Reduced hip bone mineral density is associated with high levels of calciprotein particles in patients with Fabry disease.

Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. PURPOSE: Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). METHODS: We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an age-matched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. RESULTS: CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex- and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. CONCLUSION: Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.

Outcomes of simultaneous heart-kidney and lung-kidney transplantations: the Australian and New Zealand experience.

BACKGROUND: Heart or lung transplantation alone in individuals with significant pre-existing renal impairment results in high mortality and morbidity. Simultaneous heart-kidney (SHK) or simultaneous lung-kidney (SLK) transplantation may be considered in patients with dual organ failure not suitable for single organ transplantation. AIM: We aimed to outline the Australian and New Zealand experience of SHK and SLK transplantations, focussing on patient characteristics and survival. METHODS: We analysed all SHK and SLK transplants performed in four centres across Australia and New Zealand between 1990 and 2014. RESULTS: Over the study period, 35 SHK and 3 SLK transplants were performed across 4 transplant centres. Mean age at transplantation for SHK transplants was 45 years, and for SLK transplant was 27 years. The most common aetiology of renal failure was glomerulonephritis. Most SHK transplant patients (77%) required renal replacement therapy prior to transplantation, with only one of the three patients undergoing SLK transplant, dialysis dependent. One-year survival for the cohort was 79%, which is lower than reported for single organ transplantation. However, 5- and 10-year survivals of 76% and 68%, respectively, were comparable. Isolated renal graft loss was seen in five patients, with only one patient successfully re-transplanted and the rest commencing dialysis. CONCLUSION: The Australian and New Zealand experience of SHK and SLK includes 38 patients with a high 1-year mortality, but excellent 5- and 10-year survivals. Based on this, it seems reasonable to continue to offer combined organ transplantation to select patients with dual organ failure.

Improvement in the morphology of Ti-based surfaces: a new process to increase in vitro human osteoblast response.

Surface roughness has been shown to be an influencing parameter for cell response. In this experience we attempted to compare the effect of roughness organization of Ti6A14V or pure titanium substrates on human osteoblast (hOB) response (proliferation, adhesion). Surface roughness was extensively analyzed at scales above the cell size (macro-roughness) or below the cell size (micro-roughness) by calculation of relevant classic amplitude parameters (Ra, Rt) and original frequency parameters (Order, Delta). We developed a new process to prepare isotropic surfaces (electro-erosion), which were compared to isotropic surfaces obtained by polishing and anisotropic surfaces obtained by machine-tooling. The hOB response on electro-eroded (EE) Ti6A14V surfaces or pure titanium (Ti) surfaces was largely increased when compared to polished or machine-tooled surfaces after 21 days of culture. Moreover, the polygonal morphology of hOB on these EE surfaces was very close to the aspects of hOB in vivo on human bone trabeculae. By a complete description of the surface topography of EE surfaces, we concluded that when the topography was considered below the cell scale, hOB appreciated their isotropic smooth aspect, although when the topography was considered above the cell scale they appreciated their rough isotropic 'landscape' formed by many 'bowl-like nests' favouring cell adhesion and growth. Electro-erosion is a promising method for preparation of bone implant surfaces, as it could easily be applied to preparation of most biomaterials with complex geometries.