A Matched-Pair Analysis after Robotic and Retropubic Radical Prostatectomy: A New Definition of Continence and the Impact of Different Surgical Techniques

Radical prostatectomy is considered the gold-standard treatment for patients with localized prostate cancer. The literature suggests there is no difference in oncological and functional outcomes between robotic-assisted radical prostatectomy (RARP) and open (RRP). (2) Methods: The aim of this study was to compare continence recovery rates after RARP and RRP measured with 24 h pad weights and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). After matching the population (1:1), 482 met the inclusion criteria, 241 patients per group. Continent patients with a 24 h pad test showing <20 g of urinary leakage were considered, despite severe incontinence, and categorized as having >200 g of urinary leakage. (3) Results: There was no difference between preoperative data. As for urinary continence (UC) and incontinence (UI) rates, RARP performed significantly better than RRP based on objective and subjective results at all evaluations. Univariable and multivariable Cox Regression Analysis pointed out that the only significant predictors of continence rates were the bilateral nerve sparing technique (1.25 (CI 1.02,1.54), p = 0.03) and the robotic surgical approach (1.42 (CI 1.18,1.69) p ≤ 0.001). (4) Conclusions: The literature reports different incidences of UC depending on assessment and definition of continence "without pads" or "social continence" based on number of used pads per day. In this, our first evaluation, the advantage of objective measurement through the weight of the 24 h and subjective measurement with the ICIQ-SF questionnaire best demonstrates the difference between the two surgical techniques by enhancing the use of robotic surgery over traditional surgery

Analysis of Allogenicity of Mesenchymal Stem Cells in Engraftment and Wound Healing in Mice

Studies have shown that allogeneic (allo-) bone marrow derived mesenchymal stem cells (BM-MSCs) may enhance tissue repair/regeneration. However, recent studies suggest that immune rejection may occur to allo-MSCs leading to reduced engraftment. In this study, we compared allo-BM-MSCs with syngeneic BM-MSCs or allo-fibroblasts in engraftment and effect in wound healing. Equal numbers of GFP-expressing allo-BM-MSCs, syngeneic BM-MSCs or allo-fibroblasts were implanted into excisional wounds in GFP-negative mice. Quantification of GFP-expressing cells in wounds at 7, 14 and 28 days indicated similar amounts of allogeneic or syngeneic BM-MSCs but significantly reduced amounts of allo-fibroblasts. With healing progression, decreasing amounts of allogeneic and syngeneic BM-MSCs were found in the wound; however, the reduction was more evident (2 fold) in allo-fibroblasts. Similar effects in enhancing wound closure were found in allogeneic and syngeneic BM-MSCs but not in allo-fibroblasts. Histological analysis showed that allo-fibroblasts were largely confined to the injection sites while allo-BM-MSCs had migrated into the entire wound. Quantification of inflammatory cells in wounds showed that allo-fibroblast- but not allo-BM-MSC-treated wounds had significantly increased CD45+ leukocytes, CD3+ lymphocytes and CD8+ T cells. Our study suggests that allogeneic BM-MSCs exhibit ignorable immunogenicity and are equally efficient as syngeneic BM-MSCs in engraftment and in enhancing wound healing

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Modulation of Human Mesenchymal Stem Cell Immunogenicity through Forced Expression of Human Cytomegalovirus US Proteins

BACKGROUND: Mesenchymal stem cells (MSC) are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV) has developed several strategies to evade cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity. METHODOLOGY/PRINCIPAL FINDINGS: We genetically engineered human MSC to express HCMV proteins known to downregulate HLA-I expression, and investigated whether modified MSC were protected from CTL and NK attack. Flow cytometric analysis showed that amongst the US proteins tested, US6 and US11 efficiently reduced MSC HLA-I expression, and mixed lymphocyte reaction demonstrated a corresponding decrease in human and sheep mononuclear cell proliferation. NK killing assays showed that the decrease in HLA-I expression did not result in increased NK cytotoxicity, and that at certain NK∶MSC ratios, US11 conferred protection from NK cytotoxic effects. Transplantation of MSC-US6 or MSC-US11 into pre-immune fetal sheep resulted in increased liver engraftment when compared to control MSC, as demonstrated by qPCR and immunofluorescence analyses. CONCLUSIONS AND SIGNIFICANCE: These data demonstrate that engineering MSC to express US6 and US11 can be used as a means of decreasing recognition of MSC by the immune system, allowing higher levels of engraftment in an allogeneic transplantation setting. Since one of the major factors responsible for the failure of allogeneic-donor MSC to engraft is the mismatch of HLA-I molecules between the donor and the recipient, MSC-US6 and MSC-US11 could constitute an off-the-shelf product to overcome donor-recipient HLA-I mismatch

Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.</p> <p>Methods</p> <p>In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.</p> <p>Results</p> <p>While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.</p> <p>Conclusions</p> <p>Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.</p

Are mesenchymal stromal cells immune cells?

Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system

Observation of the cosmic ray shadow of the Sun with the ANTARES neutrino telescope

[EN] The ANTARES detector is an undersea neutrino telescope in the Mediterranean Sea. The search for pointlike neutrino sources is one of the main goals of the ANTARES telescope, requiring a reliable method to evaluate the detector angular resolution and pointing accuracy. This work describes the study of the Sun ¿shadow¿ effect with the ANTARES detector. The shadow is the deficit in the atmospheric muon flux in the direction of the Sun caused by the absorption of the primary cosmic rays. This analysis is based on the data collected between 2008 and 2017 by the ANTARES telescope. The observed statistical significance of the Sun shadow detection is 3.7¿, with an estimated angular resolution of 0.59° +- 0.10°for downward-going muons. The pointing accuracy is found to be consistent with the expectations and no evidence of systematic pointing shifts is observed.The authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique, Commissariat `a l'' energie atomique et aux energies alternatives, Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France, LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), R ' egion Ile-de-France (DIM-ACAV), Region Alsace (contract CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung, Germany; Istituto Nazionale di Fisica Nucleare, Italy; Nederlandse organisatie voor Wetenschappelijk Onderzoek, the Netherlands; Council of the President of the Russian Federation for Young Scientists and Leading Scientific Schools supporting grants, Russia; Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (refs. SOMM17/6104/UGR and A-FQM-053-UGR18), Generalitat Valenciana: Grisolia (ref. GRISOLIA/2018/119), Spain; Ministry of Higher Education, Scientific Research and Professional Training, Morocco. We also acknowledge the technical support of Ifremer, AIM and Foselev Marine for the sea operation and the CC-IN2P3 for the computing facilities.Albert, A.; Andre, M.; Anghinolfi, M.; Anton, G.; Ardid Ramírez, M.; Aubert, J.; Aublin, J.... (2020). Observation of the cosmic ray shadow of the Sun with the ANTARES neutrino telescope. Physical Review D: covering particles, fields, gravitation, and cosmology. 102(12):1-7. https://doi.org/10.1103/PhysRevD.102.122007S1710212Ageron, M., Aguilar, J. A., Al Samarai, I., Albert, A., Ameli, F., André, M., … Ardid, M. (2011). ANTARES: The first undersea neutrino telescope. 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A., Ahlers, M., Ahrens, M., … Ansseau, I. (2019). Detection of the Temporal Variation of the Sun’s Cosmic Ray Shadow with the IceCube Detector. The Astrophysical Journal, 872(2), 133. doi:10.3847/1538-4357/aaffd1Albert, A., André, M., Anghinolfi, M., Anton, G., Ardid, M., Aubert, J.-J., … Barrios-Martít, J. (2018). The cosmic ray shadow of the Moon observed with the ANTARES neutrino telescope. The European Physical Journal C, 78(12). doi:10.1140/epjc/s10052-018-6451-3First search for neutrinos in correlation with gamma-ray bursts with the ANTARES neutrino telescope. (2013). Journal of Cosmology and Astroparticle Physics, 2013(03), 006-006. doi:10.1088/1475-7516/2013/03/006Aguilar, J. A., Al Samarai, I., Albert, A., André, M., Anghinolfi, M., Anton, G., … Astraatmadja, T. (2011). A fast algorithm for muon track reconstruction and its application to the ANTARES neutrino telescope. 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