Purpose Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome. Methods A retrospective and multicentre study was designed, which involved a total of 251 patients affected by different tumors (mostly non-small cell lung cancer, 68.92% and melanoma, 24.30%) and treated with the PD-1 inhibitors nivolumab (61.35%) or pembrolizumab (38.65%) for up to 60 months. Clinical and biochemical data were recorded until July 31, 2020. Results Endocrine toxicity occurred in 70 out of 251 patients (27.89%). It was mostly related to thyroid dysfunction and in 75% of cases occurred within 6 months from the beginning of therapy. A previous endocrine morbidity and female gender were predictors of endocrine toxicity. There was no association between endocrine dysfunction and patient outcome. However, when all toxicities (i.e., endocrine and non endocrine) were considered, a significant association with progression-free survival and overall survival was found. Conclusions Thyroid alterations are frequently observed in cancer patients treated with anti PD-1 drugs, particularly in women and in the presence of a previous endocrinopathy. We suggest that regular thyroid assessment should be performed in these patients, especially in the first months of therapy. Finally, the onset of side effects, related to anti PD-1 agents, appears to be associated with a better outcome.
One of the most challenging aspects in horizontal pumps design is the evaluation of the residual axial thrust acting on the rotating shaft. The thrust is affected by pump characteristics and working conditions. Solving this problem is easier for a single stage pump than for multistage pumps, even in partially self-balancing opposite impeller configuration. The challenge is then to individuate a procedure that will provide the residual thrust value with a moderate computational effort, dealing with the industrial requests of accuracy and reduced time consumption. A procedure is proposed, which consists in the numerical simulation of each pump component. For each component, the obtained mass-flow/thrust correlations are coupled by using a momentum balance equation used to calculate the axial thrust as a function of the working conditions. The main topic in multistage pump modeling is the leakage flows characterization by means of accurate numerical analysis. Therefore, the cavity flows behavior is investigated and the flow structures individuated. The numerical investigation of the pump's components provides also a thorough knowledge of fluid dynamic fields. The proposed procedure is able to predict both the direction and the variation of the thrust in a selected range of flow rates, while the value of the thrust is affected by a non-negligible error generated by "real machine" effects.
Background: To date, no biomarkers are effective in predicting the risk of developing immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). This study aims to evaluate the association between basal absolute eosinophil count (AEC) and irAEs during treatment with ICIs for solid tumors. Methods: We retrospectively evaluated 168 patients with metastatic melanoma (mM), renal cell carcinoma (mRCC), and non-small cell lung cancer (mNSCLC) receiving ICIs at our medical oncology unit. By combining baseline AEC with other clinical factors, we developed a mathematical model for predicting the risk of irAEs, which we validated in an external cohort of patients. Results: Median baseline AEC was 135/µL and patients were stratified into two groups accordingly; patients with high baseline AEC (>135/µL) were more likely to experience toxicity (p = 0.043) and have a better objective response rate (ORR) (p = 0.003). By constructing a covariance analysis model, it emerged that basal AEC correlated with the risk of irAEs (p < 0.01). Finally, we validated the proposed model in an independent cohort of 43 patients. Conclusions: Baseline AEC could be a predictive biomarker of ICI-related toxicity, as well as of response to treatment. The use of a mathematical model able to predict the risk of developing irAEs could be useful for clinicians for monitoring patients receiving ICIs.
The use of hydrogen as derived fuel for low emission gas turbine is a crucial issue of clean coal technology power plant based on IGCC (Integrated Gasification Combined Cycle) technology. Control of NOx emissions in gas turbines supplied by natural gas is effectively achieved by lean premixed combustion technology; conversely, its application to NOx emission reduction in high hydrogen content fuels is not a reliable practice yet. Since the hydrogen premixed flame is featured by considerably higher flame speed than natural gas, very high air velocity values are required to prevent flash-back phenomena, with obvious negative repercussions on combustor pressure drop. In this context, the characterization of hydrogen lean premixed combustion via experimental and modeling analysis has a special interest for the development of hydrogen low NOx combustors. This paper describes the experimental and numerical investigations carried-out on a lean premixed burner prototype supplied by methane-hydrogen mixture with an hydrogen content up to 100%. The experimental activities were performed with the aim to collect practical data about the effect of the hydrogen content in the fuel on combustion parameters as: air velocity flash-back limit, heat release distribution, NOx emissions. This preliminary data set represents the starting point for a more ambitious project which foresees the upgrading of the hydrogen gas turbine combustor installed by ENEL in Fusina (Italy). The same data will be used also for building a computational fluid dynamic (CFD) model usable for assisting the design of the upgraded combustor. Starting from an existing heavy-duty gas turbine burner, a burner prototype was designed by means of CFD modeling and hot-wire measurements. The geometry of the new premixer was defined in order to control turbulent phenomena that could promote the flame moving-back into the duct, to increase the premixer outlet velocity and to produce a stable central recirculation zone in front of the burner. The burner prototype was then investigated during a test campaign performed at the ENEL’s TAO test facility in Livorno (Italy) which allows combustion test at atmospheric pressure with application of optical diagnostic techniques. In-flame temperature profiles, pollutant emissions and OH* chemiluminescence were measured over a wide range of the main operating parameters for three fuels with different hydrogen content (0, 75% and 100% by vol.). Flame control on burner prototype fired by pure hydrogen was achieved by managing both the premixing degree and the air discharge velocity, affecting the NOx emissions and combustor pressure losses respectively. A CFD model of the above-mentioned combustion test rig was developed with the aim to validate the model prediction capabilities and to help the experimental data analysis. Detailed simulations, performed by a CFD 3-D RANS commercial code, were focused on air/fuel mixing process, temperature field, flame position and NOx emission estimation.
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