Publications by authors named "Saad Nseir"

183 Publications

Nationwide retrospective study of critically ill adults with sickle cell disease in France.

Sci Rep 2021 Nov 30;11(1):23132. Epub 2021 Nov 30.

Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Hôtel-Dieu, 30 Bd. Jean Monnet, 44093, Nantes Cedex 1, France.

Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.
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http://dx.doi.org/10.1038/s41598-021-02437-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632921PMC
November 2021

Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study.

Lancet Respir Med 2021 Nov 26. Epub 2021 Nov 26.

CHU Necker Enfants Malades-APHP, Paris, France.

Background: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care.

Methods: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221.

Findings: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001).

Interpretation: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19.

Funding: Pfizer.
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http://dx.doi.org/10.1016/S2213-2600(21)00442-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626095PMC
November 2021

Incidence, clinical characteristics, and outcome after unexpected cardiac arrest among critically ill adults with COVID-19: insight from the multicenter prospective ACICOVID-19 registry.

Ann Intensive Care 2021 Nov 13;11(1):155. Epub 2021 Nov 13.

Medical and Toxicological Intensive Care Unit, Inserm U942, Assistance Publique Hôpitaux de Paris (AP-HP), Centre Hospitalier Universitaire Lariboisière, Paris, France.

Background: Initial reports have described the poor outcome of unexpected cardiac arrest (CA) in intensive care unit (ICU) among COVID-19 patients in China and the USA. However, there are scarce data on characteristics and outcomes of such CA patients in Europe.

Methods: Prospective registry in 35 French ICUs, including all in-ICU CA in COVID-19 adult patients with cardiopulmonary resuscitation (CPR) attempt. Favorable outcome was defined as modified Rankin scale ranging from 0 to 3 at day 90 after CA.

Results: Among the 2425 COVID-19 patients admitted to ICU from March to June 2020, 186 (8%) experienced in-ICU CA, of whom 146/186 (78%) received CPR. Among these 146 patients, 117 (80%) had sustained return of spontaneous circulation, 102 (70%) died in the ICU, including 48 dying within the first day after CA occurrence and 21 after withdrawal of life-sustaining therapy. Most of CA were non-shockable rhythm (90%). At CA occurrence, 132 patients (90%) were mechanically ventilated, 83 (57%) received vasopressors and 75 (51%) had almost three organ failures. Thirty patients (21%) had a favorable outcome. Sepsis-related organ failure assessment score > 9 before CA occurrence was the single parameter constantly associated with unfavorable outcome in multivariate analysis.

Conclusions: In-ICU CA incidence remains high among a large multicenter cohort of French critically ill adults with COVID-19. However, 21% of patients with CPR attempt remained alive at 3 months with good functional status. This contrasts with other recent reports showing poor outcome in such patients.

Trial Registration: This study was retrospectively registered in ClinicalTrials.gov (NTC04373759) in April 2020 ( https://www.clinicaltrials.gov/ct2/show/NCT04373759?term=acicovid&draw=2&rank=1 ).
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http://dx.doi.org/10.1186/s13613-021-00945-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590126PMC
November 2021

Factors associated with Pneumocystis colonisation and circulating genotypes in COPD patients with acute exacerbation or at stable state and their homes.

Med Mycol 2021 Nov 3. Epub 2021 Nov 3.

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.

Pneumocystis jirovecii colonisation is frequent during COPD and patients constitute potential contributors to its interhuman circulation. However, the existence of an environmental reservoir cannot be excluded. We assessed the prevalence and factors associated with Pneumocystis colonisation during COPD, and studied circulation between patients and their domestic environment. Pneumocystis molecular detection and mtLSU genotyping were performed in oro-pharyngeal washes (OPW) sampled in 58 patients with COPD acute exacerbation, and in indoor dust, sampled in patients' homes using electrostatic dust collectors (EDCs). Lung and systemic inflammation was assessed. Pneumocystis carriage was evaluated in 28 patients after 18 months at stable state. Pneumocystis was detected in 11/58 OPWs during exacerbation (19.0%). Colonised patients presented a significantly lower body mass index, and higher serum IL-17 and CD62P. One patient presented positive detection of typable isolates in both OPW and EDC, with both isolates harbouring mtLSU genotype 3. Pneumocystis genotype 1 was further detected in EDCs from 3 non-colonised patients and 1 colonised patient with non-typable isolate. Genotypes 1 and 2 were predominant in clinical isolates (both 42%), with genotype 3 representing 16% of isolates. Pneumocystis was detected in 3/28 patients at stable state (10.7%). These data suggest that Pneumocystis colonisation could be facilitated by a lower BMI and be related to acute alteration of lung function during COPD exacerbation. It also suggests Th17 pathway and platelet activation could be involved in the anti-Pneumocystis response during colonisation. Lastly, Pneumocystis detection in EDCs supports its potential persistence in indoor dust.

Lay Summary: COPD patients tend to be more frequently colonised by Pneumocystis during exacerbation (19.0%) than at stable state (10.7%). Factors associated with colonisation include lower BMI, higher IL-17 and CD62P. Pneumocystis detection in patients' dwellings suggests potential persistence in indoor dust.
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http://dx.doi.org/10.1093/mmy/myab070DOI Listing
November 2021

Reply to: The Mystery of Futility of Appropriate Antibiotics for Co-Infection in COVID-19.

Am J Respir Crit Care Med 2021 Sep 21. Epub 2021 Sep 21.

Salengro hospital, CHRU de Lille, ICU, Lille, France;

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http://dx.doi.org/10.1164/rccm.202108-1846LEDOI Listing
September 2021

Multinational Observational Cohort Study of COVID-19-Associated Pulmonary Aspergillosis.

Emerg Infect Dis 2021 11 14;27(11):2892-2898. Epub 2021 Sep 14.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.
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http://dx.doi.org/10.3201/eid2711.211174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544971PMC
November 2021

High Incidence of Nosocomial Infections in COVID-19 Patients: Is SARS-CoV-2 the Culprit?

Chest 2021 09;160(3):e315

Médecine Intensive-Réanimation, CHU de Lille, Lille, France; Unité de Glycobiologie Structurale et Fonctionnelle, Inserm U1285, University of Lille, Lille, France. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2021.04.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413842PMC
September 2021

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.

Lancet Respir Med 2021 Dec 20;9(12):1387-1395. Epub 2021 Aug 20.

Clinical Investigation Center, INSERM 1415, CHRU Tours, Tours, France; Methods in Patients-Centered Outcomes and Health Research, INSERM UMR 1246, Nantes, France.

Background: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial.

Methods: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655.

Findings: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups.

Interpretation: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula.

Funding: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.
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http://dx.doi.org/10.1016/S2213-2600(21)00356-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378833PMC
December 2021

Response.

Chest 2021 Aug;160(2):e248-e249

Medecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes.

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http://dx.doi.org/10.1016/j.chest.2021.03.036DOI Listing
August 2021

Continuous Control of Tracheal Cuff Pressure and Ventilator-Associated Pneumonia: Beyond Agate and Feng Shui.

Chest 2021 Aug;160(2):393-395

Médecine Intensive-Réanimation, CHU de Lille, Lille, France; Centre d'Infection et d'Immunité de Lille, Univ. Lille, CHU de Lille, Institut Pasteur de Lille, Lille, France.

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http://dx.doi.org/10.1016/j.chest.2021.04.005DOI Listing
August 2021

COVID-19-associated invasive pulmonary aspergillosis: high incidence or difficult diagnosis?

Intensive Care Med 2021 11 3;47(11):1337-1338. Epub 2021 Aug 3.

Médecine Intensive-Réanimation, CHU de Lille, F-59000, Lille, France.

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http://dx.doi.org/10.1007/s00134-021-06499-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329628PMC
November 2021

Secondary pneumonias in critically ill patients with COVID-19: risk factors and outcomes.

Curr Opin Crit Care 2021 10;27(5):468-473

CHU de Lille, Centre de Réanimation.

Purpose Of Review: The aim of this review is to provide an overview of the current evidence of secondary pneumonias in COVID-19 patients, its incidence, risk factors and impact outcomes.

Recent Findings: Early studies reported low incidence of hospital-acquired infections in COVID-19 patients. More recent large studies clearly showed that the incidence of secondary pneumonias was markedly high in patients under mechanical ventilation. Duration of mechanical ventilation, acute respiratory distress syndrome, prone position and male sex were identified as risk factors. The adjunctive therapy with steroids and immunomodulators were associated with a higher risk of pneumonia and invasive pulmonary Aspergillosis. Although secondary pneumonias seemed to be associated with poor outcomes, namely mortality, in comparison with influenza, no difference was found in heterogeneity of outcomes. Immunosuppressive therapy has been studied in several observational and randomized trials with conflicting results and the true impact on superinfections, namely secondary pneumonias, has not been properly assessed.

Summary: According to the current evidence, COVID-19 patients are at an increased risk of secondary pneumonias. The impact of immunosuppressive therapies on superinfections is yet to be determined. Further studies are needed to assess the true risk of secondary infections associated with immunosuppressive therapies and to identify preventive strategies.
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http://dx.doi.org/10.1097/MCC.0000000000000860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452245PMC
October 2021

Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial.

Ann Intensive Care 2021 Jul 22;11(1):114. Epub 2021 Jul 22.

Médecine Intensive Réanimation, CHU de Poitiers, Poitiers, France.

Background: Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity.

Methods: Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO/FiO < 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure.

Results: Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI - 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77-93] with noninvasive ventilation and 86% [78-92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission.

Conclusions: Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov ).
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http://dx.doi.org/10.1186/s13613-021-00892-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295638PMC
July 2021

Hyperbaric hyperoxemia as a risk factor for ventilator-acquired pneumonia?

PLoS One 2021 23;16(6):e0253198. Epub 2021 Jun 23.

Intensive Care Unit and Hyperbaric Center, Lille University Hospital, Lille, France.

Objectives: Ventilator-acquired pneumonia (VAP) is the leading cause of serious associated infections in Intensive Care Units (ICU) and is associated with significant morbidity. The use of hyperbaric oxygen therapy (HBOT) in patients on mechanical ventilation may increase exposure to certain risk factors such as hyperoxemia and the need for multiple transfers. The aim of our study was to assess the relationship between HBOT and VAP.

Method: This retrospective observational study was performed from March 2017 to March 2018 in a 10-bed ICU using HBOT. All patients receiving mechanical ventilation (MV) for more than 48 hours were eligible. VAP was defined using clinical and radiological criteria. Data collection was carried out via digital medical records. Risk factors for VAP were determined by univariate and multivariate analysis.

Results: Forty-two (23%) of the 182 patients enrolled developed at least one episode of VAP. One hundred and twenty-four (68%) patients received HBOT. The incidence rate of VAP was 34 per 1000 ventilator days. The occurrence of VAP was significantly associated with immunosuppression (p<0.029), MV duration (5 [3-7] vs 8 [5-11.5] days, p<0.0001), length of stay (8 [5-13] vs 19.5 [13-32] days, p<0.0001), reintubation (p<0.0001), intra-hospital transport (p = 0.001), use of paralytic agents (p = 0.013), tracheotomy (p = 0.003) and prone position (p = 0.003). The use of HBOT was not associated with the occurrence of VAP. Multivariate analysis identified reintubation (OR: 8.3 [2.6-26.6]; p<0.0001), intra-hospital transport (OR: 3.5 [1.3-9.2]; p = 0.011) and the use of paralytic agents (OR: 3.3 [1.3-8.4]; p = 0.014) as independent risk factors for VAP.

Conclusion: Known risk factors for VAP are to be found within our ICU population. HBOT, however, is not an extra risk factor for VAP within this group. Further experimental and clinical investigations are needed to understand the impact of HBOT on the occurrence of VAP and on physiological microbiome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253198PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221473PMC
November 2021

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

Ann Intensive Care 2021 Jun 4;11(1):90. Epub 2021 Jun 4.

Service de Médecine Intensive Réanimation-Unité de Sevrage Ventilatoire et Réhabilitation, CH de Bethune, Bethune, France.

Background: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France.

Methods: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses.

Results: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11.

Conclusion: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).
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http://dx.doi.org/10.1186/s13613-021-00880-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177250PMC
June 2021

Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial.

Intensive Care Med 2021 06 29;47(6):674-686. Epub 2021 May 29.

Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Purpose: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA.

Methods: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population).

Results: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment.

Conclusion: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU.
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http://dx.doi.org/10.1007/s00134-021-06431-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164057PMC
June 2021

An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.

Clin Microbiol Infect 2021 Dec 26;27(12):1826-1837. Epub 2021 May 26.

CHR Metz-Thionville, Service de Réanimation Polyvalente, Ars-Laquenexy, France.

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.

Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.

Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.

Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
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http://dx.doi.org/10.1016/j.cmi.2021.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149166PMC
December 2021

Early Bacterial Identification Among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Cohort Study.

Am J Respir Crit Care Med 2021 May 26. Epub 2021 May 26.

Hôpital Pellegrin-Tripode , Service de Reanimation , Bordeaux, France.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines.

Objective: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes.

Methods: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test.

Measurements And Main Results: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients.

Conclusions: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1164/rccm.202101-0030OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491267PMC
May 2021

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.

Crit Care 2021 05 25;25(1):177. Epub 2021 May 25.

Département de Médecine Intensive-Réanimation, CHU D'Angers, Université D'Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.

Background: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients.

Methods: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event.

Findings: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups.

Interpretation: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality.

Clinical Trial Registration: The study was registered at ClinicalTrials.gov, number NCT04359693.
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http://dx.doi.org/10.1186/s13054-021-03588-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146175PMC
May 2021

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BMJ Open 2021 05 11;11(5):e045041. Epub 2021 May 11.

Service de Médecine Intensive Réanimation, Centre Hospitalier de Valenciennes, Valenciennes, France.

Introduction: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.

Methods And Analysis: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.

Ethics And Dissemination: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT03573739.
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http://dx.doi.org/10.1136/bmjopen-2020-045041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117996PMC
May 2021

Vascular access for renal replacement therapy among 459 critically ill patients: a pragmatic analysis of the randomized AKIKI trial.

Ann Intensive Care 2021 Apr 8;11(1):56. Epub 2021 Apr 8.

French National Institute of Health and Medical Research (INSERM), UMR_S1155, Remodeling and Repair of Renal Tissue, Hôpital Tenon, Sorbonne Université, 75020, Paris, France.

Background: Vascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury.

Patients And Methods: We performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected.

Results: Among the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34-4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98-1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64-1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred.

Conclusion: Femoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.
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http://dx.doi.org/10.1186/s13613-021-00843-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032839PMC
April 2021

Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial.

Lancet 2021 04;397(10281):1293-1300

Réanimation médicale, CHRU de Lille, Hôpital Roger Salengro, Lille, France.

Background: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.

Methods: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.

Findings: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.

Interpretation: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.

Funding: Programme Hospitalier de Recherche Clinique.
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http://dx.doi.org/10.1016/S0140-6736(21)00350-0DOI Listing
April 2021

Spatial and Temporal Virus Load Dynamics of SARS-CoV-2: A Single-Center Cohort Study.

Diagnostics (Basel) 2021 Mar 3;11(3). Epub 2021 Mar 3.

Laboratoire de Virologie, Univ Lille, CHU Lille, ULR3610, F-59000 Lille, France.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an ongoing pandemic. Reverse transcription polymerase chain reaction (RT-PCR) is the gold standard for the detection of SARS-CoV-2 and has been applied to different specimen types. Understanding the virus load and virus detection frequency in different specimen types is important to improve diagnosis and estimate the duration of potential infectivity. We conducted a retrospective single-center cohort study on hospitalized and outpatients with SARS-CoV-2 infection. We analyzed the frequency of virus detection, virus load, and duration of the virus excretion in upper and lower respiratory specimens as well as stool and plasma. We found that the frequency of SARS-CoV-2 detection, the virus load, and duration of virus excretion was higher in lower respiratory tract (LRT) than in upper respiratory tract (URT) specimens. The duration of virus excretion was longer in patients requiring intensive care unit (ICU) admission. In conclusion, LRT specimens are the most appropriate specimen type for the detection and follow-up of SARS-CoV-2 infection. Duration of virus excretion is longer in severe cases of SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/diagnostics11030427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999170PMC
March 2021

Neurophysiological findings and their prognostic value in critical COVID-19 patients: An observational study.

Clin Neurophysiol 2021 05 25;132(5):1009-1017. Epub 2021 Feb 25.

CHU Lille, Department of Clinical Neurophysiology, F-59000 Lille, France; Inserm, Univ Lille, CHU Lille, U1172, F-59000 Lille, France. Electronic address:

Objective: To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome.

Methods: EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations.

Results: 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions.

Conclusions: Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome.

Significance: The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19.
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http://dx.doi.org/10.1016/j.clinph.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906512PMC
May 2021

Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL.

BMJ Open 2021 02 12;11(2):e045659. Epub 2021 Feb 12.

Réanimation Médicale, CHU Dijon, Dijon, France.

Introduction: A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient's quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.

Methods And Analysis: This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.

Ethics And Dissemination: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT03673631.
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http://dx.doi.org/10.1136/bmjopen-2020-045659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883857PMC
February 2021

Impact of domestic mould exposure on Aspergillus biomarkers and lung function in patients with chronic obstructive pulmonary disease.

Environ Res 2021 04 9;195:110850. Epub 2021 Feb 9.

CHU Lille, Clinique des Maladies Respiratoires, 59000, Lille, France.

Patients with chronic obstructive pulmonary disease (COPD) are frequently colonised or sensitised by Aspergillus, but clinical significance remains unclear. Furthermore, little is known on the impact of indoor mould exposure during COPD. In this study, we assessed the relationship between domestic mould exposure, Aspergillus biomarkers and COPD severity during acute exacerbation and at stable state. Aspergillus section Fumigati culture in sputum and anti-Aspergillus antibodies detection (IgG and precipitins) were followed up in COPD patients that were prospectively recruited during exacerbation (n = 62), and underwent a visit at stable state after 18 months (n = 33). Clinical characteristics were collected at inclusion. Electrostatic dust collectors (EDCs) were used to measure domestic mould contamination. Aspergillus section Fumigati was more frequently detected during exacerbation (16.9%) than at stable state (4.0%), but the frequency of patients presenting with anti-Aspergillus antibodies was similar (32.2% and 33.3%, respectively). Aspergillus section Fumigati detection was associated with a higher body-mass index (BMI) during exacerbation, whereas patients with anti-Aspergillus antibodies presented a lower BMI and forced expiratory volume in 1 s, as well as a higher frequency of inhaled corticoids and higher total mould and Penicillium exposure at final visit (P < 0.05). The frequency of patients with anti-Aspergillus antibodies was higher for total mould counts >30 CFU/cm (P = 0.03). Aspergillosis was diagnosed in 2 patients (6.1%) who presented increased levels of antibodies. Our data suggest that anti-Aspergillus antibodies are associated with chronic lung function alteration and/or domestic mould exposure, thereby supporting the consideration of indoor mould contamination and anti-Aspergillus antibodies kinetics in COPD management.
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http://dx.doi.org/10.1016/j.envres.2021.110850DOI Listing
April 2021

Relationship Between Obesity and Ventilator-Associated Pneumonia: A Post Hoc Analysis of the NUTRIREA2 Trial.

Chest 2021 06 6;159(6):2309-2317. Epub 2021 Feb 6.

Medecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Université de Nantes, Nantes, France.

Background: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP).

Research Question: Is obesity associated with an increased incidence of VAP?

Study Design And Methods: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks.

Results: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients.

Interpretation: Our results suggest that obesity has no significant impact on the incidence of VAP.
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http://dx.doi.org/10.1016/j.chest.2021.01.081DOI Listing
June 2021
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