Serial daily lactate levels association with 30-day outcome in cardiogenic shock patients treated with VA-ECMO:a post-hoc analysis of the HYPO-ECMO study

Background: Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive.Methods: We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality. Results: Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (&lt; 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12–3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p &lt; 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p &lt; 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48–77) versus 57% (21–75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21–2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia). Conclusions: The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start. Trial Registration identifier NCT02754193 registered on 2016–04–12.</p

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

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/)

A Semi-throughput Procedure for Assaying Plant NADP-malate Dehydrogenase Activity Using a Plate Reader

Chloroplast NADP-dependent malate dehydrogenase (NADP-MDH) is a redox regulated enzyme playing an important role in plant redox homeostasis. Leaf NADP-MDH activation level is considered a proxy for the chloroplast redox status. NADP-MDH enzyme activity is commonly assayed spectrophotometrically by following oxaloacetate-dependent NADPH oxidation at 340 nm. We have developed a plate-adapted protocol to monitor NADP-MDH activity allowing faster data production and lower reagent consumption compared to the classic cuvette format of a spectrophotometer. We provide a detailed procedure to assay NADP-MDH activity and measure the enzyme activation state in purified protein preparations or in leaf extracts. This protocol is provided together with a semi-automatized data analysis procedure using an R script

Serial daily lactate levels association with 30-day outcome in cardiogenic shock patients treated with VA-ECMO:a post-hoc analysis of the HYPO-ECMO study

Background: Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive.Methods: We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality. Results: Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (&lt; 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12–3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p &lt; 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p &lt; 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48–77) versus 57% (21–75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21–2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia). Conclusions: The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start. Trial Registration identifier NCT02754193 registered on 2016–04–12.</p

Analyzing Multifactorial RNA-Seq Experiments with DicoExpress

International audienceThe proper use of statistical modeling in NGS data analysis requires an advanced level of expertise. There has recently been a growing consensus on using generalized linear models for differential analysis of RNA-Seq data and the advantage of mixture models to perform co-expression analysis. To offer a managed setting to use these modeling approaches, we developed DiCoExpress that provides a standardized R pipeline to perform an RNA-Seq analysis. Without any particular knowledge in statistics or R programming, beginners can perform a complete RNA-Seq analysis from quality controls to co-expression through differential analysis based on contrasts inside a generalized linear model. An enrichment analysis is proposed both on the lists of differentially expressed genes, and the co-expressed gene clusters. This video tutorial is conceived as a step-by-step protocol to help users take full advantage of DiCoExpress and its potential in empowering the biological interpretation of an RNA-Seq experiment

Characterization and performance of an acoustic sensor for fission gas release characterization devoted to JHR environment measurements

International audienceFor more than a decade, the IES laboratory has been working in collaboration with the CEA on the development of acoustic instrumentation in the nuclear field. Within the framework of this collaboration, the IES acoustic team is developing a miniaturized gas composition sensor for in situ measurements of gas composition in a fuel rod.The first experimental evidence of an acoustic measurement to perform a gas composition measurement date back to 2010 with the REMORA 3 experiment, which measured the release of fission gas from fissionable fuel. The first experimental evidence of an acoustic measurement to perform a gas composition measurement date back to 2010 with the REMORA 3 experiment, which measured the release of fission gas from fissionable fuel. This experiment was carried out in the OSIRIS reactor located at CEA Saclay in France. The installation allowed the devices to be tested under irradiation at 150°C [1,2], which corresponded to the maximum operating Curie temperature allowed by PZT element. But the new sensors presented in this paper will be able to operate up to 300 degrees, this performance is possible by the utilization of a modified Bismuth Titanate piezoelectric (NBT). The integration of the material is done by screen printing process on alumina substrate [3,4]. The fabrication process and first characterization have been presented in the previous version of ANIMMA 2021 [5].In this paper, we will focus on the performances of this kind of sensor. In our laboratory, we have conceived two experimental benches, the first one permitted to test the sensor in different mixes of different gas such as helium and xenon. And the second bench, measure the variation of impedance of our piezoelectric elements under temperature. This experiment will allow us to replicate the condition of temperature and pressure decorrelated, and see if the sensor can operate a gas composition measurement in JHR thermodynamic condition.These experiments will allow us to validate the concept and design of this device before final validation tests under irradiation in 2023 or 2024