24 research outputs found

    Nonpegylated liposomal doxorubicin combination regimen in patients with diffuse large B-cell lymphoma and cardiac comorbidity. Results of the HEART01 phase II trial conducted by the Fondazione Italiana Linfomi

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    The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76\ua0years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF <50% (12%). Based on the intent to treat analysis, overall response rate was 72%, including 28 patients in complete remission (complete remission rate, 56%), and 8 in partial remission (16%). At the end of treatment, grades 3 to 4 cardiac events were observed in 6 patients. No significant modifications from baseline values of LVEF were observed during treatment and follow-up. Nonpegylated liposomal doxorubicin instead of doxorubicin in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is a feasible option for patients with diffuse large B-cell lymphoma presenting with concomitant cardiac disorders

    Active Control of Aerodynamic Surfaces for Ride Control in Sport Vehicles

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    This work investigates the use of Active Aerodynamic Surfaces (AAS) to enhance ride comfort in sport vehicles. Four AAS's generate lift forces that control the vertical acceleration of the sprung mass without negatively affecting the unsprung mass. It is shown that the AAS system can overcome the trade-off between comfort and road holding. In this work a preliminary analysis of the control system is presented along with a mechatronic feasibility analysis. The required controller bandwidth, airfoils size and power requirements are analyzed in simulation. The system is validated on a complete vehicle model showing improvements of the order of 30% in ride comfort with no negative effects on road-holding at high speed

    Performance Assessment of Active Aerodynamic Surfaces for Comfort and Handling Optimization in Sport Cars

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    This paper investigates the use of active aerodynamic surfaces (AASs) to enhance the ride comfort of sport vehicles. AASs are constituted by airfoils that are properly placed on the vehicle chassis, and whose angle of attack can be modulated at high frequency (10 Hz). Thus, AASs can be used to generate a lift force that helps in controlling the vertical acceleration of the sprung mass without negatively affecting the unsprung mass. Thanks to this property, AAS systems can overcome the tradeoff between comfort and road holding. In this paper, a control system is presented along with a detailed analysis of several design choices (controller bandwidth, surface size, and actuator requirements). Furthermore, the effect of several environmental factors is considered: 1) vehicle mass; 2) vehicle velocity; and 3) road roughness. A specific analysis shows that the proposed system can be integrated with classical semiactive suspension control algorithms. The system is validated on a complete vehicle model, showing improvements of the order of 30% in ride comfort with no negative effects on road holdin

    Improving High Speed Road-Holding Using Actively Controlled Aerodynamic Surfaces

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    Semi-active and active suspension technologies have shown that vehicles road holding can be enhanced, but any such improvement implies decreasing the overall comfort. In this paper, we introduce the use of active aerodynamic surfaces to improve vehicle road-holding without affecting comfort. An H∞ closed-loop controller is developed to minimize the tire deflection variations, which are responsible for the vehicle bad road holding. The controller is designed on a quarter-car model. Extensive simulations on a multi-body vehicle simulation suit assess the performance of the proposed control scheme, and an exhaustive sensitivity analysis shows the role of road roughness, velocity and airfoil design

    Detection of Circulating Tumour Cells in Urothelial Cancers and Clinical Correlations: Comparison of Two Methods

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    Circulating tumour cells (CTC) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer (BC) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect (AT) and ScreenCell®Cyto (SC) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic (M0) and 47 metastatic (M+) BC patients, at baseline (T0) and during treatment (T1). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases (57.4% versus 25%, p = 0.041). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 (median (interquartile range, IQR): 0.18 (0.07–0.42) versus 0.84 (0.33–1.84), p=0.005) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently (25% versus 8%) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts

    Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers

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    Background Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone. Design and Methods In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1-21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months. Results The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35-68%) and 8 of 33 patients (24%; 95% CI, 13-41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5-19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%). Conclusions These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. © 2012 Ferrata Storti Foundation
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