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Objectives: The current study compared the outcome after orthopaedic surgeries in patients with rheumatoid arthritis receiving Janus kinase inhibitors (JAKis) versus biologic disease-modifying anti-rheumatic drugs (bDMARDs)., Methods: This was a retrospective observational study of Japanese patients with rheumatoid arthritis. Sixty-two patients with rheumatoid arthritis using JAKi preoperatively underwent orthopaedic surgeries. Using propensity score matching, these 62 patients were matched with 62 patients using bDMARDs preoperatively. The number of adverse events was counted. We also examined whether the drug-withholding period in the JAKi-treated group was associated with the occurrence of major postoperative adverse events, namely inflammatory flares and delayed wound healing., Results: JAKi-treated patients had a higher incidence of postoperative flares than bDMARD-treated patients (29% versus 12.1%, P = .01). The incidences of postoperative complications other than flares were not significantly different between the two groups. Among the JAKi-treated group, a longer perioperative drug-withholding period (≥11 days) was associated with a higher incidence of postoperative flares (P = .04). The incidences of delayed wound healing and surgical site infection were not associated with the duration of the JAKi-withholding period., Conclusions: JAKi-treated patients had a higher incidence of postoperative flares than bDMARD-treated patients. A total of ≥11 days of drug withdrawal was associated with postoperative flares., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro . STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

Objectives: The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA., Methods: We extracted 190 hips over two periods, i.e. the early period (1998-2003) and the late period (2013-19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty., Results: A comparison of the two periods' data showed that the degree of inward migration (-3.44 vs. -7.45 mm; P < .001) and upward migration (+4.3 vs. +0.95 mm; P < .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P < .001)., Conclusions: The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The study aimed to comprehend the clinical features and outcomes of surgical treatments for spinal disorders in patients with ankylosing spondylitis (AS)., Methods: This retrospective study enrolled patients with AS who underwent spine surgery between 2000 and 2019 in our facility., Results: Thirteen patients with AS underwent spine surgeries. The mean age was 56.2 years, and the mean disease duration was 25.1 years at the time of surgery. Nine patients had vertebral fracture, two had kyphotic deformity, and two had myelopathy due to the spinal ligament ossification. Fracture cases included five patients with secondary pseudarthrosis/delayed palsy due to conservative treatment failure. Spinal fixation was performed in all patients. Pedicle subtraction osteotomy for kyphosis and laminectomy for myelopathy were also conducted. All patients improved after surgeries. One patient with kyphotic deformity underwent additional surgery of bilateral hip prosthesis, which resulted in better spine alignment. Four cases of perioperative complications were observed., Conclusion: Myelopathy was newly found as the aetiology requiring surgery in patients with AS. This summarized case series could help physicians to identify patients with surgically treatable spinal disorders among patients with AS., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Whether the characteristics of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) have changed in the era of biologic disease-modifying antirheumatic drugs (bDMARDs) is unclear. We compared the radiographic findings of the knees in TKA recipients with RA before and after the introduction of bDMARDs., Methods: Consecutive patients who underwent primary TKA between 1999 and 2002 (115 knees; 79 patients, group A) and between 2013 and 2017 (117 knees; 95 patients, group B) were retrospectively evaluated. Clinical data, including disease duration, medication, C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were collected. The Larsen classification, joint space narrowing (JSN), bone erosion, and geode and osteophyte formation were evaluated on preoperative radiographs., Results: Osteophyte formation was significantly increased, and bone erosion and geode formation were significantly decreased in group B. In addition, medial-dominant JSN was significantly increased, and bicompartmental JSN was significantly decreased in group B. Medial-dominant JSN was positively and bone erosion was negatively associated with osteophyte formation., Conclusions: Following the introduction of bDMARDs, typical radiographic findings of rheumatoid knees have decreased, and secondary osteoarthritis-like changes, characterized by osteophyte formation and medial-dominant JSN, have increased in the knees of TKA recipients., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumors and tumor-like lesions of the foot and ankle are relatively rare and their postoperative clinical outcome has not been well reported., Methods: This study retrospectively reviewed medical records of all patients who underwent excision of tumors and tumor-like lesions of the foot and ankle from 2008 to 2020. Preoperative and postoperative clinical outcomes were evaluated by the Japanese Society for Surgery of the Foot (JSSF) scales (pain, function, and alignment)., Results: A total of 117 consecutive patients were analyzed in this study. Bone lesions accounted for 51 patients (benign: 45, intermediate malignancy: 1, malignant: 5), and soft tissue lesions accounted for 66 patients (benign: 57, intermediate malignancy: 2, malignant: 7). Four patients (8%) presenting with bone tumor and six (9%) soft tissue tumors resulted in recurrence. Eight (67%) patients with malignant lesions were alive continuously disease free and followed for a median of 50.5 (range: 18 to 82) months. Amputation at the first operation was done for five cases (33%) of malignant or intermediate malignancy (below-knee amputation: 1, Chopart disarticulation: 1, forefoot amputation: 3). Postoperative JSSF scores resulted in a significant 'positive' increase (bone lesion, 75.9 ± 13.7 to 91.4 ± 14.9, p < 0.001; soft tissue lesion, 84.7 ± 14.8 to 91.9 ± 12.5, p < 0.001). The score improvement in bone lesions was significantly higher than in soft tissue lesions (p = 0.003)., Conclusion: The surgical management of tumors and tumor-like lesions of the foot and ankle showed good post-operative functional outcomes with bone lesions exhibiting better results when compared to soft-tissue lesions., (© 2022. The Author(s).)

Background: Hallux valgus (HV) is a common foot deformity for which several corrective surgical procedures, with different osteotomy sites, have been reported. The purpose of the present study was to systematically review randomized (RCTs) or controlled (CCTs) clinical trials and perform meta-analysis on outcomes of different osteotomy sites of the first metatarsal., Methods: An extensive literature search was conducted in PubMed and the Cochrane Library from January 1983 to July 2020. Studies were identified using the terms "hallux valgus" and "osteotomy". We included RCTs or CCTs comparing different locations of osteotomy for the first metatarsal bone (distal vs. mid-shaft, distal vs. proximal, and mid-shaft vs. proximal). The surgical outcomes included postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society (AOFAS) score, pain visual analog scale (VAS) score, perioperative complications and recurrence of deformity. We enrolled 10 studies with a total of 793 feet in the qualitative synthesis following full-text screening., Results: A majority of patients included in the enrolled trials showed mild to moderate deformity, with mean HVA <40°. Out of the 10 enrolled studies; six compared distal osteotomies with mid-shaft osteotomies and showed no significant differences in the surgical outcomes between the scarf and chevron groups; three RCTs compared distal osteotomies with proximal osteotomies with conflicting results, one RCT showed the superiority of proximal osteotomy while the other two RCTs showed equivalent outcomes; one study that compared between mid-shaft and proximal osteotomies showed equivalent outcomes between the groups., Conclusion: For the management of mild to moderate HV deformity, we found no significant clinical and radiological differences between patients treated with scarf and chevron osteotomies. Further controlled trials comparing different sites of osteotomies for moderate to severe HV deformity are needed.

Background: Rheumatoid arthritis (RA) often causes cervical spine lesions as the disease condition progresses, which induce occipital neuralgia or cervical myelopathy requiring surgical interventions. Meanwhile, patients with RA are susceptible to infection or other complications in the perioperative period because they frequently have comorbidities and use immunosuppressive medications. However, the risk factors or characteristics of patients with RA who experience perioperative complications after cervical spine surgery remain unknown. A risk factor analysis of perioperative complications in patients with RA who underwent primary cervical spine surgery was conducted in the present study., Methods: A total of 139 patients with RA who underwent primary cervical spine surgery from January 2001 to March 2020 were retrospectively investigated. Age and height, weight, serum albumin, serum C-reactive protein, American Society of Anesthesiologists Physical Status (ASA-PS), Charlson comorbidity index, medications used, cervical spine lesion, surgery time, bleeding volume, and procedures were collected from medical records to compare the patients with complications to those without complications after surgery. The risk factors for perioperative complications were assessed by univariate and multivariate logistic regression analysis., Results: Twenty-eight patients (20.1%) had perioperative complications. Perioperative complications were significantly associated with the following factors [data presented as odds ratio]: lower height [0.928, p=0.007], higher ASA-PS [2.296, p=0.048], longer operation time [1.013, p=0.003], more bleeding volume [1.004, p=0.04], higher rates of vertical subluxation [2.914, p=0.015] and subaxial subluxation (SAS) [2.507, p=0.036], occipito-cervical (OC) fusion [3.438, p=0.023], and occipito-cervical/thoracic (long) fusion [8.021, p=0.002] in univariate analyses. In multivariate analyses, lower height [0.915, p=0.005], higher ASA-PS [2.622, p=0.045] and long fusion [7.289, p=0.008] remained risk factors. High-dose prednisolone use [1.247, p=0.028], SAS [6.413, p=0.018], OC fusion [17.93, p=0.034], and long fusion [108.1, p<0.001] were associated with severe complications., Conclusions: ASA-PS and long fusion could be indicators predicting perioperative complications in patients with RA after cervical spine surgery. In addition, cervical spine lesions requiring OC fusion or long fusion and high-dose prednisolone use were suggested to be risk factors for increasing severe complications., (© 2022. The Author(s).)

Background: To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient's satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients., Methods: This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient's satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment., Results: This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, "very satisfied" and "satisfied" were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50-64 years; OR 0.91; 65-74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas., Conclusions: In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs., (© 2022. The Author(s).)

Autoreactive CD4 T cells are thought to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). Recently, a subset of CD4 T cells that express high levels of programmed death-1 (PD-1) but are distinct from follicular helper T cells have been identified in the joints of RA patients and named peripheral helper T (Tph) cells. Because PD-1 is expressed on T cells chronically stimulated with the Ags, we tested a hypothesis that Tph cells are the pathogenic autoreactive CD4 T cells in RA. We found that human Tph cells in RA joints produce proinflammatory effector cytokines, including IFN-γ, TNF-α, and GM-CSF, in addition to B cell-helping cytokines, such as IL-21 and CXCL13. Flow cytometric analysis showed different bias of TCR Vβ usage between PD-1 high Tph cells and PD-1 low/neg CD4 T cells, including Th1 cells, in the joint or memory CD4 T cells in the peripheral blood, whereas there was little difference between the latter two subsets. In line with this, deep sequencing of TCR demonstrated an overlap of expanded clones between peripheral blood memory CD4 T cells and PD-1 low/neg CD4 T cells but not Tph cells in the joint. Interestingly, Tph cells preferentially exhibited autologous MLR in vitro, which required recognition of self-MHC class II and was pronounced by blocking PD-1 signaling. Taken together, these results suggest that Tph cells are the pathogenic autoreactive CD4 T cells in RA, which expand locally in the joints and are regulated by PD-1 signaling., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Objectives: Delayed wound healing is one of the most common complications following forefoot surgery in patients with rheumatoid arthritis. We aimed to identify the risk factors for delayed wound healing following rheumatoid forefoot surgery., Methods: Consecutive patients who underwent primary rheumatoid forefoot surgery (86 feet; 53 patients) between April 2008 and February 2019 were retrospectively evaluated. Clinical data, including smoking history, duration of the disease, presence of diabetes mellitus, medication, white blood cell count, erythrocyte sedimentation rate (ESR), C-reactive protein, the surgical procedure performed, and the Japanese Society for Surgery of the Foot (JSSF) scores, were collected., Results: Delayed wound healing was identified in 20 of 86 (23.3%) feet. In univariate analysis, participants showing delayed healing were older at the time of surgery ( p  = .04), their ESR was higher ( p  = .0006), and their total ( p  = .019) and pain ( p  = .016) scores on the JSSF Lesser toe scale were lower than those showing normal healing. In multivariable analysis, both the total preoperative JSSF Lesser toe scale score ( p  = .0239) and ESR ( p  = .0126) remained significant risk factors for delayed wound healing., Conclusions: After rheumatoid forefoot surgery, surgeons should pay more attention to wound care in patients with lower preoperative JSSF Lesser toe score and high ESR.

Background: Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs)., Methods: This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU., Results: Upon admission, the median age was 70 (range, 33-96) years, and RA duration was 10 (range, 0-61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson's comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission., Conclusion: Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

This study aimed to evaluate whether preparation of the subtalar joint affects the clinical outcomes after tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid ankle/hindfoot deformity. Fifty-three joints in 51 patients who underwent tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid arthritis at 2 institutions were included. Ten patients were male and 41 were female, with a mean age at surgery and follow-up period of 61.3 years and 71.6 months, respectively. Radiographic bone union was evaluated at the most recent visit. Univariate and multivariable analyses were performed to determine the risk factors associated with nonunion. The mean postoperative Japanese Society for Surgery of the Foot ankle/hindfoot scale was 65.3 (range, 5-84). The tibiotalar nonunion rate was 0%, whereas the subtalar nonunion rate was 43.3% (23 joints). Revision surgery was performed in 5, all of which were due to painful subtalar nonunion. Absence of subtalar curettage and earlier postoperative weightbearing were significantly associated with subtalar nonunion (p = .0451 and p = .0438, respectively). Subtalar nonunion after tibiotalocalcaneal arthrodesis for rheumatoid hindfoot is associated with higher revision rate. To decrease the risk of subtalar nonunion after tibiotalocalcaneal arthrodesis with an intramedullary nail in rheumatoid patients, curettage for the subtalar joint should be performed, and full weightbearing should be delayed until at least 26 days postoperatively., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) is used in many countries to determine patient expectations before surgery. This study aimed to assess the reliability and validity of the Japanese version of HSS-THRES., Methods: A total of 134 patients scheduled for total hip arthroplasty (THA) underwent a self-administered preoperative survey questionnaire. Patient's expectation and quality of life (QOL) were measured using the Japanese version of HSS-THRES, overall expectations for THA, Oxford hip score (OHS), and EuroQol-5D (EQ-5D). Some patients completed the Japanese version of HSS-THRES and the overall expectations for THA after a ten-day interval. Cross-cultural adaptation was validated by an expert committee comprising health professionals, a methodologist, language experts, and orthopedic specialists. The internal consistency was evaluated by the Cronbach α coefficient. The test-retest reliability was examined using the intraclass coefficient correlation (ICC) and the Bland and Altman analysis. To test the construct validity, nine priori hypotheses were tested by correlation analysis between the Japanese version of HSS-THRES and two QOL scales, and by examining the association with demographic variables., Results: A total of 116 patients completed four scales. Patients were predominantly female (75.9%), with an average age of 62.2 ± 11.7. In the cross-cultural adaptation, all patients responded to the questionnaire without problems. The Japanese version of HSS-THRES showed good internal consistency (Cronbach α: 0.9). ICC was 0.94 and Bland-Altman analysis indicated no bias. The correlation between Japanese HSS-THRES and overall expectations for THA was high (r = 0.67). Similarly, the correlation with the OHS was higher than that with EQ-5D. A total of 77.8% of the hypotheses were confirmed., Conclusions: The Japanese version of HSS-THRES showed good cultural acceptability, high reliability, and validity to evaluate preoperative expectations for THA patients., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Osteoarticular tuberculosis can occur in patients with rheumatoid arthritis (RA) receiving immunosuppressive therapy. Here, we describe a case of tubercular osteomyelitis in an old fused hip of a patient with RA who received prednisolone, salazosulfapyridine (SASP), and low-dose methotrexate (MTX). A 77-year-old man with a 4-year history of RA was admitted with a complaint of general fatigue. His symptoms of RA had been well controlled with a combination of prednisolone, SASP, and low-dose MTX. Because the laboratory data showed an increase in serum C-reactive protein levels, we suspected pneumonia. There was expansion of a pre-existing consolidation in the right lower lobe of his lung on chest computed tomography, and the sputum culture was positive for Klebsiella oxytoca . His family physician prescribed empiric antibiotics for pneumonia. Although the QuantiFERON ® test result was positive, the acid-fast bacillus staining result was negative in the sputum. He started complaining of pain in his left hip, where arthrodesis was performed for an unknown reason at the age of 20 years. Sonographic examination of his left thigh revealed fluid collection. The aspiration culture of the fluid was positive for Mycobacterium tuberculosis . He was initiated on rifampicin, isoniazid, pyrazinamide, and ethambutol. Surgical debridement of the fused left hip was performed twice along with a removal of previously implanted materials. Although infrequent, osteoarticular tuberculosis can occur during immunosuppressive therapy, especially in elderly patients. Physicians should be aware of a history of possible tuberculosis infection, such as hip arthrodesis, when prescribing MTX along with SASP and corticosteroid in the elderly.

Background: Although lateralized head sign (LHS) is considered indicative of structural instability, it lacks reproducibility, and its usefulness in diagnosing adult hip dysplasia is unknown. In this study, we proposed a modified LHS and aimed to determine its reliability and accuracy in diagnosing adult hip dysplasia., Methods: We reviewed anteroposterior pelvic radiographs of 94 patients (134 hips) with hip dysplasia. As controls, 133 normal hips were evaluated. We defined the modified lateralization distance (LD) as the horizontal distance between the medial aspect of the femoral head to the acetabular fossa. The sensitivity, specificity, and cutoff value of modified LD in diagnosing hip dysplasia were calculated using receiver operating characteristic curve analysis., Results: The sensitivity and specificity of the modified LD (79% and 87%, respectively) were higher than those of the conventional LD (63% and 80%, respectively). Diagnostic accuracy was further improved when patients were divided on the basis of sex. The sensitivity and specificity of the modified LD in men were 89% and 97%, respectively, with a cutoff value of 12 mm, while in women, they were 80% and 96%, respectively, with a cutoff value of 9.7 mm. Therefore, we defined the modified LHS as presentation with a modified LD ≥ 12 mm in men and ≥10 mm in women. Between three observers, the kappa value for intraobserver reliability was ≥0.9, while that for interobserver reliability was >0.8. The mean sensitivity and specificity of the modified LHS in diagnosing hip dysplasia were 85% and 99%, respectively., Conclusions: Modified LHS-a horizontal distance between the medial aspect of the femoral head and the acetabular fossa ≥12 mm in men and ≥10 mm in women-is a clinically useful marker in detecting lateral femoral head subluxation indicative of hip dysplasia or structural hip instability., (Copyright © 2019 The Japanese Orthopaedic Association. All rights reserved.)

Background: Anterior localization of the necrotic lesion was recently proposed as an important factor for the occurrence of collapse even in medially located osteonecrosis of the femoral head (ONFH). We examined the effects of the anterior boundary of the necrotic lesion on progressive collapse after varus osteotomy for ONFH., Methods: We reviewed the outcomes of 31 hips in 27 patients with ONFH treated by transtrochanteric curved varus osteotomy (CVO) from 2000 to 2012 with a mean follow-up of 10.5 years. The occurrence of progressive collapse of the anterior necrotic lesion was defined as the presence of ≥2 mm collapse using follow-up lateral radiographs. Postoperative osteoarthritic change was defined as ≥1 mm progression of joint space narrowing on follow-up radiographs. The location of the anterior boundary of the necrotic lesion was assessed using the anterior necrotic angle (the angle between the midline of the femoral neck shaft and the line passing from the femoral head center to the anterior boundary of the necrotic lesion on a mid-slice oblique magnetic resonance image)., Results: All hips had a postoperative intact ratio of ≥34% (percentage of the transposed intact articular surface of the femoral head to the weight-bearing area of the acetabulum after femoral osteotomy). Progressive collapse of the anterior necrotic lesion was seen in five hips (16%) during a mean of 2.2 years after CVO. Of these, four hips (80%) proceeded to develop osteoarthritic change at an average of 4.3 years after the collapse. Multivariate analysis revealed that the anterior necrotic angle was independently associated with progressive collapse of the anterior necrotic lesion as well as the postoperative intact ratio., Conclusions: This study suggests that hips with anterior localization of the necrotic lesion have a possible risk of progressive collapse of the anterior necrotic lesion after CVO, which can frequently lead to subsequent osteoarthritic change., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Few studies have examined the influence of dioxin-related compounds on human physical function, and existing results are inconsistent. In 1968, accidental human exposure to rice oil contaminated with dioxin-related compounds resulted in the development of Yusho oil disease in Japan. We aimed to determine whether the degree of exposure to dioxin-related compounds was associated with physical function in Yusho patients., Methods: In 2016, 65 men (average age: 65.7 years) and 77 women (average age: 64.7 years) participated in a nationwide health examination in Fukuoka prefecture. Functional reach, gait speed, hand grip strength, and toe grip strength were evaluated as part of physical function. The serum levels of polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls were measured using high-resolution gas chromatography and high-resolution mass spectrometry. We examined the association between physical function tests and serum toxic equivalency (TEQ) values., Results: A 10-fold increase in serum TEQ levels was negatively associated with functional reach (adjusted b = -4.07, p = 0.017) and hand grip strength (adjusted b = -2.20, p = 0.0245) in men. No association was observed between serum TEQ level and physical function in women., Conclusion: Our findings suggest that dioxin-related compounds have a negative influence on physical function in men. However, these findings should be interpreted carefully. Future studies examining additional data on musculoskeletal disorders are warranted., (© 2019 Published by Elsevier Ltd.)

Background: To achieve sufficient socket coverage by the native bone, high placement of cementless acetabular cup is often required. We previously reported, using computer simulation, that higher hip centre improved the bone coverage but decreased the range of motion in total hip arthroplasty (THA) for patients with hip dysplasia. However, in a clinical setting, the correlation between the hip centre height and dislocation after primary THA is still unclear. We examined whether a high hip centre affects dislocation after THA., Methods: A total of 910 patients, with 1079 dysplastic hips, who underwent primary THA were retrospectively reviewed. The age at THA averaged 63.0 years and mean follow-up was 74.3 months. Vertical centre of rotation (V-COR) was defined as the distance from the head centre to the interteardrop line. Uni- and multivariate logistic regression models were applied to identify significant factors affecting dislocation., Results: Ten hips in nine patients (0.9%) had dislocation after THA. In univariate analysis, age at surgery and V-COR were significant risk factors for dislocation. Multivariate analysis identified advanced age at operation (odds ratio [OR] 1.8/5 years), Crowe classification (OR 15.6), V-COR (OR 3.1/5 mm), and femoral head size (OR 11.6) as independent risk factors for dislocation. Receiver operating characteristic curve analysis revealed the cutoff value of the V-COR for dislocation as 23.9 mm., Conclusions: A higher hip centre with the V-COR > 23.9 mm affected dislocation after THA for DDH. Our results would be useful for reconstruction of the hip centre, particularly with cementless acetabular cups.

Background: In total hip arthroplasty (THA), placing the cup in an anatomic position is not always possible in case of deformities related to developmental dysplasia of the hip (DDH). Thus far, the influence of a hip center on the abductor moment after THA has not been clearly elucidated. Therefore, we performed a retrospective study to assess (1) how abductor muscle moment recovers postoperatively in THA and (2) whether acetabular cup position affects the recovery of abductor moment., Hypothesis: A high hip center affects the recovery of abductor moment of a dysplastic hip after THA., Patients and Methods: We evaluated 100 patients, who underwent unilateral primary THA, at 12 months postoperatively. The study included 86 women and 14 men, with a mean age of 65.5±9.9 years (range, 40 to 86 years). Patients with secondary osteoarthritis due to DDH were included (Crowe 1: 76; Crowe 2: 15, Crowe 3:9, and Crowe 4: none). A cementless straight stem was implanted in all hips. Hip abductor moment was measured using a belt-stabilized hand-held dynamometer. The ratio of moment of the affected side to that of the contralateral side was calculated as moment ratio. The horizontal and vertical centers of rotation (H-COR and V-COR) (with respect to the inter teardrop line) and vertical shift (V-shift) (difference in V-COR between the affected hip and the contralateral normal hip) were determined., Results: At 6 and 12 months postoperatively, the abductor moment ratios were 95.1 and 94.7%, respectively. Significant negative correlation was observed between the postoperative abductor moment ratio and V-COR at 6 months postoperatively (r=-0.2436, p=0.0238). Significant delay in the recovery of abductor moment ratio was observed in the groups with higher hip center (V-shift>15mm) (odds ratio=12.7; 95% CI: 2.11-232.1, p=0.0034) at 6 months postoperatively, which was fully recovered at 12 months postoperatively., Discussion: Superior placement of a hip center, more than 15mm above the true hip center, delayed the recovery of abductor muscle moment after THA., Level of Evidence: III, retrospective comparative study., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Similar to the radiological findings in rapidly destructive arthrosis of the hip joint (RDA), subchondral insufficiency fracture of the femoral head (SIF) can result in progressive femoral head collapse of unknown etiology. We thus examined the osteoclast activity of hip joint fluid in SIF with progressive collapse in comparison with that in RDA. Twenty-nine hip joint fluid samples were obtained intraoperatively with whole femoral heads from 12 SIF patients and 17 RDA patients. SIF cases were classified into subgroups based on the presence of ≥2 mm collapse on preoperative radiographs: SIF with progressive collapse (n = 5) and SIF without progressive collapse (n = 7). The levels of tartrate-resistant acid phosphatase (TRACP)-5b, interleukin-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were measured. The number of multinuclear giant cells at the subchondral region was histopathologically assessed using mid-coronal slice of each femoral head specimen. The median levels of all markers and the median number of multinuclear giant cells in SIF with progressive collapse were significantly higher than those in SIF without progressive collapse, while there were no significant differences in SIF with progressive collapse versus RDA. Regression analysis showed that the number of multinuclear giant cells was positively correlated with the level of TRACP-5b in joint fluid. The present study demonstrated the possible association of increased osteoclast activity with the existing condition of progressive collapse in SIF, which was quite similar to the findings in RDA, indicating that increased osteoclast activity may reflect the condition of progressive collapse in SIF as well as RDA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2987-2995, 2018., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The purpose of this study was to examine the minimum 10-year clinical outcomes, including patient-reported and functional outcomes, of periacetabular osteotomy in patients with advanced osteoarthritis. A total of 46 hips in 44 patients with advanced osteoarthritis who underwent periacetabular osteotomy between 1992 and 2006 were retrospectively reviewed. Mean age at surgery was 47.5 years, and mean follow-up was 16.9±4.7 years. Survivorship was determined using the Kaplan-Meier method, and the associated risk factors for the endpoint-conversion to total hip arthroplasty less than 15 years after surgery-were evaluated. The Oxford Hip Score and the University of California, Los Angeles activity score were evaluated at final follow-up. The survival rates at 15 and 20 years after surgery were 80% and 59%, respectively. Multivariate analysis indicated that body mass index greater than 24 kg/m 2 (P=.034; odds ratio, 1.72) was significantly associated with the endpoint as an independent risk factor. For 32 hips of 31 patients with preserved native joints at final follow-up, the Oxford Hip Score and the University of California, Los Angeles score averaged 41±5 and 5.2±1.8, respectively, equivalent (P=.28 and P=.215, respectively) to the scores of 14 hips of 13 patients with conversion to total hip arthroplasty (38±8.7 and 5.8±1.4, respectively). The results of this mid-term study may be useful for surgical decision-making among patients with advanced osteoarthritis who want to preserve native hip joints. [Orthopedics. 2018; 41(5):300-305.]., (Copyright 2018, SLACK Incorporated.)

Background: Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease., Case Presentation: A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded., Discussion: Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age < 8 years had no underlying disease and survived. One youngest and two immunocompromised patients died., Conclusion: Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections.

Objectives: Since the presence of IgM antibodies is a hallmark of ongoing immune response, we aimed to identify immunologically active rheumatoid arthritis (RA) patients by detecting IgM anti-citrullinated protein antibody (ACPA) levels., Methods: IgM ACPA levels were determined in the serum of 176 RA patients by enzyme-linked immunosorbent assay, in which parameters of reactivity against citrullinated and non-citrullinated peptides were compared to ensure the specificity. Influence of IgM rheumatoid factor (RF) on IgM ACPA detection was examined by removing IgG, using protein G-conjugated beads, or by purifying ACPA, using citrullinated peptide-conjugated beads., Results: Although IgM specific for citrullinated proteins was detected in some patients (11%), IgM molecules reactive to both citrullinated and non-citrullinated peptides were detected in a substantial number of patient samples (12%). IgM ACPA-positive reactions were associated with the presence of IgG ACPA and IgM RF. Surprisingly, protein G-mediated removal of IgG from the serum eliminated positivity for IgM ACPA, suggesting that IgG ACPA-IgM RF complex was being detected. This assumption was confirmed by the detection of IgM RF in the eluate of protein G beads and citrullinated peptide-conjugated beads., Conclusions: In an attempt to detect IgM ACPA, we mostly revealed false positive reactions due to the presence of IgM molecules, which were not specific for citrullinated proteins, and IgG ACPA-IgM RF immune complex. The latter complex had been proposed to play a role in the pathogenesis of RA, and here, for the first time, we have demonstrated its presence in the sera of RA patients.

Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resistant leiomyosarcoma cell line to investigate the mechanism of resistance. The IC50 of eribulin was 125 times higher in the resistant cell line than in the parental cell line, and eribulin did not induce G2/M arrest in resistant cells. The resistant cell line showed increased expression of MDR1 transcript, but protein levels and functional analysis results were similar to the parental cell line. We found that class III β -tubulin (TUBB3) was overexpressed in the resistant cell line, and siRNA knockdown of TUBB3 partially recovered sensitivity to eribulin. TUBB3 expression in clinical samples varied, suggesting that TUBB3 has the potential to be a biomarker for selection of anticancer drugs and may be a target for overcoming resistance to eribulin.

Introduction: To investigate the clinical outcome and prognostic factors of malignant spinal dumbbell tumors (m-SDTs)., Methods: We retrospectively reviewed the clinical outcome of 22 consecutive cases of m-SDTs and analyzed the prognostic factors associated with worse outcome., Results: Nineteen of the 22 cases were managed with surgery (86%), and gross total resection (GTR) was achieved in four cases (21%). The duration of overall survival (OS) ranged from 3 to 140 months, with a median survival time of 15.3 months. The 5 year OS rate was 55.6%. In multivariate analysis, histological subtype (high-grade malignant peripheral nerve sheath tumor) (hazard ratio [HR] 14.9, p = 0.0191), GTR (HR 0.07, p = 0.0343), and presence of local recurrences (HR 11.2, p = 0.0479) were significant and independent predictors of OS., Conclusions: On the basis of clinical data, we propose that GTR and prevention of local recurrence may improve the clinical outcome of m-SDTs., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflict of interest.

[This corrects the article DOI: 10.1371/journal.pone.0178064.].

Background: This study investigated the risk factors for postoperative complications requiring revision surgery within 3 years after transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH)., Methods: We reviewed 127 patients (147 hips) who underwent TRO (anterior or posterior rotational osteotomy) for ONFH between January 2002 and December 2014. Two patients were lost to follow-up, and five patients with progression of femoral head collapse requiring a salvage procedure such as total hip arthroplasty within 3 years after TRO were excluded. The better hip in patients treated bilaterally was also excluded (n = 20) to avoid duplication of patient demographics, leaving 120 hips (120 patients) for the analysis. We reviewed the medical records of each patient to screen for postoperative complications that required revision surgery within 3 years after surgery, recording the patient's age, sex, body mass index, surgical side, condition of the contralateral hip, previous alcohol intake, previous alcohol abuse, previous corticosteroid use, perioperative corticosteroid use, smoking status, preoperative stage and type of ONFH, preoperative activity level, and preoperative and final follow-up Japanese Orthopaedic Association scores. Differences between cases with and without complications were analyzed., Results: Eleven (9.2%) cases showed postoperative complications that required revision surgery. The most common complication was deep infection (n = 5), followed by nonunion of the greater trochanter (n = 3), nonunion of the intertrochanteric osteotomy site (n = 2), and femoral head fracture (n = 1). The multivariate analysis showed an independent association between previous alcohol abuse and postoperative complications (odds ratio, 13.5)., Conclusion: A correlation might exist between alcohol abuse and complications following a TRO procedure.

The purpose of the present study was to examine the clinical results of surgery for intra-articular calcaneal fractures using a calcaneal locking plate and a bone spreader as a reduction tool. Ten patients with intra-articular calcaneal fractures were treated. An extended lateral approach was used. The reduction of the intra-articular fragments of the posterior facet was temporarily held using a bone spreader and Kirschner wires. Internal fixation was achieved with a locking calcaneal plate. Böhler's angle and Preiss' angle were assessed on the day of injury and the day of the final follow-up examination. The step off and gap of the posterior facet were assessed on the day of injury and the first week after surgery. The functional outcome was evaluated using the American Orthopaedic Foot and Ankle Society ankle hindfoot scale score. The mean Böhler's angle ranged from 2.1° ± 11.0° to 30.4° ± 5.0° (p < .0001), the mean Preiss' angle ranged from 23.5° ± 4.5° to 15.5° ± 2.9° (p < .0001), the mean step off ranged from 4.0 ± 1.9 mm to 0.1 ± 0.2 mm (p = .0002), and the mean gap ranged from 2.6 ± 1.0 mm to 1.2 ± 0.6 mm (p = .0035). The mean American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale score was 89.2 (range 85 to 100) at a mean of 14.3 months after surgery. Our results suggest that a locking calcaneal plate can be used to restore and reduce an intra-articular calcaneal fracture and achieve good clinical results., (Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Since Sugioka transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) changes the morphology of the proximal femur, total hip arthroplasty (THA) after previous ARO is considered a technically demanding procedure. The purpose of this study was to compare the clinicoradiologic outcomes of THA after ARO with those of THA without any antecedent surgery for ONFH., Methods: Twenty-four hips in 20 patients who underwent cementless THA after ARO (postosteotomy group) were retrospectively reviewed and compared with patients who underwent cementless THA without any antecedent surgery for ONFH during the same period (primary group). In the postosteotomy group, the mean duration from ARO to THA was 19.7 years. All patients were followed for at least 5 years (mean, 8.3 years; follow-up rate, 78.5%). A clinical assessment was performed preoperatively and at the latest follow-up using the Harris Hip Score. A radiographic examination was performed at 3 months after THA and at the latest follow-up., Results: The Harris Hip Score at the latest follow-up in the postosteotomy group was equivalent to that in the primary group, but longer operation time and greater intraoperative blood loss were observed in the postosteotomy group. There were no significant differences in postoperative complications, including dislocation (2 hips in each group). The leg lengthening in the postosteotomy group tended to be longer. No hips showed implant malpositioning, loosening, or required any revision surgery., Conclusion: The clinicoradiologic outcomes of THA after ARO are considered to be comparable with those of THA without any antecedent surgery for ONFH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Periacetabular osteotomy (PAO) is an effective treatment for symptomatic acetabular dysplasia. However, whether postoperative participation in sports leads to progression of the Kellgren-Lawrence (KL) grade of osteoarthritis (OA) in these patients is unclear., Purpose: To investigate (1) participation in sports before and after PAO and (2) whether postoperative participation in sports leads to progression of the KL grade., Study Design: Case-control study; Level of evidence, 3., Methods: The authors retrospectively reviewed data on 161 patients (183 hips) who underwent PAO for symptomatic acetabular dysplasia with preoperative KL grade 1 or 2 between 1998 and 2011. The mean age at the time of surgery was 42.0 ± 10.9 years (range, 12-64 years), and the mean follow-up duration was 100 months (range, 13-180 months). Data included participation in sports, the University of California, Los Angeles (UCLA) activity scale score, age at the time of surgery, body mass index, follow-up duration, history of treatment for developmental hip dislocations, Merle d'Aubigné-Postel score, Oxford Hip Score, center-edge angle, and KL grade. Univariate and multivariate analyses were applied to determine which factors were associated with progression to KL grade 3 or 4 after PAO., Results: The number of patients who participated in sports significantly increased from 50 (31.1%) preoperatively to 89 (55.3%) postoperatively. The mean UCLA score significantly increased from 4.7 ± 2.1 preoperatively to 5.5 ± 2.0 postoperatively. The KL grade progressed to grade 3 or 4 in 16 hips, including 4 hips that underwent conversion to total hip arthroplasty. No significant differences were found in postoperative participation in sports (89 hips [53.3%] vs 11 hips [68.8%], respectively; P = .24) and the UCLA score (5.6 ± 2.0 vs 5.1 ± 2.0, respectively; P = .30) between hips with KL grade 1 or 2 and KL grade 3 or 4. A multivariate analysis revealed that no factors, including postoperative participation in sports, were significantly associated with progression to KL grade 3 or 4., Conclusion: Postoperative participation in sports after PAO did not significantly and negatively influence progression of the KL grade at midterm follow-up.

Competing Interests: Competing interests: None declared.

Case: A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD., Conclusion: MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy.

Objectives: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA., Methods: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan-Meier method, and the associated influencing factors were determined., Results: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals., Conclusions: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.

Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear., Methods: The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α., Results: The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis., Conclusion: Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs.

Objective: The purpose of this study was to clarify the minimum joint space width (MJSW) that leads to subchondral bone exposure (SBE) in patients with hip dysplasia., Methods: We included 82 subjects (86 hips) who had hip dysplasia with center-edge angle less than 20° and who underwent periacetabular osteotomy combined with hip arthroscopy. The acetabular and femoral cartilages were divided into three regions: anterosuperior, superior, and posterosuperior; for each region, we analyzed the correlation between the incidence of SBE and the MJSW measured on plain radiographs. The disease stage was defined according to the Kellgren and Lawrence grades (KL grade)., Results: SBE was found in 51 hips (59.3%) in total, involved the acetabulum in 49 hips (57.0%), and involved the femoral head in 26 hips (30.2%). SBE was more frequent in the acetabulum, with the highest incidence in the anterosuperior region, followed by the superior region. SBE was present in six hips (22.2%), 17 hips (56.7%), and 28 hips (96.5%), at KL-1, KL-2, and KL-3, respectively. MJSW of hips with SBE was significantly smaller than those without SBE (2.3 vs 4.0 mm, p < 0.001), and the cut-off value for MJSW that led to SBE was 3.7 mm (sensitivity: 0.902, 1 - specificity: 0.343). SBE was present in 23.3% in patients with MJSW ≥3.7 mm, whereas 76.7% in those <3.7 mm., Conclusions: Cartilage degeneration is more advanced than would be predicted on plain radiographs. The cut-off value of MJSW for SBE was 3.7 mm in patients with symptomatic hip dysplasia.

Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumour with a relatively poor prognosis despite intensive multimodal therapy. Although pazopanib, a multi-kinase inhibitor, is often used for advanced SS, most cases eventually become resistant to pazopanib. In the present study, we investigated the mechanisms of acquired pazopanib resistance in SS. To examine acquired pazopanib resistance, two SS cell lines, SYO-1 and HS-SY-II, were isolated after multiple selection steps with increasing concentrations of pazopanib. SYO-1 was also used in vivo. Then, pazopanib-resistant clones were investigated to assess potential mechanisms of acquired pazopanib resistance. Stable pazopanib-resistant clones were established and exhibited enhanced cell cycle progression, cell growth with increased ERK1/2 phosphorylation, and higher sensitivity than parental cells to a MEK-inhibitor, trametinib, both in vitro and in vivo. Furthermore, addition of low-dose trametinib partially reversed the pazopanib resistance. In the pazopanib-resistant clones, dual specificity phosphatase 6 (DUSP6) was downregulated. Inhibition of DUSP6 expression in parental HS-SY-II cells partially recapitulated acquired pazopanib resistance. Acquired pazopanib resistance in SS was associated with activation of ERK1/2 through downregulation of DUSP6 expression. Simultaneous treatment with pazopanib and a MEK inhibitor could be a promising strategy to overcome pazopanib resistance in SS.

Background and Purpose: Carbon-ion radiotherapy (C-ion RT) was effective therapy for inoperable spinal and paraspinal sarcomas. However, a significant adverse event following radiotherapies is vertebral compression fractures (VCFs). In this study, we investigated the incidence of and risk factors for post-C-ion RT VCFs in patients with spinal or paraspinal sarcomas., Material and Methods: Thirty consecutive patients with spinal or paraspinal sarcomas treated with C-ion RT were retrospectively reviewed. Various clinical parameters and the Spinal Instability Neoplastic Score (SINS) were used to evaluate the risk factors for post-C-ion RT VCFs., Results: The overall incidence of VCFs was 23% (median time: 7 months). Patients with VCFs showed a markedly higher SINS score (median value, 9 points) than those without VCF (5 points). The area under the receiver operating characteristic curve for the SINS score was 0.88, and the optimum SINS cut-off score was 8 points. The cumulative incidence of VCFs at 1 year was 9% for patients with a SINS score under 8 points, versus 80% for those with a SINS score of 8 points or higher ( p < 0.0001)., Conclusions: In patients with a SINS score of 8 points or higher, referral to a spine surgeon for stabilization and multidisciplinary discussion is appropriate.

Background and Purpose: Primary malignant spine/spinal tumors (PMSTs) are rare and life-threatening diseases. In this study, we demonstrated the advantage of volume-based 18 F-FDG PET/CT metabolic parameter, metabolic tumor volume (MTV), for assessing the aggressiveness of PMSTs., Materials and Methods: We retrospectively reviewed 27 patients with PMSTs and calculated SUV max , MTV, and total lesion glycolysis (TLG) to compare their accuracy in predicting progression-free survival (PFS) and overall survival (OS) by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to compare the reliability of the metabolic parameters and various clinical factors., Results: MTV exhibited greater accuracy than SUV max or TLG. The cut-off values for PFS and OS derived from the AUC data were MTV 45 ml and 83 ml and TLG 250 SUV⁎ml and 257 SUV⁎ml, respectively. MTV above cut-off value, but not TLG, was identified as significant prognostic factor for PFS by log-lank test ( p = 0.04). In addition, MTV was the only significant predictive factors for PFS and OS in the multivariate analysis., Conclusions: MTV was a more accurate predictor of PFS and OS in PMSTs compared to TLG or SUV max and helped decision-making for guiding rational treatment options.

Background: Avascular necrosis of the femoral head (AVN) is the most serious complication after unstable slipped capital femoral epiphysis (SCFE), and is often unsalvageable. We report a minimum 10 years of clinical results for transtrochanteric rotational osteotomy of the femoral head (TRO) for AVN., Methods: This study included 7 patients (7 hips) with a mean age at surgery of 13.3 years, and the follow-up period was 15.8 years. All patients had prior treatment via closed reduction and pinning of the unstable SCFE, and showed severely collapsed femoral heads. The direction of rotation was anterior in 3 hips and posterior in 4. The Merle d'Aubigné-Postel score (MDPS) was used for clinical assessment, and joint degeneration was assessed with the Kellgren and Lawrence classification (KL-grade)., Results: The spherical intact area of the femoral head was moved to the weight-bearing portion, and subluxation was corrected via rotation combined with intentional varus positioning. The mean MDPS improved from 10.3 points to 15.6 points at 5 years, and it was maintained at 15.0 points by 10 years; 3 hips were excellent, 1 was good, 2 were fair, and 1 showed poor outcomes. No patient experienced re-collapse after TRO or required conversion to hip replacement or arthrodesis. After 10 years, degenerative changes became evident over time, and 2 hips progressed to KL-4 with a decreased MDPS., Conclusions: Although some joint degeneration is inevitable in the long-term, TRO is an effective salvage procedure for treating AVN after unstable SCFE., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Femur deformities can make stem fixation difficult in total hip arthroplasty (THA). We report the clinical results of cementless THA using a press-fit stem in patients who had previously undergone femoral osteotomy for hip dysplasia., Methods: The subjects included 66 hips in 64 patients, with the mean follow-up period of 7.3 years. THA was performed at a mean period of 17.1 years after intertrochanteric femoral osteotomy. Valgus osteotomy was performed in 42 hips, and varus osteotomy in 24. Clinical results were evaluated by using the Merle d'Aubigne-Postel score. Implant survival was determined with revision as the end point, and any related complications were investigated., Results: The Merle d'Aubigne-Postel score improved from 9.4 to 16.1 at the final follow-up, without any implant loosening. However, periprosthetic femoral fractures were observed in four hips (6.0 %), one intra-operatively and three within three weeks after THA. Among these cases, three hips previously had varus osteotomy (12.5 %) and one hip had valgus osteotomy (2.3 %). Two hips were revised with full porous stems and circumferential wiring. The five and ten year cumulative survivorship rates were 97 % (range, 88.8-99.3 %) and 97 % (88.8-99.3 %), respectively., Conclusions: Although the use of a press-fit cementless stem yielded acceptable results in most of the patients, perioperative femoral fracture was a major complication especially in the patients previously treated with intertrochanteric varus osteotomy. Careful planning and implant selection could be emphasized for these cases.

Purpose: Dislocation is a leading cause of failure after revision total hip arthroplasty (THA). This study was conducted to examine the risk factors for dislocation as well as their recurrence after revision THA., Methods: We retrospectively reviewed 178 revision THAs in 162 patients between 1998 and 2013. The mean patient age was 65.2 years at operation and the mean follow-up period was 6.7 years. Multivariate logistic regression was performed to identify risk factors for dislocation, and further comparison was made between patients with single and recurrent dislocations., Results: Sixteen hips in 15 patients (9.0 %) dislocated at a mean of 9.1 months (range, 0-83 months) after revision THA. Multivariate analysis identified advanced age (odds ratio [OR] = 2.94/10 years) and osteonecrosis of the femoral head (OR = 7.71) as the independent risk factors for any dislocations. Risk factors for recurrent dislocations, which were observed in eight hips (50 %), were later dislocations (≥4 months) and lower BMI., Conclusion: Dislocation is a serious problem after revision THA with multiple risk factors. Although our findings were limited to revision THAs done through posterolateral approach, recognition of these factors is helpful in patient education and surgical planning.

No previous studies comparing the clinical wear rates of the two different kinds of cross-linked ultra-high-molecular-weight polyethylene (XLPE), annealed and remelted, are available. We compared the creep and steady wear rates of 36 matched pairs (72 hips in total) adjusting for baseline characteristics with propensity score matching techniques. Zirconia femoral heads with 26-mm diameter were used in all cases. The femoral-head cup penetration was measured digitally on radiographs. Significantly greater creep (p=0.006) was detected in the remelted (0.234mm) than annealed (0.159mm) XLPE. However, no significant difference (p=0.19) was found between the steady wear rates (0.003 and 0.008mm/year, respectively) of the annealed and remelted XLPE. Multiple regression analyses showed that remelted XLPE is significant independent variable (p<0.001) that is positively associated with creep. However, the patient age and body weight, cup size, the liner thickness, cup inclination, follow-up periods, and postoperative Merle d'Aubigné hip score had no significant effects (p>0.05) on the steady wear rates. No patients exhibited above the osteolysis threshold of 0.1mm/year, progressive radiolucencies, osteolysis, or polyethylene fracture. This　propensity-matched cohort study document no significant difference in wear resistant performances of annealed and remelted XLPE over an average period of 10 years., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Ewing's sarcoma family of tumours (ESFT) is a malignant small round-cell tumour of the bone and soft tissues. It is characterised by a strong tendency to invade and form metastases. The microenvironment of the bone marrow is a large repository for many growth factors, including the basic fibroblast growth factor (bFGF). However, the role of bFGF in the invasive and metastatic phenotype of ESFT has not been investigated., Methods: The motility and invasion of ESFT cells were assessed by a wound-healing assay, chemotaxis assay, and invasion assay. The expression and activation of FGF receptors (FGFRs) in ESFT cell lines and clinical samples were detected by RT-PCR, western blotting, and immunohistochemistry. The morphology of ESFT cells was investigated by phase-contrast microscopy and fluorescence staining for actin. Activation of Rac1 was analysed by a pull-down assay., Results: bFGF strongly induced the motility and invasion of ESFT cells. Furthermore, FGFR1 was found to be expressed and activated in clinical samples of ESFT. Basic FGF-induced cell motility was mediated through the FGFR1-phosphatidylinositol 3-kinase (PI3K)-Rac1 pathway. Conditioned medium from bone marrow stromal cells induced the motility of ESFT cells by activating bFGF/FGFR1 signalling., Conclusion: The bFGF-FGFR1-PI3K-Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of ESFT.