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1. The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

Author: Melissande Louis, Ali Tahrioui, Courtney J. Lendon, Thomas Clamens, Jérôme Leprince, Benjamin Lefranc, Eric Kipnis, Teddy Grandjean, Emeline Bouffartigues, Magalie Barreau, Florian Defontaine, Pierre Cornelis, Marc G.J. Feuilloley, Nicholas J. Harmer, Sylvie Chevalier, and Olivier Lesouhaitier
Subjects: Biofilm, Natriuretic peptides, Osteocrin, h-NPR-C, Bacterial adaptation, Bacterial sensor, Biotechnology, TP248.13-248.65, Microbiology, QR1-502
Abstract: Biofilms are highly tolerant to antimicrobials and host immune defense, enabling pathogens to thrive in hostile environments. The diversity of microbial biofilm infections requires alternative and complex treatment strategies. In a previous work we demonstrated that the human Atrial Natriuretic Peptide (hANP) displays a strong anti-biofilm activity toward Pseudomonas aeruginosa and that the binding of hANP by the AmiC protein supports this effect. This AmiC sensor has been identified as an analog of the human natriuretic peptide receptor subtype C (h-NPRC). In the present study, we evaluated the anti-biofilm activity of the h-NPRC agonist, osteocrin (OSTN), a hormone that displays a strong affinity for the AmiC sensor at least in vitro. Using molecular docking, we identified a pocket in the AmiC sensor that OSTN reproducibly docks into, suggesting that OSTN might possess an anti-biofilm activity as well as hANP. This hypothesis was validated since we observed that OSTN dispersed established biofilm of P. aeruginosa PA14 strain at the same concentrations as hANP. However, the OSTN dispersal effect is less marked than that observed for the hANP (−61% versus −73%). We demonstrated that the co-exposure of P. aeruginosa preformed biofilm to hANP and OSTN induced a biofilm dispersion with a similar effect to that observed with hANP alone suggesting a similar mechanism of action of these two peptides. This was confirmed by the observation that OSTN anti-biofilm activity requires the activation of the complex composed by the sensor AmiC and the regulator AmiR of the ami pathway. Using a panel of both P. aeruginosa laboratory reference strains and clinical isolates, we observed that the OSTN capacity to disperse established biofilms is highly variable from one strain to another. Taken together, these results show that similarly to the hANP hormone, OSTN has a strong potential to be used as a tool to disperse P. aeruginosa biofilms.
Published: 2023
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2. Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice

Author: Rodrigue Dessein, Marvin Bauduin, Teddy Grandjean, Rémi Le Guern, Martin Figeac, Delphine Beury, Karine Faure, Christelle Faveeuw, Benoit Guery, Philippe Gosset, and Eric Kipnis
Subjects: Antibiotics, Dysbiosis, Pseudomonas aeruginosa, Murine model, Flt3-ligand, Fecal microbial transplant, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.
Published: 2020
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3. Pseudomonas aeruginosa Biofilm Dispersion by the Human Atrial Natriuretic Peptide

Author: Mélissande Louis, Thomas Clamens, Ali Tahrioui, Florie Desriac, Sophie Rodrigues, Thibaut Rosay, Nicholas Harmer, Suraya Diaz, Magalie Barreau, Pierre‐Jean Racine, Eric Kipnis, Teddy Grandjean, Julien Vieillard, Emeline Bouffartigues, Pierre Cornelis, Sylvie Chevalier, Marc G. J. Feuilloley, and Olivier Lesouhaitier
Subjects: ami pathway, antibiotics, bacterial adaptation, bacterial sensor, biofilm dispersion, hANP, Science
Abstract: Abstract Pseudomonas aeruginosa biofilms cause chronic, antibiotic tolerant infections in wounds and lungs. Numerous recent studies demonstrate that bacteria can detect human communication compounds through specific sensor/receptor tools that modulate bacterial physiology. Consequently, interfering with these mechanisms offers an exciting opportunity to directly affect the infection process. It is shown that the human hormone Atrial Natriuretic Peptide (hANP) both prevents the formation of P. aeruginosa biofilms and strongly disperses established P. aeruginosa biofilms. This hANP action is dose‐dependent with a strong effect at low nanomolar concentrations and takes effect in 30–120 min. Furthermore, although hANP has no antimicrobial effect, it acts as an antibiotic adjuvant. hANP enhances the antibiofilm action of antibiotics with diverse modes of action, allowing almost full biofilm eradication. The hANP effect requires the presence of the P. aeruginosa sensor AmiC and the AmiR antiterminator regulator, indicating a specific mode of action. These data establish the activation of the ami pathway as a potential mechanism for P. aeruginosa biofilm dispersion. hANP appears to be devoid of toxicity, does not enhance bacterial pathogenicity, and acts synergistically with antibiotics. These data show that hANP is a promising powerful antibiofilm weapon against established P. aeruginosa biofilms in chronic infections.
Published: 2022
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4. Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU

Author: Marc Leone, Lila Bouadma, Bélaïd Bouhemad, Olivier Brissaud, Stéphane Dauger, Sébastien Gibot, Sami Hraiech, Boris Jung, Eric Kipnis, Yoann Launey, Charles-Edouard Luyt, Dimitri Margetis, Fabrice Michel, Djamel Mokart, Philippe Montravers, Antoine Monsel, Saad Nseir, Jérôme Pugin, Antoine Roquilly, Lionel Velly, Jean-Ralph Zahar, Rémi Bruyère, Gérald Chanques, ADARPEF, and GFRUP
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. Results The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Conclusions HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.
Published: 2018
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5. The ICU-Diary study: prospective, multicenter comparative study of the impact of an ICU diary on the wellbeing of patients and families in French ICUs

Author: Maïté Garrouste-Orgeas, Cécile Flahault, Léonor Fasse, Stéphane Ruckly, Nora Amdjar-Badidi, Laurent Argaud, Julio Badie, Amélie Bazire, Naike Bige, Eric Boulet, Lila Bouadma, Cédric Bretonnière, Bernard Floccard, Alain Gaffinel, Xavier de Forceville, Hubert Grand, Rebecca Halidfar, Olfa Hamzaoui, Mercé Jourdain, Paul-Henri Jost, Eric Kipnis, Audrey Large, Alexandre Lautrette, Olivier Lesieur, Virginie Maxime, Emmanuelle Mercier, Jean Paul Mira, Yannick Monseau, Erika Parmentier-Decrucq, Jean-Philippe Rigaud, Antoine Rouget, François Santoli, Georges Simon, Fabienne Tamion, Nathalie Thieulot-Rolin, Marina Thirion, Sandrine Valade, Isabelle Vinatier, Christel Vioulac, Sebastien Bailly, and Jean-François Timsit
Subjects: ICU diary, Intensive care unit, Stress disorders, post-traumatic, Family, Anxiety, Medicine (General), R5-920
Abstract: Abstract Background Post-intensive care syndrome includes the multiple consequences of an intensive care unit (ICU) stay for patients and families. It has become a new challenge for intensivists. Prevention programs have been disappointing, except for ICU diaries, which report the patient’s story in the ICU. However, the effectiveness of ICU diaries for patients and families is still controversial, as the interpretation of the results of previous studies was open to criticism hampering an expanded use of the diary. The primary objective of the study is to evaluate the post-traumatic stress syndrome in patients. The secondary objectives are to evaluate the post-traumatic stress syndrome in families, anxiety and depression symptoms in patients and families, and the recollected memories of patients. Endpoints will be evaluated 3 months after ICU discharge or death. Methods A prospective, multicenter, randomized, assessor-blind comparative study of the effect of an ICU diary on patients and families. We will compare two groups: one group with an ICU diary written by staff and family and given to the patient at ICU discharge or to the family in case of death, and a control group without any ICU diary. Each of the 35 participating centers will include 20 patients having at least one family member who will likely visit the patient during their ICU stay. Patients must be ventilated within 48 h after ICU admission and not have any previous chronic neurologic or acute condition responsible for cognitive impairments that would hamper their participation in a phone interview. Three months after ICU discharge or death of the patient, a psychologist will contact the patient and family by phone. Post-traumatic stress syndrome will be evaluated using the Impact of Events Scale-Revised questionnaire, anxiety and depression symptoms using the Hospital Anxiety and Depression Scale questionnaire, both in patients and families, and memory recollection using the ICU Memory Tool Questionnaire in patients. The content of a randomized sample of diaries of each center will be analyzed using a grid. An interview of the patients in the intervention arm will be conducted 6 months after ICU discharge to analyze in depth how they use the diary. Discussion This study will provide new insights on the impact of ICU diaries on post-traumatic stress disorders in patients and families after an ICU stay. Trial registration ClinicalTrial.gov, ID: NCT02519725 . Registered on 13 July 2015.
Published: 2017
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6. Inflammasomes in Tissue Damages and Immune Disorders After Trauma

Author: Perrine Bortolotti, Emmanuel Faure, and Eric Kipnis
Subjects: inflammasome, trauma, DAMP, inflammation, immunosuppression, Immunologic diseases. Allergy, RC581-607
Abstract: Trauma remains a leading cause of death worldwide. Hemorrhagic shock and direct injury to vital organs are responsible for early mortality whereas most delayed deaths are secondary to complex pathophysiological processes. These processes result from imbalanced systemic reactions to the multiple aggressions associated with trauma. Trauma results in the uncontrolled local and systemic release of endogenous mediators acting as danger signals [damage-associated molecular patterns (DAMPs)]. Their recognition by the innate immune system triggers a pro-inflammatory immune response paradoxically associated with concomitant immunosuppression. These responses, ranging in intensity from inappropriate to overwhelming, promote the propagation of injuries to remote organs, leading to multiple organ failure and death. Some of the numerous DAMPs released after trauma trigger the assembly of intracellular multiprotein complexes named inflammasomes. Once activated by a ligand, inflammasomes lead to the activation of a caspase. Activated caspases allow the release of mature forms of interleukin-1β and interleukin-18 and trigger a specific pro-inflammatory cell death termed pyroptosis. Accumulating data suggest that inflammasomes, mainly NLRP3, NLRP1, and AIM2, are involved in the generation of tissue damage and immune dysfunction after trauma. Following trauma-induced DAMP(s) recognition, inflammasomes participate in multiple ways in the development of exaggerated systemic and organ-specific inflammatory response, contributing to organ damage. Inflammasomes are involved in the innate responses to traumatic brain injury and contribute to the development of acute respiratory distress syndrome. Inflammasomes may also play a role in post-trauma immunosuppression mediated by dysregulated monocyte functions. Characterizing the involvement of inflammasomes in the pathogenesis of post-trauma syndrome is a key issue as they may be potential therapeutic targets. This review summarizes the current knowledge on the roles of inflammasomes in trauma.
Published: 2018
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7. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?

Author: Emmanuel Faure, Julien Poissy, Anne Goffard, Clement Fournier, Eric Kipnis, Marie Titecat, Perinne Bortolotti, Laura Martinez, Sylvain Dubucquoi, Rodrigue Dessein, Philippe Gosset, Daniel Mathieu, and Benoit Guery
Subjects: Medicine, Science
Abstract: One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.
Published: 2014
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8. Monitoring in the Intensive Care

Author: Eric Kipnis, Davinder Ramsingh, Maneesh Bhargava, Erhan Dincer, Maxime Cannesson, Alain Broccard, Benoit Vallet, Karim Bendjelid, and Ronan Thibault
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: In critical care, the monitoring is essential to the daily care of ICU patients, as the optimization of patient’s hemodynamic, ventilation, temperature, nutrition, and metabolism is the key to improve patients' survival. Indeed, the decisive endpoint is the supply of oxygen to tissues according to their metabolic needs in order to fuel mitochondrial respiration and, therefore, life. In this sense, both oxygenation and perfusion must be monitored in the implementation of any resuscitation strategy. The emerging concept has been the enhancement of macrocirculation through sequential optimization of heart function and then judging the adequacy of perfusion/oxygenation on specific parameters in a strategy which was aptly coined “goal directed therapy.” On the other hand, the maintenance of normal temperature is critical and should be regularly monitored. Regarding respiratory monitoring of ventilated ICU patients, it includes serial assessment of gas exchange, of respiratory system mechanics, and of patients' readiness for liberation from invasive positive pressure ventilation. Also, the monitoring of nutritional and metabolic care should allow controlling nutrients delivery, adequation between energy needs and delivery, and blood glucose. The present paper will describe the physiological basis, interpretation of, and clinical use of the major endpoints of perfusion/oxygenation adequacy and of temperature, respiratory, nutritional, and metabolic monitorings.
Published: 2012
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9. Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With COVID-19 Pneumonia

Author: Charles Tacquard, Alexandre Mansour, Alexandre Godon, Julien Godet, Julien Poissy, Delphine Garrigue, Eric Kipnis, Sophie Rym Hamada, Paul Michel Mertes, Annick Steib, Mathilde Ulliel-Roche, Bélaïd Bouhemad, Maxime Nguyen, Florian Reizine, Isabelle Gouin-Thibault, Marie Charlotte Besse, Nived Collercandy, Stefan Mankikian, Jerrold H. Levy, Yves Gruel, Pierre Albaladejo, Sophie Susen, Anne Godier, P. Albaladejo, N. Blais, F. Bonhomme, A. Borel-Derlon, A. Cohen, J.-P. Collet, E. de Maistre, P. Fontana, D. Garrigue Huet, A. Godier, Y. Gruel, A. Godon, B. Ickx, S. Laporte, D. Lasne, J. Llau, G. Le Gal, T. Lecompte, S. Lessire, J.H. Levy, D. Longrois, S. Madi-Jebara, A. Mansour, M. Mazighi, P. Mismetti, P.E. Morange, S. Motte, F. Mullier, N. Nathan, P. Nguyen, G. Pernod, N. Rosencher, S. Roullet, P.M. Roy, S. Schlumberger, P. Sié, A. Steib, S. Susen, C.A. Tacquard, S. Testa, A. Vincentelli, P. Zufferey, CHU Strasbourg, CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier 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)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Duke University [Durham], University Hospital of Strasbourg (Hopitaux Universitaires de Strasbourg-Direction de la Recherche Clinique et des Innovations), Université de Rennes (UR), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: BMI, body mass index, [SDV]Life Sciences [q-bio], VTE, venous thromboembolism, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, 030212 general & internal medicine, anticoagulation, Original Research, Incidence (epidemiology), Hazard ratio, INR, international normalized ratio, Vitamin K antagonist, IPTW, inverse probability treatment weighting, ICU, intensive care unit, 3. Good health, Pulmonary embolism, [SDV] Life Sciences [q-bio], Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, Critical Illness, Low molecular weight heparin, HPA, high dose prophylactic anticoagulation, 03 medical and health sciences, Internal medicine, medicine, Humans, CRRT, continuous renal replacement therapy, UFH, unfractionated heparin, APTT, activated partial thromboplastin time, Blood Coagulation, thrombosis, DOAC, direct oral anticoagulant, business.industry, SARS-CoV-2, Anticoagulants, COVID-19, Retrospective cohort study, VKA, vitamin K antagonist, medicine.disease, bleeding, HR, hazard ratio, LMWH, low molecular weight heparin, OR, odds ratio, 030228 respiratory system, COPD, chronic obstructive pulmonary disease, TC, thrombotic complication, business, ECMO, extracorporeal membrane oxygenation
Abstract: International audience; BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.
Published: 2021
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10. Classification and Regression Trees for Bacterial Vaginosis Diagnosis in Pregnant Women Based on High-Throughput Quantitative PCR

Author: Rodrigue Dessein, Teddy Grandjean, Gilles Brabant, Damien Subtil, Marvin Bauduin, Rémi Le Guern, Eric Kipnis, Aurore Loquet, Claire Duployez, CCSD, Accord Elsevier, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Saint Vincent de Paul de Lille, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Santé Publique : épidémiologie et qualité des soins (EA 2694), Faculté de Médecine Henri Warembourg - Université de Lille-Centre d'Etudes et de Recherche en Informatique Médicale [Lille] (CERIM), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Groupe Hospitalier de l'Institut Catholique de Lille (GHICL)
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, Real-Time Polymerase Chain Reaction, Asymptomatic, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Pregnancy, Obstetrics, business.industry, Vaginosis, Bacterial, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, female genital diseases and pregnancy complications, 3. Good health, 030104 developmental biology, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Medicine, Regression Analysis, Female, Nugent score, Pregnant Women, Bacterial vaginosis, medicine.symptom, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; Bacterial vaginosis (BV) diagnosis in pregnancy is based on the Nugent score, which consists of semiquantitation of bacterial morphotypes. Limited data exist concerning molecular-based diagnosis in asymptomatic pregnant women. Using high-throughput quantitative PCR, 34 microorganisms were screened in asymptomatic pregnant women and compared with the Nugent score. Three-hundred and four vaginal samples had a Nugent score
Published: 2021
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11. 2021 adaptation of the editorial policy of Anaesthesia Critical Care and Pain Medicine (ACCPM)

Author: Arthur James, Sylvain Ausset, Antoine G. Schneider, Emmanuel Lorne, Matthieu Boisson, Anaïs Caillard, Ruth Landau, Patrice Forget, Sorin J. Brull, Eric Kipnis, O. Brissaud, Morgan Le Guen, Francis Veyckemans, Antoine Rocquilly, Nicolas Mongardon, Sacha Rozencwajg, Lionel Bouvet, Marc-Olivier Fischer, Jean-Yves Lefrant, Alice Blet, Sophie Hamada, Armelle Nicolas-Robin, Sophie Bastide, Mark J. Peters, Hervé Quintard, Philippe Cuvillon, Jason A. Roberts, Frédéric J. Mercier, Anne Godier, Jean-Stéphane David, Xavier Capdevila, Matthieu Biais, Romain Pirracchio, Du Bin, Philippe Richebé, Arthur Le Gall, Olivier Joannes-Boyau, Kerstin Kolodzie, Jordi Rello, Paul Zetlaoui, Per-Arne Lönnqvist, Denis Frasca, Osama Abou Arab, Aude Carillon, Tomoko Fujii, Hervé Bouaziz, Thomas Clavier, Christophe Dadure, Sébastien Kerever, Stéphanie Sigaut, Matthieu Legrand, Rosanna Njeim, Dean Gopalan, Fanny Vardon Bounes, and Dan Benhamou
Subjects: medicine.medical_specialty, Critical Care, business.industry, Pain medicine, MEDLINE, Pain, General Medicine, Critical Care and Intensive Care Medicine, Anesthesiology and Pain Medicine, Anesthesiology, Medicine, Humans, Anesthesia, Adaptation (computer science), business, Intensive care medicine, Editorial Policies
Published: 2021

12. High incidence of postoperative infections after pancreaticoduodenectomy: A need for perioperative anti-infectious strategies

Author: Gilles Lebuffe, R. Le Guern, C. Delpierre, Perrine Bortolotti, François-René Pruvot, Stéphanie Truant, Xavier Lenne, M. El Amrani, Eric Kipnis, A. Bignon, Le Guern, Rémi, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: medicine.medical_specialty, Cephalic pancreaticoduodenectomy, medicine.drug_class, medicine.medical_treatment, Antibiotics, 030230 surgery, Gastroenterology, Bile colonization, Pancreaticoduodenectomy, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Surgical Wound Infection, Antibiotic prophylaxis, Prospective cohort study, business.industry, Incidence, Retrospective cohort study, Perioperative, Antibiotic Prophylaxis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Antimicrobial prophylaxis, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, High incidence, Perioperative infection, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Complication, Surgical site infection
Abstract: Objectives Postoperative infections occur frequently after pancreaticoduodenectomy, especially in patients with bile colonization. Recommendations for perioperative anti-infectious treatment are lacking, and clinical practice is heterogenous. We have analyzed the effects of bile colonization and antibiotic prophylaxis on postoperative infection rates, types and therapeutic consequences. Methods Retrospective observational study in patients undergoing pancreaticoduodenectomy with intraoperative bile culture. Data on postoperative infections and non-infectious complications, bile cultures and antibiotic prophylaxis adequacy to biliary bacteria were collected. Results Among 129 patients, 53% had a positive bile culture and 23% had received appropriate antibiotic prophylaxis. Postoperative documented infection rate was over 40% in patients with or without bile colonization, but antibiotic therapy was more frequent in positive bile culture patients (77% vs. 57%, P = 0,008). The median duration of antibiotic therapy was 11 days and included a broad-spectrum molecule in 42% of cases. Two-thirds of documented postoperative infections involved one or more bacteria isolated in bile cultures, which was associated with a higher complication rate. While bile culture yielded Gram-negative bacilli (57%) and Gram-positive cocci (43%), fungal microorganisms were scarce. Adequate preoperative antibiotic prophylaxis according to bile culture was not associated with reduced infectious or non-infectious complication rates. Conclusion Patients undergoing pancreaticoduodenectomy experience a high rate of postoperative infections, often involving bacteria from perioperative bile culture when positive, with no preventive effect of an adequate preoperative antibiotic prophylaxis. Increased postoperative complications in patients with bile colonization may render necessary a perioperative antibiotic treatment targeting bile microorganisms. Further prospective studies are needed to improve the anti-infectious strategy in these patients.
Published: 2021
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13. Coagulation biomarkers are independent predictors of increased oxygen requirements in COVID‐19

Author: Julien Goutay, Emmanuelle Jeanpierre, Julien Poissy, Antoine Rauch, Marc Lambert, Sophie Susen, Morgan Caplan, Karine Faure, Leslie Charbonnier, Alain Duhamel, Fanny Lassalle, Julien Labreuche, Eric Kipnis, Aurelien Rohn, Annabelle Dupont, Peter J. Lenting, Delphine Garrigue, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-16-IDEX-0004,ULNE,ULNE(2016), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, LillOA, ULNE - - ULNE2016 - ANR-16-IDEX-0004 - IDEX - VALID, and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: Male, [SDV]Life Sciences [q-bio], Comorbidity, 030204 cardiovascular system & hematology, Fibrinogen, Gastroenterology, Body Mass Index, 0302 clinical medicine, Patient Admission, Risk Factors, hemic and lymphatic diseases, Prevalence, Medicine, Platelet, Prospective Studies, Letter to the Editor, 2. Zero hunger, biology, Age Factors, Venous Thromboembolism, Hematology, Middle Aged, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Coagulation, Female, Original Article, France, medicine.drug, circulatory and respiratory physiology, medicine.medical_specialty, SARS‐CoV2, Risk Assessment, Letter to the Editors, 03 medical and health sciences, Sex Factors, Von Willebrand factor, Internal medicine, Diabetes mellitus, von Willebrand Factor, Humans, Blood Coagulation, Factor VIII, business.industry, Oxygen Inhalation Therapy, Anticoagulants, COVID-19, Original Articles, medicine.disease, Oxygen, SARS-CoV2, biology.protein, Metabolic syndrome, business, Body mass index, Biomarkers
Abstract: International audience; Background :Hypercoagulability seems to contribute to SARS-CoV-2 pneumonia pathogenesis. However, age and metabolic syndrome are potential confounders when assessing the value of coagulation biomarkers’ prediction of COVID-19 outcomes. We assessed whether coagulation biomarkers, including factor VIII (FVIII) and von Willebrand factor (VWF) levels, measured at time of admission, were predictive of COVID-19 adverse outcomes irrespective of age and major comorbidities associated with metabolic syndrome.Methods :Blood was sampled at admission in 243 adult COVID-19 patients for analysis of coagulation biomarkers including FVIII and VWF on platelet-poor plasma. The association between baseline C-reactive protein (CRP), activated partial thromboplastin time ratio, prothrombin time ratio, D-dimers, fibrinogen, FVIII, VWF antigen (VWF:Ag), and FVIII/VWF:Ag ratio levels and adverse outcomes (increased oxygen requirements, thrombosis, and death at day 30) was assessed by regression analysis after adjustment on age, sex, body mass index (BMI), diabetes, and hypertension.Results :In univariable regression analysis increased CRP (subdistribution hazard ratio [SHR], 1.68; 95% confidence interval [CI], 1.26-2.23), increased fibrinogen (SHR, 1.32; 95% CI, 1.04-1.68), and decreased FVIII/VWF:Ag ratio (SHR, 0.70; 95% CI, 0.52-0.96) levels at admission were significantly associated with the risk of increased oxygen requirement during follow-up. Leucocytes (SHR, 1.36; 95% CI, 1.04-1.76), platelets (SHR,1.71; 95% CI, 1.11-2.62), D-dimers (SHR, 2.48; 95% CI, 1.66-3.78), and FVIII (SHR, 1.78; 95% CI, 1.17-2.68) were associated with early onset of thrombosis after admission. After adjustment for age, sex, BMI, hypertension, and diabetes, these associations were not modified.Conclusion :Coagulation biomarkers are early and independent predictors of increased oxygen requirement in COVID-19 patients.
Published: 2020
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14. Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study

Author: A. Bignon, A. Elbaz, C. Vanbaelinghem, H. Abi Rached, Sébastien Preau, M. Jourdain, Eric Kipnis, Hélène Behal, François Machuron, Laurent Robriquet, Emmanuelle Jaillette, A. Ben Hamou, Alain Duhamel, S. Espiard, D. Du Cheyron, Fabienne Tamion, François Pattou, Arnaud Jannin, Benoit Voisin, Jean-Charles Preiser, Saad Nseir, Damien Thellier, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de réanimation médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Hôpital Provo, Centre Hospitalier Tourcoing, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Critical Care, Genotype, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], education, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Logistic regression, Polymorphism, Single Nucleotide, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Stress-related hyperglycaemia, law, Intensive care, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Intensive care unit, Prospective Studies, TCF7L2 polymorphism, Alleles, business.industry, Long-term mortality, Incidence (epidemiology), Diabetes, General Medicine, Middle Aged, medicine.disease, 3. Good health, Hyperglycemia, Cohort, Female, business, Transcription Factor 7-Like 2 Protein, TCF7L2
Abstract: International audience; Objective :The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose ≥ 11 mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. Methods :This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012–2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for < 48 h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded.Main results :The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB–G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P = 0.078): OR(per one T copy): 1.24, 95% CI: 0.98–1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P = 0.026), but was no longer significant at 1 year (P = 0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43–3.06; P < 0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32–2.28; P < 0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07–4.20; P = 0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71–2.96; P = 0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P = 0.72) or 1 year (P = 0.64).Conclusion :This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.
Published: 2020
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15. Clinical relevance of Clostridium bacteremia: An 8-year retrospective study

Author: Karine Faure, Marie Titecat, Claire Duployez, Rodrigue Dessein, Rémi Le Guern, Eric Kipnis, Caroline Loïez, Emmanuel Faure, Frédéric Wallet, Perrine Bortolotti, Sarah Stabler, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bactériologie-Hygiène [CHRU Lille], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Univ. Lille, CHU Lille., Le Guern, Rémi, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Adult, Male, medicine.medical_specialty, Multivariate analysis, Clostridium perfringens, Clinical significance, Bacteremia, Clostridium infections, Hypothermia, Microbiology, Cohort Studies, 03 medical and health sciences, Clostridium, Blood culture contamination, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, Humans, Mortality, 030304 developmental biology, Aged, Retrospective Studies, 0303 health sciences, biology, 030306 microbiology, business.industry, Mortality rate, Retrospective cohort study, Middle Aged, Antimicrobial, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Anaerobic bacteria, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered.
Published: 2020
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16. Spontaneous decolonization during hospitalization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales

Author: Saad Nseir, Eric Kipnis, A. El Kalioubie, Anahita Rouzé, Rodrigue Dessein, Caroline Loïez, Frédéric Wallet, R. Le Guern, Claire Duployez, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle de Biologie Pathologie Génétique [CHU Lille], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, 425779|||Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Recherche translationnelle : relations hôte-pathogènes - EA 7366, Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017, and Le Guern, Rémi
Subjects: Male, Microbiology (medical), medicine.medical_specialty, 2019-20 coronavirus outbreak, Frequency of occurrence, colonization, extended-spectrum beta-lactamase, infection control, critical care, contact precautions, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, 030501 epidemiology, beta-Lactamases, law.invention, 03 medical and health sciences, Enterobacteriaceae, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Enterobacterales, Humans, Infection control, Medicine, Aged, Retrospective Studies, Cross Infection, 0303 health sciences, 030306 microbiology, business.industry, Enterobacteriaceae Infections, Rectum, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Hospitalization, Intensive Care Units, Infectious Diseases, Carriage, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Carrier State, Beta-lactamase, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business
Abstract: International audience; This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads.
Published: 2020
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17. The ICU-Diary study: prospective, multicenter comparative study of the impact of an ICU diary on the wellbeing of patients and families in French ICUs

Author: Audrey Large, Eric Boulet, Fabienne Tamion, Jean-Philippe Rigaud, Jean Paul Mira, Marina Thirion, Olivier Lesieur, Isabelle Vinatier, Eric Kipnis, Paul-Henri Jost, Jean-François Timsit, Virginie Maxime, Lila Bouadma, Nathalie Thieulot-Rolin, Cécile Flahault, Sandrine Valade, Rebecca Halidfar, Cédric Bretonnière, Nora Amdjar-Badidi, Emmanuelle Mercier, Amélie Bazire, Christel Vioulac, Julio Badie, Yannick Monseau, Alexandre Lautrette, Mercé Jourdain, Hubert Grand, Stéphane Ruckly, Alain Gaffinel, François Santoli, Léonor Fasse, Sébastien Bailly, Olfa Hamzaoui, Georges Simon, Antoine Rouget, Xavier Forceville, Maité Garrouste-Orgeas, Erika Parmentier-Decrucq, Bernard Floccard, Laurent Argaud, and Naïke Bigé
Subjects: Time Factors, Health Status, health care facilities, manpower, and services, Medicine (miscellaneous), Anxiety, Hospital Anxiety and Depression Scale, Medical Records, law.invention, Stress Disorders, Post-Traumatic, ICU diary, Study Protocol, 0302 clinical medicine, Cost of Illness, law, Surveys and Questionnaires, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Depression (differential diagnoses), lcsh:R5-920, Narration, Depression, Syndrome, Intensive care unit, Icu admission, Intensive Care Units, Mental Health, Research Design, Family Relations, France, medicine.symptom, lcsh:Medicine (General), post-traumatic, medicine.medical_specialty, Critical Care, Patients, 03 medical and health sciences, Memory, Intervention (counseling), medicine, Humans, In patient, Family, Intensive care medicine, Stress syndrome, business.industry, 030208 emergency & critical care medicine, Stress disorders, Quality of Life, business
Abstract: Background Post-intensive care syndrome includes the multiple consequences of an intensive care unit (ICU) stay for patients and families. It has become a new challenge for intensivists. Prevention programs have been disappointing, except for ICU diaries, which report the patient’s story in the ICU. However, the effectiveness of ICU diaries for patients and families is still controversial, as the interpretation of the results of previous studies was open to criticism hampering an expanded use of the diary. The primary objective of the study is to evaluate the post-traumatic stress syndrome in patients. The secondary objectives are to evaluate the post-traumatic stress syndrome in families, anxiety and depression symptoms in patients and families, and the recollected memories of patients. Endpoints will be evaluated 3 months after ICU discharge or death. Methods A prospective, multicenter, randomized, assessor-blind comparative study of the effect of an ICU diary on patients and families. We will compare two groups: one group with an ICU diary written by staff and family and given to the patient at ICU discharge or to the family in case of death, and a control group without any ICU diary. Each of the 35 participating centers will include 20 patients having at least one family member who will likely visit the patient during their ICU stay. Patients must be ventilated within 48 h after ICU admission and not have any previous chronic neurologic or acute condition responsible for cognitive impairments that would hamper their participation in a phone interview. Three months after ICU discharge or death of the patient, a psychologist will contact the patient and family by phone. Post-traumatic stress syndrome will be evaluated using the Impact of Events Scale-Revised questionnaire, anxiety and depression symptoms using the Hospital Anxiety and Depression Scale questionnaire, both in patients and families, and memory recollection using the ICU Memory Tool Questionnaire in patients. The content of a randomized sample of diaries of each center will be analyzed using a grid. An interview of the patients in the intervention arm will be conducted 6 months after ICU discharge to analyze in depth how they use the diary. Discussion This study will provide new insights on the impact of ICU diaries on post-traumatic stress disorders in patients and families after an ICU stay. Trial registration ClinicalTrial.gov, ID: NCT02519725. Registered on 13 July 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2283-y) contains supplementary material, which is available to authorized users.
Published: 2017
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18. Impact of the Timing of Antibiotic Administration on Digestive Colonization with Carbapenemase-Producing Enterobacteriaceae in a Murine Model

Author: Karine Faure, Eric Kipnis, Teddy Grandjean, Guillaume Millot, Martin Figeac, Aurore Loquet, Rémi Le Guern, Rodrigue Dessein, Marvin Bauduin, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Le Guern, Rémi
Subjects: medicine.drug_class, Klebsiella pneumoniae, Antibiotics, Microbial Sensitivity Tests, Gut flora, beta-Lactamases, Microbiology, 03 medical and health sciences, Mice, Bacterial Proteins, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Antimicrobial stewardship, Infection control, Animals, Pharmacology (medical), Colonization, Experimental Therapeutics, 030304 developmental biology, Pharmacology, 0303 health sciences, Infection Control, biology, 030306 microbiology, business.industry, Enterobacteriaceae Infections, Clindamycin, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, 3. Good health, Anti-Bacterial Agents, Gastrointestinal Microbiome, Disease Models, Animal, Infectious Diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, medicine.drug
Abstract: While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days.
Published: 2019
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19. Early management of severe pelvic injury (first 24 hours)

Author: Pascal Incagnoli, Fréderic Rongieras, Tobias Gauss, Clément Buléon, Delphine Garrigue, Jean-Luc Hanouz, Jacques Choukroun, Eric Kipnis, Isabelle Plenier, Anatole Harrois, François Régis Desfemmes, Jean Stephane David, Xavier Combes, Pierre Bouzat, Elodie Brunel, Sylvain Ausset, Xavier Bobbia, Benoît Vivien, Jacques Bessereau, Julien Brun, Jean Paul Beregi, Alain Puidupin, Service d'anesthésie-réanimation, Hospices Civils de Lyon, centre hospitalier Lyon Sud, Direction centrale du service de santé des armées, École du Val de Grâce (EVDG), Service de Santé des Armées, Service de radiologie et d'imagerie médicale, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Assistance publique des Hôpitaux de Marseille, SAMU 13, pôle RUSH, CHU de la Timone, Division anesthésie-réanimation douleur urgences, Pôle anesthésie-réanimation, Grenoble Alpes Trauma Centre, Service d'anesthésie-réanimation, hôpital Purpan, CHU Toulouse [Toulouse], Service Réanimation médico-chirurgicale [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Hôpital Bellepierre, SAMU 974, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de chirurgie urologique, Hôpital d'instruction des Armées du Val de Grace, Service d'accueil des urgences vitales chirurgicales, CHRU de Lille, Service de chirurgie de l'urgence, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique des Hôpitaux Paris, hôpital Beaujon, servie d'anesthésie-réanimation, réanimation chirurgicale, Hôpitaux Universitaires Paris Nord Val de Seine, Service d'anesthésie-réanimation, reanimation chirurgicale, Assistance publique des Hôpitaux Paris, CHU de Bicêtre, Pôle d'anesthésie-réanimation, and CHRU de Lille, réanimation chirurgicale
Subjects: medicine.medical_specialty, Critical Care, Population, Critical Care and Intensive Care Medicine, Pelvis, Fractures, Bone, 03 medical and health sciences, BIOMECANIQUE, [SPI]Engineering Sciences [physics], 0302 clinical medicine, PELVIC TRAUMA, PREHOSPITAL SETTING, Health care, Humans, Medicine, Anesthesia, TRAUMA NETWORK, education, 030222 orthopedics, education.field_of_study, Trauma Severity Indices, business.industry, General surgery, ARTERIAL EMBOLIZATION, SEVERITY CRITERIA, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 030208 emergency & critical care medicine, General Medicine, Guideline, Evidence-based medicine, medicine.disease, 3. Good health, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Pelvic fracture, Wounds and Injuries, Abdomen, Professional association, business, Trauma surgery
Abstract: Objective Pelvic fractures represent 5% of all traumatic fractures and 30% are isolated pelvic fractures. Pelvic fractures are found in 10 to 20% of severe trauma patients and their presence is highly correlated to increasing trauma severity scores. The high mortality of pelvic trauma, about 8 to 15%, is related to actively bleeding pelvic injuries and/or associated injuries to the head, abdomen or chest. Regardless of the severity of pelvic trauma, diagnosis and treatment must proceed according to a strategy that does not delay the management of the most severely injured patients. To date, in France, there are no guidelines issued by healthcare authorities or professional societies that address this subject. Design A consensus committee of 22 experts from the French Society of Anaesthesia and Intensive Care Medicine (Societe Francaise d’Anesthesie et de Reanimation; SFAR) and the French Society of Emergency Medicine (Societe Francaise de Medecine d’Urgence; SFMU) in collaboration with the French Society of Radiology (Societe Francaise de Radiologie; SFR), French Defence Health Service (Service de Sante des Armees; SSA), French Society of Urology (Association Francaise d’Urologie; AFU), the French Society of Orthopaedic and Trauma Surgery (Societe Francaise de Chirurgie Orthopedique et Traumatologique; SOCFCOT), and the French Society of Digestive Surgery (Societe Francaise de Chirurgie digestive; SFCD) was convened. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently from any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Methods Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE® methodology. Results The SFAR Guideline panel provided 22 statements on prehospital and hospital management of the unstable patient with pelvic fracture. After three rounds of discussion and various amendments, a strong agreement was reached for 100% of recommendations. Of these recommendations, 11 have a high level of evidence (Grade 1 ± ), 11 have a low level of evidence (Grade 2 ± ). Conclusions Substantial agreement exists among experts regarding many strong recommendations for management of the unstable patient with pelvic fracture.
Published: 2019
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20. Fréquence des acrosyndromes chez les patients avec infection sévère à SARS-CoV-2 en réanimation

Author: C. Fievet, Eric Kipnis, E. Drumez, F. Dezoteux, Julien Poissy, Delphine Staumont-Sallé, S. Buche, A.S. Moreau, Alain Duhamel, B. Mille, and Daniel Mathieu
Subjects: Gynecology, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Dermatology, Pseudo-engelure, P085, medicine, SARS CoV 2, business, Acrosyndrome, COVID 19, Réanimation
Abstract: Introduction De nombreuses manifestations cliniques dermatologiques ont ete rapportees durant la pandemie mondiale de la COVID-19. Parmi elles, des phenomenes d’acrosyndromes ont ete decrits, principalement chez des patients suspects d’infection par SARS-Cov-2 mais asymptomatiques ou pauci-symptomatiques. Peu d’etudes se sont interessees a ces manifestations chez les patients admis en reanimation. Notre objectif etait donc d’evaluer la frequence instantanee des manifestations acrales cutanees chez les patients severes atteints de la COVID19 admis en reanimation. Materiel et methodes Nous avons realise une etude observationnelle et prospective, realisee du 5 au 6 mai 2020. Tout patient adulte hospitalise en reanimation au CHU de Lille dans le cadre de la COVID19 etait inclus et beneficiait d’un examen systematique du tegument par un dermatologue senior. Resultats Au total, 39 patients ont ete examines (34 hommes, 5 femmes) avec un âge moyen de 60,6 ans. Aucun patient n’avait presente de symptome dermatologique au debut de la maladie. La duree mediane d’hospitalisation en reanimation etait de 35 jours [21-41] ; 35 patients (90 %) avaient recu un support ventilatoire par intubation oro-tracheale et 21 (54 %) un support circulatoire par amines vasopressives. Nous avons observe des manifestations cutanees acrales chez 11 patients (28 %) : lesions necrotiques (5/11, 45 %), bulles hemorragiques (3/11, 27 %), livedo (1/11, 9 %), erosions (1/11, 9 %), hemorragies sous ungueales (2/11, 18 %). Un patient presentant a la fois des lesions necrotiques et des erosions cutanees. Aucun patient ne presentait de manifestations a type d’engelure ou pseudo-engelure. Il n’y avait pas de difference significative entre les patients avec et sans manifestation acrale concernant la duree d’hospitalisation et les complications thromboemboliques, les symptomes initiaux, et les caracteristiques de base des patients excepte l’IMC moyen plus bas chez les patients avec manifestations acrales. La duree moyenne de la maladie etait significativement plus longue et davantage de medicaments vasoactifs ont ete administres aux patients presentant des manifestations cutanees acrales, suggerant une gravite plus elevee de la maladie dans ce groupe et pouvant etre en lien avec les manifestations observees. Discussion Nous rapportons une serie de manifestations cutanees acrales chez seulement 28 % des patients pris en charge en reanimation au moment de l’etude. Ces manifestations sont variees et peu specifiques. Aucune manifestation a type d’engelure n’etait observee contrairement aux patients suspects de formes pauci ou asymptomatiques et inconstamment confirmees sur le plan serologique ou moleculaire. Sur le plan physiopathologique, plusieurs hypotheses sont avancees comme une reponse immune antivirale de type interferon. Des etudes sont necessaires afin de mieux comprendre les mecanismes a l’origine de ces manifestations.
Published: 2020

21. Impact of Centralized Management of Bariatric Surgery Complications on 90-day Mortality

Author: Gregory Baud, Robert Caiazzo, Guillaume Clément, Eric Kipnis, Gilles Lebuffe, François Pattou, Fanelly Torres, Benoît Dervaux, Xavier Lenne, Guelareh Dezfoulian, CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Rennes 2 (UR2), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier [Valenciennes, Nord], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationelle relations hôte-pathogènes, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Rennes (UNIV-RENNES), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], MEDLINE, Bariatric Surgery, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Humans, Medicine, 030212 general & internal medicine, Retrospective Studies, business.industry, Centralized management, Retrospective cohort study, Middle Aged, 3. Good health, Surgery, Multicenter study, 030220 oncology & carcinogenesis, Centralized Hospital Services, Female, France, business
Abstract: International audience; BACKGROUND AND AIMS: The potential benefit of the centralization of Bariatric surgery (BS) remains debated. The aim of this study was to evaluate the impact on 90-day mortality of an innovative organization aiming at centralizing the care of severe postoperative complications of BS. STUDY DESIGN: The centralization of care for postoperative complication after BS was implemented by French Authorities in 2013 in the Nord-Pas-de-Calais Region, France. This unique formalized network (OSEAN), coordinated by 1 tertiary referral center, enrolled all regional institutions performing bariatric surgery. Data were extracted from the medico-administrative database providing information on all patients undergoing BS between 2009 and 2016 in OSEAN (n = 22,928) and in Rest of France (n = 288,942). The primary outcome was the evolution of 90-day mortality before and after the implementation of this policy. Rest of France was used as a control group to adjust the results to improvement with time of BS outcomes. RESULTS: The numbers of primary procedure and reoperations increased similarly before and after 2013 within OSEAN and in Rest of France. The 90-day mortality rate became significantly lower within OSEAN than in the rest of France after 2013 (0.03% vs 0.08%, P < 0.01). This difference was confirmed in multivariate analysis after adjustment to the procedure specific mortality (P < 0.04). The reduction of 90-day mortality was most visible for sleeve gastrectomy. CONCLUSION: The implementation of centralized care for early postoperative complications after BS in OSEAN was associated with reduced 90-day mortality. Our results indicate that this reduction was not due to a lower incidence of complications but to the improvement of their management.
Published: 2018
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22. Pneumonies associées aux soins de réanimation

Author: Antoine Roquilly, Olivier Brissaud, Eric Kipnis, Philippe Montravers, Sami Hraiech, Gerald Chanques, Rémi Bruyère, Jean-Ralph Zahar, Jérôme Pugin, Djamel Mokart, Marc Leone, Fabrice Michel, Lila Bouadma, Stéphane Dauger, Sébastien Gibot, Charles-Edouard Luyt, Dimitri Margetis, Saad Nseir, Antoine Monsel, Belaid Bouhemad, Lionel Velly, Yoann Launey, Boris Jung, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bichat - Claude Bernard, Service d'anesthésie - réanimation chirurgicale [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)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Pôle de réanimation pédiatrique (CHU de Bordeaux), CHU de Bordeaux Pellegrin [Bordeaux], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de réanimation-Détresses Respiratoires et Infections Sévères [Hôpital Nord - APHM] (DRIS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Anesthésie-Réanimation, Hôpital Roger Salengro, CHRU de Lille, Hôpital Roger Salengro, CHRU de Lille, Lille, France, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Anesthésie Réanimation [Rennes], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'Anesthésie Réanimation, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Soins Intensifs [Genève], Université de Genève = University of Geneva (UNIGE)-Hôpitaux Universitaires de Genève (HUG), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Avicenne [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation - soins continus (Centre hospitalier de Bourg-en-Bresse), Centre Hospitalier de Bourg-en-Bresse, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Genève (UNIGE)-Hôpitaux Universitaires de Genève (HUG), and Hôpital Universitaire de Genève
Subjects: Gynecology, medicine.medical_specialty, Intensive care units, business.industry, 030208 emergency & critical care medicine, 3. Good health, Healthcare-associated pneumonia, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Healthcare associated, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Resume La Societe francaise d’anesthesie et de reanimation et la Societe de reanimation de langue francaise ont publie des recommandations se concentrant sur les pneumonies associees aux soins de reanimation. Le but de ces seize experts francophones etait de produire un cadre permettant une meilleure prise de decision pour les medecins reanimateurs. Ces recommandations sont liees a trois sujets precis (la prevention, le diagnostique et le traitement) chez quatre types de patients (BPCO, neutropenie, postoperation et pediatrique). L’analyse litteraire et la formulation des recommandations ont ete conduites selon le systeme GRADE. Une recherche litteraire extensive a ete conduite sur 10 ans sur les publications indexees sur les bases de donnees Cochrane et Pubmed. Les pneumonies associees aux soins doivent etre evitees grâce a une approche multimodale standardisee et en utilisant la decontamination digestive la ou la prevalence des bacteries multi resistantes aux medicaments etait inferieure a 20 %. Le diagnostique se base sur l’evaluation clinique et les analyses microbiologiques. En l’absence de facteurs de risques pour les bacteries multi resistantes, de bacille a gram-negatif non-fermentant et/ou d’une mortalite accrue (choc sceptique, defaillance organique), la monotherapie est fortement recommandee. Apres documentation microbiologique, il est recommande de reduire le spectre et de preferer la monotherapie pour l’antibiotherapie des pneumonies associees aux soins de reanimation, y compris les bacilles a gram-negatif non-fermentant.
Published: 2018
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23. Draft Genome Sequences of Two Carbapenemase-Producing Klebsiella pneumoniae Strains Isolated from Blood Cultures

Author: Eric Kipnis, Rémi Le Guern, Marvin Bauduin, Rodrigue Dessein, Karine Faure, Teddy Grandjean, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], and Le Guern, Rémi
Subjects: 0301 basic medicine, biology, Klebsiella pneumoniae, Genome Sequences, 030106 microbiology, Carbapenemase producing, biology.organism_classification, Genome, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Microbiology, 03 medical and health sciences, Resistant bacteria, 030104 developmental biology, Immunology and Microbiology (miscellaneous), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genetics, Colonization, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase)., Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase). These genome sequences should help in investigating pathophysiological mechanisms of digestive colonization or infection with these highly resistant bacteria.
Published: 2018
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24. Measure it to manage it: a bevy of ICU quality-of-care indicators

Author: Marc Leone, Eric Kipnis, Université Lille 2 - Faculté de Médecine, Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Faculté de Médecine Henri Warembourg - Université de Lille, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, Measure (data warehouse), Critical Care, 030309 nutrition & dietetics, business.industry, media_common.quotation_subject, General Medicine, Critical Care and Intensive Care Medicine, medicine.disease, Intensive Care Units, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030225 pediatrics, medicine, Humans, Quality (business), Medical emergency, Quality of care, business, ComputingMilieux_MISCELLANEOUS, media_common
Abstract: International audience
Published: 2018
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25. Early clindamycin for bacterial vaginosis in pregnancy (premeva): a multicentre, double-blind, randomised controlled trial

Author: Bruno Grandbastien, Rodrigue Dessein, Emma Tilloy, François Goffinet, Jean Louis Plennevaux, Eric Kipnis, Damien Subtil, Catherine Nolf, Karine Faure, Gilles Brabant, David Desseauve, Emmanuelle Joyez, Jean-Charles Dugimont, Marie-Christine Bissinger, Frédérique Canis, Marielle Jousse, Christine Delaeter, Patrick Devos, Anne Personne, Sophie Gautier, Elisabeth Guinard, Pierre-Yves Ancel, Annie Fruchart, Christophe Hacot, Jerome Chantrel, Sylvie Deghilage, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Centre hospitalier [Valenciennes, Nord], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier Artois-Ternois Centre Hospitalier d’Arras, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier de Calais, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Inserm, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Santé publique : épidémiologie et qualité des soins - EA 2694, Troubles cognitifs dégénératifs et vasculaires - U1171, Recherche translationnelle : relations hôte-pathogènes - EA 7366, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Centre hospitalier universitaire de Poitiers [CHU Poitiers], and Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique [CRESS - U1153]
Subjects: Adult, medicine.medical_specialty, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Placebo, Miscarriage, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Very Preterm Birth, Humans, 030212 general & internal medicine, Pregnancy Complications, Infectious, 030219 obstetrics & reproductive medicine, Intention-to-treat analysis, business.industry, Clindamycin, Pregnancy Outcome, General Medicine, Vaginosis, Bacterial, medicine.disease, 3. Good health, Anti-Bacterial Agents, Abortion, Spontaneous, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Premature Birth, Female, Bacterial vaginosis, business, medicine.drug
Abstract: International audience; Background: Preterm delivery during pregnancy (
Published: 2018
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26. Hospital-acquired pneumonia in ICU

Author: Sébastien Gibot, Antoine Monsel, Belaid Bouhemad, Antoine Roquilly, Lila Bouadma, Boris Jung, Dimitri Margetis, Philippe Montravers, Rémi Bruyère, L. Velly, Djamel Mokart, Saad Nseir, Marc Leone, Charles-Edouard Luyt, Jean-Ralph Zahar, Fabrice Michel, Sami Hraiech, Yoann Launey, O. Brissaud, Jérôme Pugin, Eric Kipnis, Gerald Chanques, Stéphane Dauger, Velly, Lionel, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU de Bordeaux Pellegrin [Bordeaux], AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de réanimation-Détresses Respiratoires et Infections Sévères [Hôpital Nord - APHM] (DRIS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'anesthésie et de réanimation [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Necker - Enfants Malades [AP-HP], Hôpital Avicenne [AP-HP], Centre Hospitalier de Bourg en Bresse, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Hôpital Universitaire de Genève
Subjects: medicine.medical_specialty, Clinical Decision-Making, MEDLINE, Healthcare-Associated Pneumonia/drug therapy/epidemiology, Guidelines as Topic, Critical Care and Intensive Care Medicine, Hospital-acquired pneumonia, Cross Infection/diagnosis/microbiology/prevention & control/therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Cross Infection, ddc:617, business.industry, Septic shock, The antibiotic, Healthcare-Associated Pneumonia, 030208 emergency & critical care medicine, Multimodal therapy, General Medicine, Guideline, Pneumonia, medicine.disease, Monotherapy, Intensive care unit, 3. Good health, Anti-Bacterial Agents, Anti-Bacterial Agents/therapeutic use, Intensive Care Units, Anesthesiology and Pain Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business
Abstract: International audience; The French Society of Anesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit (ICU). The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, postoperative and pediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. HAP should be prevented by a standardized multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.
Published: 2018
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27. Determining the editorial policy of Anaesthesia Critical Care and Pain Medicine (ACCPM)

Author: Matthieu Legrand, Pierre Beaulieu, Jean-Yves Lefrant, Jean-Pierre Tourtier, Beny Charbit, Nicolas Mongardon, Thomas Lescot, Jean-Stéphane David, Xavier Capdevila, Eric Kipnis, Souhayl Dahmani, Sébastien Pierre, Matthieu Biais, Antoine G. Schneider, Karim Asehnoune, Alexandre Ouattara, Christophe Dadure, Jean-François Brichant, Philippe Cuvillon, Anne Godier, Emmanuel Lorne, Emmanuel Marret, Thomas Fuchs-Buder, Sylvain Ausset, Romain Pirracchio, Jason A. Roberts, Vincent Laudenbach, Thomas Geeraerts, Morgan Le Guen, Jean-Michel Constantin, Olivier Joannes-Boyau, Laurie Tran, Jean-Luc Hanouz, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Amiens-Picardie, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Reims (CHU Reims), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service d'Anesthésie - Réanimation Chirurgicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université Lille 2 - Faculté de Médecine, Université Paris Diderot - Paris 7 (UPD7), Service des Soins Intensifs [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Queensland [Brisbane], Service d'Anesthésie-Réanimation [CHU HEGP], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Faculté de Médecine Henri Warembourg - Université de Lille, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Critical Care, Pain medicine, [SDV]Life Sciences [q-bio], MEDLINE, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Anesthesiology, medicine, Pain Management, Anesthesia, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, business.industry, 030208 emergency & critical care medicine, General Medicine, Pain management, 3. Good health, Anesthesiology and Pain Medicine, Policy, Publication, Periodicals as Topic, business, Editorial Policies
Abstract: International audience
Published: 2018
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28. Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig

Author: Christophe Mariette, Julien De Wolf, Eric Kipnis, Thomas Hubert, Ramadan Jashari, Pierre Fayoux, Alexandre Ung, Christophe Zawadzki, Mathias Brieu, Marie-Christine Copin, Alain Wurtz, Laboratoire de Mécanique de Lille - FRE 3723 (LML), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Centrale Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille 2 - Faculté de Médecine, European Homograft Bank [Bruxelles] (EHB), Clinique Saint-Jean [Bruxelles], Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jeanne de Flandre [Lille], Chirurgie générale et Digestive, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Département de Pathologie, Interface sang vaisseaux et réparation cardiovasculaire, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Ecole Centrale de Lille
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Transplantation, Heterotopic, Swine, Lymphocyte, medicine.medical_treatment, 030204 cardiovascular system & hematology, Revascularization, Cryopreservation, 03 medical and health sciences, 0302 clinical medicine, Immune Tolerance, medicine, Animals, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS, Tissue Survival, business.industry, Cartilage, General Medicine, Allografts, medicine.disease, Epithelium, Surgery, Trachea, Transplantation, surgical procedures, operative, medicine.anatomical_structure, 030228 respiratory system, Tissue bank, Female, Cardiology and Cardiovascular Medicine, business, Omentum, Calcification
Abstract: OBJECTIVES It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. METHODS Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups. RESULTS An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58. CONCLUSIONS Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications.
Published: 2017
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29. Modulation by Polymyxin-B Hemoperfusion of Inflammatory Response Related to Severe Peritonitis

Author: Stéphanie Chevalier, Martine Ferrandière, Matthieu Jabaudon, Thomas Kerforne, Carlos Vela, Laurent Martin-Lefevre, Antoine Dewitte, Eric Kipnis, Olivier Collange, Anne-Claire Lukaszewicz, Rémi Coudroy, Didier Payen, Benoit Veber, Jean-Claude Lecron, Mahmoud Kaaki, Jihad Mallat, René Robert, Sandrine Charreau, Yoann Launey, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Department of anesthesiology and intensive care, Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Department of anesthesiology and critical care medicine, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Anesthésie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Microcirculation, bioénergétique, inflammation et insuffisance circulatoire aiguë (URCT), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Services de soins intensifs, CHU Strasbourg, Département d'Anesthésie et Réanimation Chirurgicale [Poitiers], Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Lille 2 - Faculté de Médecine, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER Centre de Bretagne), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Faculté de Médecine Henri Warembourg - Université de Lille, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Population, Peritonitis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Critical Care and Intensive Care Medicine, Systemic inflammation, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, education, Aged, Polymyxin B, education.field_of_study, Interleukin-6, Tumor Necrosis Factor-alpha, Septic shock, business.industry, Standard treatment, Interleukin-17, 030208 emergency & critical care medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Hemoperfusion, Shock, Septic, Interleukin-10, 3. Good health, 030104 developmental biology, Cytokine, Emergency Medicine, Female, medicine.symptom, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, medicine.drug
Abstract: International audience; Conflicting results have been reported on the influence of Polymyxin-B hemoperfusion treatment on systemic inflammation markers. The aim of the study was to assess in a randomized control trial the influence on plasma cytokine concentrations of Polymyxin-B hemoperfusion in septic shock due to peritonitis. A panel of 10 pro- or anti-inflammatory cytokines was measured in 213 patients with peritonitis-induced septic shock enrolled in the randomized trial ABDOMIX testing the impact of 2 Polymyxin-B hemoperfusion sessions with standard treatment. Gram-negative bacteria were identified in 69% of patients. In the overall population, baseline plasma cytokine concentrations were not different between the two groups. Circulating tumor necrosis factor-α, interleukin (IL)-1β, IL-10, IL-6, and IL-1RA decreased significantly over time in both groups (P
Published: 2017
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30. Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties

Author: Nicolas Galanos, Marion Donnier-Maréchal, Eric Kipnis, Emilie Gillon, Lei Dong, Xiao-Peng He, Ding-Kun Ji, Anne Imberty, Yoann Pascal, Rodrigue Dessein, Teddy Grandjean, Sébastien Vidal, Chimie Organique 2-Glycochimie (CO2GLYCO), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, East China University of Science and Technology, Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Key Laboratory for Advanced Materials & Institute of Fine Chemicals, Université Lille 2 - Faculté de Médecine, Interactions cellulaires et moléculaires des bactéries pathogènes avec l'hôte, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre National de la Recherche Scientifique (CNRS)-École Supérieure Chimie Physique Électronique de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École Supérieure Chimie Physique Électronique de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon, and Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Isothermal microcalorimetry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Calorimetry, Imides, Ligands, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Epitope, law.invention, Confocal microscopy, law, Lectins, Cell Adhesion, medicine, Physical and Theoretical Chemistry, Adhesins, Bacterial, Perylene, ComputingMilieux_MISCELLANEOUS, Binding Sites, Molecular Structure, 010405 organic chemistry, Chemistry, Pseudomonas aeruginosa, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Adhesion, HEXA, Fluorescence, 0104 chemical sciences, Glycoconjugates, Linker
Abstract: International audience; The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide–alkyne “click” conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with Kd values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30–40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell–bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.
Published: 2017
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31. Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection

Author: Rémi Le Guern, Teddy Grandjean, Sarah Stabler, Marvin Bauduin, Philippe Gosset, Éric Kipnis, and Rodrigue Dessein
Subjects: Science
Abstract: Gut microbiome dysbiosis has been shown to alter the immune response to lung infection. Authors utilise a murine model to investigate if gut colonisation with carbapenemase-producing Enterobacterales altered the outcomes of Pseudomonas aeruginosa lung infection.
Published: 2023
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32. Timing of RRT initiation in critically-ill patients: time for precision medicine

Author: Eric Kipnis, Claudio Ronco, and Francesco Garzotto
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critically ill, business.industry, 030232 urology & nephrology, MEDLINE, 030204 cardiovascular system & hematology, Precision medicine, 03 medical and health sciences, 0302 clinical medicine, Editorial, medicine, Intensive care medicine, business
Published: 2016

33. Vaginal mucosal homeostatic response may determine pregnancy outcome in women with bacterial vaginosis a pilot study

Author: Emmanuel Faure, Bruno Grandbastien, Céline Villenet, Eric Kipnis, Martin Figeac, Teddy Grandjean, Sylvain Dubucquoi, Karine Faure, Rodrigue Dessein, Damien Subtil, Gilles Brabant, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Université de Lille, Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Université de Lille, LillOA, CHU Lille, Inserm, Recherche translationnelle : relations hôte-pathogènes - EA 7366, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Lille Inflammation Research International Center - U 995 [LIRIC], Institut pour la Recherche sur le Cancer de Lille [U837 INSERM - IRCL], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: 0301 basic medicine, MESH: Mucosal, [SDV]Life Sciences [q-bio], Physiology, 0302 clinical medicine, MESH: Pregnancy, Lactobacillus, MESH: Immunity, education.field_of_study, 030219 obstetrics & reproductive medicine, biology, General Medicine, [SDV] Life Sciences [q-bio], MESH: Infectious/immunology, MESH: Homeostasis, MESH: Pregnancy Complications, Anaerobic bacteria, Bacterial vaginosis, medicine.symptom, Population, Inflammation, MESH: Bacterial/immunology, 03 medical and health sciences, Immunity, MESH: Vaginosis, medicine, education, Pregnancy, MESH: Humans, business.industry, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Pilot Projects, MESH: Pregnancy Outcome, 030104 developmental biology, Immunology, Nugent score, business, MESH: Female
Abstract: International audience; Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota.
Published: 2016
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34. Erratum to: Outcome of acute mesenteric ischemia in the intensive care unit: a retrospective, multicenter study of 780 cases

Author: Marc Leone, Carole Bechis, Karine Baumstarck, Alexandre Ouattara, Olivier Collange, Pascal Augustin, Djillali Annane, Charlotte Arbelot, Karim Asehnoune, Olivier Baldési, Simon Bourcier, Laurence Delapierre, Didier Demory, Baptiste Hengy, Carole Ichai, Eric Kipnis, Etienne Brasdefer, Sigismond Lasocki, Matthieu Legrand, Olivier Mimoz, Thomas Rimmelé, Jugurtha Aliane, Pierre-Marie Bertrand, Nicolas Bruder, Fanny Klasen, Emilie Friou, Bruno Lévy, Oriane Martinez, Eric Peytel, Alexandra Piton, Elisa Richter, Toufik Kamel, Marie-Charlotte Vogler, Florent Wallet, Mourad Boufi, Bernard Allaouchiche, Jean-Michel Constantin, Claude Martin, Samir Jaber, Jean-Yves Lefrant, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], CHU Strasbourg, Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service médical des soins intensifs [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier du Pays d'Aix, Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Réanimation médico-chirurgicale [Nice], Hôpital Saint-Roch [Nice], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'anesthésie et réanimation chirurgicale, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département d'Anesthésie Réanimation SMUR [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Centre Hospitalier de Cannes, Service d'anesthésie et de réanimation [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional d'Orléans (CHRO), CHU Saint-Etienne, Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Herrada, Anthony, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département d'Anesthésie-Réanimation [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030228 respiratory system, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 3. Good health
Abstract: International audience
Published: 2015
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35. Residual rates of mortality in patients with severe sepsis: a fatality or a new challenge?

Author: Eric Kipnis, Bruno Levy, Marc Leone, Jacques Duranteau, Pierre Asfar, Jean-Paul Mira, Yann Erick Claessens, Service de Réanimation Médicale et de Médecine Hyperbare [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Service d'anesthésie-réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de réanimation médicale polyvalente [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP]
Subjects: medicine.medical_specialty, Septic shock, business.industry, Mortality rate, Phases of clinical research, Review, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, 3. Good health, law.invention, Sepsis, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Anesthesiology, Intervention (counseling), Emergency medicine, medicine, 030212 general & internal medicine, Intensive care medicine, business
Abstract: Phase III clinical trials on severe sepsis and septic shock published during the past decade have failed to reveal the superiority of any therapeutic intervention on mortality compared with evolving standards of care, with the exception of the Early-Goal Directed Therapy reported in 2001. This viewpoint paper presents an analysis of these studies in order to understand what lessons can be learned and proposes perspectives for future study designs. A total of 102 studies were selected among clinical trials published in the field of severe sepsis and septic shock from 2001 to 2013, based on the assessment of a therapeutic intervention and mortality as an outcome. Studies were further selected according to randomized, controlled trial (RCT) quality criteria and analysed according to reported data. Most (n = 61) were excluded because they did not comply with RCT quality criteria or did not report inclusion criteria or patient severity (n = 22). The 19 remaining studies were categorized into three groups depending on whether the intervention assessed led to better, worse, or equivalent outcomes. It appears that the mortality rate in the control arm, ranging from 17% to 61%, impacted the results, with a benefit reported in the studies with the highest rates. Both heterogeneous studied populations and uncontrolled diversity of care among participating centres probably contributed to discrepancies between studies assessing the same intervention. The new challenge to enhance the probability of decreasing mortality rates should include a more appropriate definition of sepsis based on more specific criteria involving biomarker use and accurate patient phenotypes.
Published: 2013
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36. Tracheal reconstruction with a composite graft: fascial flap-wrapped allogenic aorta with external cartilage-ring support

Author: Christophe Zawadzki, Ramadan Jashari, Brigitte Jude, Thomas Hubert, Ilir Hysi, Eric Kipnis, Marie-Christine Copin, and Alain Wurtz
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Neovascularization, Physiologic, Aorta, Thoracic, Revascularization, Surgical Flaps, Fasciotomy, Cartilage transplantation, medicine.artery, medicine, Thoracic aorta, Animals, Fascia, Aorta, business.industry, Cartilage, Graft Survival, Anatomy, Original Articles, Plastic Surgery Procedures, medicine.disease, Surgery, Biomechanical Phenomena, Trachea, medicine.anatomical_structure, Models, Animal, Feasibility Studies, Female, Rabbits, Cardiology and Cardiovascular Medicine, business, Calcification
Abstract: OBJECTIVES: Animal and clinical studies have demonstrated the feasibility of tracheal replacement by silicone-stented allogenic aortas. In clinical trials, however, this graft did not show mature cartilage regeneration into the grafts as was observed in animal models. To solve this issue, we investigated tracheal replacement with a composite graft based on a fascial flap-wrapped allogenic aorta with external cartilage-ring support in a rabbit model. METHODS: Seven male ’Geant des Flandres’ and ’New Zealand’ rabbits served as donors of aortas and cartilage rings, respectively. Nineteen female ’New Zealand’ rabbits were used as recipients. First, in nine animals, neoangiogenesis of the composite graft following a wrap using a pedicled lateral thoracic fascial flap and implantation under the skin of the chest wall was investigated. Animal sacrifice was scheduled at regular intervals up to 38 days. Second, 10 animals underwent tracheal replacement with the composite graft after a 7-to-9 day revascularization period, and were followed-up to death. Macroscopic and microscopic examinations were used to study the morphology, stiffness and viability of the construct. RESULTS: There was one operative death after tracheal replacement. The first group of animals was found to have a satisfactory tubular morphology and stiffness of their construct associated with preserved histological structure of cartilages and moderate to severe aortic ischaemic lesions. In the group of rabbits having undergone tracheal replacement, the anatomical results were characterized by a discrepancy between the severity of ischaemic lesions involving both allogenic aorta and cartilage rings and the satisfactory biomechanical characteristics of the graft in 7 of 10 animals, probably due to cartilage calcification deposits associated with inflammatory scar tissue ensuring the stiffness of the construct. CONCLUSIONS: Our investigations demonstrate the feasibility of the replacement of circumferential tracheal defects using our composite graft. Future experiments using therapeutic bronchoscopy tools are required to draw conclusions regarding the effectiveness of this tracheal substitute in the long-term.
Published: 2012

37. Monitoring in the Intensive Care

Author: Alain F. Broccard, Davinder Ramsingh, Benoit Vallet, Maneesh Bhargava, Maxime Cannesson, Erhan Dincer, Eric Kipnis, Ronan Thibault, and Karim Bendjelid
Subjects: medicine.medical_specialty, Resuscitation, business.industry, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Hemodynamics, Bioengineering, lcsh:RC86-88.9, Goal directed therapy, Oxygenation, Respiratory monitoring, Review Article, Critical Care and Intensive Care Medicine, Intensive care, Breathing, Medicine, business, Intensive care medicine, Perfusion, Nutrition
Abstract: In critical care, the monitoring is essential to the daily care of ICU patients, as the optimization of patient’s hemodynamic, ventilation, temperature, nutrition, and metabolism is the key to improve patients' survival. Indeed, the decisive endpoint is the supply of oxygen to tissues according to their metabolic needs in order to fuel mitochondrial respiration and, therefore, life. In this sense, both oxygenation and perfusion must be monitored in the implementation of any resuscitation strategy. The emerging concept has been the enhancement of macrocirculation through sequential optimization of heart function and then judging the adequacy of perfusion/oxygenation on specific parameters in a strategy which was aptly coined “goal directed therapy.” On the other hand, the maintenance of normal temperature is critical and should be regularly monitored. Regarding respiratory monitoring of ventilated ICU patients, it includes serial assessment of gas exchange, of respiratory system mechanics, and of patients' readiness for liberation from invasive positive pressure ventilation. Also, the monitoring of nutritional and metabolic care should allow controlling nutrients delivery, adequation between energy needs and delivery, and blood glucose. The present paper will describe the physiological basis, interpretation of, and clinical use of the major endpoints of perfusion/oxygenation adequacy and of temperature, respiratory, nutritional, and metabolic monitorings.
Published: 2012

38. Alveolar response to Pseudomonas aeruginosa: role of the type III secretion system

Author: Emmanuel Nowak, Nathalie B. Viget, Florence Ader, B. Guery, R. Le Berre, Benoît Polack, Bertrand Toussaint, Karine Faure, Eric Kipnis, Philippe Gosset, Olivier Epaulard, Biologie et physiologie des états septiques, IFR114-Université de Lille, Droit et Santé, Faculté de Médecine, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Biomolécules et inflammation pulmonaire, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service des Maladies Infectieuses, CHU Grenoble, Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), Université Grenoble Alpes (UGA)-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), Bertin Technologies (Bertin Technologies), and Bertin Technologies
Subjects: MESH: Pulmonary Alveoli, MESH: Interleukin-10, Neutrophils, MESH: Rats, Sprague-Dawley, MESH: Neutrophils, medicine.disease_cause, Type three secretion system, Rats, Sprague-Dawley, MESH: Animals, Lung, 0303 health sciences, medicine.diagnostic_test, Cytotoxins, MESH: Pseudomonas Infections, Bacterial Infections, Interleukin-10, Protein Transport, Infectious Diseases, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, Tumor necrosis factor alpha, MESH: Cytotoxins, MESH: Protein Transport, MESH: Rats, Virulence Factors, Immunology, Virulence, Lung injury, Biology, Microbiology, Cell Line, Proinflammatory cytokine, 03 medical and health sciences, medicine, Animals, Humans, Pseudomonas Infections, MESH: Lung, 030304 developmental biology, MESH: Virulence Factors, A549 cell, MESH: Humans, Tumor Necrosis Factor-alpha, 030306 microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Rats, MESH: Cell Line, Pulmonary Alveoli, Bronchoalveolar lavage, MESH: Tumor Necrosis Factor-alpha, Parasitology
Abstract: The type III secretion system (TTSS) is a specialized cytotoxin-translocating apparatus of gram-negative bacteria which is involved in lung injury, septic shock, and a poor patient outcome. Recent studies have attributed these effects mainly to the ExoU effector protein. However, few studies have focused on the ExoU-independent pathogenicity of the TTSS. For the present study, we compared the pathogenicities of two strains ofPseudomonas aeruginosain a murine model of acute lung injury. We compared the CHA strain, which has a functional TTSS producing ExoS and ExoT but not ExoU, to an isogenic mutant with an inactivatedexsAgene, CHA-D1, which does not express the TTSS at all. Rats challenged with CHA had significantly increased lung injury, as assessed by the wet/dry weight ratio for the lungs and the protein level in bronchoalveolar lavage fluid (BALF) at 12 h, compared to those challenged with CHA-D1. Consistent with these findings, the CHA strain was associated with increased in vitro cytotoxicity on A549 cells, as assessed by the release of lactate dehydrogenase. CHA was also associated at 12 h with a major decrease in polymorphonuclear neutrophils in BALF, with a proinflammatory response, as assessed by the amounts of tumor necrosis factor alpha and interleukin-1β, and with decreased bacterial clearance from the lungs, ultimately leading to an increased mortality rate. These results demonstrate that the TTSS has a major role inP. aeruginosapathogenicity independent of the role of ExoU. This report underscores the crucial roles of ExoS and ExoT or other TTSS-related virulence factors in addition to ExoU.
Published: 2005
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39. A composite score combining procalcitonin, C-reactive protein and temperature has a high positive predictive value for the diagnosis of intensive care-acquired infections

Author: Eric Kipnis, Michèle d’Herbomez, Laurent Robriquet, François Fourrier, and Caroline Séjourné
Subjects: Calcitonin, Male, medicine.medical_specialty, Calcitonin Gene-Related Peptide, Gastroenterology, Sensitivity and Specificity, Procalcitonin, law.invention, C-reactive protein, Body Temperature, Leukocyte Count, Nosocomial infection, law, White blood cell, Internal medicine, Intensive care, medicine, Humans, Intensive care unit, Prospective Studies, Protein Precursors, Prospective cohort study, Aged, Cross Infection, biology, business.industry, Middle Aged, Intensive Care Units, Infectious Diseases, medicine.anatomical_structure, Quartile, Immunology, biology.protein, Female, business, Biomarkers, Cohort study, Research Article
Abstract: Background Nosocomial infection diagnosis in the intensive care unit (ICU) remains a challenge. We compared routine measurements of procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and temperature in the detection of ICU-acquired infections. Method Prospective observational cohort study in a University hospital Medicosurgical ICU. All patients admitted to the ICU ≥ 5 days (n = 141) were included into two groups, either infected (documented infection, n = 25) or non-infected (discharged from the ICU without diagnosis of infection, n = 88). Results PCT, CRP, WBC and temperature progression from day −4 (D-4) to day 0 (D0) (day of infection diagnosis or ICU discharge) was analysed. Differences (Δ) were calculated as D0 levels minus the lowest preceding value. D0 PCT and CRP were significantly increased in infected compared to non-infected patients (median, 1st and 3rd quartiles): 3.6 ng/mL (0.92-25) for PCT, 173 mg/L (126–188) for CRP versus 0.02 ng/mL (0.1-0.9) and 57 mg/mL (31–105) respectively (p 38.6°C, PCT > 1.86 ng/mL, and CRP > 88 mg/L, performed well (AUCs of 0.88, 0.84, and 0.88 respectively). The sensitivity/specificity profiles of each marker (76%/94% for temperature, 68%/91% for PCT, and 92%/70% for CRP) led to a composite score (0.068 × D0 PCT + 0.005 × D0 CRP + 0.7 × temperature) more highly specific than each component (AUC of 0.90 and sensitivity/specificity of 80%/97%). Conclusion Combining CRP, PCT and temperature is an approach which may increase of nosocomial infection detection in the ICU.
Published: 2013

40. Time course of IL-6 and LBP, candidate biomarkers of sepsis in surgical critical care

Author: Eric Kipnis, Benoit Vallet, B Soudan, Gilles Lebuffe, L Ogé, and B Leroy
Subjects: Surgical critical care, biology, Critically ill, business.industry, Critical Care and Intensive Care Medicine, Bioinformatics, medicine.disease, Rapid identification, Sepsis, Time course, Poster Presentation, biology.protein, medicine, Interleukin 6, business, Lipopolysaccharide binding protein
Abstract: The outcome of sepsis in critically ill patients relies on rapid identification and therapy. However, identification of sepsis in these patients is challenging, and focus has shifted towards biological surrogates as diagnostic/therapeutic biomarkers. IL-6 and lipopolysaccharide binding protein (LBP) may have such a potential.
Published: 2010

41. Chronic pneumonia with Pseudomonas aeruginosa and impaired alveolar fluid clearance

Author: Eric Kipnis, Xavier Leroy, Florence Ader, Benoit Guery, Sophie Boyer, Thierry Prangère, Marie Odile Husson, and Karine Faure
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Terbutaline, Biological Transport, Active, Stimulation, Respiratory Mucosa, Biology, Pharmacology, Lung injury, medicine.disease_cause, Rats, Sprague-Dawley, Extracellular fluid, medicine, Pneumonia, Bacterial, Animals, Pseudomonas Infections, Diffuse alveolar damage, lcsh:RC705-779, Lung, Pseudomonas aeruginosa, Research, Extracellular Fluid, lcsh:Diseases of the respiratory system, respiratory system, medicine.disease, Rats, Pulmonary Alveoli, Pneumonia, medicine.anatomical_structure, medicine.drug
Abstract: Background While the functional consequences of acute pulmonary infections are widely documented, few studies focused on chronic pneumonia. We evaluated the consequences of chronic Pseudomonas lung infection on alveolar function. Methods P. aeruginosa, included in agar beads, was instilled intratracheally in Sprague Dawley rats. Analysis was performed from day 2 to 21, a control group received only sterile agar beads. Alveolar-capillary barrier permeability, lung liquid clearance (LLC) and distal alveolar fluid clearance (DAFC) were measured using a vascular (131I-Albumin) and an alveolar tracer (125I-Albumin). Results The increase in permeability and LLC peaked on the second day, to return to baseline on the fifth. DAFC increased independently of TNF-α or endogenous catecholamine production. Despite the persistence of the pathogen within the alveoli, DAFC returned to baseline on the 5th day. Stimulation with terbutaline failed to increase DAFC. Eradication of the pathogen with ceftazidime did not restore DAFC response. Conclusions From these results, we observe an adequate initial alveolar response to increased permeability with an increase of DAFC. However, DAFC increase does not persist after the 5th day and remains unresponsive to stimulation. This impairment of DAFC may partly explain the higher susceptibility of chronically infected patients to subsequent lung injury.
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42. Targeting lung coagulation disorders in acute lung injury: Easy as pie (PAI-1)?

Author: Eric Kipnis and Benoit Guery
Published: 2007
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43. Endotheliopathy Is Induced by Plasma From Critically Ill Patients and Associated With Organ Failure in Severe COVID-19

Author: Rauch, Antoine, Dupont, Annabelle, GOUTAY, Julien, Caplan, Morgan, Staessens, Senna, Moussa, Mouhamed, Jeanpierre, Emmanuelle, Corseaux, Delphine, Lefevre, Guillaume, Lassalle, Fanny, Faure, Karine, Lambert, Marc, Duhamel, Alain, Labreuche, Julien, Garrigue, Delphine, De Meyer, Simon F., Staels, Bart, Van Belle, Eric, Vincent, Flavien, Kipnis, Eric, Lenting, Peter J., Poissy, Julien, Susen, Sophie, Research Network (LICORNE), For the Lille COVID, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Université Catholique de Louvain = Catholic University of Louvain (UCL), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), This study was supported by the French government through the Program Investissement d’Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE)., Members of the LICORNE Scientific Committee: Dominique Deplanque (Clinical Investigation Center, CHU Lille, France) Karine Faure (Department of Infectious Diseases, CHU Lille, France) Guillaume Lefevre (Department of Immunology, CHU Lille, France) Enagnon Kazali Alidjinou (Department of Virology, CHU Lille, France) Régis Bordet (Department of Medical Pharmacology, CHU Lille, France) Marie-Charlotte Chopin (Department of Infectious Diseases, CHU Lille, France) Ilka Engelmann (Department of Virology, CHU Lille, France) Delphine Garrigue (Department of Emergency, CHU Lille, France) Anne Goffard (Department of Virology, CHU Lille, France) Eric Kipnis (Department of Anesthesia and Critical Care, CHU Lille, France) Myriam Labalette (Department of Immunology, CHU Lille, France) Marc Lambert (Department of Internal Medicine, CHU Lille, France) David Launay (Department of Internal Medicine, CHU Lille, France) Daniel Mathieu (Department of Intensive Care, CHU Lille, France) Claude-Alain Maurage (Department of Anatomopathology, CHU Lille, France) Julien Poissy (Department of Intensive Care, CHU Lille, France) Boualem Sendid (Department of Parasitology, CHU Lille, France) Sophie Susen (Department of Hematology, CHU Lille, France), ANR-16-IDEX-0004,ULNE,ULNE(2016), Université de Lille, LillOA, ULNE - - ULNE2016 - ANR-16-IDEX-0004 - IDEX - VALID, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: renal failure, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Severity of Illness Index, Plasma, chemistry.chemical_compound, 0302 clinical medicine, Cytotoxic T cell, 030212 general & internal medicine, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, endotheliopathy, biology, Interleukin, 3. Good health, Endothelial stem cell, [SDV] Life Sciences [q-bio], cell death, endothelial cell, Tumor necrosis factor alpha, Coronavirus Infections, Cardiology and Cardiovascular Medicine, Cell-Free Nucleic Acids, liver injury, medicine.medical_specialty, Cell Survival, Critical Illness, Multiple Organ Failure, Pneumonia, Viral, Aspartate transaminase, Proinflammatory cytokine, Betacoronavirus, 03 medical and health sciences, Immune system, Physiology (medical), Lactate dehydrogenase, Internal medicine, Correspondence, Research Letter, medicine, Humans, Pandemics, SARS-CoV-2, Interleukin-6, business.industry, respiratory failure, COVID-19, Endothelial Cells, Endocrinology, chemistry, Microvessels, biology.protein, Syndecan-1, business
Abstract: This article assessed whether plasma collected from patients with COVID-19 at different disease stages could trigger endothelial damage in vitro by using cultured human pulmonary microvascular endothelial cells (HPMVEC) This study also further investigated the association of plasma-induced cytotoxicity with levels of circulating biomarkers related to organ dysfunction (Pao2 [partial pressure of oxygen in arterial blood]/Fio2 [fraction of inspired oxygen], widely used as an indicator of oxygenation requirements, lactate dehydrogenase, creatinine, and aspartate transaminase), endothelial damage (von Willebrand factor antigen;ADAMTS13;plasminogen activator inhibitor-1;syndecan-1), tissue injury (cell-free DNA, a damage-associated molecular patterns marker), and levels of circulating cytokines related to the activation of innate (interleukin [IL]-6 and tumor necrosis factor-a) and adaptative immune cell responses (soluble IL-2 receptor) Inclusion criteria were individuals aged 18 years or older with a positive SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasal or tracheal samples This data shed new light on the pathophysiology of COVID-19 by demonstrating the direct and rapid cytotoxic effect of plasma collected from critically ill patients on vascular endothelial cells This rapid effect (1 hour after plasma exposure) excludes a direct cytopathic effect of SARS-CoV-2 infection, as the progression of viral infection and visible cytopathogenic effects are in general only apparent 12 to 24 hours after infection 5 A higher cytotoxic effect of plasma on endothelial cells was associated with a more pronounced hypoxemia and organ dysfunction as reflected by the correlation with Pao2/FiO2, lactate dehydrogenase, creatinine, and aspartate transaminase This cytotoxic effect also correlated with circulating markers of endothelial damage, indicating that this in vitro functional assay reflects microvascular endothelial damage in vivo Different pathways could be involved in endothelial cell injury during the course of COVID-19, i e , complement activation, cellular hypoxia, platelets, and direct cytotoxicity of cytokines such as IL-6, IL-1beta, and tumor necrosis factor-a The study observed a relationship between this cytotoxic effect and the level of proinflammatory cytokines, suggesting that cytotoxicity could be related to overproduction of proinflammatory cytokines
Published: 2020
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44. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

Author: Anne Goffard, Sylvie Behillil, Caroline Séjourné, Fanny Vuotto, Vincent Enouf, Valérie Caro, Julien Poissy, Daniel Mathieu, Benoit Guery, Jean Claude Manuguerra, Didier Che, Xavier Lemaire, Nicolas Ettahar, Alexandra Mailles, Loubna El Mansouf, Sylvie van der Werf, Arnaud Fontanet, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier [Douai, Nord], Centre hospitalier [Valenciennes, Nord], Centre National de Référence des virus influenzae (Grippe) (CNR), Institut Pasteur [Paris] (IP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Institut de Veille Sanitaire (INVS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), The National Reference Center for Influenza Viruses and the CIBU are supported in part by funds from the French Institute for Public Health Surveillance (Institut de veille sanitaire, InVS). Work related to collection of data, implementation of the assays, and sequencing was done with funds from ANR grant Labex Integrative Biology of Emerging Infectious Diseases (IBEID, grant number ANR-10-LABX-62-IBEID from the French Government's Investissement d'Avenir programme) and from the European Community's Seventh Framework Programme (FP7/2007–2013) under the project EMPERIE (European Community grant agreement number 223498) and under the project PREDEMICS (grant agreement number 278433), We thank the nurses and all health-care workers from the hospitals in Valenciennes, Douai, and Lille who, in this crisis situation, took care of the patients and controlled the spread of this disease. We thank P Despres, S Paulous, and M P Frenkiel (Unit of Flavivirus-Host Molecular Interactions, Institut Pasteur) for preliminary serological analyses. We thank Eric Kipnis for editing of the report., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 223498,EC:FP7:HEALTH,FP7-HEALTH-2007-B,EMPERIE(2009), European Project: 278433,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PREDEMICS(2011), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, medicine.medical_specialty, Middle East respiratory syndrome coronavirus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Intensive care medicine, 030304 developmental biology, Coronavirus, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cross Infection, medicine.diagnostic_test, business.industry, General Medicine, 3. Good health, Bronchoalveolar lavage, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sputum, Chills, medicine.symptom, business, Coronavirus Infections, Viral load, Respiratory tract
Abstract: Summary Background Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. Methods Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. Findings Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. Interpretation Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor. Funding French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.
Published: 2013
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