Genomic signature to guide adjuvant chemotherapy treatment decisions for early breast cancer patients in France: a cost-effectiveness analysis

IntroductionChemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence.MethodsClinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX® test or SoC) and a Markov model to capture long-term outcomes.ResultsIn the base case, the Oncotype DX® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX® testing was the dominant strategy.DiscussionWidespread implementation of Oncotype DX® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system

The efficacy of therapeutic plasma exchange in COVID-19 patients on endothelial tightness in vitro is hindered by platelet activation

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance

Étude des mécanismes immunitaires impliqués dans l'immonosuppression induite après autogreffe de cellules souches hématopoïétiques dans un modèle murin

Autologus stem cell transplantation (ASCT) is associated with a transient state of immunosuppression. In this study we analysed the mechanisms of immunosuppression following ASCT using a murine model of skin DTH reaction to haptens which is mediated by CD8 cytotoxic T cells and down-regulated by CD4 T cells.Oour work has demonstrated a time period after ASCT where quantitative T cell recovery is paradoxically not coupled with functional T cell resconstitution. Lack of DTH reactions was not due to an intrinsic defect in CD8 functionaltiy during lymphocyte recovery but rather under the control of CD4 T down -regulatory population. Our data show that functional immunosuppression can occur with normal numbers of peripheral T cells and that it could be due to enhanced down-regulatory mechanismsL'autogreffe de cellules souches hématopoïétiques précédée d'un conditionnement myéloablatif peut se compliquer d'un déficit de reconstitution immunitaire. Ce travail porte sur la reconstitution des lymphocytes CD8 après une autogreffe de moëlle chez la souris. Après une analyse quantitative, nous avons étudié la fonctionnalité des lymphocytes T reconstitués grâce au test d'hypersensibilité de contact au DNFB. Cette réponse immunitaire spécifique d'Ag est induite par les lymphocytes T CD8 cytotoxiques et re gulée par les lymphocytes T CD4. Ainsi, il existe, après greffe, une période d'immunosuppression pendant laquelle les lymphocytes T CD8 sont reconstitués alors que la réponse immunitaire est altérée. Nos investigations ont démontré qu'il n'existe pas de déficit de fonctionnalité intrinsèque des lympocytes T CD8 mais une régulation excessive et transitoire probablement induite par une population de lymphocytes T CD4LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Delayed hysteroscopic resection of retained tissues and uterine conservation after conservative treatment for placenta accreta

International audienceBackgroundConservative management of both the uterus and the abnormal placenta, which is left inside the uterus at the time of delivery, is one option of placenta accreta management. Complete elimination of the residual placenta is the main challenge of this procedure.AimTo report the role, efficacy and safety of hysteroscopic resection in women presenting with severe pelvic pain and chronic intra-uterine retention after conservative treatment of placenta accreta.Material and methodsFour consecutive women who were treated with hysteroscopic resection of retained tissues after conservative treatment of placenta accreta or percreta at the time of delivery. Clinical files and surgical procedures were reviewed. All procedures were performed because of chronic pelvic pain and the absence of a complete spontaneous placental elimination.ResultsAll procedures were successful and uneventful. The uterus was conserved with a complete disappearance of the symptoms in the four women, and two of them became pregnant.ConclusionHysteroscopic resection seems effective and safe for shortening the duration of placental elimination after conservative treatment in women with severe pelvic pain due to uterine retention. This approach allows conserving the uterus and future fertility

Influence of operating parameters on photocatalytic oxidation treatment efficiency: contact time investigation

International audienceThe photocatalytic oxidation (PCO) of toluene was performed in a dynamic loop reactor with control of key process parameters: UV-light intensity and air flow rate. The initial concentration of toluene was fixed at 800 ppb. The relative humidity was set at 50% (i.e. 13 000 ppm) to be close to real indoor air conditions. Two photocatalytic media geometries were used in a way to optimize the contact time. Flat and pleated geometry were studied. CFD simulations were performed with ANSYS-CFX® computational fluid software. Influence of the contact time was assessed and related to the geometry of the material. The local contact time was evaluated to be 9 times higher regarding the pleated geometry. This latter impacts the global PCO efficiency; it plays a role in the contact time between the effluent and the photocatalytic material

Étude cinétique, à lʼéchelle de la ppb, des sous-produits formés durant lʼoxydation photocatalytique du toluène

International audiencePhotocatalytic oxidation (PCO) is a technique developed for the removal of volatile organic compounds (VOC) in indoor air. The originality of this work is to investigate PCO performances under experimental conditions equivalent to indoor air in terms of VOC concentrations and relative humidity. Toluene was chosen as the model compound. Oxidation of this compound was followed in static conditions for 12 h to study: (i) oxidation kinetics, (ii) formation/disappearance of reaction intermediates and by-products. Experiments were conducted with initial concentrations of toluene ranging from 50 to 800 ppb, both under dry air and under wet air (50% RH).Seventeen reaction intermediates were detected and quantified in the gas phase (benzaldehyde, cresols, aldehydes, ketones...). Their temporal profiles are used to compare the reaction mechanism of toluene PCO at ppm level (classical literature) and at ppb level (this study). These temporal profiles clearly show that some intermediates, such as acetaldehyde and acrolein, can either disappear with slow kinetics or accumulate in the air. In addition, the presence of water vapor,although it accelerates toluene oxidation, does not induce significant effect on the nature of reaction intermediates. All these results lead to the justification for future studies of PCO to select typical indoor air concentrations in order to draw reliableconclusions about the performance and behavior of the systems of air treatment by photocatalysis.Lʼoxydation photocatalytique (OPC) est une technique développée pour lʼélimination des composés organiques volatils (COV) présents dans lʼair intérieur. Lʼoriginalité de ces travaux réside dans lʼétude des performances de lʼOPC dans des conditions expérimentales reproduisant lʼair intérieur en termes de niveaux de concentrations en COV et dʼhumidité relative. Le toluène a été retenu comme composé modèle. Lʼoxydation de ce composé a été suivie en conditions statiques pendant 12 h afin dʼétudier : (i) sa cinétique dʼoxydation ; (ii) la formation/disparition des intermédiaires réactionnels et sous-produits. Lʼétude a été réalisée pour des concentrations initiales en toluène comprises entre 50 et 800 ppb, à la fois en air sec et en air humide (50 % RH). Dix-sept intermédiaires réactionnels ont été détectés et quantifiés en phase gazeuse (benzaldéhyde, crésols, aldéhydes, cétones…). Leurs profils temporels permettent de comparer le mécanisme réactionnel de lʼOPC du toluène à lʼéchelle de la ppm (littérature classique) et à lʼéchelle de la ppb (cette étude). Ces profils temporels montrent clairement que certains des intermédiaires, tels que lʼacétaldéhyde ou lʼacroléine, peuvent soit disparaître avec une cinétique très lente, soit sʼaccumuler dans lʼair. En outre, la présence dʼeau, bien quʼelle accélère lʼoxydation du toluène, nʼinduit pas dʼeffet notable sur la nature des intermédiaires réactionnels. Lʼensemble de ces résultats justifie de conduire à lʼavenir les études dʼOPC à des concentrations correspondant à lʼair intérieur afin de tirer des conclusions fiables sur les performances et le comportement des systèmes de traitement dʼair par photocatalyse

Influence of operating parameters on photocatalytic oxidation treatment efficiency: contact time investigation

International audienceThe photocatalytic oxidation (PCO) of toluene was performed in a dynamic loop reactor with control of key process parameters: UV-light intensity and air flow rate. The initial concentration of toluene was fixed at 800 ppb. The relative humidity was set at 50% (i.e. 13 000 ppm) to be close to real indoor air conditions. Two photocatalytic media geometries were used in a way to optimize the contact time. Flat and pleated geometry were studied. CFD simulations were performed with ANSYS-CFX® computational fluid software. Influence of the contact time was assessed and related to the geometry of the material. The local contact time was evaluated to be 9 times higher regarding the pleated geometry. This latter impacts the global PCO efficiency; it plays a role in the contact time between the effluent and the photocatalytic material