Evaluation globale standardisée systématique des rhumatismes inflammatoires chroniques: intérêts et limites

Introduction: National and international recommendations call for an annual standardized systematic holistic review in the management of chronic inflammatory rheumatism (CIR). This includes an assessment of disease activity and severity, as well as patient education on the disease, knowledge of pharmacological and non-pharmacological treatments, adherence to treatment and screening for comorbidities. Our study aims to recall the definition of a holistic review (HR), to present the evidence of their effectiveness and to give an overview of HR practices in France. Methods: A literature review was conducted in the Pubmed database to identify randomized controlled trials (RCTs) or meta-analyses reporting the efficacy of a multidisciplinary intervention in ICR or other chronic diseases. Two online surveys were sent to all rheumatology departments in France and to a sample of independent rheumatologists, with 34 and 19 questions respectively. These questionnaires were used to determine the profile of the responding center/rheumatologist, the existence of an HR and the obstacles or facilitators to its implementation. Results: Literature search yielded 872 articles, 24 of which were finally included: 16 RCTs and 8 meta-analyses. Only 3 articles concerned ICRs, including one meta-analysis of 10 RCTs in rheumatoid arthritis (RA). Of these 3 studies, 2 RCTs in systemic lupus and systemic sclerosis showed a favorable impact of a multidisciplinary approach on SLEDAI and grip strength and mouth opening respectively, while the meta-analysis in RA showed no benefit on disability or disease activity.The questionnaire was answered by 72 centers and 186 rheumatologists. A third of the centers had already implemented a HR during an day hospitalization. 70 % of centers estimated that they managed more than 10 patients per month, devoting an average of 35 minutes of rheumatologist time and 90 minutes of cumulative time for all other healthcare professionals (HCPs) involved in the program. Most of the HCPs involved were nurses (92 %), dieticians (56 %) and physiotherapists (56 %). The main obstacles to setting up a HR were the lack of paramedical resources, lack of economic value and lack of support from treating rheumatologists, while patient motivation was seen as a facilitating factor. Conclusion: Although HR is recommended, there is little evidence of its effectiveness in ICR. Only 36 % of responding centers have implemented such a program. This survey helps to identify the obstacles and facilitators, and to find solutions for extending this practice

Inaugural cervical vertebral sarcoidosis.

International audienc

Acute gouty arthritis after intraarticular hyaluronate injection.

International audienc

Characterization and validation of Cre-driver mouse lines

Conditional gene manipulations in mice are increasingly popular strategies in biomedical research. These approaches rely on the production of conditional genetically engineered mutant mouse (GEMM) lines with mutations in protein-encoding genes. These conditional GEMMs are then bred with one or several transgenic mouse lines expressing a site-specific recombinase, most often the Cre recombinase, in a tissue-specific manner. Conditional GEMMs can only be exploited if Cre transgenic mouse lines are available to generate somatic mutations, and thus the number of Cre transgenic lines has significantly increased over the last 15 years. Once produced, these transgenic lines must be validated for reliable, efficient, and specific Cre expression and Cre-mediated recombination. In this overview, the minimum level of information that is ideally required to validate a Cre-driver transgenic line is first discussed. The vagaries associated with validation procedures are considered next, and some solutions are proposed to assess the expression and activity of constitutive or inducible Cre recombinase before undertaking extensive breeding experiments and exhaustive phenotyping

Role of p21Cip1/Waf1 in cell-cycle exit of endomitotic megakaryocytes

International audienceAbstract The cyclin-dependent kinase inhibitor p21Waf-1/Cip-1 is expressed at high level during megakaryocyte differentiation, but its precise function remains unknown. In this study, it is confirmed that p21 was expressed at a high level in hypoploid (2N and 4N) and polyploid (at least 8N) human megakaryocytes derived from CD34+ cells. A high expression of p27Kip1, p16, cyclin E, and cyclin D3 was also found in both populations associated with a hypophosphorylated form of retinoblastoma protein, suggesting that the majority of hypoploid and polyploid megakaryocytes are G1-arrested cells. As human megakaryocytes grown in vitro present a defect in their polyploidization, the study switched to the murine model. The modal ploidy of megakaryocytes derived from lineage-negative cells was 32N, and an elevated expression of p21 was found in high-ploidy megakaryocytes. In addition, p21 and p27 were coexpressed in the majority of mature polyploid megakaryocytes. The p21 was detected by immunofluorescence in megakaryocytes derived from p53−/− mice, demonstrating a p53-independent regulation during megakaryocyte differentiation. Megakaryocytopoiesis of p21−/− mice was subsequently studied. No marked abnormality in the ploidy of primary or cultured megakaryocytes was detected. Overexpression of p21 in p21−/− or normal murine megakaryocytes and in human megakaryocytes showed in all these cases a marked inhibition in megakaryocyte polyploidization. In conclusion, while a reciprocal relation is observed between p21 levels in megakaryocytes and the cycling state of the cells, p21 is not essential for the determination of the ploidy profile in normal megakaryocytes in vivo. However, high levels of its expression in cultured megakaryocytes arrest the endomitotic cell cycle