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Purpose: While technology in total hip arthroplasty (THA) is generally developed by experienced surgeons, particular difficulties in surgical steps and technical demands experienced by early-career surgeons remain important. This study investigated the challenges early-career surgeons currently face in THA in order to obtain insights into how they perceive future innovative technologies might reduce the difficulties and complications associated with THA. Methods: Members of the American Association of Hip and Knee Surgeons Young Arthroplasty Group were surveyed. The perceived degree of difficulty with key THA surgical steps and the utility of adjunctive technology were recorded (scale 1–10, from no difficulty/not important to very difficult/very important). Results: The membership response rate was 16.1%. The most common THA approach was the direct anterior approach (DAA) (67.4%). Four of the top five most difficult surgical steps were associated with cup preparation/placement. Fluoroscopy was the most used technology (56.7%), followed by no technology use (21.2%) and robot arm assistance (12.1%). With respect to the importance of technology, accurate cup placement ranked first. Dislocation and stem subsidence were the top two complications for which technological advances were thought to be most beneficial. Subgroup analysis based on surgical approach suggested that DAA users had significantly more difficulty with direction of stem rasping than non-DAA users (p ​

Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-β and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p

Abstract Background In recent years, the use of tapered-wedge short stems has increased due to their ability to preserve bones and tendons. Surgical techniques occasionally result in a varus position of the stem, which is particularly pronounced in short stems. Although the varus position is not clinically problematic, there are reports of an increased incidence of stress shielding and cortical hypertrophy. Thus, we evaluated and examined the acceptable range of varus angles using finite element analysis. Methods Patients diagnosed with osteoarthritis of the hip joint who had undergone arthroplasty were selected and classified into three types [champagne-flute (type A), intermediate (type B), and stovepipe (type C)]. Finite element analysis was performed using Mechanical Finder. The model was created using a Taperloc microplasty stem with the varus angle increased by 1° from 0° to 5° from the bone axis and classified into seven zones based on Gruen’s zone classification under loading conditions in a one-leg standing position. The volume of interest was set, the mean equivalent stress for each zone was calculated. Results A significant decrease in stress was observed in zone 2, and increased stress was observed in zones 3 and 4, suggesting the emergence of a distal periosteal reaction, similar to the results of previous studies. In zone 2, there was a significant decrease in stress in all groups at a varus angle ≥ 3°. In zone 3, stress increased from ≥ 3° in type B and ≥ 4° in type C. In zone 4, there was a significant increase in stress at varus angles of ≥ 2° in types A and B and at ≥ 3° in type C. Conclusion In zone 2, the varus angle at which stress shielding above Engh classification grade 3 may appear is expected to be ≥ 3°. Distal cortical hypertrophy may appear in zones 3 and 4; the narrower the medullary cavity shape, the smaller the allowable angle of internal recession, and the wider the medullary cavity shape, the wider the allowable range. Long-term follow-up is required in patients with varus angles > 3°.

Abstract Recently, we found significantly reduced total superoxide dismutase (SOD) activity in the cartilage of patients with end-stage knee osteoarthritis (OA). In this study, we aimed to evaluate the SOD activity in serum, joint fluid, cartilage, and synovial membrane samples collected from 52 patients with end-stage knee OA who underwent total knee arthroplasty. The relationship between the total SOD activity in each tissue was evaluated using Spearman’s rank correlation coefficient. The joint fluid total SOD activity was used as the objective variable, and its association with the serum, cartilage, and synovial total SOD activities was evaluated using multiple linear regression analysis. Univariate analysis revealed that joint fluid total SOD activity was positively correlated with synovial total SOD activity. Multiple linear regression analysis using joint fluid total SOD activity as the objective variable showed a positive association with synovial total SOD activity (β = 0.493, adjusted R 2 = 0.172, P

Abstract Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10−8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.

Aims: It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA. Methods: In 52 THAs performed between November 2018 and April 2022, the acoustic parameters of the hammering sound of 224 impacts of successful press-fit fixation, and 55 impacts of unsuccessful press-fit fixation, were analyzed. The successful fixation was defined if the following two criteria were met: 1) intraoperatively, the stability of the cup was retained after manual application of the torque test; and 2) at one month postoperatively, the cup showed no translation on radiograph. Each hammering sound was converted to sound pressures in 24 frequency bands by fast Fourier transform analysis. Basic patient characteristics were assessed as potential contributors to the hammering sound. Results: The median sound pressure (SP) of successful fixation at 0.5 to 1.0 kHz was higher than that of unsuccessful fixation (0.0694 (interquartile range (IQR) 0.04721 to 0.09576) vs 0.05425 (IQR 0.03047 to 0.06803), p < 0.001). The median SP of successful fixation at 3.5 to 4.0 kHz and 4.0 to 4.5 kHz was lower than that of unsuccessful fixation (0.0812 (IQR 0.05631 to 0.01161) vs 0.1233 (IQR 0.0730 to 0.1449), p < 0.001; and 0.0891 (IQR 0.0526 to 0.0891) vs 0.0885 (IQR 0.0716 to 0.1048); p < 0.001, respectively). There was a statistically significant positive relationship between body weight and SP at 0.5 to 1.0 kHz (p < 0.001). Multivariate analyses indicated that the SP at 0.5 to 1.0 kHz and 3.5 to 4.0 kHz was independently associated with the successful fixation. Conclusion: The frequency bands of 0.5 to 1.0 and 3.5 to 4.0 kHz were the key to distinguish the sound characteristics between successful and unsuccessful press-fit cup fixation. Cite this article: Bone Jt Open 2024;5(3):154–161.

Introduction: Although numerous studies have reported outcomes with various conservative approaches for the iliopsoas impingement after total hip arthroplasty (THA), reports on the use of locoregional autologous platelet rich plasma (PRP) injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA. Materials and methods: Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index, Japanese Hip Disease Evaluation Questionnaire, and Forgotten Joint Score-12. Results: Three patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male. All patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, or subcutaneous haemorrhage owing to the administration of locoregional PRP. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection. Conclusion: We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

Abstract Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments.

Introduction The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA.Methods and analysis This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively.Ethics and dissemination This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan’s Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan’s Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan’s national insurance coverage.Trial registration number jRCTc032200229.

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by β-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.

Abstract Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

Abstract We reported that the full-length width of medial tibial osteophytes comprising cartilage and bone parts correlates with medial meniscus extrusion (MME) in early-stage knee osteoarthritis (OA). However, no data exist on the prevalence of MME and its relationship with osteophytes in the elderly population. 1191 elderly individuals (females 57%; 72.9 years old on average) in the Bunkyo Health Study underwent standing plain radiograph and proton density-weighted MRI on knee joints. MRI-detected OA changes were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. A new method of assessing the cartilage and bone parts of osteophytes was developed using pseudo-coloring images of proton density-weighted fat-suppressed MRI. Most subjects showed Kellgren-Lawrence grade 1 or 2 radiographic medial knee OA (88.1%), MME (98.7%, 3.90 ± 2.01 mm), and medial tibial osteophytes (99.3%, 3.27 ± 1.50 mm). Regarding OA changes, MME was closely associated with the full-length width of medial tibial osteophytes (β = 1.114; 95% CI 1.069–1.159; p

Abstract Background Measurement of trunk muscle cross-sectional area (CSA) using axial magnetic resonance imaging (MRI) is considered clinically meaningful for understanding several spinal pathologies, such as low back pain and spinal sagittal imbalance. However, it remains unclear whether trunk muscle mass (TMM) measured using dual-energy X-ray absorptiometry (DXA) can predict the trunk muscle CSA. The aim of this study is to determine if DXA-derived TMM is associated and predicts with CSA of paraspinal muscles and gluteus maximus measured using MRI in healthy volunteers. Methods A total of 48 healthy volunteers underwent whole-body DXA and MRI of the spinopelvic region. The CSA of the psoas major, back muscles, and gluteus maximus were measured on axial MRI. Correlations and linear regressions between the TMM measured using DXA and the CSA of each musculature were investigated. Results There was a weak correlation between TMM and CSA of the psoas major in men (r = 0.39, P = 0.0678), and the linear regression was y = 301.74x – 401.24 (R2 = 0.2976, P = 0.0070). A moderate correlation was found in women (r = 0.58, P = 0.0021), and the linear regression was y = 230.21x − 695.29 (R2 = 0.4445, P = 0.0003). Moderate correlations were observed between TMM and CSA of the back muscles in both men (r = 0.63, P = 0.0012) and women (r = 0.63, P = 0.0007), the linear regression was y = 468.52x + 3688.5 (R2 = 0.5505, P

Abstract Background and Aims To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab. Methods This retrospective study included 162 osteoporotic patients treated with denosumab for 24 months between 2013 and 2019. Patients were divided according to the changes in BMD as nonresponders (NL group:

Objective To investigate whether osteoarthritis (OA) is a risk factor for cardiovascular disease (CVD); whether there are differences concerning ischaemic heart disease (IHD), congestive heart failure (CHF) and stroke; and whether there are differences between OA sites (hips, knees and hand) in predicting CVD onset.Design Population-based matched case–control study.Setting Health insurance claims data among Japanese patients.Participants Japanese patients aged ≥65 years with newly diagnosed CVD and hospitalised between January 2015 and December 2020 (cases) and age-matched and sex-matched 1:1 individuals (controls).Main outcome measures A conditional logistic regression model was used to estimate the adjusted ORs and their 95% CIs for CVD, IHD, CHF and stroke risk, adjusting for covariates.Results A total of 79 296 patients were included, with respect to CVD (39 648 patients with newly diagnosed CVD and 39 648 controls). After adjustment for covariates, the exposure odds of knee OA (KOA), hip OA (HipOA) and hand OA (HandOA) for CVD were 1.192 (95% CI 1.115 to 1.274), 1.057 (95% CI 0.919 to 1.215) and 1.035 (95% CI 0.684 to 1.566), respectively, showing an association only for KOA. The exposure odds of KOA, HipOA and HandOA for IHD were 1.187 (95% CI 1.086 to 1.297), 1.078 (95% CI 0.891 to 1.306) and 1.099 (95% CI 0.677 to 1.784), respectively. The exposure odds of KOA, HipOA and HandOA for stroke were 1.221 (95% CI 1.099 to 1.356), 0.918 (95% CI 0.723 to 1.165) and 1.169 (95% CI 0.635 to 2.151), respectively. Similar to CVD, only KOA was associated with both. For CHF, neither KOA nor HipOA and HandOA were associated with CHF development.Conclusion This study confirms the association of KOA with CVD, particularly IHD and stroke, in the Japanese population. The finding that patients with KOA have a higher CVD risk can potentially assist in guiding future treatment strategies.

Abstract Objective This study aimed to identify the risk factors for tackle-related concussion observed in matches involving under (U) 18, U 22 and professional men’s Rugby Union players through video analysis. Study Design Descriptive epidemiology study. Methods Twenty Rugby Union matches each for high school (U18), university/college (U22) and professional (Elite) were randomly selected from 202 matches in the 2018/2019 season. Both one-on-one and tackles involving multiple tacklers were analyzed for the 60 matches. The 28 categorical and continuous variables (e.g., tackle characteristics and duration before the tackle) were applied as risk factors to a least absolute shrinkage and selection operator (Lasso) regression analysis. To identify high-risk situations, a simulation model with coefficients obtained from the Lasso regression was used. Statistical analysis was conducted according to tackle direction. Results A total of 14,809 tackles and 41 concussions involving 1800 players were included in the analyses. The incidence rate of concussions (injuries/1000 tackles) was greater in Elite players (4.0) compared with U18 (1.9) and U22 (2.4) players. The factors most highly associated with concussions were head-in-front tackles (where the tackler’s head is placed forward, impeding a ball carrier’s forward movements, 11.26/1000 tackles), and were more often observed among U18 players. A simulation model predicted that the highest risk tackle situation in Elite players was a head-in-front, side-on tackle below the hip of the ball carrier (predicted incidence rate 18.07/1000 tackles). Conclusion The risk factors associated with concussion need to be assessed cautiously. Avoiding head-in-front, side-on tackles to the lower extremities of a ball carrier should be considered to reduce injury risks.

Abstract To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case–control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72–0.76). Use of anti-Parkinson’s drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention.

Abstract Background Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. Methods A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. Results A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. Conclusions The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.

Background and Objectives: This study retrospectively examined whether the incidence rates of adjacent vertebral fractures (AVFs) can be reduced through balloon kyphoplasty (BKP) for osteoporotic vertebral fractures (OVFs) in the early stages, when there is little vertebral height variation. Materials and Methods: A total of 95 patients (22 males, 73 females, mean age: 80.7 years) who had undergone BKP were divided into two groups: the Early group (underwent BKP within 2 weeks after injury, n = 62), and the Non-early group (underwent BKP > 2 weeks after injury, n = 33). The following data were analyzed: patient characteristics; fracture level; the presence of old vertebral fractures, posterior wall injury, and intravertebral cleft; duration of surgery; duration of hospitalization; cement volume; the occurrence of AVF; the timing of AVF occurrence; Numerical Rating Scale (NRS) scores at the preoperative, postoperative, and final follow-up assessments; posterior vertebral kyphosis angle of the affected vertebra on plain lateral X-ray; vertebral wedge ratio; local kyphotic angle; and changes in posterior vertebral kyphosis angle, vertebral wedge ratio, and local kyphotic angle between preoperative and postoperative assessments. The patients were divided based on the occurrence or non-occurrence of AVF after BKP: the Non-AVF group, in which AVF did not occur, and the AVF group, in which AVF occurred. Results: The incidence of AVF was 15.8% (15/95 patients), with a notably lower incidence rate in the Early group at 6.5% (4/62 patients) compared to the Non-early group at 33.3% (11/33 patients). NRS scores significantly improved in both groups at the postoperative assessment and final follow-up. The changes in posterior vertebral kyphosis angle and vertebral wedge ratio were significantly lower in the Early group. In the Non-AVF group, the time from injury to surgery was significantly shorter. Conclusions: The Early group had a significantly lower incidence of AVF. The time from injury to surgery was a risk factor for AVF occurrence, suggesting that early BKP is recommended.

Abstract The aim of this study is to investigate the association between the hip abduction angle (HAA) and lower limb alignment as well as the clinical assessments in open-wedge high tibial osteotomy (OWHTO) patients. A total of 90 patients who underwent OWHTO were included. The demographic characteristics and clinical assessments (the Visual Analogue Scale for activities of daily living, the Japanese knee osteoarthritis measure, the Knee injury and Osteoarthritis Outcome Score, the Knee Society score, the Timed Up & Go (TUG) test, the single standing (SLS) test and muscle strength) were recorded. The patients were divided into two groups according to the HAA at 1 month after operation: the HAA (−) group (HAA

Abstract Background Although it is important to consider pelvic alignment and mobility in the standing and sitting positions before THA, it is not known how to preoperatively predict individual postoperative pelvic alignment and mobility. The purpose of this study was to investigate the pelvic alignment and mobility before and after THA, and to develop a predictive formula using preoperative factors to calculate postoperative sagittal alignment and mobility. Methods One hundred seventy patients were assessed. The 170 patients were randomly divided into a prediction model analysis group (n = 85) and an external validation group (n = 85). In the prediction model analysis group, preoperative spinopelvic parameters were used to develop the predictive formulas to predict the postoperative sacral slope (SS) in standing and sitting positions and ΔSS. These were applied to the external validation group and assessed. Results R2 in multiple linear regression models for postoperative SS in standing, SS in sitting and ΔSS were 0.810, 0.672, and 0.423, respectively. The values of predicted and postoperative parameters were very close with no significant difference: SS in standing (33.87 vs. 34.23, P = 0.834), SS in sitting (18.86 vs. 19.51, P = 0.228), and ΔSS (15.38 vs. 14.72, P = 0.619). Conclusion The present study showed that the pelvic alignment and mobility after THA can be predicted using preoperative factors. Although a model with higher accuracy is needed, it is important to use a predictive formula to estimate the postoperative condition before performing THA.

Introduction: Exercise is beneficial for increasing areal bone mineral density (aBMD) in adolescence and maintaining it in old age. Moreover, high-impact sports are more effective than low-impact sports in increasing aBMD. This study aimed to determine the types of adolescent sports played in school-based sports clubs associated with aBMD in old age.Methods: In total, 1,596 older adults (681 men and 915 women, age: 65–84 years) living in an urban area of Japan were evaluated for the femoral neck and lumbar spine aBMD using dual-energy X-ray absorptiometry. The association between adolescent sports played in sports clubs and aBMD in old age was analyzed using multiple regression analysis, with femoral neck and lumbar spine aBMD as dependent variables, and sports type and participant characteristics such as age, body weight, and serum 25-hydroxyvitamin D [25(OH)D] level, as independent variables.Results: For the femoral neck, basketball was associated with aBMD in older men (β = 0.079, p < 0.05) and women (β = 0.08, p < 0.01), whereas current body weight and 25(OH)D level were associated with aBMD in both sexes. For the lumbar spine, volleyball (β = 0.08, p < 0.01) and swimming (β = 0.06, p < 0.05) was significantly associated with lumbar spine aBMD, whereas current body weight, 25(OH)D, and diabetes mellitus were associated with aBMD in older women.Conclusion: Both men and women who played basketball in adolescence had higher femoral neck aBMD in old age. Moreover, women who played volleyball in adolescence had higher lumbar spine aBMD in old age.

Background: In knee osteoarthritis (OA), medial meniscus extrudes both medially and anteriorly. We reported that full-length width of medial tibial osteophyte, which comprises cartilage and bone parts, is directly associated with medial meniscus extrusion in early-stage knee OA and hypothesized that anterior tibial osteophyte (ATO) is also associated with anterior meniscus extrusion (AME). Thus, we aimed to examine their prevalence and relationship. Methods: Elderly subjects (638 females and 507 males; average 72.9 years old) in the Bunkyo Health Study cohort were enrolled. MRI-detected OA changes were evaluated according to the Whole Organ Magnetic Resonance Imaging Score. ATO was evaluated using the method which can assess both cartilage and bone parts of osteophyte by pseudo-coloring images of proton density-weighted fat-suppressed MRI. Results: Most subjects showed the Kellgren-Lawrence grade 1/2 of the medial knee OA (88.1%), AME (94.3%, 3.7 ​± ​2.2 ​mm), and ATO (99.6%, 4.2 ​± ​1.5 ​mm). Among the OA changes, AME was most closely associated with full-length width of ATO (multivariable β ​= ​0.877, p ​

Abstract Destruction of articular cartilage in osteoarthritis (OA) is initiated by depletion of the hyaluronan (HA)-aggrecan network, followed by degradation of the collagen fibrils. Previously, we reported the implications of HA-binding protein involved in HA depolymerization (HYBID), alias cell migration-inducing protein (CEMIP) and KIAA1199, for HA degradation. However, transmembrane protein 2 (TMEM2), which is ~ 50% homologous to HYBID, was discovered as another hyaluronidase, but their expression and regulation by OA chondrocytes remain elusive. Here we report that the absolute mRNA copy numbers of HYBID are significantly (7.1-fold) higher in OA cartilage than normal cartilage, whereas TMEM2 levels are not different between the groups. HA-degrading activity of cultured OA chondrocytes disappeared by siRNA-mediated knockdown of HYBID, but not TMEM2. HYBID expression was significantly up-regulated by treatment with interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) and additively increased by the combined treatment. No significant changes in the TMEM2 expression were seen by the factors examined. IL-1α remarkably enhanced IL-6 production and increased HYBID expression when soluble IL-6 receptor was supplemented. These results demonstrate that in stark contrast to the constitutive expression of TMEM2 and its negligible HA-degrading activity, HYBID is overexpressed in OA cartilage and up-regulated by IL-6 and TNF-α in OA chondrocytes.

Abstract Background This study aimed to investigate the laterality of the pedicle morphology at the apical vertebra (AV) level and identify the radiographic factors associated with the laterality ratio of the pedicle morphology at the AV level in patients with adolescent idiopathic scoliosis (AIS). Methods Overall, 684 pedicles in 57 AIS patients aged 10–20 years, who underwent preoperative computed tomography (CT) and had Lenke type 1 or 2 with right convex main thoracic curves (MTC), were evaluated. Pedicle diameters of the MTC were assessed. We defined and compared the region containing two vertebrae adjacent to the AV (APEX±1) and the region containing two vertebrae adjacent to the neutral vertebra. We analyzed the pedicle diameter and laterality ratio of APEX±1 and performed multiple linear regression analysis to identify the radiographic factors associated with the laterality of the pedicle diameter. Results On the concave side of APEX±1, the pedicles of 15 patients (26.3%) did not accept a 4-mm-diameter pedicle screw (PS), even with 25% cortical bone width expansion. Laterality ratio differences in the pedicle diameters of the cortical bone width in APEX±1 were large in patients with more proximal AV level (p

Background: Listening to the change in the hammering sound is 1 of the elements used to assess the cementless stem stability. This study aimed to quantitatively investigate the change in the acoustic characteristics between the early and late phases of cementless stem insertion in total hip arthroplasty and to identify which patient characteristics contribute to the change in the hammering sound. Methods: The acoustic parameters of the hammering sounds in the early and late phases of cementless taper-wedged stem insertion for 51 hips in 45 patients who underwent total hip arthroplasty (mean age = 68 years, height = 1.56 m, weight = 55.0 kg) were analyzed. Parameters including patient’s basic characteristics, radiographical femoral morphology, and canal fill ratio were assessed as potential contributors to the change in the hammering sound. Results: The low-frequency bands (0.5-1.0 kHz and 1.0-1.5 kHz) showed the largest changes during stem insertion and were therefore considered key bands for the analysis of sound alterations. Multivariate linear regression analysis showed that height (β = 8.312, P = .013) and proximal canal fill ratio (β = −3.8568, P = .038) were independently associated with the sound alterations. The decision tree analysis identified height (≥1.66 m or

Mixed martial arts (MMA) is a combat sport with a high incidence of concussions, including knockouts (KO) due to direct attacks to the head. Once a concussion occurs in a fighter, the rate of concussion recurrence increases. Therefore, participation in matches may be weakened to head impacts as fighters experience repeated concussions. In this study, we investigated the relationship between the occurrence of concussions in male mixed martial arts athletes during the most recent match and their past match records. The analysis included 104 male fighters who competed in elite-level professional MMA competitions. In the most current match, 44 fighters experienced a concussion and 60 fighters did not. Previous KO losses (mean, 2.9) were significantly higher in the fighters who had experienced a concussion compared to fighters who had not (p < 0.0001). Concussion rates (65.0%) were significantly higher in fighters with three or more previous KO losses compared with the rates for fighters with less than 3 previous KO losses (p = 0.03). The odds ratio for the occurrence of concussions in fighters with a history of KO losses was 2.3 times that of fighters without a history of KO losses (p = 0.004). Fighters who had competed in more than 30 matches had a significantly higher incidence of concussions (60.8%) than fighters who had competed in less than 30 matches (37.0%) (p = 0.04). The occurrence of concussions in male MMA fighters is related to the number of previous KO losses and the number of matches.

Abstract Background An incision for total hip arthroplasty (THA) via the direct anterior approach (DAA) is generally made outside of the space between the sartorius and tensor fasciae latae muscles to prevent lateral femoral cutaneous nerve (LFCN) injury. Anatomical studies have revealed that the LFCN courses between the sartorius and tensor fasciae latae muscles. When the LFCN branches radially while distributing in the transverse direction from the sartorius muscle to the tensor fasciae latae muscle, it is called the fan type. Studies suggest that damage to the fan type LFCN is unavoidable during conventional fasciotomy. We previously demonstrated that injury to non-fan variation LFCN occurred in 28.6% of patients who underwent THA by fasciotomy performed 2 cm away from the intermuscular space. This suggests that the conventional approach also poses a risk of LFCN injury to non-fan variation LFCN. LFCN injury is rarely reported in the anterolateral approach, which involves incision of fascia further away than the DAA. The purpose of this study is to investigate how the position of fasciotomy in DAA affects the risk of LFCN injury. Methods We will conduct a prospective, randomized, controlled study. All patients will be divided into a fan variation and a non-fan variation group using ultrasonography before surgery. Patients with non-fan variation LFCN will receive conventional fasciotomy and lateral fasciotomy in the order specified in the allocation table created in advance by our clinical trial center. The primary endpoint will be the presence of LFCN injury during an outpatient visit using a patient-based questionnaire. The secondary endpoints will be assessed based on patient-reported outcomes at 3 months after surgery in an outpatient setting using the Western Ontario and McMaster Universities Osteoarthritis Index, the Japanese Orthopaedic Association Hip-disease Evaluation Questionnaire, and the Forgotten-Joint Score-12. Discussion We hypothesize that the incidence of LFCN injury due to DAA-THA is reduced by making the incision further away from where it is typically made in conventional fasciotomy. If our hypothesis is confirmed, it will reduce the disadvantages of DAA and improve patient satisfaction. Trial registration UMIN Clinical Trials Registry, UMIN000035945 . Registered on 20 February, 2019.

Introduction: Along with the accumulating reports of autologous concentrated bone marrow (CBM) grafting for osteonecrosis of the femoral head (ONFH), the related medical device, a “point-of-care device” has also been recently developed. However, no study has confirmed the feasibility, safety, and efficiency of CBM grafting using a specific point-of-care device. Materials and methods: We designed this phase I, prospective clinical study to evaluate the feasibility and safety of autologous CBM grafting processed using a point-of-care device, the BioCUE system, in patients with ONFH. The primary outcomes were the safety and adverse event (AE), the secondary outcomes included pain score; hip function score; ONFH stage using X-ray; and the volume of the osteonecrotic area on 3T MRI. Besides, safety quality tests on the final product of concentrated bone marrow were performed. Results: Two patients (a 34-year-old man and a 33-year-old woman; three hips) with systemic lupus erythematosus were included. The incidence of AEs was 100% such as pain or transient fever after the operation, but all AEs were nonserious. No peri-operative complications were observed. Pain and hip function score remained unchanged from the preoperative to the postoperative observational periods. Safety quality test demonstrated were all negative or under the threshold. Conclusion: The feasibility and safety of grafting of concentrated autologous CBM in patients with ONFH using a point-of-care device were confirmed. A further clinical study aiming for the authorization of this procedure should be conducted in the future.

Background: Fit-and-fill stems are known to have excellent outcomes; however, severe stress shielding has been reported in Japanese populations. Short fit-and-fill stems were modified for Asians; however, there have been no previous reports of its outcome. In this study, we compared the 5-year (mean 68-month) outcomes of 2 fit-and-fill stems with different lengths (standard or short). Material and methods: We reviewed 100 total hip arthroplasties in each standard- or short-stem group. Radiographs were evaluated for femoral morphology, stress shielding, bone remodeling, and fixation. Clinical evaluation was performed using the Japanese Orthopaedic Association (JOA) scores. Results: There was no difference in the degree of stress shielding between the 2 groups. Significant differences were observed in radiolucent lines in zone 4 (P = .005) and cortical hypertrophy in zone 3 (P < .0001) and 5 (P = .048) between the 2 groups. The canal flare index (P < .0003), cortical index (P < .0003), height (P < .0345), and stem size (P < .0081) individually affected stress shielding in the standard-stem group. In contrast, the cortical index (P < .0107) was the only relative factor in the short-stem group. All stems were judged to have bone ingrowth. The JOA score improved significantly (P < .0001); however, there were no significant differences between the 2 groups. Conclusion: The outcomes of both standard and short fit-and-fill stems were favorable. There were no significant differences in the stress shielding or JOA scores. Although there were a few differences in bone remodeling and factors affecting stress shielding, stem length reduction has been achieved without adverse effects with the Japanese femur.

Abstract Recent studies have focused on hammering sound analysis during insertion of the cementless stem to decrease complications in total hip arthroplasty. However, the nature of the hammering sound is complex to analyse and varies widely owing to numerous possible variables. Therefore, we performed a preliminary feasibility study that aimed to clarify the accuracy of a prediction model using a machine learning algorithm to identify the final rasping hammering sound recorded during surgery. The hammering sound data of 29 primary THA without complication were assessed. The following definitions were adopted. Undersized rasping: all undersized stem rasping before the rasping of the final stem size, Final size rasping: rasping of the final stem size, Positive example: hammering sound during final size rasping, Negative example A: hammering sound during minimum size stem rasping, Negative example B: hammering sound during all undersized rasping. Three datasets for binary classification were set. Finally, binary classification was analysed in six models for the three datasets. The median values of the ROC-AUC in models A–F among each dataset were dataset a: 0.79, 0.76, 0.83, 0.90, 0.91, and 0.90, dataset B: 0.61, 0.53, 0.67, 0.69, 0.71, and 0.72, dataset C: 0.60, 0.48, 0.57, 0.63, 0.67, and 0.63, respectively. Our study demonstrated that artificial intelligence using machine learning was able to distinguish the final rasping hammering sound from the previous hammering sound with a relatively high degree of accuracy. Future studies are warranted to establish a prediction model using hammering sound analysis with machine learning to prevent complications in THA.

Purpose: During distal tibial oblique osteotomy, external fixators can increase pin site infection risk, whereas plates can cause wound necrosis, necessitating a compromise between soft-tissue position and length. We provide the first report of the early results of intramedullary nail fixation in these osteotomies for avoiding soft tissue complications. Methods: Ten ankles, classed as Takakura–Tanaka stages 3a to 4 and unclassified and treated via distal tibial oblique osteotomy for ankle osteoarthritis between 2017 and 2021, were included. Osteotomy was performed obliquely from the distal medial tibia to the tibiofibular joint. The distal tibial fragment was rotated distally in the coronal plane for realignment. An intramedullary nail fixation was applied for stabilization. The resulting gap was filled with iliac bone graft. Ankles were evaluated on the Japanese Society for Surgery of the Foot ankle–Hindfoot Scale and Self-Administered Foot Evaluation Questionnaire before surgery and at final follow-up. Radiographic assessments were performed. Results: Bone union was achieved within 3 months in all patients. There were no cases of wound necrosis or correction loss postsurgery. Japanese Society scale scores significantly improved from 40.3 ± 15.9 to 87.5 ± 12.6 (P < 0.01). Mean self-evaluation scale scores (pain and pain-related, physical functioning and daily living, social functioning, general health and well-being) improved significantly. shoe-related scores did not change significantly but improved. There was no correction loss after surgery, with an average widening of 24.2 mm and opening angle of 22.6° at the osteotomy site. Conclusion: Our study showed that intramedullary nail for fixation of the osteotomy site in distal tibial oblique osteotomy effectively prevents soft tissues complications even in osteotomy sites with large openings.

Introduction: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, the importance of triaging surgeries was suggested to reduce burdens on the existing health system and maintaining service. The governor declared a state of emergency and requested that residents avoid going out unnecessarily (semi-lockdown) for the entire prefecture including our medical region from February 28 until May 25, 2020. However, for several spine patients, a significant delay in care may result in the progression of extremity weakness and pain. This study aimed to investigate trends of spine surgeries during the first COVID-19 semi-lockdown in the nonepidemic region in Japan. Methods: Spine surgeries performed in our institution from February 28 until May 25 between 2017 and 2020 were retrospectively reviewed and analyzed. We compared the number of spine surgeries and types of surgical spine pathologies between 2017 and 2019: previous years and 2020: a COVID-19 year. Results: The mean number of spine surgeries performed in previous years was 121 cases, and the number of spine surgeries performed in a COVID-19 year was 109 cases. The percentage of urgent surgeries was 19.6% in previous years versus 37.6% in a COVID-19 year; the difference was statistically significant (P

Introduction: For the aging population, surgery for lumbar spinal canal stenosis (LSCS) requires minimally invasive procedures. Recently, trans-sacral epiduroscopic laser decompression for lumbar disc herniation has been reported with good results. In this study, we devised a new method to perform trans-sacral epiduroscopic laser ablation of the ligamentum flavum (LF), known to be the major cause of LSCS. Using a live pig, this study aims to evaluate the efficacy, safety, and drawbacks of this procedure. Methods: Using an epiduroscope, we observed intra-spinal canal structures and then examined the feasibility and problems of a decompression procedure to ablate the LF using holmium:YAG (Ho:YAG) laser. The pig was observed for behavioral changes and neurological deficits after the procedure. Histological analysis was performed to evaluate the amount of tissue ablation and damage to surrounding tissues. Results: Although it was possible to partially ablate the LF using the Ho:YAG laser under epiduroscopy, it was difficult to maintain a clear field of view, and freely decompressing the target lesion has been a challenge. After the first two experiments, the pig neither showed abnormal behavior nor any signs of pain or paresis. However, in the third experiment, the pig died during the operation. On autopsy, no thermal or mechanical injury was noted around the ablated site, including the dura mater and nerve root. Histological analysis showed that the LF and lamina were deeply ablated as the laser power increased, and no damage was noted on surrounding tissues beyond a depth of 500 μm. Conclusions: Although Ho:YAG laser could ablate the ligamentum and bone tissues without causing damage to surrounding tissues, it was difficult to completely decompress the LF under epiduroscopy. This method is a potentially highly invasive procedure that requires caution in its clinical application and needs further improvement in terms of the instruments and techniques used.

Introduction: Platelet-rich plasma (PRP) therapy is used to treat pathological conditions such as degenerative inflammatory diseases including osteoarthritis (OA) by enhancing tissue repair and promoting anti-inflammatory effects. Although PRP therapy for patients with knee OA improved pain and functional scores, the association of clinical outcomes and quality of PRP including cell composition and concentration is unclear. Methods: Therefore, this study analyzed blood cell counts, including the immature platelet fraction (IPF), in peripheral blood and PRP of 144 patients with knee OA who underwent PRP therapy. The mean leukocyte and platelet concentrations in whole blood and PRP were analyzed using an XN-1000 automated hematology analyzer. Visual analogue scale (VAS) scores and knee injury and osteoarthritis outcome scores (KOOS) before and 1 month after a single PRP injection were also determined. Results: Higher platelet and lower leukocyte concentration rates were observed in PRP compared with whole blood. The platelet concentration in whole blood was negatively correlated with VAS improvement. The percentage of IPF (IPF%) in whole blood was positively correlated with VAS improvement and KOOS (pain) improvement, whereas the IPF% in PRP tended to correlate with VAS improvement. Furthermore, multivariate logistic regression demonstrated the high IPF% in whole blood was significantly associated with VAS improvement. The low percentage of neutrophil (neutrophil%) in PRP was significantly associated with the VAS improvement and KOOS (ADL) improvement. Conclusions: Therefore, PRP efficacy for OA might depend on the patient's biological status.

Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor. However, the therapeutic results of the advanced cases at the first visit were still extremely poor. Therefore, more effective therapeutic options based on molecular profiling of OS are needed. In this study, we investigated the functions of endoplasmic reticulum (ER) stress activities in OS and elucidated whether ER stress inhibitors could exert antitumor effects. The expression of 84 key genes associated with unfolded protein response (UPR) was assessed in four OS cells (143B, MG63, U2OS and KHOS) by RT2 Profiler PCR Arrays. Based on results, we performed both siRNA and inhibitor assays focusing on IRE1α-XBP1 and PERK pathways. All OS cell lines showed resistance to PERK inhibitors. Furthermore, ATF4 and EIF2A inhibition by siRNA did not affect the survival of OS cell lines. On the other hand, IRE1α-XBP1 inhibition by toyocamycin suppressed OS cell growth (IC50:

Introduction: Osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression is a safe technique as the exiting nerve root can be directly observed during neuroforaminal decompression without spinal fusion. Moreover, this procedure allows anatomical reconstruction of the posterior elements. However, there might be a potential risk for the progression of lumbar segmental instability after performing this procedure. This study aimed to review the radiographic and clinical outcomes of osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression. Methods: We retrospectively reviewed 51 patients who underwent osteoplastic hemilaminectomy with a minimum follow-up of 2 years. The clinical outcomes were evaluated using the visual analog scale (VAS) for low back pain, leg pain, and numbness and the Japanese Orthopaedic Association (JOA) score. Lumbar segmental instability was evaluated as a radiographic assessment using functional radiography. The mean follow-up period was 65 months. Results: The preoperative VASs for low back pain, leg pain, and numbness were 46±31, 72±26, and 43±34, respectively, which were improved to 24±23, 19±23, and 19±23, respectively. The JOA score was also improved from 14±5 to 22±4. Three patients (5.9%) were reoperated due to recurrent disc herniation within 2 years following surgery. In addition, three patients (5.9%) developed postoperative lumbar segmental instability but did not require additional surgery. Conclusions: The current study revealed that 94.1% of the patients who underwent osteoplastic hemilaminectomy achieved a significant improvement in the clinical outcomes and did not require additional surgery within 2 years following the procedure. Over a 5-year follow-up on average, 5.9% of the subjects developed postoperative lumbar segmental instability; however, they have maintained acceptable clinical conditions.

Abstract Background Cell therapy is considered a promising strategy for intervertebral disc (IVD) regeneration. However, cell products often require long‐term cryopreservation, which compromises cell viability and potency, thus potentially hindering commercialization and off‐the‐shelf availability. Dimethyl sulfoxide (DMSO) is a commonly used cryoprotectant, however, DMSO is associated with cytotoxicity and cell viability loss. This study aimed to investigate the effects of DMSO on human nucleus pulposus cells (NPC) and the role of oxidative stress in DMSO‐induced cytotoxicity. Furthermore, we examined the potential of antioxidant N‐acetylcysteine (NAC) supplementation to mitigate the negative effects of DMSO. Methods NPC were exposed to various concentrations of DMSO with or without a freezing cycle. Cell viability, cell apoptosis and necrosis rates, intracellular reactive oxygen species (ROS) levels, and gene expression of major antioxidant enzymes were evaluated. In addition, NAC was added to cryopreservation medium containing 10% DMSO and its effects on ROS levels and cell viability were assessed. Results DMSO concentrations ≤1% for 24 h did not significantly affect the NPC viability, whereas exposure to 5 and 10% DMSO (most commonly used concentration) caused cell viability loss (loss of 57% and 68% respectively after 24 h) and cell death in a dose‐ and time‐dependent manner. DMSO increased intracellular and mitochondrial ROS (1.9‐fold and 3.6‐fold respectively after 12 h exposure to 10% DMSO) and downregulated gene expression levels of antioxidant enzymes in a dose‐dependent manner. Tempering ROS through NAC treatment significantly attenuated DMSO‐induced oxidative stress and supported maintenance of cell viability. Conclusions This study demonstrated dose‐ and time‐dependent cytotoxic effects of DMSO on human NPC. The addition of NAC to the cryopreservation medium ameliorated cell viability loss by reducing DMSO‐induced oxidative stress in the freeze–thawing cycle. These findings may be useful for future clinical applications of whole cells and cellular products.

Introduction Comprehensive analyses using clinical sequences subcategorized osteosarcoma (OS) into several groups according to the activated signaling pathways. Mutually exclusive co-occurrences of gene amplification ( PDGFRA/KIT/KDR, VEGFA/CCND3, and MDM2/CDK4 ) have been identified in approximately 40% of OS, representing candidate subsets for clinical evaluation of additional therapeutic options. Thus, it would be desirable to evaluate the specific gene amplification before starting therapy in patients with OS. Materials and Methods This is a retrospective study. We examined 13 cases of clinical OS samples using NanoString-based copy number variation (CNV) analysis. Decalcification and chemotherapeutic effects on this analysis were also assessed. Results First, the accuracy of this system was validated by showing that amplification/deletion data obtained from this system using various types of cancer cell lines almost perfectly matched to that from the Cancer Cell Line Encyclopedia (CCLE). We identified potentially actionable alterations in CDK4/MDM2 amplification in 10% of samples and potential additional therapeutic targets ( PDGFRA/KIT/KDR and VEGFA/CCND3 ) in 20% of samples, which is consistent with the reported frequencies. Furthermore, this assay could identify these potential therapeutic targets regardless of the sample status (frozen vs formalin-fixed paraffin-embedded [FFPE] tissues). Conclusion We established a NanoString-based rapid and cost-effective method with a short turnaround time (TAT) to examine gene amplification status in OS. This CNV analysis using FFPE samples is recommended where the histological evaluation of viable tumor cells is possible, especially for tumors after chemotherapy with higher chemotherapeutic effects.

Objective: Anterior cruciate ligament (ACL) injury is one of the causes for post-traumatic knee osteoarthritis (OA), and ACL reconstruction surgery is reportedly unable to prevent OA development. In early-stage knee OA, medial meniscus extrusion (MME) is closely correlated with tibial medial osteophyte width, which consists of bone and cartilage -parts. However, the relationship between MME and osteophyte in ACL-injured patients remains elusive. We examined MME and osteophyte and their relationship in ACL-injured patients before and after surgery. Design: Thirty ACL-injured patients who underwent surgery (30.7 years old, on average) were enrolled. Correlations between magnetic resonance imaging (MRI)-detected OA changes and MME before and after surgery (7.6 months interval) were analyzed. Results: MME (>3 ​mm) was present in 16.7% and 26.7% of the patients before and after surgery, respectively, and MME was significantly increased after surgery (2.4 ​± ​1.3 ​mm) than before surgery (1.9 ​± ​1.2 ​mm) (p ​

Introduction The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction.Methods and analysis This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20–49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index

Abstract Background A large-diameter femoral head is effective in preventing dislocation after total hip arthroplasty. However, although rare, catastrophic stem tribocorrosion may occur at the head-stem junction. Case presentation A 70-year-old woman underwent revision surgery 7.5 years after total hip arthroplasty because of catastrophic stem corrosion with dissociation of the metal head (cobalt/chromium) and stem (TiMo12Zr6Fe2). Abnormal levels of cobalt were found in the intra-articular fluid, capsule, hip muscle, and blood. Revision surgery was performed via the direct anterior approach. The well-fixed femoral stem was explanted, and a cemented stainless stem with stainless head was implanted. Three months after the revision surgery, the cobalt concentration in the blood had decreased to normal. Conclusions Stem dissociation in the present case might have been caused by synergistic combination of a 36-mm-diameter femoral head and long neck length offset with high frictional torque, a cobalt-chromium head with a high risk of galvanic corrosion, and a TMZF (TiMo12Zr6Fe2) alloy stem with a low Young’s modulus of elasticity. The combination of these factors must be avoided.

Abstract Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94–2.48], Low; 1.86 [1.02–3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98–2.02], Low; 1.49 [1.04–2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64–11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.

Background: The femoral cortical suspension device such as fixed loop devices (FLD) and adjustable-loop device (ALD) are used for ACLR technique in recent days. However, there was few studies of clinical and radiographic results for ACLR using ALD. This study was conducted to clarify the clinical and radiographic results, stability and bone tunnel enlargement after ACLR using a ToggleLoc with a zip loop as ALD. Methods: 80 patients who had data available from the most recent follow-up at ≥2 years since ACLR were evaluated both clinical and radiographic results. They were divided into single bundle reconstruction group (SBR) and double bundle reconstruction group (DBR). Clinical scores were included subjective scores and objective scores at pre- and postoperatively 2 years. The subjective scores were the Cincinnati knee rating system, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, Tegner activity score, Visual Analog Scale (VAS) and ACL-Return to Sport after Injury (RSI) scale. The objective scores were the isokinetic muscle strength, side-to-side difference in anterior instability and single hop test. In radiographical assessment, femoral and tibial tunnel enlargement was evaluated by three-dimensional computed tomography. Results: In both SBR and DBR group, the postoperative subjective scores were significantly improved compared to the preoperative values, except for the Tegner activity score. Similarly, the side-to-side differences in muscle strength, anterior instability and single hop test were significantly improved after surgery. The changes in the femoral and tibial tunnel maximum cross section areas of SBR were 104.3 % ± 21.2 % and 89.2 % ± 15.2 %, respectively, at 2 years post-operatively. In DBR, in the femoral bone volume change of the antero medial (AM) and postero lateral (PL) bundle were 107.0 ± 3.5 % and 108.1 ± 3.3, and in the tibial bone volume change of AM and PL bundle were 90.6 ± 3.3 % and 87.0 ± 4.2 %. At the femoral site, the rate of tunnel enlargement increased for the first 12 months and then decreased through 24 months postoperatively. At the tibial site, by contrast, the rate of tunnel enlargement decreased consistently over the two-year postoperative follow-up. Conclusion: This is the first study to include clinical data on ACLR using a ToggleLoc with a zip loop device. ACLR using these devices as ALDs resulted in good clinical outcomes and provided good stability of the knee with relatively little bone tunnel enlargement in both SBR and DBR group.

Abstract There are multiple transcription start sites (TSSs) in agreement with multiple transcript variants encoding different isoforms of NKX2‐1/TTF‐1 (thyroid transcription factor 1); however, the clinicopathological significance of each transcript isoform of NKX2‐1/TTF‐1 in lung adenocarcinoma (LAD) is unknown. Herein, TSS‐level expression of NKX2‐1/TTF‐1 isoforms was evaluated in 71 LADs using bioinformatic analysis of cap analysis of gene expression (CAGE)‐sequencing data, which provides genome‐wide expression levels of the 5′‐untranslated regions and the TSSs of different isoforms. Results of CAGE were further validated in 664 LADs using in situ hybridisation. Fourteen of 17 TSSs in NKX2‐1/TTF‐1 (80% of known TSSs in FANTOM5, an atlas of mammalian promoters) were identified in LADs, including TSSs 1–13 and 15; four isoforms of NKX2‐1/TTF‐1 transcripts (NKX2‐1_001, NKX2‐1_002, NKX2‐1_004, and NKX2‐1_005) were expressed in LADs, although NKX2‐1_005 did not contain a homeodomain. Among those, six TSSs regulated NKX2‐1_004 and NKX2‐1_005, both of which contain exon 1. LADs with low expression of isoforms from TSS region 11 regulating exon 1 were significantly associated with poor prognosis in the CAGE data set. In the validation set, 62 tumours (9.3%) showed no expression of NKX2‐1/TTF‐1 exon 1; such tumours were significantly associated with older age, EGFR wild‐type tumours, and poor prognosis. In contrast, 94 tumours, including 22 of 30 pulmonary invasive mucinous adenocarcinomas (IMAs) exhibited exon 1 expression without immunohistochemical TTF‐1 protein expression. Furthermore, IMAs commonly exhibited higher exon 1 expression relative to that of exon 4/5, which contained a homeodomain in comparison with EGFR‐mutated LADs. These transcriptome and clinicopathological results reveal that LAD use at least 80% of NKX2‐1 TSSs and expression of the NKX2‐1/TTF‐1 transcript isoform without exon 1 (NKX2‐1_004 and NKX2‐1_005) defines a distinct subset of LAD characterised by aggressive behaviour in elder patients. Moreover, usage of alternative TSSs regions regulating NKX2‐1_005 may occur in subsets of LADs.

Bisphosphonate treatment has known effects of improving bone mineral density and preventing fractures in children with steroid-induced osteoporosis. However, there have been reports that high-dosage pamidronate therapy induces osteopetrosis in the borders of bones. A 10-year-old boy undergoing long-term treatment with oral alendronate developed frequent fractures throughout adolescence while playing basketball. Radiographs showed osteosclerotic bands on the metaphyses of his long bones and vertebrae, and fractures were evident in the regions surrounding the osteosclerotic lesions: a stress fracture in the fourth metatarsal, anterior limbus vertebra (T12), spondylolysis (L3 and L5), and osteochondritis dissecans of the left lateral femoral condyle. Alendronate had been taken for a period of 6 years when the treatment was discontinued. Approximately 18 months after discontinuation, sclerotic bands remained evident; however, 4 years after discontinuation, sclerotic banding still surrounded the wing of the ilium but appeared diminished in the knees. In children and adolescents who engage in sports activities and are being treated with steroids and bisphosphonates, the possibility of pathological stress fractures should be considered.

Background and Objectives: The lateral approach is commonly used for anterior column reconstruction, indirect decompression, and fusion in patients with lumbar degenerative diseases and spinal deformities. However, intraoperative lumbar plexus injury may occur. This is a retrospective comparative study to investigate and compare neurological complications between the conventional lateral approach and a modified lateral approach at L4/5. Materials and Methods: Patients with a lumbar degenerative disease requiring single-level intervertebral fusion at L4/5 were included and categorized into group X and group A. Patients in group X underwent conventional extreme lateral interbody fusion, while those in group A underwent a modified surgical procedure that included splitting of the anterior third of the psoas muscle, which was dilated by the retractor on the anterior third of the intervertebral disc. The incidence of lumbar plexus injury, defined as a decrease of ≥1 grade on manual muscle testing of hip flexors and knee extensors and sensory impairment of the thigh for ≥3 weeks, on the approach side, was investigated. Results: Each group comprised 50 patients. No significant between-group differences in age, sex, body mass index, and approach side were observed. There was a significant between-group difference in intraoperative neuromonitoring stimulation value (13.1 ± 5.4 mA in group X vs. 18.5 ± 2.3 mA in group A, p < 0.001). The incidence of neurological complications was significantly higher in group X than in group A (10.0% vs. 0.0%, respectively, p < 0.05). Conclusions: In our modified procedure, the anterior third of the psoas muscle was entered and split, and the intervertebral disc could be reached without damaging the lumbar plexus. When performing lumbar surgery using the lateral approach, lumbar plexus injury can be avoided by following surgical indication criteria based on the location of the lumbar plexus with respect to the psoas muscle and changing the transpsoas approach to the intervertebral disc.

Abstract Low bone mineral density (BMD)—diagnosed as osteoporosis or osteopenia—has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG‐A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG‐A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro‐X‐ray‐computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+—not plasma fibroblast growth factor 23 (FGF‐23) elevation—by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF‐23 levels with phosphaturic action. The expression of 1α‐hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24‐hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.