Spiritualité et cancérologie : enjeux éthiques et épistémologiques d'une intégration

"Thèse en cotutelle, Doctorat en sciences des religions, Université Laval Québec, Canada et Université Paris Descartes Paris, France"Une question nouvelle anime aujourd’hui la littérature médicale : faut-il prendre soin de la dimension spirituelle des patients atteints de maladies graves ? Alors que de nombreux chercheurs font consensus en faveur de l’intégration de la spiritualité dans le soin et que des modèles d’intervention spécifiques sont développés dans différents hôpitaux, d’importantes réserves éthiques et épistémologiques doivent être formulées. Cette thèse de doctorat en éthique médicale et en sciences des religions procède de manière critique à l’analyse de ce phénomène tel qu’il prend forme plus particulièrement en cancérologie depuis une vingtaine d’années. Nous avons mis en évidence que l’avis des patients n’était jamais pris en compte pour justifier la nécessité de prendre soin de la spiritualité ; or, nous pensons que leur implication est indispensable pour délimiter les missions du soin. Cela nous a amené à la question de recherche suivante : pour quelles raisons les patients atteints de cancer au pronostic péjoratif souhaiteraient-ils que l’hôpital public français s’ouvre à la question spirituelle ? Pour y répondre, nous avons interrogé vingt patients aux prises avec un cancer au pronostic péjoratif, suivis dans des hôpitaux publics français, par le biais d’entretiens semi-directifs. Les résultats montrent qu’ils n’attendent pas de l’hôpital un soin en matière de spiritualité. Par contre, ils expriment le besoin d’être reconnus comme des êtres à part entière et non, uniquement, comme des patients. Ces données nous invitent ainsi à penser l’intégration de la spiritualité dans l’hôpital davantage sur le registre de la reconnaissance que sur celui du soin. Mots-Clés : Spiritualité, Cancer, Ethique médicale, Religion, Soins.A new question has arisen in the medical literature recently: must spirituality be included as a specific dimension in the care system? If several scholars arrive at a consensus in favour of this integration, considerable ethical and epistemological worries have to be expressed. This thesis in medical ethics and religious studies critically analyses this phenomenon, more specifically in the context of oncology. Our main concern is to discuss the different arguments given in medical literature justifying the necessity to develop spiritual care. In doing so, we discovered that the patients’ point of view is never taken into account, posing the question: for which reasons patients with advanced cancer would (or would not) expect spiritual care from the hospital? In response, we interviewed 20 patients undergoing treatment in a French hospital, using a semi directive methodology. Results show that patients do not expect spiritual care from the hospital but wish to be recognised as human beings and not only as “patients”. Data invites us to consider the integration of spirituality in the hospital through an ethic of recognition as opposed to an ethic of care. Title : Spirituality and Cancer : Ethical and Epistemological Issues of an Integration. Key Words : Spirituality, Cancer, Medical Ethics, Religion, Care

Meisosomes, folded membrane microdomains between the apical extracellular matrix and epidermis

Apical extracellular matrices (aECMs) form a physical barrier to the environment. In Caenorhabditis elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term 'meisosomes,' in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they could conceivably act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage

Serum Proteomic Profiling of Lung Cancer in High-Risk Groups and Determination of Clinical Outcomes

HypothesisLung cancer remains the leading cause of cancer-related mortality worldwide. Currently known serum markers do not efficiently diagnose lung cancer at early stage.MethodsIn the present study, we developed a serum proteomic fingerprinting approach coupled with a three-step classification method to address two important clinical questions: (i) to determine whether or not proteomic profiling differs between lung cancer and benign lung diseases in a population of smokers and (ii) to assess the prognostic impact of this profiling in lung cancer. Proteomic spectra were obtained from 170 pathologically confirmed lung cancer or smoking patients with benign chronic lung disease serum samples.ResultsAmong the 228 protein peaks differentially expressed in the whole population, 88 differed significantly between lung cancer patients and benign lung disease, with area under the curve diagnostic values ranging from 0.63 to 0.84. Multiprotein classifiers based on differentially expressed peaks allowed the classification of lung cancer and benign disease with an area under the curve ranging from 0.991 to 0.994. Using a cross-validation methodology, diagnostic accuracy was 93.1% (sensitivity 94.3%, specificity 85.9%), and more than 90% of the stage I/II lung cancers were correctly classified. Finally, in the prognosis part of the study, a 4628 Da protein was found to be significantly and independently associated with prognosis in advanced stage non-small cell lung cancer patients (p = 0.0005).ConclusionsThe potential markers that we identified through proteomic fingerprinting could accurately classify lung cancers in a high-risk population and predict survival in a non-small cell lung cancer population

Design of a 100 kW Concentrated Solar Power on Demand Volumetric Receiver With Integral Thermal Energy Storage Prototype

A new concept of Thermal Energy Storage (TES) system based on current available technologies is being developed under the framework of the Masdar Institute (MI) and Massachusetts Institute of Technology (MIT) collaborative Flagship Program. The key feature of this concept lies on concentrating sun light directly on the molten salt storage tank, avoiding the necessity of pumping the salts to the top of a tower thereby avoiding thermal losses and pumping and electric tracing needs inherent in most conventional CSP plants. This Concentrated Solar Power on Demand (CSPonD) volumetric receiver/TES unit prototype will be tested in the existing MI heliostat field and beam down tower in Abu Dhabi (UAE) which will collect and redirect solar energy to an upwards-facing final optical element (FOE). These energy will be concentrated on the aperture of the prototype designed to store 400 kWh of energy allowing 16 hours of continuous production after sunset using Solar Salt (60%NaNO3 + 40%KNO3) as storage material. The tank is divided in two volumes: one cold in the bottom region, where Solar Salt is at 250 °C and another hot on the upper region, at 550 °C. A moving divider plate with active control separates both volumes. The plate includes mixing enhancement features to help with convection on the hot volume of salts. It’s expected that results will demonstrate the technical feasibility and economic viability of this concept allowing its scale up at commercial size

Dermatological side effects of hepatitis C and its treatment: Patient management in the era of direct-acting antivirals

SummaryDermatological adverse events (AEs) are an existing concern during hepatitis C virus (HCV) infection and peginterferon/ribavirin treatment. HCV infection leads to dermatological and muco-cutaneous manifestations including small-vessel vasculitis as part of the mixed cryoglobulinemic syndrome. Peginterferon/ribavirin treatment is associated with well-characterized dermatological AEs tending towards a uniform entity of dermatitis. New direct-acting antivirals have led to significant improvements in sustained virologic response rates, but several have led to an increase in dermatological AEs versus peginterferon/ribavirin alone. In telaprevir trials, approximately half of treated patients had rash. More than 90% of these events were Grade 1 or 2 (mild/moderate) and in the majority (92%) of cases, progression to a more severe grade did not occur. In a small number of cases (6%), rash led to telaprevir discontinuation, whereupon symptoms commonly resolved. Dermatological AEs with telaprevir-based triple therapy were generally similar to those observed with peginterferon/ribavirin (xerosis, pruritus, and eczema). A few cases were classified as severe cutaneous adverse reaction (SCAR), also referred to as serious skin reactions, a group of rare conditions that are potentially life-threatening. It is therefore important to distinguish between telaprevir-related dermatitis and SCAR. The telaprevir prescribing information does not require telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be treated using emollients/moisturizers and topical corticosteroids. For Grade 3 rash, the prescribing information mandates immediate telaprevir discontinuation, with ribavirin interruption (with or without peginterferon) within 7days of stopping telaprevir if there is no improvement, or sooner if it worsens. In case of suspicion or confirmed diagnosis of SCAR, all study medication must be discontinued

Modeling [F-18]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection

peer reviewedThe selectivity of [F-18]MPPF (fluorine-18-labeled 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [F-18]MPPF, dynamic positron emission tomography (PET) data Were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: F-v (vascular fraction). K-1, k(2) (plasma/free compartment exchange rate). k(off). k(on)/V-r (association and dissociation rate), B-max (receptor concentration), and to deduce K-d (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential Were compared With indices generated by Logan-Patlak graphical analysis. The 5HT(1A) specificity for MPPF was evidenced. A B-max of 2.9 pmol/mL and a K-d of 2.8 nmol/L were found in hippocampal regions, K-d and distribution volume in the free compartment were regionally stable. and the Logan binding potential was linearly correlated to B-max. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols

Safety and Immunogenicity of the PRAME Cancer Immunotherapeutic in Patients with Resected Non–Small Cell Lung Cancer: A Phase I Dose Escalation Study

International audience; INTRODUCTION:Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964).METHODS:Patients with PRAME-positive resected stage IB to IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose of 20 μg, 100 μg, or 500 μg, with a fixed dose of AS15). Adverse events, predefined dose-limiting toxicity, and the anti-PRAME humoral response (measured by enzyme-linked immunosorbent assay) were coprimary end points. Anti-PRAME cellular responses were assessed.RESULTS:A total of 60 patients were treated (18 received 20 μg of PRAME, 18 received 100 μg of PRAME, and 24 received 500 μg of PRAME). No dose-limiting toxicity was reported. Adverse events considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. The percentages of patients with PRAME-specific CD4-positive T cells were higher at the dose of 500 μg compared with lower doses. No predefined CD8-positive T-cell responses were detected.CONCLUSION:The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 μg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC