Comparison of the clinical outcomes of intramedullary nailing between impending and completed pathological fractures caused by metastatic femoral tumors from solid cancers.

BACKGROUND: We examined the treatment outcomes following intramedullary nailing in patients with metastatic femoral tumors, excluding those from hematological malignancies. METHODS: We retrospectively evaluated treatment outcomes following intramedullary nailing between patients who underwent preventative surgery compared with those who had surgery following pathological fracture. Patients who underwent preventative surgery (Mirels' score ≥8) were allocated to the impending fracture group (n = 11) and those who underwent surgery after pathological fracture were allocated to the completed fracture group (n = 20). RESULTS: Duration of surgery was significantly shorter in the impending fracture group than in the completed fracture group. Median blood loss was significantly less, and the median duration of hospital stay was significantly shorter in the impending fracture group than in the completed fracture group. Among patients who died following surgery, the median postoperative survival duration was significantly longer in the impending fracture group than in the completed fracture group. Significantly more patients regained walking function in the impending fracture group than in the completed fracture group. Regarding complications, infection occurred in one patient in the completed fracture group. No implant damage was observed in either group. CONCLUSIONS: Patients with metastatic femoral tumors who underwent intramedullary nailing in the impending fracture group had better postoperative survival and gait function, less blood loss, and shorter durations of surgery and hospital stay than those in the completed fracture group. These findings indicate the importance of early diagnosis and treatment and value of treatment prior to fracture occurrence.

Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization.

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

Development of Injectable Polydactyly-Derived Chondrocyte Sheets.

We are conducting a clinical study of the use of allogeneic polydactyly-derived chondrocyte sheets (PD sheets) for the repair of articular cartilage damage caused by osteoarthritis. However, the transplantation of PD sheets requires highly invasive surgery. To establish a less invasive treatment, we are currently developing injectable fragments of PD sheets (PD sheets-mini). Polydactyly-derived chondrocytes were seeded in RepCell™ or conventional temperature-responsive inserts and cultured. Cell counts and viability, histology, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), and flow cytometry were used to characterize PD sheets-mini and PD sheets collected from each culture. To examine the effects of injection on cell viability, PD sheets-mini were tested in four experimental conditions: non-injection control, 18 gauge (G) needle, 23G needle, and syringe only. PD sheets-mini produced similar amounts of humoral factors as PD sheets. No histological differences were observed between PD sheets and PD sheets-mini. Except for COL2A1, expression of cartilage-related genes did not differ between the two types of PD sheet. No significant differences were observed between injection conditions. PD sheets-mini have characteristics that resemble PD sheets. The cell viability of PD sheets-mini was not significantly affected by needle gauge size. Intra-articular injection may be a feasible, less invasive method to transplant PD sheets-mini.

Transcriptomic and Proteomic Analyses Reveal the Potential Mode of Action of Chondrocyte Sheets in Hyaline Cartilage Regeneration.

Chondrocyte sheet transplantation is a novel and promising approach to treating patients who have cartilage defects associated with osteoarthritis. Hyaline cartilage regeneration by autologous chondrocyte sheets has already been demonstrated in clinical research. In this study, the efficacy of polydactyly-derived chondrocyte sheets (PD sheets) as an allogeneic alternative to standard chondrocyte sheets was examined using an orthotopic xenogeneic transplantation model. In addition, the expression of genes and the secreted proteins in the PD sheets was analyzed using a microarray and a DNA aptamer array. The efficacy of PD sheets with respect to cartilage defects was assessed using histological scores, after which the expressions of genes and proteins exhibiting a correlation to efficacy were identified. Enrichment analysis of efficacy-correlated genes and proteins showed that they were associated with extracellular matrices, skeletal development, and angiogenesis. Eight genes (ESM1, GREM1, SERPINA3, DKK1, MIA, NTN4, FABP3, and PDGFA) exhibited a positive correlation with the efficacy of PD sheets, and three genes (RARRES2, APOE, and PGF) showed a negative correlation for both transcriptomic and proteomic analyses. Among these, MIA, DKK1, and GREM1 involved in skeletal development pathways and ESM1 involved in the angiogenesis pathway exhibited a correlation between the amount of secretion and efficacy. These results suggest that these secreted factors may prove useful for predicting PD sheet efficacy and may therefore contribute to hyaline cartilage regeneration via PD sheets.

Comparison of properties determined using electromechanical assessment (Arthro-BST™) with macroscopic and histological properties in symptomatic human articular cartilage of the hip.

BACKGROUND: Cartilage degeneration is assessed using various methods. Although macroscopic evaluation can directly measure cartilage degeneration, it cannot accurately assess cartilage properties. Histological examination is one of the most accurate methods for evaluating cartilage degeneration. However, it is invasive and requires collection of cartilage tissue. In contrast, the Arthro-BST™ probe can assess cartilage properties noninvasively. This study aimed to evaluate the effectiveness of the Arthro-BST in assessing cartilage degeneration by comparing macroscopic (International Cartilage Repair Society [ICRS] classification) and histological evaluations (modified Mankin score and Osteoarthritis Research Society International [OARSI] histological grade). METHODS: Fourteen femoral heads were excised from 13 patients during surgery to treat hip osteoarthritis or femoral fracture. The ICRS score was used for macroscopic evaluation of cartilage degeneration. The Arthro-BST was applied at sites matching the areas of cartilage damage. The sites assessed using the ICRS classification and Arthro-BST were evaluated histologically (modified Mankin score and OARSI histological grade), and these were compared with the Arthro-BST results. RESULTS: The ICRS classification identified significant differences between grades 1 and 3 (p < 0.01), between grades 1 and 4 (p < 0.01), between grades 2 and 3 (p < 0.01), and between grades 2 and 4 (p < 0.01). Significant correlations were observed between the Arthro-BST results and the ICRS score, modified Mankin score (structure, cellularity, matrix staining, total score), and OARSI histological grade. CONCLUSIONS: In the assessment of hip osteoarthritis, the Arthro-BST results correlated with those of macroscopic and histological evaluations. The Arthro-BST is useful for assessing hip osteoarthritis and may be helpful for noninvasive assessment of cartilage degeneration.

Characteristics of autologous protein solution and leucocyte-poor platelet-rich plasma for the treatment of osteoarthritis of the knee.

Recently, platelet-rich plasma (PRP) has received attention as a treatment for patients with osteoarthritis of the knee (OAK), a chronic degenerative disease, to bridge the gap between conservative and surgical treatments. Here, we investigated the differences in the humoral factors present in two types of PRP purified using the Autologous Protein Solution (APS) kit (group Z; leucocyte-rich PRP) or the Cellaid Serum Collection Set P type (group J; leucocyte-poor [LP]-PRP). Differences in humoral factors between healthy subjects (n = 10) and OAK patients (n = 12; group Z = 6, group J = 6), and the relationship between humoral factors and clinical outcome scores were investigated. Both anti-inflammatory and inflammatory cytokines were highly enriched in APS. The concentrations of tumour necrosis factor (TNF)-α, platelet-derived growth factor, fibroblast growth factor, soluble TNF-receptor 2, soluble Fas and transforming growth factor-ß1 were higher in group Z, while the total amounts were higher in group J. The concentration of interleukin-1 receptor antagonist was positively correlated with the magnitude of change in the clinical outcome score and may contribute to improving knee-joint function. This is the first description of the humoral factors in APS and LP-PRP prepared from healthy subjects or OAK patients of Asian descent.