Comparison of tissue pharmacokinetics of esflurbiprofen plaster with flurbiprofen tablets in patients with knee osteoarthritis: A multicenter randomized controlled trial.

This open-label, multicenter, prospective, randomized controlled trial aimed to determine the effectiveness of esflurbiprofen plaster (SFPP) and flurbiprofen tablets (FPTs) on knee osteoarthritis in patients scheduled for total knee arthroplasty by comparing the transfer of esflurbiprofen and flurbiprofen to tissues and fluids. Thirty-eight patients were randomly assigned in a 1:1 ratio to receive SFPP or FPT. Both groups were then divided into four subgroups, according to whether they received the final dose of SFPP or FPT at 2, 7, 12, or 24 h before planned surgery. The primary endpoints were the esflurbiprofen concentrations in synovium, synovial fluid, and plasma. Areas under concentration-time curves (AUC0-24 h ) of esflurbiprofen were calculated for each group. Pain was assessed using a numeric rating scale (NRS) 7 days before and immediately before surgery. The AUC0-24 h in the synovium were 4401.24 and 4862.70 ng·h/g in the SFPP and FPT groups, respectively. Maximum esflurbiprofen concentrations were observed in the synovium, synovial fluids, and plasma after SFPP application for 12 h. The NRS results indicated a long-lasting effect of SFPP. The AUC of the synovial esflurbiprofen concentration of SFPP indicated that the SFPP is transferred to the synovium and synovial fluid in high concentration. The efficient deep-tissue transfer of esflurbiprofen suggests that its pharmacokinetic characteristics differ from those of conventional topical NSAIDs. This study was prospectively registered in the Japan Registry of Clinical Trials (registration number: jRCTs031180228).

[Articular cartilage regeneration with synovial mesenchymal stem cells].

Cell transplantation has shown to be a promising strategy to repair cartilage defects. Mesenchymal stem cells derived from synovium have been shown to be a superior cell source for cartilage regeneration to those from other mesenchymal tissues due to their higher rates of colony formation, proliferation potential with autologous serum, and in vitro/vivo chondrogenic potentials. We have found that approximately 60% of synovial mesenchymal stem cells placed on cartilage defects adhered to the defect within 10 min, and the addition of magnesium enhanced this percentage further, which resulted in better cartilage regeneration. Based upon several basic research studies performed in our lab, we have begun the transplantation of synovial stem cells arthroscopically in a clinical study for the treatment of cartilage defects. To date, no adverse events have been reported in the study. Regeneration of cartilage, reduction in defect size and an improvement of symptoms have been obtained in most patients over the last 3 years.

Intramedullary screw fixation with bone autografting to treat proximal fifth metatarsal metaphyseal-diaphyseal fracture in athletes: a case series.

BACKGROUND: Delayed unions or refractures are not rare following surgical treatment for proximal fifth metatarsal metaphyseal-diaphyseal fractures. Intramedullary screw fixation with bone autografting has the potential to resolve the issue. The purpose of this study was to evaluate the result of the procedure. METHODS: The authors retrospectively reviewed 15 athletes who underwent surgical treatment for proximal fifth metatarsal metaphyseal-diaphyseal fracture. Surgery involved intramedullary cannulated cancellous screw fixation after curettage of the fracture site, followed by bone autografting. Postoperatively, patients remain non weight-bearing in a splint or cast for two weeks and without immobilization for an additional two weeks. Full weight-bearing was allowed six weeks postoperatively. Running was permitted after radiographic bone union, and return-to-play was approved after gradually increasing the intensity. RESULTS: All patients returned to their previous level of athletic competition. Mean times to bone union, initiation of running, and return-to-play were 8.4, 8.8, and 12.1 weeks, respectively. Although no delayed unions or refractures was observed, distal diaphyseal stress fractures at the distal tip of the screw occurred in two patients and a thermal necrosis of skin occurred in one patient. CONCLUSIONS: There were no delayed unions or refractures among patients after carrying out a procedure in which bone grafts were routinely performed, combined with adequate periods of immobilization and non weight-bearing. These findings suggest that this procedure may be useful option for athletes to assuring return to competition level.

Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.

INTRODUCTION: Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect. METHODS: For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined. RESULTS: Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment. CONCLUSION: Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.