Application in general practice of treatment guidelines for patients with dyslipidaemia: The RESPECT study

SummaryBackgroundScreening for and management of dyslipidaemia are crucial in primary and secondary prevention of cardiovascular disease. The impact on general practitioners (GP) of the 2005 French guidelines for hypercholesterolaemia has not been evaluated.AimsTo compare GP's estimation of cardiovascular risk with that from a theoretical calculation; to analyse the consequences of cardiovascular-risk estimation on the threshold of therapeutic intervention and the target low-density lipoprotein cholesterol (LDL-C) concentration; and to analyse patients’ awareness of their hypercholesterolaemia.MethodsThe RESPECT study was a transverse, multicentre, observational survey conducted between March 2006 and February 2007 by 1797 GP in France. Inclusion criteria were adults with primary hypercholesterolaemia who had not taken lipid-lowering drugs within the previous 6 months.ResultsOf the 5627 patients included (60.9% men; mean age±standard deviation 58.2±11.0 years; body mass index 27.2±4.1kg/m2; mean total cholesterol 2.68±0.37g/L; LDL-C 1.79±0.35g/L), 1963 (36.2%) had at least three cardiovascular risk factors. GP identified a high cardiovascular risk level in 40.8%, moderate risk in 45.8% and low risk in 13.4% of patients. These compared with calculated rates of 48, 23 and 29%, respectively (κ concordance 59.4%). For most patients (98.2%), GP defined the therapeutic target based on LDL-C concentration. The target LDL-C was significantly different when cardiovascular risk was estimated by GP versus that calculated theoretically. The higher the estimated risk level, the greater the rate of introduction of lipid-lowering drugs and the shorter the time to the next GP visit. Most patients considered themselves to be well or rather well informed about their cholesterol concentration (91.3%), the causes (64.3%) and consequences of cholesterol-induced diseases (83.7%), and the difference between ‘good’ and ‘bad’ cholesterol (57%). Most (81.5%) patients were aware of the benefits of lipid-lowering drugs on cardiovascular disease prevention; 95.8% considered adequate diet and compliance with pharmacological treatment to be very important.ConclusionRecent French guidelines for hypercholesterolaemia are used widely by GP in practice. They enable correct assessment of overall cardiovascular risk level, have an impact on the therapeutic threshold of intervention by physicians and improve patients’ awareness of the relevance of cholesterol concentration

Biofabrication

Fibroblasts and myofibroblasts play a central role in skin homeostasis through dermal organization and maintenance. Nonetheless, the dynamic interactions between (myo)fibroblasts and the extracellular matrix (ECM) remain poorly exploited in skin repair strategies. Indeed, there is still an unmet need for soft tissue models allowing to study the spatial-temporal remodeling properties of (myo)fibroblasts. In vivo, wound healing studies in animals are limited by species specificity. In vitro, most models rely on collagen gels reorganized by randomly distributed fibroblasts. But biofabrication technologies have significantly evolved over the past ten years. High-resolution bioprinting now allows to investigate various cellular micropatterns and the emergent tissue organizations over time. In order to harness the full dynamic properties of cells and active biomaterials, it is essential to consider ‘time’ as the 4th dimension in soft tissue design. Following this 4D bioprinting approach, we aimed to develop a novel model that could replicate fibroblast dynamic remodeling in vitro. For this purpose, (myo)fibroblasts were patterned on collagen gels with laser-assisted bioprinting (LAB) to study the generated matrix deformations and reorganizations. First, distinct populations, mainly composed of fibroblasts or myofibroblasts, were established in vitro to account for the variety of fibroblastic remodeling properties. Then, LAB was used to organize both populations on collagen gels in even isotropic patterns with high resolution, high density and high viability. With maturation, bioprinted patterns of fibroblasts and myofibroblasts reorganized into dispersed or aggregated cells, respectively. Stress-release contraction assays revealed that these phenotype-specific pattern maturations were associated with distinct lattice tension states. The two populations were then patterned in anisotropic rows in order to direct the cell-generated deformations and to orient global matrix remodeling. Only maturation of anisotropic fibroblast patterns, but not myofibroblasts, resulted in collagen anisotropic reorganizations both at tissue-scale, with lattice contraction, and at microscale, with embedded microbead displacements. Following a 4D bioprinting approach, LAB patterning enabled to elicit and orient the dynamic matrix remodeling mechanisms of distinct fibroblastic populations and organizations on collagen. For future studies, this method provides a new versatile tool to investigate in vitro dermal organizations and properties, processes of remodeling in healing, and new treatment opportunities

In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage

International audienceIntroduction: An autologous split-thickness skin graft (STSG) is a standard treatment for coverage of full-thickness skin defects. However, this technique has two major drawbacks: the use of general anesthesia for skin harvesting and scar sequelae on the donor site. In order to reduce morbidity associated with STSG harvesting, researchers have developed autologous dermo-epidermal substitutes (DESs) using cell culture, tissue engineering, and, more recently, bioprinting approaches. This study assessed the manufacturing reliability and in vivo efficacy of a large-size good manufacturing practice (GMP)-compatible bio-printed human DES, named Poieskin ® , for acute wound healing treatment. Methods: Two batches (40 cm 2 each) of Poieskin ® were produced, and their reliability and homogeneity were assessed using histological scoring. Immunosuppressed mice received either samples of Poieskin ® ( n = 8) or human STSG ( n = 8) immediately after longitudinal acute full-thickness excision of size 1 × 1.5 cm, applied on the skeletal muscle plane. The engraftment rate was assessed through standardized photographs on day 16 of the follow-up. Moreover, wound contraction, superficial vascularization, and local inflammation were evaluated via standardized photographs, laser Doppler imaging, and PET imaging, respectively. Histological analysis was finally performed after euthanasia. Results: Histological scoring reached 75% ± 8% and 73% ± 12%, respectively, displaying a robust and homogeneous construct. Engraftment was comparable for both groups: 91.8% (SD = 0.1152) for the Poieskin ® group versus 100% (SD = 0) for the human STSG group. We did not record differences in either graft perfusion, PET imaging, or histological scoring on day 16. Conclusion: Poieskin ® presents consistent bioengineering manufacturing characteristics to treat full-thickness cutaneous defects as an alternative to STSG in clinical applications. Manufacturing of Poieskin ® is reliable and homogeneous, leading to a clinically satisfying rate of graft take compared to the reference human STSG in a mouse model. These results encourage the use of Poieskin ® in phase I clinical trials as its manufacturing procedure is compatible with pharmaceutical guidelines

La classe est ouverte, qu’est-ce que ça change ?

International audience« La classe est ouverte, qu'est-ce que ça change ? », Cahiers pédagogiques. n° 564, p. 44-46. Ce fichier comporte le manuscrit auteur avant modifications introduites par les éditeurs La « classe ouverte en activité ». Un pas vers la coéducation L'équipe du LéA Delaunay Grigny 91 1 Dans la salle des professeurs du Collège Sonia Delaunay de Grigny, en REP+ 2 , au milieu des années 2010, le constat est partagé : très peu de parents viennent aux réunions de rentrée, aux remises de bulletins, au café des parents... Rentrée 2016, ce problème est à l'ordre du jour d'une réunion de « concertation », ce temps de travail collectif qu'offre désormais la « refondation de l'éducation prioritaire » et qu'accompagnent deux nouvelles formatrices académiques. Des chercheurs participent à la réflexion dans le cadre d'une recherche collaborative, et plus précisément ici recherche-intervention (Mérini & Ponté, 2009), menée avec les professeurs volontaires de l'équipe du Collège. Chacun fait part de ses questions et pistes de travail. Un professeur d'histoire-géographie rapporte ses souvenirs d'une année d'enseignement aux États-Unis, où des parents venaient assister à des cours. Les collègues du premier degré racontent que les écoles primaires sont familières de l'invitation des parents en classe. Le nouveau référentiel de l'éducation prioritaire mentionne, sans plus de détails, la possibilité de « classes ouvertes en activité » : pourquoi ne pas l'expérimenter au collège ? Ouvrir la classe aux parents pour réfléchir à l'autonomie des élèves : croisement des regards et des représentations Comment présenter et mettre en oeuvre l'invitation des parents à assister à une heure de cours ? Face aux nombreuses questions que soulève ce projet, trois années de tâtonnements permettront de concevoir un dispositif ajusté aux préoccupations et conditions de travail spécifiques à notre collège. Cette couleur local

Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC

International audienceIntroduction: Patients with advanced-stage NSCLC whose tumors harbor an ALK gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsy samples contain insufficient tissue for successful ALK molecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALK tissue analysis and as a function of the response to ALKi.Methods: We conducted a multicenter, prospective observational study (NCT02372448) of 203 patients with stage IIIB/IV NSCLC across nine French centers, of whom 81 were ALK positive (immunohistochemistry or fluorescence in situ hybridization [FISH]) and 122 ALK negative on paraffin-embedded tissue specimens. Blood samples were collected at baseline and at 6 and 12 weeks after ALKi initiation or at disease progression. ALK gene rearrangement was evaluated with CTCs using immunocytochemistry and FISH analysis after enrichment using a filtration method.Results: At baseline, there was a high concordance between the detection of an ALK rearrangement in the tumor tissue and in CTCs as determined by immunocytochemistry (sensitivity, 94.4%; specificity 89.4%). The performance was lower for the FISH analysis (sensitivity, 35.6%; specificity, 56.9%). No significant association between the baseline levels or the dynamic change of CTCs and overall survival (hazard ratio = 0.59, 95% confidence interval: 0.24-1.5, p = 0.244) or progression-free survival (hazard ratio = 0.84, 95% confidence interval: 0.44-1.6, p = 0.591) was observed in the patients with ALK-positive NSCLC.Conclusions: CTCs can be used as a complementary tool to a tissue biopsy for the detection of ALK rearrangements. Longitudinal analyses of CTCs revealed promise for real-time patient monitoring and improved delivery of molecularly guided therapy in this population

Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

International audienc