中村 順一

Abstract Purpose Recent studies have proposed optimizing the position of the acetabular component based on spinal deformity and stiffness classification to avoid mechanical complication after total hip arthroplasty (THA). The aim of this study was to characterize the dynamic changes in cup alignment post-THA based on the spinopelvic classification and to evaluate the efficacy of cup placement of preventing dislocation. Methods This prospective study included a total of 169 consecutive patients awaiting THA who were classified into four groups based on spinal deformity (pelvic incidence minus lumbar lordosis) and spinal stiffness (change in sacral slope from the standing to seated positions). The cups were aligned based on the group with fluoroscopy. Additionally, postoperative radiographic inclination (RI), radiographic anteversion (RA) in standard anteroposterior radiograph, and lateral anteinclination (AI) in sitting and standing positions were measured. The cumulative incidence of dislocation was evaluated at a follow-up two years post-THA. Result RA was significantly greater in the group with normal spine alignment and stiff spine than in other groups (P = 0.0006), and AI in the sitting position was lower than in other groups (P = 0.012). Standing AI did not significantly differ between the groups. One posterior dislocation occurred during the study period (0.6%). Conclusion AI in the sitting position was lower in patients with normal spinal alignment and stiff spine despite larger RA in the standard anteroposterior radiographs. Consequently, with more anteversion in the normal spinal alignment and stiff spine group, spinopelvic parameters can help guide cup placement to prevent short-term dislocation post-THA.

BACKGROUND: This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. METHODS: Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. RESULTS: The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten-eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. CONCLUSIONS: The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) is attracting attention as a minimally invasive surgery, but the learning curve to master this approach is a concern, and its effect on long-term results is unknown. The purpose of this prospective cohort study was to clarify how the learning curve affects the five-year results of DAA THA with a traction table. METHODS: Of 402 THA cases using DAA with a mobile traction table and fluoroscopy, 249 cases composed of the first 50 cases for each surgeon were assessed during a learning curve, and 153 cases were evaluated after more than 50 cases of experience. RESULTS: The five-year-implant survival rate was 99.2% both during and after the learning curve. The two-year complication rate in the learning curve group was 8.9 versus 5.9%, which was not statistically significant. The two-to-five-year complication rates also did not differ between cohorts (0 versus 0.7%). Both groups demonstrated decreased complication rates when comparing two-year complications to the two-to-five-year complications. Clinical scores significantly improved by two years and were maintained at five years in both groups. The cup-safe zone success rates were 96.4% during the learning curve and 98.7% after the learning curve. The stem-safe zone success rates were 97.2% during the learning curve and 96.1% after the learning curve. Surgical time was approximately 20 minutes shorter after the first 50 cases than during the learning curve (70.8 versus 90.6 minutes, P = 0.001). Intraoperative blood loss was significantly less after the learning curve than during the learning curve. CONCLUSION: This study implicates that the learning curve affects perioperative results such as surgical time and intraoperative blood loss, but has little effect on short-term results up to two years after surgery and no effect on mid-term results from two to five years after surgery.

OBJECTIVE: The goal of this study was to evaluate, using computed tomography (CT) and magnetic resonance imaging (MRI), patients who underwent oblique lateral interbody fusion (OLIF) using either expandable or static interbody spacers. METHODS: Thirty-five patients with degenerative disc disease were surgically treated with one-level OLIF and were followed up for more than 6 months. The Static group consisted of 22 patients, and 13 patients were in the Expandable group. Intraoperative findings included operative time (min), blood loss (ml), and cage size. Low back pain, leg pain, and leg numbness were measured using the Japanese Orthopedic Association score, visual analogue score, and the Roland-Morris Disability Questionnaire. Radiologic evaluation using computed tomography (CT) and magnetic resonance imaging (MRI) allowed measurement of cage subsidence, cross-sectional area (CSA) of the dural sac, disc height, segmental lordosis, foraminal height, and foraminal CSA preoperatively and 6 months postoperatively. RESULTS: The Expandable group had significantly larger cage height and lordosis than the Static group (P < 0.05). The Expandable group also had greater dural sac area expansion and enlargement of the intervertebral foramen, as well as better correction of vertebral body slip (P < 0.05). Cage subsidence was significantly lower in the Expandable group (P < 0.05). JOA and VAS scores for leg numbness were significantly better in the Expandable group (P < 0.05). CONCLUSIONS: Compared with static spacers, expandable spacers significantly enlarged the dural sac area, corrected vertebral body slippage, expanded the intervertebral foramen, and achieved good indirect decompression while reducing cage subsidence, resulting in improvement in clinical symptoms.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

BACKGROUND: Femoral neurovascular injury is a serious complication in a direct anterior approach (DAA) total hip arthroplasty. However, dynamic neurovascular bundle location changes during the approach were not examined. Thus, this study aimed to analyze the effects of leg position on the femoral neurovascular bundle location using magnetic resonance imaging (MRI). METHODS: This study scanned 30 healthy volunteers (15 males and 15 females) with 3.0T MRI in a supine and 30-degree hip extension position with the left leg in a neutral rotation position and the right leg in a 45-degree external extension position. The minimum distance from the edge of the anterior acetabulum to the femoral nerve (dFN), artery, and vein were measured on axial T1-weighted images at the hip center level, as well as the angle to the horizontal line of the femoral nerve (aFN), artery (aFA), and vein from the anterior acetabulum. RESULTS: The dFN in the supine position with external rotation was significantly larger than supine with neutral and extension with external rotation position (20.7, 19.5, and 19.0; p = 0.031 and 0.012, respectively). The aFA in supine with external rotation was significantly larger than in other postures (52.4°, 34.2°, and 36.2°, p < 0.001, respectively). The aFV in supine with external rotation was significantly larger than in supine with a neutral position (52.3° versus 47.7°, p = 0.037). The aFN in supine and external rotation was significantly larger than other postures (54.6, 38.2, and 33.0, p < 0.001, respectively). CONCLUSIONS: This radiographic study revealed that the leg position affected the neurovascular bundle location. These movements can be the risk of direct neurovascular injury or traction.

＜文献概要＞はじめに メトトレキサート(MTX)は関節リウマチ(RA)治療のアンカードラッグとして位置づけられ,RA診断後すみやかな投与がすすめられている.本邦では2022年にMTXの皮下注射製剤が承認され,本年『関節リウマチにおけるメトトレキサート(MTX)使用と診療の手引き2023年版』が発刊された.MTXの作用機序や,現在のRA治療における役割,有効性や安全性などについて解説する.

＜文献概要＞はじめに 関節リウマチ(RA)の治療にメトトレキサート(MTX)に代表される従来型合成疾患修飾性抗リウマチ薬(conventional synthetic disease-modifying antirheumatic drugs:csDMARDs)に加え,生物学的疾患修飾性抗リウマチ薬(biological DMARDs:bDMARDs)が使用されるようになり,疾患活動性は大きく改善した.2003年にインフリキシマブが発売されたのを皮切りに,現在では9種類のbDMARDsが使用可能で,3種類のバイオシミラー(biosimilar:BS)も登場した(表1).すべてのbDMARDsに共通する特徴として,(1)静注または皮下注製剤であること,(2)RA患者の臨床症状の改善,骨関節破壊の進行防止,身体機能の改善といった作用を有すること,(3)有効性は発症早期例,生物学的製剤未使用例,MTX併用例で高いことがあげられる.一方で強力な免疫抑制効果に伴い,重篤な感染症を中心とする副作用のリスクが高まることや,高額な医療費が患者や社会保障費上の問題となることに留意する必要がある.したがってbDMARDsを選択する際には,表2にある項目を検討する必要がある.本稿では,各bDMARDsについて当院での治療経験も交え解説する.

当院で2012～2021年に牽引手術台を用いてDAA-THAを施行した906例(うち初回THA 870例、再置換術36例)の脱臼率と危険因子について検討した。危険因子の候補は「股関節手術歴」「股関節の原疾患(OA/ONFH/外傷/高位脱臼)」「性別」「神経筋疾患の併存」「骨頭径」「Crowe分類」とし、ロジスティック回帰分析を行った。脱臼率は全体で2.2%、初回THA群では1.8%、再置換術群では11.1%であった。有意な危険因子として「股関節手術歴」「股関節の原疾患(ONFHまたは外傷)」「神経筋疾患の併存」が抽出された。

当院で2012～2021年に牽引手術台を用いてDAA-THAを施行した906例(うち初回THA 870例、再置換術36例)の脱臼率と危険因子について検討した。危険因子の候補は「股関節手術歴」「股関節の原疾患(OA/ONFH/外傷/高位脱臼)」「性別」「神経筋疾患の併存」「骨頭径」「Crowe分類」とし、ロジスティック回帰分析を行った。脱臼率は全体で2.2%、初回THA群では1.8%、再置換術群では11.1%であった。有意な危険因子として「股関節手術歴」「股関節の原疾患(ONFHまたは外傷)」「神経筋疾患の併存」が抽出された。

Abstract Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis. CD4+ T cells are pivotal to its pathogenesis, and our previous study revealed the expression of fibroblast growth factor receptor 1 (FGFR1) is modulated by methotrexate treatment in CD4+ T cells of RA patients; however, the roles of FGFR1 in CD4+ T cells in the pathogenesis of RA is unclear. Therefore, in this study, we aimed to characterize FGFR1-positive CD4+ T cells in RA patients. Methods The abundance of FGFR1-positive CD4+ T cells in peripheral blood and synovium was determined. Single-cell RNA sequencing (scRNA-seq) was performed on synovial CD4+ T cells to characterize FGFR1-positive cells. In addition, T cell activation status and cytokine production were determined using flow cytometry. Results The percentage of FGFR1-positive CD4+ T cells in the peripheral blood was higher in RA patients than in healthy controls (P= 0.0035). They were also present in the synovium of active RA patients. The results of scRNA-seq revealed that peripheral T helper (Tph) cells preferentially expressed FGFR1. Additionally, these FGFR1-positive Tph cells displayed a terminal effector cell phenotype. Consistent with this finding, FGFR1-positive CD4+ T cells in peripheral blood expressed interleukin-21 and interferon-γ. Conclusion Our study provides evidence that FGFR1 marks terminal effector Tph cells in patients with RA.

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim was to clarify the health-related quality of life (QOL) of patients who had adolescent idiopathic scoliosis (AIS) at a minimum of 40 years after surgery. SUMMARY OF BACKGROUND DATA: The postoperative health-related QOL of middle-aged patients with AIS has been reported to be good, but that of middle-aged and older patients with AIS has yet to be completely explored. MATERIALS AND METHODS: We included 179 patients with AIS who underwent spinal fusion(s) between 1968 and 1982. We conducted three surveys in 2009, 2014, and 2022. Patients self-administered both the Scoliosis Research Society-22 and the Roland-Morris Disability questionnaires three times (in 2009, 2014, and 2022) and the Oswestry Disability Index (ODI) questionnaire was self-administered in 2014 and 2022. We considered patients who responded to all three surveys in 2009, 2014, and 2022. RESULTS: For the Scoliosis Research Society-22 questionnaires, no significant differences were detected among the three time points (2009, 2014, and 2022) for total scores, function domain, pain domain, self-image domain, mental domain, or satisfaction domain. The results of the Roland-Morris Disability Questionnaire were also not significantly different among the surveys over time. The ODI questionnaires revealed a significant worsening of the 2022 results compared with the 2014 results. Eight patients (29.6%) who had an ODI deterioration of 10% or more had numerically fewer mobile lumbar disks than those with <10% deterioration of the ODI, although the difference did not reach statistical significance. CONCLUSION: Among patients with AIS who underwent spinal fusion(s) between 1968 and 1982, we found health-related QOL to be maintained over the last 13 years. Relatively good QOL was appreciated in this population of patients who are now middle-aged and older.

OBJECTIVE: We aimed to determine the prevalence and risk factors for osteonecrosis of the femoral head (ONFH) in a multicentre cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: One hundred and eighty-six AAV patients who underwent radiographs and MRI screening of bilateral hip joints at more than 6 months after initial remission induction therapy (RIT) were retrospectively assessed for the presence of ONFH. RESULTS: Among 186 AAV patients, 33 (18%) were diagnosed with ONFH. Among the patients with ONFH, 55% were asymptomatic and 64% had bilateral ONFH. Seventy-six per cent of ONFH joints were in precollapse stages (stage ≤2), whereas 24% of ONFH joints were in collapse stages (stage ≥3). Moreover, 56% of the precollapse stage joints were already at risk of future collapse (type ≥C-1). Even in asymptomatic ONFH patients, 39% of the precollapse stage joints were type ≥C-1. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH in AAV patients (OR 1.072, 95% CI 1.017 to 1.130, p=0.009). Rituximab use was a significant beneficial factor against ONFH (p=0.019), but the multivariate analysis rejected its significance (p=0.257). CONCLUSION: Eighteen per cent of AAV patients developed ONFH, and two-thirds of the ONFH joints were already in collapse stages or at risk of future collapse. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH. A rapid reduction of glucocorticoids in RIT and early detection of precollapse ONFH by MRI may decrease and intervene ONFH development in AAV patients.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

BACKGROUND: Osteoarthritis (OA) is the most common disease of the hip in adults, and its etiology is divided into two groups: primary and secondary. Although acetabular dysplasia is the most frequent reason for total hip arthroplasty (THA) in Japan, primary OA has increased recently. Although there are two types of femoral head migration in primary OA: superior and medial, there are some patients with prominent femoral head lateralization. This study aimed at evaluating the relationship between femoral head lateralization and bone morphology of the acetabulum and proximal femur using radiographic factors in primary OA of the hip. METHODS: A retrospective study was conducted between 2008 and 2017 to assess 1308 hips with OA who underwent primary THAs at our institute. The diagnostic criteria for primary OA were Crowe type 1, Sharp's angle <45°, and center-edge (CE) angle >25°. We classified patients with primary OA into two groups based on femoral head lateralization: group L with lateralization or group N without. Radiographic factors included Sharp's angle, CE angle, acetabular inclination, acetabular depth ratio (ADR), acetabular head index (AHI), and femoral neck-shaft angle (FNA), all examined on an anteroposterior pelvic radiograph. Femoral neck anteversion was calculated using computerized axial tomography. RESULTS: Primary OA was diagnosed in 210/1308 hips (16.1%) (group L: 112 hips (8.6%); group N: 98 (7.5%)). Patient demographics were not significantly different. Radiographic factors with observed significant differences between group L and group N were the average CE angle (33.0° vs. 35.1°, respectively, p = 0.009), ADR (251.6 vs. 273.4, p < 0.001), AHI (77.2 vs. 80.4, p < 0.001), and FNA (136.9° vs. 134.8°, p = 0.012). CONCLUSIONS: This investigation suggests that primary OA with femoral head lateralization demonstrated specific identifiable radiographic characteristics in the acetabulum and proximal femur that might contribute to hip joint instability such as the dysplastic hip.

Abstract Objectives Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA). However, the precise mechanisms by which MTX stalls RA progression and alleviates the ensuing disease effects remain unknown. The aim of the present study was to identify novel therapeutic target molecules, the expression patterns of which are affected by MTX in patients with RA. Methods CD4⁺ T cells from 28 treatment-naïve patients with RA before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression levels of semaphorin 3G, a differentially expressed gene, and its receptor, neuropilin-2, were evaluated in the RA synovium and collagen-induced arthritis synovium. Collagen-induced arthritis and collagen antibody-induced arthritis were induced in semaphorin3G-deficient mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of semaphorin 3G-stimulated bone marrow-derived macrophages were analyzed in vitro. The effect of local semaphorin 3G administration on the clinical score and number of infiltrating macrophages during collagen antibody-induced arthritis was evaluated. Results Semaphorin 3G expression in CD4⁺ T cells was downregulated by MTX treatment in RA patients. It was determined that semaphorin 3G is expressed in RA but not in the osteoarthritis synovium; its receptor neuropilin-2 is primarily expressed on activated macrophages. Semaphorin3G deficiency ameliorated collagen-induced arthritis and collagen antibody-induced arthritis. Semaphorin 3G stimulation enhanced the migration and proliferation of bone marrow-derived macrophages. Local administration of semaphorin 3G deteriorated collagen antibody-induced arthritis and increased the number of infiltrating macrophages. Conclusions Upregulation of semaphorin 3G in the RA synovium is a novel mechanism that exacerbates joint inflammation, leading to further deterioration, through macrophage accumulation.

BACKGROUND: Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). METHODS: We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. RESULTS: Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. CONCLUSION: DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.