Clinical usefulness and safety in the early phase after a newly designed rotating-platform total knee arthroplasty: A prospective multicentre cohort study with a 2-year follow up.

BACKGROUND: This study aimed to assess the clinical results and safety of a newly designed rotating-platform posterior-stabilised total knee arthroplasty (TKA) in the early postoperative phase, within 2 years of follow up. METHODS: This prospective, multicentre cohort study included 100 consecutive patients who underwent rotating-platform posterior-stabilised (PS) TKA (Vanguard PSRP). After excluding dropouts, 93 patients were analysed. The objective Knee Society Score (KSS)-2011, subjective KSS-2011, knee range of motion, EuroQol 5 Dimension index, complications, and survival rates were assessed before TKA and at 6 months, 1 year, and 2 years postoperatively. The scores at each time-point were compared, and the survival rate was assessed with revision as the endpoint. To demonstrate non-inferiority, the clinical outcomes of patients who underwent rotating-platform PS TKA were compared with those collected retrospectively from 50 patients who underwent fixed-PS TKA (Vanguard PS), defined as the control group. RESULTS: All clinical outcomes at the final follow up significantly improved compared with their preoperative values (P < 0.001). The objective KSS-2011 was 90.0 ± 8.2 points, subjective KSS-2011 satisfaction was 30.7 ± 8.6 points, expectation was 10.4 ± 2.1 points, and functional activity was 74.0 ± 18.5 points at 2 years postoperatively. Complications included knee dislocation in one patient and surgical site infection in one patient. The survival rate was 99% at 2 years postoperatively. Clinical outcomes, complications, and survival rates of newly designed TKA were not statistically different compared with the control group. CONCLUSION: The newly designed rotating-platform PS TKA showed good clinical results and suitable safety during the early postoperative phase in this prospective multicentre cohort study.

[Septic arthritis and spondylitis].

Septic arthritis and spondylitis in elderly adult are uncommon disease. But symptoms and signs of septic arthritis and spondylitis are an important medical emergency, with high mortality and morbidity. Delayed or inadequate treatment can result in irreversible joint destruction and neurological condition. Early diagnoses as well as prompt and effective treatment are essential for avoiding severe outcomes. In spite of advances in diagnostic imaging techniques, the incidence of septic arthritis and spondylitis appears to have been increased. The aging of the population, the widespread use of immunosuppressant therapies, including systemic corticosteroids, cytokines and anticytokines, and growing resistance to conventional antibiotics seem to be the major cause.

In vivo detection of amyloid plaques in the mouse brain using the near-infrared fluorescence probe THK-265.

Noninvasive detection of amyloid-ß (Aß) deposits in the brain would be beneficial for an early and presymptomatic diagnosis of Alzheimer's disease (AD). We developed THK-265 as a candidate near-infrared fluorescence (NIRF) probe for the in vivo detection of amyloid deposits in the brain. The maximal emission wavelength of THK-265 was greater than 650nm and it showed high quantum yield and molar absorption coefficients. A fluorescence binding assay showed its high binding affinity to Aß fibrils (Kd = 97 nM). THK-265 clearly stained amyloid plaques in AD neocortical brain sections and showed a moderate log p value (1.8). After intravenous administration of THK-265 in amyloid-ß protein precursor (AßPP) transgenic mice, amyloid deposits in the brain were clearly labeled with THK-265. Furthermore, in vivo NIRF imaging demonstrated significantly higher fluorescence intensity in the brains of AßPP transgenic mice than in those of wild-type mice. As THK-265 showed profound hyperchromic effect upon binding to Aß fibrils, good discrimination between AßPP transgenic and wild-type mice was demonstrated even early after THK-265 administration. Furthermore, the fluorescence intensity of THK-265 correlated with amyloid plaque burden in the brains of AßPP transgenic mice. These findings strongly support the usefulness of THK-265 as an NIRF imaging probe for the noninvasive measurement of brain amyloid load.

The effect of selective cyclooxygenase-2 inhibitor on human osteoclast precursors to influence osteoclastogenesis in vitro.

The inducible prostaglandin synthesis enzyme, cyclooxygenase-2 (COX-2), is involved in bone resorption and osteoclastogenesis, and acts indirectly through prostaglandin E2 (PG E2) produced by osteoblastic cells. This study was undertaken to investigate whether celecoxib (a selective COX-2 inhibitor) has a direct effect on human osteoclast precursors to influence osteoclastogenesis in vitro. Human peripheral blood mononuclear cells (PBMCs) were cultured on glass coverslips and dentine slices with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage colony stimulating factor (M-CSF). COX inhibitors including celecoxib were added to the cultures. Osteoclast formation was assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), and the functional evidence of lacunar resorption pits on dentine slices was assessed. Celecoxib and indomethacin inhibited osteoclast formation and the extent of lacunar resorption in a dose-dependent manner, but the effect of indomethacin was less than that of celecoxib. Mofezolac affected neither the number of TRAP-positive MNCs nor the extent of lacunar resorption pits. These results indicate that celecoxib influences not only osteoclast formation through osteoblastic cells but also acts directly on circulating osteoclast precursors to influence human osteoclast differentiation. The effect of celecoxib on osteoclast precursors may be related to the COX-2 signal pathway.

Tacrolimus and cyclosporine A inhibit human osteoclast formation via targeting the calcineurin-dependent NFAT pathway and an activation pathway for c-Jun or MITF in rheumatoid arthritis.

In the present study, we aimed to determine whether tacrolimus (FK506) and cyclosporine A act directly on human osteoclast precursors obtained from patients with rheumatoid arthritis (RA) and influence monocyte-osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL) in vitro, the stage at which differentiation was affected and the manner in which tacrolimus or cyclosporine A affected the osteoclast signaling pathway. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF). Tacrolimus or cyclosporine A was added to these cultures to determine the effect on the osteoclast differentiation. Osteoclast formation was determined by assessing the number of tartrate resistant acid phosphatase (TRAP) staining cells and measuring the extent of lacunar resorption. The expression of osteoclast transcription factors, such as TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells c1 (NFATc1), c-Fos, c-Jun, microphthalmia transcription factor (MITF) and PU.1 in mononuclear cells (MNCs) was assayed by quantitative reverse transcription-polymerase chain reaction. Addition of tacrolimus or cyclosporine A resulted in a decrease in the number of TRAP-positive multinucleated cells (TRAP+ MNCs) and a decrease in the extent of lacunar resorption pit formation as compared to the control cultures; thus, human monocyte-osteoclast differentiation was more effectively inhibited at the late stage and addition of tacrolimus or cyclosporine A resulted in a decrease in the mRNA expression of NFATc1, c-Jun, and MITF at the late stage. Our results suggest that tacrolimus or cyclosporine A acts directly on human osteoclast precursors in RA patients and exerts their immunosuppressive effects on human monocyte-osteoclast formation via targeting both the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or MITF.

Infliximab acts directly on human osteoclast precursors and enhances osteoclast formation induced by receptor activator of nuclear factor kappaB ligand in vitro.

Infliximab is known to protect against the development of joint destruction. In the present study, we sought to determine whether Infliximab acts directly on human osteoclast precursors and influences monocyte-osteoclast differentiation induced by receptor activator of nuclear factor kappaB ligand (RANKL) in vitro. Peripheral blood mononuclear cells (PBMCs) isolated from rheumatoid arthritis (RA) patients and normal controls were cultured in the presence of RANKL and macrophage colony stimulating factor. Infliximab, antihuman tumor necrosis factor alpha (TNFalpha), antihuman TNF soluble receptor p55 (TNFR p55), and antihuman TNF soluble receptor p75 (TNFR p75) antibodies were added. Osteoclast formation was determined by assessing the number of tartrate-resistant acid phosphatase (TRAP) staining cells and the extent of lacunar resorption. Addition of Infliximab resulted in a marked increase in the number of TRAP-positive multinucleated cells (TRAP(+) MNCs) and in the extent of lacunar resorption compared with the control cultures. Antihuman TNFalpha antibody showed the same effect; however, the addition of neither TNFR p55 nor TNFR p75 antibody affected the extent of TRAP(+) MNCs and lacunar resorption. Our results suggest that infliximab acts directly on early osteoclast precursors, and stimulates osteoclast formation and lacunar resorption induced by RANKL in vitro.

Macrophages that have phagocytosed particles are capable of differentiating into functional osteoclasts.

The aim of the current study was to determine whether human macrophages that have phagocytosed particles are capable of differentiating into osteoclastic bone-resorbing cells. Macrophages isolated from human peripheral blood were cultured with latex particles in the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) on dentine slices and coverslips. After 24 h incubation, particles that had not yet been phagocytosed were removed by washing the slices. Histochemistry and immunohistochemistry was used to determine expression of macrophage and osteoclast markers and lacunae resorption, scanning electron microscopy, and transmission electron microscopy were used to examine cells with phagocytosed particles. Isolated macrophages on dentine slices were noted to contain a large number of particles inside, and no particles were identified outside of culture cells after washing. After 14 days of incubation, numerous tartrate-resistant acid phosphatase-positive multinucleated cells that contained particles in their cytoplasm, capable of extensive lacunae bone resorption, formed in these cultures. Our results clearly indicated that macrophages that have phagocytosed particles were still capable of differentiating into osteoclastic bone-resorbing cells. Macrophages that have phagocytosed wear particles in the pseudomembrane surrounding an implant not only produce cytokines but also may differentiate into functional osteoclasts, and influence bone resorption and loosening of a prosthesis.

Proinflammatory cytokine (TNFalpha/IL-1alpha) induction of human osteoclast formation.

TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in vitro. Recently, it has been demonstrated that these two cytokines directly induce osteoclastogenesis in mouse marrow cultures. This study determined whether TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis. The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.