To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations.
Antioxidant containing UHMWPE particles induced similar levels of in vitro macrophage proliferation and in vivo inflammation in the mouse air pouch model as UHMWPE particles alone. Benefit of antioxidant in reducing wear particle induced inflammation requires further investigation. Wear particles derived from UHMWPE implants can provoke inflammatory reaction and cause osteolysis in the bone, leading to aseptic implant loosening. Antioxidants have been incorporated into UHMWPE implants to improve their long term oxidative stability. However it is unclear if the anti-inflammatory property of the antioxidant could reduce UHMWPE particle induced inflammation. This study evaluated the effect of cyanidin and vitamin E on UHMWPE induced macrophage activation and mouse air pouch inflammation.Summary Statement
Introduction
At present we conduct a clinical study on four bearing combinations in hip arthroplasty. Our main purpose is to assess changes in bone mineral density (BMD), function of the joint, and to monitor serum concentrations of prosthetic metals as well as plasma concentrations of a range of cytokines, chemokines, and related proteins during a ten-year follow-up. This is done in order to evaluate the potential role of these variables as predictors of dysfunction or loosening of the arthroplasty. A total of 300 patients were randomly allocated to four bearing combinations. Four years after surgery the following number of patients were available for follow-up: Type A: Zirconia ceramic head, polyethylene cup insert in the Universal RingLoc metal backed shell (n=50); Type B: Cobalt-Chrome-Molybdenum head and cup insert in the Universal RingLoc metal backed shell (n=57); Type C: Zirconia ceramic head, polyethylene moulded on the Titanium shell of the Asian cup (n=55); Type D: Alumina head and cup insert in the Universal RingLoc metal backed shell (n=45). A BiMetric Titanium-Aluminium-Vanadium (Ti6Al4V) stem was used with all four combinations (n=207). All patients, but two with rheumatoid arthritis, had primary osteoarthritis or avascular necrosis of the femoral head. Five patients had astma and eight had diabetes. At the time of surgery the groups were equal with regard to age, gender distribution, body height and weight, side of arthroplasty, and BMD in all seven Gruen zones. Harris Hip Score prior to arthroplasty was equally low in all groups (mean ± SD) (42 ± 17), and increased in all groups, with no significant differences between them (87 ± 10). At follow-up there was a significant decrease in BMD in all Gruen zones ranging from −1.9 % in zone 4 in group C to −21.7% in zone 7 in group D. However, there were no significant differences between groups. There were significantly higher blood concentrations of Chromium and Cobalt in group B patients compared to all other groups (p <
0.001). Plasma concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, TNF-α, TNF-R1, VEGF, OPG, GM-CSF, or TGF-β1 did not differ significantly between groups. Instead, elevated levels of IL-1β, IL-10 and TNF-R1 were found in patients with asthma. IL-6, TNF-α and VEGF were elevated in patients with rheumatoid arthritis or asthma. IL-8 and TGF-β1 were higher in patients with osteoarthritis, whereas GM-CSF was high in patients with asthma or diabetes.
