This article focuses on current trends in various autoimmune diseases of interest for the dermatologist. In the antiphospholipid syndrome, many news: better characterization of the severe disease, involvement of the mTOR pathway in the vasculopathy-induced renal disease, and diversification of the therapeutic approaches: use of mTOR inhibitors and several biologics, new various antiplatelet and anticoagulants. In dermatomyositis, new autoantibodies are better characterized with a good correlation with clinical disease; the results of a large study on genetic predisposition to the disease are available. There are also some therapeutic innovations in systemic sclerosis: benefit of rituximab that seems well tolerated, the results of a large controlled European study about aggressive immunoablative chemotherapy followed by autologous stem cells have just been published, intralesional stem cells injections in the fingers of sclerodactylic patients. Finally, news in celiac disease that is constantly increasing and whose mild forms often have cutaneous manifestations, leading to diagnosis.

Intra-uterine adhesions are a major cause of secondary infertility. The prevalence of adhesions is probably underestimated due to the heterogeneity of the symptoms. An exhaustive literature search using search engines MEDLINE, Pubmed, Cochrane library and Web of Science was performed to make a focus on the origins, consequences and methods of prevention of intra-uterine adhesions. Intra-uterine adhesions are likely to occur after any endo-uterine surgery via dysregulated activation of coagulation chain linked to the inflammatory process. Early and late obstetric complications are also recognized as caused by adhesions. The diagnosis is currently performed by hysteroscopy but it remains an invasive procedure even if it can be done with an ambulatory management. Several research approaches inspired by intra-abdominal surgery for the prevention of pelvic adhesions have been developed. However, no current method of prevention has proven its effectiveness in terms of improving spontaneous fertility. The improvement in surgical practices, the design of new intra-uterine medical devices and new research especially in the field of endometrial stem cells can maybe reduce the rate of adhesions end their complications after intra-uterine surgery.

The poor prognosis of inflammatory breast cancer (IBC) is due to its strong metastatic potential. During the last three decades, the introduction of neoadjuvant chemotherapy (CT), and its improvement with successive additions of anthracyclines and then taxanes, allowed to double the survival. However, the 5-year survival still remains lower than 50%, with the pathological complete response (pCR) to neoadjuvant CT being a major prognostic factor. Since 1995, several innovative approaches have been evaluated. Initially, the trials of high-dose CT with hematopoietic stem cell transplantation have generated promising results, but ultimately failed to change standards of treatment, in particular because of its toxicity. More recently, a few targeted therapies, combined to conventional CT, have been assessed, due to the frequent overexpression of HER2 and EGFR and the important vascularization of IBC. Trastuzumab, a monoclonal antibody targeting HER2, has shown a clear advantage in terms of pCR and survival in studies dedicated to, HER2-positive locally advanced breast cancers, including IBC. Lapatinib, a dual tyrosine kinase inhibitor anti-HER2 and EGFR, has shown significant activity in two phase II studies dedicated to HER2-positive IBC. The interest of HER2-double blockade by the combination of trastuzumab-pertuzumab combined to docetaxel has been demonstrated in term of pCR in the NEOSPHERE study which also included HER2-positive IBC. Among the anti-angiogenic drugs tested in studies dedicated to IBC, bevacizumab has given the most interesting results in term of efficacy/toxicity ratio. In the Beverly 2 study HER2-positive IBC patients were treated by the combination chemotherapy, trastuzumab and bevacizumab: the rate of pCR was 64%, and the 3-year disease-free and overall survivals were 68% and 90%, respectively; the increase of endothelial cells circulating was inversely correlated to the probability of pCR. All those treatments have been extrapolated from standard breast cancers. Thus, a deep molecular knowledge of IBC appears to be critical in order to develop specific treatments effectively targeting its particular aggressiveness.

Over the last decade, the clinical use of adipose-derived stromal/stem cells (ASC) in regenerative medicine is rapidly increasing. ASC belong to the mesenchymal stromal cells initially obtained from the bone marrow. Their limited differentiation capacity in vivo into functional mature cells has led to a reassessment of their mechanisms of action. One of the major clinical interests appears related to paracrine effects through a temporary production of trophic and immunomodulatory factors. Our purpose is to provide a review on the latest knowledge in the field of ASC, mechanisms of action, mainly immunomodulatory/immunosuppressive properties, methods of obtention, with a focus on clinical perspectives particularly in the field of cellular therapy and fat grafting technique in plastic surgery.

Therapeutic granulocyte transfusion remains an indication for neutropenic sepsis associated with prolonged neutropenia. However, harvest complexity and lack of proved efficacy mark the limits of its development.

Plasma cell leukemia (PCL) is a rare disorder which develops spontaneously (primary PCL) or evolves in patients with multiple myeloma (secondary PCL). It is defined by the presence of 2 × 10(9)/L peripheral blood plasma cells or plasmacytosis accounting for more than 20 % of the differential white cell count. PCL presents more often extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, as well as impaired renal function. Cytogenetic abnormalities and mutations observed in PCL lead to escape from immune surveillance and independence from the bone marrow microenvironment with changes in expression of adhesion molecules or chemokines receptors. The outcome of PCL has improved with combination approaches with novel agents (including bortezomib and immunomodulatory drugs, such as lenalidomide) and with autologous stem cell transplantation. Allogeneic hematopoietic stem cell transplantation is currently available for young patients. This article is an overview of this rare and severe disease and the different therapeutics options that are recommended.

The primary cilium is often associated with the phases G0 and G1 of the cellular cycle in most of the cells. So, recent studies show that its formation and its resorption are closely linked to molecular actors of the cellular cycle, as for example Aurora A or PLK1 (polo-like kinase 1). Furthermore, its resorption seems to be critical for the progress of the phase S and the cellular determination, in particular in the case of neural stem cells. Finally, the primary cilium acts as a cellular antenna allowing to transmit numerous signal pathways which, in their turn, contribute to the cellular fate.

Rhesus (Rh) antigens are not expressed on platelets but residual red cells carry the risk of anti-D iso-immunization in transfusion recipients of platelet concentrates (PC). The main theoretical risk associated with this reaction relates to female subjects due to potential obstetrical situations of maternal-foetal Rh incompatibility. Isogroup PC transfusion in this system is therefore advised. However, logistical constraints impose frequent Rh-incompatible transfusions that require the recommendation of anti-Rh immunoglobulin in a girl of childbearing age in this situation. This recommendation, already restricted to a group of patients deserves to be questioned over a decade after being issued. Data from published reports are difficult to interpret because of the heterogeneity of the few series (CP type, immune status, timing of biological tests) but the current techniques for preparing products and most common use of CP apheresis limited the risk of immunization. Moreover, platelet transfusions are particularly relevant to immunocompromised populations which, to what extent (heavy chemotherapy and/or hematopoietic stem cells recipients) seems to be protected from this risk. It is noteworthy that the clinical consequences that may be expected from such immunization are not reported. Although some authors emphasize significant isoimmunization rates (maximum 19%), the heterogeneous conditions and the lack of evidence of clinical consequence suggest evaluating the recommendations or revising them towards more targeted indications of seroprophylaxis.

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties.

This work aims to show, from data available in the literature and our own experience, how embryos' vitrification change and/or improve the management of infertile couples. In all, 652 cycles of frozen-thawed embryo transfers (FET) following vitrification were prospectively included and compared with 1126 FETs from slow freezing (SF) method. Primary end points were the (i) survival rate (SR) (% of embryos with>50% post-thaw intact blastomeres) and (ii) intact survival rate (ISR) (% of embryos with 100% post-thaw intact blastomeres). Secondary end point was the clinical pregnancy rate (CPR) defined as the presence of an intra uterine gestational sac with positive foetal heart beat. In all, 1097 and 2408 embryos have been thawed following vitrification and SF, respectively. We observed a highly significant increase of SR and ISR respectively when thawing concerned vitrified embryos rather than those from SF method (97.0% vs. 72.7%, P<10(-4); 91.5% vs. 49.8%, P<10(-4)). Furthermore, CPR were of 26.5% (73/652) and of 18.1% (204/1126) following FETs performed after vitrification or SF and thawing (P=0.0002), respectively. At the blastocyst stage, ISR was significantly improved following vitrification compared to SF (94.5% vs. 21.4%, P<10(-4)). In the study period, vitrification (i) reduced the mean number of fresh transferred embryos (1.5 vs. 1.6; P=0.08) and (ii) increased the rate of FETs at the blastocyst stage when compared with the control period (18.1% vs 2.5%., P<10(-4)). Embryo vitrification preserves all embryos from an ART cycle because of its excellent results regarding ISR at all stages of embryo development. This procedure allows a significant increase of pregnancy rates after thawing. In addition, there is a trend for increasing ART cycles performed using extended culture embryo and vitrification. The expected improvement of the cumulative birth rate at the blastocyst stage following vitrification remains to be demonstrated in a prospective randomized study.

The transcription of essentially the entire eukaryotic genome generates a myriad of non-coding RNA species that show complex overlapping patterns of expression and regulation. In the last decade, several large scale genomic analyses have shed light on the widespread existence of long non-coding RNAs (lncRNAs) in mammals. Although the function of most lncRNAs remains unknown, many of them have been suggested to play important roles in the regulation of gene expression during normal development and diseases, including cancers. Indeed, functional studies have demonstrated that lncRNAs participate in various biological processes, including reprogramming of pluripotent stem cells, oncogenic progression and cell cycle regulation. In this review, we summarize recent findings about the biology of lncRNAs and their functions in normal and pathological development in mammals.

The present updated guidelines on the management of extensive disease small cell lung cancer (SCLC) formulated by the ELCWP are designed to answer the following questions : 1) What is the definition of extensive disease? 2) What are the active drugs? 3) What is the best induction regimen? 4) Is there a role for maintenance chemotherapy? 5) Is there a role for dose-intensive chemotherapy (without administration of hematopoietic growth factors)-? 6) Is there a role for the use of haematopoietic growth factors and stem cells support? 7) Is there a role for alternating or sequential chemotherapy? 8) Is there a role for biological treatments? 9) Is there a place for second-line chemotherapy? 10) Is there a role for preventive brain irradiation (PCI)?