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1. Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings

Author: Charles-Hervé Vacheron, Anne Kaas, Jean-Philippe Rasigade, Frederic Aubrun, Laurent Argaud, Baptiste Balanca, Jean-Luc Fellahi, Jean Christophe Richard, Anne-Claire Lukaszewicz, Florent Wallet, Olivier Dauwalder, and Arnaud Friggeri
Subjects: Cefiderocol, ICU, Relapse, Clinical cure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients. Methods We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders. Results We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1–5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53]) Conclusion Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate.
Published: 2024
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2. Comparison of mortality and outcomes of four respiratory viruses in the intensive care unit: a multicenter retrospective study

Author: Baptiste Grangier, Charles-Hervé Vacheron, Donatien De Marignan, Jean-Sebastien Casalegno, Sandrine Couray-Targe, Audrey Bestion, Florence Ader, Jean-Christophe Richard, Emilie Frobert, Laurent Argaud, Thomas Rimmele, Anne-Claire Lukaszewicz, Frédéric Aubrun, Frédéric Dailler, Jean-Luc Fellahi, Julien Bohe, Vincent Piriou, Bernard Allaouchiche, Arnaud Friggeri, Florent Wallet, and The Lyon Sud COVID-19 ICU
Subjects: CARV, SARS COV 2, Influenza, RSV, ARDS, Medicine, Science
Abstract: Abstract This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.
Published: 2024
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3. Tailoring a specific medical leadership development program for faculty members: the Lyon-Ottawa experience

Author: Claire Falandry, Justine Bacchetta, Muriel Doret-Dion, Carole Ferraro-Peyret, Cyrille B. Confavreux, Marion Douplat, Patrick Feugier, Arnaud Friggeri, Pierre-Adrien Bolze, Yesim Dargaud, Alexandre Messager, Martine Wallon, Loïc Geffroy, Yves Matillon, and Jacques Bradwejn
Subjects: Leadership development, faculty, training, management, educational needs, Special aspects of education, LC8-6691, Medicine (General), R5-920
Abstract: ABSTRACTThe development of leadership skills has been the topic of several position statements over recent decades, and the need of medical leaders for a specific training was emphasized during the COVID-19 crisis, to enable them to adequately collaborate with governments, populations, civic society, organizations, and universities. However, differences persist as to the way such skills are taught, at which step of training, and to whom. From these observations and building on previous experience at the University of Ottawa, a team of medical professors from Lyon (France), Ottawa, and Montreal (Canada) universities decided to develop a specific medical leadership training program dedicated to faculty members taking on leadership responsibilities. This pilot training program was based on a holistic vision of a transformation model for leadership development, the underlying principle of which is that leaders are trained by leaders. All contributors were eminent French and Canadian stakeholders. The model was adapted to French faculty members, following an inner and outer analysis of their specific needs, both contextual and related to their time constraints. This pilot program, which included 10 faculty members from Lyon, was selected to favor interactivity and confidence in older to favor long-term collaborations between them and contribute to institutional changes from the inner; it combined several educational methods mixing interactive plenary sessions and simulation exercises during onescholar year. All the participants completed the program and expressed global satisfaction with it, validating its acceptability by the target. Future work will aim to develop the program, integrate evaluation criteria, and transform it into a graduating training.
Published: 2024
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4. Correction: Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings

Author: Charles-Hervé Vacheron, Anne Kaas, Jean-Philippe Rasigade, Frederic Aubrun, Laurent Argaud, Baptiste Balanca, Jean-Luc Fellahi, Jean Christophe Richard, Anne-Claire Lukaszewicz, Florent Wallet, Olivier Dauwalder, and Arnaud Friggeri
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2024
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5. Pre-anaesthesia Telephone Consultation: A Safe Alternative for Anaesthesia Assessment in Case of Repeated Low or Intermediate Risk Surgeries: A Prospective Cohort Study

Author: Charles-Herve Vacheron, Clemence Ferrier, Estelle Morau, Alexandre Theissen, Vincent Piriou, Pierre Yves Carry, and Arnaud Friggeri
Subjects: anaesthesia, consultation, telemedicine, Anesthesiology, RD78.3-87.3
Abstract: Objective:Telemedicine has widely expanded during the coronavirus disease-2019 pandemic. Our objective was to evaluate the feasibility, safety, effectiveness, and satisfaction of pre-anaesthesia telephone consultation (PATC).Methods:From December 2015 to October 2016, a prospective survey was administered to anaesthesiologists, nurse anaesthetists, and patients of the ambulatory and maxillofacial departments. Patients having a pre-anaesthesia consultation (PAC) within the previous year in the department, whose health state was considered stable, and for whom the surgical procedure was related to the previous one, were eligible for PATC. Three questionnaires concerning the pre- (Q1), per- (Q2), and postoperative (Q3) periods were answered by the patient, the anaesthesiologist, and the anaesthesiologist nurse to evaluate the feasibility and satisfaction of the PATC. We collected the cancelation rate and any incident occurring during the surgery.Results:Over the study period, 210 patients were included. The response rate was 200/210 (95.2%) for Q1, 108/208 (51.9%) for Q2 and 146/208 (70.2%) for Q3. PATC was performed in a median (IQR) of 13 (7-20) days before the procedure. Patients answered directly in 73% of cases without the need for recall. During surgery, 4 incidents occurred and none were attributable to PATC. Patient satisfaction was 93.3% and 85.8% of them preferred PATC to conventional PAC. The kilometric saving was 74 (30-196) km per PATC.Conclusion:Both patients and professionals were satisfied with PATC, which did not impact safety. On the selected patients, PATC brings many practical benefits and increases organizational flexibility.
Published: 2023
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6. Multitasking in postanesthesia care unit following nurse interruptions, an analysis of the causes and consequences using classification tree: an observational prospective study

Author: Charles-Hervé Vacheron, Olivier Peyrouset, Pascal Incagnoli, Virginie Charra, Stéphanie Parat, Jean-Stephane David, Alexandre Theissen, Vincent Piriou, and Arnaud Friggeri
Subjects: Concurrent, Multitasking, Patient safety, Task interruption, Task switching, Anesthesiology, RD78.3-87.3
Abstract: Background: Postanesthesia Care Unit (PACU) is an environment associated with an important workload which is susceptible to lead to task interruption (TI), leading to task-switching or concurrent multitasking. The objective of the study was to determine the predictors of the reaction of the nurses facing TI and assess those who lead to an alteration of the initial task. Methods: We conducted a prospective observational study into the PACU of a university hospital during February 2017. Among 18 nurses, a selected one was observed each day, documenting for each TI the reaction of the nurse (task switching or concurrent multitasking), and the characteristics associated with the TI. We performed classification tree analyses using C5.0 algorithm in order to select the main predictors of the type of multitasking performed and the alteration of the initial task. Results: We observed 1119 TI during 132 hours (8.5 TI/hour). The main reaction was concurrent multitasking (805 TI, 72%). The short duration of the task interruption (one minute or less) was the most important predictor leading to concurrent multitasking. Other predictors of response to TI were the identity of the task interrupter and the number of nurses present. Regarding the consequences of the task switching, long interruption (more than five minutes) was the most important predictor of the alteration of the initial task. Conclusions: By analysing the predictors of the type of multitasking in front of TI, we propose a novel approach to understanding TI, offering new perspective for prevention strategies.
Published: 2023
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7. Replicating finding, answering questions: closer to the truth about COVID-19 associated VAP

Author: Charles-Hervé Vacheron, Romain Fort, Tristan Dagonneau, Arnaud Friggeri, Florent Wallet, and HospiceRea Study Group
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2023
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8. Lactic alkalosis in intensive care: a red flag?

Author: Auguste Dargent, Florent Wallet, Arnaud Friggeri, Julien Bohe, and Charles-Hervé Vacheron
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2023
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9. Hyper-inflammatory profile and immunoparalysis in patients with severe Legionnaires’ disease

Author: Camille Allam, William Mouton, Hugo Testaert, Christophe Ginevra, Noémie Fessy, Marine Ibranosyan, Ghislaine Descours, Laetitia Beraud, Johann Guillemot, Annelise Chapalain, Chloé Albert-Vega, Jean-Christophe Richard, Laurent Argaud, Arnaud Friggeri, Vanessa Labeye, Yvan Jamilloux, Nathalie Freymond, Fabienne Venet, Gérard Lina, Patricia Doublet, Florence Ader, Sophie Trouillet-Assant, and Sophie Jarraud
Subjects: Legionnaires’ disease, hyper-inflammation, immunoparalysis, immune functional assays, severity, LPS stimulation, Microbiology, QR1-502
Abstract: IntroductionSevere Legionnaires’ disease (LD) can lead to multi-organ failure or death in 10%–30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity.MethodsA total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8.ResultsAmong the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status.DiscussionThe present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.
Published: 2023
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10. Prognosis of Old Intensive Care COVID-19 Patients at a Glance: The Senior COVID Study

Author: Charles-Hervé Vacheron, Laurent Bitker, Fabrice Thiolliére, Fabien Subtil, Paul Abraham, Vincent Collange, Baptiste Balança, Max Haïne, Céline Guichon, Christophe Leroy, Marie Simon, Amélie Malapert, Mélanie Roche, Jean-Baptiste Pialat, Laurent Jallades, Alain Lepape, Arnaud Friggeri, and Claire Falandry
Subjects: Anesthesiology, RD78.3-87.3
Published: 2022
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11. Intensive care-related loss of quality of life and autonomy at 6 months post-discharge: Does COVID-19 really make things worse?

Author: Fabrice Thiolliere, Claire Falandry, Bernard Allaouchiche, Victor Geoffray, Laurent Bitker, Jean Reignier, Paul Abraham, Stephanie Malaquin, Baptiste Balança, Hélène Boyer, Philippe Seguin, Céline Guichon, Marie Simon, Arnaud Friggeri, Charles-Hervé Vacheron, and AZUREA Study Group
Subjects: COVID-19, Autonomy, Quality of life, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Objective To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. Design Comparison of two prospective multi-centric studies. Setting This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). Patients We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). Interventions None. Measurements and main results A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. Conclusions COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.
Published: 2022
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12. Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation?

Author: Jean-Stephane David, Aline Lambert, Xavier-Jean Taverna, Pascal Incagnoli, Marie-Odile Geay-Baillat, Olivia Vassal, Arnaud Friggeri, and Kenji Inaba
Subjects: ROTEM, Fibrinogen, Trauma, Coagulopathy, Shock, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is 1, hemoglobin level 5 mEq L−1. Data are expressed as count (%), median [IQR]. Results 1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19–36] vs. 24 [17–29]) and had more impaired vital signs (base deficit: 5.4 [3.6–7.8] vs. 3.8 [2.0–6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level 1, a hemoglobin level 5.0 mEq L−1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06–1.82] for MFD-C, and 2.17 [1.48–3.19] for MFD-A5. Results were not modified after adjustment on the ISS. Conclusions We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.
Published: 2021
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13. Co-infection with Legionella and SARS-CoV-2, France, March 2020

Author: Camille Allam, Alexandre Gaymard, Ghislaine Descours, Christophe Ginevra, Laurence Josset, Maud Bouscambert, Laetitia Beraud, Marine Ibranosyan, Camille Golfier, Arnaud Friggeri, Bruno Lina, Christine Campèse, Florence Ader, and Sophie Jarraud
Subjects: coronavirus disease, COVID-19, Legionnaires’ disease, Legionella, pneumonia, respiratory infections, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We describe a March 2020 co-occurrence of Legionnaires’ disease (LD) and coronavirus disease in France. Severe acute respiratory syndrome coronavirus 2 co-infections were identified in 7 of 49 patients from LD case notifications. Most were elderly men with underlying conditions who had contracted severe pneumonia, illustrating the relevance of co-infection screening.
Published: 2021
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14. Septic Thrombophlebitis with Persistent Bacteremia Treated by Thrombolysis

Author: Boris Farny, Charles-Hervé Vacheron, Arnaud Friggeri, and Bernard Allaouchiche
Subjects: Anesthesiology, RD78.3-87.3
Published: 2022
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15. Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis

Author: Anne-Lise Bienvenu, Pierre Pradat, Claude Guerin, Frederic Aubrun, Jean-Luc Fellahi, Arnaud Friggeri, Céline Guichon, Romain Hernu, Jean Menotti, Céline Monard, Sylvie Paulus, Thomas Rimmele, Vincent Piriou, Christian Chidiac, Laurent Argaud, and Gilles Leboucher
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Background: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. Methods: A 3-year (2015–2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan–Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. Findings: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan–Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. Interpretation: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs. Keywords: Candidemia, Caspofungin, Fluconazole, Voriconazole, Mortality, Propensity score
Published: 2020
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16. European intensive care physicians’ experience of infections due to antibiotic-resistant bacteria

Author: Alain Lepape, Astrid Jean, Jan De Waele, Arnaud Friggeri, Anne Savey, Philippe Vanhems, Marie Paule Gustin, Dominique L. Monnet, José Garnacho-Montero, and Anke Kohlenberg
Subjects: Antimicrobial resistance, Intensive care, Antimicrobial treatment, Third-generation-cephalosporin-resistant Enterobacteriaceae, Carbapenem-resistant Enterobacteriaceae, Meticillin-resistant Staphylococcus aureus, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians’ perception of the AMR situation in the European Union/European Economic Area (EU/EEA). Methods Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent’s ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe. Results Overall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics. Conclusions The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.
Published: 2020
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17. Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol

Author: Thomas Rimmele, Julien Berthiller, Anne-Claire Lukaszewicz, Laurent Jallades, Jean-Baptiste Pialat, Céline Monard, Christophe Leroy, Vincent Collange, Arnaud Friggeri, Mélanie Roche, Christine Ravot, Amélie Malapert, Max Haïne, David Dayde, Claire Falandry, Marie Simon, Céline Guichon, Paul Abraham, Camille Boin, Justine Dubreuil, Laurent Bitker, Baptiste Balança, Sylvie Goutte, Emilie Gadea, Alain Lepape, Fabrice Thiollière, Hodane Yonis, Antoine Garnier-Crussard, Loredana Baboi, Valérie Cerro, Carlos El Khoury, Emilie Gadéa-Deschamps, Marie-Catherine Fromont, Audrey Gelot, Anthéa Loïez, Maya Perrou, Laetitia Paradisi-Prieur, Marion Provent, Gulsum Sahin, Ghyslaine Thao, and Marine Thieux
Subjects: Medicine
Abstract: Introduction With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission.Methods and analysis This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients’ outcomes.Ethics and dissemination The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals.Trial registration number NCT04422340.
Published: 2021
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18. Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient

Author: Romain Garreau, Benoît Falquet, Lisa Mioux, Laurent Bourguignon, Tristan Ferry, Michel Tod, Florent Wallet, Arnaud Friggeri, Jean-Christophe Richard, and Sylvain Goutelle
Subjects: vancomycin, pharmacokinetics, continuous infusion, ICU, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Vancomycin is widely used for empirical antimicrobial therapy in critically ill patients with sepsis. Continuous infusion (CI) may provide more stable exposure than intermittent infusion, but optimal dosing remains challenging. The aims of this study were to perform population pharmacokinetic (PK) analysis of vancomycin administered by CI in intensive care unit (ICU) patients to identify optimal dosages. Methods: Patients who received vancomycin by CI with at least one measured concentration in our center over 16 months were included, including those under continuous renal replacement therapy (CRRT). Population PK was conducted and external validation of the final model was performed in a dataset from another center. Simulations were conducted with the final model to identify the optimal loading and maintenance doses for various stages of estimated creatinine clearance (CRCL) and in patients on CRRT. Target exposure was defined as daily AUC of 400–600 mg·h/L on the second day of therapy (AUC24–48 h). Results: A two-compartment model best described the data. Central volume of distribution was allometrically scaled to ideal body weight (IBW), whereas vancomycin clearance was influenced by CRRT and CRCL. Simulations performed with the final model suggested a loading dose of 27.5 mg/kg of IBW. The maintenance dose ranged from 17.5 to 30 mg/kg of IBW, depending on renal function. Overall, simulation showed that 55.8% (95% CI; 47–64%) of patients would achieve the target AUC with suggested dosages. Discussion: A PK model has been validated for vancomycin administered by CI in ICU patients, including patients under CRRT. Our model-informed precision dosing approach may help for early optimization of vancomycin exposure in such patients.
Published: 2021
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19. The receptor for urokinase regulates TLR2 mediated inflammatory responses in neutrophils.

Author: Gang Liu, Yanping Yang, Shanzhong Yang, Sami Banerjee, Andressa De Freitas, Arnaud Friggeri, Kasey I Davis, and Edward Abraham
Subjects: Medicine, Science
Abstract: The urokinase-type plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol (GPI) anchored membrane protein, regulates urokinase (uPA) protease activity, chemotaxis, cell-cell interactions, and phagocytosis of apoptotic cells. uPAR expression is increased in cytokine or bacteria activated cell populations, including macrophages and monocytes. However, it is unclear if uPAR has direct involvement in the response of inflammatory cells, such as neutrophils and macrophages, to Toll like receptor (TLR) stimulation. In this study, we found that uPAR is required for optimal neutrophil activation after TLR2, but not TLR4 stimulation. We found that the expression of TNF-α and IL-6 induced by TLR2 engagement in uPAR-/- neutrophils was less than that in uPAR+/+ (WT) neutrophils. Pretreatment of neutrophils with PI-PLC, which cleaves GPI moieties, significantly decreased TLR2 induced expression of TNF-α in WT neutrophils, but demonstrated only marginal effects on TNF-α expression in PAM treated uPAR-/- neutrophils. IκB-α degradation and NF-κB activation were not different in uPAR-/- or WT neutrophils after TLR2 stimulation. However, uPAR is required for optimal p38 MAPK activation after TLR2 engagement. Consistent with the in vitro findings that uPAR modulates TLR2 engagement induced neutrophil activation, we found that pulmonary and systemic inflammation induced by TLR2, but not TLR4 stimulation is reduced in uPAR-/- mice compared to WT counterparts. Therefore, our data suggest that neutrophil associated uPAR could be a potential target for treating acute inflammation, sepsis, and organ injury related to severe bacterial and other microbial infections in which TLR2 engagement plays a major role.
Published: 2011
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20. Co-infection with Legionella and SARS-CoV-2, France, March 2020

Author: Laetitia Beraud, Marine Ibranosyan, C. Campèse, Camille Allam, Alexandre Gaymard, Camille Golfier, Florence Ader, Sophie Jarraud, Arnaud Friggeri, Ghislaine Descours, Laurence Josset, Maud Bouscambert, Christophe Ginevra, and Bruno Lina
Subjects: Microbiology (medical), Male, 2019-20 coronavirus outbreak, Epidemiology, Legionella, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, macromolecular substances, Infectious and parasitic diseases, RC109-216, medicine.disease_cause, respiratory infections, medicine, Humans, pneumonia, viruses, Coronavirus, Original Research, Aged, biology, business.industry, SARS-CoV-2, Coinfection, Dispatch, COVID-19, Co-infection with Legionella and SARS-CoV-2, France, March 2020, medicine.disease, biology.organism_classification, Virology, zoonoses, Pneumonia, Infectious Diseases, coronavirus disease, Medicine, Legionnaires' disease, France, business, Co infection, severe acute respiratory syndrome coronavirus 2, Legionnaires’ disease
Abstract: We describe a March 2020 co-occurrence of Legionnaires' disease (LD) and coronavirus disease in France. Severe acute respiratory syndrome coronavirus 2 co-infections were identified in 7 of 49 patients from LD case notifications. Most were elderly men with underlying conditions who had contracted severe pneumonia, illustrating the relevance of co-infection screening.
Published: 2021

21. Accelerated surgery versus standard care in hip fracture (HIP ATTACK-1) : a kidney substudy of a randomized clinical trial

Author: Flavia K. Borges, P.J. Devereaux, Meaghan Cuerden, Jessica M. Sontrop, Mohit Bhandari, Ernesto Guerra-Farfán, Ameen Patel, Alben Sigamani, Masood Umer, John Neary, Maria Tiboni, Vikas Tandon, Mmampapatla Thomas Ramokgopa, Parag Sancheti, Abdel-Rahman Lawendy, Mariano Balaguer-Castro, Richard Jenkinson, Paweł Ślęczka, Aamer Nabi Nur, Gavin C.A. Wood, Robert J. Feibel, John Stephen McMahon, Bruce M. Biccard, Alessandro Ortalda, Wojciech Szczeklik, Chew Yin Wang, Jordi Tomás-Hernández, Jessica Vincent, Valerie Harvey, Shirley Pettit, Kumar Balasubramanian, Gerard Slobogean, Amit X. Garg, Laurent Veevaete, Bernard le Polain de Waroux, Patricia Lavand'homme, Olivier Cornu, Karim Tribak, Jean C. Yombi, Nassim Touil, Jigme T. Bhutia, Carol Clinckaert, Dirk De Clippeleir, Maike Reu, Leslie P. Gauthier, Victoria RA. Avram, Mitchell Winemaker, Daniel M. Tushinski, Justin de Beer, Andrew Worster, Diane L. Simpson, Kim A. Alvarado, Krysten K. Gregus, Kelly H. Lawrence, Darryl P. Leong, Philip G. Joseph, Patrick Magloire, Benjamin Deheshi, Stuart Bisland, Thomas J. Wood, David AJ. Wilson, Sandra N. Ofori, Jessica Spence, Emmanuelle Duceppe, Maria E. Tiboni, John D. Neary, Anthony Adili, David D. Cowan, Vickas Khanna, Amna Zaki, Janet C. Farrell, Anne Marie MacDonald, David Conen, Steven CW. Wong, Arsha Karbassi, Douglas S. Wright, Harsha Shanthanna, Javier Ganame, Andrew Cheung, Ryan Coughlin, Moin Khan, Spencer Wikkerink, Faraaz A. Quraishi, Waleed Kishta, Emil Schemitsch, Timothy Carey, Mark D. Macleod, David W. Sanders, Edward Vasarhelyi, Debra Bartley, George K. Dresser, Christina Tieszer, Richard J. Jenkinson, Steven Shadowitz, Jacques S. Lee, Stephen Choi, Hans J. Kreder, Markku Nousiainen, Monica R. Kunz, Ravianne Tuazon, Mopina Shrikumar, Bheeshma Ravi, David Wasserstein, David J.G. Stephen, Diane Nam, Patrick D.G. Henry, Gavin CA. Wood, Stephen M. Mann, Melanie T. Jaeger, Marco LA. Sivilotti, Christopher A. Smith, Christopher C. Frank, Heather Grant, Leone Ploeg, Jeff D. Yach, Mark M. Harrison, Aaron R. Campbell, Ryan T. Bicknell, Davide D. Bardana, Katie McIlquham, Catherine Gallant, Samantha Halman, Venkatesh Thiruganasambandamoorth, Sara Ruggiero, William J. Hadden, Brian PJ. Chen, Stephanie A. Coupal, Stephen J. McMahon, Lisa M. McLean, Hemant R. Shirali, Syed Y. Haider, Crystal A. Smith, Evan Watts, David J. Santone, Kevin Koo, Allan J. Yee, Ademilola N. Oyenubi, Aaron Nauth, Emil H. Schemitsch, Timothy R. Daniels, Sarah E. Ward, Jeremy A. Hall, Henry Ahn, Daniel B. Whelan, Amit Atrey, Amir Khoshbin, David Puskas, Kurt Droll, Claude Cullinan, Jubin Payendeh, Tina Lefrancois, Lise Mozzon, Travis Marion, Michael J. Jacka, James Greene, Matthew Menon, Robert Stiegelmahr, Derek Dillane, Marleen Irwin, Lauren Beaupre, Chad P. Coles, Kelly Trask, Shelley MacDonald, J.A.I. Trenholm, William Oxner, C.G. Richardson, Niloofar Dehghan, Mehdi Sadoughi, Achal Sharma, Neil J. White, Loretta Olivieri, Stephen B. Hunt, Thomas R. Turgeon, Eric R. Bohm, Sarah Tran, Stephen M. Giilck, Tom Hupel, Pierre Guy, Peter J. O'Brien, Andrew W. Duncan, Gordon A. Crawford, Junlin Zhou, Yanrui Zhao, Yang Liu, Lei Shan, Anshi Wu, Juan M. Muñoz, Philippe Chaudier, Marion Douplat, Michel Henri Fessy, Vincent Piriou, Lucie Louboutin, Jean Stephane David, Arnaud Friggeri, Anthony Viste, Charles Hervé Vacheron, Frankie Ka Li Leung, Christian Xinshuo Fang, Dennis King Hang Yee, Parag K. Sancheti, Chetan V. Pradhan, Atul A. Patil, Chetan P. Puram, Madhav P. Borate, Kiran B. Kudrimoti, Bharati A. Adhye, Himanshu V. Dongre, Bobby John, Valsamma Abraham, Ritesh A. Pandey, Arti Rajkumar, Preetha E. George, Manesh Stephen, Nitheesh Chandran, Mohammed Ashraf, A.M. Georgekutty, Ahamad S. Sulthan, S. Adinarayanan, Deep Sharma, Satish P. Barnawal, Srinivasan Swaminathan, Prasanna U. Bidkar, Sandeep K. Mishra, Jagdish Menon, M. Niranjan, Z.K. Varghese, Santosh A. Hiremath, N.C. Madhusudhan, Abhijit Jawali, Kingsly R. Gnanadurai, Carolin E. George, Tatarao Maddipati, K.P. Mary, Vijay Sharma, Kamran Farooque, Rajesh Malhotra, Samarth Mittal, Chavi Sawhney, Babita Gupta, Purva Mathur, Shivanand Gamangati, Vijaylaxmi Tripathy, Prem H. Menon, Mandeep S. Dhillon, Devendra K. Chouhan, Sharanu Patil, Ravi Narayan, Purushotham Lal, Prashanth N. Bilchod, Surya U. Singh, Uttam V. Gattu, Ravi P. Dashputra, Prashant V. Rahate, Maurizio Turiel, Riccardo Accetta, Paolo Perazzo, Daniele Stella, Marika Bonadies, Chiara Colombo, Giuseppe De Blasio, Stefania Fozzato, Fabio Pino, Ilaria Morelli, Francesco De Donato, Eleonora Colnaghi, Vincenzo Salini, Giacomo Placella, Giuseppe Giardina, Gaetano Lombardi, Anna Marcato, Luca Guzzetti, Ilaria Rivetti, Massimiliano Greco, H.M. Khor, Hou Yee Lai, C.S. Kumar, K.H. Chee, P.S. Loh, Kit Mun Tan, Simmrat Singh, Li Lian Foo, Komella Prakasam, Sook Hui Chaw, Meng-Li Lee, Joanne HL. Ngim, Huck Wee Boon, Im Im Chin, Ydo V. Kleinlugtenbelt, Ellie BM. Landman, Elvira R. Flikweert, Herbert W. Roerdink, Roy BG. Brokelman, Hannie F. Elskamp-Meijerman, Bas Staffhorst, Jan-Hein MG. Cobben, Dilshad Begum, Anila Anjum, Pervaiz M. Hashmi, Tashfeen Ahmed, Haroon U. Rashid, Mujahid J. Khattak, Rizwan H. Rashid, Riaz H. Lakdawala, Shahryar Noordin, Naveed M. Juman, Robyna I. Khan, Muhammad M. Riaz, Syedah S. Bokhari, Ayesha Almas, Hussain Wahab, Arif Ali, Hammad N. Khan, Eraj K. Khan, Kholood A. Janjua, Sajjad H. Orakzai, Abdus S. Khan, Khawaja J. Mustafa, Mian A. Sohail, Muhammad Umar, Siddra A. Khan, Muhammad Ashraf, Muhammad K. Khan, Muhammad Shiraz, Ahmad Furgan, Piotr Dąbek, Adam Kumoń, Wojciech Satora, Wojciech Ambroży, Mariusz Święch, Jacek Rycombel, Adrian Grzelak, Ilona Nowak-Kózka, Jaroslaw Gucwa, Waldemar Machala, Mmampapatla T. Ramokgopa, Gregory B. Firth, Mwalimu Karera, Maria Fourtounas, Virsen Singh, Anna Biscardi, Muhammad N. Iqbal, Ryan J. Campbell, Matimba L. Maluleke, Carien Moller, Lerato Nhlapo, Sithombo Maqungo, Margot Flint, Marcin B. Nejthardt, Sean Chetty, Stephen Venter, Ernesto Guerra-Farfan, Jordi Tomas-Hernandez, Yaiza Garcia-Sanchez, Miriam Garrido Clua, Vicente Molero-Garcia, Jordi Teixidor-Serra, Maria del Mar Villar-Casares, Jordi Selga Marsa, Juan A. Porcel-Vazquez, Jose-Vicente Andres- Peiro, Jaume Mestre-Torres, Patricia Guilabert, M Luisa Paños Gozalo, Luis Abarca, Nuria Martin, Gemma Usua, Pilar Lalueza-Broto, Judith Sanchez-Raya, Jorge Nuñez Camarena, Antoni Fraguas-Castany, Carlos Piedra Calle, Diego Soza Leiva, Maria Garcia Carrasco, Montsant Jornet-Gibert, Montserrat Monfort-Mira, Alfons Gasset-Teixidor, Francesc Antoni Marcano-Fernández, Isabel Simó- Sánchez, Begoña Mari-Alfonso, Christian Yela-Verdú, Raúl Pellejero-García, Júlia Casas-Codina, Ruben Iglesias- Sanjuan, Pau Balcells-Nolla, Oriol Vila-Sánchez, Mercè Bertrana de Bustos, Pablo Castillón, Martí Bernaus, Saioa Quintas, Olga Gómez, Jordi Salvador, Javier Abarca, Cristina Estrada, Marga Novellas, Francesc Anglès, Alfred Dealbert, Oscar Macho, Alexia Ivanov, Esther Valldosera, Marta Arroyo, Borja Pey, Antoni Yuste, Llorenç Mateo, Julio De Caso, Rafael Anaya, J.L. Higa-Sansone, Angelica Millan, Victoria Baños, Sergio Herrera-Mateo, Hector J. Aguado, Virginia García-Virto, Clarisa Simón-Pérez, Sergio Chavez, María Bragado, María Plata, Enrique Guerado, Encarnacion Cruz, Juan R. Cano, Jose M. Bogallo, Paphon Sa-ngasoongsong, Noratep Kulachote, Norachart Sirisreetreerux, Nachapan Pengrung, Theerawat Chalacheewa, Vanlapa Arnuntasupakul, Teerapat Yingchoncharoen, Bundit Naratreekoon, Miriam A. Kadry, Surendini Thayaparan, Victor Babu, Arash Aframian, Souad Bentoumi, Amrinder Sayan, Ihab Abdlaziz, Marcela P. Vizcaychipi, Patricia Correia, Shashank Patil, Kevin Haire, Amy SE. Mayor, Sally Dillingham, Laura Nicholson, Ben T. Brooke, Joby John, Shashi K. Nanjayan, Martyn J. Parker, Susan O'Sullivan, Meir T. Marmor, Amir Matityahu, Robert T. McClellan, Curt Comstock, Anthony Ding, Paul Toogood, Robert O’Toole, Marcus Sciadini, Jason Nascone, Nathan O’Hara, Scott P. Ryan, Molly E. Clark, Charles Cassidy, Konstantin Balonov, Tristan Weaver, Laura S. Phieffer, Sergio D. Bergese, Andrew J. Marcantonio, Shrikant I. Bangdiwala, Michael H. McGillion, Sanela Dragic-Taylor, Chelsea Maxwell, Sarah Molnar, Jennifer R. Wells, Patrice Forget, Paul Landais, Giovanni Landoni, Ekaterine Popova, Iain K. Moppett, Robin Roberts, null Chairperson, Finlay McAlister, David Sackett, James Wright, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IREC/NMSK - Neuro-musculo-skeletal Lab, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anesthésiologie, UCL - (SLuc) Service d'orthopédie et de traumatologie de l'appareil locomoteur, and UCL - (SLuc) Service de médecine interne générale
Subjects: Hip Fractures, Nephrology, Humans, Pelvic Bones, Kidney
Abstract: To the Editor: Acute kidney injury (AKI) is a lesser-known complication of hip fracture that may come about owing to decreased kidney perfusion and heightened inflammation from trauma, pain, bleeding, and fasting. Approximately 15%-20% of patients undergoing surgery for a hip fracture develop AKI, with 0.5%-1.8% receiving dialysis. [...]
Published: 2022

22. Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis

Author: Claire Grange, Jean-Christophe Lega, Boun Kim Tan, Laurent Bertoletti, Yesim Dargaud, Marion Douplat, Sabine Mainbourg, Steeve Provencher, Hervé Lobbes, Arnaud Friggeri, Hospices Civils de Lyon (HCL), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), and Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, pulmonary embolism, Coronavirus disease 2019 (COVID-19), Critical Care, Deep vein, [SDV]Life Sciences [q-bio], Prevalence, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Thromboembolism, medicine, Humans, 030212 general & internal medicine, business.industry, COVID-19, medicine.disease, Intensive care unit, Thrombosis, 3. Good health, Pulmonary embolism, Hospitalization, medicine.anatomical_structure, Meta-analysis, viral infection, business, Venous thromboembolism
Abstract: BackgroundThe prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.MethodsIn this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020.ResultsWe analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteractioninteraction=0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates.ConclusionsPatients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.
Published: 2021

23. Trends in the proportion of resistant bacteria involved in ventilator-associated pneumonia as the first hospital-acquired infection in intensive care units between 2003 and 2016 in Lyon, France

Author: Arnaud Friggeri, C. Dananché, Jordan Teoli, Elodie Munier-Marion, Alain Lepape, Philippe Vanhems, Violette Zorio, Claude Guérin, Olivier Dauwalder, Céline Monard, Marie-Paule Gustin, Catherine-Cécile Mauranne, Solweig Gerbier-Colomban, Sophie Arnal, Thomas Rimmelé, Laurent Argaud, Sélilah Amour, Service d'Hygiène, Épidémiologie, Infectiovigilance et Prévention [HCL, Lyon] (SHEIP), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Staphylocoques, Hôpital de la Croix-Rousse [CHU - HCL], 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), Hôpital Edouard Herriot [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: Adult, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Hospital-acquired infection, medicine, Humans, Intensive care unit, 030212 general & internal medicine, 0303 health sciences, Cross Infection, Bacteria, Multidrug resistant bacteria, 030306 microbiology, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Ventilator-associated pneumonia, Pneumonia, Ventilator-Associated, medicine.disease, bacterial infections and mycoses, Hospitals, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], Pneumonia, Resistant bacteria, Intensive Care Units, Infectious Diseases, Emergency medicine, business
Abstract: International audience; The aim of this study was to describe the proportion of multidrug-resistant microorganisms (MDROs) involved in ventilator-associated pneumonia (VAP) as the first hospital-acquired infection in 536 adults with restricted risk factors for MDRO-related infection. We found a significant decrease in the percentage of MDROs involved in VAP between 2003 and 2016 and this percentage increased when VAP occurred after day 10.
Published: 2021

24. A new simplified and accurate sa-SOFA score

Author: Vincent Piriou, Martin Cour, Frédéric Aubrun, Bernard Allaouchiche, Julien Bohé, Jean Iwaz, Arnaud Friggeri, Fabienne Venet, Laurent Argaud, Alain Lepape, Delphine Maucort-Boulch, Charles-Hervé Vacheron, Thomas Rimmelé, Alexandre Pachot, Guillaume Monneret, 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), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hopital Civil, Hospices Civils de Lyon (HCL), Laboratoire d'Immunologie, Hôpital Edouard Herriot [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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-Institut National de la Recherche Agronomique (INRA), Hôpital de la Croix-Rousse [CHU - HCL], Service d'Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, parent, Service de Réanimation (Nord), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Organ Dysfunction Scores, health services administration, Statistics, Medicine, Humans, 030212 general & internal medicine, p-value, Prospective Studies, Mortality, SOFA score, Organ dysfunction scores, Aged, Retrospective Studies, Inflammation, Intensive care units, Receiver operating characteristic, Sequential organ failure assessment, business.industry, Reproducibility of Results, 030208 emergency & critical care medicine, Middle Aged, Prognosis, Systemic Inflammatory Response Syndrome, respiratory tract diseases, ROC Curve, Area Under Curve, Regression Analysis, Female, business
Abstract: Purpose Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score. Methods The study grouped four prospective cohorts (2005–2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves. Results Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712–0.768] and 0.687 [0.656–0.717], respectively (p-value of DeLong test Conclusion Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality.
Published: 2019

25. Determinants of amikacin first peak concentration in critically ill patients

Author: Frédéric Marçon, Lucie Marry, Julien Bohé, S. Ledochowski, Arnaud Friggeri, Laurent Bourguignon, Hervé Dupont, Sylvain Goutelle, Clément Boidin, Alain Lepape, Aurore Roussey-Jean, Sejad Torkmani, Nacim Ammenouche, Bernard Allaouchiche, Sophie Jenck, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, 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), Molécules bioactives et chimie médicinale (B2MC), Université de Lyon-Université de Lyon, CHU Amiens-Picardie, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Critical Illness, 030106 microbiology, Cmax, Renal function, Microbial Sensitivity Tests, Logistic regression, Gastroenterology, 03 medical and health sciences, Pharmacokinetics, Intensive care, Internal medicine, amikacin, pharmacodynamics, Medicine, Humans, Pharmacology (medical), Retrospective Studies, intensive care, Pharmacology, business.industry, Middle Aged, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Intensive Care Units, Amikacin, Pharmacodynamics, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Lean body mass, Regression Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, human activities, pharmacokinetics, medicine.drug
Abstract: International audience; Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (Cmax ) to the minimum inhibitory concentration. A target Cmax >= 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of Cmax >= 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on Cmax target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean Cmax in the 339 patients was 73.0 \textpm 23.9 mg/L, with a target attainment rate (TAR, Cmax >= 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW >= 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of Cmax . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose >= 37.8 mg/kg of LBW should be used to optimize the attainment of Cmax >= 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.
Published: 2018

26. Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study

Author: Thomas Rimmelé, Bernard Floccard, Frédéric Aubrun, Fabienne Venet, Delphine Maucort-Boulch, Julien Textoris, Martin Cour, Estelle Peronnet, Guillaume Monneret, Bernard Allaouchiche, Marie-Angélique Cazalis, Laurent Argaud, Julien Bohé, Hélène Vallin, Stéphane Morisset, Vincent Piriou, Alain Lepape, Arnaud Friggeri, Fabrice Thiollière, Alexandre Pachot, Véronique Barbalat, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire d'Immunologie, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hôpital Edouard Herriot [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon, Health Service and Performance Research (HESPER), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Service de Biostatistiques [Lyon], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Cross-infections, Original, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, law.invention, fluids and secretions, 0302 clinical medicine, law, Cumulative incidence, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cross Infection, Reverse Transcriptase Polymerase Chain Reaction, Incidence, Intensive care unit, female genital diseases and pregnancy complications, Interleukin-10, 3. Good health, Hospitalization, Intensive Care Units, Interleukin 10, embryonic structures, Biomarker (medicine), Female, Cohort study, Adult, medicine.medical_specialty, Risk Assessment, Sepsis, 03 medical and health sciences, Anesthesiology, Internal medicine, medicine, Humans, RNA, Messenger, Intensive care medicine, Immune monitoring, business.industry, Histocompatibility Antigens Class II, 030208 emergency & critical care medicine, medicine.disease, Confidence interval, Antigens, Differentiation, B-Lymphocyte, Gene Expression Regulation, CD74, business, Biomarkers, IL10
Abstract: Purpose Intensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients. Methods ICU patients were prospectively enrolled in a multicenter cohort study. Whole blood was collected on the day of admission (D1) and on day 3 (D3) and day 6 (D6) after admission. Patients were screened daily for IAI occurrence and data were censored after IAI diagnosis. mRNA expression levels of biomarkers were measured using RT-qPCR. Fine and Gray competing risk models were used to assess the association between gene expression and IAI occurrence. Results A total of 725 patients were analyzed. At least one IAI episode occurred in 137 patients (19%). After adjustment for shock and sepsis status at admission, CD74 and IL10 levels were found to be significantly associated with IAI occurrence [subdistribution hazard ratio (95% confidence interval) 0.67 (0.46–0.97) for CD74 D3/D1 expression ratio and 2.21 (1.63–3.00) for IL10 at D3]. IAI cumulative incidence was significantly different between groups stratified according to CD74 or IL10 expression (Gray tests p
Published: 2017

27. Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients

Author: Bernard Floccard, Julien Bohé, Julien Textoris, Fabienne Venet, Sophie Blein, Mathieu Page, Laurent Argaud, Stéphane Morisset, Olivier Martin, Oriane Fontaine-Kesteloot, Guillaume Monneret, Marie-Angélique Cazalis, Thomas Rimmelé, Arnaud Friggeri, Alain Lepape, Delphine Maucort-Boulch, Vincent Piriou, Hélène Vallin, Bernard Allaouchiche, Alexandre Pachot, Martin Cour, Zoé Schmitt, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Pathology, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, law.invention, Cohort Studies, 0302 clinical medicine, law, Risk Factors, Hospital Mortality, Prospective Studies, Survivors, Simplified Acute Physiology Score, Prospective cohort study, Aged, 80 and over, Middle Aged, Prognosis, Intensive care unit, Shock, Septic, Systemic Inflammatory Response Syndrome, 3. Good health, Intensive Care Units, Cohort, Biomarker (medicine), Female, France, Cohort study, medicine.medical_specialty, Critical Illness, CX3C Chemokine Receptor 1, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Internal medicine, medicine, Humans, CX3CR1 mRNA, RNA, Messenger, Mortality, Transcriptomics, Aged, business.industry, Septic shock, Research, 030208 emergency & critical care medicine, Biomarker, Length of Stay, medicine.disease, Systemic inflammatory response syndrome, 030104 developmental biology, Logistic Models, ROC Curve, business, Immunosuppression, Biomarkers
Abstract: Background Chemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients. Methods We performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion. Results In ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19–3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45–3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32–5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72–9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index. Conclusions This study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1362-x) contains supplementary material, which is available to authorized users.
Published: 2016

28. Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis

Author: Bastian Nucci, Laurent Muller, Haroun Knani, Jason A. Roberts, Arnaud Friggeri, Jean-Philippe Lavigne, Bernard Allaouchiche, Jean-Yves Lefrant, Alexandre Evrard, Claire Roger, Benjamin Louart, 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), 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), Laboratoire de Biochimie [CHRU Nîmes], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and University of Queensland [Brisbane]
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, Serum, Icu patients, Critical Illness, 030106 microbiology, Cmax, Microbial Sensitivity Tests, Sepsis, 03 medical and health sciences, Young Adult, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Pharmacology (medical), Amikacin, Severe sepsis, Aged, Pharmacology, Aged, 80 and over, Critically ill, business.industry, Serum concentration, Middle Aged, medicine.disease, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Anesthesia, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Gentamicin, Administration, Intravenous, Female, France, Gentamicins, business, medicine.drug
Abstract: International audience; OBJECTIVES:Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis.PATIENTS AND METHODS:Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured.RESULTS:Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction.CONCLUSIONS:In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients.
Published: 2016

29. Complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis: Risk factors for ICU admission and morbidity prognostic score

Author: Florent Wallet, N. Sens, Guillaume Passot, S. Malfroy, Arnaud Friggeri, Olivier Glehen, Vincent Piriou, Laurent Chardonnal, Delphine Maucort-Boulch, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 03 medical and health sciences, Peritoneal Neoplasm, Postoperative Complications, 0302 clinical medicine, Risk Factors, Peritonectomy, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Adverse effect, Peritoneal Neoplasms, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Retrospective Studies, business.industry, Septic shock, Retrospective cohort study, Cytoreduction Surgical Procedures, Hyperthermia, Induced, Perioperative, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Intensive Care Units, Oncology, Chemotherapy, Cancer, Regional Perfusion, 030220 oncology & carcinogenesis, Anesthesia, Peritoneal Cancer Index, Female, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, Morbidity, business, Follow-Up Studies
Abstract: Background and objectives For patients suffering from peritoneal carcinomatosis, cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the only curative option. We focused on severe complications in the postoperative course of HIPEC. Methods We studied perioperative data from patients who underwent HIPEC between January 2010 and August 2011. Our primary objective was to identify perioperative risk factors for ICU admission. Our secondary objective was to identify patient that may be re-admitted to the ICU thanks to a prognostic score. Results 122 patients underwent HIPEC. 32 presented severe adverse events (26.2%) and 7 died (5.7%). Reasons for ICU admission were septic shock in 28.1% of patients, hemorrhagic shock for 21.9%, hemodynamic instability for 15.6%, respiratory causes for 6.2% and post-operative acidosis for 6.2%. Vasopressors were required for 34% and 40.6% were mechanically ventilated. Conclusion Peritoneal cancer index, diaphragmatic peritonectomy, the need of vasopressive therapy, total volume of fluid leakage collected in drains and total volume of fluid therapy administered at day 1 reported on ideal body weight were the 5 significant variables that we combined to build a morbidity prognostic score. One patient over 4 is likely to present severe complications. A predictive morbidity score provide informative data for clinicians.
Published: 2016

30. Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial

Author: Dorothée Balayn, Jean-Christophe Lucet, Florent Wallet, Lila Bouadma, Stéphane Ruckly, Bertrand Souweine, Serge Alfandari, Alain Mercat, Arnaud Friggeri, Jean-François Timsit, Nicolas Allou, Julien Pascal, Sigismond Lasocki, Olivier Mimoz, Véronique Goudet, Alain Lepape, Thomas Kerforne, Service d'anesthésie réanimation [Poitiers], 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), Hôpital Bichat - Claude Bernard, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Unité de Soins Intensifs Médicaux, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Pôle d'Anesthésie Réanimation, Service des maladies infectieuses, Hospices Civils de Lyon, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation (Nord), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA)
Subjects: Male, medicine.medical_specialty, Catheterization, Central Venous, medicine.drug_class, [SDV]Life Sciences [q-bio], Population, Antisepsis, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Catheters, Indwelling, Antiseptic, Randomized controlled trial, law, Catheterization, Peripheral, Medicine, Humans, 030212 general & internal medicine, Adverse effect, education, Povidone-Iodine, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, Catheter insertion, Ethanol, business.industry, Chlorhexidine, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Surgery, Discontinuation, Catheter, Intensive Care Units, Treatment Outcome, Catheter-Related Infections, Anti-Infective Agents, Local, Drug Therapy, Combination, Female, business, Vascular Access Devices, medicine.drug
Abstract: Summary Background Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine–alcohol would be more effective than povidone iodine–alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. Methods In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine–70% isopropyl alcohol (chlorhexidine–alcohol) or 5% povidone iodine–69% ethanol (povidone iodine–alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine–alcohol versus povidone iodine–alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. Findings Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine–alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine–alcohol (580 patients with scrubbing, 588 without). Chlorhexidine–alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine–alcohol; hazard ratio 0·15, 95% CI 0·05–0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine–alcohol (27 [3%] patients vs seven [1%] with povidone iodine–alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. Interpretation For skin antisepsis, chlorhexidine–alcohol provides greater protection against short-term catheter-related infections than does povidone iodine–alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. Funding University Hospital of Poitiers, CareFusion.
Published: 2015

31. Practices of end-of-life decisions in 66 southern French ICUs 4years after an official legal framework: A 1-day audit

Author: Samir Jaber, Pierre Bouzat, Bernard Allaouchiche, B Ragonnet, Jean-Yves Lefrant, J. Morel, Emmanuel Futier, Thomas Rimmelé, Nicolas Molinari, Arnaud Friggeri, Stein Silva, Jean-Michel Constantin, Olivier Desebbe, Carole Ichai, Boris Jung, Marc Leone, Jean Christophe Orban, Claire Roger, 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), Hémostase, Inflammation et sepsis (EA 4609), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Réanimation Médico-Chirurgicale, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'anesthésiologie et de soins intensifs, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Hospices Civils de Lyon, Service d’Anesthésie Réanimation, ANTE-INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service d'anesthésie-réanimation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon, Service d’Anesthésie et de Réanimation, Service de Réanimation, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Service de réanimation, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital St Roch, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), 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)-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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), MORNET, Dominique, Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-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), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Hémostase, Inflammation et sepsis, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-VetAgro Sup ( VAS ), Institut Montpelliérain Alexander Grothendieck ( IMAG ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Département anesthésie et réanimation, CHU Clermont-Ferrand-Hôpital d'Estaing, Hospices Civils de Lyon ( HCL ) -Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon ( HCL ), Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Service d'anesthésie-réanimation, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon-Hôpital Michallon, Hospices Civils de Lyon ( HCL ) -Hôpital E. Herriot, CHU Nice-Hôpital St Roch, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes ( URMITE ), 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 ) -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 ), and Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS )
Subjects: Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Clinical Decision-Making, withdrawing, Legislation, end-of-life, Audit, Critical Care and Intensive Care Medicine, 03 medical and health sciences, family communication, 0302 clinical medicine, Intensive care, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Aged, withholding, Withholding Treatment, Clinical Audit, [ SDV ] Life Sciences [q-bio], business.industry, Medical record, 030208 emergency & critical care medicine, General Medicine, Middle Aged, humanities, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Anesthesiology and Pain Medicine, SAPS II, Family medicine, Life support, Observational study, Female, France, Guideline Adherence, business, Advance Directives
Abstract: International audience; Since the implementation of two French laws in 2002 and 2005 and the implementation of guidelines about End-of-Life (EoL) decisions, few studies concerning EoL practices in French intensive care units (ICUs) have been reported. This study was aimed at assessing compliance with recommendations and current legislation concerning EoL decisions. Prospective observational study based on 1-day audit conducted from January to May 2009 in 66 southern French ICUs. Six hundred and twenty-five patients were included (median age: 63 [52-76] years, median SAPS II: 46 [34-58]). The written designation of a surrogate decision-maker was reported for 87 (15%) patients. Advance directives were completed for only 4% of patients. The EoL decision-making process consisted in a multidisciplinary approach for 99 (47%) patients and was recorded in the medical chart for 63 (64%) cases. Families were informed about medical decisions in 58% of cases. This proportion was higher (87%) if a decision to forego life-sustaining therapy was made. EoL decisions consisted of withholding treatments for 72 (94%) patients and withdrawal of treatments for 5 (6%) patients. In the multivariate stepwise logistic regression, four variables were independently associated with a decision to forego life support: preexisting dependence on others (P
Published: 2015

32. Putative invasive pulmonary aspergillosis in critically ill patients with chronic obstructive pulmonary disease: a matched cohort study

Author: Oana Dumitrescu, Rodrigue Dessein, Florent Wallet, Arnaud Friggeri, Marion Le Maréchal, Laurent Argaud, Thomas Rimmelé, Aurélie Cottereau, Anne-Lise Bienvenu, Claire Delsuc, Florence Ader, Emilie Fréalle, Sophie Jarraud, Saad Nseir, Pillet, Lauriane, Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département Anesthésie-Réanimation, Hôpital Roger Salengro, CHRU de Lille, Hôpital Roger Salengro, CHRU de Lille, Lille, France, Laboratoire de Parasitologie et de Mycologie médicale [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de parasitologie et mycologie médicale [Hôpital de la Croix Rousse, Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Laboratoire de Bacteriologie [CHRU Lille], Département de Microbiologie Clinique [HCL Groupement Hospitalier Nord, Lyon], Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Faculté de Médecine Henri Warembourg - Université de Lille, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, Université de Lille, Recherche translationnelle : relations hôte-pathogènes - EA 7366, Lille Inflammation Research International Center (LIRIC) - U995, 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 Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon] [CNR - laboratoire associé], Recherche translationelle relations hôte-pathogènes, Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS], Maladies chroniques, santé perçue, et processus d'adaptation [APEMAC], Lille Inflammation Research International Center - U 995 [LIRIC], Université Lille 2 - Faculté de Médecine, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Mesh:Invasive Pulmonary Aspergillosis/mortality, Mesh:Prognosis, Critical Care and Intensive Care Medicine, outcomes, Cohort Studies, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Mesh:Critical Illness/therapy, Risk Factors, Mesh:Risk Factors, 030212 general & internal medicine, Mesh:Aged, fungal-infections, Aged, 80 and over, Invasive Pulmonary Aspergillosis, Mesh:Chronic Obstructive/mortality, 0303 health sciences, COPD, pseudomonas-aeruginosa, Mesh:Chronic Obstructive/microbiology, Middle Aged, Prognosis, Mesh:Intensive Care Units, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, medicine.anatomical_structure, clinical-features, Female, Allergic bronchopulmonary aspergillosis, Cohort study, Mesh:Female, medicine.medical_specialty, Critical Illness, Mesh:Chronic Obstructive/complications, Pulmonary disease, Mesh:Male, 03 medical and health sciences, Mesh:Retrospective Studies, General & Internal Medicine, Mesh:Middle Aged, Mesh:80 and over, medicine, Humans, Mesh:Cohort Studies, Intensive care medicine, Aged, Retrospective Studies, Mesh:Invasive Pulmonary Aspergillosis/etiology, 030306 microbiology, business.industry, Critically ill, Research, Retrospective cohort study, Mesh:Antifungal Agents/therapeutic use, Mesh:Invasive Pulmonary Aspergillosis/diagnosis, fumigatus, Invasive pulmonary aspergillosis, medicine.disease, Mesh:Pulmonary Disease, Mesh:Humans, biofilms, business, Respiratory tract
Abstract: Introduction Patients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA. Methods This matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed. Results Fifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p p p = 0.004 and p Conclusions PIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal.
Published: 2015

33. Exposure to Hydrogen Peroxide Induces Oxidation and Activation of AMP-activated Protein Kinase

Author: Jaroslaw W. Zmijewski, Sami Banerjee, Arnaud Friggeri, Edward Abraham, Hong-Beom Bae, and Eduardo R. Lazarowski
Subjects: Oxidative phosphorylation, AMP-Activated Protein Kinases, Biochemistry, Cell Line, Acatalasia, Mice, chemistry.chemical_compound, Adenosine Triphosphate, AMP-activated protein kinase, Catalytic Domain, Animals, Humans, Enzyme Inhibitors, Kinase activity, Protein kinase A, Molecular Biology, Amitrole, biology, Kinase, AMPK, Hydrogen Peroxide, Cell Biology, Catalase, Oxidants, Glutathione, Adenosine Monophosphate, Cell biology, chemistry, Enzyme Induction, Mutation, biology.protein, Oxidation-Reduction, Protein Processing, Post-Translational, Adenosine triphosphate
Abstract: Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5'-adenosine monophosphate-activated protein kinase (AMPK), a number of recent studies have shown that increased intracellular levels of reactive oxygen species can stimulate AMPK activity, even without a decrease in cellular levels of ATP. We found that exposure of recombinant AMPKαβγ complex or HEK 293 cells to H(2)O(2) was associated with increased kinase activity and also resulted in oxidative modification of AMPK, including S-glutathionylation of the AMPKα and AMPKβ subunits. In experiments using C-terminal truncation mutants of AMPKα (amino acids 1-312), we found that mutation of cysteine 299 to alanine diminished the ability of H(2)O(2) to induce kinase activation, and mutation of cysteine 304 to alanine totally abrogated the enhancing effect of H(2)O(2) on kinase activity. Similar to the results obtained with H(2)O(2)-treated HEK 293 cells, activation and S-glutathionylation of the AMPKα subunit were present in the lungs of acatalasemic mice or mice treated with the catalase inhibitor aminotriazole, conditions in which intracellular steady state levels of H(2)O(2) are increased. These results demonstrate that physiologically relevant concentrations of H(2)O(2) can activate AMPK through oxidative modification of the AMPKα subunit. The present findings also imply that AMPK activation, in addition to being a response to alterations in intracellular metabolic pathways, is directly influenced by cellular redox status.
Published: 2010
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34. miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses

Author: Arnaud Friggeri, Yanping Yang, Yuko Tsuruta, Edward Abraham, Gang Liu, and Young-Jun Park
Subjects: Lipopolysaccharides, Inflammation, Stimulation, Biology, Cell Line, Mice, microRNA, Macrophages, Alveolar, medicine, Animals, Humans, Receptor, Promoter Regions, Genetic, Feedback, Physiological, Mice, Knockout, Gene knockdown, Toll-like receptor, Multidisciplinary, Macrophages, Toll-Like Receptors, Biological Sciences, Cell biology, Up-Regulation, Mice, Inbred C57BL, Toll-Like Receptor 4, TLR2, MicroRNAs, TLR4, medicine.symptom
Abstract: Toll-like receptors (TLRs) are major receptors that enable inflammatory cells to recognize invading microbial pathogens. MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes. In this study, we found that a microRNA, miR-147, was induced upon stimulation of multiple TLRs and functioned as a negative regulator of TLR-associated signaling events in murine macrophages. We first demonstrated that the NMES1 transcript was a functional primary miR-147. miR-147 was induced in LPS-stimulated mouse macrophages and under in vivo conditions in the lungs of LPS-treated mice. Expression of miR-147 was greater after cellular activation by TLR4 than after engagement of either TLR2 or TLR3, suggesting that maximal induction of miR-147 required activation of both NF-κB and IRF3. TLR4-induced miR-147 expression was both MyD88- and TRIF-dependent. The miR-147 promoter was responsive to TLR4 stimulation and both NF-κB and STAT1α bound to the miR-147 promoter. miR-147 mimics or induced expression of miR-147 decreased, whereas miR-147 knockdown increased inflammatory cytokine expression in macrophages stimulated with ligands to TLR2, TLR3, and TLR4. These data demonstrate a negative-feedback loop in which TLR stimulation induces miR-147 to prevent excessive inflammatory responses.
Published: 2009

35. 3,4-Diaminopyridine may improve neuromuscular block during botulism

Author: Mélanie Levrard, Frédéric Marçon, Abdoul Aziz Seydi, Arnaud Friggeri, Hervé Dupont, François Tinturier, Michel Petitjean, Anne-Sophie Lemaire-Hurtel, Yazine Mahjoub, Norik Airapetian, Nacim Ammenouche, and Sandra Marciniak
Subjects: Mechanical ventilation, Letter, business.industry, Electromyography, medicine.medical_treatment, 3,4-diaminopyridine, Context (language use), Botulism, Food-borne diseases, Critical Care and Intensive Care Medicine, medicine.disease, Spontaneous breathing trial, Compound muscle action potential, Respiratory failure, Anesthesia, Adjunctive treatment, Paralysis, medicine, medicine.symptom, business
Abstract: In September 2011, two outbreaks of botulism toxemia (toxin A) incriminating the same artisanal product were responsible for nine cases of botulism in France. Among these cases, three women (Cases 1, 2, and 3) aged 27, 29, and 23 years, respectively, were hospitalized in our ICU for mechanical ventilation support. They rapidly received a trivalent botulism antitoxin serum. Two weeks later, Case 3 passed a spontaneous breathing trial but needed new ventilator support 24 hours after extubation. Association between respiratory failure and low compound muscle action potential (CMAP) amplitude measured at the forearm was reported in a study performed during a large outbreak in 2006 in Thailand [1]. CMAPs measured in the current Case 3 at the time of reintubation were
Published: 2013

36. Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

Author: Julie Demaret, Elisabeth Cerrato, Véronique Barbalat, Arnaud Friggeri, Alain Lepape, Guillaume Monneret, Marie-Angélique Cazalis, Fabienne Venet, Alexandre Pachot, and Laura Cavé
Subjects: Male, medicine.medical_specialty, CD74, Critical Care and Intensive Care Medicine, Gastroenterology, Sepsis, Antigens, CD, Internal medicine, Intensive care, medicine, Humans, Hospital Mortality, RNA, Messenger, Survival analysis, Aged, Septic shock, business.industry, Research, Histocompatibility Antigens Class II, HLA-DR Antigens, Middle Aged, medicine.disease, Shock, Septic, Confidence interval, Antigens, Differentiation, B-Lymphocyte, Log-rank test, Immunology, Biomarker (medicine), Female, business, Biomarkers
Abstract: Introduction Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients. Methods A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry. Results A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8). Conclusion Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients.
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37. Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial

Author: Bohé, Julien, Abidi, Hassane, Brunot, Vincent, Klich, Amna, Klouche, Kada, Sedillot, Nicholas, Tchenio, Xavier, Quenot, Jean-Pierre, Roudaut, Jean-Baptiste, Mottard, Nicolas, Thiollière, Fabrice, Dellamonica, Jean, Wallet, Florent, Souweine, Bertrand, Lautrette, Alexandre, Preiser, Jean-Charles, Timsit, Jean-François, Vacheron, Charles-Hervé, Ait Hssain, Ali, Maucort-Boulch, Delphine, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation de Coopération Scientifique Bourgogne Franche-Comté (FCS Bourgogne Franche-Comté), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital l'Archet, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université libre de Bruxelles (ULB), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), CONTROLe INdividualisé de la Glycémie (CONTROLING) Study Group: Aurèle Buzancais, Anne Marie Dupuy, Rémi Bruyère, Henri de Montclos, Marion Provent, Jocelyne Drai, Joëlle Goudable, Anne Mialon, Bernard Allaouchiche, Arnaud Friggeri, Véréna Landel, Hélène Boyer, Hervé Hyvernat, Céline Caruba-Bafghi, Edouard Soum, Christophe Leroy, Laurence Roszyk, Pierre Eric Danin, Julio Badie, Stefan Georgiev, Martine Laplace, Richard Jospe, Jérôme Morel, Ali Mofredj, Abdelbaki Azaouzi, Jean-Paul Aubry, Abdelhamid Fatah, Stanislas Ledochowski, Sabine Zaepfel, Eric Fontaine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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, École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Service de Biostatistiques [Lyon], and MORNET, Dominique
Subjects: [SDV] Life Sciences [q-bio], Glycated haemoglobin A1c, [SDV]Life Sciences [q-bio], Glucose control, Individualised glucose control, Hyperglycaemia, Insulin
Abstract: International audience; Purpose: Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient's pre-admission usual glycaemia, could improve outcome.Methods: In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.Results: Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018).Conclusion: Targeting an ICU patient's pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.
Published: 2021

38. Negative-Pressure Wound Therapy for Open Abdomen in Surgical Reintervention after Curative Surgery of Peritoneal Malignancy Increases the Risk of Recurrence.

Author: Rabel T, Bonnot PE, Hadeedi O, Kepenekian V, Bernard L, Friggeri A, Glehen O, and Passot G
Subjects: Humans, Combined Modality Therapy, Abdomen surgery, Cytoreduction Surgical Procedures adverse effects, Cytoreduction Surgical Procedures methods, Retrospective Studies, Peritoneal Neoplasms surgery, Peritoneal Neoplasms pathology, Negative-Pressure Wound Therapy, Hyperthermia, Induced
Abstract: Objective: Negative-pressure wound therapy for open abdomen (NPWTOA) helps reduce the risk of abdominal compartment syndrome. However, the risk of recurrence of cancer is unclear when NPWTOA is applied after oncologic resection. The aim of this study was to evaluate the effects of NPWTOA used for major complications on patients treated with cytoreductive surgery for peritoneal malignancy (PM)., Methods: All patients who underwent an NPWTOA after potentially curative surgery of PM in a single institution were included. These patients were pair matched 1:3 on the Peritoneal Cancer Index, completeness of cytoreduction using a scoring index, and PM origin with patients who underwent surgical reintervention without NPWTOA after curative surgery of PM. Survival among the two groups was compared using the Kaplan-Meier method., Results: Between 2011 and 2017, among 719 curative surgeries for PM, 13 patients underwent an NPWTOA after surgical reintervention. Researchers paired 9 of these patients to 27 others without NPWTOA after surgical reintervention. Median overall survival was 4.8 and 35 months (P = .391), and median disease-free survival was 4.0 and 13.9 months (P = .022) for the NPWTOA and non-NPWTOA groups, respectively., Conclusions: The use of the NPWTOA during surgical reintervention after curative surgery for PM may increase the risk of early recurrence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2023
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