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Purpose: Hemi-resurfacing arthroplasty (Hemi) and metal-on-metal hip resurfacing arthroplasty (HR) were proposed as alternatives to conventional total hip arthroplasty (THA) for patients with osteonecrosis of the femoral head (ONFH). Long-term results were evaluated. Methods: Twenty-three hips with ONFH were treated, using Hemi in 12 and HR in 11. Mean follow-up was 15 years in the Hemi group and 10 years in the HR group. Long-term outcomes were reviewed retrospectively. Results: In the Hemi group, 8 hips showed acetabular protrusion and were revised to THA. One of the 8 hips showed femoral loosening. In the HR group, pseudotumor was detected in 4 hips (36%), and 1 hip was revised due to symptomatic pseudotumor. No evidence of any femoral or acetabular loosening was seen in the HR group. Ten-year survival rates were 64.2% and 90.9% in the Hemi and HR groups, respectively. Survival rate in the Hemi group dropped to 22.9% at 15 years. Conclusions: Long-term results of Hemi for patients with ONFH were very poor, and Hemi should not continue to be used. Although HR had a concern of pseudotumor, it could offer attractive indications for 10 years. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to compare periprosthetic femoral bone remodeling after cementless total hip arthroplasty (THA) using a short-tapered wedge stem and a fully hydroxyapatite (HA)-coated stem. Materials and methods: In this retrospective study, 24 primary cementless THA procedures with short-tapered wedge stem and 24 using a fully HA-coated stem were performed. The follow-up duration was 2 years for both groups. Clinical evaluation was performed using the Merle d'Aubigné and Postel scoring systems. Standardized anteroposterior radiographs of the pelvis and femur were obtained. Dual-energy X-ray absorptiometry was performed, and the bone mineral density (BMD) around the stem was assessed in each Gruen zone at the first postoperative week as a baseline value and at 6 weeks, 3 and 6 months, and 1 and 2 years postoperatively. Results: The mean Merle d'Aubigné and Postel scores improved significantly postoperatively in both groups. None of the hips showed loosening in either group. Spot welds occurred in zones 1, 2, 6, and 7 in the short-tapered wedge group, and in all zones in the fully HA-coated group. Significant BMD loss occurred only in zone 4 in the short-tapered wedge group, and no significant bone loss occurred in any zone in the fully HA-coated stem group; a significant difference between the two groups was observed only in zone 4 at 2 years after THA. Conclusions: Clinical and radiographical outcomes in both groups were good, and both stems suppressed postoperative BMD loss at 2 years. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the accuracy of cup position and assess the changes in pelvic tilt during primary total hip arthroplasty (THA) in the lateral decubitus position using a new computed tomography (CT)-based navigation system with augmented reality (AR) technology. Materials and methods: There were 37 cementless THAs performed using a CT-based navigation system with AR technology in the lateral decubitus position and 63 cementless THAs performed using manual implant techniques in the lateral decubitus position in this retrospective study. Postoperative cup radiographic inclination and anteversion were measured using postoperative CT, and the proportion of hips within Lewinnek's safe zone was analyzed and compared between the two groups. The mean absolute values of navigation error were assessed. Intraoperative pelvic tilt angles were also recorded using navigation system. Results: The percentage of cups inside Lewinnek's safe zone was 100% in the navigation group and 35% in the control group (p < 0.001). The mean absolute values of navigation error in inclination and anteversion were 2.9° ± 2.1° and 3.3° ± 2.4°, respectively. The mean abduction angle of the pelvis was 5.1° ± 4.8° after placing the patients in the lateral decubitus position and 4.1° ± 6.0° after cup placement. The mean posterior tilt angle was 6.8° ± 5.1° after placing the patients in the lateral decubitus position and 9.3° ± 5.9° after cup placement. The mean internal rotation angle was 14.8° ± 7.4° after cup placement. There were no correlations between the navigation error in inclination or anteversion and the absolute values of changes of the pelvic tilt angle at any phase. Conclusions: Although progressive pelvic motion occurred in THA in the lateral decubitus position, especially during cup placement, the CT-based navigation system with AR technology improved cup placement accuracy. [ABSTRACT FROM AUTHOR]

Augmented reality (AR) has been used for navigation during total hip arthroplasty (THA). AR computed tomography (CT)-based navigation systems and AR-based portable navigation systems that use smartphones can also be used. This study compared the accuracy of cup insertion during THA using AR-CT-based and portable AR-based navigation systems. Patients with symptomatic hip disease who underwent primary THA in the supine position using both AR CT-based and portable AR-based navigation systems simultaneously between October 2021 and July 2023 were included. The primary outcome of this study was the absolute difference between cup angles in the intraoperative navigation record and those measured on postoperative CT. The secondary outcome was to determine the factors affecting the absolute value of the navigation error in radiographic inclination (RI) and radiographic anteversion (RA) of the cup, including sex, age, body mass index, left or right side, approach, and preoperative pelvic tilt. This study included 94 consecutive patients. There were 11 men and 83 women, with a mean age of 68 years. The mean absolute errors of RI were 2.7° ± 2.0° in the AR CT-based and 3.3° ± 2.4° in the portable AR-based navigation system. The mean absolute errors of RA were 2.5° ± 2.1° in the AR CT-based navigation system and 2.3° ± 2.2° in the portable AR-based navigation system. No significant differences were observed in RI or RA of the cup between the two navigation systems (RI: p = 0.706; RA: p = 0.329). No significant factors affected the absolute value of the navigation errors in RI and RA. In conclusion, there were no differences in the accuracy of cup insertion between the AR CT-based and portable AR-based navigation systems. [ABSTRACT FROM AUTHOR]

This study aimed to compare the cutting and component placement accuracies and early outcomes after total knee arthroplasty (TKA) between an image-free handheld robotic system (NAVIO) and a radiography-based robotic system (ROSA). This retrospective study included 88 patients (88 knees) who underwent TKA using the NAVIO (40 patients) or ROSA (48 patients) robotic systems. The accuracies of the robotic systems were compared. Clinical scores were evaluated using the Knee Society Score 2011 (KSS 2011) and the forgotten joint score (FJS)-12 at 1 year postoperatively. The femoral sagittal cutting error was smaller in the NAVIO group than in the ROSA group. The other cutting errors were not statistically different in both groups. Implantation errors did not differ between the groups. Regarding the clinical outcomes of the KSS 2011 subscales, the symptoms score was higher in knees operated using ROSA than in those using NAVIO. The other KSS 2011 subscales and the FJS-12 showed no differences between the two groups. In conclusion, the femoral sagittal cutting error was smaller in the NAVIO group than in the ROSA group, and the KSS 2011 symptom score subsection at one year was higher in the knees operated using ROSA than in those using NAVIO. [ABSTRACT FROM AUTHOR]

Robot-assisted total knee arthroplasty (TKA) has proven to be successful in improving the accuracy of component positioning and reducing radiographic outliers. This study aimed to evaluate and compare the alignment of the components using two- and three-dimensional (2D and 3D) measurements following handheld imageless robot-assisted TKA. Seventy consecutive patients underwent primary TKA at our institution using a handheld robot-assisted system. Full‐length standing anteroposterior and lateral radiographs were obtained 2 weeks after surgery for assessment of 2D component alignments. Pre- and postoperative computed tomography (CT) images were obtained to assess 3D component alignment. The reference points defined on preoperative CT images were transferred to the postoperative CT images. The absolute errors in the 2D and 3D component alignments from the planned, validated cutting, and validated implantation angles were calculated. Outliers of > ± 3° of femoral and tibial component alignments in the coronal and sagittal planes were also investigated. All absolute errors in the 2D and 3D component alignments were < 1°, except for the planned and validated cutting angles of the femoral sagittal alignment. No outliers were observed in the femoral or tibial component in the coronal plane. Significant differences between the 2D and 3D measurements were observed for the mean absolute value from the planned and validated cutting angles in the femoral sagittal plane and from the validated implantation angle in the tibial coronal plane. The handheld robot-assisted system demonstrated a high accuracy for component alignment using 2D and 3D evaluations. [ABSTRACT FROM AUTHOR]

Purpose: The impact of central sensitization (CS) on neurological symptoms and surgical outcomes in patients with lumbar spinal stenosis (LSS) remains unknown. This study aimed to investigate the influence of preoperative CS on the surgical outcomes of patients with LSS. Methods: A total of 197 consecutive patients with LSS (mean age 69.3) who underwent posterior decompression surgery with or without fusion were included in this study. The participants completed the CS inventory (CSI) scores and the following clinical outcome assessments (COAs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for back pain, JOA back pain evaluation questionnaire, and Oswestry Disability Index (ODI). The association between preoperative CSI scores and preoperative and postoperative COAs was analyzed, and postoperative changes were statistically evaluated. Results: The preoperative CSI score significantly decreased at 12 months postoperatively and was significantly correlated with all COAs preoperatively and 12 months postoperatively. Higher preoperative CSI showed worse postoperative COAs and inferior postoperative improvement rates in the JOA score, VAS score for neurological symptoms, and ODI. Multiple regression analysis demonstrated that preoperative CSI was significantly associated with postoperative low back pain (LBP), mental health, quality of life (QOL), and neurological symptoms at 12 months postoperatively. Conclusions: Preoperative CS evaluated by CSI had a significantly worse impact on surgical outcomes, including neurological symptoms, disability, and QOL, especially related to LBP and psychological factors. CSI can be used clinically as a patient-reported measure for predicting postoperative outcomes in patients with LSS. [ABSTRACT FROM AUTHOR]

Portable navigation systems have been developed for use in total hip arthroplasty (THA) in recent years. Although intraoperative registration in the lateral decubitus position or the supine position is need to create the three-dimensional coordinate system, it is not clear which position is appropriate. The purpose of this study was to assess the accuracy of cup placement in primary THA in the lateral decubitus position using an image-free handheld navigation device with registration in the lateral decubitus or the supine position, and clarify which position is appropriate. This retrospective study included 129 consecutive cementless THAs performed using an image-free handheld navigation device in the lateral decubitus position. Registration in the first 68 hips was performed in the lateral decubitus position and the last 61 hips was performed in the supine position. Postoperative cup radiographic inclination and radiographic anteversion were assessed, and the accuracy was compared between the two groups. The mean absolute errors of the postoperative measured inclination and anteversion from the target angles were 3.9° ± 2.2° and 4.8° ± 3.5° in the lateral group and 2.9° ± 2.7° and 3.2° ± 2.7° in the supine group (p < 0.05). The percentage of cups inside Lewinnek's safe zone was 94% in the lateral group and 95% in the supine group (ns). The mean absolute values of navigation error in inclination and anteversion were 3.1° ± 2.1° and 4.2° ± 2.8° in the lateral group and 2.3° ± 2.0° and 3.1° ± 2.4° in the supine group (p < 0.05 and p < 0.05). Registration in the supine position improved the accuracy of cup insertion compared with the lateral decubitus position in THA using an image-free handheld navigation device in the lateral decubitus position. [ABSTRACT FROM AUTHOR]

To clarify the association between pre- and postoperative rotational mismatches of the femorotibial components and bones for total knee arthroplasty (TKA) with bi-cruciate retaining (BCR) design and with fixed bearing posterior stabilized (PS) design. This retrospective cohort study included 40 BCR TKAs and 50 PS TKAs. Pre- and postoperative rotational mismatches of the femorotibial components and bones were measured by three-dimensional assessment based on computed tomography imaging. The mean value and percentage within ± 5° of pre- and postoperative rotational mismatches were compared between BCR TKA and PS TKA. Correlations between pre- and postoperative rotational mismatches of the femorotibial components and bones were investigated in BCR TKA and PS TKA. There was no significant difference in mean preoperative rotational mismatch of femorotibial components and bones between BCR TKA and PS TKA. Mean postoperative rotational mismatch of femorotibial components and bones was significantly greater in BCR TKA than in PS TKA. Postoperative rotational mismatch of the femorotibial components was within ± 5° in 21 knees (52.5%) for BCR TKA and in 43 knees (86.0%) for PS TKA. The rate of postoperative rotational mismatch of the femorotibial components and bones within ± 5° was significantly lower for BCR TKA than for PS TKA. In BCR TKA, there was a positive correlation between pre- and postoperative rotational mismatches of the femorotibial components and of bones. We consider these results can be attributed to the retention of both cruciate ligaments, which may affect the reduction of rotational permittance of the components and bones. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim was to evaluate the accuracy of navigation in opening wedge high tibial osteotomy (HTO). The secondary aim was to examine mid-term outcomes after HTO. Methods: Inclusion criteria were patients with medial compartment knee osteoarthritis who underwent computer-assisted HTOs. Mechanical axis (MA), percentage MA (%MA), and change in posterior tibial slope (ΔPTS) were displayed on the navigation screen. Radiographic examinations included hip–knee–ankle (HKA) angle, medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and PTS. Preoperative and 5 weeks postoperative standing radiographs of the whole lower extremity and knee were used. Clinical evaluations were performed using American Knee Society knee score and function score both preoperatively and at last follow-up. Radiographic evaluations were performed by orthopedic surgeons. Intraoperative navigation after osteotomy and postoperative standing radiograph were compared. MA (HKA), %MA, and ΔPTS were compared. Outliers were defined as > 3° in MA, > 10% in %MA, and > 10° in ΔPTS. Outlier and non-outlier groups were compared. The rate of conversion to arthroplasty was examined. Results: This study involved 38 patients (44 knees) and last follow-up was at a mean of 5 years (range, 1–9 years). Mean American Knee Society knee score and function score improved significantly from 59 to 69 preoperatively to 95 and 85 at last follow-up, respectively. Absolute values of mean errors for MA, %MA, and ΔPTS were 2.1°, 9.3%, 1.2°, respectively. Outlier rates were 18% in MA, 39% in %MA, and 5% in ΔPTS. No significant factors were found in MA and ΔPTS. In %MA, preoperative JLCA was significantly higher in the outlier group compared to the non-outlier group. No knees underwent conversion to total knee arthroplasty. No differences in outcomes were found between outlier and non-outlier groups. Conclusion: Although rates of outlier values in computer-assisted opening wedge HTO were high, mid-term outcomes were excellent. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Introduction: Although remarkable progress has been made in osteoporosis treatment over the last two decades, no study has reported the change in the prevalence of vertebral fractures (VFs) during this time. This study aimed to compare the prevalence and pattern of VFs at three time points from 1997 to 2019 in a Japanese medical examination-based study. Materials and methods: The participants of this study were inhabitants of a typical Japanese mountain village who participated in these surveys at three time points: 1997 (group A), 2009 or 2011 (group B), and 2019 (group C). The age- and sex-adjusted groups were defined as groups A', B', and C', respectively (39 men and 85 women; mean age 73.6–74.0 years old). The type and extent of deformities of the prevalent fractures from T4 to L4 on the lateral thoracic and lumbar spine radiographs were semiquantitatively evaluated. Results: The prevalence of VFs has significantly decreased over the past two decades. In group A, the percentages of thoracic level, biconcave type, and severe deformity of VFs were significantly higher than expected. The bone mineral density of the participants increased significantly over time. The treatment rate for osteoporosis in participants with osteoporosis has improved over the past two decades. Conclusion: This study demonstrated that the prevalence of VFs has decreased, and the pattern of VFs has changed over the last two decades in a typical Japanese mountain village due to multifactorial improvements in skeletal fragility, including improvement in osteoporosis treatment rate. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare acetabular offset, femoral offset, and global offset measurements obtained after total hip arthroplasty (THA) between a two-dimensional (2D) method and a three-dimensional (3D) method. The subjects were 89 patients with unilateral osteoarthritis who underwent primary THA at our institution. Acetabular, femoral, and global offsets were measured by each of the 2D and 3D methods in native and implanted hips. In native hips, mean acetabular, femoral, and global offsets were 32.4 ± 3.3, 32.7 ± 4.5, 65.1 ± 5.7 mm, respectively, by the 2D method, and 32.3 ± 3.1, 38.1 ± 4.0, 70.4 ± 4.9 mm, respectively, by the 3D method. In implanted hips, mean acetabular, femoral, and global offsets were 27.6 ± 4.1, 33.8 ± 7.8, 61.4 ± 8.5 mm, respectively, by the 2D method, and 27.6 ± 3.9, 41.8 ± 6.2, 69.4 ± 7.2 mm, respectively, by the 3D method. There was significant difference in femoral and global offsets between the 2D and 3D methods in both native and implanted hips. Comparison of the 2D and 3D methods for evaluation of acetabular, femoral, and global offsets after THA clarified the usefulness and accuracy of the 3D method. [ABSTRACT FROM AUTHOR]

Purpose of Review: Surgical resection is the standard treatment for localized soft tissue sarcoma (STS), while systemic chemotherapy for advanced STS may be considered. However, less aggressive treatment is often administered to elderly patients with STS. Undertreatment may compromise the cure rate and survival of these individuals. We review the literatures and emphasize the importance of standard treatment for STS in elderly patients. Recent Findings: The outcome of surgical resection of STS in older individuals is comparable to that of younger ones, as long as patients are selected based on American Society of Anesthesiologists Physical Status (ASA-PS). Likewise, systemic treatment may prove beneficial as long as the risk of complications is estimated with a geriatric assessment. Summary: Elderly patients with STS benefit from standard treatment as long as the risks of surgical and systemic complications are assessed respectively with the ASA-PS and GA. Novel clinical trials with broader eligibility criteria are also necessary for elderly patients because of the increasing population of the elderly patients in the future. [ABSTRACT FROM AUTHOR]

Periprosthetic bone loss due to adaptive bone remodeling is an important unresolved issue in cementless total hip arthroplasty (THA). The use of porous tantalum on the proximal surface of the femoral stem is expected to decrease postoperative bone loss around the prosthesis through early fixation. We conducted a multicenter randomized controlled study to determine if porous tantalum could reduce periprosthetic bone loss after THA. From October 2012 to September 2014, 118 patients (mean age, 61.5 years; 107 females and 11 males) were prospectively enrolled and were randomly allocated at a ratio of 1:1 to either a metaphyseal filling stem with a proximal porous tantalum coating (Trabecular Metal) or a conventional metaphyseal filling stem with fiber mesh coating (VerSys). Patients underwent dual-energy x-ray absorptiometry scans within 1 week after surgery (baseline) and at 6, 12, and 24 months after surgery to assess periprosthetic bone mineral density (BMD) in the 7 Gruen zones. In addition, the Japanese Orthopaedic Association hip score was assessed before surgery and at 6, 12, and 24 months after surgery. In the proximal periprosthetic region (zones 1 and 7), the Trabecular Metal group had significantly smaller reductions in BMD than the VerSys group throughout the study period. In the VerSys group, significant reductions in BMD compared to baseline were seen at each measurement point in all regions, except in zone 6 at 24 months. In the Trabecular Metal group, no significant reductions in BMD relative to baseline were seen in zones 1, 5, or 6 throughout the study period. Both groups demonstrated similar improvement in Japanese Orthopaedic Association hip scores over the study period. This study demonstrated that a proximally coated stem with porous tantalum has superior results over a conventional stem with titanium fiber mesh in terms of periprosthetic bone remodeling. [ABSTRACT FROM AUTHOR]

Background: Golimumab (GLM) has been reported to have lower immunogenicity than do other TNF inhibitors used for treating rheumatoid arthritis (RA). We previously found a prolonged effect of and improvement similar to that associated with infliximab (IFX) after switching to subcutaneous GLM (GLM-SC) for control of RA activity or adverse events. Thus, this study aimed to evaluate the continued maintenance of treatment efficacy and safety for > 2 years by switching to GLM-SC in RA patients with low disease activity or in remission after previous treatment with another tumor necrosis factor (TNF) inhibitor. Methods: Thirty-two patients treated with etanercept or infliximab were switched to GLM-SC and maintained low disease activity. The patients were divided into two groups (GLMq4w and GLMq8w) through discussion with each patient, considering their general condition and convenience. The groups included patients with low disease activity or in remission who switched to 50-mg GLM therapy at 4-week and 8-week intervals, respectively. Results: The mean DAS28-ESR and DAS-CRP values in the GLMq4w group (17 patients) and GLMq8w group (15 patients) were maintained from baseline throughout the 104-week treatment period. Two patients from the GLMq4w group showed disease flaring to moderate disease activity. No serious adverse events occurred, and the treatment continuation rate at 104 weeks was 100% in both groups. After > 2 years of treatment, three patients in the GLMq8w group and one patient in the GLMq4w group discontinued GLM treatment due to relapse or complications. The 5-year survival rates were 88.2% and 75.5% in the GLMq4w and GLMq8w groups, respectively. The average treatment duration was 5.0 (2.0–7.5) years. Conclusion: Administration of GLM-SC at 4-week and 8-week intervals after switching from TNF inhibitors showed sustained long-term efficacy and acceptable safety in RA patients with low disease activity. [ABSTRACT FROM AUTHOR]

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The fully porous long stem could be used for diaphyseal locking and achieve bypass fixation in revision total hip arthroplasty (THA). This study evaluated long-term results for fully porous long stems made of titanium alloy in revision THA. Methods: Between 2003 and 2010, 45 consecutive femoral revisions were performed using fully porous long stems. Thirty-eight hips had complete clinical and radiographic data for a mean of 13.8 years (range, 10–16.7 years). Femoral bone loss was Paprosky type II in 14 hips, type IIIA in 18 hips, and type IIIB in six hips. Clinical results were analyzed using the Merle d'Aubigné and Postel scoring system. Femoral stress shielding was graded. Radiological loosening of the femoral component was evaluated. Kaplan-Meier survival analysis was performed with revision for any reason as the end-point. Results: Mean Merle d'Aubigné and Postel score improved significantly from 10.7 before revision to 14.5 at latest follow-up (p < 0.001). Third-degree stress shielding was found in seven hips, and fourth degree in 11 hips. Radiological femoral loosening occurred in one hip, which was revised. Another hip was revised for stem fracture. Kaplan-Meier cumulative survival rate was 94.7% at both ten and 15 years. Conclusion: Although stress shielding is a concern with fully porous stems, this stem was useful in revision THA and provided satisfactory long-term results in hips with Paprosky types II, IIIA, and IIIB. [ABSTRACT FROM AUTHOR]

Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone. However, whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown. We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells. The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis, markedly reduced the progression of the brain tumors. The simultaneous application of fluphenazine (FP), an antipsychotic dopamine modulator, enhanced tumor suppression. Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2, respectively. Notably, dopamine downregulated Lrp5 via DRD1 in tumor cells. A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven, dopamine-mediated tumor suppression. The silencing of Lrp5 reduced CCN4, and the administration of CCN4 elevated oncogenic genes such as MMP9, Runx2, and Snail. In summary, this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1, indicating the possibility of developing an adjuvant bone-mediated loading therapy. [ABSTRACT FROM AUTHOR]

Purpose: Two-dimensional (2D) analyses of intervertebral disc (IVD) height and foramen measurements following lateral lumbar interbody fusion (LLIF) have been reported. However, three-dimensional (3D) morphometric analysis of intervertebral structure using 3D computed tomography (3D CT) provides increased precision for measuring morphological changes. The purpose of this study was to evaluate 3D changes of lumbar IVD height and foramen diameter in degenerative lumbar disease patients following LLIF.Methods: Subject-based 3D CT lumbar models were created for 26 patients before and following LLIF. IVD height (whole and five anatomical zones) and foramen diameter (minimum and maximum) were measured based on the model using custom software. The sagittal placement of cages (SPC) and cross-sectional area of the thecal sac (CSA) were measured. Changes in these parameters by LLIF were quantified and statistically analysed.Results: Following LLIF, disc height increased by an average of 2.9 mm (P < 0.01). Post-operative measurements of both minimum and maximum diameters of the foramen were significantly increased by 1.0 mm and 1.9 mm, respectively (P < 0.01). Change in maximum foramen diameter was significantly correlated with change in disc height (P < 0.05). The SPC was significantly correlated with the changes in disc height and foraminal diameters (P < 0.05, respectively). No significant change between the change in disc height and CSA was found.Conclusion: This preliminary study quantifies disc height and foramen diameter changes in 3D following LLIF. The presented data provide baseline intervertebral changes for future comparisons with follow-up studies and clinical outcomes.Level Of EvidenceI: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the accuracy of acetabular cup insertion during total hip arthroplasty (THA) in a supine position using an accelerometer-based portable navigation system. A single-surgeon study was conducted in which 62 prospective patients with navigation and 42 retrospective patients without navigation as historical controls were compared. The patients underwent THA via an anterolateral supine approach. The absolute values of errors of radiographic inclination and anteversion were calculated. The navigation error was also calculated. The factors that affected the absolute values of errors of cup alignment were determined. The mean absolute error of the postoperative CT measurement from the target angle for radiographic inclination was 3.8° in the navigation group and 6.6° in the control group (P < 0.001). The mean absolute error for anteversion was 3.3° in the navigation group and 5.9° in the control group (P < 0.001). The mean absolute values of navigation error were 3.7° ± 2.8° in inclination and 3.0° ± 2.6° in anteversion. Changes in the pelvic tilt angle among preoperative, intraoperative, and postoperative were the significant risk factors for the absolute values of navigation error of anteversion relative to the anterior pelvic plane. Other factors affecting the absolute values of errors in the navigation group were not found for radiographic inclination and anteversion. The portable navigation system significantly improved the accuracy of cup inclination and anteversion. Changes in the pelvic tilt were the risk factors for the error of anteversion relative to the anterior pelvic plane. [ABSTRACT FROM AUTHOR]

Background: We investigated the clinical outcomes of reconstruction using the latissimus dorsi (LD) flap after resection of soft-tissue sarcoma. Materials and methods: We analyzed 19 patients. Free LD flap was performed in 11 patients and pedicle flap in eight patients. The mean follow-up period after the surgery was 60 months. Results: The mean age at diagnosis was 57 years. The mean tumor size was 9.8 cm. The median size of the LD flap was 140 × 100 mm. The mean surgical duration and bleeding were 510 min and 602 mL, respectively. Complications included partial skin and soft-tissue necrosis (n = 3) and wound dehiscence (n = 2). No additional free flap was not necessary for the closure of the defect due to the complications. The longer surgical duration was significantly associated with wound complications (P = 0.048). The 5-year survival rate was 80.7%, and the local recurrence-free survival rate was 89.2%. Two patients developed local recurrence, while 6 patients developed metastasis. None of the patients had any restrictions of daily life. Conclusion: The LD flap after surgical tumor resection in patients with soft-tissue sarcoma was useful for the coverage of soft tissue. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate whether tendoscopic peroneal retinaculum repair for patients with recurrent peroneal tendon dislocation (RPTD) is more useful than an open procedure. Methods: Twenty-five patients with RPTD were retrospectively reviewed. Twelve patients (13 ankles) with RPTD underwent the open procedure (Group A) between 2008 and 2014, and 13 patients (14 ankles) underwent the tendoscopic procedure (Group B) between 2014 and 2017. Evaluation parameters included clinical results [the Japanese Society for Surgery of the Foot (JSSF) ankle-hind foot scale], operation time, complications, return to sports, and recurrence. Results: Postoperative JSSF ankle/hindfoot scale scores were significantly better than the pre-surgical scores in both groups. The mean operation time was significantly longer in Group B than in Group A (75.7 ± 20.5 vs 38.4 ± 10.5 min). There was one recurrence in Group A, but none in Group B. Group A had no complications, and Group B had one wound infection. Group B, excluding the case of infection, could return to sports earlier than Group A, excluding the recurrent case (13.4 ± 1.5 vs 12.2 ± 0.6 weeks). Conclusions: This tendoscopic procedure needs longer operation time and is more technically demanding, but it is a useful procedure, because it is less invasive and can accelerate return to sports. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The soluble form of PD-L1 (sPD-L1) is related to a poor prognosis in various cancers. Comparisons of sPD-L1 and PD-L1 expressed on tumor cells in soft tissue tumor patients have not been reported. The purpose of this study was to analyze serum sPD-L1 and PD-L1 levels in soft tissue tumor patients. A total of 135 patients with primary soft tissue tumors were enrolled in this study. The sPD-L1 level was quantitatively measured by enzyme immunoassay, and PD-L1 expression on high grade sarcoma cells was analyzed immunohistologically. There were no significant differences in sPD-L1 levels between benign (48) and soft tissue sarcoma (STS) patients (87). In STS, the high sPD-L1 (>44.26 pg/mL) group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low sPD-L1 group (≤44.26 pg/mL) at 5 years using the log-rank test. On multivariate Cox proportional hazard analysis, the high sPD-L1 group had significant differences in MS and OS compared to the low sPD-L1 group. Between positive and negative immunostaining groups, recurrence-free survival (RS), MS, and OS were not significantly different. No correlation was found between immunostaining and sPD-L1 with the Kappa coefficient. The sPD-L1 concentration could predict future metastasis and prognosis in STS patients. High sPD-L1 in STS patients may be a target for treatment with checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

The efficacy and safety of eribulin in Japanese patients with advanced soft-tissue sarcomas (STS) have not been evaluated in a large-scale cohort study. Thus, we aimed to investigate the clinical outcome of 82 Japanese patients with STS receiving eribulin across multiple study centers retrospectively. Of 82 STS patients receiving eribulin treatment, 13 were treated for locally unresectable tumor, 46 for metastasis, and 23 for both. The primary endpoint of this study was to evaluate the efficacy of eribulin against STS. The median age was 60 years. Thirty-seven were diagnosed with L-sarcoma (leiomyosarcoma or liposarcoma) and 45 had non-L-sarcoma. The median progression-free survival (PFS) for all patients was 2.7 months, with 3.4 months in those with L-sarcoma and 2.2 months in those with non-L-sarcoma. Patients with L-sarcoma showed a better PFS than those with non-L-sarcoma. Overall, the median survival time was 11.1 months, and 12.3 months and 7.9 months in patients with L-sarcoma and non-L-sarcoma, respectively; however, there was no significant differences between the groups. The prognostic significance of PS = 0 and both existence of local and metastatic STS was evaluated by multivariate analysis. We also evaluated the overall survival (OS) in patients with undifferentiated pleomorphic sarcoma (UPS) and other non-L-sarcomas. Patients with UPS had better OS than those with the other non-L-sarcomas. In conclusion, there was a significant difference in PFS between patients with L-sarcoma and non-L-sarcoma following treatment with eribulin. The anti-tumor potential of eribulin was evident in patients with UPS. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate skeletal pain associated with osteoporosis and examine the inhibitory effect of interleukin-6 (IL-6) on pain in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated by examining pain-related behavior and immunohistochemistry. The effects of IL-6 receptor inhibitor (IL-6i) on these parameters were also assessed. Eight-week-old female ddY mice were ovariectomized and assigned to three groups: OVX mice treated with vehicle (OVX); OVX mice treated with alendronate (OVX-ALN); and OVX mice treated with anti-IL-6 receptor (anti-IL-6R) antibody (OVX-IL6i). Sham-operated mice were treated with vehicle. Immediately after surgery, vehicle, ALN, or anti-IL-6R antibody was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was examined using von Frey filaments. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally with micro-computed tomography. Calcitonin gene-related peptide (CGRP) expression in L3-L5 dorsal root ganglion (DRG) neurons was examined using immunohistochemistry. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs with upregulation of CGRP expression in the DRG neurons innervating the hindlimbs. ALN treatment prevented bone loss, but anti-IL-6R antibody treatment had no effect on bone morphometry compared with that of the OVX group. However, mechanical hyperalgesia and CGRP expression were significantly decreased in the OVX-IL6i and OVX-ALN groups compared with those in the OVX group. Although anti-IL-6R antibody treatment had no effect on ovariectomy-induced bone loss, the treatment prevented ovariectomy-induced mechanical hyperalgesia in the hindlimbs and suppressed CGRP expression in DRG neurons. The results suggest that IL-6 is one of the causes of postmenopausal osteoporotic pain, and anti-IL-6R antibody might preserve bone health and decrease osteoporotic pain. [ABSTRACT FROM AUTHOR]

Summary: Here, we report the case of a 69-year-old female who discontinued denosumab to undergo dental treatment. She subsequently suffered rebound-associated vertebral fractures (RVFs) twice. Denosumab is approved in several countries for osteoporosis treatment. Its discontinuation can result in bone turnover rebound increase and rapid bone mineral density loss. Rebound-associated vertebral fractures (RVFs) after discontinuing denosumab have been widely reported. We previously reported the case of a patient who suffered RVFs after discontinuing denosumab to undergo dental treatment. A 69-year-old female suffered five acute VFs 10 months after the last denosumab injection. The current report identifies the risks associated with denosumab discontinuation to undergo dental treatment. The patient described in this report also underwent an additional clinical course after the first RVFs. Next month after the first RVFs, she developed severe back pain when she changed her posture. Magnetic resonance imaging showed new RVFs at T9 and T12 levels. This case indicates that RVFs may occur more than once. In addition, it suggests that additional denosumab injections do not completely eliminate the risk of RVFs. [ABSTRACT FROM AUTHOR]

Background: Interleukin-6 (IL-6) is a potent inflammatory cytokine that appears to play a key role in cancer growth and metastasis. In the present study, the effects of IL-6 receptor (IL-6R) on breast cancer aggressiveness and bone metastases were investigated.Methods: MDA-MB-231 (MDA-231) cells were treated in the presence or absence of anti-human IL-6 receptor (IL-6R) monoclonal antibody and examined with respect to cell survival. The expressions of signal transducer and activator of transcription 3 (Stat3), vascular endothelial growth factor (VEGF), and receptor activator of NF-κB (RANK) were analyzed by SDS-PAGE and immunoblotting. MDA-231 cells were injected into the left ventricle of mice, and then anti-human IL-6R monoclonal antibody or saline was administered intraperitoneally for 28 days. After 28 days, the incidence of bone metastases was evaluated in the hind limbs by radiography and histology.Results: Anti-human IL-6R monoclonal antibody reduced bone metastases in an animal model injected with MDA-231 cells on radiological and histomorphometric analyses. The mechanism of bone metastasis inhibition involved inhibited cell proliferation and decreased expressions of phospho-Stat3, VEGF, and RANK in MDA-231 cells.Conclusions: The results of the present study suggest that inhibition of IL-6 signaling may become a preventive therapeutic option for breast cancer and bone metastases. [ABSTRACT FROM AUTHOR]

Purpose: Quality-of-life (QOL) assessments in patients with osteonecrosis of the femoral head (ONFH) have rarely been reported. This multicentre study aimed to elucidate the relationship between disease severity, including necrotic lesion type and radiological staging, and QOL, as well as between patients' characteristics and QOL.Methods: Two hundred seventy-four patients with ONFH (108 females, 166 males; median age, 46 years) were asked to complete self-assessment QOL questionnaires including the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire, Oxford Hip Score, and SF-12v2.Results: Patients with large necrotic lesion type or collapsed ONFH had low QOL scores. Among patients with non-collapsed lesions, patients with alcohol-associated ONFH had lower QOL scores than those with steroid-associated ONFH, those with bilateral ONFH had lower mental scores, and male patients had worse social condition scores. Among patients with collapsed lesions, middle-aged patients exhibited lower mental QOL, and a strong correlation was observed between social activity and mental health.Conclusion: Collapsed ONFH was associated with low QOL scores. Among patients with non-collapsed lesions, alcohol-associated ONFH, bilateral disease, and male sex were linked to low QOL scores. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the efficacy of osteoporosis medication in patients with low levels of walking state, namely, influence by immobilization levels. We retrospectively compared the efficacy of the daily teriparatide therapy in patients with low and high levels of walking state to detect possible immobilization-related differences. Methods: We analyzed 661 patients treated with 20 μg/day of teriparatide for 24 months. We measured the changes in the bone mineral density (BMD) of the lumbar spine (LS) and of the femoral neck (FN), the changes in serum procollagen type I N-terminal propeptide (PINP) levels and urinary N-telopeptide (uNTX) excretion. To compare the results of BMD and bone turnover marker, the patients were divided into two subgroups, low levels of walking state and high levels of walking state. Results: Compared with baseline, in the low levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 12.8 ± 8.9% and 5.0 ± 13.8% at 24 months, respectively ( p < 0.01 vs baseline for LS and FN, respectively); the mean absolute LS BMD and FN BMD change was 0.101 ± 0.067 g/cm and 0.017 ± 0.063 g/cm at 24 months, respectively. In the high levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 13.4 ± 9.5% and 3.1 ± 7.8% at 24 months, respectively; the mean absolute LS BMD and FN BMD change was 0.104 ± 0.068 g/cm and 0.017 ± 0.042 g/cm at 24 months, respectively. The increases in percent and absolute BMD in LS and FN, and the changes in PINP and uNTX were similar between the subgroups. Conclusions: The efficacy of the daily teriparatide treatment is similar between low levels of walking state patients and high levels of walking state patients and was not influenced by immobilization levels. [ABSTRACT FROM AUTHOR]

Summary : Previous reports demonstrated that bone density decreased rapidly during the initial few months of steroid therapy and continued decreasing at a rate of 2 to 4% annually. Our data indicates that denosumab can also play a role in the treatment of osteoporosis in the steroid-taking population. Introduction: Respiratory physicians are often faced with the dilemma that long-term steroid use will deteriorate bone mineral density and quality. Previous reports demonstrated that bone density decreased 8 to 12% during the initial few months of steroid therapy then continued decreasing at a rate of 2 to 4% annually. Several prospective trials revealed that denosumab increased bone density in patients with osteoporosis [2-4] and decreased the rate of occurrence of fractures. The long-term efficacy of denosumab for glucocorticoid-induced osteoporosis, however, has not yet been proven. Materials: This has been an ongoing prospective study since 2014. In our respiratory centre, the first preventative measure used to combat glucocorticoid-induced osteoporosis (GIO) is oral bisphosphonates. Thirty-six patients were enlisted, and their treatment courses were changed from oral bisphosphonate, if administered, to the subcutaneous injection of denosumab 60 mg every 6 months, combined with a daily oral intake of DENOTAS® chewable combination tablets. The primary efficacy measures were changes in lumbar spine (LS) bone mineral density (BMD) and femoral BMD from baseline at 4, 8, 12 and 28 months. Results: At the 12-month follow-up, bone mineral density in the lumbar spine area of these patients increased by 3.2%, while bone mineral density in the hip area showed no significant increase. At the 28-month follow-up, 25 patients were still included in this study. Femoral BMD at 28 months increased significantly from the 12-month follow-up ( P = 0.0259), though the first 12 months showed no significant increase. LS BMD continued to increase through the 28-month period. Conclusions: Very little is known regarding the active prevention of GIO. Our data indicates that denosumab can play a promising role in the treatment of GIO. [ABSTRACT FROM AUTHOR]

The study was conducted to evaluate continued maintenance of the efficacy and safety of therapy by switching to subcutaneous golimumab (GLM-SC) in rheumatoid arthritis patients with low disease activity or remission who previously received a tumor necrosis factor (TNF) inhibitor. Thirty patients who had been treated with etanercept or infliximab were switched to GLM-SC in maintaining disease activity at a low level. The patients were divided into two groups through discussion with each patient, considering general condition and convenience: the low disease activity (LDA) group and the LDAq8w group, which included patients with low disease activity or remission who switched to 50 mg GLM therapy at 4- and 8-week intervals, respectively. The effects of the TNF inhibitors to GLM-SC switch were evaluated at 12, 24, and 52 weeks after switching. The mean DAS28-ESR and DAS-CRP values in the LDA groups (16 patients) and LDAq8w groups (14 patients) were maintained from baseline throughout the 52-week treatment period. DAS28-ESR remission (93.8 and 92.3%) rates were also maintained through week 52 from the baseline remission rate (75.0 and 78.6%) in the LDA and LDAq8w groups, respectively. Thus, both GLM-SC treatment regimens were effective in maintaining the clinical response achieved with LDA secondary to TNF inhibitors. No serious adverse events occurred, and the continuation rate at 52 weeks was 100% in both groups. Therapeutic efficacy is adequately maintained in most patients switching from TNF inhibitor to GLM-SC (50 mg/4-8 weeks). Patients receiving TNF inhibitor can seamlessly switch to GLM-SC without serious safety concerns. [ABSTRACT FROM AUTHOR]

Background: Some rheumatoid arthritis (RA) patients initially respond to treatment with infliximab (IFX), but subsequently their responsiveness decreases. Objectives: Our objective was to evaluate the efficacy and safety of switching from IFX to subcutaneous golimumab (GLM-SC) in RA patients. Methods: Thirty-three patients who had been treated for a mean 4.4 years with IFX (3-6 mg/kg/8 weeks) were switched to GLM-SC to control disease activity or adverse events. The patients with low disease activity (LDA) or remission were divided into two groups: the LDA group and the LDA every 8 weeks (q8w) group, which included patients with LDA or remission who switched to GLM therapy with 50 mg at 4- and 8-week intervals, respectively. The moderate disease activity (MDA) group included patients with MDA who switched to GLM therapy with 50 mg at 4-week intervals. Effects of the IFX to GLM-SC switch were evaluated at weeks 12, 24, and 52 after switching. Results: The mean disease activity score 28-ESR and -C-reactive protein values in the LDA and LDAq8w groups were maintained from baseline throughout the 52-week treatment period. The mean disease activity score 28 values at 12, 24, and 52 weeks in the MDA group were improved significantly compared with baseline. Treatment discontinuations due to adverse events occurred in one patient in the MDA group, and no serious adverse events occurred during the observation period in the LDA group or the LDAq8w group. The GLM continuation rates at 52 weeks were 100% in the LDA and LDAq8w groups and 83.3% in the MDA group. Thus, GLM-SC treatment regimens were effective in controlling disease activity and improving the clinical response related to adverse events caused by IFX. Conclusion: The clinical efficacy of GLM-SC was sustained or improved in patients who switched from IFX without serious safety concerns. [ABSTRACT FROM AUTHOR]

The degree of correlation between the first 12 months and the latter 12 months of increased bone mineral density (BMD) with teriparatide treatment is unknown. We retrospectively investigated the correlation between the first 12 months and the latter 12 months of increased BMD owing to teriparatide treatment. We retrospectively analyzed 357 patients (mean age, 78 years) with osteoporosis treated with teriparatide 20 μg/day for 24 months. The primary efficacy measure was the correlation between lumbar spine (LS) and femoral neck (FN) BMD increases from baseline to 12 months and from 12 to 24 months. The correlation between the first 12 months and the latter 12 months of increased BMD was evaluated. We investigated the correlation between the increases in BMD and the baseline procollagen type I N-terminal propeptide (PINP) concentration. LS BMD significantly increased by 9.7 ± 8.3 % in the first 12 months and 3.5 ± 4.8 % in the latter 12 months. FN BMD increased by 2.2 ± 8.4 % in the first 12 months and 1.3 ± 4.9 % in the latter 12 months. Increased LS and FN BMD were not significantly correlated between the first 12 months and the latter 12 months. The serum baseline PINP concentration was correlated with the LS BMD in the first 12 months, and similarly, the PINP concentration at 12 months was correlated with the latter 12 months of increased LS BMD. Increased BMD by teriparatide treatment in the first 12 months and the latter 12 months was not significantly correlated. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a common complication in patients who have undergone major orthopedic surgery, but there are few predictors of VTE after major orthopedic surgery treated with an anticoagulant. We measured levels of fibrin-related markers (FRMs), such as D-dimer, soluble fibrin (SF), and fibrinogen and fibrin degradation products (FDPs) in 66 patients with acute-phase VTE, and 367 patients undergoing major orthopedic surgery. Plasma FDP, D-dimer, and SF levels were significantly higher in patients with acute VTE, but only FDP and D-dimer levels were significantly higher in subclinical VTE. Adequate cut-off levels of D-dimer were 2.2 μg/ml for diagnosing acute VTE and 1.5 μg/ml for diagnosing subclinical VTE. D-dimer of less than 1.9 or 0.7 μg/ml ruled out acute VTE or subclinical VTE. D-dimer of more than 1.3 μg/ml preoperatively showed a moderate risk for postoperative VTE. Measurement of FRMs is useful for evaluating the risk of subclinical or postoperative VTE in patients with major orthopedic surgery. In particular, FDP is the most valuable marker for diagnosing acute VTE, whereas D-dimer is the most valuable for diagnosing subclinical VTE or predicting VTE. [ABSTRACT FROM AUTHOR]

Anti-Xa assays are useful for monitoring the effects of selective anti-Xa drugs, such as fondaparinux, in the prophylaxis of deep vein thrombosis. In the present study, anti-Xa activity was measured using three different assays, Testzym(®) Heparin S, STA(®)-Liquid Anti-Xa and HemosIL(®) Liquid Heparin. Anti-Xa activity in each assay gradually increased from day one after administration to day eight, and still remained on day 15. Although there were significant differences in anti-Xa activity among the three assays, the activity showed significant correlation across assays. There were no significant differences in the anti-Xa activity between patients with and without DVT or between patients with and without massive bleeding on day one before and after administration, day four, day eight and day 15. Anti-Xa activity in each assay was weakly correlated with antithrombin (AT) activity. The AT activity in patients were significantly higher on days four, eight and 15 compared with day one before and after administration, suggesting that AT activity increases following the administration of fondaparinux. The three anti-Xa assay kits tested are useful for monitoring fondaparinux treatment in orthopedic surgery patients. [ABSTRACT FROM AUTHOR]

Although elevated preoperative serum C-reactive protein (CRP) level is an indicator of a poorer prognosis in many cancers including non-metastatic bone and soft tissue sarcoma, there have been no reports focused on sarcoma patients with advanced stage who had distant metastases. The aim of this study is to determine whether the serum CRP level after metastasis is associated with post-metastatic survival in patients with bone and soft tissue sarcoma. A total of 71 patients were studied including 38 male and 33 female. Of all patients, 22 patients had metastases at presentation. The remaining 49 patients developed initial metastasis after the treatment of primary tumor. The average age at the diagnosis of metastasis was 55 years. Blood was obtained after initial detection of metastasis. CRP levels ranged from 0.1 to 165 mg/L with an average of 16.4 mg/L in all patients. Elevated CRP levels (>3 mg/L) were seen in 31 patients (range 3.1-165). The disease-specific survival after metastasis estimates at 3 and 5 years was 17.1 and 17.1 % for those with an elevated CRP vs. 59.5 and 45.3 % for those with a normal CRP ( p < 0.0001). In 49 patients who developed lung metastasis after initial primary treatment, patients with elevated CRP levels also had a poorer post-metastatic survival than patients with normal CRP levels ( p < 0.0001). In conclusion, we recommend routine measurement of CRP level to identify the patients who have high risk of death after metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to assess the orientation and distance of the popliteal artery (PA) from both the anteromedial and anterolateral portals. Methods: The records of 97 patients (100 knees) who underwent knee arthroscopy were reviewed. The shortest distance from the posterior tibial cortex to the PA on the lines from both the medial and lateral borders of the patellar tendon to the PA was evaluated by magnetic resonance imaging at full knee extension. The figure-of-four position was compared between patients with intact and deficient anterior cruciate ligaments (ACLs). The shortest distances from the posterior cruciate ligament (PCL) to the lines running from the medial and lateral borders of the patellar tendon to the PA were also measured. Results: The shortest distances from the posterior tibial cortex to the PA were significantly longer in the figure-of-four position than at full knee extension and during extension in the ACL-deficient than intact group. Distances did not significantly differ in the figure-of-four position. The PA was hidden from the anteromedial portal by the PCL, but remained vulnerable from the anterolateral portal. Conclusions: All-inside meniscus suturing of the posterior horn of the lateral meniscus inserted through the anteromedial portal is safer when the knee is in the figure-of-four position than fully extended. Meniscus repairs should be completed before ACL reconstruction due to vascular positions and the ease of approach. Level of evidence: Prospective correlation study, Level IV. [ABSTRACT FROM AUTHOR]

We investigated the incidence of disability and its risk factors in older Japanese adults to establish an evidence-based disability prevention strategy for this population. For this purpose, we used data from the Longitudinal Cohorts of Motor System Organ (LOCOMO) study, initiated in 2008 to integrate information from cohorts in nine communities across Japan: Tokyo (two regions), Wakayama (two regions), Hiroshima, Niigata, Mie, Akita, and Gunma prefectures. We examined the annual occurrence of disability from 8,454 individuals (2,705 men and 5,749 women) aged ≥65 years. The estimated incidence of disability was 3.58/100 person-years (p-y) (men: 3.17/100 p-y; women: 3.78/100 p-y). To determine factors associated with disability, Cox's proportional hazard model was used, with the occurrence of disability as an objective variable and age (+1 year), gender (vs. women), body build (0: normal/overweight range, BMI 18.5-27.5 kg/m; 1: emaciation, BMI <18.5 kg/m; 2: obesity, BMI >27.5 kg/m), and regional differences (0: rural areas including Wakayama, Niigata, Mie, Akita, and Gunma vs. 1: urban areas including Tokyo and Hiroshima) as explanatory variables. Age, body build, and regional difference significantly influenced the occurrence of disability (age, +1 year: hazard ratio 1.13, 95 % confidence interval 1.12-1.15, p < 0.001; body build, vs. emaciation: 1.24, 1.01-1.53, p = 0.041; body build, vs. obesity: 1.36, 1.08-1.71, p = 0.009; residence, vs. living in rural areas: 1.59, 1.37-1.85, p < 0.001). We concluded that higher age, both emaciation and obesity, and living in rural areas would be risk factors for the occurrence of disability. [ABSTRACT FROM AUTHOR]

Prevention of deep vein thrombosis (DVT) is important in patients undergoing major orthopedic surgery. Although the detection of an elevated d-dimer level is useful for predicting DVT, it is not efficacious in postoperative patients being treated with anti-Xa agents. The soluble platelet glycoprotein VI (sGPVI) level is a marker of activated platelets, but not bleeding. Therefore, sGPVI levels are usually examined as a predictor of DVT in such patients. In the present study, 83 orthopedic patients were treated with 30 mg of edoxaban for prophylaxis of DVT. Fourteen patients developed DVT and 17 patients discontinued the prophylaxis due to decreased hemoglobin levels. Plasma levels of sGPVI in the patients were significantly higher after surgery than before surgery. On day 1, the sGPVI levels increased, while the platelet counts decreased. There were no significant differences in d-dimer, soluble fibrin, or FDP levels in orthopedic patients with and without DVT before surgery and on days 1, 4, and 8. Plasma sGPVI levels were significantly higher in the patients with DVT than in those without DVT on days 1 and 4. Plasma levels of d-dimer were significantly higher in patients with withdrawal than in those without. However, there were no significant differences in sGPVI levels between those with and without withdrawal. As d-dimer levels are known to increase in patients with withdrawal, this parameter is not useful for evaluating the risk of DVT in these patients. In contrast, the sGPVI level is not increased in those with withdrawal and may therefore be useful for evaluating the risk of DVT in postoperative patients treated with an anticoagulant. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate the safety and clinical utility of radiofrequency ablation (RFA) retrospectively in non-surgical candidates with recurrent bone and soft-tissue sarcomas. Methods: Percutaneous RFA was used in 52 patients (21 female, 31 male; mean age, 52.2 ± 21.1 years; range 10-87 years) with recurrent bone and soft-tissue sarcomas. The number of tumors was 3 or fewer in 23 patients (44.2 %) and 4 or more in the others, with a mean maximum tumor diameter of 3.0 ± 3.7 cm (range 0.5-18 cm). Safety, tumor control, and prognosis were evaluated. Results: All tumors were ablated after RFA in 21 patients (40.4 %, 21/52), although 14 experienced re-recurrence. Tumors were controlled in 8 cases of recurrence by repeat RFA ( n = 7) and surgical intervention ( n = 1). Therefore, 15 patients (28.8 %, 15/52) were tumor-free at the end of follow-up (mean follow-up 25.5 ± 24.2 months; range 3.9-117 months). Residual tumors were found after RFA in the other 31 patients (59.6 %, 31/52). Overall survival rates were 73.4 % (95 % CI 61.0-85.9 %) at 1 year, 39.3 % (95 % CI 23.6-54.9 %) at 3 years, and 34.3 % (95 % CI 18.0-50.7 %) at 5 years in all patients. Recurrence-free interval ( p = 0.040), tumor number ( p = 0.0094), and complete tumor ablation ( p < 0.0001) were detected as significant prognostic factors in univariate analysis. The latter two factors were significant in multivariate analysis. The rate of major complications was 0.9 %. Conclusions: RFA is a safe and useful therapeutic option for treatment of recurrent bone and soft-tissue sarcomas. Prognostic factors found in this study will help to identify those patients who would benefit from RFA. [ABSTRACT FROM AUTHOR]

The Longitudinal Cohorts of Motor System Organ (LOCOMO) study was initiated in 2008 through a grant from the Ministry of Health, Labour, and Welfare of Japan to integrate information from several cohorts established for the prevention of musculoskeletal diseases. We integrated the information of 12,019 participants (3,959 men and 8,060 women) in the cohorts comprising nine communities located in Tokyo (two regions: Tokyo-1 and Tokyo-2), Wakayama [two regions: Wakayama-1 (mountainous region) and Wakayama-2 (seaside region)], Hiroshima, Niigata, Mie, Akita, and Gunma prefectures. The baseline examination of the LOCOMO study consisted of an interviewer-administered questionnaire, anthropometric measurements, medical information recording, X-ray radiography, and bone mineral density measurement. The prevalence of knee pain was 32.7 % (men 27.9 %; women 35.1 %) and that of lumbar pain was 37.7 % (men 34.2 %; women 39.4 %). Among the 9,046 individuals who were surveyed on both knee pain and lumbar pain at the baseline examination in each cohort, we noted that the prevalence of both knee pain and lumbar pain was 12.2 % (men 10.9 %; women 12.8 %). Logistic regression analysis showed that higher age, female sex, higher body mass index (BMI), living in a rural area, and the presence of lumbar pain significantly influenced the presence of knee pain. Similarly, higher age, female sex, higher BMI, living in a rural area, and the presence of knee pain significantly influenced the presence of lumbar pain. Thus, by using the data of the LOCOMO study, we clarified the prevalence of knee pain and lumbar pain, their coexistence, and their associated factors. [ABSTRACT FROM AUTHOR]

Purpose: The Japanese Musculoskeletal Oncology Group have developed an original prosthesis called the Kyocera Modular Limb Salvage system (KMLS system). This prosthesis has a semi-rotating hinge joint and is particularly designed for people with an Asian body type. The metallic parts of the prosthesis are made entirely of titanium alloy. The purpose of this study is to evaluate the clinical outcomes of treatment using this system following tumour resection of primary bone sarcoma of the distal femur. Methods: Between 2002 and 2010, 82 patients with primary bone sarcomas of the distal femur were treated. Seventeen patients underwent stem cementation, while 65 patients were treated with cementless prostheses. The mean follow-up period after surgery was 61 months. Results: Complications were observed in 28 of the 82 patients. Forty-one complications occurred in these 28 patients. Thirteen prostheses (16 %) required revision surgery due to complications, including five cases of stem breakage, three deep infections, three cases of aseptic loosening, one case of displacement of the shaft cap and one case of breakage of the tibial tray. The five-year overall prosthetic survival rate was 80.0 %. Four of the 82 patients underwent subsequent amputation due to local recurrence. The five-year limb salvage rate was 94.5 %. The mean function score according to the scoring system of the Musculoskeletal Tumour Society was 21.8 points (72.5 %). Conclusions: Although further follow-up is required to determine the performance, this prosthesis is considered to be satisfactory for reconstruction of the distal femur after resection of bone sarcoma. [ABSTRACT FROM AUTHOR]

Background: Breast cancer has the potential to metastasize to bone, causing debilitating symptoms. Although many tumor cells have thrombin-generating systems originating from tissue factor (TF), therapy in terms of the coagulation system is not well established. To elucidate the efficacy of the thrombin inhibitor, argatroban, on bone metastasis, we investigated TF activation and vascular endothelial growth factor (VEGF) secretion on treatment with thrombin and argatroban. Methods: MDA-231 breast cancer cells were treated with thrombin in presence or absence of argatroban, and TF activity was measured in the form of activated factor X. Enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF concentrations in the medium. MDA-231 cells were injected into the left heart ventricle of mice, and then argatroban or saline was administered intraperitoneally for 28 days. After 28 days, incidence of bone metastasis was evaluated in the limbs by radiography. Results: TF activity and VEGF secretion were upregulated by thrombin. Argatroban inhibited the enhancement of TF activity and VEGF secretion induced by thrombin. In vivo analysis revealed that the number of metastasized limbs in the argatroban group was significantly lower compared with the saline group ( P < 0.05). Conclusions: Thrombin not only enhances VEGF secretion but also has a positive feedback mechanism to reexpress TF. These results indicate that inhibition of thrombin is of great value in suppression of tumor metastasis. Argatroban is a noteworthy and useful thrombin inhibitor because it has already been used in the clinical setting and has antimetastatic effects in vivo. [ABSTRACT FROM AUTHOR]

Purpose: The disease activity score including 28 joints (DAS28), the simplified disease activity index and the clinical disease activity index (CDAI) were developed in order to provide a quantifiable measure of rheumatoid arthritis (RA) activity. Although inflamed hip joints greatly impact activities of daily living (ADL) and walking ability, the hip joint was not included in the DAS28, SDAI or CDAI assessments. Although excellent clinical results have been reported for total hip arthroplasty (THA) in RA patients, correlations between disease activity and hip function in RA patients after THA remain unknown. Methods: We analysed the effect of RA disease activity on a hip function score in an observational cohort of RA patients after THA. Twenty-five registered RA patients who had undergone THA (33 joints) were included. Hip function was recorded and RA disease activity was measured on the same day. The mean age of the patients was 65.17 years. They were followed up for a mean of 5.24 years after surgery. The mean duration of disease following RA diagnosis for this patient group was 19.47 years. The Japanese Orthopaedic Association (JOA) hip score was used as a clinical outcome measure for hip dysfunction. RA disease activity and health-related quality of life were measured using the DAS28, SDAI, CDAI and the modified health assessment questionnaire (MHAQ). Results: The mean JOA score for hip function was 80.48 at the final follow-up. The mean DAS28-ESR, DAS28-CRP, SDAI, CDAI and MHAQ measuring RA disease activity levels were 3.38, 2.65, 9.59, 8.63 and 0.44, respectively, at the final follow-up. There was a significant negative correlation between the JOA hip score and all disease activity assessments observed after THA (DAS-ESR [ P = 0.0067], DAS-CRP [ P = 0.0008]), SDAI [ P = 0.0034], CDAI [ P = 0.0003]) and MHAQ [ P = 0.0002]). Conclusion: We found significant negative correlations between JOA hip scores and all disease activity assessments in RA patients treated with THA. [ABSTRACT FROM AUTHOR]

The present study retrospectively assessed the efficacy of tocilizumab in patients with rheumatoid arthritis (RA) who failed to respond to treatment with etanercept or infliximab. A retrospective study of 33 RA patients who did not respond to etanercept or infliximab was conducted. Responses of subjects switching from etanercept to tocilizumab ( n = 17) were compared with those switching from infliximab to tocilizumab ( n = 16). Treatment with disease-modifying antirheumatic drugs before the switch, especially methotrexate (MTX), was maintained. Disease activity was assessed by the Disease Activity Score 28-C Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Patients who switched from etanercept were significantly less likely to have used MTX and were significantly older than patients who switched from infliximab. In both groups, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values at 24 weeks with no significant differences between groups. However, at week 52, DAS28-CRP, SDAI, and CDAI values in the group switched from etanercept were significantly worse than those in the group switched from infliximab. All patients switched from infliximab were using MTX. In the evaluation between patients who switched from etanercept monotherapy, etanercept plus MTX, and infliximab plus MTX, a significant improvement from baseline was seen in DAS28-CRP, SDAI, and CDAI for all patients at 24 weeks with no significant differences between groups. Disease activity was maintained at 52 weeks in the group that switched from etanercept plus MTX and infliximab plus MTX. However, the efficacy of tocilizumab was decreased in the group that switched from etanercept monotherapy. Switching from etanercept plus MTX or from infliximab plus MTX to tocilizumab plus MTX improved response to therapy, but switching from etanercept monotherapy to tocilizumab monotherapy did not improve response to therapy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the accuracy of bone cutting and implantation in minimally invasive total knee arthroplasty with image-free navigation. Methods: The alignment of the tibial and femoral bone resection was measured in 40 knees during surgery. The alignment measurement was repeated after cementing the tibial and femoral components. We evaluated the cutting error and the implanting error. Results: The mean tibial cutting errors were 0.5 and 0.7° in the frontal and sagittal planes, respectively. The mean femoral cutting errors were 0.5 and 0.9° in the frontal and sagittal planes, respectively. The mean tibial implanting errors were 1.0 and 0.9° in the frontal and sagittal planes, respectively. The mean femoral implanting error was 0.7° in the frontal plane. Conclusions: Computer-assisted navigation was useful in checking the alignment of both bone cut and cementation. [ABSTRACT FROM AUTHOR]

We determined whether repeated treatment with the tumor necrosis factor-α (TNF-α) antagonist etanercept can be effective after an initial clinical response to this drug is lost. We describe three female patients with active, refractory rheumatoid arthritis who were administered with a second course of etanercept after eventually becoming refractory to a first course. Disease activity was high in all three patients before initial etanercept therapy, and each of them had clinically responded by 24 weeks. However, the initial clinical effect was lost between 1.5 and 3.5 years thereafter, and tocilizumab was administered, but the effect was lost again between 3 and 18 months later. Two patients did not respond to subsequent treatment with adalimumab and infliximab. Etanercept administered once again reduced disease activity in all three patients, none of whom developed any acute side effects. Etanercept re-administration significantly improved clinical disease activity and inflammatory parameters in three patients with RA who were refractory to biological anti-TNF agents. [ABSTRACT FROM AUTHOR]

We evaluated hemostatic markers in patients who underwent major orthopedic surgery, including total hip and total knee arthroplasty, and were treated for the prophylaxis of deep vein thrombosis (DVT) with or without fondaparinux (anti-Xa group, n = 98 and without anti-Xa group, n = 20). The frequency of DVT was significantly higher in the without anti-Xa group than in the anti-Xa group, but the reduction of hemoglobin and fibrinolytic marker levels was significantly lower in the without anti-Xa group than in the anti-Xa group. Eighteen patients in the anti-Xa group showed a reduction in hemoglobin of more than 2 g/dl, and those individuals were considered to be the increased bleeding (IB) group. The concentration of fibrinolytic markers in the anti-Xa group was significantly higher in the IB group than in the non-IB group. There were also no significant differences in the levels of anti-Xa activity, plasminogen activator inhibitor-I, soluble fibrin and antithrombin between the IB and non-IB groups. In conclusion, elevated fibrinolysis induced by increased bleeding may lead to further increases in bleeding in patients receiving thromboprophylaxis with fondaparinux following major orthopedic surgery. [ABSTRACT FROM AUTHOR]