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Abstract The coronavirus disease (COVID-19) pandemic negatively affected the diagnosis and treatment of several cancer types. However, this pandemic’s exact impact and extent on bone and soft tissue sarcomas need to be clarified. We aimed to investigate the effect of the COVID-19 pandemic and emergency declaration by the local government on consultation behavior and clinical stage at diagnosis of bone and soft tissue sarcoma. A total of 403 patients diagnosed with bone and soft tissue sarcoma who initially visited three sarcoma treatment hospitals between January 2018 and December 2021 were included. The monthly number of newly diagnosed soft tissue sarcoma patients was reduced by 25%, and the proportion of soft tissue patients with stage IV disease at diagnosis significantly increased by 9% during the COVID-19 pandemic compared to before the COVID-19 pandemic. Furthermore, the monthly number of new primary bone and soft tissue sarcoma patients significantly decreased by 43% during the state of emergency declaration. The COVID-19 pandemic had a negative impact on soft tissue sarcoma patients’ consultation behavior and increased the proportion of advanced-stage patients at initial diagnosis. An emergency declaration by the local government also negatively affected primary bone and soft tissue sarcoma patients’ consultation behavior.

Pelvic fractures, accounting for 2–8% of skeletal injuries, present a significant burden in patients with trauma. High-energy incidents often result in severe pelvic trauma accompanied by comorbidities leading to high mortality rates. Managing these complications adds complexity to the treatment process, particularly in older patients who experience longer recovery times and higher injury severity. To improve the long-term quality of life, a multidisciplinary approach is essential. However, rehabilitation feasibility is influenced by the patient’s condition and pelvic fixation stability, necessitating individualized treatment. This study investigated the rehabilitation status and long-term outcomes of older patients with severe polytrauma and pelvic ring fractures caused by high-energy trauma. The results revealed that 79.2% of the patients achieved full weight-bearing, with a median time of 41.5 days, and eventually 58.3% were discharged home. Complications were observed in 83.3% of the patients, with various challenges affecting successful home discharge. Multidisciplinary rehabilitation programs are promising for optimizing outcomes and facilitating recovery in vulnerable patient populations. Still, larger, more focused studies are needed to gain more comprehensive insights into the treatment and recovery of older patients with pelvic ring fractures and severe polytrauma. Understanding these factors is crucial for guiding clinical decision-making and improving long-term outcomes in this population.

Background: Accurate cup placement in total hip arthroplasty (THA) for patients with dysplasia is challenging due to the distinctive bone deformities. This study aimed to compare the accuracy of cup placement position and orientation across robotic arm–assisted systems (R-THA), computed tomography–based navigation (N-THA), and manual procedure (M-THA) in THA for osteoarthritis secondary to dysplasia. Methods: A total of 167 patients (197 hips), including 88 R-THAs, 45 N-THAs, and 46 M-THAs, were analyzed. Propensity score matching was performed to align the patient backgrounds. Horizontal and vertical centers of rotation were measured for cup position, whereas radiographic inclination and anteversion were measured for cup orientation. The proportion of cases with cup placement within 3 mm and 5° from the target was compared. Results: R-THA had a significantly higher percentage of cup placement within 3 mm of the target compared to N-THA (78% vs 49%; P = .0041) and M-THA (78% vs 53%; P = .013). Similarly, R-THA was significantly more successful in placing the cup within 5° of the target compared to N-THA (84% vs 58%; P = .0049) and M-THA (91% vs 20%; P < .0001). Moreover, N-THA was significantly better at placing the cup within 5° of the target compared to M-THA (62% vs 14%; P < .0001), whereas there was no significant difference in the percentage of cup placement within 3 mm of the target (51% vs 51%; P = 1.0). Conclusions: Robotic arm–assisted system and computed tomography–based navigation improved accuracy in cup orientation compared to the manual procedure. Additionally, the robotic arm–assisted system further improved cup position accuracy.

AbstractSynovial 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.

Purpose: The aim of this study was to show a concrete setting landmark in two component types of round and anatomical oval shapes using three-dimensional (3D) simulation analyses in total knee arthroplasty (TKA). Methods: The patellar resection surface was simulated three-dimensionally using preoperative CT data of 54 patients (68 knees) who underwent TKA with varus knee osteoarthritis. The mediolateral position of the original patellar ridge was examined. The round and anatomical oval patellar components were aligned in the following cases: medial edge setting, patellar ridge setting, maximal size setting. The component ridge position from the medial edge and size in each case were examined. Results: The original patellar ridge was located nearly 40% from the medial edge. In aligning the component to reproduce the original patellar ridge, the medial bone width uncovered with the component was nearly 4 mm in both designs. The component size was significantly smaller as the component was placed more medially. In selecting the maximal size, the round component was aligned more laterally than the original patellar ridge. In contrast, the anatomical oval component enabled to be concomitant with a more appropriate position and size. Conclusion: The position where the medial bone width uncovered with the component was nearly 4 mm, not the medial edge, was found as the best place to reproduce the original patellar ridge in both round and anatomical oval components. Specifically, the anatomical oval component might be more favorable with respect to the component position and size.

Abstract Purpose This study assessed rotational mismatch between components after total knee arthroplasty (TKA) in the supine and standing positions and aimed to investigate the effect of rotational mismatch in the standing position on postoperative patient‐reported outcome measures (PROMs). Methods Seventy‐one patients (71 knees) who underwent TKA for medial knee osteoarthritis were used to investigate rotational mismatches between components. Rotational mismatches between components were examined on postoperative standing whole‐leg and supine knee radiographs using a three‐dimensional‐to‐two‐dimensional model image registration technique, and the angles between the reference axes of the components were measured. Component alignment was evaluated using postoperative computed tomography images, and a questionnaire (2011 version of the Knee Society Score: [KSS 2011]) was mailed to investigate postoperative PROMs. Results In the entire cohort, rotational mismatches in the supine and standing positions were similar (p = 0.9315). In 15% of patients, the mismatch was large (>5°) in the supine position but small (5°) in the standing position (underestimated group). The underestimated group had severe preoperative varus deformity, resulting in external rotation of both femoral and tibial components. Rotational mismatch in the standing position (p = 0.0032) was a significant risk factor for unfavourable PROMs. Patients with a mismatch in the standing position had significantly lower scores than those without a mismatch (p = 0.0215), exceeding the minimal clinically important difference values. Conclusions The underestimated group is clinically important because the surgical procedure and intraoperative assessment of component placement are performed in the supine position. In cases of severe preoperative varus deformity, care should be taken not to place the component in malrotation to avoid rotational mismatch in the standing position. Level of Evidence Ⅳ, Case series.

Abstract Background Impingement is a common complication of reverse shoulder arthroplasty. Placement of the baseplate with a wide impingement-free angle is ideal; however, there are few studies on Asian populations, which have smaller height and physique, and there is a lack of guidance on achieving optimal outcomes. The purpose of the present study was to explore the impingement-free range of motion reverse shoulder arthroplasty and analyze the suitable baseplate position or tilt for the Asian population using simulation software. Methods We uploaded computed tomography scan data from 20 Asian patients to three-dimensional (3D) simulation software. The implantation of the reverse shoulder arthroplasty component was performed on the 3D humerus and scapula using software, and range of motion was assessed until impingement occurred. Results The range of motion in flexion significantly improved when the baseplate was lowered up to 3 mm inferiorly. Range of motion in abduction and internal and external rotation significantly improved as the baseplate was lowered up to 4 mm. There was no significant difference in range of motion in any motion after changing the inferior tilt, except in internal and external rotation. Conclusions The range of motion in abduction, flexion, and internal and external rotations significantly improved with increased inferior offset. These results may prove valuable in determining the optimal baseplate position for RSA, particularly in Asian populations.

Abstract Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

Abstract In osteoclastogenesis, the metabolism of metal ions plays an essential role in controlling reactive oxygen species (ROS) production, mitochondrial biogenesis, and survival, and differentiation. However, the mechanism regulating metal ions during osteoclast differentiation remains unclear. The metal-binding protein metallothionein (MT) detoxifies heavy metals, maintains metal ion homeostasis, especially zinc, and manages cellular redox levels. We carried out tests using murine osteoclast precursors to examine the function of MT in osteoclastogenesis and evaluated their potential as targets for future osteoporosis treatments. MT genes were significantly upregulated upon differentiation from osteoclast precursors to mature osteoclasts in response to receptor activators of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation, and MT3 expression was particularly pronounced in mature osteoclasts among MT genes. The knockdown of MT3 in osteoclast precursors demonstrated a remarkable inhibition of differentiation into mature osteoclasts. In preosteoclasts, MT3 knockdown suppressed the activity of mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways upon RANKL stimulation, leading to affect cell survival through elevated cleaved Caspase 3 and poly (ADP-ribose) polymerase (PARP) levels. Additionally, ROS levels were decreased, and nuclear factor erythroid 2-related factor 2 (NRF2) (a suppressor of ROS) and the downstream antioxidant proteins, such as catalase (CAT) and heme oxygenase 1 (HO-1), were more highly expressed in the MT3 preosteoclast knockdowns. mitochondrial ROS, which is involved in mitochondrial biogenesis and the production of reactive oxygen species, were similarly decreased because cAMP response element-binding (CREB) and peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) were less activated due to MT3 depletion. Thus, by modulating ROS through the NRF2 pathway, MT3 plays a crucial role in regulating osteoclast differentiation and survival, acting as a metabolic modulator of intracellular zinc ions.

Aims: To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. Methods: The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. Results: The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. Conclusion: Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living. Cite this article: Bone Jt Open 2023;4(12):906–913.

Introduction: Intraoperative three-dimensional (3D) imaging guide technology, such as the O-arm surgical imaging system, is a beneficial tool in spinal surgery that provides real-time 3D images of a patient's spine. This study aims to determine the exposure dose from intraoperative O-arm imaging. Methods: A consecutive retrospective review of all patients undergoing spinal surgery was conducted between June 2019 and August 2022. Demographic and operative data were collected from electronic medical records. Results: Intraoperative O-arm imaging was conducted in 206 (12.9%) of 1599 patients, ranging from one to 4 scans per patient (1.17±0.43 scans). Single O-arm imaging enabled navigation of seven vertebrae in the cervical spine, seven in the thoracic spine, five in the thoracolumbar spine, and four in the lumbar spine on average. The number of O-arm shots per surgery was 1.15±0.36, 1.06±0.24, 1.61±0.7, and 1.07±0.25 for cervical, thoracic, thoracolumbar, and lumbar spinal cases, respectively. The exposure doses represented by dose length products in single O-arm imaging were 377±19 mGy-cm, 243±22 mGy-cm, 378±38 mGy-cm, and 258±11 mGy-cm for cervical, thoracic, thoracolumbar, and lumbar spine cases, respectively. We observed a weak positive correlation between the number of fused spinal levels and the exposure dose. Conclusions: Intraoperative radiation exposure from O-arm imaging was lower than the national diagnostic reference levels in Japan established based on the International Commission on Radiological Protection publication, demonstrating its safety from the standpoint of radiological protection in most cases. In surgeries with a large range of fixations, such as corrective deformity surgery, the number of imaging sessions and the amount of intraoperative radiation exposure would increase, leading surgeons to pay attention to the risk of radiation in spinal surgery.

Objectives This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity.Design Retrospective observational study of a nationwide database.Setting The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint.Participants This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018.Main outcome measure The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis.Results The median time to surgery was 9 months (IQR 4–22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p

Introduction: The objective of this study was to examine if halo vest fixation provides sufficient stabilization of cervical spine alignment to endorse its use through intraoperative positional changes in patients with cervical spine instability. Methods: The subjects of this study were 14 patients with cervical spine instability who were immobilized in halo vests until they underwent subsequent internal fixation surgery. After induction of anesthesia, the patients in halo vests were repositioned from the supine position to the prone position. The halo ring was fixed to the surgical table and the dorsal struts and vest were removed for surgery. Radiographs obtained in the preoperative sitting position and intraoperative prone position were compared for the following measures of cervical alignment: O–C2 angle, C2–C6 angle, pharyngeal inlet angle (PIA), atlantodental interval (ADI), Redlund-Johnell (R–J) value as a measure of O–C2 length, O–C6 length, and O–C2 length/O–C6 length (%). Results: There were no significant differences in O–C2 angle, C2–C6 angle, PIA, ADI, or O–C2 length/O–C6 length (%). However, the R–J value and O–C6 length were significantly higher in the intraoperative prone position than in the preoperative sitting position. None of the patients presented with any complications, including dysphagia or neurological deterioration. Conclusions: Our results suggest that when patients are repositioned to the prone position while immobilized in halo vests, the cervical spine is distracted in the cephalocaudal direction across all cervical segments but the cervical alignment is sufficiently maintained. Halo vests are a highly effective external fixation method for patients with cervical spine instability, allowing for a safe repositioning to the prone position for surgery while preserving cervical alignment and preventing neurological deterioration.

Background: Spinal metastases can impair mobility, worsening the Karnofsky Performance Status (KPS). Surgery for spinal metastases has the potential to improve KPS and extend prognosis, but it is crucial to recognize the elevated risk of perioperative complications. Therefore, the development of a new scoring system to accurately predict perioperative complications in spinal metastatic surgery is essential. Methods: We conducted a retrospective observational study with 86 patients who underwent surgical intervention for spinal metastases. Patients were divided into two groups based on the presence or absence of perioperative complications within 14 days after surgery. Various factors related to perioperative complications were assessed through univariate and multivariate analyses. We established a clinical prognostic scoring system called the Perioperative Complications following Metastatic Spinal Surgery (PERCOM) score and evaluated its precision using receiver operating characteristic (ROC) analysis. Results: Five variables (age, KPS, primary prostate cancer, Albumin, and Hemoglobin) identified in the univariate analysis were assigned binary values of 0 or 1. The PERCOM score was then calculated for each patient by summing the individual points, ranging from 0 to 5. The optimal threshold determined by ROC curve analysis for the PERCOM score was 2 points, with a sensitivity of 86 % and a specificity of 56 %. Conclusions: The composite PERCOM score effectively predicted perioperative complications in spinal metastasis surgery. To further validate its precision, a prospective multicenter study is needed.

Objectives Understanding interpatient variation in CD4+T-cell responses is the bases for understanding the pathogenesis and management of rheumatoid arthritis (RA). We examined immune responses to SARS-CoV-2 vaccine in a cohort of patients with RA and determined factors associated with the responses.Methods Four hundred and thirty-one patients with RA having received two doses of BNT162b2, a messenger RNA-based vaccine for SARS-CoV-2, were included. Vaccine antigen-specific IgG was detected by ELISA, and antigen-specific CD4+T cells were detected by CD154 expression in response to antigenic stimulation. Expression of cytokines was concomitantly detected by intracellular staining. Associations among background variables, antigen-specific antibody production and the CD4+T-cell responses were analysed. Unsupervised hierarchical clustering was performed based on the profiles of antigen-specific cytokine production by CD4+T cells to stratify patients with RA.Results Multivariate analysis indicated that ageing negatively affects CD4+T-cell response as well as antibody production. No association was detected between the presence or the levels of rheumatoid factor/anti-cyclic citrullinated peptide antibody and anti-vaccine immune responses. Methotrexate and prednisolone reduced B cell but not T-cell responses. Conventional immunophenotyping by the expression of chemokine receptors was not associated with the actual CD4+T-cell response, except for T helper cells (Th1). Functional immunophenotyping based on the profiles of antigen-specific cytokine production of CD4+T cells stratified patients with RA into three clusters, among which Th1-dominant type less frequently underwent joint surgery.Conclusions Clinical and immunological variables that are associated with antigen-specific CD4 T-cell responses in patients with RA were determined by analysing immune responses against SARS-CoV-2 vaccine.

Abstract No report has clarified the frequency and interacting factors affecting sleep disturbance among Asian patients at midterm after total knee arthroplasty (TKA). This study aimed to evaluate the frequency of sleep disturbance at midterm after TKA in a Japanese cohort and to identify intervening factors for sleep. We hypothesized that residual knee pain and decreased functional capability negatively interact with sleep quality after TKA. A total of 209 Japanese participants (average age: 77.1 ± 8.3 years; postoperative follow-up period: 4.5 ± 1.9 years) who underwent primary TKA for knee osteoarthritis were included in this study. Sleep quality, satisfaction, pain, functional capability, joint awareness, and mental condition were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Knee Society Score (KSS) 2011, Forgotten Joint Score (FJS)-12, and 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (MCS). Multivariable analysis was performed to determine the influencing factors on PSQI. The scores for the PSQI, satisfaction with pain level while lying in bed, pain during level walking, functional activity category in the KSS 2011, awareness of the artificial joint in bed at night in the FJS-12, and SF-12 MCS were 6.7 ± 3.0, 5.8 ± 1.8, 1.6 ± 2.3, 62 ± 22, 1.5 ± 1.4, and 56 ± 9.3 on average, respectively. Sleep disturbance (PSQI ≥ 5.5) occurred in 54% of the Japanese participants. Multivariable analysis revealed that high functional capability was a significant factor associated with sleep quality improvement (p

Abstract This study aimed to clarify the clinical utility of the sourcil roundness index (SRI), a novel index for quantifying the asphericity of the acetabular concavity, by determining (1) the difference in the SRI between dysplastic and normal hips and (2) the correlation between the SRI and radiographic parameters of hip dysplasia. We reviewed standing anteroposterior pelvic radiographs of 109 dysplastic and 40 normal hips. The SRI was determined as the ratio of the distance from the medial edge of the sourcil to the most concave point of the acetabular sourcil (A) to the distance from the medial to the lateral edge of the sourcil (B). The formula for SRI is (A/B) × 100–50 (%), with an SRI of 0% indicating a perfectly spherical acetabulum, and higher SRI values indicating a more aspherical shape. The median SRI was greater in patients with hip dysplasia than in normal hips (5.9% vs. − 1.4%; p

Introduction: It remains controversial whether it is better to continue oral low-dose aspirin (LDA) during the perioperative period in spinal surgery. This study aims to evaluate the safety of continued LDA administration in the perioperative periods of microendoscopic laminectomy (MEL) by assessing perioperative complications and clinical outcomes. Methods: We ultimately included 88 patients (35 males, 53 females) who underwent one level of MEL for lumbar spinal canal stenosis from April 2016 to March 2022. Patients who did not undergo anticoagulation therapy were classified into Group A (65 patients), those who stopped anticoagulation therapy at the perioperative periods were classified into Group B (9 patients), and those who continued oral administration of LDA throughout the perioperative periods were classified into Group C (14 patients). Surgery time, intraoperative estimate blood loss (EBL), differences between hemoglobin (Hb) and platelet (Plt) before and after surgery, perioperative complications, and cross-sectional area of hematoma and dural sac on MRI taken within 1 week and at 6 months or more after surgery were assessed between three groups. The EuroQol-5 dimensions (EQ-5D), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were also evaluated as the clinical outcomes. Results: There was no statistically significant difference between the three groups in operation time, intraoperative EBL, differences between Hb and Plt before and after surgery, and cross-sectional area of hematoma and dural sac on MRI. A case of hematoma removal was confirmed in Group A. There was also no statistically significant difference between the three groups in EQ-5D, ODI, and each domain of JOABPEQ. Conclusions: The continuation of LDA throughout the perioperative periods did not affect perioperative complications and clinical outcomes of one-level MEL. In MEL, it might be possible to continue oral administration of LDA throughout the perioperative periods.

Abstract After spinal cord injury (SCI), inflammatory cells such as macrophages infiltrate the injured area, and astrocytes migrate, forming a glial scar around macrophages. The glial scar inhibits axonal regeneration, resulting in significant permanent disability. However, the mechanism through which glial scar-forming astrocytes migrate to the injury site has not been clarified. Here we show that migrating macrophages attract reactive astrocytes toward the center of the lesion after SCI. Chimeric mice with bone marrow lacking IRF8, which controls macrophage centripetal migration after SCI, showed widely scattered macrophages in the injured spinal cord with the formation of a huge glial scar around the macrophages. To determine whether astrocytes or macrophages play a leading role in determining the directions of migration, we generated chimeric mice with reactive astrocyte-specific Socs3 −/− mice, which showed enhanced astrocyte migration, and bone marrow from IRF8 −/− mice. In this mouse model, macrophages were widely scattered, and a huge glial scar was formed around the macrophages as in wild-type mice that were transplanted with IRF8 −/− bone marrow. In addition, we revealed that macrophage-secreted ATP-derived ADP attracts astrocytes via the P2Y1 receptor. Our findings revealed a mechanism through which migrating macrophages attract astrocytes and affect the pathophysiology and outcome after SCI.

Abstract There are no reports on hip kinetics including contact forces and muscle activities during the golf swing after total hip arthroplasty (THA). The aim of this study was to identify the characteristics of three-dimensional dynamics during the golf swing. Ten unilateral primary THA patients participated in motion capture test of their driver golf swing. The driver swing produced approximately 20–30° of rotation in both lead and trail replaced hips. The mean hip contact forces (HCFs) of lead and trail replaced hips were 5.1 and 6.6 × body weight, respectively. Left and right THAs showed similar HCFs of lead and trail hips. More than 60% of the Percent maximum voluntary isometric contraction was found in bilateral iliopsoas muscles in all unilateral THA. Three factors [female sex, lower modified Harris Hip Score, and higher HCF of surgical side] were associated with the golf-related replacement hip pain. Golf is an admissible sport after THA because driver swings do not contribute excessive rotation or contact forces to hip prostheses. HCF could be reduced through swing adjustments, which may allow patients with golf-related replacement hip pain to develop a comfortable golf game free from pain.

Abstract This study aimed to (1) set a reference value for anterior center edge angle (ACEA) for preoperative planning of periacetabular osteotomy (PAO), (2) investigate the effects of pelvic rotation and inclination from false profile (FP) radiographs on the measured ACEA, and (3) determine the “appropriate range of positioning” for FP radiograph. This single-centered, retrospective study analyzed 61 patients (61 hips) who underwent PAO from April 2018 and May 2021. ACEA was measured in each digitally reconstructed radiography (DRR) image of the FP radiograph reconstructed in different degrees of pelvic rotation. Detailed simulations were performed to determine the “appropriate range of positioning” (0.67

Traumatic spinal cord injury (TSCI) causes an insult to the central nervous system, often resulting in devastating temporary or permanent neurological impairment and disability, which places a substantial financial burden on the health-care system. This study aimed to clarify the up-to-date epidemiology and demographics of patients with TSCI treated at the largest SCI center in Japan. Data on all patients admitted to the Spinal Injuries Center with TSCI between May 2005 and December 2021 were prospectively collected using a customized, locally designed SCI database named the Japan Single Center Study for Spinal Cord Injury Database (JSSCI-DB). A total of 1152 patients were identified from the database. The study period was divided into the four- or five-year periods of 2005-2009, 2010-2013, 2014-2017, and 2018-2021 to facilitate the observation of general trends over time. Our results revealed a statistically significant increasing trend in age at injury. Since 2014, the average age of injury has increased to exceed 60 years. The most frequent spinal level affected by the injury was high cervical (C1-C4: 45.8%), followed by low cervical (C5-C8: 26.4%). Incomplete tetraplegia was the most common cause or etiology category of TSCI, accounting for 48.4% of cases. As the number of injuries among the elderly has increased, the injury mechanisms have shifted from high-fall trauma and traffic accidents to falls on level surfaces and downstairs. Incomplete tetraplegia in the elderly due to upper cervical TSCI has also increased over time. The percentage of injured patients with an etiology linked to alcohol use ranged from 13.2% (2005-2008) to 19% (2014-2017). Given that Japan has one of the highest aging populations in the world, epidemiological studies in this country will be very helpful in determining health insurance and medical costs and deciding strategies for the prevention and treatment of TSCI in future aging populations worldwide.

BackgroundSpinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target.MethodsWe created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test.ResultsIn macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function.ConclusionWe demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.

Introduction: Tumor size is an important factor in determining the appropriate clinical management of intradural-extramedullary schwannoma. A tumor volume reduction may be achieved by conservative targeted therapy instead of invasive surgery if a molecular event related to tumor size is discovered. Insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an oncofetal tumor-associated antigen that is expected to be a target for immunotherapy, was focused on in this study. Methods: The IMP3 status was assessed by immunohistochemistry in 64 samples of intradural-extramedullary schwannoma, and the correlation between IMP3 expression and tumor size was evaluated. Results: Immunohistochemically, high IMP3 expression was observed in ～85% of schwannomas. The maximum tumor diameter of the high IMP3 expression group was significantly larger than that of the low IMP3 expression group (34.3 mm vs 18.5 mm, p=0.002). The receiver operating characteristic curve demonstrated that a maximum tumor diameter of 24 mm was a predictable factor for IMP3 expression (sensitivity, 0.7; 1−specificity, 0.2; area under the curve, 0.82). Conclusions: Upregulated IMP3 expression was associated with large tumor size, suggesting a possible therapeutic approach.

Objective Excessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post‐collapse stage ONFH. Methods This is a single‐center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z‐axis in the sagittal view (APP angle). An APP angle

Abstract This study aimed to investigate the influence of bone marrow edema (BME) for the assessment of the boundaries of necrotic lesions using unenhanced and contrast-enhanced (CE) magnetic resonance (MR) images in patients with osteonecrosis of the femoral head (ONFH). We retrospectively reviewed 72 consecutive hips in 55 patients of ONFH that were Association Research Circulation Osseous (ARCO) stage III or higher and underwent both unenhanced and contrast-enhanced MR imaging between January 2005 and February 2016. The degree of extension of BMEs, and the boundaries of the necrotic lesions were compared using unenhanced and CE MR images on both mid coronal and mid oblique-axial slices. Forty-two percent of the coronal T1 images, 40% of the coronal fat-saturated T2 images, and 48% of the oblique-axial T1 images showed differences in the boundaries of necrotic lesion, by comparison with those of CET1-weighted MR images. The boundaries of necrotic lesions were clearly detected in all hips on CE coronal slices and 97% of all hips on CE oblique-axial slices. The BME grade in the difference group was significantly higher than in the non-difference group on the coronal plane (P = 0.0058). There were significant differences between the BME grade and duration from the onset of hip pain to MR imaging examination. Multivariate analyses revealed that the duration from the onset to MR imaging examination in both coronal (P = 0.0008) and oblique-axial slices (P = 0.0143) were independently associated with differences in the boundary of necrotic lesion between T1 and CET1-weighted MR images. Our findings suggest that unenhanced MR image may be insufficient for a precise assessment of the boundaries of the necrotic lesions for ONFH cases in the early phase of subchondral collapse due to the diffuse BME.

Abstract Background X-ray images are commonly used to assess the bone destruction of rheumatoid arthritis. The purpose of this study is to propose an automatic-bone-destruction-evaluation system fully utilizing deep neural networks (DNN). This system detects all target joints of the modified Sharp/van der Heijde score (SHS) from a hand X-ray image. It then classifies every target joint as intact (SHS = 0) or non-intact (SHS ≥ 1). Methods We used 226 hand X-ray images of 40 rheumatoid arthritis patients. As for detection, we used a DNN model called DeepLabCut. As for classification, we built four classification models that classify the detected joint as intact or non-intact. The first model classifies each joint independently, whereas the second model does it while comparing the same contralateral joint. The third model compares the same joint group (e.g., the proximal interphalangeal joints) of one hand and the fourth model compares the same joint group of both hands. We evaluated DeepLabCut’s detection performance and classification models’ performances. The classification models’ performances were compared to three orthopedic surgeons. Results Detection rates for all the target joints were 98.0% and 97.3% for erosion and joint space narrowing (JSN). Among the four classification models, the model that compares the same contralateral joint showed the best F-measure (0.70, 0.81) and area under the curve of the precision-recall curve (PR-AUC) (0.73, 0.85) regarding erosion and JSN. As for erosion, the F-measure and PR-AUC of this model were better than the best of the orthopedic surgeons. Conclusions The proposed system was useful. All the target joints were detected with high accuracy. The classification model that compared the same contralateral joint showed better performance than the orthopedic surgeons regarding erosion.

Background: The purpose of this study was to investigate the size differences of 19 different femoral component placements from the standard position in total knee arthroplasty using 3-dimensional virtual surgery. Methods: Three-dimensional bone models were reconstructed from the computed tomography data of 101 varus osteoarthritic knees. The distal femoral bone was cut perpendicular to the femoral mechanical axis (MA) in the coronal plane. Twenty different component placements consisting of 5 cutting directions (perpendicular to MA, 3° and 5° extension relative to MA [3°E-MA and 5°E-MA, respectively], and 3° and 5° flexion relative to MA [3°F-MA and 5°F-MA, respectively]) in the sagittal plane, 2 rotational alignments (clinical epicondylar axis [CEA] and surgical epicondylar axis [SEA]), and 2 rotational types of anterior reference guide (central [CR] and medial [MR]) were simulated. Results: The mean anteroposterior dimension of femur ranged from 54.3 mm (5°F-MA, SEA, CR) to 62.5 mm (5°E-MA, CEA, MR). The largest and smallest differences of anteroposterior dimension from the standard position (3°F-MA, SEA, and CR) were 7.1 ± 1.3 mm (5°E-MA, CEA, and MR) and −1.2 ± 0.2 mm (5°F-MA, SEA, and CR), respectively. Multiple regression analysis revealed that flexion cutting direction, SEA, and CR were associated with smaller component size. Conclusions: The femoral component size can be affected easily by not only cutting direction but also the reference guide type and the target alignment. Our findings could provide surgeons with clinically useful information to fine-tune for unintended loose or tight joint gaps by adjusting the component size.

Abstract In crush syndrome, massive muscle breakdown resulting from ischemia–reperfusion muscle injury can be a life-threatening condition that requires urgent treatment. Blood reperfusion into the ischemic muscle triggers an immediate inflammatory response, and neutrophils are the first to infiltrate and exacerbate the muscle damage. Since free zinc ion play a critical role in the immune system and the function of neutrophils is impaired by zinc depletion, we hypothesized that the administration of a zinc chelator would be effective for suppressing the inflammatory reaction at the site of ischemia–reperfusion injury and for improving of the pathology of crush syndrome. A crush syndrome model was created by using a rubber tourniquet to compress the bilateral hind limbs of mice at 8 weeks. A zinc chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) was administered immediately after reperfusion in order to assess the anti-inflammatory effect of the chelator for neutrophils. Histopathological evaluation showed significantly less muscle breakdown and fewer neutrophil infiltration in TPEN administration group compared with control group. In addition, the expression levels of inflammatory cytokine and chemokine such as IL-6, TNFα, CXCL1, CXCL2, CXCR2, CCL2 in ischemia–reperfusion injured muscle were significantly suppressed with TPEN treatment. Less dilatation of renal tubules in histological evaluation in renal tissue and significantly better survival rate were demonstrated in TPEN treatment for ischemia–reperfusion injury in crush syndrome. The findings of our study suggest that zinc chelators contributed to the resolution of exacerbation of the inflammatory response and attenuation of muscle breakdown in the acute phase after crush syndrome. In addition, our strategy of attenuation of the acute inflammatory reaction by zinc chelators may provide a promising therapeutic strategy not only for crush syndrome, but also for other diseases driven by inflammatory reactions.

Abstract Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.

Abstract Background Adipose-derived mesenchymal stem cells (ADMSCs) are a promising source of material source for medical regeneration of cartilage. Growth factors, including transforming growth factor-β (TGFβ) subfamily members and bone morphogenetic proteins (BMPs), play important roles in inducing and promoting chondrogenic differentiation of MSCs. However, these exogenous growth factors have some drawbacks related to their cost, biological half-life, and safety for clinical application. Several studies have reported that statins, the competitive inhibitors of 3-hydroxy-2-methylglutaryl coenzyme A (HMG-CoA) reductase, induce the expression of BMP2 in multiple cell types as the pleotropic effects. The objective of this study was to investigate the effects of fluvastatin during chondrogenic differentiation of human ADMSCs (hADMSCs). Methods The effects of fluvastatin were analyzed during chondrogenic differentiation of hADMSCs in the pellet culture without exogenous growth factors by qRT-PCR and histology. For functional studies, Noggin, an antagonist of BMPs, mevalonic acid (MVA) and geranylgeranyl pyrophosphate (GGPP), metabolites of the mevalonate pathway, ROCK inhibitor (Y27632), or RAC1 inhibitor (NSC23766) were applied to cells during chondrogenic differentiation. Furthermore, RhoA activity was measured by RhoA pulldown assay during chondrogenic differentiation with or without fluvastatin. Statistically significant differences between groups were determined by Student’s t-test or the Tukey–Kramer test. Results Fluvastatin-treated cells expressed higher levels of BMP2, SOX9, ACAN, and COL2A1 than control cells, and accumulated higher levels of glycosaminoglycans (GAGs). Noggin significantly inhibited the fluvastatin-mediated upregulation of ACAN and COL2A1. Both MVA and GGPP suppressed the effects of fluvastatin on the expressions of BMP2, SOX9, ACAN, and COL2A1. Furthermore, fluvastatin suppressed the RhoA activity, and inhibition of RhoA–ROCK signaling by Y27632 increased the expressions of BMP2, SOX9, ACAN, and COL2A1, as well as fluvastatin. Conclusions Our results suggest that fluvastatin promotes chondrogenic differentiation of hADMSCs by inducing endogenous BMP2, and that one of the mechanisms underlying the effects is inhibition of RhoA–ROCK signaling via suppression of GGPP. Fluvastatin is a safe and low-cost compound that holds promise for use in transplantation of hADMSCs for cartilage regeneration.

Introduction: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. Objective: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. Methods: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. Results: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p

Background: In patients with cervical spinal cord injury (SCI), we need to make accurate prognostic predictions in the acute phase for more effective rehabilitation. We hypothesized that a multivariate prognosis would be useful for patients with cervical SCI. Methods: We made two predictive models using Multiple Linear Regression (MLR) and Artificial Neural Networks (ANNs). We adopted MLR as a conventional predictive model. Both models were created using the same 20 clinical parameters of the acute phase data at the time of admission. The prediction results were classified by the ASIA Impairment Scale. The training data consisted of 60 cases, and prognosis prediction was performed for 20 future cases (test cohort). All patients were treated in the Spinal Injuries Center (SIC) in Fukuoka, Japan. Results: A total of 16 out of 20 cases were predictable. The correct answer rate of MLR was 31.3%, while the rate of ANNs was 75.0% (number of correct answers: 12). Conclusion: We were able to predict the prognosis of patients with cervical SCI from acute clinical data using ANNs. Performing effective rehabilitation based on this prediction will improve the patient’s quality of life after discharge. Although there is room for improvement, ANNs are useful as a prognostic tool for patients with cervical SCI.

Introduction: Facet joints are anatomical structures that are known to be crucial for determining spinal biomechanical motion; however, the potential relationship between facet orientation and the development of cervical spondylolisthesis remains unclear. Thus, in this study, we aimed to explore the relationship between facet orientation and cervical spondylolisthesis as well as myelopathy. Methods: Facet orientation in the cervical spine was investigated using computed tomography in 103 patients with cervical myelopathy, and facet inclination was measured on axial, coronal, and sagittal reconstructed images. Patients were divided into anterolisthesis, retrolisthesis, and no spondylolisthesis groups at each intervertebral level (C2/3-C6/7 levels). Results: Facet joints in the anterolisthesis and retrolisthesis groups tended to slope posterolaterally and downward laterally compared with those in the no spondylolisthesis group at C3/4, C4/5, and C5/6 levels (P

Abstract Patellofemoral joint complications remain an important issue in total knee arthroplasty. We compared the patellofemoral contact status between cruciate-retaining and posterior-stabilized designs with varying degrees of tibial sagittal and rotational alignment using a computer simulation to ensure proper alignments in total knee arthroplasty. Knee kinematics, patellofemoral contact force and quadriceps force were computed using a musculoskeletal modeling program (LifeMOD/KneeSIM 2010; LifeModeler, Inc., San Clemente, California) during a weight-bearing deep knee bend. Two different posterior tibial slope (PTS)s (3° and 7°) and five different tibial tray rotational alignments (neutral, internal 5° and 10°, and external 5° and 10°) were simulated. Patellofemoral contact area and stresses were next computed using finite element analysis. The patellofemoral contact force for the posterior-stabilized design was substantially lower than the cruciate-retaining design after post-cam contact because of increasing femoral roll-back. Neutral rotational alignment of the tibial component resulted in smaller differences in patellofemoral contact stresses between cruciate-retaining and posterior-stabilized designs for PTSs of 3° or 7°. However, the patellar contact stresses in the cruciate-retaining design were greater than those in posterior-stabilized design at 120° of knee flexion with PTS of 3° combined with internal rotation of the tibial component. Our study provides biomechanical evidence implicating lower PTSs combined with internal malrotation of the tibial component and the resultant increase in patellofemoral stresses as a potential source of anterior knee pain in cruciate-retaining design.

Abstract Background The coronal whole-leg radiograph is generally used for preoperative planning in total knee arthroplasty. The distal femoral valgus angle (DFVA) is measured for distal femoral bone resection using an intramedullary guide rod. The effect of coronal and sagittal femoral shaft bowing on DFVA measurement in the presence of malrotation or knee flexion contracture has not been well reported. The objectives of this study were: (1) to investigate the effects of whole-leg malrotation and knee flexion contracture on the DFVA in detail, (2) to determine the additional effect of coronal or sagittal femoral shaft bowing. Methods We studied 100 consecutive varus and 100 valgus knees that underwent total or unicompartmental knee arthroplasty. Preoperative CT scans were used to create digitally reconstructed radiography (DRR) images in neutral rotation (NR, parallel to the surgical epicondylar axis), and at 5° and 10° external rotation (ER) and internal rotation (IR). The images were also reconstructed at 10° femoral flexion. The DFVA was evaluated in each DRR image, and the angular variation due to lower limb malposition was investigated. Results The DFVA increased as the DRR image shifted from IR to ER, and all angles increased further from extension to 10° flexion. The DFVA variation in each position was 1.3° on average. A larger variation than 2° was seen in 12% of all. Multivariate regression analysis showed that sagittal femoral shaft bowing was independently associated with a large variation of DFVA. Receiver operating characteristic analysis showed that more than 12° of sagittal bowing caused the variation. Conclusion If femoral sagittal bowing is more than 12°, close attention should be paid to the lower limb position when taking whole-leg radiographs. Preoperative planning with whole-leg CT data should be considered.

Abstract Background In performing primary constrained total knee arthroplasties (TKA) to imbalanced knees, the offset stem is sometimes compelled to use, although this is associated with surgical difficulties. We developed a modified procedure which might be able to fit the anteroposterior (AP) and mediolateral (ML) position of the femoral component simultaneously with the straight stem. Purposes of this study were to evaluate usefulness of the modified procedure both in computer simulations and actual surgeries. Methods We included 32 knees that had undergone primary TKA using constrained implants because of the coronal imbalance. In the component-first procedure, the distal femur was prepared to fit the AP and ML position of the femoral component simultaneously at first, as in primary TKA. Finally, the stem hole is created based on the femoral component position (the component-first procedure). The femoral component and extension stem were simulated using the three-dimensional planning software (ZedKnee) following the component-first procedure. We investigated the suitability of the straight stem through computer simulation and evaluation of actual surgeries. Clinical and radiographical outcomes were also evaluated at the latest follow-up. Results The component-first procedure enabled the AP and ML position of the femoral component to be fitted simultaneously with the straight stem in simulations and actual surgeries in all cases. The stem diameter was not significantly different between simulations and actual surgeries (13.9 and 13.7 mm on average, respectively, p = 0.479) and almost similar from intraclass correlation coefficient analysis (kappa value 0.790). Clinical and radiographical outcomes were almost similar to primary TKA cases and there was no case of component loosening, cortical bone hypertrophy around the stem and stem-tip pain. Conclusions Our improved surgical procedure may facilitate use of the constrained implant for more cases of primary TKA in imbalanced knees without the usual surgical difficulties. Trial registration Retrospectively registered.

Introduction In patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It is desirable to select analgesics for elderly patients based on comparative data on analgesic effect and risk of adverse events; however, there are few comparative studies so far. The purpose of this study is to determine whether the efficacy and safety of acetaminophen are non-inferior to non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain associated with osteoarthritis of the hip and knee in elderly patients.Methods and analysis This study is a multicentre, randomised controlled, double-blind, parallel-group study to compare the analgesic effect and adverse events between acetaminophen or NSAIDs (loxoprofen or celecoxib). A total of 400 elderly patients with osteoarthritis of the hip and knee will be recruited from five institutions in Japan. Patients of 65 years or older with osteoarthritis-related pain will be registered and randomly assigned to acetaminophen, loxoprofen or celecoxib with 2:1:1 allocation. The primary endpoint is change in the Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints are BPI item 3 score change from baseline to week 4, health-related QOL measured by Short Form-8 Health Survey, and occurrence of adverse events including gastrointestinal disorders and abnormal liver function. Data will be analysed in accordance with a predefined statistical analysis plan.Ethics and dissemination This study protocol was approved by the Kyushu University Hospital Certified Institutional Review Board for Clinical Trials on 28 January 2021 (KD2020004) and the chief executive of each participating hospital. The results of the study will be submitted to international peer-reviewed journals, and the main findings will be presented at international scientific conferences.Trial registration number jRCTs071200112.

Abstract Background To compare the degree of stem subsidence between two different femoral component designs and to determine the risk factors associated with stem subsidence after cementless total hip arthroplasty (THA) in Dorr type C femurs. Methods We retrospectively reviewed 104 consecutive hips in 100 patients with Dorr type C proximal femoral morphology who underwent primary cementless THA using a fit-and-fill stem or a tapered wedge femoral stem at our institution between January 2012 and June 2021. A fit-and-fill stem was used in 55 hips and a tapered wedge stem was used in 49 hips. Radiologically, the distance between the apex of the major trochanter and the stem shoulder were measured at three different time points (immediately [0W], one week [1W], and six weeks [6W] after surgery) and the degrees of stem subsidence were assessed by comparing the distance between 0 and 1W, 1W and 6W, and 0W and 6W, respectively. Results The mean degree of stem subsidence (0W vs. 1W) was 0.24 mm (standard deviation [SD] 0.36) in the fit-and-fill stem group, and 0.23 mm (SD 0.41) in the tapered wedge stem group. There was no significant difference between the two groups (P = 0.4862). However, the mean degrees of subsidence were significantly higher in the fit-and-fill stem group (1W vs. 6W, 0.38 mm [SD 0.68]; 0W vs. 6W, 0.65 mm [SD 0.87]) than in the tapered wedge stem group (1W vs. 6W, 0.16 mm [SD 0.32]; 0W vs. 6W, 0.24 mm [SD 0.38]) (P 3 mm subsidence (in which instability can be observed) were 18.2% (10 of 55 hips) and 2.0% (1 of 49 hips), respectively. There was also a significant difference between the two stems (P = 0.0091). Multivariate analysis demonstrated that fit-and-fill stem was a risk factor for > 3 mm subsidence after THA in Dorr type C femurs (P = 0.0050). Conclusion Our findings suggest that the tapered wedge stem is more suitable for Dorr type C femurs than the fit-and-fill stem to avoid early postoperative subsidence in cementless THA.

Abstract 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.

There are no studies that have investigated the characteristics of car use across THA patients, including those who do not drive. This study aimed to evaluate, in THA patients, (1) postoperative car usage, (2) comfort while entering and exiting a car, and (3) whether lower limb muscle strength affects action comfort. One hundred seventy-two post-THA patients completed the questionnaire in 2020, along with assessments of hip abductor and knee extensor muscle strength before surgery and at discharge. Patients whose overall comfort level was judged as comfortable were defined as the comfort group; others were placed in the discomfort group. Of the 172 patients, 161 reported car usage at a mean of 5.6 years after THA. Of these, 114 and 47 patients were placed in the comfort and discomfort groups, respectively. Patients in the discomfort group were three times more likely to experience discomfort using the contralateral side door than the surgical side door, and about twice as many patients experienced discomfort when entering as when exiting. Lower preoperative contralateral hip abductor muscle strength was the only independent predictor for discomfort. The take-home messages were that prevention of contralateral-side weakness may improve comfort during the action after THA.

Abstract Background The ideal acetabular position for optimizing hip joint biomechanics in periacetabular osteotomy (PAO) remains unclear. We aimed to determine the relationship between acetabular correction in the coronal plane and joint contact pressure (CP) and identify morphological factors associated with residual abnormal CP after correction. Methods Using CT images from 44 patients with hip dysplasia, we performed three patterns of virtual PAOs on patient-specific 3D hip models; the acetabulum was rotated laterally to the lateral center-edge angles (LCEA) of 30°, 35°, and 40°. Finite-element analysis was used to calculate the CP of the acetabular cartilage during a single-leg stance. Results Coronal correction to the LCEA of 30° decreased the median maximum CP 0.5-fold compared to preoperatively (p 53.2%), coronal plane correction alone may not normalize CP. Further studies are needed to clarify the effectiveness of multiplanar correction, including in the sagittal and axial planes, in optimizing the hip joint’s contact mechanics.

Abstract 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.

Objectives: The study aimed to elucidate target cup orientation and stem anteversions to avoid impingement between the liner and stem neck even at hip rotation with adduction during the deeply flexed posture.Methods: A computer simulation analysis was performed on 32 total hip arthroplasty patients applying patient-specific orientation of the components and in vivo hip kinematics obtained from three-dimensional analysis of the squatting motion. The anterior/posterior liner-to-neck distance and impingement were evaluated based on a virtual change in internal/external rotation (0°–60°) and adduction/abduction (0°–20°) at actual maximum flexion/extension during squatting. Cutoff values of cup orientations, stem anteversion, and combined anteversion to avoid liner-to-neck impingements were determined.Results: The anterior liner-to-neck distance decreased as internal rotation or adduction increased, and the posterior liner-to-neck distance decreased as external rotation or adduction increased. Negative correlations were found between anterior/posterior liner-to-neck distances at maximum flexion/extension and internal/external rotation. Anterior/posterior liner-to-neck impingements were observed in 6/18 hips (18/56%) at 45° internal/external rotation with 20° adduction. The range of target cup anteversion, stem anteversion, and combined anteversion to avoid both anterior and posterior liner-to-neck impingements during squatting were 15°–18°, 19°–34°, and 41°–56°, respectively.Conclusion: Simulated hip rotations caused prosthetic impingement during squatting. Surgeons could gain valuable insights into target cup orientations and stem anteversion based on postoperative simulations during the deeply flexed posture.

Abstract Aims/Introduction To investigate the association between midlife or late‐life diabetes and the development of sarcopenia in an older Japanese population. Materials and Methods A total of 824 Japanese residents aged 65 to 84 years without sarcopenia were followed up from 2012 to 2017. Sarcopenia was determined following the Asian Working Group for Sarcopenia definition. The time of diabetes diagnosis was classified as midlife or late‐life diabetes by the age at first diagnosis of diabetes (< 65 or ≥ 65 years) based on annual health checkups data over the past 24 years. The duration of diabetes was categorized into three groups of 15 years. The odds ratios of incident sarcopenia according to the diabetic status were estimated using a logistic regression analysis. Results During follow‐up, 47 subjects developed sarcopenia. The multivariable‐adjusted odds ratio for incident sarcopenia was significantly greater in subjects with diabetes at baseline than in those without it (odds ratio 2.51, 95% confidence interval 1.26–5.00). Subjects with midlife diabetes had a significantly greater risk of incident sarcopenia, whereas no significant association between late‐life diabetes and incident sarcopenia was observed. With a longer duration of diabetes, the risk of incident sarcopenia increased significantly (P for trend = 0.002). Conclusions The present study suggests that midlife diabetes and a longer duration of diabetes are significant risk factors for incident sarcopenia in the older population. Preventing diabetes in midlife may reduce the risk of the development of sarcopenia in later life.

Abstract Background No studies have directly evaluated kinematic changes during squatting before and after bicruciate-stabilized total knee arthroplasty (BCS-TKA) with the dual cam-post mechanism and asymmetric surfaces. This study investigated the effect of BCS-TKA on changes to pre- and postoperative skeletal knee kinematics, to identify factors associated with postoperative skeletal kinematic parameters. Methods Seventeen knees in 17 patients were prospectively recruited before primary TKA for advanced medial knee osteoarthritis. Subjects underwent BCS-TKA and were evaluated more than 1 year postoperatively. In vivo dynamic skeletal knee kinematics were evaluated using periodic radiographic images collected during squatting to quantify the tibiofemoral functional extension/flexion angle, anteroposterior (AP) translation, and axial rotation angle using image-matching techniques. Rotational alignments of femoral and tibial components were measured postoperatively using computed tomography images. Results The pre- and postoperative tibiofemoral functional extension/flexion angles during squatting were 12.2° ± 6.7°/100.1° ± 16.8° and 9.6° ± 8.6°/109.4° ± 16.8°, respectively, with a significant difference in flexion angle (p

Introduction Lower-limb osteoarthritis (OA) in the elderly can be a risk factor for frailty, which is the preliminary of disability, but it may be reversible with appropriate interventions. We aimed to use the Kihon Check List (KCL) to assess multiple domains of frailty and to identify the characteristics of frailty in patients with hip or knee OA following total joint arthroplasty. Materials and Methods This study included 136 ≥ 65-year-old patients (mean age: 73.0 years) who underwent total arthroplasty with end-stage hip and knee OA. We assessed frailty status, instrumental activities of daily living (IADL), and health-related quality of life (HRQoL) according to the KCL, functional ambulatory index (FAI) and EuroQol-5 Dimension (EQ5D), respectively, as well as the extent of pain preoperatively and at postoperative 6 months. Results Using KCL, seventy-eight (57.4%) patients were frail preoperatively, but the prevalence significantly decreased to 52 patients (38.2%) at postoperative 6 months. Total arthroplasty intervention provided significant improvements in the total KCL scores, including the physical domain ( P < .01), pain ( P < .01), FAI scores ( P < .01), and EQ5D ( P < .01), but not the social domain. Multivariate logistic regression analysis identified age at surgery (OR: .93, 95% CI: .86-.99) and preoperative FAI score (OR: 1.10, 95% CI: 1.03-1.19) as independent predictors of postoperative frailty. Conclusions Total arthroplasty procedures on patients with hip and knee OA reduced their KCL score, but social aspects were less improved than physical aspects in the shortterm. Older age and preoperative lower IADL score can be useful for accurately estimating less improvement of frailty in the early postoperative phase. Our results suggest that long term follow-up of OA is needed to provide comprehensive interventions, including in social aspects, especially for patients with lower activity.

Abstract Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

Background: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality. Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model. Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend