Pamidronate intraveineux dans le traitement de l'ostéoporose post-ménopausique : effets de différentes modalités d'administration sur le remodelage et la densité osseuse : une étude pilote

Résumé : Introduction : l'ostéoporose est une maladie caractérisée par une masse osseuse diminuée et une structure osseuse appauvrie amenant à une fragilité osseuse augmentée et par conséquent à une augmentation du risque fracturaire. Elle est associée à une morbidité et mortalité importantes. Il existe de nombreuses substances à disposition pour son traitement. La modalité d'administration est très variable selon la substance prescrite. Les bisphosphonates, puissants antirésorbeurs osseux, sont la classe médicamenteuse de référence. Malheureusement, prescrits per os, iIs ont fréquemment des effets secondaires digestifs limitant leur usage et sont donc mieux tolérés en iv. C'est le pamidronate qui a été le premier prescrit et reste le plus utilisé. Méthode : le meilleur régime d'administration du pamidronate n'étant pas connu, nous avons testé son effet à différentes doses sur les marqueurs du remodelage osseux et la densitométrie osseuse. Trois modalités d'administration pour une dose annuelle constante (30 mg tous les 3 mois, 40 mg tous les 4 mois et 60 mg tous les 6 mois) ont été comparées chez des femmes postménopausées avec une ostéoporose. 39 patientes ont été recrutées sur 2 ans et réparties en 2 groupes appelés EFAP 1 et 2 pour Evaluation de la Fréquence d'Administration du Pamidronate selon la fréquence des contrôles de sang. Résultats : au cours des 6 premiers mois de traitement, on observe une chute rapide des télopeptides sanguins dès le premier mois qui suit l'injection de 30, 40 ou 60 mg de pamidronate avec toutefois, une inhibition de la résorption osseuse plus efficace à long terme pour les traitements fractionnés (30 et 40 mg). Des résultats similaires sont obtenus pour l'ostéocalcine. Il n'existe en revanche pas de modifications significatives des autres paramètres (calcémie, PTH, vitamine D et phosphatase alcaline) dans les 3 groupes. Ces résultats se confirment après 24 mois de traitement avec une efficacité plus marquée pour les traitements 30 et 40 mg. Sur le plan des valeurs de densitométrie osseuse, après 2 ans de traitement, les valeurs sont augmentées de façon significative sur la colonne lombaire avec les trais dosages, de façon non significatives sur le col fémoral et de façon significative pour le trochanter avec le dosage de 40 mg seulement. Conclusions : bien que cette étude démontre des gains de densité osseuse quasi identiques entre les 3 modes d'administration pour une dose annuelle cumulée de 120 mg, l'inhibition du remodelage osseux est beaucoup plus importante avec les doses de 30 ou 40 mg tous les 3 ou 4 mois qu'avec 60 mg tous les 6 mois. Ces deux modes d'administration permettent de mieux expliquer le lien entre l'effet sur les marqueurs et sur la densitométrie osseuse

Centenarians in Europe.

The group of individuals aged 80 and over is growing faster than other segments of the population, and within this group the number of centenarians has risen exponentially worldwide. This paper reports the numbers of centenarians (total, and ratio relative to total population) in 32 European countries and their key characteristics: gender distribution, level of education, and type of residence. Population based study. We used national census data collected in 2011 for individuals aged 100 and over living in Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the UK. Data on gender, residence and education were used. The total number of centenarians was 89156, corresponding to 17.3 centenarians per 100000 inhabitants of the total population and 98.0 centenarians per 100000 individuals aged 65 and older. Centenarian ratios were highest in France, Italy and Greece, and lowest in Bulgaria, Romania, and Croatia. The percentage of men was 16.5% on average, and ranged from around 13% (Germany, Latvia, Belgium) to 37% (Hungary). Across Europe, 62.7% of the centenarians lived in private households, with a range from 10.9% (Iceland) to 90.0% (Romania). Education levels varied across countries, with an average of 13.6% having no formal education, ranging from 0.0% (the UK, Finland, Iceland) to 61.6% (Portugal). Centenarian numbers have increased substantially since last available data. The findings will inform specific health promotion policies, the strengthening of current services and the development of innovative care systems

VAV – Virtual Anaesthesia Visit - An online tool for the preanaesthesia visit in the CHVR (Centre hospitalier du Valais Romand)

INTRODUCTION: Safety is an important issue in anesthesia. Preoperative risk managing strategies include the designation of an ASA score and a preanesthesia visit (PAV) in order to reduce anesthesia and surgery related risk. Logistical, geographical and linguistic difficulties can be obstacles to a PAV. Computer based assessment and patient video-information to overcome some of these obstacles have been investigated. The aim of the present project was to develop an electronic alternative to the conventional PAV visit in the CHVR. METHODS: After a preliminary study based on data extracted from the Clinical Information System to delimit the target population, a group composed of senior anesthetists, a trainee anesthetist, a photographer and a computer scientist created a new online preanaesthesia assessment tool. A feasibility test was conducted with a random sample of patients. RESULTS: The 2015 patient cohort study showed a median age of 57 years, with a predominant ASA 2 status . 23,6% of the patients reside in the German speaking Upper Valais. The maximal distance for a PAV was 103km. These results were the basis for the design of the electronic alternative called VAV, composed of 3 elements: 1) a selection tool of the surgical procedure linked to a surgical risk category, and one out of four information videos about the proposed anesthesia technique; 2) an electronic patient assessment questionnaire; 3) two algorithms: one concealing a computerized ASA score (cASA) and one assigning patients at risk for a standard visit. The data of the VAV will be imported in the patient’s CIS after completion and deleted on the server. VAV is intended to be used by any adult patient scheduled for non-cardiac surgery. The VAV includes a video dedicated to pregnant woman in order to inform them at distance from the delivery about the analgesic procedures and anesthesia techniques for surgical delivery procedures. CONCLUSION: The VAV was designed for the CHVR patient population. It is adapted with contemporary web-connectivity as it combines elements of patient assessment, patient information and informed consent in one single on-line tool. The aim of the VAV is to lead to a better assessment through a standardized tool, specially for vulnerable patients in order to triage them better, and increase safety

Single cell analysis of the CD8+ T cell response to therapeutic Melan-A peptide vaccination over time

Background Therapeutic vaccines are currently being optimized to enhance melanoma patients' own immune defenses against cancer cells. The Melan-AMART-1 tumor antigen is frequently expressed in melanoma and has been widely used in clinical immunotherapy studies. We previously reported that vaccination with the native unmodified Melan-A (defined as EAA hereafter), but not the analog peptide (defined as ELA), despite its stronger binding to HLA-A2, elicited a polyfunctional phenotype (i.e. co-expressing genes associated with memory and effector attributes) by tumor-specific T cells, together with increased tumor cell killing capacities by these cells. Objective The present study aims at characterizing the timing of acquisition of memory/effector properties among individual tumor-reactive CD8 T cell clones in melanoma patients following vaccination with the native/EAA peptide, compared to responses induced with the analog/ELA peptide. Moreover, we assessed the evolution of the tumor-specific T cell clonotype repertoire across time following vaccination in both cohorts of patients and its specific selection at early time points as compared to the specific responses pre-existing before the start of immunotherapy. Methods We generated a large library of cDNAs (n = 1500) isolated from single Melan-A-specific effector- memory (EM) CD28+ (memory-like; EM28+) and CD28- (effector-like; EM28-) T cells at different time points before and after peptide vaccination. Our highly sensitive single cell gene expression approach allowed the direct ex vivo characterization of individual tumor-specific T cells in melanoma patients who received either the native/EAA (n = 4) or the analog/ELA (n = 3) peptide vaccine. PCRs specific for the TCRβ-chain variable region were further performed to determine the TRBV/CDR3-based clonotype of each individual tumor-specific T cells across time after vaccination. Results When compared to pre-vaccine T cell phenotype, tumor-specific T cells underwent a drastic differentiation change into effector-memory following CpG vaccination, regardless of the type of peptide vaccine used (native/EAA or analog/ELA). Acquisition of the EM28+ phenotype shortly after vaccination was specifically associated with the significant increase in effector gene expression and concomitant reduction of a memory gene expression pattern (IL-7R CXCR3- CCR5-). Dominant tumor-specific TCR clonotypes were expanded during this process and many of them were maintained stable over time, as they also were found present at late time points after immunotherapy. Using the advantage of the single cell resolution, a difference in CD27 gene expression could be identified between EM T cells with dominant or non-dominant TCR clonotypes. Conclusions Melan-A peptide/CpG vaccination induced the strong T cell differentiation of tumor-reactive T cells, which was accompanied by increased effector gene expression and expansion of dominant clonotypes, in both native/EAA and analog/ELA based vaccine. Moreover, our data further suggest that tumor-specific T cells may undergo a maturation process during the course of vaccination, which may account for the differences observed in the co-expression of memory and effector genes within native/EAA EM28+ T cells at later time points. Finally, once established, the clonal composition of tumor-specific T cell responses was kept stable along immunotherapy. Collectively, such analyses provide important insights on the in vivo impact of natural over analog peptide vaccination on T cell polyfunctionality and clonotype selection induced by each type of vaccination

El papel de los objectos intermediadores en la interdisciplinariedad

Muitas publicações falam de interdisciplinaridade em geral, apresentando a necessidade desta, suas vantagens e limitações. Muitas dessas publicações apresentam defesas ou críticas a este fenômeno atual, outras oferecem abordagens epistemológicas e discutem as condições epistêmicas que garantam a sua eficiência. Mas não existem muitas publicações que lidam com as condições e as práticas institucionais da interdisciplinaridade. Nesta comunicação, propomos uma abordagem destas questões a partir de vários estudos de caso, tanto ao nível de ensino como de pesquisa. Vários modelos de interdisciplinaridade serão apresentados antes de adentrarmos nas condições práticas da interdisciplinaridade, por exemplo, em ciência da informação. Introduzimos a noção de objeto intermediário e algumas das funções que desempenham nas práticas que pudemos observar