepsis. Increased plasma lactate levels and increased muscle glucose content were observed after 4 hours in the control group. In the DCA group, a decrease in the muscle content of lactate (P

Published
2004
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19. mTOR- and HIF-1 alpha-mediated aerobic glycolysis as metabolic basis for trained immunity

Author

Shih-Chin Cheng, Peter M.T. Deen, Hendrik G. Stunnenberg, Joost H.A. Martens, Jessica Quintin, Robert A. Cramer, Kelly M. Shepardson, Sadia Saeed, Rob J.W. Arts, Nagesha Appukudige Rao, Brian M. J. W. van der Veer, Cisca Wijmenga, Yang Li, Colin Logie, Frank L. van de Veerdonk, Ramnik J. Xavier, Ganesh R. Manjeri, Vinod Kumar, Jos W. M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Daniela C. Ifrim, Mihai G. Netea, Luke A. J. O'Neill, Leo A. B. Joosten, Peter H.G.M. Willems, Ali Aghajanirefah, Aylwin Ng, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Radboud University Medical Center [Nijmegen], Geisel School of Medicine at Dartmouth, Radboud university [Nijmegen], University Medical Center Groningen [Groningen] (UMCG), National and Kapodistrian University of Athens (NKUA), Trinity College Dublin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), and Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]

Subjects
Male, beta-Glucans, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], MESH: Monocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Monocytes, Epigenesis, Genetic, ACTIVATION, Mice, 0302 clinical medicine, Candida albicans, INFECTION, MESH: Staphylococcus aureus, Glycolysis, MESH: Animals, MESH: Epigenesis, Genetic, PROTECTION, MACROPHAGES, MESH: Sepsis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, Multidisciplinary, MESH: beta-Glucans, TOR Serine-Threonine Kinases, Candidiasis, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Staphylococcal Infections, Aerobiosis, MESH: Candidiasis, Cell biology, MESH: Glucose, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, 030220 oncology & carcinogenesis, MESH: Glycolysis, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunity, Innate, BETA-GLUCAN, EXPRESSION, Staphylococcus aureus, Secondary infection, MESH: Staphylococcal Infections, Biology, Article, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, 03 medical and health sciences, INFLAMMATION, Immunity, MESH: Mice, Inbred C57BL, Sepsis, MESH: Aerobiosis, Animals, Humans, REINFECTION, Protein kinase B, MESH: Mice, PI3K/AKT/mTOR pathway, MESH: TOR Serine-Threonine Kinases, 030304 developmental biology, Innate immune system, MESH: Humans, MESH: Candida albicans, MESH: Transcriptome, Hypoxia-Inducible Factor 1, alpha Subunit, Immunity, Innate, MESH: Male, Mice, Inbred C57BL, Disease Models, Animal, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Glucose, Anaerobic glycolysis, CELLS, INNATE IMMUNITY, NAD+ kinase, MESH: Disease Models, Animal, Transcriptome, Immunologic Memory, MESH: Female
Abstract

A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducing immune responses, Saeed et al. document the epigenetic changes in the genome that underlie immune cell differentiation. Cheng et al. demonstrate that trained monocytes are highly dependent on the breakdown of sugars in the presence of oxygen, which allows cells to produce the energy needed to mount an immune response. Chen et al. examine RNA transcripts and find that specific cell lineages use RNA transcripts of different length and composition (isoforms) to form proteins. Together, the studies reveal how epigenetic effects can drive the development of blood cells involved in the immune system. Science , this issue 10.1126/science.1251086 , 10.1126/science.1250684 , 10.1126/science.1251033

Published
2014
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20. Bacterial neonatal sepsis and antibiotic resistance in low-income countries

Author

Bich-Tram Huynh, Michael Padget, Benoit Garin, Elisabeth Delarocque-Astagneau, Didier Guillemot, Laurence Borand, Thida Chon, Agathe de Lauzanne, Sophie Goyet, Sopheak Hem, Alexandra Kerleguer, Siyin Lach, Veronique Ngo, Arnaud Tarantola, Sok Touch, Jean-Marc Collard, Perlinot Herindrainy, Patrice Piola, Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Awa Ndir, Vincent Richard, Abdoulaye Seck, Raymond Bercion, Amy Gassama Sow, Jean Baptiste Diouf, Pape Samba Dieye, Balla Sy, Bouya Ndao, Maud Seguy, Elsa Kermorvant-Duchemin, Laurence Watier, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prévention et Thérapie Moléculaires des Maladies Infectieuses Humaines, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], BIRDY study group : Cambodia : Laurence Borand, PharmD PhD, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Thida Chon, midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Agathe de Lauzanne, MD MPH, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sophie Goyet, midwife PhD, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sopheak Hem, Medical Biologist (Medical Laboratory– Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Alexandra Kerleguer, MD Medical Biologist (Head of Medical Laboratory – Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Siyin Lach, Midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Veronique Ngo, midwife, Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Arnaud Tarantola, MD PhD, Head of Epidemiology & Public Health Unit, Institut Pasteur du Cambodge (epi@ipc), Phnom Penh, Cambodia, Sok Touch, MD MPH (retired) Director of CDC (Communicable Disease Department) Department at Ministry of Health Cambodia. Madagascar : Jean-Marc Collard, PhD, Experimental bacteriology unit, Institut Pasteur Madagascar, Perlinot HERINDRAINY, MD MPH, Epidemiology & Public Health Unit, Institut Pasteur Madagascar, Patrice Piola, MD PhD, Epidemiology & Public Health Unit, Institut Pasteur Madagascar Bodonirina Tanjona RAHELIARIVAO, MD, Epidemiology & Public Health Unit, Institut Pasteur Madagascar, Frédérique RANDRIANIRINA, MD, Centre de Biologie Clinique, Institut Pasteur Madagascar. Senegal : Awa Ndir, PhD, Institut Pasteur de Dakar, Vincent Richard, MD MPH, Institut Pasteur de Dakar, Abdoulaye Seck, PharmD, Institut Pasteur de Dakar, Raymond Bercion, MD, Institut Pasteur de Dakar, Amy GASSAMA SOW, PhD, Institut Pasteur de Dakar, Jean Baptiste DIOUF, MD, Hôpital Roi Baudoin, Pape Samba DIEYE, MD, District Sanitaire de Guédiawaye, Balla SY, MD, District Sanitaire de Sokone Bouya NDAO, MD, District Sanitaire de Sokone, France Maud Seguy, PhD, Department of International Affairs, Institut Pasteur Paris, Elsa Kermorvant-Duchemin, MD PhD, AP-AP, Hôpital Universitaire Necker-Enfants malades, Department of Neonatology, Paris 75015, France-Université Paris Descartes, Faculté de médecine, Paris 75006, Laurence Watier, PhD, Inserm UMR 1181 « Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases » (B2PHI), F-75015 Paris, France-Institut Pasteur, UMR 1181, B2PHI, 75015 Paris., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, MESH: Drug Resistance, Microbial, MESH: Poverty, MEDLINE, Developing country, Drug resistance, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, Poverty, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, MESH: Humans, Neonatal sepsis, business.industry, MESH: Infant, Newborn, Infant, Newborn, Drug Resistance, Microbial, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infant newborn, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience

Published
2016
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21. Effects of mild induced hypothermia during experimental sepsis*

Author

Erwan L'Her, Aurélie Vettier, Aline Amérand, Philippe Sébert, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité Haute Pression et Métabolisme, UPCI-EA3879, and Université de Brest (UBO)

Subjects
Male, Resuscitation, MESH: Rats, MESH: Random Allocation, Sepsis syndrome, MESH: Rats, Sprague-Dawley, 030204 cardiovascular system & hematology, Core temperature, Critical Care and Intensive Care Medicine, Lower energy, Rats, Sprague-Dawley, Sepsis, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Hypothermia, Induced, Intensive care, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, MESH: Animals, MESH: Sepsis, MESH: Hypothermia, Induced, business.industry, 030208 emergency & critical care medicine, Hypothermia, medicine.disease, Survival Analysis, MESH: Male, Rats, 3. Good health, Sprague dawley, MESH: Survival Analysis, Anesthesia, medicine.symptom, business
Abstract

International audience; OBJECTIVES: The potential advantages of lowering core temperature during sepsis are to lower energy requirement and to activate various cell-protecting pathways. We experimentally investigated whether postconditioning temperature modifications influence survival duration during experimental sepsis. DESIGN: A prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Eighteen male Sprague-Dawley rats (median 326 g, range 310-347 g). INTERVENTIONS: After anesthesia, experimental sepsis was induced by cecal ligation and perforation. The animals were subsequently assigned a core temperature range: normothermia (37 degrees C), hyperthermia (42 degrees C), and mild hypothermia (32 degrees C). Anesthesia and analgesia were continuously maintained until death. MEASUREMENTS AND MAIN RESULTS: Plasma lactate and pyruvate concentrations were measured at sepsis induction (H0), 4 hrs later (H4), and/or at the time of death. A significant increase in lactate concentration was observed at the time of death in the 42 degrees C group (p = .04). Lactate-to-pyruvate ratio increased in the 32 degrees C (at H4) and 42 degrees C (at the time of death) groups (p = .04). A linear correlation between a longer survival duration and a lower assigned core temperature was observed (from 61 +/- 10 mins at 42 degrees C to 289 +/- 17 mins at 37 degrees C and to 533 +/- 69 mins at 32 degrees C; R = .959, p < .0001). CONCLUSIONS: The current results demonstrate that postconditioning hypothermia was associated with increased survival duration during experimental sepsis. Whether the observed benefits on survival duration are due to potential impacts on energy metabolism or to an anti-inflammatory effect of hypothermia requires further investigation.

Published
2006
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22. An Atypical Clostridium Strain Related to the Clostridium botulinum Group III Strain Isolated from a Human Blood Culture

Author

Christiane Bouchier, Nathalie Faucher, Michel R. Popoff, Christelle Mazuet, Philippe Bouvet, Raymond Ruimy, Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Hôpital l'Archet, Génomique (Plate-Forme) - Genomics Platform, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by Institut Pasteur funding., We thank S. Kozaki for kindly providing C. botulinum D/C mosaic isolates, and Institut Pasteur [Paris] (IP)

Subjects
MESH: Sequence Analysis, DNA, MESH: Fatal Outcome, Case Reports, medicine.disease_cause, Clostridium, Fatal Outcome, MESH: Aged, 80 and over, RNA, Ribosomal, 16S, Cluster Analysis, MESH: Clostridium botulinum type C, MESH: Phylogeny, MESH: Bacterial Proteins, MESH: Sepsis, Phylogeny, MESH: Clostridium botulinum type D, Aged, 80 and over, MESH: DNA, Ribosomal, biology, Strain (chemistry), 3. Good health, Housekeeping gene, MESH: RNA, Ribosomal, 16S, Blood, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, Microbiology (medical), DNA, Bacterial, Sequence analysis, Clostridium botulinum type D, Molecular Sequence Data, Clostridium botulinum type C, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, DNA, Ribosomal, Microbiology, Bacterial Proteins, Sepsis, medicine, MESH: Blood, Humans, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Sequence Analysis, DNA, 16S ribosomal RNA, biology.organism_classification, Virology, MESH: Cluster Analysis, MESH: DNA, Bacterial, Clostridium botulinum, MESH: Female
Abstract

A nontoxigenic strain isolated from a fatal human case of bacterial sepsis was identified as a Clostridium strain from Clostridium botulinum group III, based on the phenotypic characters and 16S rRNA gene sequence, and was found to be related to the mosaic C. botulinum D/C strain according to a multilocus sequence analysis of 5 housekeeping genes.

Published
2014
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23. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants

Author

Y. Aujard, Monique Kaminski, Béatrice Larroque, Antoine Burguet, Pierre-Yves Ancel, Stéphane Marret, Rachel Vieux, Gérard Thiriez, Ayoub Mitha, Patrick Truffert, Catherine Arnaud, Pascal Boileau, Laurence Foix-L’Hélias, Gilles Cambonie, Jean-Christophe Rozé, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Unité de Néonatalogie, Hôpital Jeanne de Flandre [Lille], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Unité d'Epidémiologie Clinique, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Neonatal Intensive Care Unit (NICU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service Pédiatrie, Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Unité d'Epidémiologie et Recherche Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néonatalogie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service Pédiatrique, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Médecine Néonatale, Université de Nantes (UN), CIC - Nantes, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Epidémiologique sur la Qualité des Soins, Université de Lille, Droit et Santé, EPIPAGE study group, Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Debs, Nayla, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie néonatale et réanimation - neuropédiatrie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen], Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement ( Néovasc ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institute for Research and Innovation in Biomedicine ( IRIB ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Neonatal Intensive Care Unit ( NICU ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre Hospitalier de Poissy Saint-Germain (CHIPS), Université de Nantes ( UN ), and Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Pediatrics, MESH : Infant, Premature, Diseases, Developmental Disabilities, Infant, Premature, Diseases, Neuropsychological Tests, MESH : Child, Preschool, MESH : Cerebral Palsy, Cohort Studies, 0302 clinical medicine, MESH : Cross-Sectional Studies, Risk Factors, MESH: Risk Factors, MESH: Gestational Age, Infant, Very Low Birth Weight, MESH : Female, MESH: Infant, Very Low Birth Weight, 030212 general & internal medicine, Longitudinal Studies, MESH : Infant, Very Low Birth Weight, MESH : Infectious Disease Transmission, Vertical, MESH: Longitudinal Studies, MESH: Sepsis, MESH: Cohort Studies, MESH : Longitudinal Studies, education.field_of_study, Cross Infection, MESH: Infant, Newborn, neurodevelopmental outcome, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Neuropsychological Tests, MESH : Risk Factors, MESH: Infant, MESH: Infant, Premature, Diseases, 3. Good health, MESH : Neuropsychological Tests, MESH: Infectious Disease Transmission, Vertical, population-based study, Child, Preschool, Cohort, Gestation, Female, MESH : Sepsis, France, MESH : Cross Infection, Cohort study, medicine.medical_specialty, MESH: Cerebral Palsy, MESH : Male, Population, MESH : Cohort Studies, Gestational Age, MESH : Infant, Newborn, MESH : Developmental Disabilities, Cerebral palsy, 03 medical and health sciences, MESH : Cognition Disorders, MESH: Cross-Sectional Studies, 030225 pediatrics, Sepsis, medicine, cohort study, Humans, neonatal infection, very preterm infants, education, MESH : France, MESH: Humans, business.industry, Cerebral Palsy, MESH : Humans, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Cross Infection, Odds ratio, medicine.disease, Confidence interval, Infectious Disease Transmission, Vertical, MESH: Male, MESH: France, Neonatal infection, MESH: Cognition Disorders, Cross-Sectional Studies, MESH: Developmental Disabilities, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cognition Disorders, MESH: Female, MESH : Gestational Age
Abstract

OBJECTIVE:To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children.METHODS:We included all live births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models.RESULTS:A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84−3.45]) or isolated LOS (OR: 1.71 [95% CI: 1.14−2.56]) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02−5.33]). There was no association between neonatal infection and cognitive impairment.CONCLUSIONS:Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS.

Published
2013
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24. Is diabetes a risk factor for central venous access port-related bloodstream infection in oncological patients?

Author

Cécile Chambrier, Philippe Vanhems, J. C. Souquet, Catherine Lombard-Bohas, Abdoulaye Touré, M. Lauverjat, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Hospices Civils de Lyon

Subjects
Male, [SDV]Life Sciences [q-bio], MESH: Risk Assessment, MELLITUS, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Neoplasms, Medicine, Cumulative incidence, MESH: Neoplasms, 030212 general & internal medicine, MESH: Incidence, MESH: Sepsis, MESH: Aged, MESH: Catheterization, Central Venous, MESH: Middle Aged, Mortality rate, Incidence (epidemiology), Incidence, PARENTERAL-NUTRITION, General Medicine, ASSOCIATION, MESH: Follow-Up Studies, Middle Aged, CANCER, 3. Good health, MESH: Diabetes Complications, Infectious Diseases, 030220 oncology & carcinogenesis, MESH: Survival Analysis, PANCREATICODUODENECTOMY, Female, Risk assessment, Microbiology (medical), medicine.medical_specialty, Catheterization, Central Venous, BACTEREMIA, DIAGNOSIS, Risk Assessment, Diabetes Complications, 03 medical and health sciences, HYPERGLYCEMIA, Internal medicine, Diabetes mellitus, Sepsis, Humans, Risk factor, Survival analysis, METAANALYSIS, Aged, MESH: Humans, business.industry, MESH: Catheter-Related Infections, medicine.disease, bacterial infections and mycoses, Survival Analysis, PREVENTION, MESH: Male, Surgery, Parenteral nutrition, Catheter-Related Infections, business, human activities, MESH: Female, Follow-Up Studies
Abstract

International audience; It was a dogma that patients with diabetes mellitus (DM) are at increased risk of infection or death associated with an infection. However, in cancer patients, this has not been well investigated. The aim was to investigate whether diabetic patients with cancer are at high risk of central venous access port (CVAP)-related bloodstream infection (BSI), and to analyse mortality after CVAP-BSI. A total of 17 patients with type 1 DM (T1DM), 66 with type 2 DM (T2DM) and 307 non-diabetic patients were included. Each patient was followed up until the first late CVAP-BSI or for a maximum for 1 year in the absence of a CVAP-BSI. Fifty-three CVAP-BSIs occurred in 66,528 catheter-days. The cumulative incidence of CVAP-BSI was not higher in T1DM (5.9 %; p = 0.17) and T2DM (19.7 %; p = 0.70) compared with the non-diabetic patients (12.7 %). However, in patients with CVAP-BSI, the 1-month crude mortality rate was higher in DM patients (42.9 % vs. 15.4 %; p = 0.04), whereas the mortality in patients without CVAP-BSI was similar in both groups of patients (19.8 % vs. 17.1 %; p = 0.58). Of the 12 deaths that occurred within 1 month of CVAP-BSI, 16.66 % was attributable to CVAP-BSI. The predictive factor of 1-month mortality was DM (p = 0.04). Parenteral nutrition (PN) was independently associated with CVAP-BSI in diabetic patients (p = 0.001). In this study, diabetes did not increase the risk of CVAP-BSI, but mortality was higher in diabetic patients who had a CVAP-BSI. This suggests, in addition to medical treatment, CVAP should be withdrawn after infection onset.

Published
2013
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25. Distinctive features between community-acquired pneumonia (CAP) due to Chlamydophila psittaci and CAP due to Legionella pneumophila admitted to the intensive care unit (ICU)

Author

Y. Le Tulzo, Stéphane Jouneau, Fabrice Uhel, Julien Letheulle, Arnaud Gacouin, Caroline Piau, Pierre Fillatre, Matthieu Revest, Pierre Tattevin, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Unité de maladies infectieuses, CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes], Service de pneumologie [Rennes] = Pneumology [Rennes], Microbiologie : Risques Infectieux, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Le Corre, Morgane, Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes - UFR d'Odontologie (UR Odontologie), and Université de Rennes (UR)-Université de Rennes (UR)

Subjects
Male, Time Factors, MESH: Legionnaires' Disease, MESH: Hospitalization, Psittacosis, Severity of Illness Index, MESH: Occupational Exposure, Poultry, law.invention, 0302 clinical medicine, Community-acquired pneumonia, law, MESH: Poultry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, 030212 general & internal medicine, Simplified Acute Physiology Score, MESH: Sepsis, Chlamydophila Infections, MESH: Aged, 0303 health sciences, MESH: Middle Aged, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Community-Acquired Infections, Hospitalization, Intensive Care Units, Infectious Diseases, MESH: Community-Acquired Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Disease Progression, Legionnaires' disease, MESH: Disease Progression, Female, Radiography, Thoracic, Legionnaires' Disease, Microbiology (medical), Adult, medicine.medical_specialty, MESH: Pneumonia, Bacterial, Legionella pneumophila, 03 medical and health sciences, Species Specificity, Internal medicine, MESH: Severity of Illness Index, Occupational Exposure, Sepsis, Severity of illness, medicine, Pneumonia, Bacterial, MESH: Species Specificity, Animals, Humans, MESH: Chlamydophila Infections, Aged, Retrospective Studies, MESH: Humans, 030306 microbiology, business.industry, MESH: Time Factors, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, MESH: Radiography, Thoracic, medicine.disease, MESH: Legionella pneumophila, MESH: Male, Surgery, Pneumonia, Chlamydophila psittaci, MESH: Intensive Care Units, MESH: Chlamydophila psittaci, business, MESH: Female
Abstract

International audience; The spectrum of community-acquired pneumonia (CAP) due to Chlamydophila psittaci ranges from mild, self-limited CAP, to acute respiratory failure. We performed a retrospective study of 13 consecutive patients with CAP due to C. psittaci and 51 patients with legionellosis admitted in one intensive care unit (ICU) (1993-2011). As compared to patients with legionellosis, patients with psittacosis were younger (median age 48 [38-59] vs. 60 [50-71] years, p = 0.007), less frequently smokers (38 vs. 79 %, p

Published
2012
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26. Sepsis may be a new risk factor for invasive aspergillosis in immunocompetent patients

Author

Tartière, Déborah, Seguin, Philippe, Malledant, Yannick, Gangneux, Jean -Pierre, Le Corre, Morgane, Service d'anesthésie réanimation chirurgicale [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
MESH: Aged, MESH: Fatal Outcome, MESH: Invasive Pulmonary Aspergillosis, MESH: Mediastinitis, MESH: Humans, MESH: Staphylococcal Infections, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Risk Assessment, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH: Immunocompetence, MESH: Risk Factors, MESH: Autopsy, MESH: Surgical Wound Infection, MESH: Sepsis, MESH: Female, ComputingMilieux_MISCELLANEOUS, MESH: Escherichia coli Infections
Abstract

International audience

Published
2012
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27. Oxygen blood transport during experimental sepsis: effect of hypothermia*

Author

Karelle Léon, Hélène Ollivier, Karine Pichavant-Rafini, Pierre-Yves Egreteau, Erwan L'Her, Eric Quemener, Jean-Luc Carré, Philippe Sébert, Optimisation des régulations physiologiques (ORPHY (EA 4324)), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Biochimie et Biologie Moléculaire, and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)

Subjects
Male, MESH: Rats, Perforation (oil well), chemistry.chemical_element, MESH: Rats, Sprague-Dawley, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Oxygen, Sepsis, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, MESH: Animals, MESH: Sepsis, Creatinine, business.industry, Albumin, Oxygen transport, 030208 emergency & critical care medicine, Hypothermia, medicine.disease, MESH: Male, Rats, chemistry, Anesthesia, Hemoglobin, medicine.symptom, business, MESH: Oxygen
Abstract

International audience; OBJECTIVES: The aim of this study was to highlight the link between induced hypothermia and increased survival duration as observed in the septic model developed by the laboratory. To reach this objective, survival duration and blood oxygen transport capacity were measured at two temperatures-38 °C (induced normothermia) and 34 °C (induced hypothermia)-in septic rats. DESIGN: A prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Forty-four male Sprague-Dawley rats (median weight, 232 g; range, 200-303 g). INTERVENTIONS: After anesthesia and obtention of the temperature goal, sepsis was induced by cecal ligation and perforation. MEASUREMENTS AND MAIN RESULTS: Sepsis induction led to death 5 hrs 11 mins ± 0 hr 36 mins after cecal ligation and perforation at 38 °C. At this temperature, significant changes in blood oxygen transport capacity were observed in septic rats; Hill number decreased from 2.36 ± 0.10 (baseline group) to 1.99 ± 0.17 (septic group) (p = .008) and oxygen-hemoglobin affinity decreased and P50 increased from 41.40 ± 2.4 Torr (baseline group) to 51.17 ± 14.07 Torr (septic group). Furthermore, in normothermia, a significant increase of creatinine and albumin plasmatic concentrations was observed 4 hrs after sepsis induction. Survival duration was significantly higher in induced hypothermia (7 hrs 22 mins ± 0 hr 12 mins at 34 °C) compared with induced normothermia. At 34 °C, no significant change in blood oxygen transport capacity was observed. In the same way, exposure to 34 °C induced no change in measured plasmatic parameters except an increase in albumin concentration in septic rats compared with the baseline group. CONCLUSIONS: Sepsis led to a decrease of both oxygen hemoglobin cooperativity and affinity at 38 °C. By contrast, no change in these parameters was observed when sepsis was induced during hypothermia. Taken together, these results could be interpreted in normothermia septic rats as an adaptive mechanism that could enhance the release of oxygen at the tissue level. Hypothermia by slowing down sepsis evolution could increase survival duration.

Published
2011
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28. Transfusion-Transmitted Yersinia enterocolitica Sepsis

Author

Françoise Guinet, Alexandre Leclercq, Elisabeth Carniel, Centre National de Référence de la Peste et autres Yersinioses - National Reference Center Plague and Yersinioses (CNR), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris]

Subjects
Male, Blood transfusion, medicine.medical_treatment, MESH: Yersinia enterocolitica, 030204 cardiovascular system & hematology, MESH: Transfusion Reaction, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Child, Case fatality rate, Medicine, 030212 general & internal medicine, Antibiotic prophylaxis, Yersinia enterocolitica, Child, MESH: Sepsis, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, Middle Aged, MESH: Yersinia Infections, 3. Good health, Anti-Bacterial Agents, Diarrhea, Infectious Diseases, Female, medicine.symptom, Microbiology (medical), Adult, medicine.medical_specialty, Yersinia Infections, Adolescent, Sepsis, 03 medical and health sciences, MESH: Anti-Bacterial Agents, MESH: Antibiotic Prophylaxis, Humans, Intensive care medicine, Aged, MESH: Adolescent, MESH: Humans, business.industry, Septic shock, Transfusion Reaction, MESH: Adult, Antibiotic Prophylaxis, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, business, MESH: Female
Abstract

International audience; Bacterial sepsis has become the most frequent infectious complication of transfusion. Although Yersinia enterocolitica is a common enteropathogen usually causing relatively mild disease, it is nevertheless a prominent cause of life-threatening post-transfusion infection. To gain a better understanding of the clinical presentation and prognosis of this rare occurrence, we performed a systematic and detailed review of 55 published cases, which we present here after a description of the mechanisms underlying the contamination of red blood cell preparations by Y. enterocolitica. The symptoms are rapid-onset septic shock sometimes heralded by atypical symptoms, such as explosive diarrhea, with an overall fatality rate of 54.5%. Although the pathophysiology involves transfusion of preformed bacterial endotoxin, timely administration of effective antibiotics seems to improve the prognosis. Increased vigilance of the blood supply could help mitigate this transfusion hazard, although cost-effective strategies are difficult to define for this highly serious but infrequent event.

Published
2011
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29. Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

Author

Guitton, Christophe, Gérard, Nathalie, Sébille, Véronique, Bretonnière, Cédric, Zambon, Olivier, Villers, Daniel, Charreau, Béatrice, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Réanimation Médicale Polyvalente, Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Plateforme de Biométrie, Cellule de promotion de la recherche clinique, This work was supported by grants from l'Agence de Biomédecine, La Société de Néphrologie, l'Association pour le Développement de la Réanimation (ADR, Nantes), Lilly-France. This work was also in part supported by XENOME a EU-funded Integrated Project in Life Sciences, Genomics and Biotechnology for Health (LSHBCT-2006-037377) and by a grant from la Fondation de l'Avenir (contrat ET8-498)., and Guitton, Christophe

Subjects
MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Vasculitis, MESH: Adult, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, infection, MESH: Male, severe sepsis, survival analysis, MESH: France, soluble EPCR, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Severity of Illness Index, gender, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Intensive Care Units, MESH: Sepsis, MESH: Antigens, CD, MESH: Female, MESH: Outcome Assessment (Health Care), [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Receptors, Cell Surface
Abstract

International audience; PURPOSE: The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established. METHODS: We investigated the time course of plasma sEPCR over the 5 first days (D) of severe sepsis in 40 patients. RESULTS: No significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetics profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or little critical influence on the sEPCR profile. However, we found that sEPCR kinetics was clearly associated with patient's outcome (D28 survival). We demonstrate that a significant but moderate (

Published
2011
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30. Candida bloodstream infections in intensive care units: Analysis of the extended prevalence of infection in intensive care unit study

Author

Irene Karampela, Annika Reintam Blaser, Peter Abel, Joel Starkopf, Małgorzata Mikaszewska-Sokolewicz, ZOUJAIR SALMEN HALABI, Yannick Malledant, Sharon Micallef, Michael Kuiper, Silvia Lage, Pavel Sevcik, Nicola Petrucci, Jordi Rello, Tobias Bingold, Alvaro Rea-Neto, Pablo Monedero, Manu Malbrain, Cintia Grion, Andrew Rhodes, Vera Maravic-Stojkovic, John Frater, Marc-Michael Ventzke, Gabriele Woebker, Fernando Martinez-Sagasti, Daniela Filipescu, Marc Leone, Rowan Burnstein, Uwe Trieschmann, Dmitry Popov, Antonino GIARRATANO, Tamas Szakmany, Alain LEPAPE, Matthias Gründling, Pasquale De Negri, Thomas Berlet, Margaret Herridge, Randy Wax, Piotr Smuszkiewicz, Viktor Svigelj, Dorothy Breen, Julio César Mijangos-Méndez, Oleg Malinin, Mert Akan, Andrea Morelli, Rafael Manez, Ioana Grigoras, Jean-Louis Vincent, Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP], Department of Intensive Care, Erasme Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Kett, Dh, Azoulay, E, Echeverria, Pm, Vincent, Jl, Extended Prevalence of Infection in ICU Study Group of Investigators: tra, Cui, Ferraro, Fausto, Supporting clinical sciences, Intensive Care, Kett, DH, Echeverria, PM, Vincent, JL, Giarratano, A, and RS: FHML non-thematic output

Subjects
Candida albican, Male, Antifungal Agents, Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7], Settore MED/41 - Anestesiologia, Critical Care and Intensive Care Medicine, law.invention, Echinocandins, chemistry.chemical_compound, 0302 clinical medicine, Retrospective Studie, Caspofungin, law, Candida albicans, Prevalence, Antifungal Agent, 030212 general & internal medicine, Fluconazole, MESH: Sepsis, Fungemia, intensive care, Medicine(all), MESH: Aged, Cross Infection, 0303 health sciences, education.field_of_study, MESH: Middle Aged, fungemia, biology, Candidiasis, Middle Aged, Intensive care unit, MESH: Candidiasis, bacteremia, epidemiology, outcome assessment (health care), Aged, Female, Humans, Intensive Care Units, Lipopeptides, Retrospective Studies, Sepsis, 3. Good health, bacteremia epidemiology fungemia intensive care outcome assessment (health care), Candidiasi, MESH: Fluconazole, Human, medicine.drug, medicine.medical_specialty, Sepsi, Intensive Care Unit, Population, 03 medical and health sciences, Intensive care, medicine, Echinocandin, Intensive care medicine, education, MESH: Prevalence, MESH: Humans, 030306 microbiology, business.industry, MESH: Candida albicans, MESH: Echinocandins, MESH: Cross Infection, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Antifungal Agents, medicine.disease, biology.organism_classification, MESH: Male, chemistry, Bacteremia, MESH: Intensive Care Units, business, MESH: Female
Abstract

Objectives: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. Design: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. Setting: EPIC II included 1265 intensive care units in 76 countries. Patients: Patients in participating intensive care units on study day. Interventions: None. MEASUREMENT AND MAIN RESULTS:: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. Conclusion: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use. Copyright 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Published
2011
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31. Experimental Meningococcal Sepsis in Congenic Transgenic Mice Expressing Human Transferrin

Author

Corinne Ruckly, Muhamed-Kheir Taha, Eva Hong, Marek Szatanik, Dario Giorgini, Katarzyna Jopek, Morgan Ledroit, Marie-Anne Nicola, Ala-Eddine Deghmane, Infections Bactériennes Invasives, Institut Pasteur [Paris], Imagerie Dynamique (Plate-Forme) (PFID), The work was supported exclusively by the Institut Pasteur with no external funding., and Institut Pasteur [Paris] (IP)

Subjects
Bacterial Diseases, Viral Diseases, Critical Care and Emergency Medicine, Mouse, Microarrays, Colony Count, Microbial, Gene Expression, lcsh:Medicine, Neisseria meningitidis, medicine.disease_cause, MESH: Meningococcal Infections, Mice, Molecular Cell Biology, MESH: Animals, lcsh:Science, MESH: Sepsis, Animal Management, chemistry.chemical_classification, Inhalation Exposure, Mice, Inbred BALB C, 0303 health sciences, MESH: Cytokines, Multidisciplinary, Transferrin, Acute-phase protein, Brain, Agriculture, Animal Models, MESH: Gene Expression Regulation, Bacterial Pathogens, 3. Good health, Infectious Diseases, Influenza A virus, MESH: Survival Analysis, Medicine, Cytokines, MESH: Inhalation Exposure, Transgenic Animals, Injections, Intraperitoneal, MESH: Transferrin, MESH: Injections, Intraperitoneal, Research Article, MESH: Mice, Transgenic, MESH: Influenza A virus, Congenic, MESH: Mice, Inbred BALB C, Mice, Transgenic, Biology, Meningococcal disease, Microbiology, MESH: Neisseria meningitidis, Sepsis, Mice, Congenic, 03 medical and health sciences, MESH: Brain, Model Organisms, Immune system, MESH: Mice, Congenic, medicine, Animals, Humans, MESH: Mice, MESH: Colony Count, Microbial, 030304 developmental biology, Innate immune system, MESH: Humans, 030306 microbiology, lcsh:R, Computational Biology, medicine.disease, Survival Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Influenza, Meningococcal Infections, Gene Expression Regulation, chemistry, Immunology, Meningoccal Septicemia, lcsh:Q
Abstract

International audience; Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.

Published
2011
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32. Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study

Author

Laurent Brochard, Benoit Schlemmer, Yves Cohen, François Vincent, Fabrice Zeni, Frédéric Gonzalez, Vincent Das, Frédérique Schortgen, Gilles Bernardin, Michael Darmon, Jean Dellamonica, Service de réanimation polyvalente, urgences, CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM), 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), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation médicale, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], INSERM U955, équipe 13, Medical-Surgical Intensive Care Unit, Geneva University Hospital (HUG)-Geneva University Hospital (HUG)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Financial support consisted of a grant from the Assistance-Publique Hôpitaux de Paris (CRC 07 011), a nonprofit, government-funded organization., Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), and BMC, Ed.

Subjects
Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, Critical Care and Intensive Care Medicine, urologic and male genital diseases, Gastroenterology, Cohort Studies, 0302 clinical medicine, Urea, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, MESH: Sepsis, MESH: Cohort Studies, MESH: Aged, MESH: Middle Aged, Acute kidney injury, Acute Kidney Injury, Middle Aged, female genital diseases and pregnancy complications, MESH: Predictive Value of Tests, Intensive Care Units, acute tubular necrosis, MESH: Critical Illness, Female, Cohort study, medicine.medical_specialty, MESH: Hemodynamics, Fractional excretion of sodium, Critical Illness, MESH: Acute Kidney Injury, Sepsis, Excretion, fractional excretion of sodium, 03 medical and health sciences, Predictive Value of Tests, acute kidney failure, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, MESH: Diuretics, Intensive care medicine, Acute tubular necrosis, MESH: Urea, Aged, MESH: Humans, business.industry, urogenital system, Research, Hemodynamics, MESH: Biological Markers, 030208 emergency & critical care medicine, medicine.disease, diuretics, MESH: Male, MESH: Prospective Studies, sensitivity and specificity, ICU, MESH: Intensive Care Units, Diuretic, business, MESH: Female, Biomarkers
Abstract

International audience; INTRODUCTION: Several factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea. METHODS: We conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges). RESULTS: A total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar. CONCLUSIONS: FeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.

Published
2011
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33. Severe Plasmodium malariae malaria in a patient with multiple susceptibility genes

Author

Sandrine Houzé, Anne-Pauline Bellanger, Jean-Paul Mira, Pascal Houzé, Laurence Millon, Olivier Barbot, Jean-François Faucher, Fabrice Bruneel, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), urgences médicales, CHU J Minjoz Besançon, Ministère de la santé, 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), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), réanimation chirurgicale, CH Versailles, 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 ), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), and Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC )

Subjects
Male, MESH : Polymorphism, Genetic, Plasmodium malariae, Disease, MESH : Malaria, Polymerase Chain Reaction, Severity of Illness Index, 0302 clinical medicine, Polymorphism (computer science), MESH : Plasmodium malariae, MESH : Polymerase Chain Reaction, MESH: Sepsis, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Plasmodium malariae, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, medicine.diagnostic_test, biology, MESH: Genetic Testing, musculoskeletal, neural, and ocular physiology, MESH : Sequence Analysis, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Adult, 3. Good health, MESH : Severity of Illness Index, MESH : Sepsis, Sequence Analysis, Adult, MESH : Male, 030231 tropical medicine, MESH: Malaria, Susceptibility gene, macromolecular substances, Sepsis, 03 medical and health sciences, MESH: Sequence Analysis, MESH : Genetic Testing, MESH: Severity of Illness Index, parasitic diseases, MESH: Polymorphism, Genetic, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Gene, Genetic testing, Polymorphism, Genetic, MESH: Humans, 030306 microbiology, business.industry, MESH : Humans, MESH: Adult, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, Virology, MESH: Male, Malaria, nervous system, Immunology, MESH : Genetic Predisposition to Disease, business
Abstract

International audience; We present a case of severe malaria due to Plasmodium malariae. Genetic testing showed that the patient was homozygous for five important gene polymorphisms previously shown to be associated with increased susceptibility to, and/or severity of, severe sepsis. Our case suggests that P. malariae may cause life-threatening disease, and that disease severity may be linked, at least in part, to multiple susceptibility genes.

Published
2011
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34. Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and septic shock

Author

Pierre Tattevin, Nadège Bescher, Karin Tarte, Olivier Tribut, Fabrice Uhel, Joelle Dulong, Yves Le Tulzo, Delphine Monnier, Frédéric Mourcin, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Fonction, structure et inactivation d'ARN bactériens, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Hôpital Pontchaillou, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège des Universitaires de Maladies Infectieuses et Tropicales (CMIT), Programme Hospitalier de Recherche Clinique (PHRC) inter-régional., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: CD4 Lymphocyte Count, MESH: NF-kappa B, MESH: Flow Cytometry, T-Lymphocytes, Regulatory, Immune tolerance, 0302 clinical medicine, Immunology and Allergy, Indoleamine 2,3-dioxygenase, MESH: Sepsis, Chromatography, High Pressure Liquid, MESH: Aged, 0303 health sciences, MESH: Middle Aged, NF-kappa B, Middle Aged, Flow Cytometry, MESH: Case-Control Studies, Shock, Septic, 3. Good health, Infectious Diseases, medicine.anatomical_structure, MESH: Young Adult, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, medicine.symptom, Adult, MESH: Shock, Septic, Inflammation, Biology, Peripheral blood mononuclear cell, Sepsis, 03 medical and health sciences, Young Adult, MESH: Indoleamine-Pyrrole 2,3,-Dioxygenase, medicine, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, MESH: Chromatography, High Pressure Liquid, 030304 developmental biology, Aged, MESH: Humans, Septic shock, Monocyte, MESH: T-Lymphocytes, Regulatory, MESH: Adult, HLA-DR Antigens, medicine.disease, MESH: HLA-DR Antigens, MESH: Male, CD4 Lymphocyte Count, MESH: France, Bacteremia, Case-Control Studies, Immunology, MESH: Female, 030215 immunology
Abstract

International audience; BACKGROUND: Severe sepsis results in a sustained deleterious immune dysregulation. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism, plays a pivotal role in immune tolerance and is induced during various inflammatory conditions. METHODS: Plasma samples obtained from patients with septic shock (n = 38), severe sepsis (n = 35), or sepsis (n = 10) and from healthy donors (n = 26) were analyzed for IDO activity by high-performance liquid chromatography. Lymphocyte, monocyte, and regulatory T cell counts as well as monocytic human leukocyte antigen DR (HLA-DR) expression were quantified by flow cytometry. Peripheral blood mononuclear cells and purified CD14(+) and CD14(-) fractions were assayed in vitro for spontaneous and inducible IDO expression and activity. RESULTS: IDO activity gradually increased according to sepsis severity, and septic patients who died had higher IDO activity on admission than did survivors (P = .013). Monocytes were a major source of active IDO in normal peripheral blood. The percentage and absolute number of circulating CD14(+) cells were increased in septic patients, and their monocytes remained fully able to produce functional IDO after NF-kappaB-independent interferon gamma stimulation but not through NF-kappaB-dependent Toll-like receptor engagement. CONCLUSIONS: IDO activity is increased during severe sepsis and septic shock and is associated with mortality. IDO production could be used to better characterize monocyte reprogramming in sepsis.

Published
2010
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35. Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated)

Author

Andrew F Shorr, Jonathan M Janes, Antonio Artigas, Jyrki Tenhunen, Duncan LA Wyncoll, Emmanuelle Mercier, Bruno Francois, Jean-Louis Vincent, Burkhard Vangerow, Darell Heiselman, Amy G Leishman, Yajun E Zhu, Konrad Reinhart, for the RESPOND Investigators, BMC, Ed., Washington Hospital Center, Lilly Research Laboratories, Eli Lilly and Company, Critical Care Center, Universitat Autònoma de Barcelona (UAB)-Sabadell Hospital, Critical Care Medicine Research Group, Tampere University Hospital, Adult Intensive Care Unit, Guy's and St Thomas' NHS Foundation Trust, Service de Réanimation Polyvalente, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Investigation Clinique de Limoges (CIC1435), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Service de Réanimation Polyvalente [CHU Limoges], CHU Limoges, Department of Intensive Care, Université libre de Bruxelles (ULB)-Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB), Department of Anesthesiology and Intensive Care, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Eli Lilly and Company provided financial support for this study, and funded the article-processing charge, the RESPOND investigators, Sabadell Hospital-Autonomous University of Barcelona, CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Erasme [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau

Subjects
Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Critical Care and Intensive Care Medicine, Gastroenterology, law.invention, MESH: Recombinant Proteins, 0302 clinical medicine, Randomized controlled trial, law, Biological Markers -- blood, MESH: Double-Blind Method, MESH: Sepsis, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, musculoskeletal, neural, and ocular physiology, Sciences bio-médicales et agricoles, Middle Aged, 3. Good health, Treatment Outcome, Female, medicine.symptom, medicine.drug, medicine.medical_specialty, macromolecular substances, MESH: Drug Administration Schedule, Drug Administration Schedule, Sepsis, 03 medical and health sciences, Pharmacotherapy, Double-Blind Method, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Aged, MESH: Humans, business.industry, Septic shock, Drotrecogin alfa, Research, Organ dysfunction, MESH: Biological Markers, 030208 emergency & critical care medicine, medicine.disease, MESH: Male, Surgery, Clinical trial, Protein C -- administration & dosage -- metabolism, Recombinant Proteins -- administration & dosage, Sepsis -- blood -- drug therapy, 030228 respiratory system, nervous system, business, MESH: Female, Protein C, MESH: Protein C
Abstract

Serial alterations in protein C levels appear to correlate with disease severity in patients with severe sepsis, and it may be possible to tailor severe sepsis therapy with the use of this biomarker. The purpose of this study was to evaluate the dose and duration of drotrecogin alfa (activated) treatment using serial measurements of protein C compared to standard therapy in patients with severe sepsis., Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2010
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36. Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils

Author

Benoît-Joseph Laventie, Marie-Hélène Metz-Boutigue, Thomas Lavaux, Yannick Goumon, Elise Glattard, Alain Van Dorsselaer, Didier A. Colin, Ingeborg Welters, Alexis Laux, Sylvie Dirrig-Grosch, Arnaud Muller, Alexander R. Schmidt, Francis Schneider, Dan-Dan Zhang, François Delalande, Dominique Aunis, Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), University of Liverpool, Universitatsklinikum Giessen und Marburg [Marburg,Germany], Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Goumon, Yannick

Subjects
Lipopolysaccharides, Neutrophils, Receptors, Opioid, mu, lcsh:Medicine, Endogeny, MESH: Flow Cytometry, Pharmacology, MESH: Neutrophils, Lymphocyte Activation, Biochemistry, [SCCO]Cognitive science, Critical Care and Emergency Medicine/Sepsis and Multiple Organ Failure, Tandem Mass Spectrometry, MESH: Microscopy, Confocal, lcsh:Science, MESH: Sepsis, Multidisciplinary, Microscopy, Confocal, medicine.diagnostic_test, Morphine, Chemistry, Alkaloid, MESH: Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Electrophoresis, Polyacrylamide Gel, medicine.drug, Research Article, Blotting, Western, MESH: Receptors, Opioid, mu, Enzyme-Linked Immunosorbent Assay, Flow cytometry, Sepsis, Immune system, medicine, MESH: Blotting, Western, Humans, Secretion, Interleukin 8, MESH: Lymphocyte Activation, MESH: Humans, lcsh:R, Interleukin-8, MESH: Tandem Mass Spectrometry, MESH: Immunohistochemistry, [SCCO] Cognitive science, Cell Biology, medicine.disease, MESH: Interleukin-8, MESH: Morphine, Immunology, lcsh:Q, MESH: Lipopolysaccharides, MESH: Electrophoresis, Polyacrylamide Gel
Abstract

International audience; Background: Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis.Methodology: The presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8) or lipopolysaccharide (LPS). Morphine secretion was determined by a morphine-specific ELISA. mu opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested.Principal findings: We confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca(2+). LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca(2+). LPS treatment increased mu opioid receptor expression on neutrophils. Low concentration of morphine (8 nM) significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response syndrome and healthy controls. Mass spectrometry analysis showed that endogenous morphine from serum of patient with sepsis was identical to poppy-derived morphine.Conclusions: Our results indicate that morphine concentrations are increased significantly in the serum of patients with systemic infection and that morphine is, at least in part, secreted from neutrophils during sepsis. Morphine concentrations equivalent to those found in the serum of septic patients significantly inhibited LPS-induced IL-8 secretion in neutrophils.

Published
2010
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37. Cryofibrinogenemia: new insights into clinical and pathogenic features

Author

Ismail Elalamy, Patrice Cacoub, Pascale Ghillani-Dalbin, Damien Sène, Aurélien Delluc, David Saadoun, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Signalisation cellulaire, dynamique circulatoire et athérosclérose précoce (SCDCAP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Service d'Histologie-Biologie tumorale [Hôpital Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Biologie et thérapeutique des pathologies immunitaires (BTPI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Immunochimie (APHP PSL Immuno), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Signalisation cellulaire, dynamique circulatoire et athérosclérose précoce ( SCDCAP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Histologie-Biologie tumorale, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire d'Immunochimie ( APHP PSL Immuno ), Assistance publique - Hôpitaux de Paris (AP-HP), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique ( U986 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), and Biologie et thérapeutique des pathologies immunitaires ( BTPI )

Subjects
Male, MESH: Remission Induction, MESH : Arthralgia, MESH: Gangrene, MESH : Recurrence, MESH: Cold Temperature, medicine.medical_treatment, MESH: Plasmapheresis, Gastroenterology, MESH: Plasminogen Activator Inhibitor 1, MESH: Serum Globulins, 0302 clinical medicine, Adrenal Cortex Hormones, MESH: Cryoglobulins, MESH : Gangrene, MESH : Immunosuppressive Agents, Cryoglobulins, MESH : Raynaud Disease, MESH: Middle Aged, Remission Induction, Plasmapheresis, General Medicine, MESH : Thrombosis, 3. Good health, Cold Temperature, MESH : Sepsis, Serum Globulins, MESH: Immunosuppressive Agents, medicine.medical_specialty, MESH : Urticaria, MESH : Adrenal Cortex Hormones, Gangrene, MESH: Adrenal Cortex Hormones, Necrosis, 03 medical and health sciences, Fibrinolytic Agents, MESH: Skin, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Sepsis, Euglobulin lysis time, MESH : Skin, Humans, MESH: Amputation, MESH : Middle Aged, MESH: Thrombosis, Purpura, Leg, MESH: Humans, MESH: alpha-Macroglobulins, MESH : Humans, medicine.disease, MESH : Necrosis, MESH : Cold Temperature, MESH : Amputation, MESH : Leg, MESH : Purpura, MESH: Female, Urticaria, Cryofibrinogenemia, 030204 cardiovascular system & hematology, MESH : Serum Globulins, MESH: Fibrinolysis, Recurrence, MESH: Urticaria, MESH: Fibrinolytic Agents, MESH : Female, MESH: Sepsis, Skin, MESH : Fibrinolysis, Fibrinolysis, Middle Aged, Arthralgia, MESH: Leg, Cryoglobulinemia, Female, Vasculitis, Immunosuppressive Agents, MESH : Plasminogen Activator Inhibitor 1, MESH: Cryoglobulinemia, MESH : Male, Amputation, Surgical, MESH: Arthralgia, MESH : alpha-Macroglobulins, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, MESH: Purpura, alpha-Macroglobulins, MESH : Plasmapheresis, 030203 arthritis & rheumatology, MESH: Necrosis, MESH : Remission Induction, business.industry, MESH: Raynaud Disease, MESH : Fibrinolytic Agents, Raynaud Disease, Thrombosis, MESH : Cryoglobulinemia, MESH : Cryoglobulins, MESH: Male, Surgery, MESH: Recurrence, business, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; OBJECTIVE: Cryofibrinogenemia is an under-recognized cryoprotein that can be life-threatening when untreated. Our aim was to describe the prevalence and clinical findings of patients with cryofibrinogenemia and to clarify the mechanisms involved. METHODS: Between 1996 and 2006, 2312 patients were tested for cryofibrinogenemia in a single university hospital. A total of 515 patients had positive test results, of whom 455 (88.3%) had an associated cryoglobulin. RESULTS: Sixty patients (11.7%) with persistent cryofibrinogenemia and without cryoglobulin were included in the study. Main clinical manifestations related to cryofibrinogenemia included purpura (46.6%), skin necrosis (36.6%), and arthralgia (31.6%) with cold sensitivity in 40%. Overall thrombotic events occurred in up to 40% of cases. Cryofibrinogen plasma concentration was 2 times greater in patients with thrombotic events (P=.012). Complications included gangrene (5%), septicemia (5%), and leg amputation (3.3%). Complete remission of cryofibrinogenemia was achieved in 78% of patients receiving antithrombotic agents, steroids, or immunosuppressants, whereas 41.6% of patients experienced a relapse after a median time of 9 months (range 7-42 months). After a mean follow-up of 85 months, 3 patients died of sepsis (n=2) and cardiovascular disease (n=1). Fibrinolysis status analyzed in a patient with cryofibrinogenemia showed an increase in fibrinolysis inhibitor levels, plasminogen activator inhibitor-1, alpha-2 macroglobulin, and euglobulin lysis time, which normalized after fibrinolytic therapy. CONCLUSION: Essential cryofibrinogenemia represents 12% of all the cryoproteins at Pitie-Salpêtriere Hospital. Thrombotic events are frequent and could be associated with the amount of plasma cryofibrinogen. Defects in the fibrinolysis process might lead to cryofibrinogen accumulation and clotting in small and medium arteries.

Published
2009
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38. Influence of mannose-binding lectin genotypes and serostatus in allo-SCT: analysis of 131 recipients and donors

Author

Tatjana Zabelina, R Thiébaut, Ulrike Bacher, N. Kroeger, Hartmut Kabisch, R M Haston, Boris Fehse, Michael Lioznov, F Ayuk, Axel R. Zander, P Das, Nigel Klein, Olaf Neth, Olga Waschke, Mouillet, Evelyne, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Department of Paediatric Infectious Diseases and Immunology, Hospital Universitario Virgen del Roci, Department of Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Department of Pediatric Hematology and Oncology, University of Hamburg, Department of Experimental Pediatric Oncology and Hematology, University Hospital of the Johann Wolfgang Goethe-University, Epidémiologie et Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2, and Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Tissue Donors, Graft vs Host Disease, MESH: Genotype, 0302 clinical medicine, Genotype, Prospective Studies, MESH: Sepsis, Mannan-binding lectin, MESH: Aged, 0303 health sciences, Hematology, MESH: Middle Aged, Middle Aged, Tissue Donors, 3. Good health, MESH: Mannose-Binding Lectin, Phenotype, Female, Disease Susceptibility, MESH: Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, MESH: Disease Susceptibility, MESH: Graft vs Host Disease, chemical and pharmacologic phenomena, Biology, MESH: Phenotype, Mannose-Binding Lectin, Article, Sepsis, 03 medical and health sciences, MESH: Mycoses, Internal medicine, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, 030304 developmental biology, Aged, Retrospective Studies, MESH: Adolescent, Transplantation, MESH: Humans, Lectin, MESH: Adult, MESH: Retrospective Studies, Fungal pneumonia, medicine.disease, bacterial infections and mycoses, MESH: Prospective Studies, MESH: Male, Complement system, Mycoses, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, 030215 immunology, Stem Cell Transplantation
Abstract

International audience; Mannan-binding lectin (MBL) deficiency is determined by MBL gene polymorphisms and is associated with an increased infection risk. To clarify the role of MBL in Allo-SCT, 131 recipients-donors were analysed. MBL genotypes were determined by PCR and heteroduplex analyses, MBL serum levels by ELISA, and MBL oligomers by western blotting. MBL levels

Published
2009
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39. Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

Author

Jean Chastre, Jordi Mancebo, Duncan MacRae, Daniel De Backer, Marc Bonten, Herwig Gerlach, Haibo Zhang, Giorgio Conti, Giuseppe Citerio, Elie Azoulay, Salvatore Maurizio Maggiore, Jérôme Pugin, François Lemaire, Philipp Metnitz, Massimo Antonelli, Göran Hedenstierna, Alexandre Mebazaa, Jan Wernerman, Johan Groeneveld, Department of Intensive Care and Anesthesiology, Università cattolica del Sacro Cuore [Milano] (Unicatt), 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), Department of Medical Microbiology Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurointensive Care Unit, Ospedale S. Gerardo, Service des Soins Intensifs, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Anesthesiology, Intensive Care Medicine, and Pain Management, Vivantes-Klinikum Neukoelln, Intensive Care Medicine Unit, Free University Medical Centre, Department of Clinical Physiology, Uppsala University, Pediatric Intensive Care Unit, Royal Brompton Hospital, Hospital de la Santa Creu i Sant Pau, Service d'anesthésie - réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Department of Anesthesiology and General Intensive Care, University Hospital of Vienna, University Hospital of Geneva, Department of Anesthesiology and Intensive Care Medicine, Karolinska Institutet [Stockholm], Interdepartmental Division of Critical Care Medicine, University of Toronto, Vesin, Aurélien, Intensive care medicine, ICaR - Ischemia and repair, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Antonelli, M, Azoulay, E, Bonten, M, Chastre, J, Citerio, G, Conti, G, De Backer, D, Lemaire, F, Gerlach, H, Groeneveld, J, Hedenstierna, G, Macrae, D, Mancebo, J, Maggiore, S, Mebazaa, A, Metnitz, P, Pugin, J, Wernerman, J, and Zhang, H

Subjects
Resuscitation, ARDS, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Hypoxia-Ischemia, Brain/epidemiology, 0302 clinical medicine, Intubation, Respiratory Insufficiency/*diagnosis/epidemiology/*therapy, Sepsis/epidemiology, MESH: Respiration, Artificial, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, Respiratory Distress Syndrome, Intensive Care/*methods, ddc:617, Lung Injury, 3. Good health, Reperfusion Injury, Hypoxia-Ischemia, Brain, Acute Disease, MESH: Lung Injury, MESH: Acute Disease, Respiratory Insufficiency, Human, medicine.medical_specialty, Critical Care, Sepsi, Lung injury, Sepsis, 03 medical and health sciences, Intensive care, Anesthesiology, medicine, Intubation, Intratracheal, Humans, MESH: Intensive Care, Intensive care medicine, Lung Injury/epidemiology/therapy, Mechanical ventilation, MESH: Humans, MESH: Intubation, Intratracheal, business.industry, Reperfusion Injury/epidemiology, Intensive Care, Respiratory Distress Syndrome, Adult, Year in Review 2008, 030208 emergency & critical care medicine, medicine.disease, Respiration, Artificial, Intubation, Intratracheal/*methods, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Respiratory Distress Syndrome, Adult, MESH: Hypoxia-Ischemia, Brain, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Respiratory Distress Syndrome, Adult/epidemiology/physiopathology/*therapy, MESH: Reperfusion Injury, business, Respiration, Artificial/*methods, MESH: Respiratory Insufficiency
Abstract

Year in review in Intensive Care Medicine, 2008 : II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

Published
2009
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40. Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients

Author

André Pechinot, Aurélie Snauwaert, Jean-Pierre Quenot, Jean-Marc Doise, Sébastien Prin, Niels-Olivier Olsson, Serge Aho, Sylvain Ladoire, Pierre Emmanuel Charles, Bernard Blettery, Lipides - Nutrition - Cancer (U866) (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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire de Microbiologie Médicale et Moléculaire, Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) ( 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), and Université de Bourgogne ( UB )

Subjects
Male, MESH: Protein Precursors, MESH : Retrospective Studies, MESH : Aged, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Critical Illness, MESH : Early Diagnosis, Procalcitonin, law.invention, Leukocyte Count, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Early Diagnosis, law, MESH : Female, 030212 general & internal medicine, MESH : Protein Precursors, MESH: Sepsis, Aged, 80 and over, MESH: Aged, First episode, MESH: Middle Aged, Middle Aged, MESH : Leukocyte Count, Intensive care unit, MESH: Predictive Value of Tests, 3. Good health, C-Reactive Protein, Infectious Diseases, Predictive value of tests, MESH: Critical Illness, Female, MESH : Sepsis, SOFA score, Research Article, Calcitonin, medicine.medical_specialty, Calcitonin Gene-Related Peptide, Critical Illness, MESH : Male, MESH: Multivariate Analysis, lcsh:Infectious and parasitic diseases, Sepsis, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Intensive care, MESH: C-Reactive Protein, medicine, Humans, MESH : Middle Aged, lcsh:RC109-216, MESH : Predictive Value of Tests, Protein Precursors, MESH : Aged, 80 and over, Intensive care medicine, Aged, Retrospective Studies, MESH: Humans, MESH: Calcitonin, business.industry, MESH : Humans, MESH : Multivariate Analysis, MESH: Retrospective Studies, 030208 emergency & critical care medicine, MESH : C-Reactive Protein, medicine.disease, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH : Calcitonin, Systemic inflammatory response syndrome, Early Diagnosis, MESH: Leukocyte Count, Multivariate Analysis, business, MESH: Female
Abstract

Background Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT. Methods review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007. Results 179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; p < 0.050). Conclusion In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.

Published
2008
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41. [Septicemia]

Author

Timsit, Jean-François, Dubois, Yohann, Clinique de réanimation médicale, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon

Subjects
MESH: Humans, MESH: Diagnosis, Differential, MESH: Anti-Bacterial Agents, MESH: Patient Care Planning, MESH: Systemic Inflammatory Response Syndrome, MESH: Monitoring, Physiologic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Bacteriological Techniques, MESH: Bacteremia, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008

42. [Septicemia]

Author

Timsit, Jean-François, Dubois, Yohann, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, and Vesin, Aurélien

Subjects
MESH: Humans, MESH: Diagnosis, Differential, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Anti-Bacterial Agents, MESH: Patient Care Planning, MESH: Systemic Inflammatory Response Syndrome, MESH: Monitoring, Physiologic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Bacteriological Techniques, MESH: Bacteremia, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008

43. Imaging host-pathogen interactions

Author

Nicolas Glaichenhaus, Laura Campisi, Frédéric Brau, Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Diagnostic Imaging, 0303 health sciences, MESH: Humans, MESH: Diagnostic Imaging, Immunology, MESH: Host-Pathogen Interactions, Computational biology, Biology, 3. Good health, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Sepsis, Host-Pathogen Interactions, Immunology and Allergy, Animals, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, Host (network), Pathogen, MESH: Sepsis, 030304 developmental biology, 030215 immunology
Abstract

Imaging techniques have been revolutionized by advancements in both microscope instrumentation and data collection processing software. Immunologists and microbiologists now have access to a large panel of powerful technologies that are characterized by different spatial and time resolutions. In this review, we discuss recent studies in which emerging imaging technologies have been used to decipher the complexity of the interactions between pathogens and their mammalian hosts. By focusing on two very different pathogens, Plasmodium and Salmonella, we emphasize the critical role of imaging studies in the understanding of the host's immune system response to a pathogen.

Published
2008
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44. Diagnosis and prevention of catheter-related infections

Author

J.-F. Timsit, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, and Vesin, Aurélien

Subjects
medicine.medical_specialty, Catheterization, Central Venous, Quality Assurance, Health Care, medicine.drug_class, MESH: Quality Assurance, Health Care, medicine.medical_treatment, MESH: Catheters, Indwelling, MESH: Bacteriological Techniques, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, MESH: Infection Control, 0302 clinical medicine, Catheters, Indwelling, MESH: Anti-Infective Agents, Local, Antiseptic, Fibrinolytic Agents, law, 030225 pediatrics, Intensive care, Sepsis, MESH: Anti-Bacterial Agents, medicine, Infection control, Humans, MESH: Fibrinolytic Agents, Blood culture, 030212 general & internal medicine, Intensive care medicine, MESH: Sepsis, Bacteriological Techniques, Infection Control, MESH: Catheterization, Central Venous, MESH: Humans, medicine.diagnostic_test, business.industry, Risk of infection, Intensive care unit, 3. Good health, Anti-Bacterial Agents, Catheter, Intensive Care Units, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Anti-Infective Agents, Local, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Central venous catheter
Abstract

International audience; PURPOSE OF REVIEW: To highlight the major advances in diagnosing and preventing catheter-related infections published in research articles published between March 2004 and May 2007. RECENT FINDINGS: The challenge remains to make the diagnosis of catheter-related infection with good accuracy without catheter removal. The differential time to obtain positive qualitative blood culture appeared to be the most accurate available technique. Many catheter-related bloodstream infections are preventable. Simple interventions are often useful and multimodal programs are very efficacious, particularly in the intensive care setting. For long-term catheter-related bloodstream infection prevention, patient education appeared promising. Interesting evidence suggested that anticoagulant, by decreasing the biofilm formation, could decrease the risk of infection. For short-term central venous catheter-related infections research is ongoing on antiseptic dressings. Antiseptic lock appeared promising for preventing long-term central venous catheter bloodstream infections. SUMMARY: Nowadays, multimodal programs of catheter infection prevention are efficacious. Levels of catheter-related bloodstream infection of more than one or two per 1000 catheter-days are usually only found in the intensive care unit. It is a prerequisite to evaluate the cost-effectiveness of new techniques of prevention. As catheter-related bloodstream infections become rarer, strategies limiting unnecessary removal of catheters need to be developed and tested.

Published
2007
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45. Rac2 is a major actor of Drosophila resistance to Pseudomonas aeruginosa acting in phagocytic cells

Author

Amélie Avet-Rochex, Jackie Perrin, Marie-Odile Fauvarque, Evelyne Bergeret, Transduction du signal : signalisation calcium, phosphorylation et inflammation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fauvarque, Marie-Odile

Subjects
MESH: ADP Ribose Transferases, MESH: rac GTP-Binding Proteins, CDC42, medicine.disease_cause, 0302 clinical medicine, MESH: Gram-Negative Bacteria, MESH: Animals, cdc42 GTP-Binding Protein, MESH: Phagocytosis, Pathogen, MESH: Sepsis, Host factor, ADP Ribose Transferases, 0303 health sciences, MESH: Plasma Cells, MESH: Antimicrobial Cationic Peptides, rac GTP-Binding Proteins, Drosophila melanogaster, Host cell cytoplasm, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, MESH: Mitogen-Activated Protein Kinase 8, Phagocytosis, Bacterial Toxins, Plasma Cells, RAC1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Models, Biological, Microbiology, MESH: Drosophila melanogaster, 03 medical and health sciences, Immune system, Sepsis, Gram-Negative Bacteria, Genetics, medicine, Animals, Mitogen-Activated Protein Kinase 8, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, MESH: cdc42 GTP-Binding Protein, Macrophages, MESH: Models, Biological, MESH: Macrophages, Cell Biology, MESH: Bacterial Toxins, 030217 neurology & neurosurgery, Antimicrobial Cationic Peptides
Abstract

International audience; Pathogen recognition and engulfment by phagocytic cells of the blood cell lineage constitute the first line of defense against invading pathogens. This cellular immune response is conserved throughout evolution and depends strictly on cytoskeletal changes regulated by the RhoGTPases family. Many pathogens have developed toxins modifying RhoGTPases activity to their own benefit. In particular, the Exoenzyme S (ExoS) toxin of the Gram-negative bacteria Pseudomonas aeruginosa is directly injected into the host cell cytoplasm and contains a GAP domain (ExoSGAP) targeting RhoGTPases. Searching for the contribution of each RhoGTPases, Rho1, Rac1, Rac2, Mtl (Mig2-like) and Cdc42 to fly resistance to P. aeruginosa infections, we found that Rac2 is required to resist to P. aeruginosa and to other Gram-negative or Gram-positive bacteria. The Rac2 immune-deficient phenotype is attributable to defective engulfment of pathogens since Rac2-mutant macrophages exhibited strong reduction in the phagocytosis level of both Gram-negative and Gram-positive bacterial particles whereas systemic immune signaling pathways, including Toll, Immune deficiency and Jun kinases, were not affected. Co-expression of Rac2 and ExoSGAP rescued the increased sensitivity to P. aeruginosa observed in ExoSGAP-expressing flies suggesting that Rac2 is the main host factor whose function is inhibited by the GAP domain of the ExoS toxin.

Published
2007
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46. Mitochondrial function and substrate availability

Author

Xavier Leverve, Hamant, Sarah, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Mitochondria, Multiple Organ Failure, Respiratory chain, Oxidative phosphorylation, Nicotinamide adenine dinucleotide, Biology, Critical Care and Intensive Care Medicine, Oxidative Phosphorylation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adenosine Triphosphate, MESH: Oxidative Phosphorylation, Intensive care, Sepsis, MESH: Adenosine Triphosphate, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Multiple Organ Failure, MESH: Sepsis, 030304 developmental biology, chemistry.chemical_classification, Flavin adenine dinucleotide, 0303 health sciences, Reactive oxygen species, MESH: Electron Transport Complex I, MESH: Humans, Electron Transport Complex I, MESH: Energy Metabolism, MESH: Reactive Oxygen Species, Metabolism, 3. Good health, Mitochondria, chemistry, Biochemistry, 030220 oncology & carcinogenesis, Energy Metabolism, Reactive Oxygen Species, Adenosine triphosphate
Abstract

International audience; Carbohydrates and lipid oxidations support energy metabolism by distinct pathways exhibiting similarities and differences. Alterations of energy metabolism during sepsis are well recognized; however, failure of oxygen or substrate supply is not a prominent cause. The occurrence of a "mitochondrial cytopathy" induced by sepsis explains some of these abnormalities, which may represent a "metabolic hibernation," a potential strategy of defense during the very acute phase of the illness. Our view of the involvement of mitochondrial metabolism in cell signaling has evolved considerably. Because of the structure of the respiratory chain, the way electrons are provided (upstream or downstream of complex 1 [i.e., nicotinamide adenine dinucleotide {reduced form} or flavin adenine dinucleotide {reduced form}]) plays an important role in the regulation of several functions, including the yield of adenosine triphosphate synthesis and the production of reactive oxygen species. Moreover, the modern view of energy channeling and compartmentation in the cell may open attractive hypotheses regarding the changes in cellular energy distribution in pathologic states, such as sepsis.

Published
2007
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47. Structure-based design, synthesis, and A-site rRNA cocrystal complexes of functionally novel aminoglycoside antibiotics: C2' ether analogues of paromomycin

Author

Jiro Kondo, Eric Westhof, Susanta Adhikari, Michael T. Migawa, Stephen Hanessian, Ray Ranken, Eric E. Swayze, Boris François, Julia Wirmer-Bartoschek, Pachamuthu Kandasamy, Janek Szychowski, Guillermo Vasquez, Department of Chemistry, Université de Montréal (UdeM), Isis Pharmaceuticals, IBIS THERAPEUTICS-ISIS Therapeutics, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), and Université de Montréal [Montréal]

Subjects
Models, Molecular, MESH: Paromomycin, Paromomycin, MESH: Drug Design, Crystallography, X-Ray, Cocrystal, chemistry.chemical_compound, Mice, MESH: Structure-Activity Relationship, Drug Discovery, MESH: Staphylococcus aureus, MESH: Animals, MESH: Sepsis, Antibacterial agent, Mice, Inbred BALB C, MESH: Microbial Sensitivity Tests, Molecular Structure, MESH: Escherichia coli, Aminoglycoside, Kanamycin, Neomycin, Staphylococcal Infections, 3. Good health, Anti-Bacterial Agents, Biochemistry, Molecular Medicine, Female, MESH: Models, Molecular, medicine.drug, Ethers, Staphylococcus aureus, Stereochemistry, MESH: Molecular Structure, MESH: Staphylococcal Infections, MESH: Mice, Inbred BALB C, Ether, Microbial Sensitivity Tests, Structure-Activity Relationship, Sepsis, MESH: Anti-Bacterial Agents, medicine, Escherichia coli, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Binding Sites, MESH: Crystallography, X-Ray, Aminocyclitol, chemistry, MESH: Binding Sites, RNA, Ribosomal, Drug Design, MESH: RNA, Ribosomal, MESH: Ethers, MESH: Female
Abstract

International audience; A series of 2"-O-substituted ether analogues of paromomycin were prepared based on new site-selective functionalizations. X-ray cocrystal complexes of several such analogues revealed a new mode of binding in the A-site rRNA, whereby rings I and II adopted the familiar orientation and position previously observed with paromomycin, but rings III and IV were oriented differently. With few exceptions, all of the new analogues showed potent inhibitory activity equal or better than paromomycin against a sensitive strain of S. aureus. Single digit microM MIC values were obtained against E. coli, with some of the ether appendages containing polar or basic end groups. Two analogues showed excellent survival rate in a mouse septicemia protection assay. Preliminary histopathological analysis of the kidney showed no overt signs of toxicity, while controls with neomycin and kanamycin were toxic at lower doses.

Published
2007
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48. Caenorhabditis elegans as a simple model to study phenotypic and genetic virulence determinants of extraintestinal pathogenic Escherichia coli

Author

François Taddei, Olivier Clermont, Médéric Diard, Bertrand Picard, Simon Baeriswyl, Ivan Matic, Erick Denamur, Stéphanie Gouriou, Génétique moléculaire, évolutive et médicale, IFR65-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR65-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecologie et Evolution des Microorganismes ( EEM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne ( LUBEM ), Université de Brest ( UBO ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Gouriou, Stéphanie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]

Subjects
Serum, MESH : Virulence Factors, MESH : Escherichia coli, MESH : Movement, MESH: Movement, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Virulence, medicine.disease_cause, Mice, MESH : Serum, Bile, MESH: Animals, MESH : Anti-Bacterial Agents, MESH : Muramidase, MESH: Sepsis, Caenorhabditis elegans, Escherichia coli Infections, 2. Zero hunger, 0303 health sciences, Extraintestinal Pathogenic Escherichia coli, biology, Virulence, Virulence factors, MESH: Escherichia coli, MESH : Growth Inhibitors, MESH : Virulence, Experimental animal model, MESH: Serum, Enterobacteriaceae, Phenotype, Growth Inhibitors, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, MESH : Escherichia coli Infections, MESH: Models, Animal, MESH: Survival Analysis, Models, Animal, MESH : Sepsis, MESH : Bile, Movement, Immunology, Microbiology, Caenorhabdilis elegans, MESH : Caenorhabditis elegans, 03 medical and health sciences, Phylogenetics, Sepsis, MESH: Anti-Bacterial Agents, MESH: Caenorhabditis elegans, MESH : Mice, medicine, Escherichia coli, Animals, Humans, MESH: Mice, MESH: Bile, 030304 developmental biology, MESH: Virulence Factors, MESH: Escherichia coli Infections, MESH: Humans, 030306 microbiology, MESH : Humans, biology.organism_classification, Survival Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Models, Animal, MESH: Growth Inhibitors, MESH: Muramidase, Muramidase, MESH : Animals, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Survival Analysis, Bacteria
Abstract

Caenorhabditis elegans as a simple model to study phenotypic and genotypic determinants of pathogenicity of extraintestinal pathogenic Escherichia coli Virulence of extraintestinal pathogenic Escherichia coli strains in Caenorhabditis elegans Virulence of extraintestinal pathogenic Escherichia coli strains in Caenorhabditis elegans and mice Comparison of the virulence of extraintestinal pathogenic Escherichia coli in Caenorhabditis elegans and mice; International audience; Extraintestinal pathogenic Escherichia coli (ExPEC) strains cause disease by invading normally sterile niches within the host body, e.g., urinary tract, blood and cerebrospinal fluid. Infections due to ExPEC strains, in particular urinary tract infections, cause considerable morbidity and significant health-care costs. The goal of our study is to evaluate whether Caenorhabditis elegans can be used as a model to study phenotypic and genetic virulence determinants of ExPEC strains. For this purpose, we used a collection of 31 E. coli strains isolated during acute extra-intestinal infections or from the feces of healthy individuals. For all strains, the phylogeny, the presence of ExPEC virulence factors, the resistance to biologically relevant stressors (bile, human serum and lysozyme), the motility, the growth rate, the virulence in C. elegans and in a murine septicaemia model has been established. The results show that there is a strong link between virulence in C. elegans and certain phenotypic and genetic virulence predictors of ExPEC strains determinable in vitro. Furthermore, there is a significant correlation between virulence of different ExPEC strains in C. elegans and in the murine model. Therefore, our results suggest that C. elegans can be used as a model to study virulence determinants of ExPEC strains.

Published
2007
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49. Year in review in Intensive Care Medicine, 2006. II. Infections and sepsis, haemodynamics, elderly, invasive and noninvasive mechanical ventilation, weaning, ARDS

Author

Christian Richard, Philipp Metnitz, Elie Azoulay, Daniel De Backer, Herwig Gerlach, Laurent Brochard, Peter J. D. Andrews, Geoffrey J. Dobb, Jérôme Pugin, Jordi Mancebo, Massimo Antonelli, Christian Brun-Buisson, Jean-Yves Fagon, Stefano Nava, Johan Groeneveld, Duncan Macrae, Michael R. Pinsky, Peter Radermacher, Intensive Care Medicine Unit, Western General Hospital, 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), Department of Intensive Care and Anesthesiology, Università cattolica del Sacro Cuore [Milano] (Unicatt), Fonctions Cellulaires et Moleculaires de l'Appareil Respiratoire et des Vaisseaux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service des Soins Intensifs, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Royal Perth Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Department of Anesthesiology, Intensive Care Medicine, and Pain Management, Vivantes-Klinikum Neukoelln, VUmc, Pediatric Intensive Care Unit, Royal Brompton Hospital, Hospital de la Santa Creu i Sant Pau, Department of Anesthesiology and General Intensive Care, University Hospital of Vienna, Fondazione S. Maugeri, University Hospital of Geneva, University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Department of Anesthesia, Universitätsklinikum Ulm - University Hospital of Ulm, Intensive Care Unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Vesin, Aurélien

Subjects
ARDS, MESH: Heart Arrest, medicine.medical_treatment, Respiratory Tract Diseases, Hemodynamics, MESH: Geriatrics, Critical Care and Intensive Care Medicine, Severe Acute Respiratory Syndrome, 0302 clinical medicine, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, MESH: Aged, Respiratory Distress Syndrome, Pulmonary Arterial Hypertension, Year in review, Acute Respiratory Distress Syndrome Patient, 3. Good health, MESH: Communicable Diseases, Ventilator Weaning, medicine.medical_specialty, Critical Care, Pain medicine, Communicable Diseases, Sepsis, 03 medical and health sciences, Anesthesiology, medicine, Weaning, Humans, MESH: Intensive Care, Intensive care medicine, Intensive Care Unit Patient, Medical Emergency Team, Aged, Mechanical ventilation, MESH: Humans, business.industry, 030208 emergency & critical care medicine, MESH: Ventilator Weaning, medicine.disease, Heart Arrest, Year in Review 2006, 030228 respiratory system, Geriatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Respiratory Distress Syndrome, Adult, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Respiratory Tract Diseases, business
Abstract

This review summarizes all articles published in Intensive Care Medicine in 2006, grouped by specific topic.

Published
2007
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50. [Case no. 4. Pyelonephritis complicated by suppurative thrombosis of the renal vein, with septic pulmonary embolism]

Author

Laissy, J. P., Fernandez, P., Rouvière, O., Besançon, Isabelle, Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Applications des ultrasons à la thérapie, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Venous Thrombosis, MESH: Aged, MESH: Pulmonary Embolism, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Humans, Pyelonephritis, MESH: Pyelonephritis, Renal Veins, MESH: Male, Sepsis, MESH: Renal Veins, MESH: Venous Thrombosis, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Pulmonary Embolism, MESH: Sepsis, ComputingMilieux_MISCELLANEOUS, Aged
Abstract

International audience

Published
2007

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