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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. Multitasking in postanesthesia care unit following nurse interruptions, an analysis of the causes and consequences using classification tree: an observational prospective study

Author: Pascal Incagnoli, Arnaud Friggeri, Alexandre Theissen, Virginie Charra, Jean-Stéphane David, Stéphanie Parat, Charles-Hervé Vacheron, Vincent Piriou, and Olivier Peyrouset
Subjects: Task switching, biology, business.industry, Workload, General Medicine, biology.organism_classification, Pacu, Task (project management), 03 medical and health sciences, Patient safety, 0302 clinical medicine, Nursing, 030202 anesthesiology, Human multitasking, Medicine, Observational study, Prospective cohort study, business
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

21. Effect of SARS-CoV-2 infection and pandemic period on healthcare-associated infections acquired in intensive care units

Author: Alain, Lepape, Anaïs, Machut, Cedric, Bretonnière, Arnaud, Friggeri, Charles-Hervé, Vacheron, and Anne, Savey
Subjects: Microbiology (medical), Infectious Diseases, General Medicine
Abstract: To compare the occurrence of healthcare-associated infections acquired in intensive care units (HAI-ICUs) in France among patients with COVID-19 and those without it in 2020 and the latter with that in patients before the COVID-19 pandemic.Multicentre HAI-ICU surveillance network (REA-REZO) data were used to identify 3 groups: 2019 patients (2019Control), a COVID-19 group (2020Cov), and a non-COVID-19 group (2020NonCov). The primary outcome was the occurrence of HAI-ICU (ventilator-associated pneumonia [VAP], bloodstream infections [BSIs], catheter-related bacteraemia). Standardized infection ratios of VAP were calculated for each quarter in 2020 and compared with those in 2019.A total of 30 105 patients were included in 2020: 23 798 in the 2020NonCov group, 4465 in 2020Cov group, and 39 635 patients in the 2019Control group. The frequency of VAP was strikingly greater in the 2020Cov group: 35.6 (33.4-37.8) episodes/1000 days of mechanical ventilation versus 18.4 (17.6-19.2) in the 2020NonCov group. VAP standardized infection ratio was high in 2020 patients, particularly during the 2 quarters corresponding to the 2 waves. BSI/1000 days were more frequent in the 2020Cov group (6.4% [6.4-6.4%] vs. 3.9% [3.8-3.9%] in the 2020NonCov group). VAP and BSI were also more frequent in the 2020NonCov group than in the 2019Control group. The microbial epidemiology was only slightly different.The data presented here indicate that HAI-ICUs were more frequent during the COVID-19 period, whether the patients were admitted for COVID-19 or, to a lesser extent, for another cause. This implies that managing patients with severe disease in a pandemic context carries risks for all patients.
Published: 2023

22. Outcome in Multiple Myeloma Patients Treated in the Era of Modern Therapies Who Were Admitted to Intensive Care: A Retrospective Analysis from a Teaching Hospital between 2014 and 2019

Author: Zofia Gross, Maryam Idlhaj, Lionel Karlin, Arnaud Friggeri, Anne Lazareth, Camille Golfier, Helene Lequeu, Fadhela Bouafia Sauvy, Pierre Sesques, Violaine Safar, Emmanuelle Ferrant, Dana Ghergus, Alizee Maarek, Guillaume Aussedat, Gilles Salles, Emmanuel Bachy, Florent Wallet, and Herve Ghesquieres
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

23. 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

24. Association Between Short-, Intermediate-, and Long-term Mortality and Myocardial Injury After Noncardiac Surgery After Hip Fracture Surgery: A Retrospective Cohort

Author: Vincent Piriou, Pascal Incagnoli, Arnaud Friggeri, Jean Stephane David, Charles-Hervé Vacheron, Verena Landel, Julie Hentzen, Michel Fessy, Philippe Chaudier, and Mathieu Fauvernier
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Time Factors, Heart Diseases, Population, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Fracture Fixation, Risk Factors, 030202 anesthesiology, Internal medicine, Risk of mortality, Humans, Medicine, education, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Hip fracture, Hip Fractures, business.industry, Proportional hazards model, Myocardium, Hazard ratio, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Troponin, Up-Regulation, Treatment Outcome, Anesthesiology and Pain Medicine, Cardiology, Female, France, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: BACKGROUND For more than 20 years, hip fracture 1-year mortality has remained around 20%. An elevation of the postoperative troponin peak within 72 hours (myocardial injury after noncardiac surgery [MINS]) is associated with a greater risk of short-term mortality in the general population. However, there seem to be conflicting results in the specific population who undergo hip fracture surgery, with some studies finding an association between troponin and mortality and some not. The objective of the present study was to investigate the association of MINS and the short- (before 28th day), intermediate- (before 180th day), and long-term (before 365th day) mortality after hip fracture surgery. METHODS We conducted a single-center retrospective cohort of patients undergoing hip fracture surgery from November 2013 to December 2015. MINS was defined as postoperative troponin peak within the 72 hours >5 ng/L. Four MINS subgroups were defined according to the value of troponin peak (ie, ≥5
Published: 2021

25. Télémédecine, téléconsultation en médécine périopératoire

Author: Charlotte Ceruti, Clémence Ferrier, Pierre Yves Carry, Vincent Piriou, and Arnaud Friggeri
Subjects: 2019-20 coronavirus outbreak, 020205 medical informatics, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 02 engineering and technology, Emergency Nursing, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Political science, Emergency, 0202 electrical engineering, electronic engineering, information engineering, Emergency Medicine, 030212 general & internal medicine, Humanities
Abstract: Resume La telemedecine est en plein essor dans tous les domaines medicaux. En plus d’etre l’une des priorites de l’OMS afin de repondre aux problemes des couts et de l’accessibilite a des soins de qualite, que ce soit dans les pays developpes ou en voie de developpement, la crise sanitaire recente liee au COVID-19 a montre qu’elle pouvait etre un atout certain pour la permanence des soins en situation de crise. Si la telemedecine en anesthesie se developpe pour l’ensemble de la prise en charge peri-operatoire des patients, cette mise au point vise a presenter les donnees recentes de la litterature concernant la place de la telemedecine en anesthesie pour l’evaluation pre-operatoire. Quatre points principaux sont abordes : (1) l’eligibilite et la faisabilite de la teleconsultation d’anesthesie; (2) son efficacite en terme de temps passe en consultation d’anesthesie, taux d’annulation d’intervention et concordance de l’examen physique; (3) la satisfaction des patients, et enfin; (4) son potentiel impact economique.
Published: 2020

26. 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

27. 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, P, Danin, 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), 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), Hospices Civils de Lyon (HCL), Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-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 universitaire de Nantes (CHU Nantes), Hôpital Edouard Herriot [CHU - HCL], CHU Amiens-Picardie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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 Universitaire [Rennes], Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Pôle de Santé Publique [Lyon], AZUREA Study Group: Laurent Argaud, Bernard Floccard, Thomas Rimmele, Albrice Levrat, Stanislas Ledechowski, Remi Bruyere, Carole Schwebel, Benedicte Zerr, Luc Jarrige, Quentin Blanc, Jerome Morel, Olivier Baldesi, Gaëtan Plantefeve, Philippe Seguin, Claire Dahyot-Fizelier, Michel Bonnivard, J Roustan, S Vimeux, Ali Mofredj, Sami Alaya, Adel Maamar, Julio Badie, Bertrand Souweine, Gerald Choukroun, Oriane Fontaine, Jean Michel Constantin, Marc Gainier, Benoit Misset, Jean Claude Orban, Jean Reignier, Jean-Marc Doise, Olivier Millet, Laurent Favier, Berangere Jany, Ramin Ravan, Delphine Roux, Pierre Marie Bertrand, Nicolas Bele, Stéphanie Malaquin, Pierre Grégoire Guinot, Jean Pierre Quenot, Fanny Bounes, Claude Koubi, P Danin., CarMeN, laboratoire, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Quality of life, Critical Care, [SDV]Life Sciences [q-bio], Aftercare, COVID-19, Critical Care and Intensive Care Medicine, Patient Discharge, [SDV] Life Sciences [q-bio], Intensive Care Units, Outcome Assessment, Health Care, Quality of Life, Humans, Prospective Studies, Autonomy, Aged
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: 2021

28. Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study

Author: Charles-Hervé, Vacheron, Alain, Lepape, Anne, Savey, Anaïs, Machut, Jean Francois, Timsit, Philippe, Vanhems, Quoc Viet, Le, Julia, Egbeola, Maelle, Martin, Virginie, Maxime, Paul-Simon, Pugliesi, Delphine, Maucort-Boulch, Arnaud, Friggeri, and Christine, Venot
Subjects: Male, medicine.medical_specialty, Population, Critical Care and Intensive Care Medicine, Internal medicine, Epidemiology, Drug Resistance, Bacterial, medicine, Humans, Cumulative incidence, Prospective Studies, Simplified Acute Physiology Score, education, Aged, education.field_of_study, business.industry, SARS-CoV-2, Incidence (epidemiology), COVID-19, Pneumonia, Ventilator-Associated, Middle Aged, medicine.disease, Respiration, Artificial, Pneumonia, Intensive Care Units, Cohort, Female, France, business, Cohort study
Abstract: OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network. SETTING: Multicentric; ICUs in France. PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013). CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.
Published: 2021

29. 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

30. The Absence of Rehabilitation During the ICU Stay of Elderly Patients is Associated with a Decreased Long-Term Autonomy

Author: Fabrice Thiolliere, Bernard Allaouchiche, Manon Marie, AZUREA Study group, Arnaud Friggeri, and Charles-Hervé VACHERON
Subjects: medicine.medical_specialty, Rehabilitation, Long term autonomy, business.industry, medicine.medical_treatment, Emergency medicine, medicine, Icu stay, business
Abstract: Background: The intensive care unit (ICU) stay is associated with a loss of autonomy, especially for elderly patients. We therefore conducted a study to estimate the impact of the rehabilitation performed during the ICU stay on the loss of autonomy at 6 months. Methods: We conducted an ancillary study of the multicenter FRAGIREA study, including patients between April 2018 and January 2019 aged over 70 years, admitted in ICU for an expected length of stay of more than 48 hours. We excluded the patients who died before day 180, who were lost to follow-up, and for whom the baseline autonomy (ADL) score was not available. We collected the baseline characteristics of patients, the ICU stay characteristics, and the 6-month follow-up. Were also collected the detailed rehabilitation therapy carried out during the ICU stay (passive mobilization, upright sitting, transfer to chair, standing, walking, and cycle ergometers.). Patients were classified into the rehabilitation (out of bed) or non-rehabilitation group, and the impact of rehabilitation on the decreased 6-month autonomy (loss of ADL score >1 point) was estimated after the selection of 17 potential confounders. Results: Among the 548 patients of the FRAGIREA cohort, 276 were included in the present study. Among them, 226 were rehabilitated and 50 were not. 220/276 (80%) patients benefited from the transfer to chair as rehabilitation therapy, passive mobilization and transfer to upright sitting were also frequently performed. A decrease in the 6-month autonomy was observed for 63 (23%) patients. After the elimination of potential confounders, non-rehabilitated patients had a greater risk of 6-month decreased autonomy (adjusted Odds Ratio 2.43, 95% confidence interval [1.18; 4.98]). Conclusions: Rehabilitation during the ICU stay of elderly ICU patient survivors was associated with a lower decreased autonomy at 6 months. Tweet: The absence of rehabilitation during the ICU stay of elderly patients is associated with 2.4 higher risk of a decreased 6 month autonomy
Published: 2021

31. 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: Claire, Falandry, Amélie, Malapert, Mélanie, Roche, Fabien, Subtil, Julien, Berthiller, Camille, Boin, Justine, Dubreuil, Christine, Ravot, Laurent, Bitker, Paul, Abraham, Vincent, Collange, Baptiste, Balança, Sylvie, Goutte, Céline, Guichon, Emilie, Gadea, Laurent, Argaud, David, Dayde, Laurent, Jallades, Alain, Lepape, Jean-Baptiste, Pialat, Arnaud, Friggeri, Fabrice, Thiollière, Marine, Thieux, 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 Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université de Lyon, 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), Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Médipôle Lyon-Villeurbanne, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de recherche en neurosciences de Lyon (CRNL), 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), L'Hôpital Nord-Ouest [Villefranche sur Saône], Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), Senior-COVID-Rea study Group: Christophe Leroy, Anne-Claire Lukaszewicz, Thomas Rimmelé, Marie Simon, Charles-Hervé Vacheron, Hodane Yonis, Antoine Garnier-Crussard, Max Haïne, Loredana Baboi, Camille Boin, Valérie Cerro, David Dayde, Justine Dubreuil, Carlos El Khoury, Emilie Gadéa-Deschamps, Marie-Catherine Fromont, Audrey Gelot, Anthéa Loïez, Amélie Malapert, Céline Monard, Maya Perrou, Laetitia Paradisi-Prieur, Marion Provent, Mélanie Roche, Gulsum Sahin, Ghyslaine Thao, Marine Thieux., Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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 - 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), CarMeN, laboratoire, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: intensive & critical care, SARS-CoV-2, geriatric medicine, [SDV]Life Sciences [q-bio], Intensive Care, COVID-19, Middle Aged, [SDV] Life Sciences [q-bio], Intensive Care Units, Risk Factors, Surveys and Questionnaires, Prohibitins, Humans, Multicenter Studies as Topic, France, Aged
Abstract: International audience; 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

32. Safety and efficacy of a strategy of vitamin K antagonist reversal with prothrombin complex concentrates compared to vitamin K in patients with hip fracture

Author: Lucille, Jay-Caillierez, Arnaud, Friggeri, Anthony, Viste, Mathilde, Lefevre, Evelyne, Decullier, Lorraine, Bernard, Vincent, Piriou, and Jean-Stéphane, David
Subjects: Aged, 80 and over, Male, Vitamin K, Heparin, Hip Fractures, Research, Anticoagulants, Pilot Projects, Length of Stay, Blood Coagulation Factors, Time-to-Treatment, Case-Control Studies, Humans, Female, Aged, Retrospective Studies
Abstract: Increased preoperative delay in patients with hip fractures may be responsible for increased morbidity and mortality. We hypothesized that a strategy of reversal of vitamin K antagonist (VKA) by prothrombin complexes concentrates (PCCs), as compared to vitamin K, is safe and reduces preoperative delay and hospital length of stay (LOS).In this pilot study, we reviewed the records of patients admitted to a university-affiliated hospital for hip fracture between Jan. 1, 2012, and Dec. 31, 2016, who were taking VKA. Patients were stratified according to reversal strategy (vitamin K v. PCC). Adverse effects, time to surgery, LOS and mortality were collected from the electronic medical record and were compared between the 2 study groups and a control group not treated with VKA.A total of 141 patients were included in the study: 65 in the vitamin K group, 26 in the PCC group and 50 in the control group. The median preoperative delay in the PCC group (20 h [interquartile range (IQR)] 13-25 h]) and the control group (20 h [IQR 15-33 h]) was lower than that in the vitamin K group (45 h [IQR 31-52 h]) (p0.001). Patients in the PCC group had a shorter median hospital LOS than those in the vitamin K group (6 d [IQR 4-9 d] v. 8 d [IQR 6-11 d], p0.05). No difference was observed in the proportion of patients who received a red blood cell transfusion, or had thrombotic or hemorrhagic complications. No difference in mortality at 12 months was observed between the groups.In patients with hip fracture, the use of PCCs as compared to vitamin K to reverse the effect of VKA significantly reduced preoperative delay and hospital LOS, and was not associated with an increase in the rates of thrombotic or hemorrhagic complications. Prospective studies involving a greater number of patients are required to confirm these promising results.L’allongement du délai préopératoire chez les patients atteints d’une fracture de la hanche pourrait expliquer l’augmentation de la morbidité et de la mortalité. Selon notre hypothèse, une stratégie d’inversion des antagonistes de la vitamine K (AVK) au moyen de concentrés de complexes prothrombiques (CCP), plutôt que de vitamine K, est sécuritaire et réduit le délai préopératoire et la durée du séjour hospitalier.Pendant cette étude pilote, nous avons passé en revue les dossiers de patients sous AVK admis dans un centre universitaire pour fracture de la hanche entre le 1er janvier 2012 et le 31 décembre 2016. Les patients ont été stratifiés selon la stratégie d’inversion choisie (vitamine K c. CCP). Les effets indésirables, le délai préopératoire, la durée du séjour hospitalier et la mortalité ont été recueillis à partir des dossiers médicaux électroniques et ont été comparés entre les 2 groupes de l’étude et un groupe témoin non sous AVK.En tout, 141 patients ont été inclus dans l’étude, 65 dans le groupe sous vitamine K, 26 dans le groupe sous CCP et 50 dans le groupe témoin. Le délai préopératoire médian pour le groupe sous CCP (20 h [éventail interquartile (ÉIQ)] 13–25 h]) et le groupe témoin (20 h [ÉIQ 15–33 h]) a été plus bref que pour le groupe sous vitamine K (45 h [ÉIQ 31–52 h]) (p0,001). Les patients du groupe sous CCP ont eu un séjour hospitalier médian plus bref que les patients du groupe sous vitamine K (6 j [ÉIQ 4–9 j] c. 8 j [ÉIQ 6–11 j]) (p0,05). Aucune différence n'a été observée quant à la proportion de patients ayant reçu une transfusion de culot globulaire ou ayant manifesté des complications thrombotiques ou hémorragiques. Aucune différence quant à la mortalité à 12 mois n'a été observée entre les groupes.Chez les patients atteints d’une fracture de la hanche, l’utilisation des CCP plutôt que de la vitamine K pour inverser l’effet des AVK a significativement abrégé le délai préopératoire et la durée du séjour hospitalier, et n’a pas été associée à une augmentation des taux de complications thrombotiques ou hémorragiques. Des études prospectives sur un plus grand nombre de patients sont nécessaires pour confirmer ces résultats prometteurs.
Published: 2021

33. Effects of modification of trauma bleeding management: A before and after study

Author: Pierre-Francois Wey, Cécile Guth, François-Xavier Ageron, Evelyne Decullier, Kenji Inaba, O. Vassal, Arnaud Friggeri, Jean-Stéphane David, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, University of Southern California (USC), Pôle Information Médicale Evaluation Recherche (IMER), and Hospices Civils de Lyon (HCL)
Subjects: business.industry, [SDV]Life Sciences [q-bio], 030208 emergency & critical care medicine, General Medicine, Critical Care and Intensive Care Medicine, University hospital, medicine.disease, Fibrinogen, 03 medical and health sciences, Thromboelastometry, 0302 clinical medicine, Anesthesiology and Pain Medicine, Coagulation, 030202 anesthesiology, Anesthesia, Coagulopathy, medicine, Before and after study, Platelet, business, Tranexamic acid, medicine.drug
Abstract: Objective We hypothesised that the association of tranexamic acid (TXA) administration and thromboelastometry-guided haemostatic therapy (TGHT) with implementation of Damage Control Resuscitation (DCR) reduced blood products (BP) use and massive transfusion (MT). Methods Retrospective comparison of 2 cohorts of trauma patients admitted in a university hospital, before (Period 1) and after implementation of DCR, TXA (first 3-hours) and TGHT (Period 2). Patients were included if they received at least 1 BP (RBC, FFP or platelet) or coagulation factor concentrates (fibrinogen or prothrombin complex) during the first 24-hours following the admission. Results 380 patients were included. Patients in Period 2 (n = 182) received less frequently a MT (8% vs. 33%, P Conclusion Following the implementation of a bundle of care including DCR, TGHT and administration of TXA, we observed a decrease to the use of blood products, need for MT and an improvement of survival.
Published: 2019

34. Réalisation d’un simulateur de trachée avec des outils du bloc opératoire

Author: Vincent Piriou, Charles-Hervé Vacheron, P.-Y. Carry, and Arnaud Friggeri
Subjects: 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Emergency Medicine, 030208 emergency & critical care medicine, Emergency Nursing
Abstract: Resume Les rares situations de « cannot intubate cannot ventilate » necessitent un acces tracheal rapide afin de maintenir une oxygenation, associe ou non a des strategies de ventilation. Cette faible frequence de survenue explique le peu d’experience des praticiens en anesthesie-reanimation a la realisation des techniques de sauvetage. Les mises en situation lors de seances de simulation sur mannequin pourraient pallier cette inexperience. Cependant, la capacite de formation en simulation en France est limitee, pour des raisons d’accessibilite et de cout. Nous vous presentons ici les differentes etapes de realisation d’un simulateur tracheal in situ avec des materiaux exclusivement du bloc operatoire.
Published: 2019

35. Recommandation sur l’anesthésie du sujet âgé : l’exemple de fracture de l’extrémité supérieure du fémur

Author: Frédérique Servin, Serge Molliex, Christelle Mouchoux, Jacques Boddaert, Valérie Billard, Arnaud Friggeri, Nicolas Dufeu, Eric Boulanger, Frédéric Aubrun, Vincent Minville, Jean-Baptiste Beuscart, Matthieu Raux, Pierre Krolak Salmon, Christophe Baillard, Philippe Merloz, Frédéric Khiami, Laure Pain, and Vincent Piriou
Subjects: 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, 030212 general & internal medicine
Abstract: Resume Le vieillissement de la population est associee a une augmentation d’actes chirurgicaux et donc du nombre d’anesthesie generales et locoregionales. A ce titre, la fracture du col femoral concerne plus de 75 000 patients par an et constitue donc un enjeu de sante publique du fait d’une morbi-mortalite non negligeable. Les experts issus de quatre societes savantes, la SFAR, la SOFCOT, la SFGG et la SFPC ont redige 26 recommandations concernant la prise en charge perioperatoire du patient âge en s’interessant plus particulierement a la fracture de l’extremite superieure du femur. Une premiere partie concernait l’evaluation en preoperatoire du risque cardiovasculaire, des fonctions cognitives et de la fonction renale. Les auteurs ont recommande une prise en charge pluridisciplinaire et une gestion preoperatoire rationnelle des traitements afin de reduire le risque de confusion. Le delai d’intervention des FESF a ete fixe a 48 h et les modalites de monitorage precisees (monitorage hemodynamique, de la pression arterielle de l’oxygenation et de la temperature). Une technique d’anesthesie n’a pas ete privilegiee pour la chirurgie de la FESF mais une titration des agents anesthesiques a ete recommandee. Les experts ont egalement recommande la mise en place d’un programme de prevention non medicamenteuse de la confusion postoperatoire ainsi qu’une strategie de gestion des episodes confusionnels postoperatoires tels que l’usage d’une benzodiazepine a demi-vie courte ou d’un neuroleptique de derniere generation. Le bloc femoral ou iliofascial ont ete probablement recommandes en postoperatoire a la difference des infiltrations, peu contributives dans ce type de chirurgie.
Published: 2019

36. Troponin measurement for risk stratification after cytoreductive surgery

Author: Guillaume Passot, Florent Wallet, C.-H. Vacheron, Vincent Piriou, Naoual Bakrin, A. Lambert, Arnaud Friggeri, Delphine Vaudoyer, M. Fauvernier, V. Kepenekian, Olivier Glehen, and Olivia Vassal
Subjects: medicine.medical_specialty, biology, business.industry, macromolecular substances, Cytoreduction Surgical Procedures, Debulking, Troponin, Risk Assessment, Stratification (mathematics), Internal medicine, Risk stratification, medicine, biology.protein, Cardiology, Troponin measurement, Humans, Surgery, Postoperative Period, Cytoreductive surgery, business, Biomarkers
Abstract: Several studies have raised interest in the use of postoperative troponin levels to stratify risk of postoperative morbidity and mortality. In this study, postoperative troponin concentration after cytoreductive surgery (with or without hyperthermic intraoperative intraperitoneal chemotherapy) was associated with severe postoperative complications, and enhanced the predictive capability of a multivariable model focusing on postoperative complications.
Published: 2021

37. 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

38. [Telehealth in peroperative medicine]

Author: Charlotte, Ceruti, Pierre Yves, Carry, Clémence, Ferrier, Arnaud, Friggeri, and Vincent, Piriou
Subjects: Anaesthesia, Telehealth, Télémédecine, Teleconsultation, Mise Au Point, Anesthésie, Telemedicine, Téléconsultation
Abstract: La télémédecine est en plein essor dans tous les domaines médicaux. En plus d’être l’une des priorités de l’OMS afin de répondre aux problèmes des coûts et de l’accessibilité à des soins de qualité, que ce soit dans les pays développés ou en voie de développement, la crise sanitaire récente liée au COVID-19 a montré qu’elle pouvait être un atout certain pour la permanence des soins en situation de crise. Si la télémédecine en anesthésie se développe pour l’ensemble de la prise en charge péri-opératoire des patients, cette mise au point vise à présenter les données récentes de la littérature concernant la place de la télémédecine en anesthésie pour l’évaluation pré-opératoire. Quatre points principaux sont abordés : (1) l’éligibilité et la faisabilité de la téléconsultation d’anesthésie; (2) son efficacité en terme de temps passé en consultation d’anesthésie, taux d’annulation d’intervention et concordance de l’examen physique; (3) la satisfaction des patients, et enfin; (4) son potentiel impact économique.
Published: 2020

39. Effectiveness and Safety of the Combined Use of Tranexamic Acid: A Comparative Observational Study of 1909 Cases

Author: Michel Fessy, Pierre Yves Petit, Arnaud Friggeri, Charles-Hervé Vacheron, Pascal Roy, Anthony Viste, Vincent Piriou, and James Appery
Subjects: Antifibrinolytic, medicine.drug_class, medicine.medical_treatment, Deep vein, tranexamic acid, 03 medical and health sciences, 0302 clinical medicine, lcsh:Orthopedic surgery, medicine, Orthopedics and Sports Medicine, combined, 030222 orthopedics, business.industry, Hazard ratio, Blood loss, Liter, 030229 sport sciences, medicine.disease, Thrombosis, Arthroplasty, intraarticular, Confidence interval, lcsh:RD701-811, medicine.anatomical_structure, Anesthesia, intravenous, Original Article, business, Tranexamic acid, medicine.drug
Abstract: BACKGROUND: Tranexamic acid (TA) use in lower‑limb arthroplasty has been valued in these surgeries high‑risk hemorrhagic due to its antifibrinolytic action. The objective of the present study was to determine the effectiveness of the combined intravenous (IV) and intraarticular (IA) administration of TA in lower‑limb arthroplasty. METHODS: We conduct a prospective observational study between January 1, 2014, and December 31, 2017, including all programmed lower‑limb arthroplasties. Patients were divided into four groups: no TA, 15 mg/kg IV TA, 3 g IA TA, and 15 mg/kg IV and 3 g IA. The effect on calculated total blood loss (milliliter of red blood cell [RBC]), hemoglobin, transfusion, and duration of hospitalization was studied after adjustment on age, American Society of Anesthesiologists, surgery, and postoperative curative anticoagulation. Complications related to TA administration were systematically reported. RESULTS: A total of 1909 patients were included – “no TA,” n = 184; “IV,” n = 1137; “IA,” n = 214; and “IV + IA,” n = 374. In the IV + IA group, a decrease in blood loss was observed compared to the no TA group (+ 220 ml 95% confidence interval [CI] [184; 255] of RBC P
Published: 2020

40. Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

Author: Flavia K Borges, Mohit Bhandari, Ernesto Guerra-Farfan, Ameen Patel, Alben Sigamani, Masood Umer, Maria E Tiboni, Maria del Mar Villar-Casares, Vikas Tandon, Jordi Tomas-Hernandez, Jordi Teixidor-Serra, Victoria RA Avram, Mitchell Winemaker, Mmampapatla T Ramokgopa, Wojciech Szczeklik, Giovanni Landoni, Chew Yin Wang, Dilshad Begum, John D Neary, Anthony Adili, Parag K Sancheti, Abdel-Rahman Lawendy, Mariano Balaguer-Castro, Paweł Ślęczka, Richard J Jenkinson, Aamer Nabi Nur, Gavin CA Wood, Robert J Feibel, Stephen J McMahon, Alen Sigamani, Ekaterine Popova, Bruce M Biccard, Iain K Moppett, Patrice Forget, Paul Landais, Michael H McGillion, Jessica Vincent, Kumar Balasubramanian, Valerie Harvey, Yaiza Garcia-Sanchez, Shirley M Pettit, Leslie P Gauthier, Gordon H Guyatt, David Conen, Amit X Garg, Shrikant I Bangdiwala, Emilie P Belley-Cote, Maura Marcucci, Andre Lamy, Richard Whitlock, Yannick Le Manach, Dean A Fergusson, Salim Yusuf, PJ Devereaux, Laurent Veevaete, Bernard le Polain de Waroux, Patricia Lavand'homme, Olivier Cornu, Karim Tribak, Jean Cyr Yombi, Nassim Touil, Maike Reul, Jigme Tshering Bhutia, Carol Clinckaert, Dirk De Clippeleir, Justin de Beer, Diane L Simpson, Andrew Worster, Kim A Alvarado, Krysten K Gregus, Kelly H Lawrence, Darryl P Leong, Philip G Joseph, Patrick Magloire, Benjamin Deheshi, Stuart Bisland, Thomas J Wood, Daniel M Tushinski, David AJ Wilson, Clive Kearon, David D Cowan, Vickas Khanna, Amna Zaki, Janet C Farrell, Anne Marie MacDonald, Steven CW Wong, Arsha Karbassi, Douglas Steven Wright, Harsha Shanthanna, 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, Steven Shadowitz, Jacques S Lee, Stephen Choi, Hans J Kreder, Markku Nousiainen, Monica R Kunz, Ravianne Tuazon, Mopina Shrikumar, Bheeshma Ravi, David Wasserstein, David JG Stephen, Diane Nam, Patrick DG Henry, 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 P-J Chen, Stephanie A Coupal, 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 Andrew I Trenholm, William Oxner, C Glen 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 Manuel Muñoz, Philippe Chaudier, Marion Douplat, Michel Henri Fessy, Vincent Piriou, Lucie Louboutin, Jean Stephane David, Arnaud Friggeri, Sebastien Beroud, Jean Marie Fayet, Frankie Ka Li Leung, Christian Xinshuo Fang, Dennis King Hang Yee, Parag Kantilal Sancheti, Chetan Vijay Pradhan, Atul Ashok Patil, Chetan Prabhakar Puram, Madhav Pandurang Borate, Kiran Bhalchandra Kudrimoti, Bharati Anil Adhye, Himanshu Vijaykumar Dongre, Bobby John, Valsamma Abraham, Ritesh Arvind Pandey, Arti Rajkumar, Preetha Elizabeth George, Manesh Stephen, Nitheesh Chandran, Mohammed Ashraf, AM Georgekutty, Ahamad Shaheel Sulthan, S Adinarayanan, Deep Sharma, Satish Prasad Barnawal, Srinivasan Swaminathan, Prasanna Udupi Bidkar, Sandeep Kumar Mishra, Jagdish Menon, Niranjan M, Varghese Zachariah K, Santosh Angad Hiremath, Madhusudhan NC, Abhijit Jawali, Kingsly Robert Gnanadurai, Carolin Elizabeth George, Tatarao Maddipati, Mary KP KP, Vijay Sharma, Kamran Farooque, Rajesh Malhotra, Samarth Mittal, Chavi Sawhney, Babita Gupta, Purva Mathur, Shivanand Gamangati, Vijaylaxmi Tripathy, Prem Haridas Menon, Mandeep S Dhillon, Devendra K Chouhan, Sharanu Patil, Ravi Narayan, Purushotham Lal, Prashanth Nabhirajappa Bilchod, Surya Udai Singh, Uttam Vaidya Gattu, Ravi Prabhakar Dashputra, Prashant Vitthal Rahate, Maurizio Turiel, Giuseppe De Blasio, Riccardo Accetta, Paolo Perazzo, Daniele Stella, Marika Bonadies, Chiara Colombo, Stefania Fozzato, Fabio Pino, Ilaria Morelli, Eleonora Colnaghi, Vincenzo Salini, Giuseppe Denaro, Luigi Beretta, Giacomo Placella, Giuseppe Giardina, Mirko Binda, Anna Marcato, Luca Guzzetti, Fabio Piccirillo, Maurizio Cecconi, HM Khor, Hou Yee Lai, CS Kumar, KH Chee, PS 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 B.G. Brokelman, Hannie F Elskamp-Meijerman, Maarten R Horst, Jan-Hein MG Cobben, Anila Anjum, Pervaiz Mehmood Hashmi, Tashfeen Ahmed, Haroon Ur Rashid, Mujahid Jamil Khattak, Rizwan Haroon Rashid, Riaz Hussain Lakdawala, Shahryar Noordin, Naveed Muhammed Juman, Robyna Irshad Khan, Muhammad Mehmood Riaz, Syedah Saira Bokhari, Ayesha Almas, Hussain Wahab, Arif Ali, Hammad Naqi Khan, Eraj Khurshid Khan, Kholood Abid Janjua, Sajjad Hassan Orakzai, Abdus Salam Khan, Khawaja Junaid Mustafa, Mian Amjad Sohail, Muhammad Umar, Siddra Ahmed Khan, Muhammad Ashraf, Muhammad Kashif Khan, Muhammad Shiraz, Ahmad Furgan, Piotr Dąbek, Adam Kumoń, Wojciech Satora, Wojciech Ambroży, Mariusz Święch, Jacek Rycombel, Adrian Grzelak, Jaroslaw Gucwa, Waldemar Machala, Mmampapatla Thomas Ramokgopa, Gregory Bodley Firth, Mwalimu Karera, Maria Fourtounas, Virsen Singh, Anna Biscardi, Muhammad Nasir Iqbal, Ryan Jonathan Campbell, Matimba Lenny Maluleke, Carien Moller, Lerato Nhlapo, Sithombo Maqungo, Margot Flint, Marcin B Nejthardt, Sean Chetty, Rubendren Naidoo, Miriam Garrido Clua, Vicente Molero-Garcia, Joan Minguell-Monyart, Jordi Selga Marsa, Juan A Porcel-Vazquez, Jose-Vicente Andres-Peiro, Marc Aguilar, Jaume Mestre-Torres, Maria J Colomina, Patricia Guilabert, M Luisa Paños Gozalo, Luis Abarca, Nuria Martin, Gemma Usua, Pedro Martinez-Ripol, MA Gonzalez Posada, Pilar Lalueza-Broto, Judith Sanchez-Raya, Jorge Nuñez Camarena, Antoni Fraguas-Castany, Pere Torner, Monsant Jornet-Gibert, Jorge Serrano-Sanz, Jaume Cámara-Cabrera, Mònica Salomó-Domènech, Christian Yela-Verdú, Anna Peig-Font, Laura Ricol, Anna Carreras-Castañer, Luis Martínez-Sañudo, Susana Herranz, Carlos Feijoo-Massó, Mònica Sianes-Gallén, Pablo Castillón, Martí Bernaus, Saioa Quintas, Olga Gómez, Jordi Salvador, Javiera Abarca, Cristina Estrada, Marga Novellas, Mercè Torra, Alfred Dealbert, Oscar Macho, Alexia Ivanov, Esther Valldosera, Marta Arroyo, Borja Pey, Antoni Yuste, Llorenç Mateo, Julio De Caso, Rafael Anaya, JL Higa-Sansone, Angelica Millan, Victoria Baños, Sergio Herrera-Mateo, Hector J Aguado, Gonzalo Martinez-Municio, Ricardo León, Silvia Santiago-Maniega, Ana Zabalza, Gregorio Labrador, Enrique Guerado, Encarnacion Cruz, Juan Ramon Cano, Jose Manuel Bogallo, Paphon Sa-ngasoongsong, Noratep Kulachote, Norachart Sirisreetreerux, Nachapan Pengrung, Theerawat Chalacheewa, Vanlapa Arnuntasupakul, Teerapat Yingchoncharoen, Bundit Naratreekoon, Miriam Adel Kadry, Surendini Thayaparan, Ihab Abdlaziz, Arash Aframian, Arjuna Imbuldeniya, Souad Bentoumi, Sherif Omran, Marcela Paola Vizcaychipi, Patricia Correia, Shashank Patil, Kevin Haire, Amy SE Mayor, Sally Dillingham, Laura Nicholson, Mohamed Elnaggar, Joby John, Shashi Kumar Nanjayan, Martyn J Parker, Susan O'Sullivan, Meir T Marmor, Amir Matityahu, Robert Trigg McClellan, Curt Comstock, Anthony Ding, Paul Toogood, Gerard Slobogean, Katherine Joseph, Robert O'Toole, Marcus Sciadini, Scott P Ryan, Molly E Clark, Charles Cassidy, Konstantin Balonov, Sergio D Bergese, Laura S Phieffer, Alicia A Gonzalez Zacarias, Andrew J Marcantonio, Sanela Dragic-Taylor, Chelsea Maxwell, Sarah Molnar, Jennifer R Wells, Sandra N Ofori, Stephen S Yang, Michael K Wang, Emmanuelle Duceppe, Jessica Spence, Javiera P Vasquez, Francesc Marcano-Fernández, Hyungjoo Ham, Carlos Prada, Terence CH Yung, Isidro Sanz Pérez, Michael J Bosch, Michael R Prystajecky, Chinmoy Chowdhury, James S Khan, Steffan F Stella, Behrouz Heidary, Allen Tran, Katarzyna Wawrzycka-Adamczyk, Yu Chiao Peter Chen, Aránzazu González-Osuna, Grzegorz Biedroń, Anna Wludarczyk, Marco Lefebvre, Jaclyn A Ernst, Bas Staffhorst, Jason D Woodfine, Emad M Alwafi, Marko Mrkobrada, Simon Parlow, Robin Roberts, Finlay McAlister, David Sackett, James Wright, (HIP ATTACK, Investigators), Landoni, G., Faculty of Medicine and Pharmacy, Orthopaedics - Traumatology, Supporting clinical sciences, Emergency Medicine, UCL - SSS/IONS - Institute of NeuroScience, 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: Postoperative Complications/epidemiology, Male, Internationality, Femoral Neck Fractures/epidemiology, Arthroplasty, Replacement, Hip, Myocardial Ischemia, Comorbidity, Time-to-Treatment/statistics & numerical data, 030204 cardiovascular system & hematology, law.invention, Fracture Fixation, Internal, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, Residence Characteristics, law, Activities of Daily Living, Fracture fixation, Risk of mortality, Medicine and Health Sciences, Fracture Fixation, Internal/methods, Sepsis/epidemiology, 030212 general & internal medicine, Cardiovascular Diseases/mortality, Stroke, Aged, 80 and over, Hip fracture, Residence Characteristics/statistics & numerical data, Infections/epidemiology, General Medicine, Middle Aged, Open Fracture Reduction, Treatment Outcome, Cardiovascular Diseases, Diabetes Mellitus/epidemiology, Female, medicine.medical_specialty, Hip Fractures/epidemiology, Postoperative Hemorrhage, Infections, Early Medical Intervention/methods, Time-to-Treatment, 03 medical and health sciences, Arthroplasty, Replacement, Hip/methods, Early Medical Intervention, Sepsis, Diabetes Mellitus, medicine, Humans, Mortality, Myocardial Ischemia/epidemiology, Aged, Proportional Hazards Models, Postoperative Hemorrhage/epidemiology, Hip Fractures, Proportional hazards model, business.industry, Hemiarthroplasty/methods, Dementia/epidemiology, Delirium, Delirium/epidemiology, medicine.disease, Femoral Neck Fractures, Nursing Homes, Surgery, Open Fracture Reduction/methods, Dementia, Observational study, Hemiarthroplasty, business
Abstract: © 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p
Published: 2020

41. Amikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize

Author: Clément, Boidin, Laurent, Bourguignon, Sabine, Cohen, Claire, Roger, Jean-Yves, Lefrant, Jason A, Roberts, Bernard, Allaouchiche, Alain, Lepape, Arnaud, Friggeri, and Sylvain, Goutelle
Subjects: Adult, Aged, 80 and over, Male, Pharmacology, Models, Statistical, Critical Illness, Microbial Sensitivity Tests, Middle Aged, Anti-Bacterial Agents, Young Adult, Area Under Curve, Sepsis, Humans, Drug Dosage Calculations, Female, Amikacin, Aged
Abstract: Amikacin is commonly used for probabilistic antimicrobial therapy in critically ill patients with sepsis. Its narrow therapeutic margin makes it challenging to determine the right individual dose that ensures the highest efficacy target attainment rate (TAR) in this setting. This study aims to develop a new initial dosing approach for amikacin by optimizing the a priori TAR in this population. A population pharmacokinetic model was built with a learning data set from critically ill patients who received amikacin. It was then used to design an initial dosing approach maximizing a priori TAR for a target ratio of ≥8 for the peak concentration to the MIC (C(max)/MIC) or of ≥75 for the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC(0–24)/MIC). In the 166 patients included, 53% had amikacin C(max) of ≥64 mg/liter with a median dose of 23.4 mg/kg. A two-compartment model with creatinine clearance and body surface area as covariates best described the data and showed good predictive performance. Our dosing approach was successful in optimizing TAR for C(max)/MIC, with a rate of 92.9% versus 67.9% using a 30-mg/kg regimen, based on an external subset of data and assuming a MIC of 8 mg/liter. Mean optimal doses were higher (3.5 ± 0.5 g) than with the 30-mg/kg regimen (2.1 ± 0.3 g). Suggested doses varied with the MIC, the target index, and desired TAR threshold. A dosing algorithm based on the method is proposed for a large range of patient covariates. Clinical studies are necessary to confirm efficacy and safety of this optimized dosing approach.
Published: 2019

42. 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

43. Marked alterations of neutrophil functions during sepsis-induced immunosuppression

Author: Françoise Poitevin-Later, Christophe Malcus, Marie-Angélique Cazalis, Alain Lepape, Fabienne Venet, Julie Demaret, Julien Textoris, Arnaud Friggeri, Guillaume Monneret, Jonathan Plassais, and Laurent Jallades
Subjects: Male, Time Factors, Neutrophils, medicine.medical_treatment, Immunology, CD16, Biology, Sepsis, Chemokine receptor, Immune Tolerance, medicine, Humans, Immunology and Allergy, Aged, Aged, 80 and over, Septic shock, Immunosuppression, Cell Biology, medicine.disease, Acquired immune system, Respiratory burst, Gene Expression Regulation, Myeloperoxidase, biology.protein, Female, Receptors, Chemokine, Follow-Up Studies
Abstract: Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3–4 and d 6–8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10dimCD16dim). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations.
Published: 2015

44. 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

45. Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation

Author: Guillaume Monneret, Fabienne Venet, Julien Textoris, Alain Lepape, Jeremy Schilling, Arnaud Friggeri, Fanny Poujol, Julie Demaret, Alexandre Pachot, Thomas Rimmelé, Christelle Rouget, Marie-Angélique Cazalis, and Thibaut Girardot
Subjects: 0301 basic medicine, Lipopolysaccharides, Male, Risk, Lipopolysaccharide, Immunology, Biology, Monocytes, Andrology, Sepsis, Cohort Studies, Immunomodulation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, LILRB2, medicine, Immunology and Allergy, Humans, RNA, Messenger, Receptors, Immunologic, Receptor, Cells, Cultured, Aged, Aged, 80 and over, Membrane Glycoproteins, Septic shock, Monocyte, General Medicine, Middle Aged, medicine.disease, Shock, Septic, Survival Analysis, 030104 developmental biology, medicine.anatomical_structure, chemistry, Gene Expression Regulation, Female, Ex vivo, 030215 immunology
Abstract: Septic patients develop immune dysfunctions, the intensities and durations of which are associated with deleterious outcomes. LILRB2 (leukocyte immunoglobulin-like receptors subfamily B, member 2), an inhibitory member of the LILR family of receptors, is known for its immunoregulatory properties. In a microarray study, we identified LILRB2 as an upregulated gene in septic shock patients. On monocytes primed with LPS ex vivo, LILRB2 mRNA and protein expressions were dose-dependently downregulated and subsequently highly upregulated versus non-stimulated cells. This is concordant with clinical data, since both LILRB2 mRNA and protein expressions were significantly increased in septic shock patients at day 3. In a cohort of more than 700 patients, only after septic shock were LILRB2 mRNA levels increased compared with non-infected or less severely infected patients. This was preceded by a phase of downregulated mRNA expression during the first hours after septic shock. Interestingly, the intensity of this decrease was associated with increased risk of death after septic shock. LILRB2 protein and mRNA expressions are deregulated on monocytes after septic shock and this can be reproduced ex vivo after LPS challenge. Considering LILRB2 inhibitory properties, we can hypothesize that LILRB2 may participate in the altered immune response after septic shock.
Published: 2016

46. 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

47. 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

48. Identification of TLT2 as an Engulfment Receptor for Apoptotic Cells

Author: Edward Abraham, Andressa de Freitas, Mingui Fu, Arnaud Friggeri, Kasey I. Davis, Sami Banerjee, Na Xie, Gang Liu, and Huachun Cui
Subjects: Immunology, Apoptosis, Enzyme-Linked Immunosorbent Assay, chemical and pharmacologic phenomena, Inflammation, Biology, Real-Time Polymerase Chain Reaction, Article, Mice, Immune system, Phagocytosis, medicine, Animals, Immunology and Allergy, Macrophage, Receptors, Immunologic, Efferocytosis, Mice, Knockout, Innate immune system, Macrophages, TLR9, Flow Cytometry, Acquired immune system, Immunity, Innate, Toll-Like Receptor 3, Cell biology, Mice, Inbred C57BL, TLR2, Female, medicine.symptom, Signal Transduction
Abstract: Clearance of apoptotic cells (efferocytosis) is critical to the homeostasis of the immune system by restraining inflammation and autoimmune response to intracellular Ags released from dying cells. TLRs-mediated innate immunity plays an important role in pathogen clearance and in regulation of the adaptive immune response. However, the regulation of efferocytosis by activation of TLRs has not been well characterized. In this study, we found that activation of TLR3 or TLR9, but not of TLR2, enhances engulfment of apoptotic cells by macrophages. We found that the activation of TLR3 upregulates the expression of triggering receptor expressed on myeloid cells (TREM)-like protein 2 (TLT2), a member of the TREM receptor family, on the surface of macrophages. Blocking TLT2 on the macrophage surface by either specific anti-TLT2 Ab or soluble TLT2 extracellular domain attenuated the enhanced ability of macrophages with TLR3 activation to engulf apoptotic cells. To the contrary, overexpression of TLT2 increased the phagocytosis of apoptotic cells. We found that TLT2 specifically binds to phosphatidylserine, a major “eat me” signal that is exposed on the surface of apoptotic cells. Furthermore, we found that TLT2 mediates phagocytosis of apoptotic cells in vivo. Thus, our studies identified TLT2 as an engulfment receptor for apoptotic cells. Our data also suggest a novel mechanism by which TREM receptors regulate inflammation and autoimmune response.
Published: 2012

49. Extracellular Histones Inhibit Efferocytosis

Author: Huachun Cui, Andressa de Freitas, Mourad Zerfaoui, Gang Liu, Edward Abraham, Sami Banerjee, Hervé Dupont, Arnaud Friggeri, and Na Xie
Subjects: Male, medicine.medical_treatment, Phagocytosis, Inflammation, C-Mer Tyrosine Kinase, Histones, Mice, Histone H3, Histone H1, Proto-Oncogene Proteins, Genetics, medicine, Animals, Receptors, Vitronectin, Efferocytosis, Molecular Biology, Protein Kinase C, Genetics (clinical), c-Mer Tyrosine Kinase, biology, Macrophages, Growth factor, Receptor Protein-Tyrosine Kinases, Articles, Opsonin Proteins, Milk Proteins, Molecular biology, Cell biology, Mice, Inbred C57BL, Kinetics, Histone, Antigens, Surface, biology.protein, Intercellular Signaling Peptides and Proteins, Molecular Medicine, medicine.symptom, Extracellular Space, Protein Binding
Abstract: The uptake and clearance of apoptotic cells by macrophages and other phagocytic cells, a process called efferocytosis, is a major component in the resolution of inflammation. Increased concentrations of extracellular histones are found during acute inflammatory states and appear to contribute to organ system dysfunction and mortality. In these studies, we examined the potential role of histones in modulating efferocytosis. We found that phagocytosis of apoptotic neutrophils or thymocytes by macrophages was significantly diminished in the presence of histones H3 or H4, but not histone H1. Histone H3 demonstrated direct binding to macrophages, an effect that was diminished by preincubation of macrophages with the opsonins growth arrest-specific gene 6 (Gas6) and milk fat globule-epidermal growth factor (EGF) 8 (MFG-E8). Incubation of histone H3 with soluble α(v)β₅ integrin and Mer, but not with α(v)β₃, diminished its binding to macrophages. Phagocytosis of apoptotic cells by alveolar macrophages in vivo was diminished in the presence of histone H3. Incubation of histone H3 with activated protein C, a treatment that degrades histones, abrogated its inhibitory effects on efferocytosis under both in vitro and in vivo conditions. The present studies demonstrate that histones have inhibitory effects on efferocytosis, suggesting a new mechanism by which extracellular histones contribute to acute inflammatory processes and tissue injury.
Published: 2012

50. Poly(ADP-Ribosyl)ation of High Mobility Group Box 1 (HMGB1) Protein Enhances Inhibition of Efferocytosis

Author: Celeste P. Bell, Sami Banerjee, Kasey I. Davis, Edward Abraham, Arnaud Friggeri, and Mourad Zerfaoui
Subjects: Male, rac1 GTP-Binding Protein, Phagocytosis, Poly ADP ribose polymerase, Receptor for Advanced Glycation End Products, Poly (ADP-Ribose) Polymerase-1, chemical and pharmacologic phenomena, Inflammation, HMGB1, Cell Line, RAGE (receptor), Mice, Genetics, medicine, Animals, HMGB1 Protein, Receptors, Immunologic, Efferocytosis, Molecular Biology, Genetics (clinical), Thymocytes, biology, Neuropeptides, Articles, Molecular biology, rac GTP-Binding Proteins, Mice, Inbred C57BL, Toll-Like Receptor 4, Apoptosis, Macrophages, Peritoneal, biology.protein, TLR4, Molecular Medicine, Poly(ADP-ribose) Polymerases, medicine.symptom
Abstract: Phagocytosis of apoptotic cells by macrophages, known as efferocytosis, is a critical process in the resolution of inflammation. High mobility group box 1 (HMGB1) protein was first described as a nuclear nonhistone DNA-binding protein, but is now known to be secreted by activated cells during inflammatory processes, where it participates in diminishing efferocytosis. Although HMGB1 is known to undergo modification when secreted, the effect of such modifications on the inhibitory actions of HMGB1 during efferocytosis have not been reported. In the present studies, we found that HMGB1 secreted by Toll-like receptor 4 (TLR4) stimulated cells is highly poly(ADP-ribosyl)ated (PARylated). Gene deletion of poly(ADP)-ribose polymerase (PARP)-1 or pharmacological inhibition of PARP-1 decreased the release of HMGB1 from the nucleus to the extracellular milieu after TLR4 engagement. Preincubation of macrophages or apoptotic cells with HMGB1 diminished efferocytosis through mechanisms involving binding of HMGB1 to phosphatidylserine on apoptotic cells and to the receptor for advanced glycation end products (RAGE) on macrophages. Preincubation of either macrophages or apoptotic cells with PARylated HMGB1 inhibited efferocytosis to a greater degree than exposure to unmodified HMGB1, and PARylated HMGB1 demonstrated higher affinity for phosphatidylserine and RAGE than unmodified HMGB1. PARylated HMGB1 had a greater inhibitory effect on Ras-related C3 botulinum toxin substrate 1 (Rac-1) activation in macrophages during the uptake of apoptotic cells than unmodified HMGB1. The present results, showing that PARylation of HMGB1 enhances its ability to inhibit efferocytosis, provide a novel mechanism by which PARP-1 may promote inflammation.
Published: 2011

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