Comparative retrieval analysis of a novel anatomic tibial tray backside: alterations in tibial component design and surface coating can increase cement adhesions and surface roughness

Background: With the Persona® knee system a novel anatomic total knee design was developed, which has no pre-coating, whereas the predecessor knee system is pre-coated with polymethylmethacrylate (PMMA). Joint registry data have shown no decrease in risk of aseptic revision of PMMA pre-coated tibial components compared with non-pre-coated implants. The aim of this retrieval study was to compare the amount of cement adhesions, geometry and surface features between the two knee designs and to correlate them with the underlying reason for revision surgery. / Methods: Retrieval analysis was performed of 15 NexGen® and 8 Persona® fixed-bearing knee implants from the same manufacturer retrieved from two knee revision centres. A photogrammetric method was used to grade the amount of cement attached to the tibial tray backside. The geometry and dimensions of the tibial trays, tray projections and peripheral lips were measured using digital callipers and compared between the two different designs. To measure the surface roughness on the backside of the tibial tray, a contact profilometer was used. To investigate differences between the two designs statistical analyses (t-test) were performed. / Results: All Persona® trays showed evidence of cement adhesion with a % area of 75.4%; half of the NexGen® trays had cement adhesions, with a mean value of 20%. There was a significant difference in the percentage of area covered by cement between the two designs (p < 0.001). Results from the contact profilometer revealed that Persona® and NexGen® tray backsides showed a similar lateral (1.36 μm and 1.10 μm) and medial (1.39 μm and 1.12 μm) mean surface roughness with significant differentiation (p < 0.05) of the lateral and medial roughness values between the two designs. Persona® stems showed a significantly higher mean surface roughness (1.26) compared to NexGen® stems (0.89; p < 0.05). / Conclusion: The novel anatomic knee system showed significantly more cements adhesions and a higher surface roughness which was most likely attributed to the most obvious design and coating alteration of the tibial tray. This study provides first retrieval findings of a novel TKA design recently introduced to the market

Therapeutic drug monitoring for everolimus in heart transplant recipients based on exposure-effect modeling

Everolimus, a proliferation signal inhibitor, is an immunosuppressant that targets the primary causes of progressive allograft dysfunction, thus improving the long-term outcome after heart transplantation. The present study investigated whether therapeutic drug monitoring (TDM) of everolimus would benefit heart transplant patients. Data from a twelve-month phase III trial comparing everolimus (1.5 or 3 mg daily) with azathioprine were used to evaluate everolimus pharmacokinetics, exposure-efficacy/safety and TDM prognostic simulations. Everolimus trough levels were stable in the first year post-transplant and averaged 5.2 +/- 3.8 and 9.4 +/- 6.3 ng/mL in patients treated with 1.5 and 3 mg/day, respectively. Cyclosporine trough levels were similar in all treatment groups. Biopsy-proven acute rejection (BPAR) was reduced with everolimus trough levels > or =3 ng/mL. Intravascular ultrasound (IVUS) analysis showed evidence of reduced vasculopathy at 12 months with increasing everolimus exposure. Unlike cyclosporine, increasing everolimus exposure was not related to a higher rate of renal dysfunction. The TDM simulation, which was based on two everolimus dose adjustments and an initial starting dose of 1.5 mg/day, showed that the simulated BPAR rate (with TDM) was 21% versus 26% in the group with fixed dosing. Therefore, TDM in heart transplantation could optimize immunosuppressive efficacy and reduce treatment-related toxicity