Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

This paper presents the closing step of a synthesis process aiming at deriving, from a previously developed more complex model, a simple design formula to evaluate the shear strength contribution provided by a system of Near Surface Mounted (NSM) Fiber Reinforced Polymer (FRP) strips to a Reinforced Concrete (RC) beam. The self-contained and ready-to-implement set of analytical equations and logical operations is presented along with the main underlying physical-mechanical principles and assumptions. The formulation proposed is appraised against some of the most recent experimental results and its predictions are also compared with those obtained by the two previous and more sophisticated versions of the same modeling strategy. Monte Carlo simulations are carried out in order to appraise the sensitivity of the NSM shear strength contribution prediction to the value assumed by the input parameters. © 2013 Elsevier Ltd. All rights reserved

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment.

The need to provide a rational explanation to the observed peculiar failure mode affecting the behaviour, at ultimate, of a Reinforced Concrete (RC) beam strengthened in shear by Near Surface Mounted (NSM) Fibre Reinforced Polymer (FRP) strips, led the authors to develop a comprehensive numerical model for simulating the NSM shear strength contribution to RC beams throughout the entire loading process as function of the Critical Diagonal Crack (CDC) opening angle. That model was respectful of equilibrium, kinematic compati-bility and constitutive laws. Despite its high level of prediction accuracy, taking into account all of the possible failure modes, as well as the interaction among adjacent strips, that model resulted relatively complex to be easily implemented in a practitionersaddressed building regulations code. Yet, it can be conveniently simplified into a more user-friendly and closed-form design formula. Crucial point of that simplification is the development of a reliable constitutive analytical law providing the single strip strength as function of the imposed end slip. This paper presents the modelling strategy adopted to determine that constitutive law, as well as its final analytical expression. © Tsinghua University Press, Beijing and Springer-Verlag Berlin Heidelberg 2011