Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.

Neuromuscular electrical stimulation, muscle mass, and physical function decline in the early phase after living donor liver transplantation.

This study aims to investigate the effects of neuromuscular electrical stimulation (NMES) in addition to conventional early mobilization in the early postoperative period after living donor liver transplantation (LTx) on body composition and physical function. This was a retrospective single-center cohort study. Adult subjects who were admitted for living donor LTx from 2018 to 2023 were included in the analysis. After April 2020, patients underwent 4 weeks of NMES in addition to conventional rehabilitation. The skeletal muscle mass index, body cell mass, and physical function, including the 6-minute walking distance, were assessed before surgery and at discharge, and changes in these outcomes were compared before and after the introduction of NMES. Sixty-one patients were in the NMES group, and 53 patients before the introduction of NMES were in the control group. ANCOVA with etiology, obstructive ventilatory impairment, Child-Pugh classification, and initial body composition value as covariates demonstrated that there was a significantly smaller decline of body cell mass (-2.9±2.7 kg vs. -4.4±2.7 kg, p = 0.01), as well as of the skeletal muscle mass index (-0.78±0.73 kg/m2 vs. -1.29±1.21 kg/m2, p = 0.04), from baseline to discharge in the NMES group than in the control group; thus, the decline after surgery was suppressed in the NMES group. Four weeks of NMES, in addition to conventional rehabilitation in the early period after LTx, may attenuate the deterioration of muscle mass. It is suggested that NMES is an option for developing optimized rehabilitation programs in the acute postoperative period after LTx.

IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumor resection.

INTRODUCTION: Recycled bone autografts prepared using extracorporeal irradiation (ECIR) or liquid nitrogen freezing (LNF) methods have been used for the reconstruction of skeletal elements after wide resection of sarcomas involving bone tissues. Few reports include long-term follow-up data for histological analyses of recycled autografts, particularly in the case of ECIR autografts. MATERIALS: A total of 34 malignant bone and soft tissue tumors were resected and reconstructed using 11 ECIR- and 23 LNF-recycled autografts; the mean postoperative follow-ups were 14 and 8 years, respectively. ECIR was used for either osteosarcomas or Ewing sarcomas, whereas in addition to these tumors LNF was used for chondrosarcomas and soft tissue sarcomas involving bone tissues. Recycled bone was implanted as total bone, osteoarticular, or intercalary grafts, with or without prosthesis or vascularized fibular grafts. RESULTS: The 10-year graft survival rate was similar between groups, 81.8% using ECIR and 70.2% using LNF. There were no autograft-related tumor recurrences in either group. Graft survival was unrelated to type of graft or additional procedures. Complication rates tended to be higher using ECIR (64%) compared with LNF (52%) and the infection rate was significantly higher with ECIR (27%) versus LNF (0%). At the final assessment, plain radiographs revealed original recycled bone was present in 7 of 11 ECIR cases and in zero cases treated with LNF autografts, indicating that recycled bone treated with LNF autografts was remodeled into new bone. Histological examination of ECIR-treated bones revealed a delayed and incomplete endochondral ossification process, necrosis and empty lacunae. Conversely, LNF autografts showed remodeled bones with normal trabecular structures. CONCLUSIONS: ECIR and LNF treatment of autografts provided adequate tumor control with acceptable clinical results as a reconstruction method.

Are Dental Procedures Associated With Pyogenic Vertebral Osteomyelitis?

BACKGROUND: Dental procedures can lead to bacteremia and have been considered a potential risk factor for pyogenic vertebral osteomyelitis (PVO). However, data on the association between dental procedures and PVO are limited. QUESTIONS/PURPOSES: (1) After controlling for relevant confounding variables, are dental procedures associated with an increased risk of PVO? (2) Does antibiotic prophylaxis before dental procedures effectively decrease the risk of PVO? METHODS: A case-crossover study was conducted to investigate the association between dental procedures and PVO using a Japanese claims database. The advantage of this study design is that confounding factors that do not vary over time are automatically adjusted for, because cases act as their own controls. From April 2014 to September 2021, the database included 8414 patients who were hospitalized for PVO. Of these, 50% (4182 of 8414) were excluded because they had not undergone any dental procedures before the index date, a further 0.1% (10 of 8414) were excluded because they were younger than 18 years at the index date, and a further 7% (623 of 8414) were excluded because they did not have at least 20 weeks of continuous enrollment before the index date, leaving 43% (3599 of 8414) eligible for analysis here. The mean age was 77 ± 11 years, and 55% (1985 of 3599) were men. Sixty-five percent (2356 of 3599) of patients had a diagnosis of diabetes mellitus, and 42% (1519 of 3599) of patients had a diagnosis of osteoporosis. We compared the frequency of dental procedures between a 4-week hazard period before the admission date for PVO and two control periods, 9 to 12 weeks and 17 to 20 weeks before the admission date for PVO, within individuals. We calculated odds ratios and 95% confidence intervals using conditional logistic regression analysis. RESULTS: Comparing the hazard and matched control periods within individuals demonstrated that dental procedures were not associated with an increased risk of PVO (OR 0.81 [95% CI 0.72 to 0.92]; p < 0.001). Additional analysis stratified by antibiotic prophylaxis use showed that antibiotic prophylaxis was not associated with a lower OR of developing PVO after dental procedures (with antibiotic prophylaxis: OR 1.11 [95% CI 0.93 to 1.32]; p < 0.26, without antibiotic prophylaxis: OR 0.72 [95% CI 0.63 to 0.83]; p < 0.001). Our sensitivity analyses, in which the exposure assessment interval was extended from 4 to 8 or 12 weeks and exposure was stratified by whether the dental procedure was invasive, demonstrated results that were consistent with our main analysis. CONCLUSION: Dental procedures were not associated with an increased risk of subsequent PVO in this case-crossover study. The effectiveness of antibiotic prophylaxis was not demonstrated in the additional analysis that categorized exposure according to the use of antibiotic prophylaxis. Our results suggest that the association between dental procedures and PVO may have been overestimated. Maintaining good oral hygiene may be important in preventing the development of PVO. The indications for antibiotic prophylaxis before dental procedures should be reconsidered in view of the potential risk of adverse drug reactions to antibiotic prophylaxis and the emergence of drug-resistant pathogens. Larger randomized controlled trials are needed to confirm these findings and assess the role of antibiotic prophylaxis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Association of physical activity with fatty infiltration of muscles after total hip arthroplasty.

OBJECTIVE: This study aimed to investigate the association between muscle density as an indicator of fatty infiltration of lower extremity muscles and physical activity (PA) after total hip arthroplasty (THA) and identify the patient characteristics with high postoperative PA. METHODS: This study included 62 female patients who underwent THA for unilateral hip osteoarthritis. Muscle density of the gluteus maximus, gluteus medius, iliopsoas, and quadriceps muscles was measured using computed tomography (CT). PA was assessed using University of California, Los Angeles (UCLA) activity scores. CT and UCLA activity score were obtained before and 1 year after THA. The patients were divided into two groups, sufficient (score ≥ 6) and insufficient (score < 6) activity groups, based on their level of PA as determined by their UCLA activity score 1 year after THA. The association of PA with the amount of changes in muscle density was examined with Spearman's rank correlation coefficient. Logistic regression analysis was performed to identify postoperative factors determining PA at 1 year after THA. RESULTS: Spearman's rank correlation coefficient showed a significantly positive association between recovery in PA and an increase in muscle density of the gluteus maximus, gluteus medius, iliopsoas, and quadriceps muscles. Additionally, logistic regression analysis confirmed that postoperative muscle densities of the gluteus maximus and quadriceps muscles were variables determining the PA 1 year after THA. CONCLUSION: The findings of this study indicated that the improvement of fatty infiltration in lower limb muscles, especially in the gluteus maximus and quadriceps, is likely to promote the increase in postoperative PA.

Small medial proximal tibial angle is a radiographic finding strongly associated with less coronal alignment correction under valgus stress in medial knee osteoarthritis.

PURPOSE: The degree to which varus knees can be corrected manually is important when considering total versus unicompartmental knee arthroplasty (UKA). The primary aim was to clarify the relationship between the degree of coronal alignment correction and radiographic parameters involved in UKA prognosis using preoperative full-length lower extremity valgus stress radiography. The secondary aim was to identify the factors affecting alignment correction. METHODS: This retrospective observational study included 115 knees with medial osteoarthritis that underwent knee osteotomy or arthroplasty. Percent mechanical axis without valgus stress (%MA: neutral, 50%; varus, <50% and valgus, >50%), mechanical lateral distal femoral angle, lateral bowing femoral angle, medial proximal tibial angle (MPTA), joint line convergence angle, medial and lateral joint space width (LJSW) and medial femoral and tibial joint osteophyte size were measured using preoperative full-length weight-bearing radiographs. Correlation and multiple linear regression analyses were used to assess associations between parameters and %MA with valgus stress or amount of %MA change (%MA with valgus stress minus %MA without valgus stress). RESULTS: %MA with valgus stress was correlated with all radiographic parameters. %MA change was correlated with parameters except for MPTA and LJSW. Multiple regression analyses showed that %MA without valgus stress and MPTA were associated with both %MA with valgus stress and %MA change. When %MA with valgus stress was set at 30%, 40% and 50%, MPTA cutoff values were 81.6°, 83.5° and 84.9°, and cutoffs for %MA without valgus stress were 10.7%, 17.1% and 25.1%, respectively. CONCLUSION: Small MPTA is strongly associated with less alignment correction under valgus stress in varus knees. The finding is useful in surgical planning, especially to avoid undercorrection with UKA when valgus stress radiographs are unavailable. LEVEL OF EVIDENCE: Level III.

Anterior Position of the Femoral Condyle During Mid-Flexion Worsens Knee Activity After Cruciate-Retaining Total Knee Arthroplasty.

BACKGROUND: The effects of kinematics on patient-reported outcome measures (PROMs) after cruciate-retaining (CR) total knee arthroplasty (TKA) remain unclear. This study investigated the effects of kinematic patterns after CR-TKA on PROMs. METHODS: We examined 35 knees (27 patients) undergoing primary CR-TKA. Knee kinematics and 2011 Knee Society Score were evaluated at a mean follow-up of 72.4 (± 28.2) months. Knee kinematics was analyzed using fluoroscopy, and the femoral antero-posterior position relative to the tibial component was assessed separately for medial and lateral compartments during a squat. The correlations between kinematics and PROMs were evaluated. RESULTS: The average amount of posterior femoral translation from full extension to maximum flexion was 0.2 (± 2.6) mm for the medial femoral condyle and 4.1 (± 2.9) mm for the lateral condyle. Medial pivot motion was observed in 24 knees (68.6%) with a low rate (14.3%) of paradoxical anterior translation. The anterior position of the medial femoral condyle at 60° had a negative impact on discretionary activities (ρ = -0.37; P = .039), and at maximum flexion, had a negative impact on total functional activities (ρ = -0.46; P = .005), advanced activities (ρ = -0.45; P = .006), and discretionary activities (ρ = -0.63; P < .001). Anterior position of the lateral femoral condyle at 30° had a negative impact on total functional activities (ρ = -0.48; P = .005), walking and standing (ρ = -0.56; P < .001), and advanced activities (ρ = -0.49; P = .004), and at 60° had a negative impact on walking and standing (ρ = -0.45; P = .010). CONCLUSIONS: The anterior positions of the medial and lateral femoral condyles at mid-flexion and maximum flexion had negative impacts on PROMs. Soft tissue conditions should be carefully managed to achieve medial knee joint stability, which can improve PROMs.

How Do Spinal Parameters Change in Patients Who Have Improvement of Low Back Pain After Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.

BACKGROUND: Many studies have demonstrated that low back pain (LBP) improves after total hip arthroplasty (THA). However, the mechanism underlying this improvement remains unclear. We aimed to investigate changes in the spinal parameters of patients who had LBP improvement after THA to elucidate the mechanism of LBP improvement. METHODS: We included 261 patients who underwent primary THA between December 2015 and June 2021 and had a preoperative visual analog scale score of ≥ 2 for LBP. The patients were classified into the LBP-improved or LBP-continued groups based on the visual analog scale for LBP at 1 year after THA. Preoperative and postoperative changes in the coronal and sagittal spinal parameters were compared between the 2 groups after propensity score matching for age, sex, body mass index, and preoperative spinal parameters. RESULTS: A total of 161 patients (61.7%) were classified into the LBP-improved group. After 85 patients in both groups were matched, the LBP-improved group showed significant differences in spinal parameter changes, which were a higher lumbar lordosis (LL) (P = .04) and lower sagittal vertical axis (SVA) (P = .02) and pelvic incidence (PI) minus LL (PI-LL) (P = .01) postoperatively, whereas the LBP-continued group showed worsened changes in LL and SVA and PI-LL mismatch. CONCLUSION: Patients who had LBP improvement after THA had significant differences in spinal parameter changes in LL, SVA, and PI-LL. These spinal parameters may be the key factors in the mechanism of LBP improvement after THA.

Measurement of the Acetabular Cup Orientation after Total Hip Arthroplasty Based on Three-Dimensional Reconstruction from a Single X-ray Image Using Generative Adversarial Networks.

BACKGROUND: The purpose of this study was to reconstruct three-dimensional (3D) computed tomography (CT) images from single anteroposterior (AP) postoperative total hip arthroplasty (THA) X-ray images using a deep learning algorithm known as generative adversarial networks (GANs) and to validate the accuracy of cup angle measurement on GAN-generated CT. METHODS: We used two GAN-based models, CycleGAN and X2CT-GAN, to generate 3D CT images from X-ray images of 386 patients who underwent primary THAs using a cementless cup. The training dataset consisted of 522 CT images and 2,282 X-ray images. The image quality was validated using the peak signal-to-noise ratio (PSNR) and the structural similarity index measure (SSIM). The cup anteversion and inclination measurements on the GAN-generated CT images were compared with the actual CT measurements. Statistical analyses of absolute measurement errors were performed using Mann-Whitney U tests and nonlinear regression analyses. RESULTS: The study successfully achieved 3D reconstruction from single AP postoperative THA X-ray images using GANs, exhibiting excellent PSNR (37.40) and SSIM (0.74). The median absolute difference in radiographic anteversion (RA) was 3.45° and the median absolute difference in radiographic inclination (RI) was 3.25°, respectively. Absolute measurement errors tended to be larger in cases with cup malposition than in those with optimal cup orientation. CONCLUSION: This study demonstrates the potential of GANs for 3D reconstruction from single AP postoperative THA X-ray images to evaluate cup orientation. Further investigation and refinement of this model are required to improve its performance.

Total Knee Arthroplasty Kinematics Predict Patient-Reported Outcome Measures: Implications for Clinical Kinematic Examinations.

BACKGROUND: A core tenet of total knee arthroplasty (TKA) is that achieving more natural kinematics will lead to superior patient outcomes. Yet this relationship has not been proven for large representative cohorts of TKA patients because accurately measuring 3-dimensional TKA kinematics is time-consuming and expensive. But advanced imaging systems and machine learning-enhanced analysis software will soon make it practical to measure knee kinematics preoperatively and postoperatively in the clinic using radiographic methods. The purpose of this study was to assess the reported relationships between TKA kinematics and outcomes and distill those findings into a proposal for a clinically practical protocol for a clinical kinematic exam. METHODS: This study reviewed the recent literature relating TKA kinematics to patient outcomes. There were 10 studies that reported statistical associations between TKA kinematics and patient outcome scores utilizing a range of functional activities. We stratified these activities by the complexity of the radiographic examination to create a proposed examination protocol, and we generated a list of requirements and characteristics for a practical TKA clinical kinematic examination. RESULTS: Given considerations for a clinically practical kinematic exam, including equipment, time and other resources, we propose 3 exam levels. With basic radiographs, we suggest studying single-leg stance in extension, lunge or squat, and kneeling. For fluoroscopic systems with X-ray pulses up to 20 ms, we propose chair-rise or stair ascent to provide additional dynamic information. For fluoroscopic systems with X-ray pulses of less than 10 ms, we propose rapid open-chain knee flexion-extension to simulate the highly dynamic swing phase of gait. CONCLUSIONS: It is our hope that this proposed examination protocol spurs discussion and debate so that there can be a consensus approach to clinical examination of knee and TKA kinematics when the rapidly advancing hardware and software capabilities are in place to do so.

What are the differences in the recovery of physical function and clinical score between patients with steroid-related osteonecrosis of the femoral head and hip osteoarthritis undergoing total hip arthroplasty? A propensity score-matched study.

PURPOSE: Steroid-related osteonecrosis of the femoral head (ONFH), arising from steroid administration for underlying diseases, represents a unique pathology for total hip arthroplasty (THA) and typically affects a younger demographic compared to osteoarthritis (OA). Given the significant age-related differences, this study aims to employ propensity score matching to align patient backgrounds between these two diseases and compare physical function. Additionally, our objective is to scrutinize the patterns of clinical score recovery over the course of one year following THA. METHODS: Using propensity score matching, 29 patients each with steroid-related ONFH and OA were selected. Muscle strength (hip abductor and knee extensor) were assessed before and after THA. Additionally, recovery of the Harris Hip Score (HHS) and Oxford Hip Score (OHS) up to one year postoperatively was analyzed. RESULTS: The steroid-related ONFH group exhibited gender bias and significantly younger age compared to the OA group. Propensity score matching achieved balanced patient backgrounds. Physical function showed trends of lower hip abduction and knee extensor strength on the operative side in the steroid-related ONFH group. Notably, nonoperative knee extensor strength decreased significantly after matching. HHS and OHS were poor in steroid-related ONFH up to three months postoperatively but recovered after six months. CONCLUSIONS: Patients with steroid-related ONFH experience positive outcomes in clinical score following THA. Propensity score matching effectively identified muscle weakness on both operative and nonoperative sides, highlighting its utility in comparative analyses.

The relationship between spino-pelvic-hip mobility and quality of life before and after total hip arthroplasty.

INTRODUCTION: Total hip arthroplasty (THA) can significantly improve quality of life (QOL) in patients with hip osteoarthritis. A relationship exists between activity levels and postoperative QOL, but its determinants are not well known. The aim of this work was to investigate the relationship between hip, pelvis and lumbar spine mobility and alignment before and after THA with QOL. MATERIAL AND METHODS: Consecutive patients with hip arthrosis and an indication for THA were included prospectively between July 2019 and December 2020, and they underwent lateral radiographs in free-standing, extension, relaxed- and flexed-seated position. Spinopelvic and hip parameters were measured, as well as their changes between positions to assess hip, pelvis and lumbar spine mobility. Patients were also administered QOL questionnaires. Data were collected preoperatively and 6 and 12 months postoperatively. RESULTS: Seventy patients were included; QOL significantly increased 6 months after THA (from 18 [10; 27] to 61 [48; 72], p < 0.001). QOL further increased by 10 points or more after 6 months in 18% of patients, while it decreased in 16%. The latter showed higher pelvic range of motion (between flexion and extension) than the former. CONCLUSIONS: This study confirmed that QOL is significantly improved by THA, and that spinopelvic alignment and function can play a role. Future work should elucidate how to better predict postoperative QOL from preoperative patient characteristics to improve patient treatment and establish early postoperative physical therapy for patients who could benefit from postoperative improvement of activity-related QOL.

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

Investigating sagittal spinopelvic alignment and equivalent stress on the femoral head in patients with rapidly destructive coxarthrosis.

PURPOSE: Rapidly destructive coxarthrosis (RDC) is a rare syndrome of unknown etiology. This study evaluated sagittal spinopelvic alignment (SSPA) in patients with RDC and compared it with that in patients with hip osteoarthritis (HOA). In addition, finite element analysis (FEA) was performed to investigate the distribution of stress on the femoral head in RDC versus HOA. METHODS: This retrospective study included patients who had undergone primary total hip arthroplasty for RDC (n = 33) and HOA (n = 99; age- and sex-matched to patients with RDC) at three hospitals from June 2014 to September 2020. Preoperative SSPA parameters and inflammatory blood markers were compared between the two groups. FEA on the computed tomography data was performed for four patients from each group with similar pelvic tilt (PT) and lateral center-edge angle (LCEA). The distribution of Drucker-Prager equivalent stress was assessed at the loaded area of the femoral head. RESULTS: Patients with RDC had significantly higher PT, lower sacral slope, decreased lumbar lordosis (LL), higher sagittal vertical axis, and higher pelvic incidence minus LL than patients with HOA, indicating sagittal spinal imbalance. Blood test revealed patients with RDC had higher levels of inflammation markers than patients with HOA. FEA revealed no statistically significant difference in the degree of stress concentration or the maximum equivalent stress between the two groups when PT and LCEA were comparable. CONCLUSION: Patients with RDC tend to have sagittally imbalanced spine. Decreased acetabular coverage of the femoral head may heighten mechanical load of the hip joint in patients with RDC.

The impact of concomitant Sjögren's disease on rheumatoid arthritis disease activity: a systematic review and meta-analysis.

OBJECTIVES: Rheumatoid arthritis (RA) and Sjögren's syndrome (SS) frequently co-exist but the consequence for RA disease activity of having concomitant SS (RA/SS) is not well established. We conducted a systematic review and meta-analysis to investigate the impact of SS on disease outcomes in individuals with RA. METHODS: We searched Web of Science (Core Collection, FSTA, Medline), PubMed and Cochrane databases, without language restriction. Studies reporting RA disease activity scores, joint counts, visual analogue scales (VAS), disability and joint damage, and comparing RA and RA/SS were selected. Outcomes reported in at least 3 studies in which the diagnosis of SS fulfilled classification criteria underwent meta-analysis, using a random effects model where heterogeneity was detected. RESULTS: The literature search identified 2991 articles and abstracts; 23 underwent full-text review and 16 were included. The studies included a total of 29722 patients (8614 with RA/SS and 21108 with RA). Using studies eligible for meta-analysis (744 patients with RA/SS and 4450 with RA), we found higher DAS-28 ESR scores (mean difference 0.50, 95% CI -0.008-1.006; p=0.05), higher swollen joint count scores (mean difference 1.05, 95% CI 0.42-1.67; p=0.001), and greater functional disability as measured by HAQ (mean difference 0.19, 95% CI 0.05-0.34; p=0.009) in RA/SS compared to RA alone. Other outcome measures (tender joint count, fatigue VAS) showed a numerical trend towards higher scores in RA/SS but were not statistically significant. CONCLUSIONS: RA/SS patients appear to have higher disease activity and more functional disability than patients with RA alone. The aetiology and clinical implications of this are unclear and warrant further investigation.

Clinical Outcomes of Patients With Osteosarcoma Experiencing Relapse or Progression: A Single-institute Experience.

BACKGROUND: Patients with osteosarcoma who experience relapse or progression [R/P] have a poor prognosis. METHODS: Data from 30 patients who experienced R/P among 59 with a diagnosis of high-grade osteosarcoma, who were younger than 40 years old between 2000 and 2019, were retrospectively analyzed to identify prognostic and therapeutic factors influencing their outcomes. RESULTS: The 5-year overall survival [OS] rates after the last R/P of patients experiencing first [n=30], second [n=14], and third [n=9] R/P were 50.3%, 51.3%, and 46.7%, respectively. Multivariate analysis did not identify any independent risk factors affecting OS. The 5-year PFS rate of the 30 patients after first R/P was 22.4%, and multivariate analysis identified histologic subtype and curative local surgery as independent risk factors influencing PFS. Long [>6 mo] partial response was observed in three patients treated using temozolomide+etoposide, irinotecan+carboplatin, or regorafenib. CONCLUSIONS: OS rate in the patients with osteosarcoma experiencing R/P included in this study was markedly higher than that reported previously, mainly due to the surgical total removal of tumors, even after subsequent R/P. The recent establishment of salvage chemotherapy or molecular targeted therapy may also increase survival rates in a subgroup of patients.

Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response. A single-center, retrospective study was conducted using the Kyoto University Rheumatoid Arthritis Management Alliance cohort database between 2011 and 2020. Serum IFX levels were measured using liquid chromatography-tandem mass spectrometry. An electrochemiluminescence assay was used to quantify serum levels of tumor necrosis factor-α and interleukin-6 and detect anti-drug antibodies. Eighty-four out of 310 patients were eligible for this study. The cutoff levels of biomarkers were determined by receiver operating characteristic analysis. IFX persistence was similar between groups stratified using IFX levels, tumor necrosis factor-α levels, interleukin-6 levels, and anti-drug antibodies positivity. The group with lower IFX and higher interleukin-6 levels had the worst therapy persistence (p = 0.017) and the most frequent disease worsening (90.0%, p < 0.001). Evaluating both interleukin-6 and IFX levels, not just IFX alone, enabled us to identify patients at risk of discontinuing IFX treatment. These findings support the utility of measuring IFX and interleukin-6 levels for successful maintenance therapy for RA.

Interactive Combinations Between Gait Speed and Physical Function at Acute Phase Can Predict the Physical Activity at 2 Years After Total Knee Arthroplasty Using Classification and Regression Tree Analysis.

OBJECTIVE: To clarify the interactive combinations of various clinical factors associated with physical activity (PA) at 2 years after total knee arthroplasty (TKA) using classification and regression tree (CART) analysis. DESIGN: A retrospective cohort study. SETTING: A single university hospital. PARTICIPANTS: 286 patients who underwent TKA (N=286). MAIN OUTCOME MEASURES: PA was assessed preoperatively, 3 weeks, and 2 years after TKA. Physical functions, namely, 10 m walking test (10MWT), timed Up and Go test, 1-leg standing time, isometric knee extension and flexion strength, knee joint stability, knee pain, femora-tibial angle, and the passive knee extension and flexion angle, were measured before surgery as a baseline and 3 weeks after TKA as acute phase. CART analysis was conducted to clarify the interactive combinations that accurately predict the PA at 2 years after TKA. RESULTS: The results of CART analysis indicated that gait speed (≥1.05 m/s) at the acute phase after TKA was the primal predictor for the postoperative PA at 2 years. The highest postoperative PA at 2 years was determined by gait speed (≥1.05 m/s) and PA (>74.5) at the acute phase. The PA at baseline and at acute phase, as well as the body mass index were also selected as predictors of postoperative PA at 2 years. CONCLUSION: The present study suggested that acquiring gait speed (≥1.05 m/s) and PA (>74.5) in the postoperative acute phase is the predictive of a high PA at 2 years after TKA.