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/)

Organisation de la réanimation « hors les murs » en salle de surveillance post-interventionnelle et au bloc opératoire en phase d’épidémie de COVID-19

International audienceWe report here the implementation and the use during 24 days of critical care beds beyond the walls during the COVID-19 outbreak in a teaching university hospital in Paris. These beds were settled in a 14-bed recovery room and two adjacent operating theatres leading to 20 additional critical care beds. The historical timeline, architectural elements, human resources, organisation and medical devices issues are presented. The benefits and limitations of this organisation are discussed.Nous rapportons la mise en place et l’utilisation pendant 24 jours de lits de réanimation « hors les murs » à l’occasion de l’épidémie de COVID-19 dans un hôpital universitaire parisien. Ces lits créés dans une salle de surveillance post-interventionnelle de 14 postes et dans deux blocs opératoires attenants ont permis l’ouverture de 20 lits supplémentaires de réanimation. Les aspects chronologiques, architecturaux, de ressources humaines, d’organisation et de matériel sont présentés. Les avantages et inconvénients de cette organisation sont discutés

Bacteraemia Is Associated with Increased ICU Mortality in the Postoperative Course of Lung Transplantation

We aimed to describe the prevalence, risk factors, morbidity and mortality associated with the occurrence of bacteraemia during the postoperative ICU stay after lung transplantation (LT). We conducted a retrospective single-centre study that included all consecutive patients who underwent LT between January 2015 and October 2021. We analysed all the blood cultures drawn during the postoperative ICU stay, as well as samples from suspected infectious sources in case of bacteraemia. Forty-six bacteria were isolated from 45 bacteraemic patients in 33/303 (10.9%) patients during the postoperative ICU stay. Staphylococcus aureus (17.8%) was the most frequent bacteria, followed by Pseudomonas aeruginosa (15.6%) and Enterococcus faecium (15.6%). Multidrug-resistant bacteria accounted for 8/46 (17.8%) of the isolates. The most common source of bacteraemia was pneumonia (38.3%). No pre- or intraoperative risk factor for bacteraemia was identified. Recipients who experienced bacteraemia required more renal replacement therapy, invasive mechanical ventilation, norepinephrine support, tracheotomy and more days of hospitalization during the ICU stay. After adjustment for age, sex, type of LT procedure and the need for intraoperative ECMO, the occurrence of bacteraemia was associated with a higher mortality rate in the ICU (aOR = 3.55, 95% CI [1.56&ndash;8.08], p = 0.003). Bacteraemia is a major source of concern for lung transplant recipients

Personalized risk predictor for acute cellular rejection in lung transplant using soluble CD31

International audienceWe evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO 2 /FiO 2 ) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a “peace-maker” at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO 2 /FiO 2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort

Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy

First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation

High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study

International audienceSARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study

International audienceAbstract Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively ( p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable ( n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study

INTRODUCTION: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. METHODS: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. RESULTS: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5–0.9] mmol/L; [LDL-C] = 1.8[1.3–2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5–0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3–0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9–3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9–2.0] mmol/L in nonsurvivors, p = 0.006). CONCLUSION: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis