Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

Employing Distances in Design-based Spatial Estimation

In the last couple of decades we assisted to a reappraisal of spatial design-based techniques. Usually the spatial information regarding the spatial location of the individuals of a population has been used to develop efficient sampling designs. This thesis aims at offering a new technique for both inference on individual values and global population values able to employ the spatial information available before sampling at estimation level by rewriting a deterministic interpolator under a design-based framework. The achieved point estimator of the individual values is treated both in the case of finite spatial populations and continuous spatial domains, while the theory on the estimator of the population global value covers the finite population case only. A fairly broad simulation study compares the results of the point estimator with the simple random sampling without replacement estimator in predictive form and the kriging, which is the benchmark technique for inference on spatial data. The Monte Carlo experiment is carried out on populations generated according to different superpopulation methods in order to manage different aspects of the spatial structure. The simulation outcomes point out that the proposed point estimator has almost the same behaviour as the kriging predictor regardless of the parameters adopted for generating the populations, especially for low sampling fractions. Moreover, the use of the spatial information improves substantially design-based spatial inference on individual values.

Outcomes feto-neonatali dell'infezione non primaria da Cytomegalovirus

OBIETTIVI: Valutazione del rischio di trasmissione verticale e delle conseguenze dell’infezione congenita da cytomegalovirus (CMV) in caso di infezione non primaria versus l’outcome delle gravidanze complicate da infezione primaria. MATERIALI E METODI: Studio retrospettivo di coorte di gravide con infezione recente da CMV diagnosticata c/o il nostro centro negli anni 2000-2013. Le pazienti sono state suddivise in 2 gruppi in base al risultato delle indagini sierologiche (avidità IgG e immunoblot): il primo con profilo sierologico compatibile con infezione non primaria e l'altro compatibile con infezione primaria da CMV. Sono stati confrontati il rischio di trasmissione e di infezione congenita sintomatica nei due gruppi. RISULTATI: Il follow-up è risultato disponibile in 1122 casi di cui 182 con infezione materna non-primaria e 940 con infezione primaria materna. L’infezione congenita è stata diagnosticata in 7 (3.86%) feti/neonati nei casi di infezione non primaria e in 217 (23%) feti/neonati nei casi di infezione primaria (p<0.001). Tra gli infetti, erano sintomatici 43 (19,8%) e 3 (42,8%) rispettivamente nell’infezione primaria e non primaria. COMMENTO: La preesistente immunità materna offre una protezione contro la trasmissione intrauterina nell’infezione da CMV ma non protegge dalla malattia congenita sintomatica.