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Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have closely investigated the factors contributing to the quality of life (QOL) in the chronic phase after thoracolumbar OVFs using detailed radiographic evaluation.This study aimed to identify factors associated with the QOL in the chronic phase after thoracolumbar OVF.Post-hoc analysis of a prospective randomized study.Participants included 195 patients with fresh thoracolumbar OVF managed conservatively with a brace who were available for radiographic analysis 48 weeks after injury.The degree of QOL impairment at 48 weeks after thoracolumbar OVF was assessed using the Japanese three-level version of the EuroQol five-dimensional questionnaire (EQ-5D) score.Univariate and multivariate regression analyses were used to evaluate the relationships between the QOL and radiographic factors.The univariate analysis showed that age, analgesic use, T10/L5 Cobb angle on magnetic resonance imaging (MRI), subsequent vertebral fracture, and nonunion were significantly associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. The multiple regression analysis showed that nonunion, analgesic use, subsequent vertebral fracture, and sacral slope on MRI were independently associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. Receiver operating characteristic analysis for the deterioration of QOL showed that the cutoff value for sacral slope on MRI was 35 degrees.This study demonstrated that nonunion, subsequent vertebral fracture, and lower sacral slope were independently associated with poorer QOL in the chronic phase of thoracolumbar OVF managed conservatively with a brace. Therefore, improving or preventing these factors in patients with thoracolumbar OVF in the chronic phase may improve the QOL of the affected patients.

No study has investigated the clinical and radiographic risk factors for the deterioration of quality of life (QOL) beyond 6 months after osteoporotic vertebral fractures (OVF). The purpose of this study was to identify the predictors associated with poor QOL improvement after OVF. This post hoc analysis included 166 women aged 65–85 years with acute 1-level OVFs. For the patient-reported outcome measures, scores on the European Quality of Life-5 Dimensions (EQ-5D) scale, and visual analogue scale (VAS) for low back pain were used. Lateral radiography at 0, 12, and 48 weeks and magnetic resonance imaging (MRI) at enrollment and at 48 weeks were performed. The associations between baseline variables with change scores for EQ-5D were investigated using a multiple linear regression model. Univariate analysis showed that time since fracture, EQ-5D score, and VAS for low back pain at 0 week showed significant association with increased EQ-5D score from 0 to 48 weeks. According to the multiple regression analysis, the following equation was obtained: increased EQ-5D score from 0 to 48 weeks = 1.305 – 0.978 × EQ-5D at 0 week – 0.021 × VAS for low back pain at 0 week – 0.006 × age + (fluid-intensity T2-weighted MR image patterns: − 0.037, except for fluid-intensity T2-weighted MR image patterns: + 0.037). In conclusion, older patients with severe low back pain and fluid-intensity T2-weighted MR image patterns were more likely to have lower QOL improvements after OVFs and may therefore need extra support to improve QOL

Study design Prospective cohort study. Objective To characterize a patient population with nonunion after acute osteoporotic vertebral fractures (OVFs) and compare the union and nonunion groups to identify risk factors for nonunion. Summary of background data While OVFs are the most common type of osteoporotic fracture, the predictive value of a clinical assessment for nonunion at 48 weeks after OVF has not been extensively studied. Methods This prospective multicenter cohort study included female patients aged 65 to 85 years with acute one-level osteoporotic compression fractures. 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 at 48 weeks to confirm the diagnosis and union status. The patient-reported outcome measures included scores on the European Quality of Life-5 Dimensions (EQ-5D), a visual analogue scale for low back pain, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) at 0, 12, and 48 weeks. Results In total, 166 patients completed the 12-month follow-up, 29 of whom had nonunion. Patients with nonunion at 48 weeks after OVF had lower EQ-5D and JOABPEQ walking ability, social life function, mental health, and lumbar function scores than those with union at 48 weeks after injury. The independent risk factors for nonunion after OVF in the acute phase were a diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI. The anterior vertebral body compression percentage and JOABPEQ social life function scores were independent risk factors at 12 weeks. Conclusion A diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI were independent risk factors for nonunion in the acute phase. Patients who have acute OVFs with these risk factors should be carefully monitored for nonunion. Level of evidence 2.

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.

Survivin is overexpressed in various cancers and is correlated with treatment resistance and prognosis. MicroRNAs (miRNAs) directly regulate several target genes and are potential therapeutic agents for various cancers. The present study evaluated multiple gene targets of miR‑218, including survivin, in osteosarcoma and compared the anti‑tumor effects of miR‑218 with those of YM155, an anti‑survivin agent. It assessed the expression levels of miR‑218 and survivin in osteosarcoma and osteoblast cell lines, as well as the proliferative, migratory and invasive capacities of cells following treatment with miR‑218 or YM155. The form of cell death was assessed using fluorescence‑activated cell sorting analysis to examine the expression of invasion ability‑related genes. Osteosarcoma cell lines were subcutaneously injected into immunodeficient mice; the mice were then treated with miR‑218 or YM155 to assess the anti‑tumor effects of these agents. The results showed that miR‑218 was downregulated, whereas survivin was overexpressed in the osteosarcoma cell line compared with normal osteoblast cells. The expression of survivin was suppressed upon overexpression of miR‑218 (miR‑218 group) or administration of YM155 (YM155 group), leading to apoptosis and inhibition of osteosarcoma cell proliferation. Invasion and migration abilities were inhibited in the miR‑218 group, but not in the YM155 group. In the animal model, both the miR‑218 and YM155 groups showed a reduced tumor volume and decreased survivin expression. In osteosarcoma, miR‑218 showed a wider range of therapeutic efficacy compared with YM155, suggesting that miR‑218 should be evaluated as a treatment target.

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.

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.

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.]

To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65–85 years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6 months. At 48 weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0 weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. III

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 mm2 and 58.0 ± 24.6 mm2, 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.

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.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.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.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.

Background When the surgeons perform total knee arthroplasty (TKA), PT and LCL iatrogenic injury are worried because those femoral footprints are relatively close to the bone resection lesion. The purpose of this study was to evaluate the distance between PT or LCL footprint and TKA implant using the three-dimensional (3D) template system.Methods Eighteen non-paired formalin fixed cadaveric lower limbs were used. All the surrounded soft tissue except the PT and knee ligaments were removed from the limb. Careful dissection of the PT and LCL was performed, and those femoral footprints were detected. Each footprint was periphery marked with a K-wire. CT scanning of the whole lower limb was then performed. The CT data was analyzed with 3D template system. Simulated models of TKA were Journey II BCS and Persona PS. The area of each footprint, and the length between most distal or posterior point of femur and the edge of each footprint were measured. When the implant model was matched to the CT image, the shortest length between each footprint and the bone resection were evaluated.Results The area of PT and LCL footprint were, 38.7±17.7mm 2 , and 58±24.6mm 2 , respectively. The length between most distal or posterior point of femur and the edge of the PT footprint were 10.3±2.4mm, and 14.2±2.8mm, respectively. The length between most distal or posterior point of femur and the edge of the LCL footprint were 16.3±2.3mm, and 15.5±3.3mm, respectively. When simulated the TKA, the shortest length between PT footprint and bone resection lesion of Journey II BCS and Persona PS were, 4.3±2.5mm, and 3.2±2.9mm, respectively. The shortest length between PT footprint and bone resection lesion of Journey II BCS and Persona PS were, 7.2±2.3mm, and 5.6±2.1mm, respectively. PT footprint was suffered by the bone resection of Journey II BCS TKA in 3 knees, and also by the Persona PS’s bone resection in 9 knees.Conclusion The PT and LCL femoral footprint existed close to the femoral bone resection lesion of the TKA. Careful attention is needed not to injure the PT and LCL in the surgical procedures.

Study Design. A prospective multicenter cohort study.Objective. To assess the clinical accuracy of six commonly cited prognostic scoring systems for patients with spinal metastases.Summary of Background Data. There are presently several available methods for the estimation of prognosis in metastatic spinal disease, but none are universally accepted by surgeons for clinical use. These scoring systems have not been rigorously tested and validated in large datasets to see if they are reliable enough to inform day-to-day patient management decisions. We tested these scoring systems in a large cohort of patients. A total of 1469 patients were recruited into a secure internet database, and prospectively collected data were analyzed to assess the accuracy of published prognostic scoring systems.Methods. We assessed six prognostic scoring systems, described by the first authors Tomita, Tokuhashi, Bauer, van der Linden, Rades, and Bollen. Kaplan-Meier survival estimates were created for different patient subgroups as described in the original publications. Harrell's C-statistic was calculated for the survival estimates, to assess the concordance between estimated and actual survival.Results. All the prognostic scoring systems tested were able to categorize patients into separate prognostic groups with different overall survivals. However none of the scores were able to achieve "good concordance" as assessed by Harrell's C-statistic. The score of Bollen and colleagues was found to be the most accurate, with a Harrell's C-statistic of 0.66.Conclusion. No prognostic scoring system was found to have a good predictive value. The scores of Bollen and Tomita were the most effective with Harrell's C-statistic of 0.66 and 0.65, respectively. Prognostic scoring systems are calculated using data from previous years, and are subject to inaccuracies as treatments advance in the interim. We suggest that other methods of assessing prognosis should be explored, such as prognostic risk calculation.

Spontaneous spinal epidural hematoma (SSEH) very rarely develops in infants younger than 1 year old. To our knowledge, no previous case of delayed-onset paralysis induced by SSEH communicated with hematoma in the paraspinal muscle has been reported in the literature. The authors present the case of a 6-month-old girl with a tumor mass on her back who developed a paresis of her bilateral lower limbs. On spinal magnetic resonance imaging, the epidural mass appeared to be a dumbbell type and communicated with the mass in the paraspinal muscle through T12/L1 intervertebral foramen at the right side. After excision of the mass in the paraspinal muscle, hemi-laminectomy of T10-L3 was performed. No solid lesion was also present in the spinal canal and it was found to be an epidural hematoma. No malignancy was observed on pathological examination, and vascular and nerve system tumors were negative. When a tumor mass suddenly develops on the back of an infant and motor impairment of the lower limbs develops as the mass gradually enlarges, differential diagnosis should be performed taking SSEH into consideration.

OBJECTIVEThe range of decompression in posterior decompression and fixation for ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL) can be established using an index of spinal cord decompression based on the ossification-kyphosis angle (OKA) measured in the sagittal view on MRI. However, an appropriate OKA cannot be achieved in some cases, and posterior fixation is applied in cases with insufficient decompression. Moreover, it is unclear whether spinal cord decompression of the ventral side is essential for the treatment of OPLL. In this retrospective analysis, the efficacy of posterior decompression and fixation performed for T-OPLL was investigated after the range of posterior decompression had been set using the OKA.METHODSThe MRI-based OKA is the angle from the superior margin at the cranial vertebral body of the decompression site and from the lower posterior margin at the caudal vertebral body of the decompression site to the prominence of the maximum OPLL. Posterior decompression and fixation were performed in 20 patients. The decompression range was set so that the OKA was ≤ 23° or the minimum if this value could not be achieved. Cases in which an OKA ≤ 23° could and could not be achieved were designated as groups U (13 patients) and O (7 patients), respectively. The mean patient ages were 50.5 and 62.1 years (p = 0.03) and the mean preoperative Japanese Orthopaedic Association (JOA) scores were 5.9 and 6.0 (p = 0.9) in groups U and O, respectively. The postoperative JOA score, rate of improvement of the JOA score, number of levels fused, number of decompression levels, presence of an echo-free space during surgery, operative time, intraoperative blood loss, and perioperative complications were examined.RESULTSIn groups U and O, the mean rates of improvement in the JOA score were 50.0% and 45.6% (p = 0.3), the numbers of levels fused were 6.7 and 6.4 (p = 0.8), the numbers of decompression levels were 5.9 and 7.4 (p = 0.3), an echo-free space was noted during surgery in 92.3% and 42.9% of cases (p = 0.03), the operative times were 292 and 238 minutes (p = 0.3), and the intraoperative blood losses were 422 and 649 ml (p = 0.7), and transient aggravation of paralysis occurred as a perioperative complication in 2 and 1 patient, respectively.CONCLUSIONSThere was no significant difference with regard to the recovery rate of the JOA score between patients with (group U) and without (group O) sufficient spinal cord decompression. The first-line surgical procedure of posterior decompression and fixation with the range of posterior decompression set as an OKA ≤ 23° before surgery involves less risk of postoperative aggravation of paralysis and may result in a better outcome.

The prognosis of hepatocellular carcinoma (HCC) used to be poor, but it has recently improved, which has meant that clinicians have greater opportunity to treat spinal metastases and the associated epidural spinal cord compression. However, there have been few systematic functional studies about HCC-derived spinal metastases. The treatment outcomes of surgical treatment for HCC-derived metastatic spinal tumors were investigated. The post-treatment survival period and pain, paralysis, and disturbance of activities of daily living (ADL) were investigated in 60 patients (surgery 25, conservative treatment 35). The mean post-treatment survival period was 7.4 ± 8.2 months (range 0.3–36 months). Univariate analysis indicated that the following factors influenced survival: the patient’s general condition, presence/absence of major internal organ metastasis, serum albumin level, Child–Pugh classification, surgical treatment for spinal metastasis, and bone-modifying agent treatment. In the multivariate analysis of these 6 items, 3 significant factors were extracted: the patient’s general condition, the serum albumin level, and bone-modifying agent treatment. Pain significantly improved in both groups (p

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.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 SVA50 mm and PI-fLL10°were regarded as the "good GSB group (G group). The radiographic parameters affecting the achievement of G group were statistically evaluated.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).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.

Surgical treatment of multiple vertebral fractures in patients with glucocorticoid-induced osteoporosis is difficult because of a high rate of secondary fracture postoperatively. A case is described in which initial treatment with teriparatide to improve osteoporosis followed by treatment of kyphosis with correction fusion achieved a favorable outcome. Secondary fracture frequently occurs after treatment of vertebral fracture with vertebroplasty and balloon kyphoplasty in patients with glucocorticoid-induced osteoporosis, but effective treatment of multiple vertebral fractures has rarely been reported. Thus, a treatment of kyphosis following multiple vertebral fractures associated with glucocorticoid-induced osteoporosis is required. The patient was a 24-year-old woman diagnosed with glucocorticoid-induced osteoporosis who was under treatment with oral alendronate, vitamin D, and elcatonin injection. Secondary multiple vertebral fractures occurred despite these treatments and low back pain gradually aggravated. Vertebroplasty or balloon kyphoplasty was not performed in the early phase. Instead, treatment with teriparatide was used for initial improvement of osteoporosis. Kyphosis in the center of the residual thoracolumbar junction was then treated with posterior correction fusion. At 2 years after surgery, the corrected position has been maintained and no new fracture has occurred. There is no established method for treatment of multiple vertebral fractures caused by glucocorticoid-induced osteoporosis. Initial treatment with teriparatide to improve osteoporosis followed by treatment of kyphosis with correction fusion may result in a more favorable outcome.

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

Study Design.A retrospective, single-center study.Objective.Investigation of the changes in the treatment outcomes of patients with lung cancer derived metastatic spine tumors.Summary of Background Data.Metastatic spine tumors derived from lung cancer had been progressive, and their prognosis is poo

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent with high tumor-selective cytotoxicity. The congenital and acquired resistance of some cancer types including malignant melanoma and osteosarcoma impede the current TRAIL therapy of these cancers. Since fine tuning of the intracellular Ca2+ level is essential for cell function and survival, Ca2+ dynamics could be a promising target for cancer treatment. Recently, we demonstrated that mitochondrial Ca2+ removal increased TRAIL efficacy toward malignant melanoma and osteosarcoma cells. Here we report that mitochondrial Ca2+ overload leads to tumor-selective sensitization to TRAIL cytotoxicity. Treatment with the mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157 and oxidative phosphorylation inhibitor antimycin A and FCCP resulted in a rapid and persistent mitochondrial Ca2+ rise. These agents also increased TRAIL sensitivity in a tumor-selective manner with a switching from apoptosis to a nonapoptotic cell death. Moreover, we found that mitochondrial Ca2+ overload led to increased mitochondrial fragmentation, while mitochondrial Ca2+ removal resulted in mitochondrial hyperfusion. Regardless of their reciprocal actions on the mitochondrial dynamics, both interventions commonly exacerbated TRAIL-induced mitochondrial network abnormalities. These results expand our previous study and suggest that an appropriate level of mitochondrial Ca2+ is essential for maintaining the mitochondrial dynamics and the survival of these cells. Thus, disturbing mitochondrial Ca2+ homeostasis may serve as a promising approach to overcome the TRAIL resistance of these cancers with minimally compromising the tumor-selectivity.

The purpose of this study was to evaluate the detailed anatomy of the femoral anterior cruciate ligament (ACL) insertion site, with special attention given to the morphology of the mid-substance insertion areas and the fan-like extension fibers. Twenty-three non-paired human cadaver knees were used (7 Males, 16 Females, median age 83, range 69–96). All soft tissues around the knee were resected except the ligaments. The ACL was divided into antero-medial (AM) and postero-lateral (PL) bundles according to the difference in macroscopic tension patterns. The ACL was carefully dissected and two outlines were made of the periphery of each bundle insertion site: those which included and those which excluded the fan-like extension fibers. An accurate lateral view of the femoral condyle was photographed with a digital camera, and the images were downloaded to a personal computer. The area of each bundle, including and excluding the fan-like extension fibers, was measured with Image J software (National Institution of Health). The width and length of the mid-substance insertion sites were also evaluated using same image. The femoral ACL footprint was divided into four regions (mid-substance insertion sites of the AM and PL bundles, and fan-like extensions of the AM and PL bundles). The measured areas of the mid-substance insertion sites of the AM and PL bundles were 35.5 ± 12.5, and 32.4 ± 13.8 mm2, respectively. Whole width and length of the mid-substance insertion sites were 5.3 ± 1.4, and 15.5 ± 2.9 mm, respectively. The measured areas of the fan-like extensions of the AM and PL bundles were 27 ± 11.5, and 29.5 ± 12.4 mm2, respectively. The femoral ACL footprint was divided into quarters of approximately equal size (mid-substance insertion sites of the AM and PL bundles, and fan-like extensions of the AM and PL bundles). For clinical relevance, to perform highly reproducible anatomical ACL reconstruction, the presence of the fan-like extension fibers should be taken into consideration.

The objective of this study is to clarify the surgical indication for rheumatoid forefoot deformity according to background characteristics and plantar pressure.Patients with rheumatoid arthritis were divided into a non-surgical group (group N) and a surgical group (group S). The former consisted of 225 ft, and the latter consisted of 88 ft. DAS28, Japanese Society for Surgery of the Foot rheumatoid arthritis foot and ankle scale (JSSF scale) and hallux valgus angle (HVA) were evaluated as background characteristics. Distribution of peak pressure as plantar pressure was measured in nine sections.In groups N and S, the mean DAS28 was 3.6 and 3.0, the mean JSSF scale was 81.1 and 63.0, and the mean HVA was 19.9° and 35.3°, respectively. The mean peak pressure of group S at the first and third metatarsophalangeal joints was significantly higher compared with group N. Significant differences between the two groups were also seen in Δ pressure (the difference between the maximum and minimum peak pressure values). The cut-off values were 75.0 for JSSF scale, 24.9° for HVA and 3.94 kg/cmThe combined assessment of HVA and Δ pressure was found to be useful as an indication for surgical treatment of the forefoot.

The purpose of this study was to compare muscle recovery in the lower extremities following the newly developed bi-cruciate substituting (BCS) to posterior stabilized (PS) total knee arthroplasty (TKA) in the Asian population. Forty-one knees in 41 patients undergoing BCS-TKA (41 female, average age: 71 ± 8.8) and 34 knees in 34 patients undergoing PS-TKA (33 female, average age: 73 ± 7.2) were included in this study. The maximum isometric power of the quadriceps and hamstring muscles was measured preoperatively, and at 1, 3, 6, and 12 months after surgery using a handheld dynamometer. Postoperative muscle recovery was calculated regarding preoperative muscle power as 100%. Pre- and postoperative range of knee motion, femorotibial angle, and clinical scores (Knee Society score and function score) were also compared. No significant difference in sex, age, preoperative quadriceps, or preoperative hamstring power was observed between the BCS and PS-TKA groups. When regarding the preoperative muscle power as 100%, quadriceps power at 1, 3, 6, and 12 months following BCS-TKA was 61.2 ± 22%, 86.3 ± 28.3%, 97 ± 27.4%, and 112.4 ± 30.8%, respectively. Quadriceps power at 1, 3, 6, and 12 months following PS-TKA was 72.4 ± 20.8%, 84 ± 16.9%, 95 ± 20.7%, and 110.8 ± 27%, respectively. Hamstring power at 1, 3, 6, and 12 months following BCS-TKA was 96.3 ± 30%, 111.4 ± 35%, 120 ± 37%, and 125 ± 31%, respectively. Hamstring power at 1, 3, 6, and 12 months following PS-TKA was 95 ± 25%, 112.4 ± 27%, 117 ± 38.5%, and 120.4 ± 18.5%, respectively. No significant difference in muscle power recovery was observed at 3 (p = 0.995), 6 (p = 0.944), and 12 (p = 0.917) months after surgery between the two groups. No significant difference of the clinical score was observed between the groups (Knee Society score: p = 0.479, function score: p = 0.342). No significant difference in muscle recovery and clinical score were observed between the BCS and PS-TKA groups. Longer follow-up is needed for the evaluation of efficacy of BCS-TKA in the Asian populations.

Objective Caudal epidural blocks often fail due to the difficulty of appropriate needle insertion. This study aimed to evaluate the anatomy of the sacral hiatus using ultrasound imaging. Methods This was a retrospective study involving 76 patients with spinal disorders. The following factors were analyzed to see if they affected the palpability of the sacral hiatus: sex, body mass index (BMI), and the morphology of the sacral hiatus on ultrasound imaging. The difficulty of needle insertion and the factors that influenced it were investigated in 28 of the 76 patients, who underwent landmark-based caudal epidural block procedures performed by the same doctor. Results Among the 76 patients, the mean length of the sacral hiatus was 21.3 ± 5.6 mm, the mean distance from the skin to the sacral cornua was 5.2 ± 3.4 mm, and the mean angle of the sacral hiatus was 16.4 ± 5.5 degrees. Sacral base protrusion was present and absent in 35 and 41 cases, respectively. The sacral hiatus exhibited good and poor palpability in 53 and 23 cases, respectively. The mean distance from the skin to the sacral cornua and BMI were found to significantly influence the palpability of the sacral hiatus. Only sacral base protrusion significantly influenced the difficulty of needle insertion. Conclusion The mean distance from the skin to the sacral cornua and BMI were found to be associated with the palpability of the sacral hiatus, and sacral base protrusion was demonstrated to be associated with the difficulty of needle insertion into the sacral hiatus.

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&ndash, 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.

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.

“Anatomical” anterior cruciate ligament (ACL) reconstruction is defined as the functional restoration of the ACL to its native dimensions. It is essential to obtain more accurate predictors of ACL size before surgery. The purpose of this study was to investigate the correlation between the native femoral ACL footprint size and the morphology of the distal femur using three-dimensional CT (3D-CT). Thirty non-paired Japanese human cadaver knees were used. All soft tissues around the knee were resected except the ACL. For the evaluation of femoral condyle morphology, trans-epicondylar length (TEL), notch outlet length, axial notch area, and notch width index were measured using 3D-CT. The ACL was cut in the middle, and the femoral bone was cut at the most proximal point of the femoral notch. The ACL was carefully dissected, and the boundaries of the ACL insertion site were outlined on the femoral side. An accurate lateral view of the femoral condyle was photographed with a digital camera. The size of the femoral ACL footprint, length of Blumensaat’s line, and the height and area of the lateral wall of the femoral intercondylar notch were measured with ImageJ software. Notch height, lateral notch area, and TEL were significantly correlated with the femoral ACL footprint area. Both axial notch area and notch outlet length were significantly correlated with the femoral mid-substance insertion area. Morphological evaluation using 3D-CT preoperatively may be useful in predicting the femoral ACL footprint size.

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

BACKGROUND: Indications for surgery for symptomatic spinal metastases have become better defined in recent years, and suitable outcome measures have been established against a changing backdrop of patient characteristics, tumor behavior, and oncologic treatments. Nonetheless, variations still exist in the local management of patients with spinal metastases. In this study, we aimed to review global trends and habits in the surgical treatment of symptomatic spinal metastases, and to examine how these have changed over the last 25 years. METHODS: In this cohort study of consecutive patients undergoing surgery for symptomatic spinal metastases, data were collected using a secure Internet database from 22 centers across 3 continents. All patients were invited to participate in the study, except those unable or unwilling to give consent. RESULTS: There was a higher incidence of colonic, liver, and lung carcinoma metastases in Asian countries, and more frequent presentation of breast, prostate, melanoma metastases in the West. Trends in surgical technique were broadly similar across the centers. Overall survival rates after surgery were 53% at 1 year, 31% at 2 years, and 10% at 5 years after surgery (standard error 0.013 for all). Survival improved over successive time periods, with longer survival in patients who underwent surgery in 2011-2016 compared with those who underwent surgery in earlier time periods. CONCLUSIONS: Surgical habits have been fairly consistent among countries worldwide and over time. However, patient survival has improved in later years, perhaps due to medical advances in the treatment of cancer, improved patient selection, and operating earlier in the course of disease. ispartof: WORLD NEUROSURGERY vol:114 pages:E809-E817 ispartof: location:United States status: published

We aimed to elucidate the molecular changes in intervertebral discs (IVDs) caused by passive smoking. Rats were subjected to 8 weeks of passive smoking; thereafter, their lumbar vertebrae were harvested. The annulus fibrosus and cartilage endplate (AF/CEP) were harvested together, and the nucleus pulposus (NP) was isolated separately. The expression of 27,342 rat genes was analyzed. In 3 “nonsmoking” rats, 96 of 112 genes whose expression varied ≥10-fold between the AF/CEP and NP were more highly expressed in the AF/CEP. With these differentially expressed genes, we uncovered novel AF/CEP and NP marker genes and indicated their possible novel functions. Although passive smoking induced less marked alteration in the gene expression profiles of both the AF/CEP and NP, multiple clock-related genes showed altered expression. These genes were expressed with a circadian rhythm in IVD cells, and most genes showed a phase shift of −6 to −9 h induced by passive smoking. Some clock-related genes showed abolished oscillation in the NP. Passive smoking also changed the expression levels of proteases and protease inhibitors and reduced the expression of NP marker genes. Thus, passive smoking induces changes in the circadian rhythm of a peripheral clock (IVD clock) that might be involved in molecular events related to IVD degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Study Design. A retrospective, single-institute, and radiographic study. Objective. To evaluate the relationship between the epidural spinal cord compression (ESCC) scale and the severity of metastatic spine tumor–induced paralysis. Summary of Background Data. The ESCC scale is used to evaluate the grade of spinal cord compression on T2-weighted magnetic resonance imaging (MRI). However, few studies have investigated the relationship between such MRI findings and paralysis. Methods. The subjects were 467 patients with metastatic spine tumors and grade 1b or worse spinal cord compression according to the ESCC scale. Evaluations using this scale were performed by three spine surgeons, and results that were obtained by two or more surgeons were adopted. We also examined patients whose spinal cord compression deteriorated by one grade or more to American Spinal Injury Association (ASIA) grade C or worse within the first 3 weeks after MRI. Results. The kappa coefficients for inter- and intraexaminer variability were 0.90 and 0.95, respectively. ASIA grade D or worse paralysis developed in at least 50% of the patients with ESCC grade 1b or worse spinal cord compression at the C1-T2 and at least 50% of those with ESCC grade 1c or worse spinal cord compression at the T3-L5. The frequency of ASIA grade C or worse paralysis was high among the patients with ESCC grade 2 or worse spinal cord compression at the C7-L1. Nineteen patients experienced rapid deterioration of one grade or more to ASIA grade C or worse paralysis within the first 3 weeks after MRI. Of these, paralysis occurred in at least 30% of the patients with anterolateral or circumferential cord compression combined with ESCC grade 2 or 3 compression at the C7-L1. Conclusion. The severity of paralysis was not correlated with the ESCC scale. Patients with anterolateral or circumferential ESCC grade 2 or 3 cord compression at the C7-L1 are at high risk of rapidly progressive paralysis. Level of Evidence: 4

Ca2+ has emerged as a new target for cancer treatment since tumor-specific traits in Ca2+ dynamics contributes to tumorigenesis, malignant phenotypes, drug resistance, and survival in different tumor types. However, Ca2+ has a dual (pro-death and pro-survival) function in tumor cells depending on the experimental conditions. Therefore, it is necessary to minimize the onset of the pro-survival Ca2+ signals caused by the therapy. For this purpose, a better understanding of pro-survival Ca2+ pathways in cancer cells is critical. Here we report that Ca2+ protects malignant melanoma (MM) and osteosarcoma (OS) cells from tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) cytotoxicity. Simultaneous measurements using the site-specific Ca2+ probes showed that acute TRAIL treatment rapidly and dose-dependently increased the cytosolic Ca2+ concentration ([Ca2+]cyt) and mitochondrial Ca2+ concentration ([Ca2+]mit) Pharmacological analyses revealed that the [Ca2+]mit remodeling was under control of mitochondrial Ca2+ uniporter (MCU), mitochondrial permeability transition pore (MPTP), and a Ca2+ transport pathway sensitive to capsazepine and AMG9810. Ca2+ chelators and the MCU inhibitor ruthenium 360, an MPTP opener atractyloside, capsazepine, and AMG9810 all decreased [Ca2+]mit and sensitized these tumor cells to TRAIL cytotoxicity. The Ca2+ modulation enhanced both apoptotic and non-apoptotic cell death. Although the [Ca2+]mit reduction potentiated TRAIL-induced caspase-3/7 activation and cell membrane damage within 24 h, this potentiation of cell death became pronounced at 72 h, and not blocked by caspase inhibition. Our findings suggest that in MM and OS cells mitochondrial Ca2+ removal can promote apoptosis and non-apoptotic cell death induction by TRAIL. Therefore, mitochondrial Ca2+ removal can be exploited to overcome the resistance of these cancers to TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment, but some cancer cell types are resistant to TRAIL cytotoxicity. Therefore, overcoming this resistance is necessary for effective TRAIL therapy. Mitochondrial morphology is important for the maintenance of cell function and survival, and is regulated by the delicate balance between fission and fusion. However, the role of mitochondrial morphology dynamics in TRAIL-induced apoptosis is unknown. Here we show that mitochondrial division inhibitor-1 (mdivi-1), an inhibitor of dynamin-related protein1 (Drp1), modulates mitochondrial morphology and TRAIL-induced apoptosis in human cancer cells. mdivi-1 treatment (≥12.5 µM) caused dose- and time‑dependent cell death in malignant melanoma, lung cancer and osteosarcoma cells, while sparing normal cells. mdivi-1 also sensitized cancer cells to TRAIL-induced apoptosis. This potentiation of apoptosis occurred through a caspase-depependent mechanism including the mitochondrial and endoplasmic reticulum (ER) stress pathways. Mdivi-1 potentiated mitochondrial oxidative stress, a major cause of mitochondrial and ER stresses, as evidenced by increases in mitochondrial reactive oxygen species levels, mitochondrial mass, and cardiolipin oxidation. Live cell fluorescence imaging using MitoTracker Red CMXRos revealed that Mdivi-1 caused substantial mitochondrial hyperfusion. Moreover, silencing of Drp1 expression also caused mitochondrial hyperfusion and sensitized cancer cells to TRAIL-induced apoptosis. Our results suggest that cancer cells are more vulnerable than normal cells to a perturbation in mitochondrial morphology dynamics and that this higher susceptibility can be exploited to selectively kill cancer cells and sensitize to TRAIL.

SummaryObjectivesThe purpose of this study was to reveal the accurate prevalence and related factors to the presence of calcium pyrophosphate dihydrate (CPPD) crystal deposition in cadaveric knee joints.DesignControlled laboratory study.MethodsSix hundred and eight knees from 304 cadavers (332 male knees and 276 female knees, formalin fixed, Japanese anatomical specimens) were included in this study. The average age of the cadavers was 78.3 ± 10.7 years. Knees were macroscopically evaluated for the existence of CPPD, and the depth of cartilage degeneration of the femoro-tibial joint following the Outerbridge's classification. CPPD crystal was confirmed under Fourier transform infrared spectroscopy (FTIR) analysis using light microscopy. Statistical analysis was performed to reveal the correlation between the occurrence of CPPD deposition in the knee joint and gender, age, and the depth of cartilage degeneration of the femoro-tibial joint.ResultsThe prevalence of grossly visible CPPD crystal was 13% (79 knees). In all of these knees, CPPD crystal was confirmed under FTIR analysis. Statistical analysis showed significant correlation between the occurrence of CPPD deposition and gender (P

Highlights • We generated pyrrole–imidazole (PI) polyamides that could bind to an E-box motif. • PI polyamide Myc-6 induces G1 arrest and apoptosis in human osteosarcoma MG63 cells. • Myc-6 represses tumor growth both in vitro and in vivo. • Myc-6 binds to the 5′-upstream region of noncoding RNA MALAT1 and reduces its expression. • Myc-6 exerts its tumor-suppressive ability through the down-regulation of MALAT1., 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.

Background Sixteen sacral chordoma surgeries performed at a single institution during the 1983–2008 period were retrospectively studied. Our aim is to assess surgical treatment and long-term outcomes. Methods Fifteen patients underwent primary wide excision, and one intralesional excision using ethanol for local control and radiation therapy (RT). A combined anteroposterior approach for large tumors above S2, and wide excision was performed with the modified threadwire-saw (MT-saw) after 1997. Results Fourteen of the 15 patients had wide margins, one a wide margin with contamination. The MT-saw was facilitated sacral excision with wide margins. Eleven patients are alive for 5–28 years. Five patients died before 10 years, two patients experienced sepsis, and one of another disease. Two patients died of local recurrence (LR) and another of multiple metastases after intralesional excision and wide excision with contamination, respectively. LR and complications occurred 4 each of 11 patients with tumors ≥10 cm, neither with tumors

We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a β-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the β-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis.

The purpose of this study was to reveal the prevalence of the subtypes of the meniscus using human cadaver knees. Four hundred and thirty-seven cadaveric knees in 219 subjects (formalin fixed, Japanese population) with a median age of 83 years (54–97) were included in this study. All soft tissues surrounding the knee, excluding the meniscus, were resected, and macroscopic assessment of the meniscus was performed. Meniscus subtypes were classified as: (1) normal meniscus, (2) complete discoid, (3) incomplete discoid, (4) ring-shaped, and (5) double-layered. All subtypes of the meniscus were observed in the lateral meniscus. Complete discoid lateral meniscus was observed in 27 knees (6.2 %), incomplete discoid lateral meniscus was observed in 139 knees (31.8 %), ring-shaped lateral meniscus was observed in 4 knees (0.9 %), and double-layered meniscus was observed in 2 knees (0.5 %). This study reports the accurate prevalence of ring-shaped and double-layered meniscus. None of the subtypes were detected in the medial meniscus in this study. For clinical relevance, the results of this study can be useful in assisting the diagnosis of meniscus tear in clinical situations.