Suivi du patient oncologique, garant de la permanence de soi [Follow-up of the cancer patient, maintaining self-identity]

L'individu confronté au diagnostic de cancer subit un bouleversement brutal de ses repères et de ses habitudes. La maladie représente une menace pour son équilibre de vie et sa stabilité sociale. Sa capacité à faire face et à opérer différents remaniements dans sa façon d'être au monde et d'envisager l'avenir est en partie déterminée par ses ressources personnelles. Toutefois, le soutien émotionnel peut également représenter un moyen privilégié de donner du sens à cette expérience singulière qu'est la maladie. La reconstruction narrative dans un cadre soutenant, caractérisé par une écoute bienveillante, offre au patient la possibilité de reconnaître sa souffrance comme partie intégrante de lui-même. Un récit de vie qui intègre la maladie lui permet de se réapproprier son histoire. Cette démarche nécessite de la part du thérapeute une disponibilité psychique et temporelle et la capacité de soutenir le patient dans un processus de liaison à travers les différentes étapes de la maladie. The individual facing the diagnosis of cancer is subjected to abrupt changes with regard to his inner world, his life, habits and social relationships. The patient's capacity to cope, to integrate changes in the way of living and to face the future is determined by his personal resources. However, psychological support may also be an important mean to search for and find sense to the singular experience of the illness. The narrative reconstruction within a supportive setting provides the patient a possibility to recognise his sufferance as an integral part of himself. A life narrative, which integrates the illness, allows the patient to re-appropriate his history again. Such a therapeutic project necessitates from the therapist a psychological and temporal disponibility and a capacity to create links all along the different stages of the disease.

Forecasting the effects of global warming on biodiversity

The demand for accurate forecasting of the effects of global warming on biodiversity is growing, but current methods for forecasting have limitations. in this article, we compare and discuss the different uses of four forecasting methods: (1) models that consider species individually, (2) niche-theory models that group species by habitat (more specifically, by environmental conditions under which a species can persist or does persist), (3) general circulation models and coupled ocean-atmosphere-biosphere models, and (4) specics-area curve models that consider all species or large aggregates of species. After outlining the different uses and limitations of these methods, we make eight primary suggestions for improving forecasts. We find that greater use of the fossil record and of modern genetic studies would improve forecasting methods. We note a Quaternary conundrum: While current empirical and theoretical ecological results suggest that many species could be at risk from global warming, during the recent ice ages surprisingly few species became extinct. The potential resolution of this conundrum gives insights into the requirements for more accurate and reliable forecasting. Our eight suggestions also point to constructive synergies in the solution to the different problems.

Cancer du sein : la pathologie, pierre angulaire de la décision therapeutique [Breast cancer: pathology, the cornerstone of therapeutic decision]

Tailoring adjuvant therapy in breast cancer patients relies on prognostic and predictive factors, most of which are currently established by histopathological analysis of tumors. The quality of the assessment of the former (i.e.: tumor size, lymph node status, tumor grade, HER2 status, and lymphovascular invasion) and the latter (estrogen and progesteron receptors expression, HER2 overexpression or amplification) is an essential prerequisite for an optimal therapeutic decision. If the prognostic and predictive values of multigenes signatures are confirmed by on-going clinical studies, this approach could enter the clinical practice in the coming years and result in improved accuracy of adjuvant therapies in breast cancer patients. This approach might especially allow avoiding overtreatment in patients at low risk of recurrence.

La fonction de Moi auxiliaire dans la prise en charge des douloureux chroniques [The role of the auxiliary ego in the care of the chronic pain patient]

La prise en charge des patients souffrant de douleurs chroniques, à l'interface entre corps et psyché, nécessite une approche globale et souvent un réseau de soins coordonnés, contenant et stable. La psychiatrie de liaison a naturellement trouvé sa place dans ce réseau de soins spécifiques auprès des différents soignants impliqués. Les réflexions issues de cette expérience ont pour objectif de mieux comprendre le rôle thérapeutique des soignants et font émerger la notion de Moi auxiliaire comme élément clé dans le traitement de ces patients. Dans cet article, nous reprendrons les fondements historiques et conceptuels de la fonction de Moi auxiliaire pour nous intéresser à ses différentes applications dans ces prises en charge : consultation médicale, psychothérapie individuelle ou de groupe, colloque interdisciplinaire. The management of the patient suffering from chronic pain, situated on the interface between body and psyche, necessitates a global approach and often a coordinated, stable and containing network of care. Liaison psychiatry has become part of this network, together with various health care professionals from somatic disciplines. Based on these experiences, this article aims to better understand the therapeutic role of those who take care of the chronic pain patient by identifying the auxiliary ego as a key element of care. The historical development and conceptual framework of the auxiliary ego are utilized to highlight its roles in the different aspects of care of these patients:in the medical consultation, individual psychotherapy, group psychotherapy and in the interdisciplinary meetings.

The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network.

PURPOSE: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). METHODS AND MATERIALS: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. RESULTS: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). CONCLUSIONS: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.

Viability of brown trout embryos positively linked to melanin-based but negatively to carotenoid-based colours of their fathers.

'Good-genes' models of sexual selection predict significant additive genetic variation for fitness-correlated traits within populations to be revealed by phenotypic traits. To test this prediction, we sampled brown trout (Salmo trutta) from their natural spawning place, analysed their carotenoid-based red and melanin-based dark skin colours and tested whether these colours can be used to predict offspring viability. We produced half-sib families by in vitro fertilization, reared the resulting embryos under standardized conditions, released the hatchlings into a streamlet and identified the surviving juveniles 20 months later with microsatellite markers. Embryo viability was revealed by the sires' dark pigmentation: darker males sired more viable offspring. However, the sires' red coloration correlated negatively with embryo survival. Our study demonstrates that genetic variation for fitness-correlated traits is revealed by male colour traits in our study population, but contrary to predictions from other studies, intense red colours do not signal good genes.

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

Implementation of guidelines on delirium in a General Hospital: a before-after study of their impact on caregivers' knowledge and clinical skills

INTRODUCTION: Delirium is a highly prevalent disorder, with serious consequences for the hospitalised patient. Nevertheless, it remains under-diagnosed and under-treated. We developed evidence-based clinical practice guidelines (CPGs) focusing on prevention, screening, diagnosis, and treatment of delirium in a general hospital. This article presents the implementation process of these CPGs and a before-after study assessing their impact on healthcare professionals' knowledge and on clinical practice. METHODS: CPGs on delirium were first implemented in two wards (Neurology and Neurosurgery) of the Lausanne university hospital. Interactive one-hour educational sessions for small groups of nurses and physicians were organised. Participants received a summary of the guidelines and completed a multiple choice questionnaire, assessing putative changes in knowledge, before and three months after the educational session. Other indicators such as "diagnosis of delirium" reported in the discharge letters, and mean duration of patients' hospital stay before and after implementation were compared. RESULTS: Eighty percent of the nurses and physicians from the Neurology and Neurosurgery wards attended the educational sessions. Both nurses and physicians significantly improved their knowledge after the implementation (+9 percentage-points). Other indicators were not modified by the intervention. CONCLUSION: A single interactive intervention improved both nurses' and physicians' knowledge on delirium. Sustained and repeated interventions are probably needed to demonstrate changes in clinical practice.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Novel micropatterns mechanically control fibrotic reactions at the surface of silicone implants.

Over the past decade, various implantable devices have been developed to treat diseases that were previously difficult to manage such diabetes, chronic pain, and neurodegenerative disorders. However, translation of these novel technologies into clinical practice is often difficult because fibrotic encapsulation and/or rejection impairs device function after body implantation. Ideally, cells of the host tissue should perceive the surface of the implant being similar to the normal extracellular matrix. Here, we developed an innovative approach to provide implant surfaces with adhesive protein micropatterns. The patterns were designed to promote adhesion of fibroblasts and macrophages by simultaneously suppressing fibrogenic activation of both cell types. In a rat model, subcutaneously implanted silicone pads provided with the novel micropatterns caused 6-fold lower formation of inflammatory giant cells compared with clinical grade, uncoated, or collagen-coated silicone implants. We further show that micropatterning of implants resulted in 2-3-fold reduced numbers of pro-fibrotic myofibroblast by inhibiting their mechanical activation. Our novel approach allows controlled cell attachment to implant surfaces, representing a critical advance for enhanced biointegration of implantable medical devices.

Complications liées aux piercings [Complications of body piercing].

Au sein de la population générale, de plus en plus de personnes arborent des piercings, en particulier parmi les jeunes adultes. Hormis les réactions inflammatoires et les infections locales, les complications liées à ces piercings sont méconnues. Les personnes ne sont en général pas informées des risques avant de réaliser un piercing et leurs antécédents, traitements médicamenteux ou comorbidités éventuelles, sont largement négligés par les personnes qui réalisent le geste. Les complications sont le plus souvent locales et bénignes, mais des complications sérieuses et parfois mortelles ont été décrites dans la littérature. Cet article propose une revue des problématiques possibles auxquelles pourrait être confronté un médecin de premier recours, face à un patient qui souhaiterait réaliser un piercing ou présenterait des complications suite à la mise en place d'un tel dispositif. The trend of body piercing has grown in popularity in the past decade within the general population and especially among young adults. Complications of body piercing include local inflammation and infections, but severe complications are also possible and largely underestimated. People are usually not aware of the risks before making a piercing, and their medical history, medication and comorbidities are largely neglected by the people who realise the piercing. This article presents a review of the complications that a primary care physician may observe, for a patient who wishes to make a piercing, or presents complications due to the implementation of such a device.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.

Interleukin 17-producing helper T cells (TH17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human TH17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of TH17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.