Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials.

BACKGROUND:Siltuximab is recommended by international consensus as a first-line treatment for idiopathic multicentric Castleman disease on the basis of durable efficacy and safety data. This study was done to assess the long-term safety and activity of siltuximab over up to 6 years of treatment. METHODS:This study is a prespecified open-label extension analysis of a phase 1 trial (NCT00412321) and a phase 2 trial (NCT01024036), done at 26 hospitals worldwide. Patients in both studies were at least 18 years old with histologically confirmed, symptomatic Castleman disease. This extension study enrolled 60 patients who completed the previous trials without disease progression on siltuximab. Patients received siltuximab infusions of 11 mg/kg every 3 weeks (which could be extended to 6 weeks) for up to 6 years. Descriptive statistics were used to summarise the data. No formal hypothesis testing was performed. The primary endpoint was the safety of siltuximab, assessed at each dosing cycle. The study was registered with ClinicalTrials.gov, number NCT01400503 and with EudraCT, number 2010-022837-27. FINDINGS:Patient enrolment into the phase 1 trial was from June 20, 2005, to Sept 15, 2009, and enrolment into the phase 2 trial was from Feb 9, 2010, to Feb 3, 2012. Patients were enrolled in this long-term extension from April 1, 2011, to Jan 15, 2014. Median follow-up was 6 years (IQR 5·11-7·76). Median treatment duration, from the beginning of the previous trials to the end of the present study, was 5·5 years (IQR 4·26-7·14). Siltuximab was well tolerated; however, adverse events of grade 3 or worse were reported in 36 (60%) of 60 patients with the most common being hypertension (eight [13%]), fatigue (five [8%]), nausea (four [7%]), neutropenia (four [7%]), and vomiting (three [5%]). 25 (42%) patients reported at least one serious adverse event, which most commonly was an infection (eight [13%]). Only two serious adverse events, polycythaemia and urinary retention, were considered related to siltuximab treatment. 18 patients discontinued before study completion, either to receive siltuximab locally (eight) or because of progressive disease (two), adverse events (two), or other reasons (six). No deaths were reported. INTERPRETATION:These results show that siltuximab is well tolerated long term and provides important evidence for the feasibility of the life-long use required by patients with idiopathic multicentric Castleman disease. FUNDING:Janssen R&D and EUSA Pharma

Infinite ergodic theory and Non-extensive entropies

We bring into account a series of result in the infinite ergodic theory that we believe that they are relevant to the theory of non-extensive entropie

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques.M.R.D and D.E.N are supported by the British Heart Foundation (CH/09/002 to D.E.N., FS/14/78/31020 to M.R.D). M.R.D is the recipient of the Sir Jules Thorn Biomedical Research Award 2015 (M.R.D.) E.A. research is supported by R01HL 114805 and R01HL 109506.This is the final version of the article. It first appeared from Lippincott, Williams & Wilkins via http://dx.doi.org/10.1161/CIRCRESAHA.116.30797

68Ga-DOTATATE PET Identifies Residual Myocardial Inflammation and Bone Marrow Activation After Myocardial Infarction.

Myocardial infarction (MI) healing occurs in two phases: first an inflammatory phase, where clearance of necrotic debris occurs, followed by a reparative phase characterized by angiogenesis, granulation tissue formation and attempts to repair the extracellular matrix. While efficient healing relies on co-ordinated mobilization of monocytes to the damaged myocardium, with resolution of the acute inflammatory response by ~10-14 days, excessive inflammation impairs myocardial salvage and promotes adverse cardiac remodelling

Building a Open Source Framework for Virtual Medical Training

This paper presents a framework to build medical training applications by using virtual reality and a tool that helps the class instantiation of this framework. The main purpose is to make easier the building of virtual reality applications in the medical training area, considering systems to simulate biopsy exams and make available deformation, collision detection, and stereoscopy functionalities. The instantiation of the classes allows quick implementation of the tools for such a purpose, thus reducing errors and offering low cost due to the use of open source tools. Using the instantiation tool, the process of building applications is fast and easy. Therefore, computer programmers can obtain an initial application and adapt it to their needs. This tool allows the user to include, delete, and edit parameters in the functionalities chosen as well as storing these parameters for future use. In order to verify the efficiency of the framework, some case studies are presented

(Non)Invariance of dynamical quantities for orbit equivalent flows

We study how dynamical quantities such as Lyapunov exponents, metric entropy, topological pressure, recurrence rates, and dimension-like characteristics change under a time reparameterization of a dynamical system. These quantities are shown to either remain invariant, transform according to a multiplicative factor or transform through a convoluted dependence that may take the form of an integral over the initial local values. We discuss the significance of these results for the apparent non-invariance of chaos in general relativity and explore applications to the synchronization of equilibrium states and the elimination of expansions

Epstein-Barr virus infection and chronic lymphocytic leukemia: a possible progression factor?

Epstein-Barr virus is pathogenically associated with a well defined group of lymphoid and epithelial tumors in which the virus directly drives transformation of infected cells. Recent evidence however indicates that this virus may infect a subpopulation of tumor cells in patients with chronic lymphocytic leukemia (CLL) and EBV infection has been also associated with Richter transformation in a fraction of cases. We herein review available data suggesting a possible role of EBV as a direct or micro-environmental progression factor in a subset of CLL