Nivolumab in patients with advanced renal cell carcinoma in France: interim results of the observational, real-world WITNESS study.

Background: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452).

Impact of First Line Antiangiogenic Therapy Duration on Nivolumab Outcome in Metastatic Renal Cell Carcinoma Patients Treated in the GETUG-AFU 26 NIVOREN.

Background: In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC.

Methods: Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included.

Comparison of spatio-temporal gait parameters between the GAITRite® platinum plus classic and the GAITRite® CIRFACE among older adults: a retrospective observational study.

Background: The GAITRite® system is one of the gold standards for gait electronic analysis, especially for older adults. Previous GAITRite® systems were composed of an electronic roll-up walkway. Recently, a new GAITRite® electronic walkway, named CIRFACE, was commercialized.

TGFβ Programs Central Memory Differentiation in -Stimulated Human T Cells.

The adoptive transfer of -expanded T cells is a promising approach to treat several malignancies. Several lines of evidence support that the infusion of T cells with early memory features, capable of expanding and persisting after transfer, are associated with better outcomes. We report herein that exposure to exogenous TGFβ during human T-cell stimulation leads to the accumulation of early/central memory (Tcm) cells.

Sequencing of Taxanes and New Androgen-targeted Therapies in Metastatic Castration-resistant Prostate Cancer: Results of the International Multicentre Retrospective CATS Database.

Background: The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown.

Objective: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences.

Design, Setting, And Participants: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016.

A standardized immune phenotyping and automated data analysis platform for multicenter biomarker studies.

The analysis and validation of flow cytometry-based biomarkers in clinical studies are limited by the lack of standardized protocols that are reproducible across multiple centers and suitable for use with either unfractionated blood or cryopreserved PBMCs. Here we report the development of a platform that standardizes a set of flow cytometry panels across multiple centers, with high reproducibility in blood or PBMCs from either healthy subjects or patients 100 days after hematopoietic stem cell transplantation. Inter-center comparisons of replicate samples showed low variation, with interindividual variation exceeding inter-center variation for most populations (coefficients of variability <20% and interclass correlation coefficients >0.

Clinical-Scale Rapid Autologous BK Virus-Specific T Cell Line Generation From Kidney Transplant Recipients With Active Viremia for Adoptive Immunotherapy.

Background: Polyomavirus-associated nephropathy (PVAN) after BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulation/expansion offers the possibility to generate BK-specific T cell lines for adoptive immunotherapy.

Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene.

IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC). Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease.

Early exposure to interleukin-21 limits rapidly generated anti-Epstein-Barr virus T-cell line differentiation.

Background Aims: The adoptive transfer of ex vivo-expanded Epstein-Barr virus (EBV)-specific T-cell lines is an attractive strategy to treat EBV-related neoplasms. Current evidence suggests that for adoptive immunotherapy in general, clinical responses are superior if the transferred cells have not reached a late or terminal effector differentiation phenotype before infusion. The cytokine interleukin (IL)-21 has shown great promise at limiting late T-cell differentiation in vitro, but this remains to be demonstrated in anti-viral T-cell lines.

Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene.

Background: The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C.

Nystatin nanosizing enhances in vitro and in vivo antifungal activity against Candida albicans.

Objectives: In this study, we developed a nanoparticulate nystatin formulation and performed a comparative evaluation against a commercial nystatin preparation of its in vitro and in vivo antifungal activities.

Methods: A nystatin nanosuspension was prepared from a commercially available suspension by wet-media milling. The nanosuspension was characterized for particle size by laser diffraction and assayed for content by HPLC.

Altered immune response differentially enhances susceptibility to Cryptococcus neoformans and Cryptococcus gattii infection in mice expressing the HIV-1 transgene.

Cryptococcus neoformans var. grubii is the most frequent cause of AIDS-associated cryptococcosis worldwide, while Cryptococcus gattii usually infects immunocompetent people. To understand the mechanisms which cause differential susceptibility to these cryptococcal species in HIV infection, we established and characterized a model of cryptococcosis in CD4C/HIV(MutA) transgenic (Tg) mice expressing gene products of HIV-1 and developing an AIDS-like disease.

The colocalization potential of HIV-specific CD8+ and CD4+ T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid.

CD4(+) T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8(+) T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8(+) and CD4(+) T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression.

Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars.

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes.

Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDS-like phenotypes.

We previously reported that CD4C/human immunodeficiency virus (HIV)(Nef) transgenic (Tg) mice, expressing Nef in CD4(+) T cells and cells of the macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease, characterized by depletion of CD4(+) T cells, as well as lung, heart, and kidney diseases. In order to determine the contribution of distinct populations of hematopoietic cells to the development of this AIDS-like disease, five additional Tg strains expressing Nef through restricted cell-specific regulatory elements were generated. These Tg strains express Nef in CD4(+) T cells, DCs, and macrophages (CD4E/HIV(Nef)); in CD4(+) T cells and DCs (mCD4/HIV(Nef) and CD4F/HIV(Nef)); in macrophages and DCs (CD68/HIV(Nef)); or mainly in DCs (CD11c/HIV(Nef)).

Macrophage-mediated responses to Candida albicans in mice expressing the human immunodeficiency virus type 1 transgene.

The critical impairments of innate and adaptive immunity that cause susceptibility to mucosal candidiasis in human immunodeficiency virus (HIV) infection have not been fully determined. We therefore conducted an analysis of macrophage-mediated responses to Candida albicans in transgenic (Tg) mice expressing Nef, Env, and Rev of HIV type 1 (HIV-1) in CD4(+) T cells, dendritic cells, and macrophages and developing an AIDS-like disease (CD4C/HIV(MutA) Tg mice). Macrophages were successfully recruited to the oral and gastric mucosae of these Tg mice in response to chronic carriage of C.

Solar-like oscillations in a massive star.

Seismology of stars provides insight into the physical mechanisms taking place in their interior, with modes of oscillation probing different layers. Low-amplitude acoustic oscillations excited by turbulent convection were detected four decades ago in the Sun and more recently in low-mass main-sequence stars. Using data gathered by the Convection Rotation and Planetary Transits mission, we report here on the detection of solar-like oscillations in a massive star, V1449 Aql, which is a known large-amplitude (beta Cephei) pulsator.

Sequential therapy in renal cell carcinoma.

Because of the recent approval of several drugs for the treatment of renal cell carcinoma (including sorafenib, sunitinib, temsirolimus, and, in Europe, bevacizumab plus interferon), the use of sequential therapy has become routine practice. There is now evidence that administering these targeted agents sequentially provides clinical benefit by inducing tumor shrinkage and prolonged progression-free survival (PFS) in a large number of patients. However, data regarding overall survival (OS) are still pending.

CoRoT measures solar-like oscillations and granulation in stars hotter than the Sun.

Oscillations of the Sun have been used to understand its interior structure. The extension of similar studies to more distant stars has raised many difficulties despite the strong efforts of the international community over the past decades. The CoRoT (Convection Rotation and Planetary Transits) satellite, launched in December 2006, has now measured oscillations and the stellar granulation signature in three main sequence stars that are noticeably hotter than the sun.

Single-implant segmental osteotomy: a case report.

This case report describes the use of a single-implant osteotomy in repositioning a significantly malaligned, osseointegrated endosseous implant. This technique represents a modification of the single-tooth osteotomy that has been used for many years to reposition the natural dental unit. It provides the dental practitioner with a treatment alternative that is safe, cost-effective, and predictable.

Incremental bolus versus a continuous infusion of propofol for deep sedation/general anesthesia during dentoalveolar surgery.

Purpose: This article compared the use of the traditional incremental bolus technique with the continuous infusion technique for the administration of propofol for deep sedation/general anesthesia.

Patients And Methods: Patients were sedated with midazolam and fentanyl and then had maintenance of an anesthetic state achieved with propofol administered by either of the two techniques. Data were collected to evaluate the overall surgical/anesthetic procedure, movement of the patient, and his or her hemodynamic status.

Occupational health and safety emergencies.

When considering potentials emergencies in the dental office, one usually first thinks about potential drug reactions or adverse response to underlying systemic diseases. The rare, but potential, emergencies arising from the office environment itself also exist. Toxic reactions to various chemicals found in the office must be considered also.