Mise en place de l'extraction liquide-liquide en microsystèmes établir des écoulements segmentés à façon pour optimiser le transfert de masse

National audienceLiquid-liquid extraction is commonly used for radiochemical analysis. When miniaturized, it can benefitfrom the advantages of microfluidic tools i.e. possible coupling, precise control of the interfacial areabetween the aqueous and organic phases, and contact time. A first study, dedicated to liquid-liquidextraction with parallel flows of europium diluted in nitric acid by the N,N′-dimethyl-N,N′-dibutyltetradecylmalonic diamide [1, 2], allowed us to highlight the limitations of parallel flows for aslow chemical system. One way to optimize yields of extraction of the kinetically slow systems is toincrease the specific interfacial area. For this reason, segmented flows formation and characteristicswere investigated, as a function of the physicochemical properties of a biphasic system, flow rates andthe dimensions of a focalized flux junction. In the following, two multiphase models of the droplets sizecorresponding to the transition and dripping regimes were validated and will be used for theoptimization of the specific interfacial area.L’extraction liquide-liquide est couramment utilisée pour les analyses radiochimiques. Miniaturisée,elle peut bénéficier des avantages des outils microfluidiques qui sont la possibilité de réaliser descouplages, le contrôle précis de l’aire interfaciale entre les phases aqueuse et organique en présence,et des temps de contact. Une première étude, dédiée à l’extraction liquide-liquide en flux parallèlesd’europium en milieu nitrique par le N,N’-dimethyl N,N’-dibutyl tetradecylmalonamide [1, 2], a permisde mettre en évidence les limitations des flux parallèles pour un système chimique lent. Une façond’optimiser les rendements d’extraction des systèmes cinétiquement lents est de mettre en œuvre desécoulements permettant d’augmenter l’aire interfaciale spécifique. C’est pourquoi nous étudions laformation d’écoulements segmentés à façon en fonction des propriétés physico-chimiques d’un systèmechimique biphasique, des débits et des dimensions d’une jonction en flux focalisé. L’utilisation de deuxmodèles de calcul des tailles de gouttes en régimes d’écoulements transitoire

A microfluidic tool for the investigation of liquid-liquid extraction kinetics

International audienceTechniques devoted to liquid-liquid extraction kinetics studies have seen a tremendous development in the last decades. Various contactors, including Lewis-type cells, moving drops, and Rotating Membrane Cells (RMC) are used. However, these standard methods suffer from major drawbacks, i.e. poor definition of the diffusing films thickness at the liquid-liquid interface 1, large volumes of solvents and reagents needed, and potential effect of the membrane in RMC technique. In order to decrease the manipulated quantities of reagents that could be expensive and to rise and control accurately the specific interfacial area segmented flow in microsystems were investigated as a new tool to determine kinetics of liquid-liquid extraction. Indeed, internal mixing of the solutes and complexes within the dispersed and continuous phases is ensured by both diffusion at small scale (microchannels width < 100 micro meter) and recirculation circles2. Therefore, the kinetics of the extraction of a well-known chemical system (Eu(III) by the N,N’-dimethyl N,N’-dibutyl tetradecylmalonamide, in nitric media) was studied. The determined value of pseudokinetic mass transfer coefficient K (m.s-1) is in good agreement with the values obtained with standard techniques, including Nitsch cell3 and RMC4. Then, the use of segmented flow microfluidics should therefore be considered in the future of liquid-liquid extraction kinetics studies

A Simple and Adaptive Methodology to use a Commercial Solvent Extraction Microsystem as Screening Tool Validation with the U-TBP Chemical System

International audienceThe solvent extraction of a U (VI) present at several g.L-1 from the aqueous phase (HNO3) = 3 M to the organic one (30 percent TBP) involves a change of the viscosity of the two phases during the extraction process in microsystem. This shifts the position of the interface between the two phases and then affects the quality of the separation at the outlet of the microsystem. The aim of this study is to present a simple method to stabilize the quality of the separation by controlling the interface position during solvent extraction in microsystem. First, a study at low concentration is operated in order to set flow rates and contact time that allow optimal parallel flows and mass transfer. Second, the influence of the high grade concentration (up to 140 g.L-1) of solute on the flows and extraction yield is studied

Flavor enhancement as a strategy to improve food liking in cancer patients with taste and smell alterations

Summary: Food liking is an essential component of the food intake experience. However, some conditions may alter the perception, thus the liking of food, leading to a reduced intake and increasing the risk of malnutrition. Particularly, in the context of cancer and related therapies, malnutrition is a major challenge with 25%–80% of cancer patients experiencing malnutrition at different degrees. The aim of the present exploratory study was to examine the effect of flavor enhancement on food liking in a group of cancer patients undergoing chemotherapy and with varying self-reported taste/smell abilities.The liking of four eggplant creams enhanced with either salt, lemon, garlic or cumin was evaluated in comparison to a reference eggplant cream by a group of 154 cancer patients. Patients were stratified in two subgroups according to their self-reported taste and smell perception abilities. Results showed that adding salt and garlic significantly increased patients' liking of the eggplant cream (P0.05), while adding lemon reduced liking compared to the reference (P<0.001).Enhancing food flavor is likely to be a promising way to increase food liking in cancer patients undergoing chemotherapy. Future studies should include measurements of food intake during a full meal and over a defined period to examine whether increasing food liking helps to reduce risks of malnutrition by improving food intake in cancer patients

Microsystèmes d'extraction par solvant pour l'analyse radiochimique

National audienceL’analyse des radionucléides dans les solutions de combustibles irradiés ou dans les déchets de haute ou moyenne activité implique l’enchaînement de plusieurs opérations de séparation/purification avant la mesure par spectroscopies nucléaires ou ICP-MS. Ces étapes sont sources de déchets et d’exposition aux radiations, et implique l’utilisation de volumes non négligeables de réactifs chimiques ou de solvants. Résoudre ce problème passe par la miniaturisation des outils d’analyse et le développement de laboratoires sur puce dédiés aux analyses liées au domaine nucléaire. La micro extraction liquide-liquide ($\mu$-ELL) a été développée pour des applications d’analyse de radionucléides dans des effluents radioactifs

Liquid-liquid extraction of two radiochemical systems at micro-scale predict and achieve segmented flow to optimize mass transfer

International audienceOne of the most important separation techniques in radiochemical procedures is solvent extraction. In the last decade, a growing interest in its use in microsystems with multiphase micro-flows has emerged because such systems allow a good control of the interface area between aqueous and organic phases as well as of the contact time of the two phases.A previous study was devoted to the micro-extraction in parallel flows of uranium in chloride media by Aliquat 336 and europium in nitric acid by the N,N'-dimethyl N,N'-dibutyl tetradecylmalonamide. While in the first case an optimal extraction yield could be obtained, slower reaction kinetics prevented the second chemical system extraction from being complete. A way to improve mass transfer for slow systems is to increase the specific interfacial area. We therefore investigated liquid-liquid extraction for the same chemical systems by implementing segmented flows. Both the internal circulation stimulated within droplets by their passage along micro-channels and the increase in the interfacial area are responsible for a large enhancement in the interfacial mass transfer and reaction rate. Therefore, an improvement in liquid-liquid extraction yield could be expected. Based on previous works from Van Steijn and Xu, a numerical model was developed to accurately predict the characteristics of droplet production at a T-junction (volumes, frequency, spacing, and specific interfacial area) for the two aforementioned chemical systems. Using parameters screening, the respective influence of liquids viscosities, dimensional parameters and flow rates was evidenced. This numerical model was verified experimentally by generating on-chip segmented flows, and offered ways of improvement in both operating parameters and chip design. Finally, phase separation was obtained using selective membrane, and radionuclides micro-extractions were performed. Micro-extraction yields were compared to conventional batch extraction

Prediction of the formation of segmented flow in microsystems for radiochemical liquid-liquid extraction

International audienceOne of the most important separation techniques in radiochemical procedures is solvent extraction. It involves concentrated acids and corrosive solvents that require microsystems built with robust materials. In the last decade, a growing interest in its use in microsystems has emerged because such systems allow a good control of both the interface area between aqueous and organic phases, and the contact time of the two phases. After a study of parallel flow [1], our goal is to understand and compare the formation of segmented flow for T, flow focusing, and co-flow junctions, and to predict the optimal design in order to enhance solvent extraction

Predict and compare the formation of segmented flow in microsystems: Interest for radiochemical liquid-liquid extraction

International audienceOne of the most important separation techniques in radiochemical procedures is solvent extraction. In the last decade, a growing interest in its use in microsystems has emerged because such systems allow a good control of both the interface area between aqueous and organic phases, and the contact time of the two phases.To improve mass transfer in liquid-liquid extraction reactions for radiochemical separation relevant to the nuclear field, our goal is to implement liquid-liquid extraction with segmented flows in microsystems in order to increase the interfacial area. The optimization of the interfacial area requires taking into account the hydrodynamics of biphasic systems. This study is dedicated to the understanding of segmented flows in a T-junction with the aim to form tailor-made droplets for given organic and aqueous phases

Cetuximab versus methotrexate in first-line treatment of older, frail patients with inoperable recurrent or metastatic head and neck cancer (ELAN UNFIT): a randomised, open-label, phase 3 trial

International audienceBACKGROUND: At present, there is no established standard treatment for frail older patients with recurrent or metastatic head and neck squamous cell carcinoma. We aimed to compare the efficacy and safety of cetuximab to those of methotrexate (the reference regimen) in this population. METHODS: This randomised, open-label, phase 3 trial was done at 20 hospitals in France. Patients aged 70 years or older, assessed as frail by the ELAN Geriatric Evaluation, with recurrent or metastatic head and neck squamous cell carcinoma in the first-line setting and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were eligible for inclusion. Patients were randomly assigned (1:1) to receive cetuximab 500 mg/m(2) intravenously every 2 weeks or methotrexate 40 mg/m(2) intravenously every week, with minimisation by ECOG performance status, type of disease evolution, Charlson Comorbidity Index score, serum albumin concentration, and geriatrician consultation. To avoid deterministic minimisation and assure allocation concealment, patients were allocated with a probability of 0·80 to the treatment that most reduced the imbalance. Treatment was continued until disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint was failure-free survival (defined as the time from randomisation to disease progression, death, discontinuation of treatment, or loss of 2 or more points on the Activities in Daily Living scale, whichever occurred first) and was analysed in the intention-to-treat population. 151 failures expected out of 164 patients were required to detect a hazard ratio (HR) of 0·625 with 0·05 alpha error, with 80% power. A futility interim analysis was planned when approximately 80 failures were observed, based on failure-free survival. Safety analyses included all patients who received at least one dose of the study drug. This study is registered on ClinicalTrials.gov (NCT01884623) and was stopped for futility after the interim analysis. FINDINGS: Between Nov 7, 2013, and April 23, 2018, 82 patients were enrolled (41 to the cetuximab group and 41 to the methotrexate group); 60 (73%) were male, 37 (45%) were aged 80 years or older, 35 (43%) had an ECOG performance status of 2, and 36 (44%) had metastatic disease. Enrolment was stopped for futility at the interim analysis. At the final analysis, median follow-up was 43·3 months (IQR 30·8-52·1). At data cutoff, all 82 patients had failure; failure-free survival did not differ significantly between the groups (median 1·4 months [95% CI 1·0-2·1] in the cetuximab group vs 1·9 months [1·1-2·6] in the methotrexate group; adjusted HR 1·03 [95% CI 0·66-1·61], p=0·89). The frequency of patients who had grade 3 or worse adverse events was 63% (26 of 41) in the cetuximab group and 73% (30 of 41) in the methotrexate group. The most common grade 3-4 adverse events in the cetuximab group were fatigue (four [10%] of 41 patients), lung infection (four [10%]), and rash acneiform (four [10%]), and those in the methotrexate group were fatigue (nine [22%] of 41), increased gamma-glutamyltransferase (seven [17%]), natraemia disorder (four [10%]), anaemia (four [10%]), leukopenia (four [10%]), and neutropenia (four [10%]). The frequency of patients who had serious adverse events was 44% (18 of 41) in the cetuximab group and 39% (16 of 41) in the methotrexate group. Four patients presented with a fatal adverse event in the cetuximab group (sepsis, decreased level of consciousness, pulmonary oedema, and death of unknown cause) as did two patients in the methotrexate group (dyspnoea and death of unknown cause). INTERPRETATION: The study showed no improvement in failure-free survival with cetuximab versus methotrexate. Patients with an ECOG performance status of 2 did not benefit from these systemic therapies. New treatment options including immunotherapy should be explored in frail older patients with recurrent or metastatic head and neck squamous cell carcinoma, after an initial geriatric evaluation, such as the ELAN Geriatric Evaluation. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC and the Ligue Contre le Cancer), GEMLUC, GEFLUC, and Merck Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Nutrition and physical activity: French intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC, SFP-APA, SFNCM, AFSOS)

International audienceThis document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated