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1. SAME day amBulatory Appendectomy (SAMBA): a multicenter, prospective, randomized clinical trial protocol

Author

Catherine Arvieux, Fatah Tidadini, Sandrine Barbois, Eric Fontas, Michel Carles, Victor Gridel, Jean-Christophe Orban, Jean-Louis Quesada, Alison Foote, Coralie Cruzel, Sabine Anthony, Julie Bulsei, Céline Hivelin, and Damien Massalou

Subjects
Appendectomy, Ambulatory surgery, Outpatient surgery, Postoperative morbi-mortality, Randomized controlled trial, Medicine (General), R5-920
Abstract

Abstract Background A recent meta-analysis concluded that outpatient appendectomy appears feasible and safe, but there is a lack of high-quality evidence and a randomized trial is needed. The aim of this trial is to demonstrate that outpatient appendectomy is non-inferior to conventional inpatient appendectomy in terms of overall morbi-mortality on the 30th postoperative day (D30). Methods SAMBA is a prospective, randomized, controlled, multicenter non-inferiority trial. We will include 1400 patients admitted to 15 French hospitals between January 2023 and June 2025. Inclusion criteria are patients aged between 15 and 74 years presenting acute uncomplicated appendicitis suitable to be operated by laparoscopy. Patients will be randomized to receive outpatient care (day-surgery) or conventional inpatient care with overnight hospitalization in the surgery department. The primary outcome is postoperative morbi-mortality at D30. Secondary outcomes include time from diagnosis to appendectomy, length of total hospital stay, re-hospitalization, interventional radiology, re-interventions until D30, conversion from outpatient to inpatient, and quality of life and patient satisfaction using validated questionnaires. Discussion The SAMBA trial tests the hypothesis that outpatient surgery (i.e., without an overnight hospital stay) of uncomplicated acute appendicitis is a feasible and reliable procedure in establishments with a technical platform able to support this management strategy. Trial registration ClinicalTrials.gov NCT05691348. Registered on 20 January 2023.

Published
2024
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2. One-year survival of aneurysmal subarachnoid hemorrhage after airplane transatlantic transfer – a monocenter retrospective study

Author

Frédéric Martino, Antoine Fleuri, Nicolas Engrand, Amélie Rolle, Michel Piotin, Michel Carles, Delphine Delta, Laurent Do, Adrien Pons, Patrick Portecop, Mathys Sitcharn, Marc Valette, Laurent Camous, Jean-David Pommier, and Alexandre Demoule

Subjects
Aneurysmal subarachnoid hemorrhage, Airplane transfer, One-year mortality, Safety, Mechanical ventilation, Anesthesiology, RD78.3-87.3
Abstract

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is preferentially treated by prompt endovascular coiling, which is not available in Guadeloupe. Subsequently, patients are transferred to Paris, France mainland, by commercial airplane (6751 km flight) after being managed according to guidelines. This study describes the characteristics, management and outcomes related to these patients. Methods Retrospective observational cohort study of 148 patients admitted in intensive care unit for a suspected aSAH and transferred by airplane over a 10-year period (2010–2019). Results The median [interquartile range] age was 53 [45–64] years and 61% were female. On admission, Glasgow coma scale was 15 [13–15], World Federation of Neurological Surgeons (WFNS) grading scale was 1 [1–3] and Fisher scale was 4 [2–4]. External ventricular drainage and mechanical ventilation were performed prior to the flight respectively in 42% and 47% of patients. One-year mortality was 16% over the study period. By COX logistic regression analysis, acute hydrocephalus (hazard ratio [HR] 2.34, 95% confidence interval [CI] 0.98–5.58) prior to airplane transfer, WFNS grading scale on admission (HR 1.53, 95% CI 1.16–2.02) and age (OR 1.03, 95% 1.00–1.07) were associated with one-year mortality. Conclusion When necessary, transatlantic air transfer of patients with suspected aSAH after management according to local guidelines seems feasible and safe.

Published
2024
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3. Organ Involvement Related to Death in Critically Ill Patients With Leptospirosis: Unsupervised Analysis in a French West Indies ICU

Author

Laurent Camous, MD, MSC, Jean-David Pommier, MD, MPH, Benoît Tressières, Msc, Frederic Martino, MD, Mathieu Picardeau, MD, PhD, Cecile Loraux, MD, MSC, Marc Valette, MD, Hugo Chaumont, MD, PhD, Michel Carles, MD, PhD, Alexandre Demoule, MD, PhD, and Sebastien Breurec, MD, PhD

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To identify distinct phenotypes of critically ill leptospirosis patients upon ICU admission and their potential associations with outcome. DESIGN:. Retrospective observational study including all patients with biologically confirmed leptospirosis admitted to the ICU between January 2014 and December 2022. Subgroups of patients with similar clinical profiles were identified by unsupervised clustering (factor analysis for mixed data and hierarchical clustering on principal components). SETTING:. All patients admitted to the ICU of the University Hospital of Guadeloupe on the study period. PATIENTS:. One hundred thirty critically ill patients with confirmed leptospirosis were included. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. At ICU admission, 34% of the patients had acute respiratory failure, and 26% required invasive mechanical ventilation. Shock was observed in 52% of patients, myocarditis in 41%, and neurological involvement in 20%. Unsupervised clustering identified three clusters—“Weil’s Disease” (48%), “neurological leptospirosis” (20%), and “multiple organ failure” (32%)—with different ICU courses and outcomes. Myocarditis and neurological involvement were key components for cluster identification and were significantly associated with death in ICU. Other factors associated with mortality included shock, acute respiratory failure, and requiring renal replacement therapy. CONCLUSIONS AND RELEVANCE:. Unsupervised analysis of critically ill patients with leptospirosis revealed three patient clusters with distinct phenotypic characteristics and clinical outcomes. These patients should be carefully screened for neurological involvement and myocarditis at ICU admission.

Published
2024
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4. Efficacy of an antimicrobial stewardship intervention for early adaptation of antibiotic therapy in high-risk neutropenic patients

Author

Claire Durand, Karine Risso, Michael Loschi, Nicolas Retur, Audrey Emery, Johan Courjon, Thomas Cluzeau, and Michel Carles

Subjects
Antibiotic, Antimicrobial stewardship, Hematology, Febrile neutropenia, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The 4th European Conference on Infections in Leukemia recommends early adaptation of empirical antibiotic therapy (EAT) for febrile neutropenia in stable patients. Objectives To assess the efficacy of an antimicrobial stewardship (AMS) intervention promoting early de-escalation and discontinuation of EAT in high-risk neutropenic patients. Methods This before-after study was conducted in the hematology department of the University Hospital of Nice, France. The AMS intervention included the development of clinical decision support algorithms, a twice-weekly face-to-face review of all antibiotic prescriptions and monthly feedback on the intervention. The primary endpoint was overall antibiotic consumption during hospital stay, expressed as days of therapy (DOT). Results A total of 113 admissions were included: 56 during the pre-intervention period and 57 during the intervention period. Induction chemotherapy and conditioning for allogeneic stem cell transplantation were the most frequent reasons for admission. In the intervention period, there was a significant decrease in overall antibiotic consumption (median DOT 20 vs. 28 days, p = 0.006), carbapenem consumption (median DOT 5.5 vs. 9 days, p = 0.017) and anti-resistant Gram-positive agents consumption (median DOT 8 vs. 11.5 days, p = 0.017). We found no statistical difference in the rates of intensive care unit admission (9% in each period) and 30-day mortality (5% vs. 0%, p = 0.243). Compliance with de-escalation and discontinuation strategies was significantly higher in the intervention period (77% vs. 8%, p

Published
2024
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6. Time-to-detection in culture of Mycobacterium tuberculosis: performance for assessing index cases contact-positivity

Author

Karine Risso, Céline Michelangeli, Alice Gaudart, Mathieu Buscot, Emmanuel Chamorey, Johan Courjon, and Michel Carles

Subjects
Transmission, Time-to-detection, Index cases, Contact screening, Smear status, Mycobacterium tuberculosis, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Time-to-detection (TTD) in culture on liquid media is inversely correlated to bacillary load and should be a contributing factor for assessing tuberculosis transmission. We wanted to assess if TTD was a better alternative than smear status to estimate transmission risk. Methods: From October 2015 to June 2022, we retrospectively studied a cohort of index cases (IC) with pulmonary tuberculosis (tuberculosis disease [TD]) from which samples were culture-positive before treatment. We studied the correlation between TTD and contact-positivity (CP) of IC contacts: CP was defined as CP = 1 (CP group) in case of TD or latent tuberculosis infection (LTI) in at least one screened contact of an IC, and CP = 0 otherwise (contact-negativity [CN] group). Univariate and multivariable analyses (logistic regression) were done. Results: Of the 185 IC, 122 were included, generating 846 contact cases of which 705 were assessed. A transmission event (LTI or TD) was identified in 193 contact cases (transmission rate: 27%). At day 9, 66% and 35% of the IC had their sample positive in culture for CP and CN groups, respectively. Age and TTD ≤9 days were independent criteria of CP (odds ratio 0.97, confidence interval [0.95-0.98], P = 0.002 and odds ratio 3.52, confidence interval [1.59-7.83], P = 0.001, respectively). Conclusion: TTD was a more discriminating parameter than smear status to evaluate the transmission risk of an IC with pulmonary tuberculosis. Therefore, TTD should be considered in the contact-screening strategy around an IC.

Published
2023
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7. COVID-19 patient experiences in prehospital pathways: a processual approach using life-events calendar method and state sequence analysis shows detrimental delays

Author

Patrick Peretti-Watel, Sébastien Cortaredona, Christian Pradier, Gaetan Gentile, Stéphanie Gentile, Philippe Brouqui, Michel Carles, Romain Lutaud, Lea Delorme, Juliette Mirouse, Manon Borg, Lucie Cattaneo, Didier Thery, Touitou Irit, and Sophie Tardieu

Subjects
Medicine (General), R5-920
Abstract

Objectives To our best knowledge, no study in France has comprehensively investigated the prehospital history of patients admitted for severe cases of COVID-19. ‘Patients’ voice is an excellent means to capture data on primary care pathways.We aimed to identify clusters of COVID-19 hospitalised patients with similar prehospital symptom sequences, and to test whether these clusters were associated with a higher risk of poor clinical outcomes.Design Cross-sectional online survey using life-event calendars.Setting All patients hospitalised for COVID-19 between September 2020 and May 2021 in the Infectious Disease Departments in Nice and in Marseilles in France.Participants 312 patients responded to the survey.Main outcome measures From the day of symptom onset to the day of hospitalisation, we defined a symptom sequence as the time-ordered vector of the successive symptom grades (grade 1, grade 2, grade 3). State sequence analysis with optimal matching was used to identify clusters of patients with similar symptom sequences. Multivariate logistic regressions were performed to test whether these clusters were associated with admission to intensive care unit (ICU) and COVID-19 sequelae after hospitalisation.Results Three clusters of symptom sequences were identified among 312 complete prehospital pathways. A specific group of patients (29%) experienced extended symptoms of severe COVID-19, persisting for an average duration of 7.5 days before hospitalisation. This group had a significantly higher probability of being admitted to ICU (adjusted OR 2.01). They were less likely to know a loved one who was a healthcare worker, and more likely to have a lower level of education. Similarly, this group of patients, who were more likely to have previously visited the emergency room without exhibiting severe symptoms at that time, may have been inclined to postpone reassessment when their health worsened.Their relatives played a decisive role in their hospitalisation.Conclusion and relevance This study highlights the negative impact of delayed hospitalisation on the health outcomes of French patients with severe COVID-19 symptoms during the first wave and underscores the influence of socioeconomic factors, such as lower education levels and limited connections to the medical field, on patients’ experiences.

Published
2024
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8. Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies

Author

Daniel Re, Barbara Seitz-Polski, Vesna Brglez, Michel Carles, Daisy Graça, Sylvia Benzaken, Stéphane Liguori, Khaled Zahreddine, Margaux Delforge, Béatrice Bailly-Maitre, Benjamin Verrière, Emmanuel Chamorey, and Jérôme Barrière

Subjects
Science
Abstract

Vaccination is effective in preventing severe COVID-19 symptoms. Here the authors monitor patients with hematopoietic malignancy to find the third dose of the mRNA vaccine, BNT162b2, only boosts the humoral immunity in those showing responses to 2nd dose vaccination but can induce an independent T-cell response in a fraction of seronegative patients.

Published
2022
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9. Breakthrough infections due to SARS-CoV-2 Delta variant: relation to humoral and cellular vaccine responses

Author

Matthieu Buscot, Marion Cremoni, Daisy Graça, Vesna Brglez, Johan Courjon, Jonathan Allouche, Maxime Teisseyre, Laurent Boyer, Jérôme Barrière, Emmanuel Chamorey, Michel Carles, and Barbara Seitz-Polski

Subjects
COVID-19, breakthrough infections, vaccination, humoral response, cellular response, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionCOVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood.MethodsHere, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease.ResultsIn this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form.DiscussionKnowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters.Trial registration numbershttps://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.

Published
2023
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10. COVID-19 patients age, comorbidity profiles and clinical presentation related to the SARS-CoV-2 UK-variant spread in the Southeast of France

Author

Johan Courjon, Julie Contenti, Elisa Demonchy, Jacques Levraut, Pascal Barbry, Géraldine Rios, Jean Dellamonica, David Chirio, Caroline Bonnefoy, Valérie Giordanengo, and Michel Carles

Subjects
Medicine, Science
Abstract

Abstract The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p

Published
2021
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11. Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a before-and-after, propensity-matched cohort study in a Caribbean intensive care unit

Author

Christophe Le Terrier, Marco Vinetti, Paul Bonjean, Régine Richard, Bruno Jarrige, Bertrand Pons, Benjamin Madeux, Pascale Piednoir, Fanny Ardisson, Elain Elie, Frédéric Martino, Marc Valette, Edouard Ollier, Sébastien Breurec, Michel Carles, and Guillaume Thiéry

Subjects
Intensive care unit, Caribbean, Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Antimicrobial resistance, Antibiotic stewardship, Intestinal microbiota, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). Methods We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. Results The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p

Published
2021
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12. Low baseline IFN-γ response could predict hospitalization in COVID-19 patients

Author

Marion Cremoni, Jonathan Allouche, Daisy Graça, Kevin Zorzi, Céline Fernandez, Maxime Teisseyre, Sylvia Benzaken, Caroline Ruetsch-Chelli, Vincent L. M. Esnault, Jean Dellamonica, Michel Carles, Jérôme Barrière, Michel Ticchioni, Vesna Brglez, and Barbara Seitz-Polski

Subjects
SARS-CoV-2, viral infection, IFN-γ, functional immunoassay, predictive biomarker, personalized medicine, Immunologic diseases. Allergy, RC581-607
Abstract

The SARS-CoV-2 infection has spread rapidly around the world causing millions of deaths. Several treatments can reduce mortality and hospitalization. However, their efficacy depends on the choice of the molecule and the precise timing of its administration to ensure viral clearance and avoid a deleterious inflammatory response. Here, we investigated IFN-γ, assessed by a functional immunoassay, as a predictive biomarker for the risk of hospitalization at an early stage of infection or within one month prior to infection. Individuals with IFN-γ levels below 15 IU/mL were 6.57-times more likely to be hospitalized than those with higher values (p65 years, and no vaccination were independently associated with hospitalization. In addition, we found a significant inverse correlation between low IFN-γ response and high level of IL-6 in plasma (Spearman’s rho=-0.38, p=0.003). Early analysis of the IFN-γ response in a contact or recently infected subject with SARS-CoV-2 could predict hospitalization and thus help the clinician to choose the appropriate treatment avoiding severe forms of infection and hospitalization.

Published
2022
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13. Critical care medicine in the French Territories in the Americas: Current situation and prospects

Author

Hatem Kallel, Dabor Resiere, Stéphanie Houcke, Didier Hommel, Jean Marc Pujo, Frederic Martino, Michel Carles, and Hossein Mehdaoui

Subjects
critical care, tropical medicine, french guiana, guadeloupe, martinique, Medicine, Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Hospitals in the French Territories in the Americas (FTA) work according to international and French standards. This paper aims to describe different aspects of critical care in the FTA. For this, we reviewed official information about population size and intensive care unit (ICU) bed capacity in the FTA and literature on FTA ICU specificities. Persons living in or visiting the FTA are exposed to specific risks, mainly severe road traffic injuries, envenoming, stab or ballistic wounds, and emergent tropical infectious diseases. These diseases may require specific knowledge and critical care management. However, there are not enough ICU beds in the FTA. Indeed, there are 7.2 ICU beds/100 000 population in Guadeloupe, 7.2 in Martinique, and 4.5 in French Guiana. In addition, seriously ill patients in remote areas regularly have to be transferred, most often by helicopter, resulting in a delay in admission to intensive care. The COVID-19 crisis has shown that the health care system in the FTA is unready to face such an epidemic and that intensive care bed capacity must be increased. In conclusion, the critical care sector in the FTA requires upgrading of infrastructure, human resources, and equipment as well as enhancement of multidisciplinary care. Also needed are promotion of training, research, and regional and international medical and scientific cooperation.

Published
2021
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14. Emergence of Lyme Disease on the French Riviera, a Retrospective Survey

Author

Jacques Sevestre, Antoine Benichou, Vanessa Rio, Pascal Delaunay, Géraldine Gonfrier, Cécile Martaresche, Virginie Carlo, Sarah Nakam, Véronique Mondain, Michel Carles, Pierre Yves Jeandel, and Jacques Durant

Subjects
Lyme, Borrelia, French Riviera, borreliosis, Ixodes ricinus, Medicine (General), R5-920
Abstract

BackgroundThe French Riviera has been declared free of Lyme Borreliosis (LB) for years. Many patients are referred for presumed LB, sometimes with atypical clinical signs and/or doubtful serology, calling the diagnosis into question.MethodsPatients were assessed for LB diagnosis, depending on clinical presentation, laboratory findings, and further examination by other medical professionals.ResultsAmong 255 patients, 45 (18%) were classified as confirmed LB cases [including 28 ongoing LB (10%) and 17 past LB (8%)], and for 210 (82%) a Lyme borreliosis diagnosis was ruled out. Among ongoing LB, 56% had been exposed to or bitten by ticks, exclusively in rural locations of the Alpes-Maritimes. As a result of the diagnostic procedure, 132 (52%) patients had been treated. An alternative diagnosis was established for 134 (52%) patients, covering a wide range of conditions, including mainly psychological (28%) and neurological conditions (25%) or inflammatory and systemic diseases (22%).ConclusionsOur results strongly suggest the endemicity of LB in the Alpes-Maritimes region. Confirmed LB accounted for 18% of patients while 52% were diagnosed with other conditions.

Published
2022
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15. Case Report: Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium falciparum Malaria

Author

Marion Louvois, Loïc Simon, Christelle Pomares, Pierre-Yves Jeandel, Elisa Demonchy, Michel Carles, Pascal Delaunay, and Johan Courjon

Subjects
hemolytic anemia, malaria, artemisinin-based combination, artemisinin derivatives, autoimmune, direct antiglobulin test, Medicine (General), R5-920
Abstract

Malaria is still an endemic disease in Africa, with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described, and guidelines recommend biological monitoring until 1 month after the end of the treatment. A link with an autoimmune process is still unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only few cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. We report the case of a 42-year-old man returning from Togo. He was treated with dihydroartemisinin/piperaquine combination for uncomplicated Plasmodium falciparum malaria, with low parasitemia. Nine days after the end of the treatment, the patient developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. After excluding common causes of autoimmune hemolytic anemia, we considered that dihydroartemisinin/piperaquine treatment was involved in this side effect.

Published
2022
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16. Salivary detection of COVID-19: clinical performance of oral sponge sampling for SARS-CoV-2 testing

Author

Jacques Boutros, Jonathan Benzaquen, Charles Hugo Marquette, Marius Ilié, Mickelina Labaky, Didier Benchetrit, Thibaut Lavrut, Sylvie Leroy, Richard Chemla, Michel Carles, Virginie Tanga, Charlotte Maniel, Olivier Bordone, Maryline Allégra, Virginie Lespinet, Julien Fayada, Jennifer Griffonnet, Véronique Hofman, and Paul Hofman

Subjects
Medicine
Abstract

Background The current diagnostic standard for coronavirus disease 2019 (COVID-19) is reverse transcriptase-polymerase chain reaction (RT-PCR) testing with nasopharyngeal (NP) swabs. The invasiveness and need for trained personnel make the NP technique unsuited for repeated community-based mass screening. We developed a technique to collect saliva in a simple and easy way with the sponges that are usually used for tamponade of epistaxis. This study was carried out to validate the clinical performance of oral sponge (OS) sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Methods Over a period of 22 weeks, we collected prospectively 409 paired NP and OS samples from consecutive subjects presenting to a public community-based free screening centre. Subjects were referred by their attending physician because of recent COVID-19 symptoms (n = 147) or by the contact tracing staff of the French public health insurance because they were considered as close contacts of a laboratory-confirmed COVID-19 case (n = 262). Results In symptomatic subjects, RT-PCR SARS-CoV-2 testing with OS showed a 96.5% (95% CI: 89.6–94.8) concordance with NP testing, and a 93.2% (95% CI: 89.1–97.3) sensitivity when using the IdyllaTM platform and a sensitivity of 76.3% (95% CI: 69.4–83.2) on the Synlab Barla laboratory platform. In close contacts the NP-OS concordance (93.8%, 95% CI: 90.9–96.7) and OS sensitivity (71.9%, 95% CI: 66.5–77.3) were slightly lower. Conclusion These results strongly suggest that OS testing is a straightforward, low-cost and high-throughput sampling method that can be used for frequent RT-PCR testing of COVID-19 patients and mass screening of populations.

Published
2021
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17. Spontaneous community-acquired bacterial meningitis in adults admitted to the intensive care units in the Caribbean French West Indies: Unusual prevalence of Klebsiella pneumonia

Author

Pascale Piednoir, Ulrich Clarac, Amélie Rolle, Sylvaine Bastian, Gaelle Gruel, Frédéric Martino, Hossein Mehdaoui, Marc Valette, Sébastien Breurec, and Michel Carles

Subjects
Meningitis, Klebsiella pneumonia, Virulence, Epidemiology, Infectious and parasitic diseases, RC109-216
Abstract

An unusual prevalence of Klebsiella pneumoniae (24%) was observed in 25 adults admitted to the intensive care units of two University Hospitals in the French West Indies, for spontaneous community-acquired bacterial meningitis. All tested isolates had several prominent features of hypervirulent isolates, including rmpa and iuc genes, K1 or K2 capsular serotypes.

Published
2020
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18. Three New Cases of Melioidosis, Guadeloupe, French West Indies

Author

Bénédicte Melot, Sylvaine Bastian, Nathalie Dournon, Eric Valade, Olivier Gorgé, Anne Le Fleche, Charlotte Idier, Mireille Vernier, Elisabeth Fernandes, Bruno Hoen, Sébastien Breurec, and Michel Carles

Subjects
melioidosis, Burkholderia pseudomallei, endemicity, Caribbean, Guadeloupe, French West Indies, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Melioidosis has been detected in the Caribbean, and an increasing number of cases has been reported in the past few decades, but only 2 cases were reported in Guadeloupe during the past 20 years. We describe 3 more cases that occurred during 2016–2017 and examine arguments for increasing endemicity.

Published
2020
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19. Sciatic nerve block or not for outpatient total knee arthroplasty? Study protocol for a randomized controlled trial

Author

Laurie Tran, Melissa Barthelemy, Pascal Boileau, Marc Raucoules-Aime, Michel Carles, and Christophe Trojani

Subjects
Total knee arthroplasty, Outpatient procedure, Sciatic nerve block, Randomized controlled study, Medicine (General), R5-920
Abstract

Abstract Background The number of patients operated on for total knee arthroplasty (TKA) is growing worldwide. Outpatient surgery is defined by a length of stay (LOS) in the hospital of less than 12 h. This can be limited for TKA, with the efficient management of pain and perioperative complications, such as blood loss, affecting a safe hospital discharge. Outpatient TKA with a suitable protocol, including multimodal measures, could improve the success rate of this procedure. Among the main measures, single-shot sciatic nerve block in association with continuous femoral nerve block for pain control needs to be evaluated in outpatient TKA. Furthermore, to promote the safety of the postoperative period and to accelerate rehabilitation, patients who undergo ambulatory TKA could be discharged to a rehabilitation center on the day of surgery to screen adverse events and to optimize the rehabilitation process. This study is designed to assess the benefits of sciatic nerve block in postoperative pain relief for outpatient TKA. Methods/design This randomized prospective controlled study will be conducted in the knee unit of the teaching hospital of the Nice university and will include 40 patients undergoing primary unilateral outpatient TKA, discharged the day of surgery to a private rehabilitation center for enhanced recovery after surgery, after a hospital stay of less than 12 h. Before surgery, all patients will receive a continuous femoral nerve block with 2 mg/ml ropivacaine 20 ml, and then patients will be randomly assigned to receive or not receive a single-shot sciatic nerve block with 2 mg/ml ropivacaine, 20 ml. The primary outcome measure is the success rate of outpatient TKA. This rate is defined by patients discharged from the hospital to a rehabilitation center the day of surgery with no re-hospitalization due to insufficient pain control before the fifth postoperative day. Secondary outcomes include the incidence of major and minor adverse events during the first five postoperative days and measurement of the quality of recovery using the Knee injury and Osteoarthritis Outcome Score and the new International Knee Society scores plus the Quality of Recovery-40 questionnaire. Discussion The assessment of anesthesia and rehabilitation protocols enabling major orthopedic surgery, such as TKA, is necessary. This randomized controlled study will address the hypothesis that a suitable multimodal protocol including sciatic nerve block could improve pain control and thus improve the success rate of outpatient TKA. Trial registration EudraCT, 2016-000226-19. Registered on 15 April 2016.

Published
2019
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20. Clindamycin Efficacy for Cutibacterium acnes Shoulder Device-Related Infections

Author

Audrey Courdurié, Romain Lotte, Raymond Ruimy, Vincent Cauhape, Michel Carles, Marc-Olivier Gauci, Pascal Boileau, and Johan Courjon

Subjects
Cutibacterium acnes, shoulder implant, clindamycin, Therapeutics. Pharmacology, RM1-950
Abstract

Clindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines for C. acnes prosthetic joint infections. We aimed to evaluate the efficacy of clindamycin in the treatment of C. acnes shoulder implant joint infections (SIJI). Methods: A retrospective analysis was conducted at the University Hospital of Nice (France) between 2010 and 2019. We included patients with one shoulder implant surgical procedure and at least one C. acnes positive sample. We selected the C. acnes SIJI according to French and international recommendations. The primary endpoint was favorable outcome of C. acnes SIJI treatment after at least 1-year follow-up in the clindamycin group compared to another therapeutic group. Results: Forty-eight SIJI were identified and 33 were treated with clindamycin, among which 25 were treated with monotherapy. The median duration of clindamycin antibiotherapy was 6 weeks. The average follow-up was 45 months; one patient was lost to follow-up. Twenty-seven patients out of 33 (82%) were cured with clindamycin, compared to 9/12 (75%) with other antibiotics. The rate of favorable outcomes increased to 27/31 (87%) with clindamycin and to 9/10 (90%) for other antibiotics when no septic revision strategies were excluded (P = 1.00). Conclusions: The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective.

Published
2022
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21. Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial

Author

Audrey De Jong, Anne Bignon, François Stephan, Thomas Godet, Jean-Michel Constantin, Karim Asehnoune, Aude Sylvestre, Juliette Sautillet, Raiko Blondonnet, Martine Ferrandière, Philippe Seguin, Sigismond Lasocki, Amélie Rollé, Pierre-Marie Fayolle, Laurent Muller, Emmanuel Pardo, Nicolas Terzi, Séverin Ramin, Boris Jung, Paer-Selim Abback, Philippe Guerci, Benjamine Sarton, Hadrien Rozé, Claire Dupuis, Joel Cousson, Marion Faucher, Virginie Lemiale, Bernard Cholley, Gerald Chanques, Fouad Belafia, Helena Huguet, Emmanuel Futier, Elie Azoulay, Nicolas Molinari, Samir Jaber, AUDREY DE JONG, ANNE BIGNON, FRANÇOIS STEPHAN, THOMAS GODET, JEAN-MICHEL CONSTANTIN, KARIM ASEHNOUNE, AUDE SYLVESTRE, JULIETTE SAUTILLET, RAIKO BLONDONNET, MARTINE FERRANDIERE, PHILIPPE SEGUIN, SIGISMOND LASOCKI, AMELIE ROLLE, PIERRE-MARIE FAYOLLE, LAURENT MULLER, EMMANUEL PARDO, NICOLAS TERZI, SEVERIN RAMIN, BORIS JUNG, PAER-SELIM ABBACK, PHILIPPE GUERCI, BENJAMINE SARTON, HADRIEN ROZE, CLAIRE DUPUIS, JOEL COUSSON, MARION FAUCHER, VIRGINIE LEMIALE, BERNARD CHOLLEY, GERALD CHANQUES, FOUAD BELAFIA, HELENA HUGUET, EMMANUEL FUTIER, CLAUDINE GNIADEK, AURELIE VONARB, ALBERT PRADES, CARINE JAILLET, XAVIER CAPDEVILA, JONATHAN CHARBIT, THIBAUT GENTY, SAIDA REZAIGUIA-DELCLAUX, AUDREY IMBERT, CATHERINE PILORGE, ROMAN CALYPSO, ASTRID BOUTEAU-DURAND, MICHEL CARLES, HOSSEN MEHDAOUI, BERTRAND SOUWEINE, LAURE CALVET, MATTHIEU JABAUDON, BENJAMIN RIEU, CLARA CANDILLE, FLORIAN SIGAUD, BEATRICE RIU, LAURENT PAPAZIAN, SABINE VALERA, DJAMEL MOKART, LAURENT CHOW CHINE, MAGALI BISBAL, CAMILLE POULIQUEN, JEAN-MANUEL DE GUIBERT, MAXIME TOURRET, DAMIEN MALLET, MARC LEONE, LAURENT ZIELESKIEWICZ, JEANNE COSSIC, MONA ASSEFI, ELODIE BARON, CYRIL QUEMENEUR, ANTOINE MONSEL, MATTHIEU BIAIS, ALEXANDRE OUATTARA, ELINE BONNARDEL, SIMON MONZIOLS, MARTIN MAHUL, JEAN-YVES LEFRANT, CLAIRE ROGER, SABER BARBAR, FABIEN LAMBIOTTE, PIEHR SAINT-LEGER, CATHERINE PAUGAM, JULIEN POTTECHER, PIERRE-OLIVIER LUDES, LUCIE DARRIVERE, MARC GARNIER, ERIC KIPNIS, GILLES LEBUFFE, MATTHIAS GAROT, JEREMY FALCONE, BENJAMIN CHOUSTERMAN, MAGALI COLLET, ETIENNE GAYAT, JEAN DELLAMONICA, WILLY-SERGE MFAM, EVELINA OCHIN, MOHAMED NEBLI, NEJLA TILOUCHE, BENJAMIN MADEUX, DAVID BOUGON, YASSIR AARAB, FANNY GARNIER, ELIE AZOULAY, NICOLAS MOLINARI, and SAMIR JABER

Subjects
Pulmonary and Respiratory Medicine
Published
2023
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22. Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE])*

Author

Julien, Carvelli, Ferhat, Meziani, Jean, Dellamonica, Pierre-Yves, Cordier, Jerome, Allardet-Servent, Megan, Fraisse, Lionel, Velly, Saber Davide, Barbar, Samuel, Lehingue, Christophe, Guervilly, Maxime, Desgrouas, Fabrice, Camou, Christelle, Piperoglou, Frederic, Vely, Olivier, Demaria, Joyson, Karakunnel, Joanna, Fares, Luciana, Batista, Federico, Rotolo, Julien, Viotti, Agnes, Boyer-Chammard, Karine, Lacombe, Erwan, Le Dault, Michel, Carles, Nicolas, Schleinitz, Eric, Vivier, Sarah, Djabarouti, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, CHU Nice, Hopital l'Archet 1, Centre Hospitalier Universitaire de Nice (CHU Nice), Réanimation Polyvalente, HIA Laveran - Department of Intensive Care - Marseille, Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Victor Dupouy, Aix Marseille Université (AMU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nîmes University Hospital, Department of Intensive Care, Hôpital Saint-Joseph [Marseille], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Saint-André, Université de Bordeaux (UB), Innate Pharma, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HIA Laveran a Marseille, European Project: 694502,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,TILC(2017), and European Project: 875102,MInflaTILC

Subjects
Oxygen, sepsis, Treatment Outcome, SARS-CoV-2, inflammation, [SDV]Life Sciences [q-bio], Humans, COVID-19, complement, Antibodies, Monoclonal, Humanized, avdoralimab, Critical Care and Intensive Care Medicine
Abstract

International audience; OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Spo 2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of-0.26 (95% CI,-1.2 to 0.7; p = 0.7) in cohort 1 and-0.28 (95% CI,-1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of-6.3 (95% CI,-13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Published
2022
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23. The Effect of an Accelerated Renal Replacement Therapy Initiation Is Not Modified by Baseline Risk

Author

Federico Angriman, Bruno L. Ferreyro, Natalia Angeloni, Bruno R. da Costa, Ron Wald, Sean M. Bagshaw, Neill K.J. Adhikari, Rinaldo Bellomo, Didier Dreyfuss, Bin Du, Martin P. Gallagher, Stéphane Gaudry, François Lamontagne, Michael Joannidis, Kathleen D. Liu, Daniel F. McAuley, Shay P. McGuinness, Alistair D. Nichol, Marlies Ostermann, Paul M. Palevsky, Haibo Qiu, Ville Pettilä, Antoine G. Schneider, Orla M. Smith, Suvi T. Vaara, Matthew Weir, Glenn M. Eastwood, Leah Peck, Helen Young, Peter Kruger, Gordon Laurie, Emma Saylor, Jason Meyer, Ellen Venz, Krista Wetzig, Craig French, Forbes McGain, John Mulder, Gerard Fennessy, Sathyajith Koottayi, Samantha Bates, Miriam Towns, Rebecca Morgan, Anna Tippett, Andrew Udy, Chris Mason, Elisa Licari, Dashiell Gantner, Jason McClure, Alistair Nichol, Phoebe McCracken, Jasmin Board, Emma Martin, Shirley Vallance, Meredith Young, Chelsey Vladic, Steve McGloughlin, David Gattas, Heidi Buhr, Jennifer Coles, Debra Hutch, James Wun, Louise Cole, Christina Whitehead, Julie Lowrey, Kristy Masters, Rebecca Gresham, Victoria Campbell, David Gutierrez, Jane Brailsford, Loretta Forbes, Lauren Murray, Teena Maguire, Martina NiChonghaile, Neil Orford, Allison Bone, Tania Elderkin, Tania Salerno, Tim Chimunda, Jason Fletcher, Emma Broadfield, Sanjay Porwal, Cameron Knott, Catherine Boschert, Julie Smith, Angus Richardson, Dianne Hill, Graeme Duke, Peter Oziemski, Santiago Cegarra, Peter Chan, Deborah Welsh, Stephanie Hunter, Owen Roodenburg, John Dyett, Nicos Kokotsis, Max Moser, Yang Yang, Laven Padayachee, Joseph Vetro, Himangsu Gangopadhyay, Melissa Kaufman, Angaj Ghosh, Simone Said, Alpesh Patel, Shailesh Bihari, Elisha Matheson, Xia Jin, Tapaswi Shrestha, Kate Schwartz, Rosalba Cross, Winston Cheung, Helen Wong, Mark Kol, Asim Shah, Amanda Y. Wang, Zoltan Endre, Celia Bradford, Pierre Janin, Simon Finfer, Naomi Diel, Jonathan Gatward, Naomi Hammond, Anthony Delaney, Frances Bass, Elizabeth Yarad, Hergen Buscher, Claire Reynolds, Nerilee Baker, Romuald Bellmann, Andreas Peer, Julia Hasslacher, Paul Koglberger, Sebastian Klein, Klemens Zotter, Anna Brandtner, Armin Finkenstedt, Adelheid Ditlbacher, Frank Hartig, Dietmar Fries, Mirjam Bachler, Bettina Schenk, Martin Wagner, Philipp Eller, Thomas Staudinger, Esther Tiller, Peter Schellongowski, Andja Bojic, Eric A. Hoste, Stephanie Bracke, Luc De Crop, Daisy Vermeiren, Fernando Thome, Bianca Chiella, Lucia Fendt, Veronica Antunes, Frédérick D'Aragon, Charles St-Arnaud, Michael Mayette, Élaine Carbonnaeu, Joannie Marchand, Marie-Hélène Masse, Marilène Ladouceur, Alexis F. Turgeon, François Lauzier, David Bellemare, Charles Langis Francoeur, Guillaume LeBlanc, Gabrielle Guilbault, Stéphanie Grenier, Eve Cloutier, Annick Boivin, Charles Delisle-Thibault, Panagiota Giannakouros, Olivier Costerousse, Jean-François Cailhier, François-Martin Carrier, Ali Ghamraoui, Martine Lebrasseur, Fatna Benettaib, Maya Salamé, Dounia Boumahni, Ying Tung Sia, Jean-François Naud, Isabelle Roy, Henry T. Stelfox, Stacey Ruddell, Braden J. Manns, Shelley Duggan, Dominic Carney, Jennifer Barchard, Richard P. Whitlock, Emilie Belley-Cote, Nevena Savija, Alexandra Sabev, Troy Campbell, Thais Creary, Kelson Devereaux, Shira Brodutch, Claudio Rigatto, Bojan Paunovic, Owen Mooney, Anna Glybina, Oksana Harasemiw, Michelle Di Nella, John Harmon, Navdeep Mehta, Louis Lakatos, Nicole Haslam, Francois Lellouche, Mathieu Simon, Ying Tung, Patricia Lizotte, Pierre-Alexandre Bourchard, Bram Rochwerg, Tim Karachi, Tina Millen, John Muscedere, David Maslove, J. Gordon Boyd, Stephanie Sibley, John Drover, Miranda Hunt, Ilinca Georgescu, Randy Wax, Ilan Lenga, Kavita Sridhar, Andrew Steele, Kelly Fusco, Taneera Ghate, Michael Tolibas, Holly Robinson, Matthew A. Weir, Ravi Taneja, Ian M. Ball, Amit Garg, Eileen Campbell, Athena Ovsenek, Sean van Diepen, Nadia Baig, Sheldon Magder, Han Yao, Ahsan Alam, Josie Campisi, Erika MacIntyre, Ella Rokosh, Kimberly Scherr, Stephen Lapinsky, Sangeeta Mehta, Sumesh Shah, Daniel J. Niven, Michael Russell, Kym Jim, Gillian Brown, Kerry Oxtoby, Adam Hall, Luc Benoit, Colleen Sokolowski, Bhanu Prasad, Jag Rao, Shelley Giebel, Demetrios J. Kutsogiannis, Patricia Thompson, Tayne Thompson, Robert Cirone, Kanthi Kavikondala, Mark Soth, France Clarke, Alyson Takaoka, David Mazer, Karen Burns, Jan Friedrich, David Klein, Gyan Sandhu, Marlene Santos, Imrana Khalid, Jennifer Hodder, Peter Dodek, Najib Ayas, Victoria Alcuaz, Gabriel Suen, Oleksa Rewa, Gurmeet Singh, Sean Norris, Neil Gibson, Castro Arias, Aysha Shami, Celine Pelletier, Alireza Zahirieh, Andre Amaral, Nicole Marinoff, Navjot Kaur, Adic Perez, Jane Wang, Gregory Haljan, Christopher Condin, Lauralyn McIntyre, Brigette Gomes, Rebecca Porteous, Irene Watpool, Swapnil Hiremath, Edward Clark, Margaret S. Herridge, Felicity Backhouse, M. Elizabeth Wilcox, Karolina Walczak, Vincent Ki, Asheer Sharman, Martin Romano, R.T. Noel Gibney, Adam S. Romanovsky, Lorena McCoshen, Gordon Wood, Daniel Ovakim, Fiona Auld, Gayle Carney, Meili Duan, Xiaojun Ji, Dongchen Guo, Zhili Qi, Jin Lin, Meng Zhang, Lei Dong, Jingfeng Liu, Pei Liu, Deyuan Zhi, Guoqiang Bai, Yu Qiu, Ziqi Yang, Jing Bai, Zhuang Liu, Haizhou Zhuang, Haiman Wang, Jian Li, Mengya Zhao, Xiao Zhou, Xianqing Shi, Baning Ye, Manli Liu, Jing Wu, Yongjian Fu, Dali Long, Yu Pan, Jinlong Wang, Huaxian Mei, Songsong Zhang, Mingxiang Wen, Enyu Yang, Sijie Mu, Jianquan Li, Tingting Hu, Bingyu Qin, Min Li, Cunzhen Wang, Xin Dong, Kaiwu Wang, Haibo Wang, Jianxu Yang, Chuanyao Wang, Dongxin Wang, Nan Li, Zhui Yu, Song Xu, Lan Yao, Guo Hou, Zhou Liu, Liping Lu, Yingtao Lian, Chunting Wang, Jichen Zhang, Ruiqi Ding, Guoqing Qi, Qizhi Wang, Peng Wang, Zhaoli Meng, Man Chen, Xiaobo Hu, Xiandi He, Shibing Zhao, Lele Hang, Rui Li, Suhui Qin, Kun Lu, Shijuan Dun, Cheng Liu, Qi Zhou, Zhenzhen Chen, Jing Mei, Minwei Zhang, Hao Xu, Jincan Lin, Qindong Shi, Lijuan Fu, Qinjing Zeng, Hongye Ma, Jinqi Yan, Lan Gao, Hongjuan Liu, Lei Zhang, Hao Li, Xiaona He, Jingqun Fan, Litao Guo, Yu Liu, Xue Wang, Jingjing Sun, Zhongmin Liu, Juan Yang, Lili Ding, Lulu Sheng, Xingang Liu, Jie Yan, Quihui Wang, Yifeng Wang, Dan Zhao, Shuangping Zhao, Chenghuan Hu, Jing Li, Fuxing Deng, Haibo Qui, Yi Yang, Min Mo, Chun Pan, Changde Wu, Yingzi Huang, Lili Huang, Airan Liu, Anna-Maija Korhonen, Sanna Törnblom, Sari Sutinen, Leena Pettilä, Jonna Heinonen, Eliria Lappi, Taria Suhonen, Sari Karlsson, Sanna Hoppu, Ville Jalkanen, Anne Kuitunen, Markus Levoranta, Jaakko Långsjö, Sanna Ristimäki, Kaisa Malila, Anna Wootten, Simo Varila, Mikko J Järvisalo, Outi Inkinen, Satu Kentala, Keijo Leivo, Paivi Haltia, Jean-Damien Ricard, Jonathan Messika, Abirami Tiagarajah, Malo Emery, Aline Dechanet, Coralie Gernez, Damien Roux, Laurent Martin-Lefevre, Maud Fiancette, Isabelle Vinatier, Jean Claude Lacherade, Gwenhaël Colin, Christine Lebert, Marie-Ange Azais, Aihem Yehia, Caroline Pouplet, Matthieu Henry- Lagarrigue, Amélie Seguin, Laura Crosby, Julien Maizel, Dimitri Titeca-Beauport, Alain Combes, Ania Nieszkowska, Paul Masi, Alexandre Demoule, Julien Mayaux, Martin Dres, Elise Morawiec, Maxens Decalvele, Suela Demiri, Morgane Faure, Clémence Marios, Maxime Mallet, Marie Amélie Ordon, Laura Morizot, Marie Cantien, François Pousset, Florent Poirson, Yves Cohen, Laurent Argaud, Martin Cour, Laurent Bitker, Marie Simon, Romain Hernu, Thomas Baudry, Sylvie De La Salle, Adrien Robine, Nicholas Sedillot, Xavier Tchenio, Camille Bouisse, Sylvie Roux, Fabienne Tamion, Steven Grangé, Dorothée Carpentier, Guillaume Chevrel, Luis Ensenyat-Martin, Sophie Marque, Jean-Pierre Quenot, Pascal Andreu, Auguste Dargent, Audrey Large, Nicolas Chudeau, Mickael Landais, Benoit Derrien, Jean Christophe Callahan, Christophe Guitton, Charlène Le Moal, Alain Robert, Karim Asehnoune, Raphaël Cinotti, Nicolas Grillot, Dominique Demeure, Christophe Vinsonneau, Imen Rahmani, Mehdi Marzouk, Thibault Dekeyser, Caroline Sejourne, Mélanie Verlay, Fabienne Thevenin, Lucie Delecolle, Didier Thevenin, Bertrand Souweine, Elisabeth Coupez, Mireille Adda, Jean-Pierre Eraldi, Antoine Marchalot, Nicolas De Prost, Armand Mekontso Dessap, Keyvan Razazi, Ferhat Meziani, Julie Boisrame-Helms, Raphael Clere-Jehl, Xavier Delabranche, Christine Kummerlen, Hamid Merdji, Alexandra Monnier, Yannick Rabouel, Hassene Rahmani, Hayat Allam, Samir Chenaf, Vincenta Franja, Bertrand Pons, Michel Carles, Frédéric Martino, Régine Richard, Benjamin Zuber, Guillaume Lacave, Karim Lakhal, Bertrand Rozec, Hoa Dang Van, Éric Boulet, Fouad Fadel, Cedric Cleophax, Nicolas Dufour, Caroline Grant, Marie Thuong, Jean Reignier, Emmanuel Canet, Laurent Nicolet, Thierry Boulain, Mai-Anh Nay, Dalila Benzekri, François Barbier, Anne Bretagnol, Toufik Kamel, Armelle Mathonnet, Grégoire Muller, Marie Skarzynski, Julie Rossi, Amandine Pradet, Sandra Dos Santos, Aurore Guery, Lucie Muller, Luis Felix, Julien Bohé, Guillaume Thiéry, Nadia Aissaoui, Damien Vimpere, Morgane Commeureuc, Jean-Luc Diehl, Emmanuel Guerot, Orfeas Liangos, Monika Wittig, Alexander Zarbock, Mira Küllmar, Thomas van Waegeningh, Nadine Rosenow, Kathy Brickell, Peter Doran, Patrick T. Murray, Giovanni Landoni, Rosalba Lembo, Alberto Zangrillo, Giacomo Monti, Margherita Tozzi, Matteo Marzaroli, Gaetano Lombardi, Gianluca Paternoster, Michelangelo Vitiello, Shay McGuinness, Rachael Parke, Magdalena Butler, Eileen Gilder, Keri-Anne Cowdrey, Samantha Wallace, Jane Hallion, Melissa Woolett, Philippa Neal, Karina Duffy, Stephanie Long, Colin McArthur, Catherine Simmonds, Yan Chen, Rachael McConnochie, Lynette Newby, David Knight, Seton Henderson, Jan Mehrtens, Stacey Morgan, Anna Morris, Kymbalee Vander Hayden, Tara Burke, Matthew Bailey, Ross Freebairn, Lesley Chadwick, Penelope Park, Christine Rolls, Liz Thomas, Ulrike Buehner, Erin Williams, Jonathan Albrett, Simon Kirkham, Carolyn Jackson, Troy Browne, Jennifer Goodson, David Jackson, James Houghton, Owen Callender, Vicki Higson, Owen Keet, Clive Dominy, Paul Young, Anna Hunt, Harriet Judd, Cassie Lawrence, Shaanti Olatunji, Yvonne Robertson, Charlotte Latimer-Bell, Deborah Hendry, Agnes Mckay-Vucago, Nina Beehre, Eden Lesona, Leanlove Navarra, Chelsea Robinson, Ryan Jang, Andrea Junge, Bridget Lambert, Michel Thibault, Philippe Eckert, Sébastien Kissling, Erietta Polychronopoulos, Elettra Poli, Marco Altarelli, Madeleine Schnorf, Samia Abed Mallaird, Claudia Heidegger, Aurelie Perret, Philippe Montillier, Frederic Sangla, Seigenthaller Neils, Aude De Watteville, Mandeep-Kaur Phull, Aparna George, Nauman Hussain, Tatiana Pogreban, Steve Lobaz, Alison Daniels, Mishell Cunningham, Deborah Kerr, Alice Nicholson, Pradeep Shanmugasundaram, Judith Abrams, Katarina Manso, Geraldine Hambrook, Elizabeth McKerrow, Juvy Salva, Stephen Foulkes, Matthew Wise, Matt Morgan, Jenny Brooks, Jade Cole, Tracy Michelle Davies, Helen Hill, Emma Thomas, Marcela Vizcaychipi, Behrad Baharlo, Jaime Carungcong, Patricia Costa, Laura Martins, Ritoo Kapoor, Tracy Hazelton, Angela Moon, Janine Musselwhite, Ben Shelley, Philip McCall, Gill Arbane, Aneta Bociek, Martina Marotti, Rosario Lim, Sara Campos, Neus Grau Novellas, Armando Cennamo, Andrew Slack, Duncan Wyncoll, Luigi Camporota, Simon Sparkes, Rosalinde Tilley, Austin Rattray, Gayle Moreland, Jane Duffy, Elizabeth McGonigal, Philip Hopkins, Clare Finney, John Smith, Harriet Noble, Hayley Watson, Claire-Louise Harris, Emma Clarey, Eleanor Corcoran, James Beck, Clare Howcroft, Nora Youngs, Elizabeth Wilby, Bethan Ogg, Adam Wolverson, Sandra Lee, Susie Butler, Maryanne Okubanjo, Julia Hindle, Ingeborg Welters, Karen Williams, Emily Johnson, Julie Patrick-Heselton, David Shaw, Victoria Waugh, Richard Stewart, Esther Mwaura, Lynn Wren, Louise Mew, Sara-Beth Sutherland, Jane Adderley, Jim Ruddy, Margaret Harkins, Callum Kaye, Teresa Scott, Wendy Mitchell, Felicity Anderson, Fiona Willox, Vijay Jagannathan, Michele Clark, Sarah Purv, Andrew Sharman, Megan Meredith, Lucy Ryan, Louise Conner, Cecilia Peters, Dan Harvey, Ashraf Roshdy, Amy Collins, Malcolm Sim, Steven Henderson, Nigel Chee, Sally Pitts, Katie Bowman, Maria Dilawershah, Luke Vamplew, Elizabeth Howe, Paula Rogers, Clara Hernandez, Clara Prendergast, Jane Benton, Alex Rosenberg, Lui G. Forni, Alice Grant, Paula Carvelli, Ajay Raithatha, Sarah Bird, Max Richardson, Matthew Needham, Claire Hirst, Jonathan Ball, Susannah Leaver, Luisa Howlett, Carlos Castro Delgado, Sarah Farnell-Ward, Helen Farrah, Geraldine Gray, Gipsy Joseph, Francesca Robinson, Ascanio Tridente, Clare Harrop, Karen Shuker, Derek McLaughlan, Judith Ramsey, Sharon Meehan, Bernd Oliver Rose, Rosie Reece-Anthony, Babita Gurung, Tony Whitehouse, Catherine Snelson, Tonny Veenith, Andy Johnston, Lauren Cooper, Ron Carrera, Karen Ellis, Emma Fellows, Samanth Harkett, Colin Bergin, Elaine Spruce, Liesl Despy, Stephanie Goundry, Natalie Dooley, Tracy Mason, Amy Clark, Gemma Dignam, Geraldine Ward, Ben Attwood, Penny Parsons, Sophie Mason, Michael Margarson, Jenny Lord, Philip McGlone, Luke E. Hodgson, Indra Chadbourn, Raquel Gomez, Jordi Margalef, Rinus Pretorius, Alexandra Hamshere, Joseph Carter, Hazel Cahill, Lia Grainger, Kate Howard, Greg Forshaw, Zoe Guy, Kianoush B. Kashani, Robert C. Albright, Amy Amsbaugh, Anita Stoltenberg, Alexander S. Niven, Matthew Lynch, AnnMarie O'Mara, Syed Naeem, Sairah Sharif, Joyce McKenney Goulart, Ashita Tolwani, Claretha Lyas, Laura Latta, Azra Bihorac, Haleh Hashemighouchani, Philip Efron, Matthew Ruppert, Julie Cupka, Sean Kiley, Joshua Carson, Peggy White, George Omalay, Sherry Brown, Laura Velez, Alina Marceron, Javier A. Neyra, Juan Carlos Aycinena, Madona Elias, Victor M. Ortiz-Soriano, Caroline Hauschild, and Robert Dorfman

Subjects
Renal Replacement Therapy, Pulmonary and Respiratory Medicine, Critical Illness, Medicine and Health Sciences, Humans, Acute Kidney Injury
Published
2022
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24. Who Were Hospitalized Deceased Patients from COVID-19 During the First Year of Pandemic? Retrospective Analysis of 1104 Deceased Patients in South of France

Author

Sylvie Arlotto, Kevin Legueult, Alice Blin, Sebastien Cortaredona, Audrey Giraud-Gatineau, Laurent Bailly, Marie-Thérèse Jimeno, Léa Delorme, Philippe Brouqui, Jean-Christophe Lagier, Matthieu Million, Jean Dellamonica, Philippe Colson, Michel Carles, Didier Raoult, Christian Pradier, Stéphanie Gentile, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Hôpital l'Archet, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de l'Information Médicale [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre d'Information et de Soin de l'Immuno-déficience Humaine Nice, and CISIH Nice

Subjects
Aged, 80 and over, Hospitalization, Frailty, SARS-CoV-2, [SDV]Life Sciences [q-bio], Humans, COVID-19, Comorbidity, Mortality, Pandemics, Aged, Retrospective Studies, premature
Abstract

Introduction Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. Methods Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital’s electronic medical records was performed. Results Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients’ profiles varied according to the epidemic periods: during the first period (March–June 2020), more patients were institutionalized. The second period (September–December2020) coincided with a higher mortality rate. Conclusions This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.

Published
2022
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26. Obesity, diabetes, hypertension and severe outcomes among inpatients with coronavirus disease 2019: a nationwide study

Author

Christian Pradier, Jean Dellamonica, Michel Carles, Laurent Bailly, Roxane Fabre, and Johan Courjon

Subjects
Microbiology (medical), Mechanical ventilation, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Retrospective cohort study, General Medicine, medicine.disease, Obesity, Index score, Infectious Diseases, Internal medicine, Diabetes mellitus, Cohort, medicine, Medical history, business
Abstract

Objectives Initial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death. Methods All French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account. Results A total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9–2.1 and aOR 1.5, 95% CI 1.4–1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0–2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8–3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5–18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1–1.2) and diabetes (aOR 1.2, 95% CI 1.1–1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8–2.0), diabetes (aOR 1.4, 95% CI 1.3–1.4) and hypertension (aOR 1.7, 95% CI 1.6–1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3–3.7), diabetes (aOR 2.0, 95% CI 1.8–2.1) and hypertension (aOR 2.5, 95% CI 2.4–2.6). Conclusions Among 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.

Published
2022
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27. Accurate Detection of SARS-CoV-2 by Next-Generation Sequencing in Low Viral Load Specimens

Author

Marius Ilié, Jonathan Benzaquen, Véronique Hofman, Elodie Long-Mira, Sandra Lassalle, Jacques Boutros, Christophe Bontoux, Virginie Lespinet-Fabre, Olivier Bordone, Virginie Tanga, Maryline Allegra, Myriam Salah, Julien Fayada, Sylvie Leroy, Matteo Vassallo, Irit Touitou, Johan Courjon, Julie Contenti, Michel Carles, Charles-Hugo Marquette, and Paul Hofman

Subjects
Inorganic Chemistry, next generation sequencing, SARS-CoV-2, Organic Chemistry, COVID-19, General Medicine, Physical and Theoretical Chemistry, Genexus, Molecular Biology, low viral load, Spectroscopy, Catalysis, Computer Science Applications
Abstract

As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the city of Nice (France) over a period of 32 weeks (from 19 July 2021 to 11 February 2022). In total, 76% of cases were identified with a low viral load (Ct ≥ 32, and ≤200 copies/µL). The NGS analysis was successful in 91% of cases, among which 57% of cases harbored the Delta variant, and 34% the Omicron BA.1.1 variant. Only 9% of cases had unreadable sequences. There was no significant difference in the viral load in patients infected with the Omicron variant compared to the Delta variant (Ct values, p = 0.0507; copy number, p = 0.252). We show that the NGS analysis of the SARS-CoV-2 genome provides reliable detection of the Delta and Omicron SARS-CoV-2 variants in low viral load samples.

Published
2023
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30. Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a before-and-after, propensity-matched cohort study in a Caribbean intensive care unit

Author

Paul Bonjean, Frederic Martino, Régine Richard, Christophe Le Terrier, Sébastien Breurec, Elain Elie, Guillaume Thiery, Marco Vinetti, Marc Valette, Bertrand Pons, Bruno Jarrige, Edouard Ollier, Pascale Piednoir, Benjamin Madeux, Fanny Ardisson, and Michel Carles

Subjects
Male, Endemic Diseases, Intestinal microbiota, Antibiotics, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, Antimicrobial resistance, law.invention, Cohort Studies, Antimicrobial Stewardship, 0302 clinical medicine, law, 030212 general & internal medicine, Antibiotic stewardship, Health Policy, Incidence (epidemiology), Hazard ratio, Enterobacteriaceae Infections, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Intensive care unit, Anti-Bacterial Agents, Female, Meningitis, Adult, medicine.medical_specialty, medicine.drug_class, Enterobacter, Statistics, Nonparametric, beta-Lactamases, 03 medical and health sciences, Antibiotic resistance, Internal medicine, medicine, Humans, Propensity Score, Aged, Retrospective Studies, Caribbean, Septic shock, business.industry, RC86-88.9, Research, 030208 emergency & critical care medicine, medicine.disease, Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Propensity score matching, ESBL-E colonization, business
Abstract

Background High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). Methods We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. Results The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p p p p p = 0.02, and hazard ratio 0.751 [95% CI 0.578–0.977]; p = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p Conclusions Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.

Published
2021

31. 24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management

Author

David Chirio, Elisa Demonchy, Marion Le Marechal, Alice Gaudart, Romain Lotte, Michel Carles, and Raymond Ruimy

Subjects
Sepsis, Biochemistry (medical), Clinical Biochemistry, Humans, Bacteremia, General Medicine, Laboratories, Workflow, Retrospective Studies, Anti-Bacterial Agents
Abstract

Objectives We aimed to evaluate the impact of an uninterrupted workflow regarding blood cultures on turnaround time and antibiotic prescription. Methods Monomicrobial episodes of bacteremia were retrospectively evaluated before and after a continuous 24/7 workflow was implemented in our clinical microbiology laboratory (pre- and post-intervention periods; PREIP and POSTIP). Primary outcome was the time from specimen collection to the first change in antibiotic therapy. Secondary outcomes included the time from specimen collection to effective antibiotic therapy and to antibiotic susceptibility testing results (or turnaround time), as well as hospital length of stay and all-cause mortality at 30 days. Results A total of 548 episodes of bacteremia were included in the final analysis. There was no difference in PREIP and POSTIP regarding patient characteristics and causative bacteria. In POSTIP, the mean time to the first change in antibiotic therapy was reduced by 10.4 h (p Conclusions Around the clock processing of blood cultures allows for a reduction in turnaround time, which in turn reduces the delay until effective antibiotic therapy prescription.

Published
2022

32. Current perspectives for SARS-CoV-2 vaccination efficacy improvement in patients with active treatment against cancer

Author

Jérôme Barrière, Daniel Re, Michel Carles, and Frederic Peyrade

Subjects
0301 basic medicine, Cancer Research, COVID-19 Vaccines, Time Factors, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Third dose, Disease, medicine.disease_cause, Antibodies, Viral, Risk Assessment, 03 medical and health sciences, Current Perspective, 0302 clinical medicine, Immune system, Tumours, Immunogenicity, Vaccine, Risk Factors, Cause of Death, Neoplasms, Pandemic, Medicine, Humans, Coronavirus, Cancer, business.industry, Immunogenicity, Heterologous prime-boost vaccination, Vaccination, COVID-19, ARNm, medicine.disease, Immunity, Humoral, Hospitalization, 030104 developmental biology, SARS-CoV-2 vaccination, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Immunology, Double-dose, business, Vaccine
Abstract

A higher risk of death from coronavirus disease 19 has been shown for patients with solid cancers or haematological malignancies (HM). Thanks to the accelerated development of anti-SARS-SoV-2 vaccines in less than a year since the start of the global pandemic, patients with cancer were quickly prioritised in early 2021 for vaccination, however dependent on the very unequal availability at the global level. Impaired immunogenicity of SARS-CoV-2 mRNA vaccines in immunocompromised patients was rapidly reported as early as April 2021, although the vaccination fortunately appears to be generally effective without increasing the spacing. Worryingly, the humoral response of the SARS-CoV-2 vaccination is, however, considered insufficient in patients followed for HM, in particular when they are on anti-CD20 treatment. Thus, improving vaccination coverage by strengthening immune stimulation should be evaluated in patients under active treatment against cancer. Here, we discuss three different approaches: a third dose of early vaccine (repeated immune stimulation), heterologous prime-boost vaccination (multimodal immune stimulation) and a double-dose strategy (maximisation of immune response). Dedicated therapeutic trials, currently almost non-existent, seem rapidly necessary.

Published
2021

33. Decompressive craniectomy as a rescue treatment in Herpes simplex encephalitis-related cerebral edema: a case report and literature review

Author

Rémi Malhomme, Laurent Do, Michel Carles, Jean-David Pommier, and Laure Flurin

Subjects
medicine.medical_specialty, business.industry, Decompression, medicine.medical_treatment, Guideline, Emergency department, Emergency Nursing, medicine.disease, medicine.disease_cause, Cerebral edema, Surgery, Herpes simplex virus, Emergency Medicine, Medicine, Decompressive craniectomy, business, Encephalitis, Intracranial pressure
Abstract

We present a case of herpes simplex encephalitis requiring decompressive craniectomy for high intracranial pressure, and a review of decompressive craniectomy in herpes simplex encephalitis. Case description and review: a 32-year-old man was brought to emergency department for headache and fever. The cerebral spinal fluid examination found lymphocytic meningitis; treatment by acyclovir was initiated 4 days after admission. At day 5, patient developed clinical signs of high intracranial pressure and CT-scan showed cerebral herniation. After medical management fail, a decompressive craniectomy was performed on the same day. The procedure resulted in a good clinical recovery with minor neurological sequelae. A literature review, presented here, found few cases of decompressive craniectomy in herpes simplex encephalitis. Due to a lack of robust clinical data, no guideline are yet available. In summary, a surgical approach, such as a decompressive craniectomy, in herpes simplex encephalitis with high intracranial pressure should be discussed early, in association with the medical treatment. Prospective data are needed to better define timing of surgery and decision-making criteria.

Published
2021
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34. Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity

Author

Géraldine Gonfrier, Laurent Yvan-Charvet, Laurent Bailly, Julie Contenti, Christelle Pomares-Estran, David Chirio, Laurent Boyer, Céline Loubatier, Orane Visvikis, Michel Carles, Océane Dufies, Patrick Munro, Arnaud Jacquel, Cedric Torre, Sébastien Vitale, Anne Doye, Valérie Giordanengo, Johan Courjon, Stoyan Ivanov, Jean Dellamonica, Romain Lotte, Patrick Auberger, and Alexandre Robert

Subjects
0301 basic medicine, Clinical Trials and Observations, Inflammasomes, Stimulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, Myeloid Cells, Prospective Studies, Prospective cohort study, Innate immune system, business.industry, SARS-CoV-2, Case-control study, COVID-19, Inflammasome, Hematology, Middle Aged, Peripheral, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Immunology, Biomarker (medicine), business, Biomarkers, medicine.drug
Abstract

Key Points Measurement of NLRP3 inflammasome activation in the blood of patients reveals an impaired immature neutrophil response in severe COVID-19. Inflammasome signature analysis in circulating myeloid cells allows COVID-19 patients to be stratified and predicts evolution., Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017., Visual Abstract

Published
2021

35. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

Author

David Hajage, Alain Combes, Christophe Guervilly, Guillaume Lebreton, Alain Mercat, Arthur Pavot, Saad Nseir, Armand Mekontso-Dessap, Nicolas Mongardon, Jean Paul Mira, Jean-Damien Ricard, Alexandra Beurton, Guillaume Tachon, Loay Kontar, Christophe Le Terrier, Jean Christophe Richard, Bruno Mégarbane, Ruth H. Keogh, Aurélien Belot, Camille Maringe, Clémence Leyrat, Matthieu Schmidt, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W. Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, Sébastian Voicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Meriam Lamraoui, Claire Alessandri, Quentin de Roux, Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien Pili Floury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris-Saclay, CHU Lille, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS [Créteil] (UPEC/Faculté de Médecine de Créteil), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Foch [Suresnes], CHU Amiens-Picardie, Geneva University Hospital (HUG), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], London School of Hygiene and Tropical Medicine (LSHTM), RICHARD, Jean-Christophe, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, Adult, Respiratory Distress Syndrome, SARS-CoV-2, [SDV]Life Sciences [q-bio], acute respiratory distress syndrome (ARDS), COVID-19, extracorporeal membrane oxygenation, Critical Care and Intensive Care Medicine, Cohort Studies, [SDV] Life Sciences [q-bio], emulated target trial, acute respiratory distress syndrome, Treatment Outcome, surgical procedures, operative, Humans, Retrospective Studies
Abstract

International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2

Published
2022
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36. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study

Author

Philippe PETUA, Xavier MONNET, Michael Levy, Alexy Tran Dinh, Rabih Hage, Marie Cantier, Nicolas WEISS, Marc Danguy des Déserts, Nicolas DUFOUR, Adrien Bouglé, Anne Godier, MICHEL CARLES, Laurent Bitker, Benjamin Glenn Chousterman, Olivier Lesieur, Céline Grégoire, Mathieu Page, Christophe LE TERRIER, Stephane Dauger, Hafid Ait-Oufella, Matthieu Daniel, Lionel Lamhaut, Martin Dres, Anatole Harrois, Jean-Pierre QUENOT, Sebastien Preau, Guillaume Louis, Valentin Pointurier, Pierre-Henri Moury, Alexandre Mebazaa, Thibault MARTINEZ, Maxime Léger, Sebastien Gette, Frank Chemouni, Benjamin Rohaut, GUILLAUME VOIRIOT, Nicolas TERZI, David Hajage, Tristan Morichau-Beauchant, International Network (INet), and Mégarbane, Bruno

Subjects
Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Original, medicine.medical_treatment, Critical Illness, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mechanical ventilation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Belgium, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Mortality risk factor, medicine, Humans, Hospital Mortality, Prospective Studies, Prospective cohort study, Outcome, Aged, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Respiratory Distress Syndrome, Acute respiratory distress syndrome, business.industry, SARS-CoV-2, Patient Acuity, COVID-19, Middle Aged, Respiration, Artificial, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Emergency medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, business
Abstract

Purpose To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. Methods COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. Results From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54–71] years and SAPS II 37 [28–50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10–14) cmH2O, and 24 (21–27) cmH2O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6–34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO2/FiO2 ratio and a shorter time between first symptoms and ICU admission. Conclusion Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients. Electronic supplementary material The online version of this article (10.1007/s00134-020-06294-x) contains supplementary material, which is available to authorized users.

Published
2020
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37. Prothèse totale de genou bilatérale en une session opératoire : complications tardives et courbe de survie

Author

Michel Carles, Yoann Lévy, Pascal Boileau, Antoine Raffaelli, Laurie Tran, Michel Azar, and Christophe Trojani

Subjects
030222 orthopedics, 03 medical and health sciences, 0302 clinical medicine, Orthopedics and Sports Medicine, Surgery, 030212 general & internal medicine
Abstract

Resume Introduction La morbi-mortalite precoce du remplacement prothetique bilateral de genou (PTG Bi) en une session operatoire est un sujet d’interet dans la litterature medicale. L’evolution clinique a long terme de cette strategie est quant a elle bien moins etudiee. L’objectif de cette etude etait de rapporter les complications tardives (> 90 jours), les resultats cliniques, KOOS et new IKS, ainsi que la survie prothetique des PTG Bi en une session operatoire. L’hypothese etait qu’une strategie de PTG Bi en une session operatoire entrainait peu de complications tardives et une survie prothetique compatible avec les criteres du National Institute of health and Clinical Excellence (NICE). Methode Cette etude retrospective monocentrique a analyse sur une periode de 8 ans, entre 2009 et 2016, une cohorte de patients ASA 1 et 2 operes par PTG bilaterales en une session operatoire. La population se composait de 116 patients, en majorite des femmes (65,5 % femmes vs 34,5 % d’hommes) avec un âge moyen a l’inclusion de 69 ans (32–85 ans) ; 22,4 % des patients etaient ASA 1 et 77,6 % ASA 2. Les complications tardives prothetiques, mecaniques ou infectieuses survenues apres les 90 premiers jours postoperatoires, les resultats cliniques (scores KOOS, new IKS) et radiographiques, ainsi que la courbe de survie, ont ete enregistres lors des consultations de controle systematiques a 3 mois, 6 mois et 1 an postoperatoire et lors du suivi a long terme ou lors d’un evenement intercurrent. Resultats Aucun patient n’etait perdu de vue. Quinze complications etaient recensees (6,5 %) : 4 infections, 4 problemes rotuliens (3 « clunck syndrome » et un syndrome douloureux rotulien), 4 raideurs, 2 douleurs inexpliquees et une fracture periprothetique femorale. Huit patients ont ete readmis (6,9 %) ; il y a eu 7 re-operations (3 %) et 2 revisions prothetiques (0,9 %). Les scores fonctionnels (KOOS et new IKS) etaient ameliores de maniere significative et 87 % des patients se disaient satisfaits ou tres satisfaits par cette intervention. A 5 ans de recul moyen, l’estimation de la survie prothetique par la methode de Kaplan-Meier etait de 98,4 % (IC 95 % = 0,933–0,996) Conclusion La realisation de PTG Bi en une session operatoire est une strategie fiable car elle engendre un faible taux de complications tardives, d’excellents resultats a moyen terme ainsi qu’une courbe de survie compatible avec les criteres du NICE, permettant ainsi de verifier l’hypothese de cette etude. Niveau de preuve IV, etude retrospective.

Published
2020
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38. PTH bilatérales en une session opératoire versus PTH unilatérales : analyse comparative rétrospective

Author

Christophe Trojani, Michel Carles, Grégoire Micicoi, Lolita Micicoi, Pascal Boileau, Régis Bernard de Dompsure, and Laurie Tran

Subjects
Gynecology, 030222 orthopedics, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, Medicine, Orthopedics and Sports Medicine, Surgery, 030212 general & internal medicine, business
Abstract

Resume Introduction Le remplacement prothetique bilateral de hanche offre l’avantage d’une seule anesthesie, d’un sejour hospitalier unique et d’une seule reeducation. L’ecueil theorique de cette strategie est une majoration du risque operatoire. Il existe peu de series francaises et aucune n’est comparative avec des arthroplasties unilaterales. Aussi, nous avons mene une etude comparative cas temoin de protheses bilaterales une seule seance (PTH Bi) versus unilaterales (PTH Uni) avec pour objectifs de : 1) comparer la morbi-mortalite, 2) la survie, 3) les scores fonctionnels et le taux de hanche oubliee. Hypothese Sur une population selectionnee ASA 1 ou 2 les PTH Bi ne modifiaient ni le le taux de complications ni la survie par rapport aux PTH unilaterales. Materiel et methode Entre 2004 et 2018, 327 patients ont ete inclus comportant 109 operes par PTH Bi et 218 operes par PTH Uni. Un patient opere par PTH bilaterale etait apparie a deux patients operes par PTH unilaterale selon l’âge, le sexe, le diagnostic, le score ASA 1 ou 2 et la voie d’abord anterieure ou posterieure. Le recul minimum etait de 12 mois et le recueil des complications dans les deux groupes a ete realise pour tous les patients. La morbi-mortalite precoce (≤ 90 jours) ou tardive (> 90 jours) etait renseignee ainsi que la survie prothetique des deux groupes. Les criteres secondaires concernaient la strategie d’epargne et les pertes sanguines, les scores fonctionnels et de satisfaction des patients. Resultats La mortalite etait nulle dans les deux groupes. Aucune difference significative concernant le taux de complications globales n’etait observee entre les groupes PTH Bi (38,5 %) versus PTH Uni (40,8 %) (p = 0,69) que les complications soient precoces (PTH Bi = 8,3 % [9/109] ; PTH Uni = 7,8 % [17/218] [p = 0,89]) ou tardives (PTH Bi = 30,3 % [33/109] ; PTH Uni = 33,0 % [72/218] [p = 0,61]). Le taux d’inegalite de longueur des membres inferieurs etait significativement inferieur dans le groupe PTH Bi (PTH Uni = (29/218) 13,3 % ; PTH Bi = [6/109] 5,5 % [p = 0,03]). Le taux de hanche oubliee etait significativement plus important dans le groupe PTH Bi (94/109 [86 %]) que dans le groupe PTH Uni (152/218 70 %) (p = 0,01). La survie de l’implant a 5 ans selon l’analyse de Kaplan-Meier etait de 97,2 % (IC 95 % = [91,9–99,1]) dans le groupe PTH Bi et de 96,6 % (IC 95 % = [93,0–98,4]) dans le groupe PTH Uni (p = 0,08). Discussion Cette etude montre que le remplacement prothetique bilateral en une session operatoire est une strategie recevable et non prejudiciable pour les patients presentant une coxarthrose bilaterale invalidante a faible risque operatoire (ASA 1 et 2). En effet sans modifier la mortalite, les complications ou la survie, la procedure bilaterale en une seance permet un meilleur controle des longueurs de membre et un taux de hanche oubliee plus important. Niveau de preuve III, etude cas temoin appariee.

Published
2020
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39. One-stage bilateral total hip arthroplasty versus unilateral total hip arthroplasty: A retrospective case-matched study

Author

Lolita Micicoi, Michel Carles, Laurie Tran, Pascal Boileau, Régis Bernard de Dompsure, Christophe Trojani, and Grégoire Micicoi

Subjects
musculoskeletal diseases, medicine.medical_specialty, Arthroplasty, Replacement, Hip, medicine.medical_treatment, Population, Osteoarthritis, Hip replacement (animal), 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Patient satisfaction, medicine, Humans, Orthopedics and Sports Medicine, education, Retrospective Studies, 030222 orthopedics, education.field_of_study, Rehabilitation, business.industry, 030229 sport sciences, medicine.disease, Arthroplasty, Surgery, Treatment Outcome, Case-Control Studies, Implant, business, Total hip arthroplasty
Abstract

Background One-stage bilateral hip replacement has the advantage of involving a single anesthesia, single hospital admission and single rehabilitation program. The theoretic drawback is increased surgical risk. Few French series have been reported, and none with comparison versus unilateral arthroplasty. We therefore conducted a comparative case-control study between 1-stage bilateral (1B-THA) and unilateral total hip arthroplasty (U-THA), assessing (1) morbidity/mortality, (2) survival, and (3) functional scores and forgotten hip rates. Hypothesis In a selected ASA 1 or 2 population, 1B-THA shows complications rates and implant survival comparable to U-THA. Material and method Between 2004 and 2018, 327 patients were included: 109 with 1B-THA, 218 with U-THA. One 1B-THA patient was matched to 2 U-THA patients on age, gender, diagnosis, ASA score 1 or 2, and anterior or posterior approach. Minimum follow-up was 12 months. Complications were collected for all patients in both groups. Early (≤ 90 days) or late (> 90 days) morbidity/mortality and implant survival were recorded for both groups. Secondary endpoints concerned blood-sparing strategy and blood loss, functional scores, and patient satisfaction. Results Mortality was zero in both groups. There was no significant difference in complications rates (1B-THA 38.5%, U-THA 40.8%) (p = 0.69), whether early (8.3% [9/109] and 7.8% [17/218] respectively [p = 0.89]) or late (30.3% [33/109] and 33.0% [72/218] respectively [p = 0.61]). Limb-length discrepancy was significantly less frequent in 1B-THA (5.5% [6/109] versus 13.3% [29/218] [p = 0.03]). Forgotten hip rate was significantly more frequent in 1B-THA (86% [94/109] versus 70% [152/218] [p = 0.01]). Five-year Kaplan-Meier implant survival was 97.2% (95% CI [91.9–99.1]) in 1B-THA and 96.6% (95% CI [93.0–98.4]) in U-THA (p = 0.08). Discussion One-stage bilateral total hip arthroplasty gave acceptable results in disabling bilateral osteoarthritis of the hip with low surgical risk in selected patients (ASA 1 or 2). Mortality, complications and implant survival were unaffected, but the 1-stage bilateral procedure allowed better control of limb-length and provided a higher rate of forgotten hip. Level of evidence III, matched case-control study.

Published
2020
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40. Clindamycin Efficacy for

Author

Audrey, Courdurié, Romain, Lotte, Raymond, Ruimy, Vincent, Cauhape, Michel, Carles, Marc-Olivier, Gauci, Pascal, Boileau, and Johan, Courjon

Abstract

Clindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines forA retrospective analysis was conducted at the University Hospital of Nice (France) between 2010 and 2019. We included patients with one shoulder implant surgical procedure and at least oneForty-eight SIJI were identified and 33 were treated with clindamycin, among which 25 were treated with monotherapy. The median duration of clindamycin antibiotherapy was 6 weeks. The average follow-up was 45 months; one patient was lost to follow-up. Twenty-seven patients out of 33 (82%) were cured with clindamycin, compared to 9/12 (75%) with other antibiotics. The rate of favorable outcomes increased to 27/31 (87%) with clindamycin and to 9/10 (90%) for other antibiotics when no septic revision strategies were excluded (The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective.

Published
2022

41. Avdoralimab (anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FORCE)

Author

Julien Carvelli, Ferhat Meziani, Jean Dellamonica, Pierre-Yves Cordier, Jerome Allardet-Servent, Megan Fraisse, Lionel Velly, Saber Barbar, Samuel Lehingue, Christophe Guervilly, Maxime Desgrouas, Fabrice Camou, Christelle Piperoglou, Frederic Vely, Robert Zerbib, Emmanuel Mitry, Joyson Karakunnel, Joanna Fares, Luciana Batista, Federico Rotolo, Julien Viotti, Agnès Boyer-Chammard, Sabrina Carpentier, Olivier Demaria, Karine Lacombe, Erwan Le Dault, Nassima Chouaki-Benmansour, michel Carles, Nicolas Schleinitz, Eric Vivier, and The Force Study Group

Published
2022
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42. Low IFN-γ Response after Cell Stimulation Predicts Hospitalization in COVID-19 Patients

Author

Marion Cremoni, Jonathan Allouche, Daisy Graça, Kevin Zorzi, Céline Fernandez, Maxime Teisseyre, Sylvia Benzaken, Caroline Ruetsch-Chelli, Vincent LM Esnault, Jean Dellamonica, michel Carles, Jérôme Barrière, Vesna Brglez, and Barbara Seitz-Polski

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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43. MPox virus: an unusual aetiology of peritonitis

Author

Audrey Courdurié, Matthieu Buscot, Géraldine Gonfrier, Johan Courjon, Constantin Oncioiu, Elisa Demonchy, and Michel Carles

Subjects
Infectious Diseases, Dermatology
Abstract

We describe a rare case of severe disseminated monkeypox (MPox) virus infection complicated by peritonitis in a 44-year-old man living with well-controlled HIV. The patient was successfully treated with tecovirimat without requiring surgery. MPox should be considered in the differential diagnosis of non-bacterial peritonitis in patients at risk of infection.

Published
2023
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46. Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position paper

Author

Jérôme Barrière, Michel Carles, Clarisse Audigier-Valette, Daniel Re, Zoubir Adjtoutah, Barbara Seitz-Polski, Valérie Gounant, Diane Descamps, and Gérard Zalcman

Subjects
Cancer Research, COVID-19 Vaccines, Time Factors, Immunization, Secondary, Vaccine Efficacy, Review, anti-Spike antibodies, Antibodies, Viral, Immunocompromised Host, Monitoring, Immunologic, Neoplasms, vaccine, Humans, cancer, booster dose, Immunization Schedule, SARS-CoV-2, COVID-19, vaccination, Immunity, Humoral, monitoring, Treatment Outcome, Oncology, Seroconversion, Host-Pathogen Interactions, Spike Glycoprotein, Coronavirus, third dose, humoral response
Abstract

Taking into account higher risk of severe coronavirus disease 2019 (COVID-19) or death among patients with cancer, as well as impaired immunogenicity following anti-SARS-CoV-2 vaccines, in addition to waning immunity, booster dosing appears mandatory in this patient population. This review sought to provide reasonable evidence so as to assist oncologists in their daily practice, helping them decide when an anti-SARS-Cov2 antibodies (Abs) dosage should be scheduled following a full two-dose vaccination and if necessary, propose an early third dose (D3). Such D3 could apply to non-responder patients with anti-Spike (S) Abs titers < 40 binding antibody units (BAU)/mL. For low-responder patients with anti-S Abs titers between 40 BAU/mL and 100/260 BAU/mL (suggested area of uncertainty), an early D3 may similarly be proposed. Nevertheless, this D3 could be administered in a less urgent manner, taking into account associated co-morbidities and regional epidemic incidence rates. This latter strategy may comprise a monthly dosage of anti-S titers so as to better assess the kinetics of waning immunity. For responder patients with anti-S titers above 260 BAU/mL, we suggest to follow the recommendations outlined for the general population. Given this context, patients with anti-S titers above 1000 BAU/mL should be given the possibility to undergo anti-S titer control after 3 months, designed to assess rapid humoral waning immunity. We strongly recommend that patients with cancer be included into observational serological monitoring studies or clinical trials that are dedicated to severe immunocompromised patients without any humoral seroconversion after D3.

Published
2021

47. Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies

Author

Daniel Re, Barbara Seitz-Polski, Vesna Brglez, Michel Carles, Daisy Graça, Sylvia Benzaken, Stéphane Liguori, Khaled Zahreddine, Margaux Delforge, Béatrice Bailly-Maitre, Benjamin Verrière, Emmanuel Chamorey, and Jérôme Barrière

Subjects
Adult, Aged, 80 and over, Male, Immunity, Cellular, Multidisciplinary, SARS-CoV-2, T-Lymphocytes, Immunization, Secondary, General Physics and Astronomy, COVID-19, General Chemistry, Middle Aged, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, Immunity, Humoral, Hematologic Neoplasms, Spike Glycoprotein, Coronavirus, Humans, Female, Multiple Myeloma, BNT162 Vaccine, Aged
Abstract

Patients with hematological malignancies have impaired immune response after two doses of BNT162b2 (Pfizer/BioNTech) vaccine against SARS-CoV-2. Here, in this observational study (registration number HDH F20210324145532), we measure SARS-CoV-2 anti-Spike antibodies, neutralizing antibodies and T-cell responses after immune stimulation with a third dose (D3) of the same vaccine in patients with chronic lymphocytic leukemia (n = 13), B cell non-Hodgkin lymphoma (n = 14), and multiple myeloma (n = 16)). No unexpected novel side effects are reported. Among 25 patients with positive anti-S titers before D3, 23 (92%) patients increase their anti-S and neutralizing antibody titer after D3. All 18 (42%) initially seronegative patients remain negative. D3 increases the median IFN-γ secretion in the whole cohort and induces IFN-γ secretion in a fraction of seronegative patients. Our data thus support the use of a third vaccine dose amongst patients with lymphoid malignancies, even though some of them will still have vaccine failure.

Published
2021

48. COVID-19 patients age, comorbidity profiles and clinical presentation related to the SARS-CoV-2 UK-variant spread in the Southeast of France

Author

Pascal Barbry, Johan Courjon, Jean Dellamonica, Michel Carles, Géraldine Rios, Julie Contenti, Valérie Giordanengo, David Chirio, Caroline Bonnefoy, Jacques Levraut, and Elisa Demonchy

Subjects
Male, medicine.medical_specialty, Wastewater-Based Epidemiological Monitoring, Coronavirus disease 2019 (COVID-19), Respiratory distress syndrome, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, Nice, Comorbidity, Article, Hospitals, University, Internal medicine, Pandemic, medicine, Humans, computer.programming_language, Aged, Aged, 80 and over, Multidisciplinary, Sewage, business.industry, SARS-CoV-2, Incidence (epidemiology), Incidence, Age Factors, COVID-19, Emergency department, Middle Aged, medicine.disease, United Kingdom, Hospitalization, Viral infection, COVID-19 Nucleic Acid Testing, Medicine, Female, France, Presentation (obstetrics), business, computer
Abstract

The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p

Published
2021

49. Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

Author

Daniel Re, Barbara Seitz-Polski, Michel Carles, Vesna Brglez, Daisy Graça, Sylvia Benzaken, Stéphane Liguori, Khaled Zahreddine, Margaux Delforge, Benjamin Verrière, Emmanuel Chamorey, and Barrière Jérôme

Abstract

BACKGROUNDImmunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODSa vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTSAmong the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

Published
2021
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50. Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

Author

Margaux Delforge, Emmanuel Chamorey, Barbara Seitz-Polski, Benjamin Verrière, Stéphane Liguori, Vesna Brglez, Michel Carles, Khaled Zahreddine, Daisy Graça, Daniel Re, Jérôme Barrière, and Sylvia Benzaken

Subjects
medicine.medical_specialty, biology, business.industry, Chronic lymphocytic leukemia, medicine.disease, Gastroenterology, Chemotherapy regimen, Lymphoma, QuantiFERON, Titer, Immune system, Internal medicine, medicine, biology.protein, Antibody, business, Vaccine failure
Abstract

BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

Published
2021
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