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Many factors contribute to the development and progression of intervertebral disc (IVD) degeneration. This study was designed to assess the effects of compressive load magnitude on IVD metabolism. It was hypothesized that as load magnitude increased, there would be a significant increase in release of proinflammatory and degradative biomarkers, and a significant decrease in tissue proteoglycan (GAG) and collagen contents compared with unloaded controls. IVD whole organ functional spinal units (FSU) consisting of cranial and caudal body halves, cartilage endplates, and IVD (n = 36) were harvested from the tails of six Sprague Dawley rats, and FSUs were cultured at 0.0 MPa, 0.5 MPa, or 1.0 MPa at 0.5 Hz for 3 days. After culture, media were collected for biomarker analysis and FSUs were analyzed for extracellular matrix composition. Significant differences were determined using a one-way analysis of variance or Kruskal-Wallis test and post hoc analyses. Media concentrations of IFN-γ, IL-6, IL-1β, and MMP-8 were significantly higher in the 0.5 MPa compared with the 0.0 MPa group. Media concentrations of PGE2 and TIMP-1 were significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and media PGE2 was significantly higher in the 1.0 MPa group compared with the 0.5 MPa group. Media GAG content was significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and percent GAG in the tissue was significantly lower in 0.5 MPa and 1.0 MPa groups compared with the 0.0 MPa group. Clinical Significance: These data suggest that there are magnitude-dependent inflammatory and degradative IVD responses to cyclic loading, which may contribute to IVD degeneration.

The S-phase Kinase-Associated Protein 1 (SKP1) is a core component of the SKP1, Cullin 1, F-box protein (SCF) complex, an E3 ubiquitin ligase that serves to poly-ubiquitinate a vast array of protein targets as a signal for their proteasomal degradation, thereby playing a critical role in the regulation of downstream biological processes. Many of the proteins regulated by SKP1 and the SCF complex normally function within pathways that are essential for maintaining genome stability, including DNA damage repair, apoptotic signaling, and centrosome dynamics. Accordingly, aberrant SKP1 and SCF complex expression and function is expected to disrupt these essential pathways, which may have pathological implications in diseases like cancer. In this review, we summarize the central role SKP1 plays in regulating essential cellular processes; we describe functional models in which SKP1 expression is altered and the corresponding impacts on genome stability; and we discuss the prevalence of SKP1 somatic copy number alterations, mutations, and altered protein expression across different cancer types, to identify a potential link between SKP1 and SCF complex dysfunction to chromosome/genome instability and cancer pathogenesis. Ultimately, understanding the role of SKP1 in driving chromosome instability will expand upon our rudimentary understanding of the key events required for genome/chromosome stability that may aid in our understanding of cancer pathogenesis, which will be critical for future studies to establish whether SKP1 may be useful as prognostic indicator or as a therapeutic target.

The SKP1, CUL1, F-box protein (SCF) complex encompasses a group of 69 SCF E3 ubiquitin ligase complexes that primarily modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation. These SCF complexes are distinguishable by variable F-box proteins, which determine substrate specificity. Although the function(s) of each individual SCF complex remain largely unknown, those that have been characterized regulate a wide array of cellular processes, including gene transcription and the cell cycle. In this regard, the SCF complex regulates transcription factors that modulate cell signaling and ensures timely degradation of primary cell cycle regulators for accurate replication and segregation of genetic material. SCF complex members are aberrantly expressed in a myriad of cancer types, with altered expression or function of the invariable core SCF components expected to have a greater impact on cancer pathogenesis than that of the F-box proteins. Accordingly, this review describes the normal roles that various SCF complexes have in maintaining genome stability before discussing the impact that aberrant SCF complex expression and/or function have on cancer pathogenesis. Further characterization of the SCF complex functions is essential to identify and develop therapeutic approaches to exploit aberrant SCF complex expression and function.

Background High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Chromosome instability (CIN, an increased rate of chromosome gains and losses) is believed to play a fundamental role in the development and evolution of HGSOC. Importantly, overexpression of Cyclin E1 protein induces CIN, and genomic amplification of CCNE1 contributes to HGSOC pathogenesis in ~20% of patients. Cyclin E1 levels are normally regulated in a cell cycle-dependent manner by the SCF (SKP1–CUL1–FBOX) complex, an E3 ubiquitin ligase that includes the proteins SKP1 and CUL1. Conceptually, diminished SKP1 or CUL1 expression is predicted to underlie increases in Cyclin E1 levels and induce CIN. Methods This study employs fallopian tube secretory epithelial cell models to evaluate the impact diminished SKP1 or CUL1 expression has on Cyclin E1 and CIN in both short-term (siRNA) and long-term (CRISPR/Cas9) studies. Results Single-cell quantitative imaging microscopy approaches revealed changes in CIN-associated phenotypes and chromosome numbers and increased Cyclin E1 in response to diminished SKP1 or CUL1 expression. Conclusions These data identify SKP1 and CUL1 as novel CIN genes in HGSOC precursor cells that may drive early aetiological events contributing to HGSOC development.

Micronuclei are small, extranuclear bodies that are distinct from the primary cell nucleus. Micronucleus formation is an aberrant event that suggests a history of genotoxic stress or chromosome mis-segregation events. Accordingly, assays evaluating micronucleus formation serve as useful tools within the fields of toxicology and oncology. Here, we describe a novel micronucleus formation assay that utilizes a high-throughput imaging platform and automated image analysis software for accurate detection and rapid quantification of micronuclei at the single cell level. We show that our image analysis parameters are capable of identifying dose-dependent increases in micronucleus formation within three distinct cell lines following treatment with two established genotoxic agents, etoposide or bleomycin. We further show that this assay detects micronuclei induced through silencing of the established chromosome instability gene, SMC1A. Thus, the micronucleus formation assay described here is a versatile and efficient alternative to more laborious cytological approaches, and greatly increases throughput, which will be particularly beneficial for large-scale chemical or genetic screens.

Resume Objectifs En France le pharmacien d’officine realise l’accompagnement pharmaceutique des patients traites par anti-vitamines K (AVK). Alors que ce dispositif se deploie dans d’autres pathologies chroniques, nous avons voulu evaluer la perception des pharmaciens d’officine sur l’initiation et le suivi de ce dispositif 2 ans apres sa mise en place. Methodes Une etude evaluative et prospective a ete realisee du 1er aout au 31 decembre 2015 aupres des 400 pharmacies d’officine de Champagne-Ardenne. Un questionnaire a porte sur 3 thematiques : mise en application ; profil des patients cibles ; approche globale du pharmacien. Resultats Sur les 47 retours, 72 % des pharmaciens realisent des entretiens pharmaceutiques. La majorite d’entre eux a suivi une formation (96 %). La remuneration etait jugee insuffisante au regard du temps dedie pour 73 % des pharmaciens. La majorite des pharmaciens a eu au moins un refus (95 %), motive par le manque d’interet (54 %) ou de temps (22 %). Selon les pharmaciens, les 3 principales lacunes des patients etaient la connaissance des medicaments a eviter (28 %), les signes cliniques d’un surdosage (27 %) et les interactions avec l’alimentation (23 %). L’approche globale du pharmacien vis-a-vis de ce dispositif etait positive (81 %) avec notamment une amelioration de la relation avec le patient (66 %). Conclusion La perception des pharmaciens de l’accompagnement des patients est globalement positive. Cependant, les contraintes organisationnelles et economiques peuvent entrainer une perte d’adhesion des pharmaciens. Une reflexion autour d’une revalorisation financiere et d’actions de communication permettrait de perenniser cette mission et l’etendre a d’autres pathologies.

IF 3.061; International audience; Introduction : Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.Aim :PRODIGE 41–BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC.Materials and methods : The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy.Results : A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response.Conclusion :The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.

Injectable substances known as fillers are used to palliate age-related atrophy and ptosis, and for their so-called "pseudo-lifting" action. They do not replace face and neck lift, but allow it to be postponed or, when injected after surgical lifting, make the result durable. Hyaluronic acid has a predominant and unchallenged place among fillers, well ahead of poly-L-lactic acid or calcium hydroxyapatite. Approaches and injection methods are the same for all fillers, corresponding to those for autologous fat injection, the reference substance, with a few particularities. The substance used, the level of hyaluronic acid reticulation, and the depth of the injection depend on the injection site and intended effect. Effects range from smoothing superficial wrinkles to remodeling whole parts of the face. Complications related to such fillers are well known, especially in the case of hyaluronic acid, where overcorrection is the most frequent. To limit the risk of complications and also to offer each patient the most individually adapted corrections, before any procedure, the plastic surgeon needs to question the patient and perform precise medical examination.

Resume Depuis quelques annees, une approche volumetrique par injections de graisse autologue vient completer le lifting cervicofacial afin d’en ameliorer le resultat esthetique et de perenniser le rajeunissement facial. Si l’utilisation de graisse autologue comme tissu de comblement en chirurgie plastique date de la fin du 19 e siecle, son association avec le lifting cervicofacial ne s’est repandue que recemment. L’interet d’associer ces deux methodes repose d’une part sur les caracteristiques physiopathologiques du vieillissement facial qui associe relâchement cutane et perte de volume, et d’autre part sur les proprietes d’induction tissulaire du greffon graisseux, source de « rajeunissement » des zones injectees. La methodologie stricte qui consiste a prelever, traiter, puis injecter un greffon de graisse autologue porte le nom de LipoStructure ® ou lipofilling. Cette methode est decrite dans sa globalite, puis region par region. Si cette methode, aujourd’hui bien connue, semble simple, efficace, et reproductible, elle n’en demeure pas moins delicate. Elle exige de restituer a chaque patient un visage harmonieux aux volumes bien distribues. En associant la volumetrie au lifting, le chirurgien esthetique change de role, de tailleur, retirant l’exces de peau, il devient sculpteur, remodelant les visages avec pour objectif de restaurer l’harmonie propre aux visages jeunes.

Introduction Sleep disturbance in children with attention-deficit/hyperactivity disorder (ADHD) is frequent, and lead to shorter sleep duration which has been associated with lower performance on sustained attention tasks. However, no study has investigated this association in adolescents with ADHD. We sought to explore whether the association between sleep and sustained attention performance of children with ADHD is similar in adolescents with ADHD given that sleep patterns are different. Methods Parents of 32 children (mean age = 8.0; SD = 1.3) and 10 adolescents (mean = 15.2; SD = 1.3) with ADHD completed a developmental questionnaire including sleep questions. Children and adolescents were medication free and underwent a comprehensive neuropsychological evaluation. Three sleep variables were extracted from the questionnaire, namely the duration of the sleep period during week nights and weekends as well as the difference between the two (“weekend shift”). The Continuous Performance Test was used to measure sustained attention (omission, commission, hit reaction time). Pearson correlations between sleep variables and sustained attention measures were calculated. Results Children showed a positive correlation between hit reaction time and the duration of the sleep period during week nights (r = 0.37; p =0.04), weekends (r = 0.51; p = 0.004) and the weekend shift (r = 0.37; p =0.04). No significant correlations were found in the adolescent group. Conclusion The fact that no significant associations were found in the adolescent group suggest an improvement of the arousal system through brain development in ADHD, or that other mechanisms could be involved in the etiology of ADHD in adolescents. Support Centre d’apprentissage aux 1001 astuces; Fonds de recherche du Québec - Santé

International audience; Few data are available about the epidemiology of digestive neuroendocrine tumours (NETs). Malignant digestive (MD) NETs remain as a rare cancer representing 1 % of digestive cancers. In France, the incidence rates of MD-NETs are estimated to around 1.1/100,000 inhabitants in males and 0.9/100,000 in females which then increased over time, with probably more than 1,000 new cases per year. Due to the relative good prognosis, NETs are the second more prevalent digestive cancer next to colorectal cancer. Most gastroenteropancreatic NETs are well-differentiated (WD-NETs); poorly differentiated neuroendocrine carcinomas (PDNEC) account for less than 20% of the cases in most of the series. Among WD-NETs, the most frequent anatomical localisations are small bowel and pancreas. Functional NETs are rare (< 20%); most of them are carcinoids, insulinomas and gastrinomas. More than half NETs are metastatic at diagnosis, mainly in the liver. Tumour differentiation, histologic grade, anatomic site and stage are the main prognostic factors. WD-NETs are slow-growing tumours (relative survival rate of 55% in 5 years), whereas PDNEC are highly aggressive (relative survival rate of 4.5% in 5 years).; Peu de données sont disponibles concernant l'incidence et les facteurs pronostiques des tumeurs neuroendocrines (TNE) digestives malignes. Les TNE sont rares et représentent environ 1 % des cancers digestifs. En France, l'incidence des TNE digestives malignes est estimée dans le registre Bourguignon à 1,1/100 000 chez l'homme et à 0,9/100 000 chez la femme. L'incidence augmente au cours du temps. Du fait de leur longue survie, les TNE constituent, après le cancer colorectal, le cancer digestif dont la prévalence est la plus élevée. La plupart des TNE sont bien différenciées, les carcinomes neuroendocrines peu différenciés représentent moins de 20 % des TNE digestives. Parmi les TNE bien différenciées, les localisations les plus fréquentes sont l'intestin grêle et le pancréas. Plus de la moitié des TNE sont diagnostiquées au stade métastatique, principalement au niveau hépatique. Le degré de différenciation, le grade histologique, la localisation du primitif et le stade sont les principaux facteurs pronostiques. Les taux de survie relative à cinq ans étaient de 4,5 % pour les tumeurs peu différenciées versus plus de 55 % pour les TNE bien différenciées.

International audience; Using structural composite materials for the fabrication of Radar Absorbing Materials (RAM) allows combining the strong load bearing capability with the radar absorbing functionality in a unique structure. This article shows the possibility to transpose an already existing metamaterial absorber to the domain of composite materials. The dielectric layers of the absorber initially designed with radio-frequency (RF) materials are replaced with fiber-reinforced composite materials and their thickness is optimized again. The working principle of the absorber is explained layer by layer on the Smith chart. The performances of the composite absorber are compared against the initial RF design and against other classical absorbers. The composite design has a total thickness of 8.9 mm and achieves a reflection coefficient below 14 dB within the band 4.6 GHz - 17.2 GHz at normal incidence. The reflection coefficient remains under -10 dB at oblique incidence up to 45°.; L'utilisation de matériaux composites structurels pour la fabrication de matériaux absorbants radar permet de combiner la capacité de charge élevée avec la fonctionnalité d'absorption radar dans une structure unique. Cet article montre la possibilité de transposer un méta matériaux absorbant déjà existant, dans le domaine des matériaux composites. Les couches diélectriques de l'absorbant initialement conçues avec des matériaux radiofréquences (RF) sont remplacées par des matériaux composites renforcés de fibres et leur épaisseur est à nouveau optimisée. Le principe de fonctionnement de l'absorbant est expliqué couche par couche sur la carte de Smith. Les performances de l'absorbant composite sont comparées à la conception RF initiale et à d'autres absorbants classiques. La conception composite a une épaisseur totale de 8,9 mm et atteint un coefficient de réflexion inférieur à -14 dB dans la bande 4,6 GHz - 17,2 GHz à incidence normale. Le coefficient de réflexion reste inférieur à -10 dB en incidence oblique jusqu'à 45 °.

BACKGROUND: The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined this question as an ancillary study of the PETACC8 phase III trial.PATIENTS AND METHODS: We analyzed the prognostic impact of KRAS exon 2 mutations in stage III colon cancer patients (n = 1657) receiving adjuvant FOLFOX ± cetuximab therapy included in the PETACC8 trial. Patients with BRAF-mutated cancers were excluded and, as no difference was found for time to recurrence (TTR) and disease-free survival (DFS) between treatment arms, both were pooled for analysis. Associations with TTR and DFS were analyzed using a Cox proportional hazards model.RESULTS: KRAS mutations were found in 638 of 1657 tumors and linked to shorter TTR (P < 0.001). However, when specific mutations were compared with wild-type, codon 12 mutations [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.35-2.04; P < 0.001] but not codon 13 (HR 1.23, 95% CI 0.85-1.79; P = 0.26) were significantly associated with shorter TTR, independently of other covariates. The interaction test showed that, regarding tumor location (distal versus proximal), KRAS genotype affects differently on recurrence (P = 0.02) and DFS (P = 0.042). Subgroup analysis showed that KRAS only affected TTR and DFS in distal tumors (n = 1043; 692 wild type; 351 mutated), with an increased risk of relapse (HR 1.96, 95% CI 1.51-2.56; P < 0.0001) for KRAS codon 12 mutations and a borderline significance for codon 13 mutations (HR 1.59, 95% CI 1.00-2.56; P = 0.051).CONCLUSION: KRAS exon 2 mutations are independent predictors of shorter TTR in patients with resected stage III distal colon cancers receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors.CLINICAL TRIAL NUMBER: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

// Erin N. McAndrew 1, 2 , Chloe C. Lepage 1, 2 , Kirk J. McManus 1, 2 1 University of Manitoba, Department of Biochemistry & Medical Genetics, Winnipeg, Manitoba, Canada 2 Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada Correspondence to: Kirk J. McManus, email: Kirk.McManus@umanitoba.ca Keywords: cancer, RAD54B, PARP1, synthetic lethality, precision medicine Received: October 12, 2016 Accepted: November 07, 2016 Published: November 26, 2016 ABSTRACT Colorectal cancer (CRC) is a leading cause of cancer-related death throughout the world. Despite improved screening efforts, most CRCs are diagnosed at late stages when surgery alone is not curative. Moreover, the low 5-year survival rate (~8-13%) for those living with stage IV CRC highlights the need for better treatment options. Many current chemotherapeutic approaches are non-specific and associated with side effects due to their tendency to target both normal and cancer cells. To address this issue, synthetic lethal (SL) approaches are now being explored in cancer and are defined as the lethal combination of two independently viable mutations/deletions. From a therapeutic perspective, SL interactors of genes mutated in cancer serve as candidate drug targets. The present study focuses on RAD54B , a gene that is aberrantly expressed in many cancer types, including CRC. We show that PARP1 silencing or inhibition (BMN673 or Olaparib) leads to selective killing within RAD54B -deficient cells relative to controls, and is accompanied by increases in γ-H2AX (a surrogate marker of DNA double strand breaks) and cleaved Caspase-3 (an apoptotic indicator). We further show that BMN673 synergizes with LCS-1 (an inhibitor of an established RAD54B SL interactor) to induce enhanced killing in RAD54B -deficient cells. Collectively, these data identify RAD54B and PARP1 as SL interactors, and thus reveal PARP1 as a novel candidate drug target in RAD54B -deficient CRCs. These findings further show that combinatorial chemotherapies involving multiple SL targets may promote synergistic killing within cancer cells, a strategy that may hold potential in many cancer contexts.

Background Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 +/- cetuximab in the PETACC8 study. Methods Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade ≥3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS. Table . 549P Overall analysis DFS OS HR [95%CI] p HR [95%CI] p Anticoagulants Intake vs no 1.33 [1.10–1.62] .003 1.34 [1.07–1.67] .01 Antidiarrheals Intake vs no 0.87 [0.73–1.04] .12 0.78 [0.63–0.96] .02 Cardiovascular trts Intake vs no 1.20 [1.03–1.41] .02 1.28 [1.07–1.54] .01 Antidiabetics Intake vs no 1.37 [1.07–1.76] .01 1.45 [1.09–1.92] .01 Conclusions Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification PETACC8; 2005-003463-23. Legal entity responsible for the study Federation Francophone de Cancerologie Digestive, Dijon. Funding Merck and Sanofi. Disclosure J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

Background/Objectives: Data on the time between colorectal cancer diagnosis and treatment in real-life practice for elderly patients are scarce. We measured times from diagnosis to first-course therapy in elderly patients with colon and rectal cancers. Design: The study was carried out on the population-based Burgundy Digestive Cancer Registry (France). Setting: Therapeutic delays were described by medians and interquartile ranges and compared by the Kruskal-Wallis rank test. Factors associated with changes in therapeutic delay were identified using a multivariate Cox model. Participants: The analysis was carried out on 2,884 patients aged 60 years and over with colorectal adenocarcinoma diagnosed between 2005 and 2011. Measurements and Results: The median therapeutic delay for colon cancer was 25 days in patients aged 60 to 69 years and 24 days for those aged 70-79 years. The delay fell significantly to 19 days in patients aged 80 and over (p

Resume Les auteurs ont effectue une etude retrospective des reconstructions mammaires par lambeau libre (Deep Inferior Epigastric Flap) DIEP entre 1994 et 2014 par une seule equipe. Materiel et methode Une analyse retrospective de l’ensemble des comptes rendus operatoires et d’hospitalisation a ete effectuee portant sur la periode de 1994 a 2014. Le nombre de cas par an, le taux de complication sur le site donneur et le site receveur et le temps operatoire etaient releves. Une analyse sequentielle etait faite pour determiner les elements ayant pu permettre d’implementer de maniere fiable cette technique et les effets de la courbe d’apprentissage. La serie a ete separee en deux periodes (1994–2011 et 2012–2014) correspondant a deux hopitaux differents avec la meme equipe. Resultats Le nombre total de lambeaux est de 1138 entre novembre 1994 et decembre 2014 avec respectivement 477 la periode 1994–2011 et 661 pour la periode 2012–2014. Le taux d’echec est passe de 8 % a 2,2 %. Conclusion La mise en place d’unites dediees principalement a la reconstruction microchirurgicale permet d’offrir la technique DIEP de maniere fiable et reproductible.

Resume La fragilite des personnes polyhandicapees en grande dependance globale, face aux affections respiratoires, est connue. Une maladie, simple chez le sujet ordinaire, pourra chez elle se compliquer. S’intriquant avec d’autres elements pathologiques, elle evolue volontiers vers l’insuffisance respiratoire chronique. Les complications du decubitus dorsal dans lequel sont maintenues ces personnes, du fait de leur insuffisance motrice, expliquent en partie la constitution de ces tableaux. Pour traiter ces complications dont la permanence positionnelle semble etre une des causes importantes, il parait logique d’apporter au sujet souffrant de cet etat du changement de position. La demarche qui a permis d’installer les polyhandicapes en position assise est allee dans le bon sens ; celui de la prise en compte de leurs besoins posturaux. Par-la, certaines complications du decubitus dorsal, comme l’hypoventilation, ont ete attenuees. Mais la station assise n’agit pas favorablement sur les deformations thoraciques et les deficits musculaires. Elle peut meme provoquer et aggraver des deformations si l’installation qui la permet n’est pas suffisamment adaptee aux besoins neuro-orthopediques individuels. L’abord de l’action des autres positions, laterales puis ventrales notamment, sur la fonction respiratoire par exemple, parait apporter d’autres perspectives, celles d’un traitement positionnel des affections respiratoires de la personne polyhandicapee. Alors, et si de surcroit l’approche est globale, l’idee d’un traitement specifique, traitement de fond des problemes respiratoires de la personne gravement polyhandicapee, apparait.

International audience

A wideband dual-polarized coplanar waveguide (CPW) fed antenna integrating a wide stop-band filter is presented. The designed filter is based on a nonuniform defected ground structure (DGS) in order to obtain a wide stop-band and a compact size. This filter is used to reject harmonics and spurious radiation arising from the RF front end. The complete structure (antenna and filter) has been optimized to have a compact size of0.6×0.6λ02(λ0being the free-space wavelength at the lowest operating frequency). The realized antenna operates in the frequency range between 2.7 GHz and 5.9 GHz (bandwidth of about 74%). The isolation between feeding ports is more than 18 dB. The complete structure has a wide stop-band characteristic (103%) for harmonic rejection. The simulated numerical results have been confirmed with measurements.

Cancer is a devastating disease that claims over 8 million lives each year. Understanding the molecular etiology of the disease is critical to identify and develop new therapeutic strategies and targets. Chromosome instability (CIN) is an abnormal phenotype, characterized by progressive numerical and/or structural chromosomal changes, which is observed in virtually all cancer types. CIN generates intratumoral heterogeneity, drives cancer development, and promotes metastatic progression, and thus, it is associated with highly aggressive, drug-resistant tumors and poor patient prognosis. As CIN is observed in both primary and metastatic lesions, innovative strategies that exploit CIN may offer therapeutic benefits and better outcomes for cancer patients. Unfortunately, exploiting CIN remains a significant challenge, as the aberrant mechanisms driving CIN and their causative roles in cancer have yet to be fully elucidated. The development and utilization of CIN-exploiting therapies is further complicated by the associated risks for off-target effects and secondary cancers. Accordingly, this review will assess the strengths and limitations of current CIN-exploiting therapies, and discuss emerging strategies designed to overcome these challenges to improve outcomes and survival for patients diagnosed with cancer.

IF 11.855; International audience

Injectable substances known as fillers are used to palliate age-related atrophy and ptosis, and for their so-called "pseudo-lifting" action. They do not replace face and neck lift, but allow it to be postponed or, when injected after surgical lifting, make the result durable. Hyaluronic acid has a predominant and unchallenged place among fillers, well ahead of poly-L-lactic acid or calcium hydroxyapatite. Approaches and injection methods are the same for all fillers, corresponding to those for autologous fat injection, the reference substance, with a few particularities. The substance used, the level of hyaluronic acid reticulation, and the depth of the injection depend on the injection site and intended effect. Effects range from smoothing superficial wrinkles to remodeling whole parts of the face. Complications related to such fillers are well known, especially in the case of hyaluronic acid, where overcorrection is the most frequent. To limit the risk of complications and also to offer each patient the most individually adapted corrections, before any procedure, the plastic surgeon needs to question the patient and perform precise medical examination.

Since 2013 French community pharmacist are involved in pharmaceutical care program (PCP) for patients treated with vitamin K antagonist (VKA). While PCPs are now extending to other patient populations, we aimed to evaluate pharmacists' perception after 2-years implementation and leading of PCP.A prospective investigational survey from 1st August to 31st December, 2015 from 400 community pharmacies in Champagne-Ardenne Region. Survey focuses on 3 points: first about implementation and leading of PCP; secondly about patient's population description; finally on the global perception by CP about new tasks.Among n=47, 72% of pharmacists performed VKA PCP. Almost all received appropriate training (96%). Remuneration appears to be insufficient given the time spent for 73%. Ninety-five percent met patient's refusal mainly because of interest lacking or time lacking (54% and 22%, respectively). Pharmacists reported 3 main lacks of knowledges of patients: drugs, which increase drug-drug interaction risk (28%), VKA overdose effects (27%) and VKA-food interactions (23%). Overall view of pharmacist for PCP appears to be positive (81%) in part because of improvement of pharmacist-patient relationship perception for 66%.Community pharmacists' perception for PCP for patients treated by VKA is broadly positive. However, organizational or economic constraints can lead to a decreasing adherence by pharmacists to PCPs. A global issue about amount of compensation and communications campaigns to patients and others health professionals will be useful in order to reinforced PCP implementation and leading taxonomy.

International audience

Background Nivolumab is indicated for the treatment of patients with squamous and non-squamous non-small cell lung cancer (NSCLC) locally advanced or metastatic after failure of chemotherapy. French marketing authorisation approval for this immunotherapy was based on two pivotal studies, Checkmate-017 and Checkmate-057 for squamous and non-squamous NSCLC, respectively. They demonstrated a significant responder rate (20%) and a good safety profile: 10% serious adverse events (SAE). Immunotherapy represents an innovative therapeutic alternative, but financial costs are high. Purpose To present the safety and efficacy of nivolumab in patients treated for lung cancer. Material and methods A retrospective cohort study was conducted on patients who received at least one cycle of nivolumab from March 2015 to February 2016, with follow up until September 2016. A scan was performed every 2 months and evaluated using RECIST 1.1 criteria. In the case of progression on the first scan, depending on the patient’s clinical condition, the treatment could be continued until the second assessment. In case of progression or SAE, treatment was discontinued. Results 73 patients were included in the study (35–90 years old, mean age 66 years), 28% squamous and 72% non-squamous NSCLC. 33 patients followed a secondline treatment, 21 a thirdline and 19 a fourthline or more. After the fourth cycle (C4), the first evaluation revealed partial or complete response for 25% of patients, stability for 30% of patients and progression for 37% of patients. 8% of patients discontinued the treatment early. Among progressions, 16 patients continued treatment until the C6 evaluation, assuming a pseudo-progression, and the response was seen in only 2 patients. At 1 March 2016, 22% patients were still under treatment, with an average of 21.9 cures (range 12–35). 12% of patients experienced SAE: 5 pneumonitis grades 3 and 4, 1 grade 3 diarrhoea, 1 grade 3 colitis, 1 grade 4 hepatitis and 1 grade 4 diabetic ketoacidosis. Conclusion The responder rate in C4 patient and the safety profile of nivolumab (25%) seem to be consistent with pivotal studies. The high number of pneumonitis among SAE justify particular vigilance. The long term follow-up of this cohort will consolidate these results. No conflict of interest