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Di Cristofori A.,University of Milan | Carrabba G.,University of Milan | Lanfranchi G.,University of Milan | Menghetti C.,IRCCS Galeazzi Orthopedic Institute | And 2 more authors.
Anticancer Research | Year: 2013

Background: The current standard-of-care for glioblastoma (GBM) is represented by concomitant radiotherapy (RT) and temozolomide (TMZ), according to Stupp's protocol. Second-line treatments for GBM have not been yet defined. Tamoxifen is an anti-estrogen molecule with anti-neoplastic effects whose role is under investigation. tamoxifen is generally well tolerated but thromboembolic complications have been reported. In this study, we report our experience on the administration of tamoxifen plus dosedense TMZ in patients with recurrent GBM. Patients and Methods: All patients underwent surgical resection of GBM and completed concomitant RT and TMZ. Eligibility criteria also included evidence of GBM recurrence and good general conditions [Karnofsky Performance Score (KPS) >70] at recurrence. Patients with rapidly progressive disease, clearly unfavorable prognosis, or history of deep-venous thrombosis were excluded. The second-line treatment consisted of dosedense TMZ (75-150 mg/m2 one week on/ one week off) plus daily tamoxifen (80 mg/m2). Follow-up was performed with contrast-enhanced brain Magnetic Resonance Imaging (MRI) every three months. Results: Thirty-two patients (18 males, 14 females; median age 57 years) with GBM relapse were included. Median overall survival time (OS) and time to tumor progression after recurrence (TTP-2) were 17.5 and 7 months, respectively. Interestingly, no differences in OS and TTP-2 were noted in GBM between those with methylated and unmethylated MGMT. None of the patients had complications related to TMZ plus tamoxifen administration. Conclusion: The combinatorial administration of tamoxifen and TMZ appeared to be well-tolerated, and potentially effective in increasing the efficacy of dose-dense TMZ schedule as a second-line therapeutic strategy. Source


Freutel M.,University of Ulm | Galbusera F.,IRCCS Galeazzi Orthopedic Institute | Ignatius A.,University of Ulm | Durselen L.,University of Ulm
Journal of Biomechanics | Year: 2015

Meniscal properties for computational methods have already been proposed. However, it is well known that there is high intra subject variability in the material properties of soft tissues and that disruption of the fiber network alters the biomechanics of the meniscus. Therefore, the objective of this study was to establish a non invasive method to determine the material properties of the individual menisci and their attachments using inverse FE-analyses.In a previous study, the 3D displacements of the meniscus and its attachments under axial joint loads were determined for intact porcine knees. To simulate the experimental response in individual FE-analyses (n=5), an anisotropic, hyperelastic meniscus matrix was embedded in a poroelastic model. During a particle swarm optimization, the difference between the force applied to the meniscus during the experiment and the femoral surface reaction force of the FE model at equilibrium was minimized by varying four material parameters. Afterwards, a prediction error was determined to describe how well the material parameter fit to each of the three displacement directions. Additionally, the stresses occurring in the meniscus were evaluated.The error of the material parameter optimization was on average 6.5±4.4%. The best fitting material parameter combination revealed an error of 1.2%. The highest stresses occurred in the region between the pars intermedia and posterior horn of the meniscus.The individual material properties of the meniscus were successfully obtained with a combination of previously reported, noninvasively measured 3D displacements and inverse FE-analyses. The methodology presented in this study is a promising contribution to the detection of degeneration within the meniscus. © 2015 Elsevier Ltd. Source


Pecoraro V.,IRCCS Galeazzi Orthopedic Institute | Germagnoli L.,Unilabs Ticino | Banfi G.,University of Milan
Clinical Chemistry and Laboratory Medicine | Year: 2014

Point-of-care testing (POCT) has had rapid technological development and their use is widespread in clinical laboratories to assure reduction of turn-aroundtime and rapid patient management in some clinical settings where it is important to make quick decisions. Until now the papers published about the POCT have focused on the reliability of the technology used and their analytical accuracy. We aim to perform a systematic survey of the evidence of POCT efficacy focused on clinical outcomes, selecting POCT denoted special analytes characterized by possible high clinical impact. We searched in Medline and Embase. Two independent reviewers assessed the eligibility, extracted study details and assessed the methodological quality of studies. We analyzed 84 studies for five POCT instruments: neonatal bilirubin, procalcitonin, intra-operative parathyroid hormone, troponin and blood gas analysis. Studies were at high risk of bias. Most of the papers (50%) were studies of correlation between the results obtained by using POCT instruments and those obtained by using laboratory instruments. These data showed a satisfactory correlation between methods when similar analytical reactions were used. Only 13% of the studies evaluated the impact of POCT on clinical practice. POCT decreases the time elapsed for making decisions on patient management but the clinical outcomes have never been adequately evaluated. Our work shows that, although POCT has the potential to provide beneficial patient outcome, further studies may be required, especially for defining its real utility on clinical decision making. Source


Faes L.,University of Trento | Porta A.,University of Milan | Porta A.,IRCCS Galeazzi Orthopedic Institute | Nollo G.,University of Trento
Entropy | Year: 2015

In the framework of information dynamics, the temporal evolution of coupled systems can be studied by decomposing the predictive information about an assigned target system into amounts quantifying the information stored inside the system and the information transferred to it. While information storage and transfer are computed through the known self-entropy (SE) and transfer entropy (TE), an alternative decomposition evidences the so-called cross entropy (CE) and conditional SE (cSE), quantifying the cross information and internal information of the target system, respectively. This study presents a thorough evaluation of SE, TE, CE and cSE as quantities related to the causal statistical structure of coupled dynamic processes. First, we investigate the theoretical properties of these measures, providing the conditions for their existence and assessing the meaning of the information theoretic quantity that each of them reflects. Then, we present an approach for the exact computation of information dynamics based on the linear Gaussian approximation, and exploit this approach to characterize the behavior of SE, TE, CE and cSE in benchmark systems with known dynamics. Finally, we exploit these measures to study cardiorespiratory dynamics measured from healthy subjects during head-up tilt and paced breathing protocols. Our main result is that the combined evaluation of the measures of information dynamics allows to infer the causal effects associated with the observed dynamics and to interpret the alteration of these effects with changing experimental conditions. © 2015 by the authors. Source


Moja L.,University of Milan | Moja L.,IRCCS Galeazzi Orthopedic Institute | Danese S.,center | Fiorino G.,center | And 3 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015

Background Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease. Aim To assess their comparative efficacy and harm using the methodology of network meta-analysis. Methods A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug. Results Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases. Conclusions Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice. © 2015 John Wiley & Sons Ltd. Source

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