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/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Etude des variations de l'amplitude de la réflectivité du sous-sol après imagerie sismique en profondeur

In oil exploration, seismic reflexion imaging is commonly used. This method gives a first estimation of the structures of the sub-surface and also an estimation of the reflection coefficients changes which are related to changes in petrophysics parameters (density, compression and shear velocities). An analysis of these variations allows us to estimate the elastics parameters which are essential and complementary to the interpretation of the reservoirs. The classical processing consists in studying the amplitude variation directly on data recorded as a function of offset and time of propagation. The analysis is done using an inversion of a linear approximation of the Zoeppritz's equations governing the theoretical amplitude changes. In our case, we consider the analysis of the amplitude variation after the imaging step, directly in the depth domain. In order to success in this analysis, we propose a post-imaging processing before the amplitude versus angle analyse to compensate for erroneous migration velocity fields, interference of the wavelet in the case of thin bed and the wavelet stretching. This processing also gives us a skeleton which represents a depth interpretation of the geologic structure.En exploration pétrolière, la technique d'imagerie la plus couramment utilisée reste l'imagerie par sismique réflexion. Elle permet d'obtenir une première représentation des structures géologiques mais aussi une estimation du coefficient de réflexion des interfaces du sous-sol. Les variations de ce coefficient dépendent des paramètres pétrophysiques des milieux situés de part et d'autre de la discontinuité donnant naissance à la réflexion (densité et vitesses des ondes de propagation et de cisaillement). Une analyse de ces variations permet ainsi d'évaluer les paramètres élastiques qui sont des données indispensables et complémentaires à l'interprétation des réservoirs. Les traitements classiques consistent à étudier ces variations directement sur des données enregistrées en fonction du déport et du temps de propagation. L'analyse s'effectue par inversion d'une approximation linéaire des équations de Zoeppritz régissant les variations théoriques de l'amplitude. Nous proposons ici d'étudier les variations de l'amplitude après la phase d'imagerie, directement dans le domaine profondeur. Pour réaliser cette analyse, nous proposons un traitement spécifique après l'imagerie et avant l'analyse de l'amplitude pour corriger les impacts liés à la qualité du modèle de vitesse, à l'interférence des ondelettes entre deux réflexions proches et à l'étirement de l'ondelette. Ce traitement a aussi permis l'obtention d'un squelette du sous-sol conduisant à une première interprétation en profondeur des réflecteurs majeurs

Etude des variations de l'amplitude de la réflectivité du sous-sol après imagerie sismique en profondeur

PARIS-MINES ParisTech (751062310) / SudocSudocFranceF

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME)

International audienceIntroduction: Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysis: HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C-35°C) and normothermia (36.5°C-37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and dissemination: The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

© 2017 Elsevier Ltd Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.Link_to_subscribed_fulltex

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