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

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 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. 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/)

Genre, histoire des femmes et histoire sociale

Tilly Louise A., Yvon-Deyme Brigitte, Deyme Michel. Genre, histoire des femmes et histoire sociale. In: Genèses, 2, 1990. A la découverte du fait social, sous la direction de Robert Salais. pp. 148-167

Aggregation of hydrophobically modified polysaccharides in solution and at the air–water interface

International audienceThe present article focuses on the comparative study of physicochemical properties of two ionic pullulan derivatives modified by 10 or 35 C8 chains per 100 anhydroglucose units, named CMP10C8 and CMP35C8, respectively. In aqueous solutions, these derivatives exhibited an associative behavior as evidenced by pyrene fluorescence spectroscopy. This phenomenon, which stems from intra- and/or intermolecular interactions between the hydrophobic groups grafted on the polymer backbone, results in the formation of more or less condensed aggregates depending on the C8 ratio and the ionic strength of the media. The hydrophobically modified pullulans also displayed surface properties. Their adsorption at the air–solution interface was assessed from surface tension measurements. The results showed that both hydrophobized polymers adsorb in a coil conformation occupying a large interfacial molecular area. The comparison of these molecular areas indicated that CMP35C8 adopts a more shrunken conformation at the interface than CMP10C8, due to stronger intramolecular interactions. The stability of the adsorbed monolayer under bulk dilution was investigated by ellipsometric measurements. Whereas bulk dilution had no effect on the stability of the adsorbed CMP35C8 film, it provoked significant changes in the adsorbed CMP10C8 monolayer. The stability of the CMP35C8 monolayers was attributed to the existence of intermolecular associations between the adsorbed coils

Enhancement of the Solubility and Efficacy of Poorly Water-Soluble Drugs by Hydrophobically-Modified Polysaccharide Derivatives

International audiencePurposeThis work was intended to develop and evaluate a new polymeric system based on amphiphilic carboxymethylpullulans (CMP49C8 and CMP12C8) that can spontaneously self-assemble in aqueous solutions and efficiently solubilize hydrophobic drugs.MethodsThe self-assembling properties of CMP49C8 and CMP12C8 were characterized by fluorescence spectroscopy and surface tension measurements. The solubilization of benzophenone and docetaxel was assessed from surface tension measurements, UV spectrometry and HPLC assays. The in vitro cytoxicity of CMP49C8 solutions and the docetaxel commercial vehicle (Tween 80®/Ethanol–water) were evaluated in the absence and in the presence of docetaxel.ResultsCompared to CMP12C8, CMP49C8 in aqueous solutions appeared to self-organize into monomolecular aggregates containing hydrophobic nanodomains, and to significantly increase the apparent solubility of benzophenone. Docetaxel solubility could also be improved in the presence of CMP49C8 but to a lower extent due to the surface properties of the drug. Nevertheless, in vitro, the cytotoxicity studies revealed that against cancer cells, the CMP49C8-docetaxel formulation was equipotent to the commercial docetaxel one. Furthermore, in the absence of the drug, CMP49C8 appeared less cytotoxic against macrophages than the Tween® 80/Ethanol–water.ConclusionsCMP49C8 is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations

Influence of alkyl chains length on the conformation and solubilization properties of amphiphilic carboxymethylpullulans

International audienceThe existence of inter- and/or intramolecular interactions in aqueous solutions of hydrophobically modified polysaccharides induces specific macromolecular conformations at the air–solution interface and in the bulk, where hydrophobic microdomains may be formed. The present work focuses on the interfacial and solubilizing properties of amphiphilic pullulans (CMP12C8, CMP7C14, and CMP4C16) differing in the length and percentage of alkyl chains grafted to the anhydroglucose units. The surface tension studies of these polymers evidence a marked difference between the interfacial properties of CMP12C8 on one hand and those of CMP7C14 and CMP4C16 on the other hand. Pyrene fluorescence spectroscopy and benzophenone solubilization experiments demonstrate a similar partition. Increasing alkyl chains length from eight up to 14 or 16 carbons improves the solubilization properties of nonpolar molecules, even though at the same time, the average number of grafted chains per 100 anhydroglucose units is decreased from 12 down to seven and four for the three compounds, respectively

Influence of alkyl chains length on the conformation and solubilization properties of amphiphilic carboxymethylpullulans

International audienceThe existence of inter- and/or intramolecular interactions in aqueous solutions of hydrophobically modified polysaccharides induces specific macromolecular conformations at the air–solution interface and in the bulk, where hydrophobic microdomains may be formed. The present work focuses on the interfacial and solubilizing properties of amphiphilic pullulans (CMP12C8, CMP7C14, and CMP4C16) differing in the length and percentage of alkyl chains grafted to the anhydroglucose units. The surface tension studies of these polymers evidence a marked difference between the interfacial properties of CMP12C8 on one hand and those of CMP7C14 and CMP4C16 on the other hand. Pyrene fluorescence spectroscopy and benzophenone solubilization experiments demonstrate a similar partition. Increasing alkyl chains length from eight up to 14 or 16 carbons improves the solubilization properties of nonpolar molecules, even though at the same time, the average number of grafted chains per 100 anhydroglucose units is decreased from 12 down to seven and four for the three compounds, respectively

Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

International audienceBackground: The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (&gt; 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods: Characteristics, management, and prognosis of critically ill old patients (&gt; 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results: The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p &lt; 0·001). Conclusion: Patients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission

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

International audienc