•Robust and sensitive LC–MS/MS method to simultaneously quantify five tyrosine kinase inhibitors.•First bioanalytical assay for the simultaneous analysis of three generations of EGFR ...inhibitors.•First validated bioanalytical assay for nintedanib in human plasma.•Suitable for therapeutic drug monitoring in lung cancer.
A new method for the quantitative analysis by liquid chromatography-tandem mass spectrometry (LC–MS/MS) of five tyrosine kinase inhibitors (afatinib, crizotinib, osimertinib, erlotinib and nintedanib) used in the treatment of non-small cell lung cancer (NSCLC) was developed and validated in human plasma. Separation was performed on an Accucore® C18 (2.1 × 50 mm; 2.6 μm) column using a gradient elution of water acidified with 0.1% (v/v) formic acid (A) and acetonitrile containing 0.1% (v/v) formic acid (B) at a flow rate of 500 μL/min. The analytes were detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer after positive ionization with heated electrospray interface. After addition of three isotopically labeled internal standards, plasma pretreatment consisted in a simple protein precipitation. This method presented satisfactory results in terms of sensitivity, specificity, precision (intra- and inter-assay coefficient of variation from 2.6% to 10.6%), accuracy (from 96.1% to 108.5%), recovery and matrix effects. The lower limit of quantification and the linearity of these five tyrosine kinases inhibitors are suitable with the expected concentrations in clinical practice. This new bioanalytical method can be used in daily clinical practice for therapeutic drug monitoring of these tyrosine kinase inhibitors in NSCLC patients.
Savoirs de la fiction Amadieu, Jean-Baptiste; Arzoumanov, Anna; Baron, Christine ...
Presses universitaires de Rennes eBooks,
2021
133
eBook, Book
Open access
Dès les années 2000, la fiction a cessé d’occuper le devant de la scène théorique en littérature, et pourtant, plus que jamais, sa capacité à configurer notre expérience est en débat. Expériences de ...pensée, phénomènes de réception de masse ou récits exemplaires, de nombreux textes littéraires modèlent non seulement notre expérience mais aussi notre capacité même à comprendre le monde dans lequel nous vivons. Cette fonction heuristique fait de la fiction un instrument de connaissance et un objet de savoir, notamment pour le droit. À travers des contributions de spécialistes issus de disciplines variées (philosophie, histoire, droit, sociologie), cet ouvrage comporte trois axes de réflexion. Tout d’abord, quels types de savoirs supposent (et développent) notre usage des fictions littéraires ou mentales ? Ensuite, les lectures juridico-historiques de la fiction seront évoquées : quel droit de la fiction ? Quelles réécritures cinématographiques ou littéraires de procès ? Quelles analogies structurelles entre texte littéraire et texte juridique ? Enfin, le rôle de la fiction dans la constitution d’imaginaires sociaux sera questionné à l’aune de ses effets sur la perception des conditions représentées et de l’efficacité critique qui en découle.
Cet article montre comment l’observation des enfants dans les marges des entretiens constitue un matériau particulièrement utile pour mettre au jour la différenciation sociale des pratiques ...éducatives des familles. À partir d’une enquête menée dans 18 familles portant sur les appropriations des jeux Montessori, nous questionnons les conditions de l’accueil du sociologue chez les enquêtés, l’enrôlement des enfants dans la situation d’enquête ethnographique et les circonstances entourant la mise en place de l’entretien en démontrant que, loin de ne constituer qu’une condition de réalisation de l’enquête et un préalable nécessaire à l’enregistrement efficace des matériaux, ces marges méthodologiques des entretiens offrent un matériau à analyser pour lui-même.
Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome ...under ICI.
Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expenditure (REE) was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) provided by the Harris and Benedict formula. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR) based on investigator review per RECIST v1.1. and overall survival (OS). The association of patient's metabolism with 6-month PFS was first explored in a single-center training cohort to estimate the effect size. The relationship between patient's metabolism and 6-month PFS was then tested in an independent non interventional observational prospective cohort (ELY) of 100 patients recruited in two tertiary university centers.
In the entire cohort, the ORR was 14% for the hypermetabolic group (n = 10/74) vs 38% for the normometabolic group (n = 26/68), respectively (estimated difference 25%, 95CI 9–40%, p = 0.001). The DCR was 28% for the hypermetabolic group (n = 21/74) vs 53% for the normometabolic group (n = 36/68), respectively (estimated difference 25%, 95CI 7–42%, p = 0.005). In the validation cohort (100 patients, 2 centers), normometabolic patients (defined as mREE/tREE < 110%) had increased 6-month PFS (57% versus 22%; odds ratio: 4.76; IC95 1.87 – 12.89; p<0.001) and improved overall survival (HR 2.20; IC95: 1.41–3.44; p<0.001). The positive and negative predictive values of normometabolism to identify non-progressive patients at 6 months, were 57% and 78% respectively, sensitivity was 72% and specificity was 66%. In multivariate analysis including PD-L1 tumor status, basal metabolism was an independent predictive factor for 6-month PFS.
Normometabolism is a new independent parameter to identify mNSCLC patients who will benefit from ICI, with both improved tumor response, 6-month PFS, and survival.
This work was supported by Baxter (04012016).
À l’occasion du centenaire de la mort d’Émile Zola en 2002 s’est tenu un colloque « Lire/Dé-lire Zola » qui avait pour ambition de suggérer de nouvelles approches de l’œuvre zolienne. La question qui ...fonde le présent dossier et la perspective sociologique que nous proposons pour y répondre sont selon nous un moyen de prendre cette invitation au mot. Cet article, qui prend appui sur notre travail de thèse, cherche à rendre raison d’un point de vue sociologique des modes d’investissements litté...
Le dossier que le lecteur s’apprête à ouvrir prend le relais d’une journée d’étude intitulée « Socialisations et création littéraire » que nous avions organisée l’École Normale Supérieure de Lyon le ...12 janvier 2012. Celle-ci se voulait le point d’aboutissement d’un programme de recherche collective autour de la création littéraire qui avait été mené dans le cadre d’un cluster financé par la région Rhône-Alpes, ainsi qu’un point d’ancrage pour un élargissement de cette réflexion. Celle menée ...
The occurrence of severe, acute limiting toxicity in patients receiving anti–programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found ...to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.
From June 2015 to January 2017, all consecutive patients treated with nivolumab in our institution were prospectively included. We studied the relationship between muscle mass assessed by computed tomography, nivolumab trough level (Cmin) at day 14 assessed using the enzyme-linked immunosorbent assay method, and the occurrence of immune grade III or IV toxicity or any toxicity leading to treatment discontinuation (immune-related acute limiting toxicity irALT).
In our population (n = 92) with a majority of lung cancer (72%), forty-five (51.7%) patients were sarcopenic. The median plasma nivolumab Cmin at day 14 was 15.4 μg/mL (interquartile range = 11.8–21.0). In multivariate analysis, hypoalbuminaemia (<35 g/L) was independently associated with low nivolumab Cmin on day 14 (odds ratio OR = 0.09; 95% confidence interval CI = 0.01–0.59, p = 0.01) and overweight/obesity with high nivolumab Cmin on day 14 (OR = 5.94; 95% CI = 1.25–28.29, p = 0.03). We observed 22 irALTs in 19 patients (21%). The most frequent irALT was respiratory (6.5%) disorders and gastrointestinal (4.3%) disorders. Patients with sarcopenia were at significantly increased risk of experiencing an irALT (OR = 3.84; 95% CI = 1.02–14.46, p = 0.047). No association was found between toxicity and nivolumab plasma Cmin at day 14.
Our results highlight the importance of assessing body composition and suggest that sarcopenia could predict severe immune-related toxicity of nivolumab in real life.
•Patients with sarcopenia are more likely to experience severe toxicity to nivolumab.•Sarcopenia is not associated with plasma nivolumab trough level at day 14.•Plasma nivolumab trough level at day 14 is not associated with nivolumab toxicity.•Body mass index is associated with plasma nivolumab trough level at day 14.
Sur la base d’une enquête sociologique menée auprès de trois échantillons de lecteurs tchèques, français et allemands, les auteurs de L’engagement de l’axiologie nationale dans la lecture d’un roman ...souhaitent mettre à jour l’approche culturelle, et précisément nationale, qu’investissent les lecteurs dans l’interprétation du roman tchèque de Bohumil Hrabal Moi qui ai servi le roi d’Angleterre. Il s’agit« d’analyser sous un angle sociologique l’approche tchèque du roman de Bohumil Hrabal ; les...
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