25 research outputs found

    The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

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    Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

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

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    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/)

    Le concept du ganglion sentinelle dans le cancer du sein et l'expérience de l'équipe du CHRU de Limoges

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    LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    False positive morphologic diagnoses at the anomaly scan: marginal or real problem, a population-based cohort study.

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    This work was funded as part of the Hospital Clinical Research Programme, in 2010, by the French Health Ministry.International audienceBACKGROUND: Congenital malformations occur in 3-4% of live births. Their prenatal detection is performed by ultrasound screening. Any announcement about a suspected malformation is a source of stress for the parents, and misdiagnosis during ultrasound screening can lead to expensive and sometimes iatrogenic medical interventions. In this study, we aim to determine the false-positive rate, first overall and then by anatomical system, of ultrasound screening for congenital malformations in the second and third trimesters of pregnancy. METHODS: Our sample includes all children born between 1 January, 2006, and 31 December, 2009, in the French region of Auvergne, whose mother had a prenatal ultrasound diagnosis of a congenital malformation during the second or third trimester of pregnancy confirmed by a follow-up ultrasound examination by an expert consultant ultrasonographer. The study included 526 fetuses, divided in 3 groups: false positives, diagnostic misclassifications, and true positives. The rates of false positives and diagnostic misclassifications were calculated for the sample as a whole and then by anatomical system. RESULTS: Overall, the false-positive rate was 8.8% and the rate of diagnostic misclassification 9.2%. The highest false-positive rates were found for renal and gastrointestinal tract malformations, and the highest diagnostic misclassification rates for cerebral and cardiac malformations. The diagnostic misclassification rate was significantly higher than the false-positive rate for cardiac malformations. CONCLUSION: The false-positive rate during prenatal ultrasound is not insignificant; these misdiagnoses cause psychological stress for the parents and overmedicalisation of the pregnancy and the child

    In situ pelagic dataset from continuous monitoring: a mesocosm experiment in Lake Geneva (MESOLAC)

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    International audienceThis dataset corresponds to a data series produced from automated data loggers during the MESOLAC experimental project. Nine pelagic mesocosms (about 3000 L, 3 m depth) were deployed in July 2019 in Lake Geneva near the shore of Thonon les Bains (France), simulating predicted climate scenarios (i.e. intense weather events) by applying a combination of forcing. The design consisted of three treatments each replicated three times: a control treatment (named C - no treatment applied) and two different treatments simulating different intensities of weather events. The high intensity treatment (named H) aimed to reproduce short and intense weather events such as violent storms. It consisted of a short-term stress applied during the first week, with high pulse of dissolved organic carbon (5x increased concentration, i.e. total DOC similar to 6 mg L-1), transmitted light reduced to 15% and water column manual mixing. The medium intensity treatment (named M) simulated less intense and more prolonged exposures such as during flood events. It was maintained during the 4 weeks of the experiment and consisted of 1.5x increased concentration of dissolved organic carbon (i.e. total DOC similar to 2 mg L-1), 70% transmitted light and water column manual mixing. Automated data loggers were placed for the entire period of the experiment in the mesocosms and in the lake for comparison with natural conditions. Temperature, conductivity, dissolved oxygen and CO2 were monitored every 15 min at different depths (0.15, 0.25, 1 and 2 m). This data set aims to contribute our understanding of the effect of environmental forcing on lake ecosystem processes (such as production, respiration and CO2 exchange) under simulated intense weather events and the ability of the planktonic community to recover after perturbation. To a broader extent, the presented data can be used for a wide variety of applications, including monitoring of lake community functioning during a period of high productivity on a large peri-alpine lake and being included in further meta-analysis aiming at generalising the effect of climate change on large lakes

    Terahertz Spectroscopy Sheds Light on Real‐Time Exchange Kinetics Occurring through Plasma Membrane during Photodynamic Therapy Treatment

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    International audienceMethods to follow in real time complex processes occurring along living cell membranes such as cell permeabilization are rare. Here, the terahertz spectroscopy reveals early events in plasma membrane alteration generated during photodynamic therapy (PDT) protocol, events which are not observable in any other conventional biological techniques performed in parallel as comparison. Photodynamic process is examined in Madin-Darby canine kidney cells using Pheophorbide (Pheo) photosensitizer alone or alternatively encapsulated in poly(ethylene oxide)-block-poly(ε-caprolactone) micelles for drug delivery purpose. Terahertz spectroscopy (THz) reveals that plasma membrane permeabilization starts simultaneously with illumination and is stronger when photosensitizer is encapsulated. In parallel, the exchange of biological species is assessed. Over several hours, this conventional approach demonstrates significant differences between free and encapsulated Pheo, the latter leading to high penetration of propidium iodide, Na+ and Ca2+ ions, and a high level of leakage of K+, ATP, and lactate dehydrogenase. THz spectroscopy provides, in a single measurement, the relative number of defects per membrane surface created after PDT, which is not achieved by any other method, providing early, sensitive real-time information. THz spectroscopy is therefore a promising technique and can be applied to any biological topic requiring the examination of short-term plasma membrane permeabilization

    Physico-chemical dataset from an in situ mesocosm experiment simulating extreme climate events in Lake Geneva (MESOLAC)

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    International audienceThis dataset complement a previously published dataset [1] and corresponds to the physico-chemical parameters data series produced during the MESOLAC experimental project [2]. The presented dataset is composed of: 1. In situ profiles (0–3m) of temperature, conductivity, pH, dissolved oxygen (concentration and saturation). 2. In situ measurements of light spectral UV/VIS/IR irradiance (300–950 nm wavelength range) taken at 0, 0.25, 0.5, 1, 1.5, 2 and 2.5m. 3. Laboratory chemical analysis of samples collected at 0 and 2 m (conductivity, pH, total alkalinity, NH4, NO2, NO3, total and particulate nitrogen (Ntot, Npart), PO4, total and particulate phosphorus (Ptot, Ppart), total, organic particulate and total particulate carbon (Ctot, Cpart-org, Cpart-tot), Cl, SO4, SiO2. 4. Laboratory analysis of pigments extracted from samples collected at 0 and 2 m (Chla, Chlc, carotenoids, phaeopigments).The experimental design is the same as in Tran-Khac et al [1]. Briefly, it consisted of nine pelagic mesocosms (about 3000 L, 3m depth) deployed in July 2019 in Lake Geneva near the shore of Thonon les Bains (France) aiming to simulate predicted climate scenarios (i.e. extreme events) and assess the response of planktonic communities, ecosystem functioning and resilience.During the experiment, physical parameters were measured twice a week. At the same time, samples were collected at 0 and 2m of depth for subsequent chemical laboratory analyses. These data are presented in the dataset file, ordered by sampling event (numbered from S1 to S8), treatment (Control-C, High-H and Medium-M) and replicates (1 to 3). For each sampling point the measured parameters are listed in columns, missing data and values below the detection limit are marked as NA (not available).This data set aims to contribute to the understanding of the effect of environmental forcing on lake physico-chemical characteristics (such as temperature, oxygen and nutrient concentration) under simulated intense weather events. To a broader extent, the presented data can be used for a wide variety of applications, including monitoring of a large peri-alpine lake functioning under environmental stress and being included in further meta-analysis to generalise the effect of climate change on large lakes. The two complementary dataset differ in the acquired data and methods, temporal and spatial resolution. They complete each other in terms of physico-chemical characterization of the experimental treatments and together can allow comparison of the two different monitoring strategies (continuous vs punctual) during in situ experimental manipulations

    Aquaporins and Fetal Membranes From Diabetic Parturient Women: Expression Abnormalities and Regulation by Insulin

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    International audienceDuring pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women
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