Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab

Human biomonitoring in the area around the petrochemical site in Gela, Sicily-Italy

Close to the town of Gela (Sicily, Italy) a petrochemical site is operating since 1962. A power station, chemical plants and an oil refiney plant incleded. In 1990 a large area around the site was declared " at high risk of environmental cirsis" in 2000 a subarea was designated " Reclamation Site of National Inerest" Extremely high concentrations of hazardous chemicals have been measured in soil, surface and groundwater, in marine water and sediments. Mortality, hospital discharges and birth defects were reported higher than neighbouring areas and other references

Surface Properties and Antioxidant Activity of Silicate and Borosilicate Bioactive Glasses

Herein, silicate and borosilicate bioactive glasses are synthetized and characterized. The antioxidant activity, in the presence and absence of human osteoblasts' progenitor cells, of the different glass compositions, is correlated to the surface properties: wettability, zeta potential, hydroxylation degree, reactivity in simulated body fluid (SBF), and Tris buffer. An enhancing effect of boron in glass reactivity and a stabilizing role of Sr and Mg are evidenced. The scavenging potential of the analyzed bioactive glasses toward reactive oxygen species (ROS) is clearly proved. Moreover, cellular tests confirm the protective effect of the bioactive glasses toward viable cells acting as ROS/RNS species scavenger. The obtained results represent an original improvement of the knowledge concerning the intrinsic antioxidant ability of bioactive glasses with different compositions and the mechanisms involved

The MHC-II transactivator CIITA, a viral restriction factor inhibiting the replication of Human T-Cell Lymphotropic Virus Type 1

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