Palliative Care Interventions and End-of-Life Care for Patients with Metastatic Breast Cancer: A Multicentre Analysis.

BACKGROUND: The aim of this study was to describe the implementation of integrated palliative care (PC) and the intensity of care in the last 3 months before death for patients with metastatic breast cancer. MATERIALS AND METHODS: We conducted a multicentric study of all adult patients with metastatic breast cancer who died over a 4-month period. Complete data were collected and checked from clinical records, including PC interventions and criteria regarding EOL care aggressiveness. RESULTS: A total of 340 decedent patients from 12 comprehensive cancer centres in France were included in the study. Sixty-five percent met the PC team with a median time of 39 days between the first intervention and death. In the last month before death, 11.5% received chemotherapy, the frequency of admission to intensive care unit was 2.4%, and 83% experienced acute hospitalization. The place of death was home for 16.7%, hospitalization for 63.3%, PC unit for 20%. Univariate and multivariate analyses showed factors independently associated with a higher frequency of chemotherapy in the last month before death: having a dependent person at home, meeting for the first time with a PC team < 30 days before death, and time between the first metastasis and death below the median. CONCLUSION: PC team integration was frequent and late for patients with metastatic breast cancer. However, PC intervention > 30 days is associated with less chemotherapy in the last month before death. Further studies are needed to better understand how to implement a more effective mode of PC integration for patients with metastatic breast cancer.

Eicosapentaenoic Acid Influences the Lipid Profile of an In Vitro Psoriatic Skin Model Produced with T Cells.

Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid mediators is reported in the disease with a predominance of the inflammatory cascade derived from n-6 polyunsaturated fatty acids (n-6 PUFAs). Bioactive lipid mediators derived from arachidonic acid (AA) are involved in the inflammatory functions of T cells in psoriasis, whereas n-3 PUFAs' derivatives are anti-inflammatory metabolites. Here, we sought to evaluate the influence of a supplementation of the culture media with eicosapentaenoic acid (EPA) on the lipid profile of a psoriatic skin model produced with polarized T cells. Healthy and psoriatic skin substitutes were produced following the auto-assembly technique. Psoriatic skin substitutes produced with or without T cells presented increased epidermal and dermal linolenic acid (LA) and AA levels. N-6 PUFA lipid mediators were strongly measured in psoriatic substitutes, namely, 13-hydroxyoctadecadienoic acid (13-HODE), prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE). The added EPA elevated the amounts of EPA, n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in the epidermal and dermal phospholipids. The EPA supplementation balanced the production of epidermal lipid mediators, with an increase in prostaglandin E3 (PGE3), 12-hydroxyeicosapentaenoic acid (12-HEPE) and N-eicosapentaenoyl-ethanolamine (EPEA) levels. These findings show that EPA modulates the lipid composition of psoriatic skin substitutes by encouraging the return to a cutaneous homeostatic state.

Eicosapentaenoic acid reduces the proportion of IL-17A-producing T cells in a 3D psoriatic skin model.

Psoriasis is a skin disease presenting as erythematous lesions with accentuated proliferation of epidermal keratinocytes, infiltration of leukocytes, and dysregulated lipid metabolism. T cells play essential roles in the disease. n-3 polyunsaturated fatty acids are anti-inflammatory metabolites, which exert an immunosuppressive effect on healthy T cells. However, the precise mechanistic processes of n-3 polyunsaturated fatty acids on T cells in psoriasis are still unrevealed. In this study, we aimed to evaluate the action of eicosapentaenoic acid (EPA) on T cells in a psoriatic skin model produced with T cells. A coculture of psoriatic keratinocytes and polarized T cells was prepared using culture media, which was either supplemented with 10 µM EPA or left unsupplemented. Healthy and psoriatic skin substitutes were produced according to the self-assembly method. In the coculture model, EPA reduced the proportion of IL-17A-positive cells, while increasing that of FOXP3-positive cells, suggesting an increase in the polarization of regulatory T cells. In the 3D psoriatic skin model, EPA normalized the proliferation of psoriatic keratinocytes and diminished the levels of IL-17A. The expression of the proteins of the signal transducer and activator of transcription was influenced following EPA supplementation with downregulation of the phosphorylation levels of signal transducer and activator of transcription 3 in the dermis. Finally, the NFκB signaling pathway was modified in the EPA-supplemented substitutes with an increase in Fas amounts. Ultimately, our results suggest that in this psoriatic model, EPA exerts its anti-inflammatory action by decreasing the proportion of IL-17A-producing T cells.

N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model.

Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the N-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptors and are referred to as part of the endocannabinoidome. Their implication in psoriasis remains unknown. The aim of the present study was to characterize the endocannabinoid system and evaluate the effects of n-3-derived NAEs, namely N-eicosapentaenoyl-ethanolamine (EPEA), in psoriatic keratinocytes using a psoriatic skin model produced by tissue engineering, following the self-assembly method. Psoriatic skin substitutes had lower FAAH2 expression and higher MAGL, ABHD6 and ABHD12 expression compared with healthy skin substitutes. Treatments with alpha-linolenic acid (ALA) increased the levels of EPEA and 1/2-docosapentaenoyl-glycerol, showing that levels of n-3 polyunsaturated fatty acids modulate related NAE and MAG levels. Treatments of the psoriatic substitutes with 10 µM of EPEA for 7 days resulted in decreased epidermal thickness and number of Ki67 positive keratinocytes, both indicating decreased proliferation of psoriatic keratinocytes. EPEA effects on keratinocyte proliferation were inhibited by the CB1 receptor antagonist rimonabant. Exogenous EPEA also diminished some inflammatory features of psoriasis. In summary, n-3-derived NAEs can reduce the psoriatic phenotype of a reconstructed psoriatic skin model.

Current knowledge of the implication of lipid mediators in psoriasis.

The skin is an organ involved in several biological processes essential to the proper functioning of the organism. One of these essential biological functions of the skin is its barrier function, mediated notably by the lipids of the stratum corneum, and which prevents both penetration from external aggression, and transepidermal water loss. Bioactive lipid mediators derived from polyunsaturated fatty acids (PUFAs) constitute a complex bioactive lipid network greatly involved in skin homeostasis. Bioactive lipid mediators derived from n-3 and n-6 PUFAs have well-documented anti- and pro-inflammatory properties and are recognized as playing numerous and complex roles in the behavior of diverse skin diseases, including psoriasis. Psoriasis is an inflammatory autoimmune disease with many comorbidities and is associated with enhanced levels of pro-inflammatory lipid mediators. Studies have shown that a high intake of n-3 PUFAs can influence the development and progression of psoriasis, mainly by reducing the severity and frequency of psoriatic plaques. Herein, we provide an overview of the differential effects of n-3 and n-6 PUFA lipid mediators, including prostanoids, hydroxy-fatty acids, leukotrienes, specialized pro-resolving mediators, N-acylethanolamines, monoacylglycerols and endocannabinoids. This review summarizes current findings on lipid mediators playing a role in the skin and their potential as therapeutic targets for psoriatic patients.

Alpha-Linolenic Acid Modulates T Cell Incorporation in a 3D Tissue-Engineered Psoriatic Skin Model.

Psoriasis is an autoimmune skin disease with an increased number of leukocytes infiltrating the dermal and epidermal compartments compared with normal skin. N-3 polyunsaturated fatty acids (n-3 PUFAs) are frequently used in the clinic in order to attenuate the symptoms of psoriasis. For psoriatic patients, a supplementation of the diet with alpha-linolenic acid (ALA) reduces the activation of T cell signaling pathways, leading to a significant reduction in inflammatory cytokine secretion. However, the precise mechanism of action of n-3 PUFAs in psoriasis is still not understood. In the present study, we elucidated the bioaction of ALA on the adaptive immune component of psoriasis by using a psoriatic skin model produced with the addition of activated T cells. Healthy and psoriatic skin substitutes were produced according to the self-assembly method, using culture media supplemented with 10 µM of ALA. T cells were isolated from blood samples using a negative selection isolation method. ALA supplementation regulated the hyperproliferation and abnormal cell differentiation of psoriatic keratinocytes stimulated by T cells. Additionally, the exogenous ALA was correctly incorporated into the phospholipids of keratinocytes, which resulted in increased levels of ALA, eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA). The infiltration of T cells into the epidermis was reduced when ALA was added to the culture medium, and significant decreases in the levels of inflammatory cytokines and chemokines such as CXCL1, interleukin-6 (IL-6) and interleukin-8 (IL-8) were consequently measured in psoriatic substitutes supplemented with this n-3 PUFA. Altogether, our results showed that in this psoriatic skin model enriched with T cells, ALA exerted its beneficial effect by decreasing the quantities of inflammatory mediators released by T cells.

α-Linolenic acid and linoleic acid modulate the lipidome and the skin barrier of a tissue-engineered skin model.

Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived lipid mediators remains unclear. Skin substitutes were engineered according to the self-assembly method with a culture medium supplemented with 10 µM of both α-linolenic acid (ALA) and linoleic acid (LA). The supplementation with ALA and LA decreased testosterone absorption through a tissue-engineered reconstructed skin model, thus indicating an improved skin barrier function following supplementation. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes. Indeed, the dual supplementation increased the levels of eicosapentaenoic acid (EPA) (15-fold), docosapentaenoic acid (DPA) (3-fold), and LA (1.5-fold) in the epidermal phospholipids while it increased the levels of ALA (>20-fold), DPA (3-fold) and LA (1.5-fold) in the epidermal triglycerides. The bioactive lipid mediator profile of the skin substitutes, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols, was next analyzed using liquid chromatography-tandem mass spectrometry. The lipid supplementation further modulated bioactive lipid mediator levels of the reconstructed skin substitutes, leading to a lipid mediator profile more representative of the one found in normal human skin. These findings show that an optimized supply of PUFAs via culture media is essential for the establishment of improved barrier function in vitro. STATEMENT OF SIGNIFICANCE: Supplementation of the culture medium with 10 µM of both α-linolenic acid (ALA) and linoleic acid (LA) improved the skin barrier function of a tissue-engineered skin model. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes and further modulated bioactive lipid mediator levels, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols. These findings highlight the important role of ALA and LA in skin homeostasis and show that an optimized supply of polyunsaturated fatty acids via culture media is essential for the establishment of improved barrier function in vitro.

Agricultural intensification alters marbled newt genetic diversity and gene flow through density and dispersal reduction.

Recent agricultural intensification threatens global biodiversity with amphibians being one of the most impacted groups. Because of their biphasic life cycle, amphibians are particularly vulnerable to habitat loss and fragmentation that often result in small, isolated populations and loss of genetic diversity. Here, we studied how landscape heterogeneity affects genetic diversity, gene flow and demographic parameters in the marbled newt, Triturus marmoratus, over a hedgerow network landscape in Western France. While the northern part of the study area consists of preserved hedged farmland, the southern part was more profoundly converted for intensive arable crops production after WWII. Based on 67 sampled ponds and 10 microsatellite loci, we characterized regional population genetic structure and evaluated the correlation between landscape variables and (i) local genetic diversity using mixed models and (ii) genetic distance using multiple regression methods and commonality analysis. We identified a single genetic population characterized by a spatially heterogeneous isolation-by-distance pattern. Pond density in the surrounding landscape positively affected local genetic diversity while arable crop land cover negatively affected gene flow and connectivity. We used demographic inferences to quantitatively assess differences in effective population density and dispersal between the contrasted landscapes characterizing the northern and southern parts of the study area. Altogether, results suggest recent land conversion affected T. marmoratus through reduction in both effective population density and dispersal due to habitat loss and reduced connectivity.

Docosahexaenoic Acid Modulates Paracellular Absorption of Testosterone and Claudin-1 Expression in a Tissue-Engineered Skin Model.

Healthy skin moLEdels produced by tissue-engineering often present a suboptimal skin barrier function as compared with normal human skin. Moreover, skin substitutes reconstructed according to the self-assembly method were found to be deficient in polyunsaturated fatty acids (PUFAs). Therefore, in this study, we investigated the effects of a supplementation of the culture media with docosahexaenoic acid (DHA) on the barrier function of skin substitutes. To this end, 10 µM DHA-supplemented skin substitutes were produced (n = 3), analyzed, and compared with controls (substitutes without supplementation). A Franz cell diffusion system, followed by ultra-performance liquid chromatography, was used to perform a skin permeability to testosterone assay. We then used gas chromatography to quantify the PUFAs found in the epidermal phospholipid fraction of the skin substitutes, which showed successful DHA incorporation. The permeability to testosterone was decreased following DHA supplementation and the lipid profile was improved. Differences in the expression of the tight junction (TJ) proteins claudin-1, claudin-4, occludin, and TJ protein-1 were observed, principally a significant increase in claudin-1 expression, which was furthermore confirmed by Western blot analyses. In conclusion, these results confirm that the DHA supplementation of cell culture media modulates different aspects of skin barrier function in vitro and reflects the importance of n-3 PUFAs regarding the lipid metabolism in keratinocytes.

Development of a 3D psoriatic skin model optimized for infiltration of IL-17A producing T cells: Focus on the crosstalk between T cells and psoriatic keratinocytes.

Psoriasis is a chronic inflammatory skin disease involving several cell types, including T cells, via the IL-23/IL-17 axis. IL-17A acts on the surrounding epithelial cells thus resulting in an inflammatory feedback loop. The development of immunocompetent models that correctly recapitulate the complex phenotype of psoriasis remains challenging, which also includes both the T cell isolation and activation methods. The purpose of this work was to develop an advanced in vitro 3D psoriatic skin model that enables the study of the impact of T cells on psoriatic epithelial cells. To reach that aim, healthy and psoriatic fibroblasts and keratinocytes were used to reproduce this tissue-engineered skin model in which activated T cells, isolated beforehand from human whole blood, have been incorporated. Our study showed that isolation of T cells with the EasySep procedure, followed by activation with PMA/ionomycin, mimicked the psoriatic characteristics in an optimal manner with the production of inflammatory cytokines important in the pathogenesis of psoriasis, as well as increased expression of Ki67, S100A7, elafin and involucrin. This psoriatic model enriched in activated T cells displayed enhanced production of IL-17A, IFN-Æ´, CCL2, CXCL10, IL-1ra, IL-6 and CXCL8 compared with the healthy model and whose increased secretion was maintained over time. In addition, anti-IL17A treatment restored some psoriatic features, including epidermal thickness and basal keratinocytes proliferation, as well as a downregulation of S100A7, elafin and involucrin expression. Altogether, our study demonstrated that this model reflects a proper psoriatic inflammatory environment and is effective for the investigation of epidermal and T cell interaction over time. STATEMENT OF SIGNIFICANCE: The aim of this study was to provide an innovative 3D immunocompetent human psoriatic skin model. To our knowledge, this is the first immunocompetent model that uses skin cells from psoriatic patients to study the impact of IL-17A on pathological cells. Through the use of this model, we demonstrated that the T-cell enriched psoriatic model differs from T-cell enriched healthy model, highlighting efficient crosstalk between pathologic epithelial cells and T cells. This advanced preclinical model further mimics the original psoriatic skin and will prove relevant in predicting clinical outcomes, thereby decreasing inaccurate predictions of compound effects.

Biological action of docosahexaenoic acid in a 3D tissue-engineered psoriatic skin model: Focus on the PPAR signaling pathway.

N-3 polyunsaturated fatty acids (n-3 PUFAs), and in particular docosahexaenoic acid (DHA), have many beneficial metabolic effects, including reducing epidermal thickness in patients with psoriasis. The positive impacts of DHA in psoriasis could be mediated by its interactions with the PPAR signaling pathway, as well as by its secretion of anti-inflammatory bioactive metabolites, but the detailed metabolism is still not understood. In the present study, we evaluated the influence of DHA on the main features of psoriasis and its effects on the PPAR signaling pathway, in a psoriatic in vitro skin model. Healthy and psoriatic skin substitutes were produced according to the tissue-engineered self-assembly method, using culture media supplemented with 10 µM of DHA. The presence of DHA led to a reduction in the abnormal cell differentiation of psoriatic keratinocytes, seen in the increased expression of filaggrin and keratin 10. DHA was incorporated into the membrane phospholipids of the epidermis and transformed principally into eicosapentaenoic acid (EPA). Furthermore, the addition of DHA into the culture medium led to a decrease in the levels of lipid mediators derived from n-6 PUFAs, mainly prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE). Finally, DHA supplementation rebalanced the expression of PPAR receptors and caused a decrease in the secretion of TNF-α. Altogether, our results show that DHA possesses the ability to attenuate the psoriatic characteristics of psoriatic skin substitutes, mostly by restoring epidermal cell differentiation and proliferation, as well as by reducing inflammation.

Iron deficiency in patients with cancer: a prospective cross-sectional study.

BACKGROUND: Despite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration and transferrin coefficient saturation (iron-saturation of transferrin, TSAT) index, as well as ID anaemia in patients with cancer. METHODS: This prospective cross-sectional study was conducted in 15 oncology units in France in 2019. All patients present in the medical unit during the 2-week study period, regardless of the type of tumour (solid or haematological) and treatment, were eligible. Serum ferritin concentration, TSAT index and haemoglobin level were determined. ID and ID-associated anaemia were defined according to European Society of Medical Oncology 2018 Guidelines: ID was defined either as ferritin <100 µg/L (absolute ID) or as ferritin ≥100 µg/L and TSAT <20% (functional ID). RESULTS: A total of 1221 patients with different types of solid malignant tumours were analysed: median age 64 years; 89.4% under treatment for their cancer, mainly by chemotherapy (75.4%). Overall, ID was found in 57.9% (55.1-60.6) of patients. Among them, functional ID accounted for 64% of cases. ID anaemia was reported in 21.8% (19.6-24.2) of all patients with cancer. ID was highly prevalent in untreated (75/130, 57.4%) and non-anaemic (419/775, 54.1%) patients. CONCLUSION: This study highlights the high prevalence of ID in patients with cancer, whether or not associated with anaemia or treatment. These results emphasise the need to a better detection and management of ID in cancer, thereby optimising overall patient care. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03924271.

Investigation of Omega-3 Polyunsaturated Fatty Acid Biological Activity in a Tissue-Engineered Skin Model Involving Psoriatic Cells.

Clinical studies have shown that diets enriched with omega-3 (also know as n-3) polyunsaturated fatty acids could relieve the symptoms of patients with psoriasis. However, the mechanisms involved remain poorly understood. The aim of this study was to investigate the effects of α-linolenic acid (ALA) on the proliferation and differentiation of psoriatic keratinocytes in a three-dimensional skin model. Skin models featuring healthy (healthy substitute) or psoriatic (psoriatic substitute) cells were engineered by the self-assembly method of tissue engineering using a culture medium supplemented with 10 µM ALA in comparison with the regular unsupplemented medium. ALA decreased keratinocyte proliferation and improved psoriatic substitute epidermal differentiation, as measured by decreased Ki67 staining and increased protein expression of FLG and loricrin. The added ALA was notably incorporated into the epidermal phospholipids and metabolized into long-chain n-3 polyunsaturated fatty acids, mainly eicosapentaenoic acid and n-3 docosapentaenoic acid. ALA supplementation led to increased levels of eicosapentaenoic acid derivatives (15-hydroxyeicosapentaenoic acid and 18-hydroxyeicosapentaenoic acid) as well as a decrease in levels of omega-6 (also know as n-6) polyunsaturated fatty acid lipid mediators (9-hydroxyoctadecadienoic acid, 12-hydroxyeicosatetraenoic acid, and leukotriene B4). Furthermore, the signal transduction mediators extracellular signal‒regulated kinases 1 and 2 were the kinases most activated after ALA supplementation. Taken together, these results show that ALA decreases the pathologic phenotype of psoriatic substitutes by normalizing keratinocyte proliferation and differentiation in vitro.

Lignocellulosic fibres surface interactions in enzymatic reaction using data-mining.

Lignocellulosic fibres modification focused so far essentially on the resulting material properties to create functional fibres instead of determining the reaction influencing parameters. Using a data-mining algorithm, surface chemical composition of the fibres after modifications was compared to multiple signals. A 24 h reaction at either 25 °C or 60 °C, pH5 was conducted in presence of trans-ferulic acid, laccase, and lignocellulosic fibres (flax, hemp, or cellulose) having different chemical surface composition. Dimers and trimers were detected in variable concentrations in the reaction filtrate and extractive. At 25 °C, crystalline cellulose, amorphous cellulose, xylans, mannans, and lignins were well correlated to specific reaction products while at 60 °C, only lignins and xylan were found correlated to reaction products. Fibres surface composition affected the extractive profile. Lignocellulosic surface composition influence on the product formed was unveiled using a data mining approach. This study presents a way to unveil non-evident chemical interface interaction in reactions.

A Tissue-Engineered Human Psoriatic Skin Model to Investigate the Implication of cAMP in Psoriasis: Differential Impacts of Cholera Toxin and Isoproterenol on cAMP Levels of the Epidermis.

Pathological and healthy skin models were reconstructed using similar culture conditions according to well-known tissue engineering protocols. For both models, cyclic nucleotide enhancers were used as additives to promote keratinocytes' proliferation. Cholera toxin (CT) and isoproterenol (ISO), a beta-adrenergic agonist, are the most common cAMP stimulators recommended for cell culture. The aim of this study was to evaluate the impact of either CT or ISO on the pathological characteristics of the dermatosis while producing a psoriatic skin model. Healthy and psoriatic skin substitutes were produced according to the self-assembly method of tissue engineering, using culture media supplemented with either CT (10-10 M) or ISO (10-6 M). Psoriatic substitutes produced with CT exhibited a more pronounced psoriatic phenotype than those produced with ISO. Indeed, the psoriatic substitutes produced with CT had the thickest epidermis, as well as contained the most proliferating cells and the most altered expression of involucrin, filaggrin, and keratin 10. Of the four conditions under study, psoriatic substitutes produced with CT had the highest levels of cAMP and enhanced expression of adenylate cyclase 9. Taken together, these results suggest that high levels of cAMP are linked to a stronger psoriatic phenotype.

Effect of a low melting temperature mixture on the surface properties of lignocellulosic flax bast fibers.

Bast flax fibers were treated, with or without ultrasound assistance, using a low melting mixture (LMM) composed of lactic acid, d-glucose and water. This LMM treatment affected both lignin and hemicelluloses contents and modified the fibers properties identified as crucial parameters in an industrial context, i.e. coloration, wettability, crystallinity, fibers diameter and chemical composition. Surface chemistry of the fibers were investigated through fluorescent tagged carbohydrates binding modules revealing macromolecular rearrangements responsible of both a fibers crystallinity enhancement and an unexpected hydrophobicity. It has been found that LMM treatments bleach fibers, which is considered a beneficial effect independent of the treatments.

Infiltration of T Cells into a Three-Dimensional Psoriatic Skin Model Mimics Pathological Key Features.

Psoriasis is an autoimmune chronic dermatosis that is T cell-mediated, characterized by epidermal thickening, aberrant epidermal differentiation and inflammatory infiltrates, with a dominant Th1 and Th17 profile. Additional in vitro models are required to study the complex interactions between activated T cells and skin cells, and to develop new, more effective treatments. We have therefore sought to model this psoriatic inflammation by the generation of tissue-engineered immunocompetent tissues, and we have investigated the response of activated T-cell infiltration in models produced with lesional psoriatic skin cells on major hallmarks of psoriasis. The immunocompetent lesional skin model displayed a delayed onset of epidermal differentiation, an hyperproliferation of the basal keratinocytes, a drastic increase in the secretion of proinflammatory cytokines, and a disturbed expression of key transcription factors, as observed in lesional plaques, suggesting a crucial importance of combining the pathological phenotype of cutaneous cells to T cells in order to generate a relevant model for psoriasis. Finally, we found this skin model to be responsive to methotrexate treatment, making it a valuable tool for drug development.

Supportive Care Organization in France: a national in-depth survey among patients and oncologists.

PURPOSE: Medical doctors' (MDs), but not patients', perception of supportive care in cancer (SCC) in France has been previously assessed in a national survey. This study evaluated MDs and patients' perceptions of the SCC organization and implementation in France. METHODS: The French SCC Association conducted two observational studies: study 1 (S1), containing a 30-point questionnaire sent to 2263 MDs, and study 2 (S2), containing a 40-point questionnaire sent to 2000 patients. RESULTS: Overall, 711 MDs completed S1 and 1562 patients completed S2. In S1, 81% of MDs reported relying on a SCC organization and 76% attended SCC multidisciplinary discussions. MDs considered palliative (98%), psychological (98%), and social care (98%) as the top 3 SCC areas of importance for patients. In contrast, patients' priorities were psychology (61%), nutrition (55%) and organization of intake consultations (55%). The concept of SCC was familiar to 34% of patients; according to MDs, this concept was introduced mainly by MDs (78%) and admission nurses (41%). Outpatients identified as professional resources for SCC information general practitioners (84%), nurses (58%), and pharmacists (52%). Patients reported supportive treatment being prescribed in 63% of cases, with 64% receiving information on the negative side-effects. Among MDs, 87% reported proposing palliative and 41% adjuvant SCC treatment. Furthermore, 72% of MDs recommended SCC treatment at the metastatic stage, and 36% immediately following diagnosis. DISCUSSION: Oncologists play a vital role in enhancing SCC efficacy. This can be increased by implementing a multidisciplinary integrated approach or by assuring the availability of patient information.

[Perceptual gap between oncologists/oncology nurses and patients in the management and impact of chemotherapy/radiotherapy-induced nausea and vomiting: French results of the GAP survey]. / Écarts d'évaluation entre oncologues, infirmiers et patients dans la prise en charge et l'impact des nausées et vomissements chimio/radio-induits : résultats français de l'enquête GAP.

INTRODUCTION: Despite progress in the treatment of chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV), their management remains insufficient. METHODS: In order to evaluate the incidence and impact of CINV/RINV on the quality of life perceived by patients and estimated by clinicians, a declarative, cross-sectional survey was conducted in France through an online questionnaire. RESULTS: This survey included 187 participants: 75 oncologists, 35 oncology nurses and 77 patients. Clinicians over-estimated the incidence of CINV/RINV, but underestimated their impact on the quality of life of patients. The sub-optimal prescription of anti-emetic treatments was more prominent when the therapy administered had low or medium emetogenic potential. Only 30% of patients rated their nausea and vomiting as controlled from the start. A major proportion of patients (68%) declared poor compliance with their anti-emetic regimen. The acceptance of CINV/RINV as normal side effects of the chemotherapy/radiotherapy (51%) led the patients not to report them, thus limiting their active management. The number of drugs to absorb, and the fear that the action of swallowing the pill would induce nausea or vomiting were also quoted by the patients as compliance-limiting factors. CONCLUSION: The perceptual gap between clinicians and patients regarding the incidence and impact of CINV/RINV contributes to a sub-optimal level of anti-emetic cover and control. The anti-emetic regimen needs to be regularly assessed and adapted to the patient in order to improve CINV/RINV management.