Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

Bone safety of dual-release hydrocortisone in patients with autoimmune primary adrenal insufficiency

BackgroundConventional glucocorticoids (C-GC) replacement regimens have a detrimental effect on skeletal health in patients with adrenal insufficiency (AI), ultimately leading to an increased fracture risk. The novel dual-release hydrocortisone (DR-HC) formulations are characterized by a more favourable safety profile on various clinical endpoints. Data comparing the impact of C-GC and DR-HC on bone, however, are scarce.MethodsTwenty-seven patients with autoimmune primary AI (PAI; 13 treated with C-GC and 14 treated with DR-HC) were evaluated to compare bone-related parameters between the two treatment groups.ResultsNo significant differences between the two treatments groups were observed with respect to bone turnover markers. Patients treated with C-GC showed a lower bone mineral density (BMD) at lumbar spine (LS; 0.791 ± 0.195 vs. 0.942 ± 0.124 g/cm2, p=0.025) and at femoral neck (FN; 0.633 ± 0.114 vs. 0.716 ± 0.088 g/cm2, p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 ± 0.035 vs. 1.383 ± 0.030, p=0.004) and by a higher mean number of vertebral fractures per patient (0.75 vs. 0 fractures, p=0.002). TBS was the best predictor of fracture risk, with a pseudo-R2 of 0.593; moreover, at mediation analysis, it was able to fully explain the observed detrimental effect of C-GC, compared to DR-HC, on fracture risk.ConclusionsThese results suggest that DR-HC is associated with less bone-related complications compared to C-GC in patients with PAI. Moreover, TBS seems to play a pivotal role in the mediation of the relationship between glucocorticoid treatment regimens and fracture risk

Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Abstract Background: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as diseaserelated survival improves. There are few data on the natural history of bone disease in RCC

A Rapid and Cheap Method for Extracting and Quantifying Lycopene Content in Tomato Sauces: Effects of Lycopene Micellar Delivery on Human Osteoblast-Like Cells

Identifying and quantifying the beneficial molecules contained in nutraceuticals is essential to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lycopene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lycopene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p ® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors

Efficient organocatalyst supported on a simple ionic liquid as a recoverable system for the asymmetric Diels–Alder reaction in the presence of water

The synthesis, characterization and evaluation of a new highly efficient organocatalyst, namely (5S)-2,2,3-trimethyl-5-thiobenzylmethyl-4-imidazolidinone hydrochloride has been achieved. The catalyst possesses important structural features that should increase the catalytic efficiency and solubility in polar media. The application of ionic liquid-supported imidazolidinone catalyst in enantioselective Diels–Alder reactions was investigated. The Diels–Alder reactions of several dienes and dienophiles proceeded efficiently in the presence of the catalyst to provide the desired products in a range from moderate to good yields and from good to excellent enantioselectivities. The conformational study confirms that in the transition state the Re face is completely shielded by phenyl ring preferring approach on less hindered Si face. Particularly remarkable is the fact that the entire system IL/HCl 0.01 M/Catalyst can be recovered and reused for up to six runs without appreciable loss of catalytic activity.This work was supported by the Ministerio de Ciencia e Innovación (MICINN) and FEDER Program (Madrid, Spain, project CTQ2013-44367-C2-1-P) and the Gobierno de Aragón (Zaragoza, Spain. D.R.-L. thanks the Spanish Ministry of Education (MEC) for a pre-doctoral grant (FPU program). We thank the Italian Ministry of University and Scientific Research (MIUR) for a doctoral grant and the University of Calabria for financial support.Peer reviewe

An EMG-Controlled Robotic Hand Exoskeleton for Bilateral Rehabilitation

This paper presents a novel electromyography (EMG)-driven hand exoskeleton for bilateral rehabilitation of grasping in stroke. The developed hand exoskeleton was designed with two distinctive features: (a) kinematics with intrinsic adaptability to patient's hand size, and (b) free-palm and free-fingertip design, preserving the residual sensory perceptual capability of touch during assistance in grasping of real objects. In the envisaged bilateral training strategy, the patient's non paretic hand acted as guidance for the paretic hand in grasping tasks. Grasping force exerted by the non paretic hand was estimated in real-time from EMG signals, and then replicated as robotic assistance for the paretic hand by means of the hand-exoskeleton. Estimation of the grasping force through EMG allowed to perform rehabilitation exercises with any, non sensorized, graspable objects. This paper presents the system design, development, and experimental evaluation. Experiments were performed within a group of six healthy subjects and two chronic stroke patients, executing robotic-assisted grasping tasks. Results related to performance in estimation and modulation of the robotic assistance, and to the outcomes of the pilot rehabilitation sessions with stroke patients, positively support validity of the proposed approach for application in stroke rehabilitation

Light alcohol drinking and the risk of cancer development: a controversial relationship

In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12,5g per day) is still unknown