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Abstract Background Obesity is a risk factor for knee arthritis. Total knee arthroplasty is the definitive surgical treatment of this disease. Therefore, a high percentage of subjects treated are overweight. Since 2000 in the Emilia-Romagna Region the Register of Orthopedic Prosthetic Implantology, RIPO, has recorded data of all the primary and revision operations performed on the knee; height and weight of patients at the time of surgery have also been recorded. Methods To understand how overweight and obesity affect the outcome of knee arthroplasty, a population of subjects treated with cemented total knee arthroplasty between 2000 and 2005 was studied. 9735 knee prostheses were implanted in 8892 patients; 18.9% of the patients were normal weight, 48.2% were overweight (25 < Body Mass Index 40). Mean and range of follow-up were respectively 3.1 and 1.5–6 yrs. Implant failure was defined as the exchange of at least one component for whatever reason. Results In normal weight patients there were 36 failures out of 1840 implants (1.96%), in overweight patients there were 87 out of 4692 (1.85%), in obese 59 out of 3031 (1.94%), and in morbidly obese there were 4 out of 172 (2.3%). The mean time to failure for each class was 1.57, 1.48, 1.60, 1.77 yrs. Cox regression analyses showed that the risk of implant failure was not influenced by BMI, absolute body weight, or sex. Conversely, an increased failure risk was observed in mobile meniscus prostheses in comparison with those with a fixed meniscus (Rate Ratio 1.88); an increased failure risk was also related to age (Rate Ratio 1.05 per year). These results were also confirmed when considering septic loosening as the end-point. There were no differences in the rate of perioperative complications and death in the 4 classes of BMI. Conclusion In conclusion, cemented knee prostheses, implanted in patients with arthritis do not have significantly different rates of survival or perioperative complications in obese subjects compared with normal weight subjects, at least up to 5 years after surgery. The conclusion also applies to subjects affected by morbid obesity, altough this findings should be regarded with caution due to the small sample examined.

Background: Tuberculosis (TB) represents a worldwide cause of mortality (it infects one third of the world’s population) affecting mostly developing countries, including India, and recently also developed ones due to the increased mobility of the world population and the evolution of different new bacterial strains capable to provoke multidrug resistance phenomena. Currently, antitubercular drugs are unable to eradicate subpopulations of Mycobacterium tuberculosis (MTB) bacilli and therapeutic vaccinations have been postulated to overcome some of the critical issues related to the increase of drug-resistant forms and the difficult clinical and public health management of tuberculosis patients. The Horizon 2020 EC funded project “In Silico Trial for Tuberculosis Vaccine Development” (STriTuVaD) to support the identification of new therapeutic interventions against tuberculosis through novel in silico modelling of human immune responses to disease and vaccines, thereby drastically reduce the cost of clinical trials in this critical sector of public healthcare. Results: We present the application of the Universal Immune System Simulator (UISS) computational modeling infrastructure as a disease model for TB. The model is capable to simulate the main features and dynamics of the immune system activities i.e., the artificial immunity induced by RUTI® vaccine, a polyantigenic liposomal therapeutic vaccine made of fragments of Mycobacterium tuberculosis cells (FCMtb). Based on the available data coming from phase II Clinical Trial in subjects with latent tuberculosis infection treated with RUTI® and isoniazid, we generated simulation scenarios through validated data in order to tune UISS accordingly to STriTuVaD objectives. The first case simulates the establishment of MTB latent chronic infection with some typical granuloma formation; the second scenario deals with a reactivation phase during latent chronic infection; the third represents the latent chronic disease infection scenario during RUT® vaccine administration. Conclusions: The application of this computational modeling strategy helpfully contributes to simulate those mechanisms involved in the early stages and in the progression of tuberculosis infection and to predict how specific therapeutical strategies will act in this scenario. In view of these results, UISS owns the capacity to open the door for a prompt integration of in silico methods within the pipeline of clinical trials, supporting and guiding the testing of treatments in patients affected by tuberculosis. [ABSTRACT FROM AUTHOR]

Innovations in information and communication technology infuse all branches of science, including life sciences. Nevertheless, healthcare is historically slow in adopting technological innovation, compared with other industrial sectors. In recent years, new approaches in modelling and simulation have started to provide important insights in biomedicine, opening the way for their potential use in the reduction, refinement and partial substitution of both animal and human experimentation. In light of this evidence, the European Parliament and the United States Congress made similar recommendations to their respective regulators to allow wider use of modelling and simulation within the regulatory process. In the context of in silico medicine, the term ' in silico clinical trials' refers to the development of patient-specific models to form virtual cohorts for testing the safety and/or efficacy of new drugs and of new medical devices. Moreover, it could be envisaged that a virtual set of patients could complement a clinical trial (reducing the number of enrolled patients and improving statistical significance), and/or advise clinical decisions. This article will review the current state of in silico clinical trials and outline directions for a full-scale adoption of patient-specific modelling and simulation in the regulatory evaluation of biomedical products. In particular, we will focus on the development of vaccine therapies, which represents, in our opinion, an ideal target for this innovative approach. [ABSTRACT FROM AUTHOR]