REACTIONS SECONDAIRES AUX ANESTHESIQUES LOCAUX (PLACE DE L'ALLERGIE ET METHODES D'EXPLORATIONS A PROPOS DE 70 CAS)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Generation and processing of urinary and plasmatic metabolomic fingerprints to reveal an illegal administration of recombinant equine growth hormone from LC-HRMS measurements

Growth hormones are proteins produced by the anterior pituitary gland responsible for bone and tissue growth through their effects on carbohydrates, lipids and proteins metabolisms. Despite strict regulations banning the use of recombinant equine growth hormone, this substance is suspected to be misused to improve the horse physical performances. In order to check whether the regulation is fulfilled or not, controls are organized and a new analytical screening tool potentially able to detect such abuse was investigated in this paper. An untargeted metabolomics approach, based on liquid chromatography coupled to high resolution mass spectrometry, was developed and applied to characterize and compare horse urinary and plasmatic metabolic profiles upon reGH administrations. After minimal sample preparation, biological fluids were analyzed by LC-ESI(+/-)-Q-TOF. Data processing was performed by XCMS software and multivariate data analysis applied to the generated data set allowed building OPLS models to discriminate control versus treated populations. Results demonstrated significant metabolic modifications consecutively to the reGH treatment. A comparative study between urinary and plasmatic signatures was performed to evaluate the resulting metabolomic models and to asses their respective interests in the scope of real application for screening reGH administration

Human epidemiological evidence about the associations between exposure to organochlorine chemicals and endometriosis: Systematic review and meta-analysis

Background: Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. Objectives: A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. Data sources: The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Study eligibility criteria: Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated bi-phenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. Study appraisal and synthesis methods: A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/ OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/ OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n=10), 1.70 (1.20; 2.39) for PCBs (n=9), and 1.23 (1.13; 1.36) for OCPs (n=5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. Limitations, conclusions, and implications of key findings: The level of evidence was considered to be "moderate" with "serious" risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged

Brief Report on the Efficacy of Nivolumab in Patients With Previously Treated Advanced Large-Cell Neuroendocrine Cancer of the Lung

International audienceINTRODUCTION: The optimal management of large cell neuroendocrine cancer of the lung (LCNEC) is unclear, and data regarding anti-programmed cell death protein 1 (PD-1) antibodies are scarce. This study reports the clinical efficacy of a PD-1 inhibitor in patients with advanced LCNEC. METHODS: All patients with stage III to IV LCNEC treated with at least one previous cycle of chemotherapy between January 1, 2015 and December 31, 2018 were reviewed retrospectively. Patients were divided into two groups depending on their exposure to nivolumab as second-line treatment or beyond. The primary objective was to assess nivolumab’s efficacy. RESULTS: A total of 51 patients with advanced LCNEC from eight centers were analyzed, including 17 who received nivolumab. The PD-1 inhibitor was used as second-line treatment in 77% of cases, with a median number of eight doses (range: 1-62). After nivolumab treatment, the median overall survival was 12.1 months (95% confidence interval [CI]: 7.10-14.20). The objective response rate was 29.4% (95% CI: 10.3-56.0), and median progression-free survival was 3.9 months (95% CI: 1.68-7.17). The programmed death-ligand 1 status was unknown. There was no difference in the efficacy of first-line chemotherapy; the objective response rate was 23.5% (n = four of 17) in the nivolumab group versus 32.4% (n = 11 of 34) in the conventional treatment group, and progression-free survival was 3.5 months (95% CI: 1.7-4.4) versus 2.1 months (95% CI: 1.4-4.2), respectively. CONCLUSIONS: In a real-world setting, nivolumab seems to be an effective second-line treatment in patients with advanced LCNEC. Large prospective studies in this setting are still required

High-flow nasal oxygen a safe, efficient treatment for COVID-19 patients not in an ICU

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Duration of nivolumab for pretreated, advanced non–small‐cell lung cancer

Abstract Background A standard of care for pretreated, advanced non–small‐cell lung cancers (NSCLCs), nivolumab has demonstrated long‐term benefit when administered for 2 years. We aimed to better discern an optimized administration duration by retrospectively analyzing real‐life long‐term efficacy in a prospective cohort. Methods All nivolumab‐treated adults with advanced NSCLCs (01/09/2015 to 30/09/2016) from nine French centers were eligible. On 31/12/2018, patients who are alive ≥ 2 years after starting nivolumab were defined as long‐term survivors (LTSs) and were divided into three nivolumab treatment groups:  2 years. Co‐primary endpoints were LTSs’ progression‐free survival (PFS) and overall survival (OS). Results The median follow‐up was 32 months (95% CI, 31.0 to 34.0). The 3‐year OS rate for the 259 cohort patients was 16.6%. Among them, 65 were LTSs: 47 treated  2 years. Their respective characteristics were: median age: 59, 52, and 58 years; smoking history: 92.9, 100, and 100%; adenocarcinomas: 66, 57.1, and 54.5%. LTSs’ median (m)PFS was 28.4 months; mOS was not reached. LTSs’ objective response rate was 61.6%. mOS was 32.7 months for those treated  2‐year group's 3‐year OS was longer. Twenty‐eight LTSs experienced no disease progression; 7 had durable complete responses. However, LTSs had more frequent and more severe adverse events. Conclusion In real‐life, prolonged nivolumab use provided long‐term benefit with 16.6% 3‐year OS and 25% LTSs. Survival tended to be prolonged with nivolumab continued beyond 2 years. Prospective randomized trials with adequate design are needed

First‐line pembrolizumab for non–small cell lung cancer patients with PD‐L1 ≥50% in a multicenter real‐life cohort: The PEMBREIZH study

Background: The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions. Method: This was a French retrospective multicenter longitudinal study of 108 consecutive patients with advanced NSCLC, a PD-L1 TPS ≥50% and without EGFR/ ALK aberrations who were treated by pembrolizumab, in first line. Patient data were obtained from medical files. Results: The main characteristics of the cohort were: median age [range] 66.7 [37-87] years, 64.8% male, 23.1% with a performance status (PS) of 2, and 88.9% current or former smokers. Eighty-seven percent had stage IV NSCLC at diagnosis, 9.2% untreated brain metastases at inclusion,. With a median follow-up of 8.2 months, the median PFS was 10.1 months (95% CI, 8.8-11.4). The objective response rate was 57.3% (complete response 2.7%, partial response 54.6%). Disease control rate was 71.1%. At 6 months, the OS rate estimated was 86.2%. Treatment-related adverse events (AE) of grade 3 occurred in 8% of patients. There were no grade 4 or 5 AEs. Conclusion: In a real-life cohort of advanced NSCLC patients (including PS 2 and untreated brain metastases), with PD-L1 TPS ≥50%, pembrolizumab demonstrates similar PFS to the pivotal clinical trial

Hormones et promoteurs de croissance en productions animales : de la physiologie à l'évaluation du risque

National audienceDuring the last fifty years, considerable progress in breeding performances of domestic species has been obtained due to a better knowledge obtained in physiology and in particular nutrition, growth, reproduction and lactation. This progress has been united with that of genetic progress accomplished in the different animal species in a context of an improved control of sanitary conditions of herds and a more accurate control of the existing breeding systems. The use of hormonal substances to better control reproduction functions and growth has become decisive within this progress. However, a profound tendency that restrains their use to certain critical moments in the life of an animal has appeared in Europe these last fifteen years, obliging researchers to search for alternatives via a better control of food, genetics and breeding systems, in order to guarantee to consumers a better, a priori, quality of animal products. Physiological functions that offer possibilities of exogenous hormonal control, usable hormonal substances and animal speculations are presented. A clarification of the toxicological risks that these substances present, the control and traceability of their use and the current regulations are given. Finally, the research that will allow making progress around the question of hormone use in breeding in a context of a remodelled society is evoked.Au cours des cinquante dernières années, des progrès considérables dans les performances d’élevage des espèces domestiques ont été obtenus grâce à une meilleure connaissance acquise dans le domaine de la physiologie, en particulier en ce qui concerne la nutrition, la croissance, la reproduction et la lactation, et qui s’est conjuguée aux progrès génétiques accomplis dans les différentes espèces animales dans un contexte de meilleure maîtrise sanitaire des troupeaux et de maîtrise plus fine des systèmes d’élevage en place. Le recours aux substances hormonales pour mieux maîtriser les fonctions de reproduction et de croissance a pris une place déterminante dans ce progrès. Néanmoins, une tendance profonde consistant à restreindre leur utilisation à certains moments critiques de la vie de l’animal est apparue en Europe ces quinze dernières années, obligeant à rechercher des alternatives par le biais d’une meilleure maîtrise alimentaire, génétique et des systèmes d’élevage, ceci afin de garantir aux consommateurs une meilleure qualité définie a priori des produits animaux. Les fonctions physiologiques qui offrent des possibilités d’un contrôle hormonal exogène, les substances hormonales utilisables et les spéculations animales concernées sont présentées tour à tour. Un éclaircissement sur les risques toxicologiques que présentent ces substances, le contrôle et la traçabilité de leur utilisation et les réglementations en vigueur sont ensuite rappelés. Enfin, sont évoquées les recherches qui permettront de faire progresser sensiblement la question de l’utilisation des hormones en élevage dans un contexte sociétal renouvelé