Abstract
Rationale
Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid ...therapy.
Objectives
To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP).
Methods
We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics.
Measurements and main results
Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio aHR 1.29; 95% confidence interval 95% CI 1.05–1.58;
P
= 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53;
P
= 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60;
P
= 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61;
P
= 0.0003).
Conclusions
Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.
Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients ...are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation.
We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation.
Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio HR, 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57).
Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.
Background
Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a ...multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation.
Methods
We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC.
Results
During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (
p
< 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 0.38–0.83;
p
= 0.004) (Table
2
). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 0.33–0.89;
p
= 0.005) but not of BSI (IRR = 0.58, 0.25–1.34,
p
= 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%,
p
= 0.017).
Conclusions
In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence.
Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using ...poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers. This study showed that the cellular uptake and the phototoxicity of loaded Pheo-a are ten times higher than those of the free drug and revealed a very low cellular penetration of the fluorescence-labeled micelles. Neither loaded nor free Pheo-a displayed the same cellular localization as the labeled micelles. These results imply that the drug entered the cells without its carrier and probably without a disruption, as suggested by their stability in cell culture medium. These data allowed us to propose that Pheo-a directly migrates from the micelle to the cell without disruption of the vector. This mechanism will be discussed.
INRA, UR1282 Infectiologie Animale et Santé Publique, F-37380 Nouzilly, France
In Escherichia coli, the assembly of outer-membrane proteins (OMP) requires the BAM complex and periplasmic chaperones, ...such as SurA or DegP. Previous work has suggested a potential link between OMP assembly and expression of the genes encoding type-III secretion systems. In order to test this hypothesis, we studied the role of the different lipoproteins of the BAM complex (i.e. BamB, BamC, BamD and BamE), and the periplasmic chaperones SurA and DegP, in these two phenotypes in Salmonella . Analysis of the corresponding deletion mutants showed that, as previously described with the bamB mutant, BamD, SurA and, to a lesser extent, BamE play a role in outer-membrane biogenesis in Salmonella Enteritidis, while the membrane was not notably disturbed in bamC and degP mutants. Interestingly, we found that BamD is not essential in Salmonella, unlike its homologues in Escherichia coli and Neisseria gonorrhoeae . In contrast, BamD was the only protein required for full expression of T3SS-1 and flagella, as demonstrated by transcriptional analysis of the genes involved in the biosynthesis of these T3SSs. In line with this finding, bamD mutants showed a reduced secretion of effector proteins by these T3SSs, and a reduced ability to invade HT-29 cells. As surA and bamE mutants had lower levels of OMPs in their outer membrane, but showed no alteration in T3SS-1 and flagella expression, these results demonstrate the absence of a systematic link between an OMP assembly defect and the downregulation of T3SSs in Salmonella ; therefore, this link appears to be related to a more specific mechanism that involves at least BamB and BamD.
Correspondence Isabelle Virlogeux-Payant Isabelle.Virlogeux-Payant{at}tours.inra.fr
Abbreviations: OM, outer membrane; OMP, outer-membrane protein; T3SS, type-III secretion system
La valeur du désaccord Aubert, Isabelle; Ballangé, Aliénor; Debono, Marc ...
2020
eBook, Book
Odprti dostop
Aussi familier soit-il, le désaccord déconcerte et déroute. Qu’on s’en délecte ou qu’on le fuit, objet secret de désir ou de crainte, le désaccord reste une énigme. Le concept, sans cesse, se dérobe ...et résiste. Il échappe aux tentatives de le réduire à une définition trop étroite, sans souplesse ni texture. À contre-courant des idées reçues, à rebours de la doxa philosophique, le présent ouvrage travaille à révéler l’unité structurelle et la valeur profonde du désaccord. Dès lors, les vingt-trois contributions réunies ici en dévoilent le sens et la grandeur, par contraste avec ce qu’il n’est pas. Dans la diversité des approches, elles incitent à une conversion du regard et permettent de percevoir le désaccord comme une occasion, une chance et une richesse. Elles aident à en cerner la variété des fonctions, logiques et usages. Une variété qui, tout compte fait, raconte l’histoire de la démocratie – sa complexité et les doutes permanents qui l’habitent. Distincts et pourtant complémentaires, tous ces points de vue éclairent un même enjeu, d’une actualité brûlante : la liberté et les défis posés par sa pratique. En effet, que serait la liberté sans la possibilité même du désaccord, sans les occasions multiples, et parfois contradictoires, de le faire valoir, de le revendiquer, de l’assumer ? Une coquille vide et un terrain sur lequel rien ne pousse ! Arpenter le chemin démocratique du désaccord, n’est-ce pas, dès lors, redonner à la liberté son courage et sa vitalité ?
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