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Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin., Methods: In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 10 6 DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of PTGS2 , TNFAIP6, PRG4, BMP2, and BMP6 under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of ADAMTS4 and IL-6 were evaluated., Results: Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as PTGS2 , TNFAIP6 , and BMP2 , under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of ADAMTS4 and IL6 in synovial fibroblasts., Conclusions: The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment., Competing Interests: None., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Background: Mesenchymal stem cells (MSCs) are known to have different differentiation potential depending on the tissue of origin. Dedifferentiated fat cells (DFATs) are MSC-like multipotent cells that can be prepared from mature adipocytes by ceiling culture method. It is still unknown whether DFATs derived from adipocytes in different tissue showed different phenotype and functional properties. In the present study, we prepared bone marrow (BM)-derived DFATs (BM-DFATs), BM-MSCs, subcutaneous (SC) adipose tissue-derived DFATs (SC-DFATs), and adipose tissue-derived stem cells (ASCs) from donor-matched tissue samples. Then, we compared their phenotypes and multilineage differentiation potential in vitro. We also evaluated in vivo bone regeneration ability of these cells using a mouse femoral fracture model., Methods: BM-DFATs, SC-DFATs, BM-MSCs, and ASCs were prepared from tissue samples of knee osteoarthritis patients who received total knee arthroplasty. Cell surface antigens, gene expression profile, and in vitro differentiation capacity of these cells were determined. In vivo bone regenerative ability of these cells was evaluated by micro-computed tomography imaging at 28 days after local injection of the cells with peptide hydrogel (PHG) in the femoral fracture model in severe combined immunodeficiency mice., Results: BM-DFATs were successfully generated at similar efficiency as SC-DFATs. Cell surface antigen and gene expression profiles of BM-DFATs were similar to those of BM-MSCs, whereas these profiles of SC-DFATs were similar to those of ASCs. In vitro differentiation analysis revealed that BM-DFATs and BM-MSCs had higher differentiation tendency toward osteoblasts and lower differentiation tendency toward adipocytes compared to SC-DFATs and ASCs. Transplantation of BM-DFATs and BM-MSCs with PHG enhanced bone mineral density at the injection sites compared to PHG alone in the mouse femoral fracture model., Conclusions: We showed that phenotypic characteristics of BM-DFATs were similar to those of BM-MSCs. BM-DFATs exhibited higher osteogenic differentiation potential and bone regenerative ability compared to SC-DFATs and ASCs. These results suggest that BM-DFATs may be suitable sources of cell-based therapies for patients with nonunion bone fracture., (© 2023. The Author(s).)

Background: Although artificial joints using polyethylene have been developed for various joints, the development of Posterior Dynamic Stabilization system of the spine using polyethylene has proceeded at a much slower pace. There are no studies which compare the abrasion resistance of vitamin-E-blended crosslinked polyethylene (VE) and conventional polyethylene (Virgin) in the spinal region. The purpose of this study was to compare the wear resistance of VE and Virgin in a Posterior Dynamic Stabilization System of the spine., Methods: Posterior Dynamic Stabilization System of the spine uses a polyethylene ball as a sliding surface. A fatigue wear test was repeated up to 1 million cycles at a speed of ±5°, 1 Hz while the rod was being pulled at a load of 50 N. Balls were compared using VE and Virgin in 6 samples each. Ti-6AL-4 V (Ti 64) and Co-Cr-Mo (CoCr) rods were used. Abrasion loss and shape change of the polyethylene balls were compared., Results: When Ti 64 was used as the rod, the average wear amount was -0.01 mg (0.02 mg, 0.01 mg, -0.06 mg) for VE, and 0.23 mg (0.18 mg, 0.13 mg, 0.38 mg) for Virgin. When CoCr was used as the rod, the average wear amount was 0.42 mg (0.71 mg, -0.06 mg, 0.61 mg) for VE, and 0.73 mg (0.72 mg, 0.70 mg, 0.76 mg) for Virgin. Most polyethylene samples showed indentations of 0.1 m or less at the contact point with the set screw. In the combination of Virgin and CoCr, a white patch was observed on the inner side of the polyethylene samples, with a maximum depression of 0.1 mm., Conclusions: A fatigue wear test showed VE to be more efficient in abrasion resistance than Virgin in a Posterior Dynamic Stabilization System of the spine in the laboratory., Competing Interests: Declaration of competing interest We received assistance from Teijin Nakashima Medical for the production of screws and materials. We bought prototype screws and materials from Teijin Nakashima Medical. The research was funded by Teijin Nakashima Medical, Neither the funding agency nor any outside organization has participated in study design or have any competing of interest., (Copyright © 2021 The Japanese Orthopaedic Association. All rights reserved.)

Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have investigated the factors contributing to residual low back pain in the chronic phase after OVFs by using radiographic evaluation. We examined the contribution of nonunion, vertebral deformity, and thoracolumbar alignment to the severity of residual low back pain post-OVF. This post hoc analysis of a prospective randomized study included 195 patients with a 48-week follow-up period. We investigated the associations between radiographic variables with the visual analog scale (VAS) scores for low back pain at 48 weeks post-OVF using a multiple linear regression model. Univariate analysis revealed that analgesic use, the local angle on magnetic resonance imaging, anterior vertebral body compression percentage on X-ray, and nonunion showed a significant association with VAS scores for low back pain. Multiple regression analysis produced the following equation: VAS for low back pain at 48 weeks = 15.49 + 0.29 × VAS for low back pain at 0 weeks + (with analgesics: +8.84, without analgesics: -8.84) + (union: -5.72, nonunion: -5.72). Among local alignment, thoracolumbar alignment, and nonunion, nonunion independently contributed to residual low back pain at 48 weeks post-OVF. A treatment strategy that reduces the occurrence of nonunion is desirable.

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) are mesenchymal stem cell (MSC)-like cells with high proliferative ability and multilineage differentiation potential. In this study, we first examined whether DFATs can be prepared from infrapatellar fat pad (IFP) and then compared phenotypic and functional properties of IFP-derived DFATs (IFP-DFATs) with those of subcutaneous adipose tissue (SC)-derived DFATs (SC-DFATs)., Methods: Mature adipocytes isolated from IFP and SC in osteoarthritis patients (n = 7) were cultured by ceiling culture method to generate DFATs. Obtained IFP-DFATs and SC-DFATs were subjected to flow cytometric and microarray analysis to compare their immunophenotypes and gene expression profiles. Cell proliferation assay and adipogenic, osteogenic, and chondrogenic differentiation assays were performed to evaluate their functional properties., Results: DFATs could be prepared from IFP and SC with similar efficiency. IFP-DFATs and SC-DFATs exhibited similar immunophenotypes (CD73 + , CD90 + , CD105 + , CD31 - , CD45 - , HLA-DR - ) and tri-lineage (adipogenic, osteogenic, and chondrogenic) differentiation potential, consistent with the minimal criteria for defining MSCs. Microarray analysis revealed that the gene expression profiles in IFP-DFATs were very similar to those in SC-DFATs, although there were certain number of genes that showed different levels of expression. The proliferative activity in IFP-DFATs was significantly (p < 0.05) higher than that in the SC-DFATs. IFP-DFATs showed higher chondrogenic differentiation potential than SC-DFATs in regard to production of soluble galactosaminogalactan and gene expression of type II collagen., Conclusions: IFP-DFATs showed higher cellular proliferative potential and higher chondrogenic differentiation capacity than SC-DFATs. IFP-DFAT cells may be an attractive cell source for chondrogenic regeneration., Competing Interests: The authors declare that there is no conflict of interests in this article., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown., Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury., Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020., Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment., Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury., Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients)., Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation., Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.

Background: Adjacent vertebral fracture (AVF) is a major complication following Balloon Kyphoplasty (BKP). There is no scoring system for predicting AVF using only preoperative elements. The purposes of this study were to develop a scoring system for predicting early AVF after BKP based on preoperative factors and to investigate the appropriate surgical indication for BKP., Methods: Of 220 patients who underwent BKP at a single institution since 2011, 65 patients over the age of 60 who had undergone a standing whole spine X-ray preoperatively were enrolled. Factors affecting the occurrence of early AVF were examined. A scoring system was created consisting of the factors exhibiting significant differences, and the correlation between the total score and the incidence of early AVF was investigated., Results: Twenty of the 65 patients (30.8%) had early AVF. In a univariate analysis, age, previous vertebral fracture, pelvic tilt, and Local kyphosis significantly influenced early AVF. In a multivariate logistic regression analysis, age had an odds ratio of 1.136 (95% CI 1.001-1.289), previous vertebral fractures 4.181 (1.01-17.309), and Local kyphosis 1.103 (1.021-1.191). The scoring system was set as follows: ①Age (<75 years: 0 points(P), 75years≦: 1P), ②The number of previous vertebral fractures (0: 0 P, 1: 1P, 2: 2P, 3 or more: 3P), and ③Local kyphosis (<10°: 0P, 10°≦: 1P). There was a correlation between the total score and the incidence of early AVF (r = 0.812, ∗P = 0.05). The incidence of early AVF was 6.4% (2 cases/31 cases) for a score of ≦1P and 54.5% (18 cases/33 cases) for a score of ≧2P., Conclusions: There was a correlation between the total score and the incidence of early AVF. A score of 1 point or less may represent the appropriate surgical indication for BKP., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Studies on the clinical and radiographic risk factors for the residual low back pain beyond 6 months after osteoporotic vertebral fractures (OVFs) are lacking. Hence, this study aimed to characterize a patient population with residual low back pain 48 weeks after acute OVFs and to identify the risk factors associated with residual low back pain., Methods: This prospective multicenter study included 166 female patients aged 65-85 years with acute one-level OVFs. We defined the residual low back pain as visual analog scale (VAS) for low back pain ≥3.5 at 48 weeks in this study, as VAS score ≥3.5 is used to describe moderate or severe pain. Thus, outcome and risk factor analyses were performed by comparing patients with VAS scores <3.5 and ≥ 3.5. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and 48 weeks., Results: Of the 166 patients analyzed, 58 complained of residual low back pain at 48 weeks after OVFs. At 0 weeks, the VAS score was significantly higher, and the JOABPEQ mental health score and anterior vertebral body compression percentage were significantly lower in patients with persistent pain 48 weeks after OVFs. The independent risk factors in the acute phase for persistent pain 48 weeks after OVFs were a high VAS score, MRI T2 fluid-intensity image pattern, and a lower anterior vertebral body compression percentage., Conclusions: Severe low back pain, MRI T2 fluid-intensity image pattern, and severe vertebral body collapse in the acute phase were significant risk factors for residual low back pain 48 weeks after OVFs. Patients with acute OVFs who have these risk factors should be carefully monitored for the possible development of residual chronic low back pain., Competing Interests: Declaration of Competing Interest Hiroaki Nakamura is an associate editor of Journal of Orthopaedic Science. There are no other conflicts of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Patients with metastatic spinal tumors often experience paralysis caused by spinal cord compression. Several studies have investigated metastatic lesion-related spinal cord compression. This study is the first to examine the relationship between the epidural spinal cord compression (ESCC) scale, which measures circumferential compression, and the functional outcomes of treatment, which were assessed at regular intervals after treatment until death. A total of 191 patients who had grade D or worse paralysis on the American Spinal Injury Association (ASIA) classification scale and a grade 1b or more severe cord compression on the ESCC scale were included in the study. Patients had been treated with surgery combined with radiotherapy (n=146) or radiotherapy alone (n=45). Three spinal surgeons assessed the ESCC grade of for patient, and the grade agreed to by at least 2 surgeons was adopted. After 4 weeks, re-evaluations were conducted by the same examiners. The authors also calculated the mean kappa coefficients for inter- and intra-examiner variability (0.88 and 0.93, respectively). The distribution of the ASIA grade differed significantly among the ESCC scale grades (P=.0102). However, the degree of improvement in paralysis in terms of the ASIA grade (≥1 grade of improvement, no change, or ≥1 grade of aggravation) was not significantly associated with the ESCC grade (P=.2334). The ESCC scale was found to be a useful indicator of circumferential spinal cord compression but was not identified as a significant functional prognostic factor for paralysis. [Orthopedics. 2020;43(6):e567-e573.]., (Copyright 2020, SLACK Incorporated.)

Background: The popliteus tendon (PT) or lateral collateral ligament (LCL) stabilizes the postero-lateral aspects of the knees. When surgeons perform total knee arthroplasty (TKA), PT and LCL iatrogenic injuries are a risk because the femoral attachments are relatively close to the femoral bone resection area. The purpose of this study was to evaluate the distance between the PT or LCL footprint and the TKA implant using a 3D template system and to evaluate any significant differences according to the implant model., Methods: Eighteen non-paired formalin fixed cadaveric lower limbs were used (average age: 80.3). Whole length lower limbs were resected from the pelvis. All the surrounding soft tissue except the PT, knee ligaments and meniscus were removed from the limb. Careful dissection of the PT and LCL was performed, and the femoral footprints were detected. Each footprint periphery was marked with a 1.5 mm K-wire. Computed tomography (CT) scanning of the whole lower limb was then performed. The CT data was analyzed with a 3D template system. This simulation models for TKA were the Journey II BCS and the Persona PS. The area of each footprint, and the length between the most distal and posterior point of the lateral femoral condyle and the edge of each footprint were measured. Matching the implant model to the CT image of the femur, the shortest length between each footprint and the bone resection area were calculated., Results: PT and LCL footprint were detected in all knees. The area of the PT and LCL footprints was 38.7 ± 17.7 mm 2 and 58.0 ± 24.6 mm 2 , respectively. The length between the most distal and posterior point of the lateral femoral condyle and the edge of the PT footprint was 10.3 ± 2.4 mm and 14.2 ± 2.8 mm, respectively. The length between most distal and most posterior point of the lateral femoral condyle and the edge of the LCL footprint was 16.3 ± 2.3 mm and 15.5 ± 3.3 mm, respectively. Under TKA simulation, the shortest length between the PT footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 4.3 ± 2.5 mm and 3.2 ± 2.9 mm, respectively. The shortest length between the LCL footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 7.2 ± 2.3 mm and 5.6 ± 2.1 mm, respectively. The PT attachment was damaged by the bone resection of the Journey II BCS and the Persona PS TKA in 3 and 9 knees, respectively., Conclusion: The PT and LCL femoral attachments existed close to the femoral bone resection area of the TKA. To prevent postero-lateral instability in TKA, careful attention is needed to avoid damage to the PT and LCL during surgical procedures.

Purpose: The prognosis of hepatocellular carcinoma (HCC) has recently improved, and so clinicians have greater opportunity to treat HCC-derived spinal metastases. Therefore, predicting life expectancy is important for determining the optimal treatment strategy for such tumors. This study aimed to investigate the prognostic factors for HCC-derived metastatic spine tumors and to develop a scoring system for predicting life expectancy in such cases., Methods: The posttreatment survival time and factors that might influence it were investigated in 62 patients with HCC-derived metastatic spine tumors who were treated at our department (surgery: 27 patients and conservative treatment: 35 patients), and a prognostic scoring system for predicting life expectancy was developed by combining the factors that significantly influenced survival., Results: In the univariate analyses, sex, the patient's general condition, the presence/absence of major internal organ metastasis, the total revised Tokuhashi score, the serum albumin level, Child-Pugh class, spinal surgery, and bone-modifying agent (BMA) treatment were found to influence the posttreatment survival time. These factors were subjected to multivariate analysis, and a novel scoring system for predicting life expectancy based on the patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment was developed. In the retrospective analysis, the concordance rate between the patients' life expectancy and actual survival times was 90.3%., Conclusion: The patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment influenced the posttreatment survival times of patients with HCC-derived metastatic spine tumors. A prognostic scoring system based on these factors was proposed.

The patient was a 40-year-old female who had been treated at our hospital for left peroneal tendonitis due to an ankle sprain 2 years earlier. She re-injured that ankle while dancing. The pain in the lateral left foot soon improved, but she had difficulty standing with the left foot in equinus. Complete peroneus longus and brevis tendon ruptures were diagnosed. The ipsilateral semitendinosus and gracilis tendons were harvested and used to reconstruct the tendons. Three months after surgery, the patient was able to stand in equinus, and at 5 months after surgery she resumed her original level of sports activities., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Therapeutic intervention has recently been actively performed for metastatic spine tumor even though spinal cord paralysis is not clearly observed, but there has been no report in which the degree of spinal cord compression by tumor was taken into consideration for the paralysis-preventing effect of treatment. Thus, we investigated the neurological outcome after treatment of patients with spinal cord compression in a state of impending paralysis., Methods: A retrospective cohort study. The subjects were 88 patients with epidural spinal cord compression (ESCC) scale 1b or severer compression with American Spinal Injury Association (ASIA) E spinal metastasis. The neurological outcome after the therapeutic intervention was investigated at regular intervals until death. The therapeutic intervention was posterior decompression and stabilization in 18 patients, stabilization without posterior decompression in 15, and radiotherapy in 55 patients (3 groups)., Results: The ASIA aggravation group was comprised of 15 patients, and the severity of paralysis was ASIA A in 3, B in 3, C in 6, and D in 3. Paralysis appeared in 16.7% in the posterior decompression and stabilization group, 13.3% in the posterior stabilization without decompression group, and 18.8% in the radiotherapy group. In the transverse view, the incidence was high in cases with advancement to the intervertebral foramen and circumferential-type advancement, and paralysis developed in more than 20% of ESCC 1c or severer cases. Factors influencing neurological aggravation were investigated, but there was no significant factor., Conclusion: In ESCC 1b or severer cases with ASIA E spinal metastasis, paralysis aggravated after therapeutic intervention in 16.7% in the posterior decompression and stabilization group, 13.3% in the stabilization without decompression group, and 16.7% in the radiotherapy group. There was no significant factor influencing the development of paralysis.

Although low-back pain is considered to be associated with cigarette smoking, the influence of cigarette smoking on the intervertebral discs (IVD) has not been confirmed. We established a rat model of passive cigarette smoking-induced IVD degeneration, and investigated the cytohistological changes in the IVD and the accompanying changes in gene expression. IVD from rats exposed to 8 weeks of passive cigarette smoking were stained with Elastica van Gieson, and exhibited marked destruction of the supportive structure of the reticular matrix in the nucleus pulposus (NP). Positive signals on safranin O, alcian blue, type II collagen and aggrecan staining were decreased in the destroyed structure. Safranin O and type II collagen signals were also decreased in the cartilage end-plate (CEP) after 4- and 8-weeks of cigarette smoking. In the CEP, the potential for apoptosis was increased significantly, as demonstrated by staining for single-strand DNA. However, there were no signs of apoptosis in the NP or annulus fibrosus cells. Based on these findings, we hypothesized that passive cigarette smoking-induced stress stimuli first affect the CEP through blood flow due to the histological proximity, thereby stimulating chondrocyte apoptosis and reduction of the extracellular matrix (ECM). This leads to reduction of the ECM in the NP, destroying the NP matrix, which can then progress to IVD degeneration., Competing Interests: This work was funded in part by Ono Pharmaceutical Co., Ltd., Stryker Japan K. K. and Nakashima Medical Co., Ltd. received by YT. There are no patents, products in development or marketed products associated with this research to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: Percutaneous pedicle screw (PPS) fixation has been introduced into palliative surgery for metastatic spine tumors; however, the therapeutic effects of PPS on the outcomes of multidisciplinary treatment for such tumors are unclear. Therefore, the therapeutic impact of PPS was investigated among patients with metastatic spine tumors and with revised Tokuhashi scores of ≤8., Materials and Methods: A total of 47 patients who underwent conventional palliative surgery (posterior decompression and stabilization, 33; posterior stabilization alone, 14) before the introduction of PPS and 38 patients who underwent PPS (posterior decompression and stabilization, 19; posterior stabilization alone, 19) were included. Surgical stress (operative time, blood loss, complications, etc.) and treatment outcomes (postoperative survival time, visual analog scale scores, Frankel classification, and the Barthel index at the final followup) were compared between the conventional and PPS groups., Results: The age of the indicated patients significantly increased after the introduction of PPS ( P < 0.05). Regarding posterior decompression and stabilization, there were no significant intergroup differences in surgical stress or treatment outcomes. As for posterior stabilization alone, there were significant preoperative differences in various parameters between the conventional and PPS groups ( P < 0.01) and also significant postoperative intergroup differences between surgical stress and treatment outcomes ( P < 0.01)., Conclusions: For patients with early-stage metastatic spine tumors, the use of PPS-based posterior stabilization combined with multidisciplinary adjuvant therapy has changed the age range of the patients indicated for surgery and caused significant improvements in surgical stress, postoperative survival time, and Barthel index., Competing Interests: There are no conflicts of interest.

Background: There have been only a few reports of subsequent postoperative vertebral fracture following posterior spinal instrumentation fusion, especially in elderly female patients. This study attempted to evaluate the long-term prevalence of subsequent postoperative vertebral fracture in female patients aged 70 years and older who underwent spine decompression and fusion surgery with pedicle screw fixation., Methods: We retrospectively reviewed prospectively collected data from 125 patients who met our inclusion and exclusion criteria. Patients were divided into 2 groups according to age: patients aged 70 years and older (Group A) and patients aged under 70 years of age (Group B). We evaluated incidence of subsequent postoperative vertebral fractures, type and timing of vertebral fractures, preoperative bone mineral density (BMD), preoperative diagnosis, surgical procedure, number of levels fused, extension of fusion to the lumbosacral junction, and presence of a transverse fixator., Results: Baseline characteristics excluding patients' age were not statistically different between the two groups. Preoperative BMD of Group A was an average 81.7% of the young adult mean (YAM) value and that of Group B was an average 85.1% YAM value. Subsequent postoperative vertebral fractures occurred in 22 (41.5%) of 53 in Group A. On the other hand, fracture occurred in 17 (23.6%) of 72 in Group B. There were significant differences between the groups (p = 0.02). The odds ratio for subsequent vertebral fracture was 2.4 (95% confidence interval: 1.1-5.2) in favor of Group A. Survival analysis showed that the rate of subsequent vertebral fracture was significantly higher in Group A (log-rank test, P = 0.007)., Conclusions: The incidence of subsequent vertebral fracture in patients aged 70 years and older was significantly higher than in patients aged under 70 years of age. In the case of pedicle screw fixation in elderly female patients, it is necessary to note the high risk of subsequent vertebral fracture despite short or non-rigid fusion. Vertebral fracture after posterior fusion surgery even for degenerative lumbar pathology could occur in more than one-third of female patients aged 70 years and older.

While bracing is the standard conservative treatment for acute osteoporotic compression fracture, the efficacy of different brace treatments has not been extensively studied. We aimed to clarify and compare the preventive effect of the different brace treatments on the deformity of the vertebral body and other clinical results in this patient cohort. This multicenter nationwide prospective randomized study included female patients aged 65⁻85 years with acute one-level osteoporotic compression fractures. We assigned patients within four weeks of injury to either a rigid-brace treatment or a soft-brace treatment. The main outcome measure was the anterior vertebral body compression percentage at 48 weeks. Secondary outcome measures included scores on the European Quality of Life-5 Dimensions (EQ-5D), visual analog scale (VAS) for lower back pain, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). A total of 141 patients were assigned to the rigid-brace group, whereas 143 patients were assigned to the soft-brace group. There were no statistically significant differences in the primary outcome and secondary outcome measures between groups. In conclusion, among patients with fresh vertebral compression fractures, the 12-week rigid-brace treatment did not result in a statistically greater prevention of spinal deformity, better quality of life, or lesser back pain than soft-brace., Competing Interests: The authors declare no conflict of interest.

Background/aim: miRNA-1(miR-1) is down-regulated in various cancer cells including osteosarcoma cells. This study was conducted to analyze the function of miR-1 in osteosarcoma cells., Materials and Methods: miR-1 expression in osteosarcoma cells was evaluated by qRT-PCR. Cell proliferation was evaluated after transfecting miR-1 by WST8 assay and FACS analysis, both in vitro and in vivo., Results: Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G 0 -G 1 phase by increasing p21 levels via a p53-independent pathway. Overexpression of miR-1 down-regulated PAX3, a potential p21-regulating gene. Moreover, knockdown of PAX3 suppressed cell proliferation by increasing p21 levels, and induced arrest at the G 0 /G 1 phase. Administration of miR-1 showed an in vivo antitumor effect., Conclusion: Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G 0 /G 1 phase by increasing p21 levels via a p53-independent pathway through PAX3 suppression. These results indicate that miR-1 could be a therapeutic target for osteosarcoma., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Minimally invasive spine stabilization (MISt) using percutaneous pedicle screws plays a significant role in palliative surgery for metastatic spinal tumors. However, few studies have investigated surgical outcomes based on the epidural spinal cord compression scale (ESCCS). The purpose of this study was to examine outcomes of metastatic spinal tumors as evaluated by ESCCS in patients treated by MISt., Methods: The subjects were 56 patients who underwent MISt for metastatic spinal tumors, including 34 patients with ESCCS 2 or milder (group A) and 22 patients with ESCCS 3 (group B). We analyzed baseline characteristics, perioperative factors and clinical results such as postoperative survival time, neurological outcomes, Barthel Index for activities of daily living (ADL), visual analogue scale (VAS), and the rate of discharge to home., Results: The baseline age (P=0.07), tumor diagnosis (P=0.23), spinal level of compression (P=0.35), American Spinal Injury Association classification (P=0.49), revised Tokuhashi score (P=0.92), spinal instability neoplastic score (P=0.28), VAS (P=0.35), Barthel Index (P=0.07), American Society of Anesthesiologists physical status classification (P=0.76), and type of surgery (P=0.40) did not differ significantly between the two groups. The median postoperative survival time did not differ significantly between the groups (12.0 versus 15.0 months, P=0.60). Neurological improvement by at least 1 grade or maintenance of grade E was favorable in group A. Patients in group A had less posterior decompression (P=0.006), a higher rate of chemotherapy (P=0.009), a higher postoperative Barthel Index (P=0.04), and a higher rate of discharge to home (P=0.01) and no patients died in the hospital (P=0.004)., Conclusions: No significant difference was noted in the postoperative survival time between the 2 groups. Patients in the ESCCS 2 or milder group had favorable neurological improvement, higher rates of chemotherapy, better postoperative ADL, and the higher rate of discharge to home.

Metastases to the skull or upper cervical spine from hepatocellular carcinoma (HCC) are very rare. We herein report a unique case of two-site surgery for both skull and upper cervical spine metastases from HCC. The patient was a 64-year-old man with cervical pain. Computed tomography (CT) revealed osteolytic change related to metastatic cervical spine and occipital bone tumors. Two-stage surgery involving posterior occipitocervical fusion and occipital bone tumor resection was performed. The patient's pain decreased in severity, and postoperative radiotherapy and chemotherapy could be conducted. The postoperative course was favorable, and the patient exhibited improvement in his activities of daily living. Neither cervical spine X-ray examination nor CT showed any instrumentation failure, such as screw loosening, before the patient died of liver failure 13 months after surgery. Patients with both skull and upper cervical spine metastases from liver cancer may have a markedly unfavorable prognosis. Even in these patients, however, surgery as an aggressive palliative treatment may prolong the survival period or maintain the quality of life as long as the patient's general condition permits.

Background: The Magerl and Goel-Harms techniques have been reported to produce excellent treatment outcomes in cases of atlantoaxial subluxation, but they also carry a risk of vertebral artery injuries. In order to completely prevent such injuries, we developed a surgical procedure, involving bone grafting between the C1 posterior arch and C2 lamina with clamp- or hook-and-rod-based fixation combined with the insertion of an interference screw into the posterior atlantoaxial joint., Methods: This was a retrospective single-center study. The subjects were 58 patients in whom atlantoaxial subluxation was treated with the abovementioned procedure after 1995 (33 patients with rheumatoid arthritis (RA group) and 25 patients without rheumatoid arthritis (non-RA group)). The clinical outcomes and imaging findings of anterior subluxation at ≥ 2 years after surgery were compared between the RA and non-RA groups., Results: No vertebral artery injuries occurred during surgery. Seven and two patients died during the follow-up period in the RA and non-RA groups, respectively, but none of these deaths were associated with surgery. At ≥ 2 years after surgery, the visual analogue scale score, Japanese Orthopaedic Association score, and Ranawat classification had significantly improved in both groups (p < 0.001). Radiologically, bone fusion was noted in all patients. Significant changes in the atlas-dens interval (ADI) were seen immediately after surgery in both groups (p < 0.001). In the non-RA group, significant changes in the corrected atlantoaxial height were observed immediately after surgery (p < 0.01), and loss of correction was seen at the final follow-up, but it was not significant (p = 0.1965). No significant changes were noted in any other parameter. Regarding the postoperative alignment of the cervical spine, lordosis tended to decrease, but additional surgery was only performed in one patient, who had developmental stenosis at the mid-lower level and belonged to the RA group. No reoperations due to fused adjacent segmental disease or exacerbated curvature were required., Conclusion: In the present study, no vertebral artery injuries occurred during surgery, and no major perioperative complications developed. Favorable clinical outcomes were observed at ≥ 2 postoperative years although the patients' diseases varied. This procedure produced superior outcomes, especially in terms of spinal correction and the maintenance of the ADI.

Background: Proximal junctional kyphosis (PJK) following adult spinal deformity (ASD) surgery in elderly patients is markedly influenced by osteoporosis causing additional vertebral fracture and loosening of pedicle screws (PS). This study aimed to investigate the association between mean bone density represented in Hounsfield units (HU) on spinal computed tomography (CT) and revision surgery for PJK or postoperative additional vertebral fracture following ASD surgery in elderly patients., Methods: The subjects were 54 ASD patients aged 65 years or older who were treated with correction and fusion surgery of four or more levels and could be followed for 2 years or longer. Bone density was measured before surgery using lumbar dual-energy X-ray absorptiometry (DXA) and spinal CT in all patients. The patients were divided into group A (n = 14) in which revision surgery was required for PJK or additional vertebral fracture and group B (n = 40) in which revision surgery was not required. We retrospectively investigated incidences of PJK, additional vertebral fracture, and PS loosening, perioperative parameters, radiographic parameters before and after surgery, and osteoporosis treatment administration rate., Results: No significant difference was noted in young adult mean (YAM) on DXA between groups A and B, respectively (P = 0.62), but the mean bone densities represented in HU of the T8 (P = 0.002) and T9 (P = 0.01) vertebral bodies on spinal CT were significantly lower in group A, whereas those of the L4 (P = 0.002) and L5 (P = 0.01) vertebral bodies were significantly higher in group A. The incidence of PJK was not significantly different (P = 0.07), but the incidence of additional vertebral fracture was significantly higher in group A (P < 0.001). The incidences of uppermost PS loosening within 3 months after surgery were 71% and 40% in groups A and B, respectively (P = 0.04)., Conclusions: In elderly patients who required revision surgery, the mean bone densities of vertebral bodies at T8 and T9 were significantly lower. The mean bone density represented in HU on spinal CT may be useful for risk assessment of and countermeasures against revision surgery after ASD surgery in elderly patients.

Objective: The purpose of this study was to evaluate the durability and biological response of a new Posterior Dynamic Stabilization system using polyethylene with vitamin E on the sliding surface., Summary of Background Data: The use of polyethylene with vitamin E on the sliding surface in Posterior Dynamic Stabilization has not been reported previously., Methods: A developed pedicle screw-based Posterior Dynamic system consists of four parts: a set screw, a rod, a ball, and a pedicle screw. The rod is inserted into the through hole of the ball, and the ball is sandwiched by the set screw. (1) Fatigue Wear Test . Testing was conducted under a dynamic compressive load of 50N at a speed of 1 Hz for 1 million cycles. We examined the loss of polyethylene due to abrasion in 3 units. (2) Biological Response in Pigs . In two pigs, a new pedicle screw and a conventional pedicle screw were inserted in L2 and L3/4, and L4 and L2/3, respectively. After breeding for 6 months, autopsies were performed. CT imaging was used to evaluate bone union of the facet joint. Abrasive specimens were prepared, and abrasion powder and inflammatory cell infiltration were evaluated microscopically., Results: The average loss of polyethylene due to abrasion was -0.01 mg. In all units, polyethylene showed a decrease of 0.1 mm or less at the contact point with the set screw. The facet joints between the conventional screws exhibited bone fusion, but the facet joint between the conventional and the new screw retained mobility with no bony fusion. No abrasion powder was found and inflammatory cell infiltration was only minimally observed., Conclusion: The new Posterior Dynamic Stabilization system exhibited a high level of durability and biological safety.

Background: Recently, molecule-targeting and bone-modifying agents have improved the treatment outcomes of lung cancer-derived metastatic spine tumors. Therefore, the prognostic factors for such tumors were examined, and novel scoring systems for predicting the life expectancy of patients with such tumors were proposed., Methods: In 207 patients with lung cancer-derived metastatic spine tumors (surgery 49; conservative therapy 158), we retrospectively examined the factors that influenced the post-treatment survival time (age, sex, the affected site, pathology, general condition, the number of extraspinal bone metastases, the number of spinal metastases, the presence/absence of major internal organ metastasis, paralysis state, the total Tokuhashi score, the serum alkaline phosphatase level, the serum carcinoembryonic antigen level, molecule-targeting drug treatment, and bone-modifying agent treatment). Based on the results, we devised novel scoring systems for predicting the prognosis of such patients., Results: Univariate analyses showed that the pathology of the primary lung tumor, the patient's general condition and paralysis state, and the presence/absence of molecule-targeting drug treatment significantly influenced survival. We performed a Cox regression analysis of these four factors and developed criteria for a novel scoring system based on the patient's general condition and paralysis state, which exhibited significance in the regression analysis. A retrospective review indicated that the consistency rate between predicted life expectancy and actual survival was 67.3%. When criteria based on the four factors that exhibited significance in the univariate analyses were adopted, the consistency rate was 76.2%., Conclusion: The patient's general condition and paralysis state, the pathology of the primary lung tumor, and molecule-targeting drug treatment influenced survival among patients with lung cancer-derived metastatic spine tumors. Novel scoring systems based on these four factors were proposed.

Background: Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects., Methods: Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen., Results: DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation., Conclusions: Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Posterior decompression and stabilization plays significant roles in palliative surgery for metastatic spinal tumor. However, the indication for addition of posterior decompression have not been examined. The purpose of this study was to investigate a retrospective cohort of outcomes of metastatic spinal tumor treated with minimally invasive spine stabilization (MISt) with or without posterior decompression., Methods: The subjects were 40 patients who underwent MISt using percutaneous pedicle screws for metastatic spinal tumor, including 20 patients treated with stabilization alone (group A) and 20 patients with added posterior decompression (group B). We analyzed baseline characteristics, postoperative survival time, and perioperative factors such as neurological outcomes, Barthel Index, VAS, and rate of discharge to home., Results: The mean ages were 70 and 66 years old (P = 0.06), the mean revised Tokuhashi scores were 7.2 and 5.8 (P = 0.1), the mean spinal instability neoplastic scores (SINS) were 10.5 and 9.0 (P = 0.04), and the mean Barthel Index for ADL were 65.5 and 41.0 (P = 0.06) in groups A and B, respectively. The median postoperative survival time did not differ significantly between groups A and B (12.0 vs. 6.0 months, P = 0.09). Patients in group A had a significantly shorter operation time (166 vs. 232 min, P = 0.004) and lower intraoperative blood loss (120 vs. 478 mL, P < 0.001). Postoperative paralysis (P = 0.1), paralysis improvement rate (P = 0.09), postoperative Barthel Index (P = 0.06), and postoperative VAS (P = 0.6) did not differ significantly between the groups. The modified Frankel classification improved from D1 or D2 before surgery to D3 or E after surgery in 4 of 10 cases (40%) in group A and 8 of 8 patients (100%) in group B (P = 0.01). Significantly more patients were discharged to home in group A (P = 0.02), whereas significantly more patients died in the hospital in group B (P = 0.02)., Conclusions: Patients treated without decompression had a shorter operation time, less blood loss, a higher rate of discharge to home, and lower in-hospital mortality, indicating a procedure with lower invasiveness. MISt without decompression is advantageous for patients with D3 or milder paralysis, but decompression is necessary for patients with D2 or severer paralysis.

Background: It remains unclear whether long fusion including lumbar-sacral fixation is needed in corrective surgery to obtain good global sagittal balance (GSB) for the treatment of traumatic thoracolumbar kyphotic spine deformity. The purposes of this study were to evaluate compensatory mechanism of the spine after corrective surgery without lumbar-sacral fixation and to evaluate the parameters affecting the achievement of good GSB post-operatively., Methods: Twenty (20) subjects requiring corrective surgery (distal end of fixation was L3) were included in this study. The radiographic parameters were measured pre-operatively and at one month after surgery. Sagittal Vertical Axis (SVA), Lumber Lordosis angle altered by fracture (fLL), Thoracic Kyphosis angle altered by fracture (fTK), Pelvic Tilt (PT), Sacral Slope (SS), Pelvic Incidence (PI), Segmental Lumbar Lordosis (sLL: L3-S/L4-S), and local kyphotic angle were measured. The correlation between correction of local kyphotic angle (CLA) and the change in radiographic parameters was evaluated. Post-operatively, subjects with SVA<50 mm and PI-fLL<10°were regarded as the "good GSB group (G group). The radiographic parameters affecting the achievement of G group were statistically evaluated., Results: fLL, sLL:L3-S and sLL:L4-S were decreased indirectly because the local kyphosis was corrected directly (CLA: 26.5 ± 8.6°) (P < 0.001). CLA and the change in fLL showed significant correlation (r = 0.821), the regression equation being: Y = -0.63X+3.31 (Y: The change in fLL, X: CLA). The radiographic parameters significantly affecting the achievement of G group were: SVA, PT, PI-fLL, sLL: L3-S, and sLL: L4-S (P < 0.01)., Conclusion: The main compensatory mechanism was the decrease of lordosis in the lumbar spine. fLL was decreased to approximately 60% of CLA after surgery. SVA was not corrected by the compensatory mechanism., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Surgeries performed for metastatic spinal tumor are mostly palliative and are controversial for patients with short life expectancy. We investigated whether palliative posterior spinal stabilization surgery with postoperative multidisciplinary therapy results in improvement of life prognosis and activities of daily living (ADL) in patients with metastatic spinal tumor., Methods: The subjects were 55 patients who underwent palliative posterior-only instrumentation surgery for metastatic spinal tumor at our hospital between 2012 and 2015. Postoperative survival, early paralysis improvement, ADL improvement, and rate of discharge to home were examined., Results: The patients included 37 males and 18 females, and the mean age at the time of surgery was 66.8 years old. The mean Tokuhashi score was 7.1, the mean spinal instability neoplastic score (SINS) was 9.4, and the epidural spinal cord compression scale (ESCCS) was grade 3 in 20 patients (36.3%). The mean Barthel index for ADL was 48.7. The median postoperative survival time determined using the Kaplan-Meier method was 12.0 months (95% confidence interval 2.4-21.5). Regarding improvement of paralysis, the modified Frankel scale was improved by one grade or more or grade E was maintained in 35 patients (63.6%), whereas paralysis aggravated in 2 (3.6%). In surgery, conventional posterior decompression and fixation were applied in 31 patients (56.3%), and minimally invasive spine stabilization was applied in 24 (43.6%). Postoperative chemotherapy was performed in 31 patients (56.3%), radiotherapy was used in 38 (69.0%), and a bone-modifying agent was administered in 39 (70.2%). Regarding ADL, the mean Barthel index improved from 48.5 before surgery to 74.5 after surgery. Thirty-seven patients (67.2%) were discharged to home., Conclusions: ADL improved and allowed discharge to home, and postoperative adjuvant therapy could be administered at a high rate in patients who received palliative posterior spinal stabilization surgery. Survival time extended beyond the preoperative life expectancy in many patients. Patients with a metastatic spinal tumor have short life expectancy and paralysis caused by spinal instability and spinal cord compression. However, multidisciplinary therapy including palliative posterior spinal stabilization surgery with reduced invasiveness and postoperative adjuvant therapy are effective in these patients.

Introduction: Accurate evaluation of metastasis and life prognosis is essential for selecting a suitable therapeutic strategy for metastatic spine tumors owing to limitations in treatment options. For this purpose, various classification, evaluation, and scoring systems have been developed., Methods: Classification, evaluation, and scoring systems for metastatic spine tumors reported to date were identified by performing a literature search on PubMed. We reviewed the most cited classifications and scorings before 2009, and all classifications and scorings reported after 2010 from the search results., Results: Six classifications and 23 scorings were reviewed. The classification/evaluation methods are divided into 1) anatomical classification/evaluation methods, 2) evaluation methods for neurological symptoms/instability, and 3) scoring systems for predicting life expectancy. The first 2 were useful for the planning and evaluation of surgical indications. Scoring systems for life prognosis also permitted rough prediction of the outcomes and were useful for the selection of a suitable treatment. However, variation of the patient background, diversity of adopted prognostic factors, and the absence of scoring systems that could predict the outcome with an accuracy of 90% or higher introduced some limitations., Conclusion: The identified classification, evaluation, and scoring systems have been generally useful for treatment strategies. However, we emphasize the necessity of multidisciplinary development and revision of classification and evaluation methods to adapt to the prolongation of survival associated with increased diversity and improvement of treatment options., Competing Interests: Conflicts of Interest: The authors declare that there are no conflicts of interest.

Background: Neural pathways are thought to be directly involved in the pathogenesis of rheumatoid arthritis (RA). Although synovial mast cells (MCs) are activated by substance P (SP), the role of MCs in neural pathways in RA remains unknown. The aims of this study were to investigate 1) whether tachykinins are produced by synovial MCs and whether production differs in RA and osteoarthritis (OA) patients, and 2) what is the responsible receptor for SP in synovial MCs., Methods: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery. Cultured synovium-derived MCs were generated by culturing dispersed synovial cells with stem cell factor. SP expression was investigated using immunofluorescence and enzyme immunoassays. Mas-related gene X2 (MrgX2) expression was reduced in human MCs using a lentiviral shRNA silencing technique., Results: SP expression was localized around the cell membrane in 41% (median) of the MCs in synovium from RA but in only 7% of that from OA, suggesting the activation of MCs. Synovial MCs expressed tachykinin (TAC) 1 mRNA, the expression of which was upregulated by the aggregation of FcɛRI or the addition of aggregated IgG. However, the released SP appeared to be rapidly degraded by MC chymase. Synovial MCs were activated with SP through MrgX2 to release histamine without producing proinflammatory cytokines., Conclusions: Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Interleukin (IL)-17A plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The expression of IL-17A in synovial mast cells (MCs) in RA and osteoarthritis (OA) has been reported, but the frequencies of IL-17A expression in synovial MCs have varied. The aim of this study was to investigate whether IL-17A expression is upregulated in human synovial MCs in RA and to elucidate the mechanism of IL-17A expression in synovial MCs., Methods: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Synovium-derived cultured MCs were generated by culturing synovial cells with stem cell factor. IL-17A expression was investigated using immunofluorescence in synovial tissues. IL-17A mRNA expression and its production from MCs were examined using RT-PCR and ELISA, respectively., Results: The number of IL-17A-positive ((+)) synovial MCs and the percentage of IL-17A(+) MCs among all the IL-17A(+) cells from RA patients were not significantly increased compared with those from OA subjects. The synovium-derived cultured MCs spontaneously released small amounts of IL-17A. Neither IgE- nor IgG-dependent stimulation increased IL-17A production from the MCs. IL-33, tumor necrosis factor-α, C5a, lipopolysaccharide or IL-23 plus IL-1β did not affect IL-17A production in MCs., Conclusions: The synovial MCs are not a main source of IL-17A in RA., (Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Malignant transformation of giant cell tumors of bones, that is, secondary malignant giant cell tumor of bone, is rare. The most common symptoms are local pain and swelling. There are no prior reports of giant cell tumor of bone with fever of unknown origin at the onset. Here we present a case of a secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin., Case Presentation: A 75-year-old Asian man presented with a 3-week history of continuous pyrexia and left knee pain and swelling. He had been diagnosed at age 35 years with a giant cell tumor of bone of his left distal femur and underwent bone curettage and avascular fibula grafting at that time. Postoperative radiation therapy was not performed. He remained recurrence-free for 40 years after surgery. At age 75, histopathological findings suggested a secondary malignant giant cell tumor of bone. The tumor specimen expressed tumor necrosis factor-α. Neoplastic fever was suspected, and a naproxen test was conducted. His pyrexia showed immediate resolution. Surgery was performed under a diagnosis of a secondary malignant giant cell tumor of bone with neoplastic fever. His pyrexia and inflammatory activities diminished postoperatively., Conclusions: This is the first reported case, to the best of our knowledge, of the detection of a secondary malignant giant cell tumor of bone based on fever of unknown origin after long-term (40 years) follow-up. After curettage and bone grafting, giant cell tumor of bone may transform to malignancies within a few years or even decades after surgery. Therefore, meticulous follow-up is essential. The fever might be attributable to the tumor releasing inflammatory cytokines. Not only pain and swelling but also continuous pyrexia may suggest the diagnosis of a secondary malignant giant cell tumor of bone.

A 63-year-old man revealed a four-month history of muscle weakness of the lower limbs, hypoesthesia of the L5 and S1 area and ischuria. On MRI, the spinal cord was compressed by an encircled mass, which showed hypointensity on T1- and T2-weighted images with gadolinium enhancement at the Th11 to Th12 vertebra. Because of the rapid progression of myelopathy, posterior decompression was performed and idiopathic hypertrophic spinal pachymeningitis (HSP) was finally diagnosed. The patient's neurological signs markedly improved with postoperative corticosteroid treatment. Idiopathic HSP is a clinical emergency and early surgical intervention is essential to prevent irreversible damage to the nervous system.

Assessing the prognosis before treatment for metastatic spine tumor is extremely important in therapy selection. Therefore, we review some prognostic scoring systems and their outcomes. Articles with combinations of two keywords among "metastatic spine tumor" and "prognosis", "score", "scoring system", "predicting", or "life expectancy" were searched for in PubMed. As a result, 236 articles were extracted. Those referring to representative scoring systems about predicting the survival of patients with metastatic spine tumors were used. The significance and limits of these scoring systems, and the future perspectives were described. Tokuhashi score, Tomita score, Baur score, Linden score, Rades score, and Katagiri score were introduced. They are all scoring systems prepared by combining factors that affect prognosis. The primary site of cancer and visceral metastasis were common factors in all of these scoring systems. Other factors selected to influence the prognosis varied. They were useful to roughly predict the survival period, such as, "more than one year or not" or "more than six months or not". In particular, they were utilized for decision-making about operative indications and avoidance of excessive medical treatment. Because the function depended on the survival period in the patients with metastatic spine tumor, it was also utilized in assessing functional prognosis. However, no scoring system had more than 90% consistency between the predicted and actual survival periods. Future perspectives should adopt more oncological viewpoints with adjustment of the process of treatment for metastatic spine tumor.

Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors. In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo. Intriguingly, knockdown of the putative Myc-6 target MALAT1 encoding long noncoding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

Osteosarcoma is one of the most prevalent bone tumors, occurring mostly in adolescence. However, no noticeable progress has been achieved in developing new therapeutic agents for this disease. Matrix metalloproteinase 9 (MMP9), a type IV collagenase, is a known anticancer target and is overexpressed in osteosarcomas. MMPs can degrade components of the extracellular matrix and are known to be involved in tumor invasion and metastasis. In the present study, we designed and synthesized a pyrrole-imidazole polyamide (HN.49), a gene-silencing agent that specifically targets the nuclear factor-kappa B (NF-κB) binding site of the human MMP9 promoter. We then examined the effect of HN.49 on the enzyme activity of MMP9 and the migration activity of osteosarcoma cells in vitro. It was clearly shown that HN.49 polyamide reduced the expression level of MMP9 mRNA and the enzymatic activity of MMP-9 in SaOS-2 cells. Moreover, HN.49 polyamide inhibited migration and invasion by SaOS-2 cells in in vitro wound-closure and matrigel-invasion assays. These results indicate that HN.49 may be a potential therapeutic agent for inhibiting the invasion and metastasis of osteosarcoma.

To prevent adjacent disc problems after spinal fusion, a pedicle screw with a mobile junction between the head and threaded shaft was newly developed. The threaded shaft of the screw has 10 degrees mobility in all directions, but its structure is to prevent abnormal translation and tilting. This screw was evaluated as follows: (1) endurance test: 10(6) times rotational stress was applied; (2) biological reactions: novel screws with a mobile head and conventional screws with a fixed head were inserted into the bilateral pedicles of the L3, L4, and L5 in two mini pigs with combination. Eight months after surgery, vertebral units with the screw rod constructs were collected. After CT scan, the soft and bony tissues around the screws were examined grossly and histologically. As a result, none of the screws broke during the endurance test stressing. The mean amount of abrasion wear was 0.0338 g. In the resected mini pig section, though zygapophyseal joints between fixed-head screws showed bony union, the amount of callus in the zygapophyseal joints connected with mobile-head screws was small, and joint space was confirmed by CT. No metalloses were noted around any of the screws. Novel screws were suggested to be highly durable and histologically safe.

Objective: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). A plausible pathway for the activation of synovial MCs is through IgG receptors, given the prevalence of circulating IgG isotype autoantibodies and synovial immune complexes in patients with RA. However, IgG receptor expression on human synovial MCs remains uncharacterized. The aim of this study was to identify which IgG receptor(s) on synovial MCs are responsible for MC activation in immune complexes., Methods: Synovial tissue specimens were obtained from patients with RA or patients with osteoarthritis (OA) who were undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting. Mediators released from MCs were measured using enzyme immunoassays or enzyme-linked immunosorbent assays., Results: Primary synovial MCs and cultured synovium-derived MCs obtained from both patients with RA and patients with OA expressed Fcε receptor I (FcεRI), FcγRI, and FcγRII but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNFα) through FcγRI. The aggregation of FcγRII caused histamine release from cultured MCs but not from primary MCs. Histamine release induced by aggregated IgG was significantly inhibited by neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody., Conclusion: With regard to the FcR expression profile, synovial MCs from patients with RA and patients with OA were similar. FcγRI was responsible for producing abundant TNFα from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII., (Copyright © 2013 by the American College of Rheumatology.)

Incisional biopsy and intramedullary pinning were performed for pathological fracture associated with a malignant bone tumor of the proximal humerus. Osteosarcoma, for which preoperative chemotherapy had been performed, was confirmed by postoperative pathological examination. To achieve wide resection and acquire a safe resected margin, total humerus replacement was performed, and the whole humerus was reconstructed using the Howmedica Modular Reconstruction system. The patient resumed normal activities, although mild contracture of the elbow joint remains 8 years after surgery.

We report a 38-year old man with a giant-cell tumor in a rare site, the patella. Primary patellar neoplasms are highly unusual. According to a survey by the Bone and Soft Tissue Tumor Committee of the Japanese Orthopaedic Association, of more than 2,126 giant-cell tumors of bone reported since 1972, only 22 were primary patellar neoplasms. We present a case of this rare entity along with its clinical and radiographic features. The first clinical symptom was anterior knee pain. Though anterior knee pain has numerous and varied causes, it is necessary to consider patellar bone tumors in the differential diagnosis.

Background: Knee size and body size differ in Asians compared with Caucasians. Nevertheless, many total knee arthroplasty (TKA) prostheses used worldwide are made for Western Caucasian subjects. As a result, an Asian's knee might not fit these prostheses. We studied the Flexible Nichidai Knee (FNK) system, a new model of TKA for Asian patients. The purpose of this report is to investigate the outcomes of this prosthesis retrospectively., Methods: We investigated 1055 primary TKAs in 595 patients who underwent FNK for osteoarthritis (OA) in Japan and were followed for > 5 years. The knee score and function score were used for clinical evaluation. We examined the range of motion (ROM) preoperatively and at final follow-up and radiographic assessments. In addition, postoperative complications were investigated. A survivorship analysis was also conducted using two endpoints: revision for any reason and aseptic failure., Results: 890 knees in 502 patients were available for study (follow-up rate of 96.0%). The mean follow-up term was 8.3 years (range, 5.0-14.1 years). The knee and function score significantly improved from 41.3 to 90.3 and from 39.1 to 76.2 points, respectively (p < 0.001). The mean ROM in FNK posterior cruciate retaining (CR) type and FNK posterior-stabilized (PS) type ameliorated significantly from 107.8° and 95.6° to 110.7° and 110.4°, respectively (p < 0.01). Ten knees underwent revision surgery (infection in 3 cases, instability in 2, loosening in 2, and non-union of femoral supracondylar fracture, severe pain, and recurrent hemarthrosis in 1 each). The survivorship rate was 99.4% (95% CI, 99.0-99.8) at 5 years (n = 952 patients at risk) and 96.2% (95% CI, 91.9-100) at 12.5 years (n = 49 patients at risk)., Conclusion: The FNK prosthesis for Asians achieved excellent mid- to long-term survivorship and clinical results.