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/)

Qualité du sevrage ventilatoire des patients dépendant de la nicotine (rôle potentiel du syndrome de sevrage nicotinique)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Application of genetic and Spatially Explicit Capture-Recapture analyses to design adaptive feral cat control in a large inhabited island

Faunas of oceanic islands have a high proportion of endemic species which contribute to the uniqueness of island communities. Island species are particularly naïve and vulnerable to alien predators, such as cats (Felis catus). On large, inhabited islands, where the complete eradication of feral cat populations is not considered feasible, control represents the best management option to lower their detrimental effects on native fauna. The first objective of our study was to investigate population genetics of feral cats of Réunion Island. The second objective was to understand the space use of feral cats established near the breeding colonies of the two endemic and endangered seabirds of Réunion Island, the Barau’s Petrel (Pterodroma baraui) and the Mascarene Petrel (Pseudobulweria aterrima). We evaluated genetic diversity, population structure and gene flow amongst six groups of feral cats located at a maximum of 10 km from known petrel colonies. We also analysed the behaviour and space use of one of these feral cat groups using camera-trap data and Spatially Explicit Capture-Recapture (SECR) models. Genetic analyses revealed that feral cats were structured in three genetic clusters explained mostly by the island topography. Two clusters were observed at five sampled sites, suggesting high connectivity amongst these sites. The last cluster was found in only one site, suggesting high isolation. This site was a remote mountain area located in the vicinity of one of the main Barau’s Petrel colonies. The behavioural study was conducted on this isolated feral cat population. Mark recapture analysis suggested that feral cats were present at low density and had large home ranges, which is probably explained by reduced food availability. Finally, we make several recommendations for refining feral cat management programmes on inhabited islands

Application of genetic and Spatially Explicit Capture-Recapture analyses to design adaptive feral cat control in a large inhabited island

International audienceFaunas of oceanic islands have a high proportion of endemic species which contribute to the uniqueness of island communities. Island species are particularly naïve and vulnerable to alien predators, such as cats (Felis catus). On large, inhabited islands, where the complete eradication of feral cat populations is not considered feasible, control represents the best management option to lower their detrimental effects on native fauna. The first objective of our study was to investigate population genetics of feral cats of Réunion Island. The second objective was to understand the space use of feral cats established near the breeding colonies of the two endemic and endangered seabirds of Réunion Island, the Barau’s Petrel (Pterodroma baraui) and the Mascarene Petrel (Pseudobulweria aterrima). We evaluated genetic diversity, population structure and gene flow amongst six groups of feral cats located at a maximum of 10 km from known petrel colonies. We also analysed the behaviour and space use of one of these feral cat groups using camera-trap data and Spatially Explicit Capture-Recapture (SECR) models. Genetic analyses revealed that feral cats were structured in three genetic clusters explained mostly by the island topography. Two clusters were observed at five sampled sites, suggesting high connectivity amongst these sites. The last cluster was found in only one site, suggesting high isolation. This site was a remote mountain area located in the vicinity of one of the main Barau’s Petrel colonies. The behavioural study was conducted on this isolated feral cat population. Mark recapture analysis suggested that feral cats were present at low density and had large home ranges, which is probably explained by reduced food availability. Finally, we make several recommendations for refining feral cat management programmes on inhabited islands

Barau's petrel, Pterodroma baraui, as a bioindicator of plastic pollution in the South-West Indian Ocean: A multifaceted approach

International audienceMarine plastic pollution is well described by bioindicator species in temperate and polar regions but remains understudied in tropical oceans. We addressed this gap by evaluating the seabird Barau's petrel as bioindicator of plastic pollution in the South-West Indian Ocean. We conducted a multifaceted approach including necropsies of birds to quantify plastic ingestion; GPS tracking of breeding adults to identify their foraging areas; manta trawling of plastic debris to measure plastic pollution at sea and modelling of plastic dispersal. We developed a spatial risk index of seabird exposure to plastic ingestion. Seventy-one percent of the analysed birds had ingested plastic. GPS tracking coupled with manta trawling and dispersal modelling show that adults consistently foraged at places with high level of plastic concentration. The highest ingestion risk occurred in the northwest of Reunion Island and at latitude 30 degrees S. Our findings confirm that Barau's petrel is a reliable bioindicator of plastic pollution in the region

Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta

PurposeDominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.MethodsWe used in&nbsp;vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.ResultsWe found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.ConclusionOur study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity

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

Predicting 90-day survival of patients with COVID-19: Survival of Severely Ill COVID (SOSIC) scores

International audienceBackground Predicting outcomes of critically ill intensive care unit (ICU) patients with coronavirus-19 disease (COVID-19) is a major challenge to avoid futile, and prolonged ICU stays. Methods The objective was to develop predictive survival models for patients with COVID-19 after 1-to-2 weeks in ICU. Based on the COVID–ICU cohort, which prospectively collected characteristics, management, and outcomes of critically ill patients with COVID-19. Machine learning was used to develop dynamic, clinically useful models able to predict 90-day mortality using ICU data collected on day (D) 1, D7 or D14. Results Survival of Severely Ill COVID (SOSIC)-1, SOSIC-7, and SOSIC-14 scores were constructed with 4244, 2877, and 1349 patients, respectively, randomly assigned to development or test datasets. The three models selected 15 ICU-entry variables recorded on D1, D7, or D14. Cardiovascular, renal, and pulmonary functions on prediction D7 or D14 were among the most heavily weighted inputs for both models. For the test dataset, SOSIC-7’s area under the ROC curve was slightly higher (0.80 [0.74–0.86]) than those for SOSIC-1 (0.76 [0.71–0.81]) and SOSIC-14 (0.76 [0.68–0.83]). Similarly, SOSIC-1 and SOSIC-7 had excellent calibration curves, with similar Brier scores for the three models. Conclusion The SOSIC scores showed that entering 15 to 27 baseline and dynamic clinical parameters into an automatable XGBoost algorithm can potentially accurately predict the likely 90-day mortality post-ICU admission (sosic.shinyapps.io/shiny). Although external SOSIC-score validation is still needed, it is an additional tool to strengthen decisions about life-sustaining treatments and informing family members of likely prognosis

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

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Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

International audienceAbstract Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) ( P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% ( P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed