Fungal Arthritis of a Lumbar Facet Joint Because of Candida albicans: A Case Report.

CASE: A 73-year-old man who was treated in our hospital for pyelonephritis because of left ureteral stones and fungemia was referred to our orthopaedic department for persistent right lower-back pain. Magnetic resonance imaging and computed tomography findings showed pyogenic arthritis of the right L4/5 facet joint with a paraspinal muscle abscess. Based on cultures of samples aspirated from the lesions, we diagnosed the patient with fungal arthritis of the lumbar facet joint. We treated him conservatively with an antifungal agent for a year, and the infection resolved. CONCLUSION: This is the first report of hematogenous fungal arthritis of a lumbar facet joint.

Predictive factors of non-treatment and non-persistence to osteoporosis medication after fragility hip fractures at 3 years after discharge: a multicentre, prospective cohort study in the northern Kyushu district of Japan.

We examined osteoporosis medication use and factors affecting persistence in 497 patients with fragility hip fractures. Only 25.5% of patients received continuous medication for 3 years, and 44.1% of patients received no treatment. Low Barthel index at discharge was a risk factor for both non-treatment and non-persistence to osteoporosis medication. PURPOSE: Fragility hip fractures (FHF) caused by osteoporosis decrease the quality of life and worsen life expectancy. Use of osteoporosis medication may be an efficient method in the prevention of secondary FHF. However, previous studies have reported low rates of osteoporosis medication and persistence after FHF. This study aimed to evaluate osteoporosis medication use and factors affecting persistence in patients with FHF in the northern Kyushu area of Japan. METHODS: A total of 497 FHF patients aged ≥ 60 years with a 3-year follow-up were included. We prospectively collected data from questionnaires sent every 6 months regarding compliance with osteoporosis medication. We compared baseline characteristics among three groups: no treatment (NT), no persistence (NP), and persistence (P), and conducted multivariable regression models to determine covariates associated with non-treatment (NT vs. NP/P) and non-persistence (NP vs. P). RESULTS: There were 219 (44.1%), 151 (30.4%), and 127 (25.5%) patients in the NT, NP, and P groups, respectively. Factors associated with non-treatment were male sex, chronic kidney disease, no previous osteoporosis treatment, and low Barthel index (BI) at discharge. The only factor associated with non-persistence was a low BI at discharge. Factors associated with a low BI at discharge were male sex, older age, trochanteric fracture, and surgical delay. CONCLUSION: Low BI at discharge is a risk factor for both non-treatment and non-persistence to osteoporosis medication. Therefore, appropriate interventions to improve BI may result in persistence to osteoporosis medication.

Cylinder-Shaped Bone Graft for Scaphoid Nonunion.

BACKGROUND: Wedge-shaped bone grafts that are internally fixed by a Herbert-type screw are a well-established surgical treatment for scaphoid nonunion. A procedure using cylinder-shaped bone grafts was also reported, but preoperative wrist functions were not assessed. In addition, it was not reported whether the humpback deformity of the scaphoid nonunion was corrected. The purpose of the current study was to compare preoperative wrist functions in cases of scaphoid nonunion with those observed at final follow-up, using cylinder-shaped bone grafts The humpback deformity of the scaphoid nonunion was also evaluated. METHODS: We conducted a retrospective study to examine operative outcomes from 2008 to 2015. Twelve wrists in 12 patients (average age, 41 years; range, 17-67), with a mean follow-up of 19 months, were included in the current study. Cylinder-shaped bone grafts were obtained from the iliac crest with a newly designed trephine and fixed with a Herbert-type screw. We reviewed both the preoperative wrist functions and those obtained at final follow-up. RESULTS: Union was achieved in 11 of 12 nonunion cases. Preoperative wrist functions, except for the range of wrist motion, significantly improved by final follow-up. CONCLUSIONS: We conclude that the use of cylinder-shaped bone grafts improves preoperative wrist functions in cases of scaphoid nonunion.

Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in Ewing Family Tumors.

The chromosomal translocation t(11;22)(q24;q12) generates the EWS-Fli1 fusion gene, which contributes to the development of Ewing Family Tumors (EFTs). Although p53 mutations are found only in 5-20% of EFTs, the p53 pathway is thought to be abrogated in EFTs. The role of EWS-Fli1 in the p53 pathway in the tumor is still poorly understood. In this study, using immunoprecipitation and co-localization, we show that EWS-Fli1 interacts with p53 within the nucleus in vivo. The introduction of EWS-Fli1 resulted in significant reduction of promoter activities and mRNA levels of p21 and mdm2, meanwhile it canceled p53-dependent growth suppression. In contrast, knockdown of EWS-Fli1 expression mediated by small interfering RNAs (siRNA) also augmented the induction of p21 and mdm2 in response to DNA damage. Furthermore, using serial deletion constructs of the EWS-Fli1 fusion protein, we determined that EWS-Fli1 binding to p53 as well as inhibition of p21 and mdm2 promoter activities was mediated by its N-terminal domain (amino acid residues 65-109). These observations suggest that the N-terminal region of EWS-Fli1 might associate with p53 and impair its transcriptional activity, subsequently inhibiting the expression of its downstream genes. These results might provide new insight into the oncogenesis of EFTs by EWS-Fli1 via the inhibition of p53 function.

Accuracy of image-free navigation for severely deformed knees.

This study evaluated the accuracy of an image-free navigated total knee arthroplasty (TKA) system when used to align deformed tibia bone models. The accuracy was assessed in normal, 10 degrees varus, 20 degrees varus, 10 degrees valgus, and 20 degrees valgus tibia bone models (a total of five tibial models) by direct measurement of the navigated cutting guide. The mean angular errors in the tibial mechanical axes of the normal, 10 degrees, and 20 degrees varus models, respectively, were 0.0 degree, 0.7 degree varus, and 2.4 degrees varus. Thus, the errors seen with the two varus models were significantly larger than that associated with the normal model. The mean angular errors were 0.1 degree varus and 0.4 degree valgus in the 10 degrees and 20 degrees valgus models, respectively. These errors were not significantly different from those obtained with the normal model. These results suggest that in varus-deformed knees, image-free navigation has a tendency to cut the tibia in varus. This fact is considered to be one of the reasons for the lack of superiority of TKA alignment in severely deformed knees when using image-free navigation. Therefore, special attention must be paid when using image-free navigation TKA in such cases.

Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in chondrosarcoma cell lines.

BACKGROUND: Since chondrosarcoma has a high resistance to conventional chemotherapy and radiotherapy, surgical resection is currently the only effective treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but have not been tested in chondrosarcoma. MATERIALS AND METHODS: We investigated the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability assay, Western blot, flow cytometric analysis and electron microscopy. RESULTS: SAHA inhibited the growth of chondrosarcoma cell lines and induced apoptosis in SW1353 with a cleaved-PARP expression and sub-G1 fragmentation according to flow cytometric analysis. On the other hand, in RCS and OUMS-27, SAHA induced autophagy-associated cell death as shown by the detection of autophagosome-specific protein and specific ultrastructural morphology in the cytoplasm. In addition, SAHA significantly inhibited tumor growth in an in vivo xenograft model. CONCLUSION: These results suggest that SAHA might be a promising agent for performing clinically useful chemotherapy against chondrosarcomas.

Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing's family tumor cells.

Multimodal therapies play important roles in the treatment of osteosarcoma (OS) and Ewing's family of tumors (EFTs), two most frequent malignant bone tumors. Although the clinical outcome of primary OS and EFTs is greatly improved, the relapsed cases often are associated with multidrug resistance of the tumors and the prognosis of these patients is still poor. Flavopiridol, a pan cyclin-dependent kinase (CDK) inhibitor is a novel antitumor agent that can induce cell cycle arrest and apoptosis in many cancer cells. However, there have been no studies about the effects of flavopiridol on drug-resistant OS and EFTs. Here, we demonstrated that flavopiridol induced the cleavage of poly-ADP-ribose polymerase (PARP) in a time and dose dependent manner in adriamycin-resistant OS and EFTs cells expressing P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP(1)) as effectively as in their parental cells. Our data also showed that flavopiridol caused the release of mitochondrial cytochrome c and the activation of caspase-9, caspase-8 and caspase-3, with an increase ratio of the proapoptotic protein level (Bax) to the antiapoptotic protein level (Bcl-2 and Bcl-X(L)), while apoptosis was inhibited by pan caspase inhibitor (Z-VAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK), not by caspase-8 inhibitor (Z-IETD-FMK). The treatment with flavopiridol further inhibited the tumor growth in mouse models of the drug-resistant OS and EFTs. These results suggest that flavopiridol might be promising in clinical therapy for the relapsed OS and EFTs.

Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is overexpressed in several human cancers, and induces survival, proliferation and motility of cells in culture. Phosphorylation of FAK has been studied extensively in vitro, but little is known about its regulation during tumor invasion in vivo. In the current study, green fluorescent protein (GFP) was expressed stably in an invasive murine fibrosarcoma cell line for the purpose of discrimination between tumor and normal cells. Under fluorescence microscopy, the tumor was highly fluorescent, and the margin between the tumor and normal tissue was clearly demarcated. Using this invasion model, we showed localization of pY397-FAK expression in the infiltrative edge of tumors. We reproduced local invasion in vivo using a tumor tissue culture method in a three dimensional collagen gel. Phosphorylation of FAK is also upregulated in invading fibrosarcoma cells under in vitro conditions. Expression of the FAK C-terminal domain termed FRNK (FAK-related non-kinase) in 2,472 cells decreased FAK phosphorylation without changing total FAK levels. FRNK inhibited the motility of 2,472 cells, and reduced invasion in vitro. Although FRNK did not affect cell growth, it inhibited experimental metastases in syngenic mice. These results demonstrate that the phosphorylation of FAK might be specifically upregulated in invading fibrosarcoma cells and regulate their invasion and metastasis.