Kyushu University Academic Staff Educational and Research Activities Database
List of Reports
Yasuharu Nakashima Last modified date:2020.06.26

Professor / Department of Orthopaedic Surgery / Department of Clinical Medicine / Faculty of Medical Sciences


Reports
1. Masato Kiyohara, Satoshi Hamai, Hirotaka Gondo, Hidehiko Higaki, Satoru Ikebe, Tetsuro Ushio, Koji Murakami, Yasuharu Nakashima, Tibiofemoral kinematics in healthy and osteoarthritic knees during twisting, Journal of Orthopaedics, 10.1016/j.jor.2020.03.051, 2020.09, Purpose: The purpose of this study was to determine the in vivo kinematics of healthy knees and those with osteoarthritis (OA), during twisting using density-based image-matching techniques. Methods: Five healthy subjects and 26 patients with medial knee OA performed twisting under periodic X-ray imaging. Results: The tibiofemoral rotation at the ipsilateral/contralateral twist in healthy and OA knees were 11° ± 9.3° externally/9.5° ± 5.6° internally (p < 0.05) and 4.4° ± 7.2° externally/2.7° ± 8° internally (p < 0.05), respectively. Conclusions: The kinematic analysis of OA knees during twisting revealed significantly smaller tibiofemoral rotation than those of healthy knees..
2. Norio Goto, Yukio Akasaki, Ken Okazaki, Umito Kuwashima, Kenyu Iwasaki, Hideya Kawamura, Hideki Mizu-uchi, Satoshi Hamai, Hidetoshi Tsushima, Shinya Kawahara, Yasuharu Nakashima, The influence of post-operative knee coronal alignment parameters on long-term patient-reported outcomes after closed-wedge high tibial osteotomy, Journal of Orthopaedics, 10.1016/j.jor.2020.01.042, 2020.07, Background: Both intra-articular and extra-articular knee alignment pathologies can affect clinical outcomes after high tibial osteotomy. The purpose of this study was to investigate post-operative knee coronal alignment parameters that affect long-term patient-reported outcomes after closed-wedge high tibial osteotomy (CW-HTO). Methods: This study included 105 osteoarthritic knees that underwent CW-HTO. Long-term patient-reported outcomes were defined by the 2011 Knee Society Score (KSS) and were collected at an average follow-up of 10.2 years. Post-operative knee coronal alignment parameters, consisting of the femoral tibial angle (FTA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), tibial plateau inclination (TPI), and joint line convergence angle (JLCA), were measured using standing radiographs of the knee at an average follow-up of 11.0 months. The correlations between these parameters and KSS were then assessed by Spearman's correlation analysis. Comparisons of groups classified by MPTA and TPI cutoff values were performed by the Wilcoxon rank-sum test. Results: Post-operative JLCA showed a significant negative correlation with two KSS sub-scores: satisfaction (R = −0.2232, P = 0.022) and total function (R = −0.2059, P = 0.035). There was no significant difference in any KSS sub-score between the “low” groups (MPTA and TPI less than 95 and 5°, respectively) and the “high” groups (MPTA and TPI greater than 98 and 7°, respectively). Conclusions: Among knee coronal alignment parameters, a large post-operative residual JLCA, which is an intra-articular varus deformity, was independently associated with worsened long-term clinical outcomes after CW-HTO. Level of evidence: Level Ⅳ, Retrospective cohort study..
3. Taro Mawatari, Satoshi Ikemura, Gen Matsui, Takahiro Iguchi, Hiroaki Mitsuyasu, Shinya Kawahara, Masayuki Maehara, Ryoichi Muraoka, Yukihide Iwamoto, Yasuharu Nakashima, Assessment of baseline bone turnover marker levels and response to risedronate treatment
Data from a Japanese phase III trial
, Bone Reports, 10.1016/j.bonr.2020.100275, 2020.06, Background: Risedronate increases bone mineral density (BMD) and reduces fracture risk, but treatment response may depend on the baseline state of bone turnover. Data regarding the selection of therapeutic drugs or the prediction of therapeutic effects with baseline levels of bone turnover markers (BTMs) as a reference are insufficient. We hypothesized that when the baseline levels of BTMs are higher, baseline BMD might be lower, changes in BMD at 12 months after risedronate treatment might be higher, and the reduction of fracture incidence might be greater. This study aimed to analyze the data of a phase III clinical trial of risedronate from Japan to investigate the relationships between baseline BTM levels and (1) baseline BMD, (2) changes in BMD at 12 months after the start of treatment, and (3) the incidence of new vertebral fractures. Methods: This post-hoc analysis included 788 postmenopausal women with osteoporosis whose baseline BTM levels as well as baseline and endpoint BMDs were measured. Relationships between baseline BTM levels and BMD at baseline and 12 months after risedronate treatment and new vertebral fractures were examined. One-way analysis of variance, two-tailed Student's t-test, and Fisher's exact test were used to analyze the data. Results: Baseline BMD showed a significant upward trend when baseline BTM levels were lower in the analysis by tertiles. New vertebral fractures tended to occur in patients with prevalent vertebral fractures, but the relationship between new fractures and BTM levels was not statistically significant. Regardless of BTM types, BMD percentage increments (%) and increments (g/cm2) with the 12-month treatment were high when pretreatment BTM levels were high (P < 0.0001), and a >5.0% increase in BMD was observed even if baseline BTM levels were within the normal range. A new vertebral fracture occurred in only six patients (0.77%), and there was not enough statistical power to clarify the relationship between baseline BTM levels and fracture risk reduction. Conclusions: When pretreatment BTM levels increased, baseline BMD tended to be lower and the increase in BMD with 12-month risedronate treatment was higher. However, BMD could still be increased even if the baseline BTM levels are within the normal range. Combined with available evidence, baseline BTMs may not have an important role in deciding the optimal therapy. To elucidate the relationship between baseline BTM levels and long-term fracture risk, it will be necessary to conduct more large-scale studies with a longer follow-up period in severe osteoporotic patients with a high fracture risk. Mini abstract: We evaluated the significance of baseline bone turnover markers in the response to risedronate treatment. The increase in the bone mineral density (BMD) with the 12-month treatment may be higher when the state of bone turnover at baseline is higher, and BMD could still be increased even if the baseline bone turnover is within the normal range..
4. Kenichiro Yahiro, Yoshihiro Matsumoto, Hisakata Yamada, Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Makoto Nakagawa, Atsushi Kimura, Eijiro Shimada, Seiji Okada, Yoshinao Oda, Yasuharu Nakashima, Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes, Cancer Immunology, Immunotherapy, 10.1007/s00262-020-02508-9, 2020.05, Background: Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis of advanced cases is still poor. Recently, there have been several reports suggesting the relationship between innate immunity and OS, but the detailed mechanism is unknown. We demonstrate the relationship between OS and Toll-like receptor 4 (TLR4) which is one of the most important factors in innate immunity. Methods: We established a syngenic mouse tumor model using C3H/HeN, C3H/HeJ mouse and a highly metastatic OS cell line, LM8. TLR4 activation with lipopolysaccharide (LPS) was performed on both mice and its influence on the progression of OS was evaluated. We also performed CD8 + cells depletion to examine the influence on TLR4 activation effects. Results: Tumor volume of C3H/HeN mice was significantly smaller and overall survival of C3H/HeN mice was significantly longer than C3H/HeJ mice. We found more CD8+ cells infiltrating in lung metastases of C3H/HeN mice and depletion of CD8+ cells canceled the antitumor effects of LPS. Conclusion: TLR4 activation by LPS increased CD8+ cells infiltrating into lung metastases and suppressed OS progression in the mouse model. TLR4 activation may suppress the progression of OS via stimulating CD8+ cells and can be expected as a novel treatment for OS..
5. Kazuya Yokota, Osamu Kawano, Hironari Kaneyama, Takeshi Maeda, Yasuharu Nakashima, Acute spinal subdural hematoma
A case report of spontaneous recovery from paraplegia
, Medicine, 10.1097/MD.0000000000020032, 2020.05, RATIONALE: Spontaneous spinal subdural hematoma (SSDH) is a rare disease that can cause severe permanent neurological dysfunction. Here we present a case of spontaneous SSDH, in which a series of magnetic resonance images (MRIs) taken through the course of the disease facilitated understanding of the resolution process of the hematoma and the diagnosis of SSDH. PATIENT CONCERNS: A 59-year-old male presented with sudden severe back pain and rapid onset of paraplegia. This symptom had continued developing while he was transferred to the emergency department. Initial physical examination showed flaccid paralysis of both lower limbs with areflexia and loss of all sensation below T6 bilaterally. MRI images showed an anterior subdural hematoma from C7 to T7 with spinal cord compression. DIAGNOSIS: Based on MRI findings, the diagnosis was SSDH. INTERVENTIONS: We chose conservative treatment of 1-week bed rest and intensive rehabilitation for the patient due to the presence of sacral sparing and the slight motor recovery at 24 hours after the onset. OUTCOMES: Frequent MRI images demonstrated that the spinal cord compression was surprisingly mitigated only 2 days and mostly absorbed 4 days after the onset. The patient's motor function was recovered completely and he was discharged after 8 weeks of hospitalization. LESSONS: Our chronological MRI findings provide crucial information for diagnosing SSDH and also suggest that spinal surgeons should consider the potential option of a conservative approach for treating SSDH. Although prompt selection of a therapeutic strategy for SSDH could be challenging, the surgeons could observe the course of the patient's neurological status for a few days to detect signs of spontaneous recovery..
6. Kyohei Shiomoto, Satoshi Hamai, Daisuke Hara, Hidehiko Higaki, Hirotaka Gondo, Yifeng Wang, Satoru Ikebe, Kensei Yoshimoto, Keisuke Komiyama, Satoru Harada, Yasuharu Nakashima, In vivo kinematics, component alignment and hardware variables influence on the liner-to-neck clearance during chair-rising after total hip arthroplasty, Journal of Orthopaedic Science, 10.1016/j.jos.2019.05.012, 2020.05, Background: There is an interest in quantifying dynamic hip kinematics before and after total hip arthroplasty (THA) during chair-rising: one of daily life activities. Methods: The study consisted of 21 patients who underwent unilateral total hip arthroplasty for symptomatic osteoarthritis. We obtained continuous radiographs using a flat-panel X-ray detector while the participants rose from chair. We assessed the pre and postoperative hip joint's movements using three-dimensional-to-two-dimensional model-to-image registration techniques. We also measured minimum liner-to-neck distances at maximum hip flexion and extension as anterior and posterior liner-to-neck distances, respectively. Multivariate analyses were applied to determine which factors were associated with liner-to-neck distances. Results: The cup inclination, cup anteversion, and stem anteversion averaged 37.4°, 23.1°, and 30.1°, respectively. Significantly larger maximum hip flexion angle (72°) was found during chair-rising after THA compared to that before THA (63°, P < 0.01). The anterior pelvic tilt at the maximum hip flexion after THA (3° of anterior tilt) was significantly (P < 0.05) anterior compared to that before THA (1° of posterior tilt). The anterior and posterior liner-to-neck distances averaged 12.3 mm and 8.1 mm, respectively, with a significant difference (P < 0.01). No liner-to-neck contact was found in any hips. In multivariate analysis, the hip flexion angle, cup inclination, stem anteversion and head diameter were significantly associated with the anterior liner-to-neck distance (P < 0.05), the hip extension angle, cup anteversion, neck length and with or without elevated rim were significantly associated with the posterior liner-to-neck distance (P < 0.05, 0.01, 0.05, 0.01, respectively). Conclusion: This study indicates that well-positioned THA provide increased range of hip flexion with sufficient anterior liner-to-neck clearance during chair-rising. Dynamic hip kinematics, component position, and hardware variables significantly influenced on the liner-to-neck clearance under weight-bearing conditions..
7. Kyohei Shiomoto, Satoshi Hamai, Goro Motomura, Satoshi Ikemura, Masanori Fujii, Yasuharu Nakashima, Influencing Factors for Joint Perception After Total Hip Arthroplasty
Asian Cohort Study
, Journal of Arthroplasty, 10.1016/j.arth.2019.12.039, 2020.05, Background: Perceiving replaced joints as natural is one of the best scenario after total hip arthroplasty (THA). We investigated the distribution of and influencing factors for patient's joint perception after THA in Asian cohort, which is not well known. Methods: We mailed a questionnaire to Asian patients who had undergone THA in our institution between 2012 and 2016, and this study included 318 Asian patients. The questionnaire assessed patient's joint perception, Oxford Hip Score (OHS), Short Form-12 Health Survey (SF-12) physical, mental, and role component summaries, and satisfaction score. Leg length discrepancy and global femoral offset before and after THA were measured using radiographs. The patients were divided into 2 groups with patient's joint perception: natural and artificial perception groups. OHS, SF-12, satisfaction, leg length discrepancy, and global femoral offset were compared between natural and artificial perception groups, and which factors significantly influenced joint perception were determined. Results: Of the 318 patients, 165 patients (51.8%) perceived their replaced joint as a natural joint. OHS, SF-12 physical and role component summaries, and satisfaction score in natural perception group were significantly higher than those in artificial perception group, without significant difference in SF-12 mental component summary. Multivariate analysis showed that less of usual pain, easier to get in or out of a car, and osteoarthritis in the contralateral hip were positively associated with natural joint perception after THA. Conclusion: This study indicated to surgeons that pain relief and improvement in getting in or out of a car after THA could lead to even better patient's joint perception..
8. Tetsuya Tachibana, Masanori Fujii, Kenji Kitamura, Satoshi Ikemura, Satoshi Hamai, Goro Motomura, Jun ichi Fukushi, Yasuharu Nakashima, Modified lateralized head sign
An accurate marker in diagnosing adult hip dysplasia
, Journal of Orthopaedic Science, 10.1016/j.jos.2019.05.015, 2020.05, Background: Although lateralized head sign (LHS) is considered indicative of structural instability, it lacks reproducibility, and its usefulness in diagnosing adult hip dysplasia is unknown. In this study, we proposed a modified LHS and aimed to determine its reliability and accuracy in diagnosing adult hip dysplasia. Methods: We reviewed anteroposterior pelvic radiographs of 94 patients (134 hips) with hip dysplasia. As controls, 133 normal hips were evaluated. We defined the modified lateralization distance (LD) as the horizontal distance between the medial aspect of the femoral head to the acetabular fossa. The sensitivity, specificity, and cutoff value of modified LD in diagnosing hip dysplasia were calculated using receiver operating characteristic curve analysis. Results: The sensitivity and specificity of the modified LD (79% and 87%, respectively) were higher than those of the conventional LD (63% and 80%, respectively). Diagnostic accuracy was further improved when patients were divided on the basis of sex. The sensitivity and specificity of the modified LD in men were 89% and 97%, respectively, with a cutoff value of 12 mm, while in women, they were 80% and 96%, respectively, with a cutoff value of 9.7 mm. Therefore, we defined the modified LHS as presentation with a modified LD ≥ 12 mm in men and ≥10 mm in women. Between three observers, the kappa value for intraobserver reliability was ≥0.9, while that for interobserver reliability was >0.8. The mean sensitivity and specificity of the modified LHS in diagnosing hip dysplasia were 85% and 99%, respectively. Conclusions: Modified LHS—a horizontal distance between the medial aspect of the femoral head and the acetabular fossa ≥12 mm in men and ≥10 mm in women—is a clinically useful marker in detecting lateral femoral head subluxation indicative of hip dysplasia or structural hip instability..
9. Hirokazu Saiwai, Seiji Okada, Mitsumasa Hayashida, Katsumi Harimaya, Yoshihiro Matsumoto, Ken Ichi Kawaguchi, Kazu Kobayakawa, Takeshi Maeda, Hideki Ohta, Kenzo Shirasawa, Kuniyoshi Tsuchiya, Kazumasa Terada, Kouzo Kaji, Takeshi Arizono, Taichi Saito, Masami Fujiwara, Yukihide Iwamoto, Yasuharu Nakashima, Surgery-related predictable risk factors influencing postoperative clinical outcomes for thoracic myelopathy caused by ossification of the posterior longitudinal ligament
A multicenter retrospective study
, Journal of Neurosurgery: Spine, 10.3171/2019.10.SPINE19831, 2020.05, OBJECTIVE Compression of the spinal cord by thoracic ossification of the posterior longitudinal ligament (T-OPLL) often causes severe thoracic myelopathy. Although surgery is the most effective treatment for T-OPLL, problems associated with surgical intervention require resolution because surgical outcomes are not always favorable, and a small number of patients experience deterioration of their neurological status after surgery. The aim of the present study was to examine the surgery-related risk factors contributing to poor clinical outcomes for myelopathy caused by T-OPLL. METHODS Data were extracted from the records of 55 patients with thoracic myelopathy due to T-OPLL at institutions in the Fukuoka Spine Group. The mean follow-up period was 5.3 years. Surgical outcomes were assessed using the Japanese Orthopaedic Association (JOA) scale. To investigate the definitive factors associated with surgical outcomes, univariate and multivariate regression analyses were performed with several patient-related and surgery-related factors, including preoperative comorbidities, radiological findings, JOA score, surgical methods, surgical outcomes, and complications. RESULTS Neurological status improved in 33 patients (60.0%) and deteriorated in 10 patients (18.2%) after surgery. The use of instrumentation was significantly associated with an improved outcome. In the comparison of surgical approaches, posterior decompression and fusion resulted in a significantly higher neurological recovery rate than did anterior decompression via a posterior approach and fusion or decompression alone. It was also found that postoperative neurological status was significantly poorer when there were fewer instrumented spinal levels than decompression levels. CSF leakage was a predictable risk factor for deterioration following surgery. CONCLUSIONS It is important to identify preventable risk factors for poor surgical outcomes for T-OPLL. The findings of the present study suggest that intraoperative CSF leakage and a lower number of instrumented spinal fusion levels than decompression levels were exacerbating factors for the neurological improvement in T-OPLL surgery..
10. Shingo Yoshizaki, Kazuya Yokota, Kensuke Kubota, Takeyuki Saito, Masatake Tanaka, Dai jiro Konno, Takeshi Maeda, Yoshihiro Matsumoto, Yasuharu Nakashima, Seiji Okada, The beneficial aspects of spasticity in relation to ambulatory ability in mice with spinal cord injury, Spinal Cord, 10.1038/s41393-019-0395-9, 2020.05, Study design: Experimental study with mice. Objectives: Spasticity is a common complication after spinal cord injury (SCI) and has detrimental aspects, such as persistent pain and involuntary muscle spasms. This study aimed to assess the influence of antispastic therapy on locomotor function after SCI. Setting: University-based laboratory in Fukuoka, Japan. Methods: A mouse model of spasticity was developed by producing incomplete SCI at the 9th thoracic level. At 8 weeks after SCI, an antispastic drug, baclofen, was intraperitoneally administered to six injured and two sham-operated mice. The severity of spasticity was evaluated by the modified Ashworth scoring (MAS) system, and locomotor function was evaluated by the Basso–Beattie–Bresnahan (BBB) scale/Basso mouse score (BMS). Results: The administration of baclofen significantly improved spasticity in the SCI mice and the mean MAS decreased to from 6.2 to 2.8. However, at the same time, it significantly exacerbated the locomotor dysfunction of the SCI mice and the mean BMS decreased from 4.7 to 2.3. The time-course of the changes in locomotor function coincided with the time-course of the spasticity score. We also confirmed that the administration of baclofen was not associated with any changes in either locomotor function or spasticity of the sham-operated control mice. Conclusions: Our results suggest that spasticity has a certain beneficial effect on ambulation ability. It is important to note that antispastic treatments may be associated with a risk of impairing the preserved function of chronic SCI patients..
11. Kenji Kitamura, Masanori Fujii, Takeshi Utsunomiya, Miho Iwamoto, Satoshi Ikemura, Satoshi Hamai, Goro Motomura, Mitsugu Todo, Yasuharu Nakashima, Effect of sagittal pelvic tilt on joint stress distribution in hip dysplasia
A finite element analysis
, Clinical Biomechanics, 10.1016/j.clinbiomech.2020.02.011, 2020.04, Background: Physiologic pelvic tilt can change acetabular orientation and coverage in patients with hip dysplasia. In this study, we aimed to clarify the impact of change in sagittal pelvic tilt on joint stress distribution in dysplastic hips. Methods: We developed patient-specific finite element models of 21 dysplastic hips and 21 normal hips. The joint contact area, contact pressure, and equivalent stress of the acetabular cartilage were assessed at three pelvic tilt positions relative to the functional pelvic plane: 10° anterior tilt, no tilt, and 10° posterior tilt. Findings: The mean contact area was 0.6–0.7 times smaller, the mean maximum contact pressure was 1.8–1.9 times higher, and the mean maximum equivalent stress was 1.3–2.8 times higher in dysplastic hips than in normal hips at all three pelvic positions. As the pelvis tilted from 10° anterior to 10° posterior, the mean contact area decreased, and the mean maximum contact pressure and median maximum equivalent stress increased. The latter two changes were more significant in dysplastic hips than in normal hips (total increment was 1.3 MPa vs. 0.4 MPa, P = 0.001, and 3.6 MPa vs. 0.4 MPa, P < 0.001, respectively). The mean equivalent stress increased in the anterosuperior acetabulum during posterior pelvic tilt in dysplastic and normal hips, while the change was not significant in the superior and posterosuperior acetabulum in both groups. Interpretation: Sagittal pelvic tilt alters the loading environment and joint stress distribution of the hip joint and may impact the degeneration process in dysplastic hips..
12. Takuya Sueishi, Yukio Akasaki, Norio Goto, Ichiro Kurakazu, Masakazu Toya, Masanari Kuwahara, Taisuke Uchida, Mitsumasa Hayashida, Hidetoshi Tsushima, Hirofumi Bekki, Martin K. Lotz, Yasuharu Nakashima, GRK5 Inhibition Attenuates Cartilage Degradation via Decreased NF-κB Signaling, Arthritis and Rheumatology, 10.1002/art.41152, 2020.04, Objective: NF-κB–dependent signaling is an important modulator in osteoarthritis (OA), and G protein–coupled receptor kinase 5 (GRK5) regulates the NF-κB pathway. This study was undertaken to investigate the functional involvement of GRK5 in OA pathogenesis. Methods: GRK5 expression in normal and OA human knee joints was analyzed immunohistochemically. Gain- or loss-of-function experiments were performed using human and mouse chondrocytes. OA was induced in GRK5-knockout mice by destabilization of the medial meniscus, and histologic examination was performed. OA was also induced in wild-type mice, which were then treated with an intraarticular injection of amlexanox, a selective GRK5 inhibitor, every 5 days for 8 weeks. Results: GRK5 protein expression was increased in human OA cartilage. In vitro, expression levels of OA-related factors and NF-κB transcriptional activation were down-regulated by suppression of the GRK5 gene in human OA chondrocytes (3.49-fold decrease in IL6 [P < 0.01], 2.43-fold decrease in MMP13 [P < 0.01], and 2.66-fold decrease in ADAMTS4 [P < 0.01]). Conversely, GRK5 overexpression significantly increased the expression of OA-related catabolic mediators and NF-κB transcriptional activation. On Western blot analysis, GRK5 deletion reduced IκBα phosphorylation (up to 4.4-fold decrease [P < 0.05]) and decreased p65 nuclear translocation (up to 6.4-fold decrease [P < 0.01]) in mouse chondrocytes. In vivo, both GRK5 deletion and intraarticular amlexanox protected mouse cartilage against OA. Conclusion: Our results suggest that GRK5 regulates cartilage degradation through a catabolic response mediated by NF-κB signaling, and is a potential target for OA treatment. Furthermore, amlexanox may be a major compound in relevant drugs..
13. Kensei Yoshimoto, Satoshi Hamai, Hidehiko Higaki, Hirotaka Gondoh, Kyohei Shiomoto, Satoru Ikebe, Daisuke Hara, Keisuke Komiyama, Yasuharu Nakashima, Dynamic hip kinematics before and after periacetabular osteotomy in patients with dysplasia, Journal of Orthopaedic Science, 10.1016/j.jos.2019.03.019, 2020.03, Background: We prospectively analyzed the hip kinematics in patients with developmental dysplasia of the hip (DDH) before and after periacetabular osteotomy (PAO) and in healthy subjects while squatting to determine the influence of coverage of the femoral head on hip kinematics. Methods: 14 hips in 14 patients with DDH and 10 hips in 10 volunteers were included. Continuous radiographs while squatting and computed tomography images were obtained to assess the in vivo kinematics of the hip and the rim-neck distance using density-based 3D-to-2D model-to-image registration techniques. Results: The maximum hip flexion angles were 100.4° and 94.9° before and after PAO (p = 0.0863), respectively. The maximum hip flexion angles after PAO did not significantly differ from those of normal hips (102.2°; p = 0.2552). The hip abduction angles at maximum hip flexion were 31.7° and 26.2° before and after PAO (p = 0.1256), respectively. The rim-neck distance decreased from averaged 12.2 mm–8.9 mm (p = 0.0044) after PAO. The lateral center edge angle (LCEA) and anterior center edge angle (ACEA) significantly improved 14.7°–42.4° and 50.4°–54.0° after PAO (p < 0.0001, p = 0.0347), respectively; in particular, the ACEA after PAO did not significantly differ from that in the normal hips (p = 0.1917). The ACEA was not correlated with hip flexion, or the rim-neck distance (p = 0.9601, 0.8764). The LCEA was also not correlated with hip abduction (p = 0.1683). Conclusion: Patients after PAO showed no significant difference in maximum hip flexion while squatting compared to before PAO and normal hips. Horizontalized weight-bearing acetabulum with normalized ACEA could be adequate correction of the acetabular fragment to restore hip RoM without coxalgia that induce the inability to perform squats after PAO..
14. Hisakata Yamada, Tomomi Tsuru, Takeshi Otsuka, Masayuki Maekawa, Hiroshi Harada, Takaaki Fukuda, Hiroshi Tsukamoto, Akira Maeyama, Shigeru Yoshizawa, Ken Wada, Yasuharu Nakashima, Eisuke Shono, Seiji Yoshizawa, Hiroshi Jojima, Masakazu Kondo, Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production, Immunological Medicine, 10.1080/25785826.2020.1718833, 2020.01, Abatacept may exert its clinical effect on rheumatoid arthritis (RA) by suppressing anti-cyclic citrullinated peptide (CCP) antibody production. This study was undertaken to test this hypothesis by examining the changes of disease activity of RA and anti-CCP antibody levels over time after starting abatacept. Sixty Japanese RA patients who started abatacept were included in this multicenter, prospective observational study. Simple Disease Activity Index (SDAI) and anti-CCP antibody levels were evaluated at 12, 24, and 52 weeks. The mean SDAI score significantly decreased within 12 weeks after starting abatacept and was maintained thereafter. On the contrary, the mean anti-CCP antibody levels did not change until 52 weeks. At the individual level, there were substantial changes of anti-CCP antibody levels, but these were not correlated with the changes of disease activity at any time points. Thus, abatacept reduces the disease activity of RA independently of modulating anti-CCP antibody production..
15. Masato Yoshimoto, Yuichi Yamada, Shin Ishihara, Kenichi Kohashi, Yu Toda, Yoshihiro Ito, Hidetaka Yamamoto, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda, Comparative Study of Myxofibrosarcoma with Undifferentiated Pleomorphic Sarcoma
Histopathologic and Clinicopathologic Review
, American Journal of Surgical Pathology, 10.1097/PAS.0000000000001389, 2020.01, Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with the prominent myxoid area. It has the clinical features of frequent local recurrence and occasional distant metastasis. Morphologically, MFS is occasionally difficult to distinguish from undifferentiated pleomorphic sarcoma (UPS), especially in the case of high-grade MFS. Here, we reviewed clinical and histologic data of 162 MFS cases and 43 UPS cases. MFS was distinguished from UPS with the criterion of 10% myxoid area as a cutoff value. Overall, 52 MFS (34.4%) and 9 UPS (20.9%) cases showed local recurrence, 18 MFS (12.2%) and 19 UPS (44.2%) cases developed distant metastasis, and 13 MFS (9.5%) and 14 UPS (32.6%) cases resulted in tumor-related death. Statistically, MFS had a better prognosis than UPS. Moreover, MFS with less myxoid area had a tendency to present a poorer prognosis. FNCLCC grade was a statistically significant prognostic factor (distant metastasis: P=0.0021, tumor-related death: P=0.0021). Cellularity and nuclear atypia had only a statistical tendency for associations with a poorer prognosis. The overall survival rate of MFS after transformation into a UPS-like condition (<10% myxoid area) was close to that of UPS. It was suggested that MFS is a biologically distinct tumor from UPS, and MFS with less myxoid area had a tendency to present a poorer prognosis. We considered that evaluation of the amount of myxoid area, cellularity, and nuclear atypia may be important as prognostic predictors. MFS may become similar to histologic malignancy of UPS in terms of morphology and biology via local recurrence..
16. Yusuke Kubo, Goro Motomura, Satoshi Ikemura, Hiroyuki Hatanaka, Takeshi Utsunomiya, Satoshi Hamai, Masanori Fujii, Jun ichi Fukushi, Yasuharu Nakashima, Effects of anterior boundary of the necrotic lesion on the progressive collapse after varus osteotomy for osteonecrosis of the femoral head, Journal of Orthopaedic Science, 10.1016/j.jos.2019.02.014, 2020.01, Background: Anterior localization of the necrotic lesion was recently proposed as an important factor for the occurrence of collapse even in medially located osteonecrosis of the femoral head (ONFH). We examined the effects of the anterior boundary of the necrotic lesion on progressive collapse after varus osteotomy for ONFH. Methods: We reviewed the outcomes of 31 hips in 27 patients with ONFH treated by transtrochanteric curved varus osteotomy (CVO) from 2000 to 2012 with a mean follow-up of 10.5 years. The occurrence of progressive collapse of the anterior necrotic lesion was defined as the presence of ≥2 mm collapse using follow-up lateral radiographs. Postoperative osteoarthritic change was defined as ≥1 mm progression of joint space narrowing on follow-up radiographs. The location of the anterior boundary of the necrotic lesion was assessed using the anterior necrotic angle (the angle between the midline of the femoral neck shaft and the line passing from the femoral head center to the anterior boundary of the necrotic lesion on a mid-slice oblique magnetic resonance image). Results: All hips had a postoperative intact ratio of ≥34% (percentage of the transposed intact articular surface of the femoral head to the weight-bearing area of the acetabulum after femoral osteotomy). Progressive collapse of the anterior necrotic lesion was seen in five hips (16%) during a mean of 2.2 years after CVO. Of these, four hips (80%) proceeded to develop osteoarthritic change at an average of 4.3 years after the collapse. Multivariate analysis revealed that the anterior necrotic angle was independently associated with progressive collapse of the anterior necrotic lesion as well as the postoperative intact ratio. Conclusions: This study suggests that hips with anterior localization of the necrotic lesion have a possible risk of progressive collapse of the anterior necrotic lesion after CVO, which can frequently lead to subsequent osteoarthritic change..
17. Nobuhiko Haga, Yasuharu Nakashima, Hiroshi Kitoh, Junji Kamizono, Takenobu Katagiri, Hideto Saijo, Sho Tsukamoto, Yusuke Shinoda, Ryoko Sawada, Yasuo Nakahara, Fibrodysplasia ossificans progressiva
Review and research activities in Japan
, Pediatrics International, 10.1111/ped.14065, 2020.01, Fibrodysplasia ossificans progressiva (FOP) is a rare genetic skeletal disorder manifesting progressive heterotopic ossification (HO) and congenital malformation of the great toes. Since 2007, we have conducted research on FOP. Here, we review the findings on FOP published to date, including the results of our research. Epidemiological studies in Japan have indicated that FOP has nearly the same prevalence in Japan as in the rest of the world. Basic research on its pathoetiology has progressed rapidly since the identification of the causal gene in 2006. Clinical and radiological findings have been thoroughly researched, including early radiological signs, and diagnostic criteria were established, designating FOP as an intractable disease in Japan. In patients with FOP, the progression of HO is associated with numerous disabilities, often manifesting in vicious cycles that can lead to early mortality. Through cross-sectional and short-term longitudinal studies, we have explored patient education, quality of life, and activities of daily living among Japanese patients. The management of FOP requires education of patients and caregivers, the use of medications to settle inflammation and flare-ups, instructions to ensure proper oral care, and other compensatory approaches that aid in rehabilitation. An avoidance of medical intervention, which may cause HO to progress, is also important. The advent of new drugs to prevent HO could have clinical benefit..
18. Masanori Fujii, Tetsuro Nakamura, Toshihiko Hara, Yasuharu Nakashima, Is Ranawat triangle method accurate in estimating hip joint center in Japanese population?, Journal of Orthopaedic Science, 10.1016/j.jos.2020.03.007, 2020.01, Background: Little information has been available regarding the usefulness of Ranawat triangle method in estimating anatomical hip joint center in the Japanese population. In this study, we aimed to determine the accuracy of the method in estimating hip joint center. Methods: Using digitally reconstructed radiographs of 123 normal hips (123 patients), we measured the hip joint center coordinates (Cx, Cy) with reference to the ipsilateral lowest point of the teardrop, the pelvic width, and the pelvic height. Using these measurement values, we performed the following analyses: (1) the relationship of hip joint center location with pelvic dimensions; (2) accuracy of Ranawat method in estimating hip joint center; (3) alternative methods to estimate hip joint center using pelvic height. Results: The mean Cx and Cy were 32 ± 3.0 mm and 13 ± 2.1 mm, respectively. Pelvic height was positively correlated with Cx (r = 0.51, p < 0.001) and Cy (r = 0.69, p < 0.001), but the correlations of pelvic width with Cx and Cy were negligible. The mean estimation error of the Ranawat method was −6.7 ± 2.6 mm in x-axis and 6.6 ± 1.9 mm in y-axis, respectively. The hip joint center was estimated within a 5 mm error in both axes in only 8 hips (6.5%). Thus, we developed two estimating methods using pelvic height, modified Ranawat method and pelvic height ratio method, and the estimation errors of these methods were within 5 mm in both axes in 118 hips (96%) and 116 hips (94%), respectively. Conclusions: Ranawat method showed poor accuracy in estimating anatomical hip joint center and is not recommended for clinical use. Our alternative methods may be useful for surgeons planning the position of the acetabular component in total hip arthroplasty..
19. Shoji Baba, Goro Motomura, Satoshi Ikemura, Ryosuke Yamaguchi, Takeshi Utsunomiya, Hiroyuki Hatanaka, Koichiro Kawano, Mingjian Xu, Yasuharu Nakashima, Is bone mineral density lower in the necrotic lesion in pre-collapse osteonecrosis of the femoral head?, Journal of Orthopaedic Research, 10.1002/jor.24674, 2020.01, The purpose of this study was to clarify whether bone mineral density (BMD) of the necrotic lesion in precollapse osteonecrosis of the femoral head (ONFH) is reduced according to Hounsfield unit (HU) values on computed tomography (CT). The superior one-third of the femoral head in the coronal section was set as the region of interest (ROI) for the measurement of HU values. First, HU values of 101 control participants were assessed to identify relevant confounding factors. Next, the relationship between HU values and BMD on dual-energy X-ray absorptiometry (DXA) was verified. Then the mean HU value of the ROI in patients with pre-collapse ONFH was compared with that in propensity score-matched control participants. Finally, the HU values of the lateral boundary in the patients with and without subsequent collapse were compared. Multivariable analysis showed that both age and BMI were significantly correlated with the HU value, which showed a strong correlation with the BMD of the femoral neck on DXA (r = 0.92). In 25 ONFH patients and 25 propensity-matched control participants, no significant difference was found in the HU value of the ROI (p =.54). The mean HU value of the lateral boundary in patients with subsequent collapse was found to be significantly higher than that in patients without subsequent collapse (p <.01). The assessment of HU values on CT was useful for the evaluation of BMD of the femoral head. The current assessment did not demonstrate reduced bone mineral density of the necrotic lesion in pre-collapse ONFH..
20. Miho Iwamoto, Masanori Fujii, Keisuke Komiyama, Yuta Sakemi, Kyohei Shiomoto, Kenji Kitamura, Ryosuke Yamaguchi, Yasuharu Nakashima, Is lateral acetabular rotation sufficient to correct anterolateral deficiency in periacetabular reorientation osteotomy? A CT-Based simulation study, Journal of Orthopaedic Science, 10.1016/j.jos.2019.12.014, 2020.01, Background: Residual acetabular deficiency after periacetabular reorientation osteotomy can result in suboptimal outcome. The optimal algorithm of acetabular fragment correction to achieve normal anterolateral acetabular coverage is not well characterized. The aim of this study was to determine the prevalence of residual anterolateral deficiency after lateral acetabular rotation and to evaluate the ability of additional sagittal and axial rotation of the acetabulum to normalize the acetabular coverage in periacetabular osteotomy. Methods: We performed computed tomography-based simulated periacetabular osteotomy on 85 patients (85 hips) with hip dysplasia. The acetabular fragment was rotated laterally to achieve a lateral center-edge angle (CEA) of 30°. For hips with residual anterolateral deficiency, which were identified based on the reference interval of the anterior CEA, the acetabulum was further rotated in the sagittal or axial direction in 5-degree increments from 5° to 20°, and the ability of these two manoeuvres to restore a normal anterior CEA was assessed. Results: After lateral acetabular rotation, 16 hips (19%) had residual anterolateral deficiency, 67 hips (79%) had normal acetabular coverage, and 2 hips (2.4%) had acetabular overcoverage. A preoperative anterior CEA <37° predicted residual deficiency (sensitivity, 94%; specificity, 81%). Additional anterior sagittal rotation was more effective than posterior axial rotation in normalizing the anterior CEA, while minimizing the decrease in posterior CEA. The highest number of hips with normal anterior and posterior CEA was noted at 10° sagittal rotation (81%), which was followed by 15° sagittal rotation (63%). Conclusions: Normal anterolateral coverage was achieved in 79% of patients after rotating the acetabulum laterally. However, lateral rotation of the acetabulum may be insufficient to correct the anterolateral deficiency in patients with an anterior CEA of <37°. In them, additional 10°–15° anterior sagittal rotation may be appropriate to achieve sufficient anterolateral coverage while retaining posterolateral coverage..
21. Koichiro Kawano, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Junichi Fukushi, Satoshi Hamai, Masanori Fujii, Yasuharu Nakashima, Long-term hip survival and factors influencing patient-reported outcomes after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head
A minimum 10-year follow-up case series
, Modern Rheumatology, 10.1080/14397595.2018.1558917, 2020.01, Objectives: This retrospective study aimed to assess long-term hip survival after transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) and identify factors influencing patient-reported outcome measures (PROMs) in patients with preserved joints. Methods: Altogether, 95 consecutive hips in 85 ONFH patients who underwent ARO during 2000–2007 (86.7% follow-up) were studied. Controls were 35 patients with 41 hips with ONFH managed conservatively for >1 year after collapse. We analyzed hip survival using the Kaplan–Meier method, with the endpoint defined as any therapeutic surgery related to ONFH. We also evaluated PROMs for both groups in patients with surviving hips and available radiographs at the final follow-up. Results: The 10-year hip survival rate after ARO was 85.4%, which was significantly higher than the 5-year rate in the control group (50.4%). Multiple regression analyses showed that the presence of osteoarthritic change after ARO was significantly associated with poor scores for both the Oxford Hip Score and the Short Form-12 Health Survey Physical Component Summary. Conclusions: ARO could effectively preserve hip joints with post-collapse ONFH, although the presence of osteoarthritic change could lead to lower satisfaction even among patients with long-term hip survival after ARO..
22. Noriko Oyama, Kanako Kojima-Ishii, Naoko Toda, Terumichi Matsuo, Vlad Tocan, Kazuhiro Ohkubo, Utako Oba, Yuhki Koga, Nokitaka Setsu, Yuichi Yamada, Kenichi Kohashi, Yasuharu Nakashima, Yoshinao Oda, Kenji Ihara, Shouichi Ohga, Malignant transformation of phosphaturic mesenchymal tumor
A case report and literature review
, Clinical Pediatric Endocrinology, 10.1297/cpe.29.69, 2020.01, Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMT-MCT) causes tumor-induced osteomalacia (TIO). Most cases follow a benign clinical course, with rare occurrences of malignant transformation. We report a case of malignant PMT-MCT and review previous malignant cases to identify predictive factors for transformation. A 13-yr-old female, who presented with hypophosphatemic rickets, elevated serum intact fibroblast growth factor 23 (FGF23) levels, and a nodule in the back, received a diagnosis of TIO because of the benign PMT histopathology. After resection of the primary tumor, regular imaging analyses did not indicate any relapse. At 17 years of age, a tumor developed in the left leg and increased in size. The resected tumor showed a histopathology of pleomorphic sarcoma positive for the TP53 mutation. Despite amputation of the affected leg, the patient died due to multiple metastases at 18 years of age. A literature review revealed that 14 out of 15 reported malignant PMT-MCT tumors occurred in adults, and found no predictive factors for malignant transformation and treatment outcome. Changes in size or number of the tumors along with intact FGF23 levels have been considered as the only sign of malignant transformation. This pediatric case report and literature review indicate the need for prolonged regular monitoring for PMT-MCT..
23. Yu Toda, Kenichi Kohashi, Yuichi Yamada, Masato Yoshimoto, Shin Ishihara, Yoshihiro Ito, Takeshi Iwasaki, Hidetaka Yamamoto, Yoshihiro Matsumoto, Yasuharu Nakashima, Masaaki Mawatari, Yoshinao Oda, PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients
comparative study of primary and metastatic lesions
, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-020-03242-6, 2020.01, Purpose: Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunosuppressive proteins known to be associated with poor prognosis in various cancers. However, their expression and clinical relevance in osteosarcoma remain unknown. In this study, the relationships of PD-L1 and IDO1 expression with clinicopathological features and prognosis were explored. Methods: The expression of PD-L1, IDO1, CD3, CD4, and CD8 in 112 formalin-fixed, paraffin-embedded tumor tissues collected by biopsy or surgical resection from 56 osteosarcoma patients was evaluated immunohistochemically. Moreover, four osteosarcoma cell lines were evaluated for the effects of IFNγ on PD-L1 and IDO1 mRNA expression by real-time reverse-transcription polymerase chain reaction. Results: In pre-neoadjuvant chemotherapy (NAC) primary specimens, 10 cases (17%) showed PD-L1 expression and 12 (21%) showed IDO1 expression. Six of ten cases (60%) with PD-L1 positivity co-expressed IDO1. In post-NAC metastatic lesions, the frequency of immunoexpression of PD-L1 and IDO1 was increased compared with that in pre-NAC specimens. PD-L1 and/or IDO1 expression was not associated with poor prognosis. PD-L1 immunoexpression was significantly associated with the infiltration of CD3+ T cells, CD4+ T cells, and CD8+ T cells; while, IDO1 immunoexpression was significantly associated with the infiltration of CD3+ T cells and CD4+ T cells. In all osteosarcoma cell lines, PD-L1 and IDO1 expression was upregulated by stimulation with IFNγ. Conclusion: Our results suggest that the PD-L1 and IDO1 immune checkpoint inhibitors may provide clinical benefit in osteosarcoma patients with metastatic lesions after conventional chemotherapy..
24. Shoji Baba, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Takeshi Utsunomiya, Hiroyuki Hatanaka, Koichiro Kawano, Yasuharu Nakashima, Quantitative evaluation of bone-resorptive lesion volume in osteonecrosis of the femoral head using micro-computed tomography, Joint Bone Spine, 10.1016/j.jbspin.2019.09.004, 2020.01, Objectives To quantify the volume of bone-resorptive lesions in post-collapse osteonecrosis of the femoral head (ONFH) using micro-computed tomography (micro-CT) and assess their characteristics in post-collapse ONFH. Methods We investigated 35 femoral heads resected from 35 patients with ONFH (20 men and 15 women; mean age, 47.2 years). On each of seven coronal high-resolution micro-CT slices of the femoral head, the bone-resorptive areas were extracted using bone microstructure measurement software. Next, the total bone-resorptive volume ratio, defined as the ratio of all bone-resorptive cross-sectional areas to all femoral head cross-sectional areas in all seven slices, was calculated. Associations between total bone-resorptive volume ratio and sex, age, ONFH-associated factors, patient workload levels, ONFH stage, ONFH type, necrotic volume on magnetic resonance imaging, and duration from the onset of pain to surgery were analyzed. Lesion location and the association between bone-resorptive lesion and collapse were also evaluated. Results The mean total bone-resorptive volume ratio was 7.0 ± 6.0%, which varied significantly by ONFH stage (ARCO collapse quantitation 3A, 3.5 ± 2.1%; 3B, 6.8 ± 3.0%; and 3 C, 13.6 ± 8.8%). ONFH stage was independently associated with total bone-resorptive volume ratio (P < 0.05). Furthermore, high bone-resorptive volume ratios were found in the anterior femoral head and were associated with collapse. Conclusions This study demonstrated that bone-resorptive volume in post-collapse ONFH was significantly associated with the disease stage, which was more widespread in the anterior portion of the femoral head than in the posterior portion..
25. Nobuaki Tsukamoto, Takao Mae, Akihisa Yamashita, Takahiro Hamada, Tatsuhiko Miura, Takahiro Iguchi, Masami Tokunaga, Toshihiro Onizuka, Kenta Momii, Eiji Sadashima, Yasuharu Nakashima, Refracture of pediatric both-bone diaphyseal forearm fracture following intramedullary fixation with Kirschner wires is likely to occur in the presence of immature radiographic healing, European Journal of Orthopaedic Surgery and Traumatology, 10.1007/s00590-020-02689-0, 2020.01, Purpose: Refracture of pediatric both-bone diaphyseal forearm fractures (PBDFFs) may occur, even if the fractures are treated with intramedullary nailing. The purpose of this study was to investigate the risk of refracture of PBDFFs treated with intramedullary Kirschner wires (K-wires), which are commonly used in our clinic. Methods: The present multicenter retrospective study included 60 consecutive patients with 60 PBDFFs who were treated with intramedullary K-wires at 5 hospitals between 2007 and 2016. The age of the patients at the time of the primary fracture ranged from 2 to 15 years. The characteristics of the primary fractures and treatment course were evaluated. Results: Refracture occurred in 6 patients (10.0%). Three of the patients were young girls; the other 3 were adolescent boys. Refractures were caused by falling or during sports activity. The duration from primary fracture to refracture ranged from 46 to 277 days, and in 5 of the 6 patients refractures occurred within 6 months. Although we were unable to identify factors significantly contributing to refracture (e.g. fracture type or treatment procedures), radiographs at the latest visit before refracture demonstrated findings of immature healing in five of six patients. Both K-wires and external immobilization had been removed before complete fracture healing in a large proportion of patients with refracture (80.0%). Conclusions: Refracture of PBDFF may occur several months after treatment with intramedullary K-wires if the primary fracture shows immature healing. Physicians should pay special attention when judging radiographic fracture healing, even when the fracture is deemed to have clinically healed..
26. Masato Yoshimoto, Yuichi Yamada, Shin Ishihara, Kenichi Kohashi, Yu Toda, Yoshihiro Ito, Yosuke Susuki, Izumi Kinoshita, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda, Retroperitoneal Myxofibrosarcoma
A Controversial Entity
, Pathology Research and Practice, 10.1016/j.prp.2020.152969, 2020.01.
27. Yuta Sakemi, Koichiro Hayashi, Akira Tsuchiya, Yasuharu Nakashima, Kunio Ishikawa, Fabrication and histological evaluation of porous carbonate apatite block from gypsum block containing spherical phenol resin as a porogen, Materials, 10.3390/ma12233997, 2019.12, The utility of carbonate apatite (CO3Ap) as a bone substitute has been demonstrated. The feasibility of fabricating macroporous CO3Ap was evaluated through a two-step dissolution-precipitation reaction using gypsum as the precursor and spherical phenol resin as the porogen. Porogen-containing gypsum was heated to burn out the porogen and to fabricate macroporous structures. Gypsum transformed into CaCO3 upon immersion in a sodium carbonate solution, while maintaining its macroporous structure. Next, CaCO3 transformed into CO3Ap upon immersion in a Na2HPO4 solution while maintaining its macroporous structure. The utility of the macroporous CO3Ap for histologically reconstructing bone defects was evaluated in rabbit femurs. After 4 weeks, a much larger bone was formed inside the macroporous CO3Ap than that inside non-macroporous CO3Ap and macroporous hydroxyapatite (HAp). A larger amount of bone was observed inside non-macroporous CO3Ap than inside macroporous HAp. The bone defects were completely reconstructed within 12 weeks using macroporous CO3Ap. In conclusion, macroporous CO3Ap has good potential as an ideal bone substitute..
28. Yoshitaka Nakanishi, Takamitsu Okada, Naohide Takeuchi, Naoya Kozono, Takahiro Senju, Koichi Nakayama, Yasuharu Nakashima, Histological evaluation of tendon formation using a scaffold-free three-dimensional-bioprinted construct of human dermal fibroblasts under in vitro static tensile culture, Regenerative Therapy, 10.1016/j.reth.2019.02.002, 2019.12, Introduction: Tendon tissue engineering requires scaffold-free techniques for safe and long-term clinical applications and to explore alternative cell sources to tenocytes. Therefore, we histologically assessed tendon formation in a scaffold-free Bio-three-dimensional (3D)construct developed from normal human dermal fibroblasts (NHDFs)using our Bio-3D printer system under tensile culture in vitro. Methods: Scaffold-free ring-like tissues were constructed from 120 multicellular spheroids comprising NHDFs using a bio-3D printer. Ring-like tissues were cultured in vitro under static tensile-loading with or without in-house tensile devices (tension-loaded and tension-free groups), with increases in tensile strength applied weekly to the tensile-loaded group. After a 4 or 8-week culture on the device, we evaluated histological findings according to tendon-maturing score and immunohistological findings of the middle portion of the tissues for both groups (n = 4, respectively). Results: Histology of the tension-loaded group revealed longitudinally aligned collagen fibers with increased collagen deposition and spindle-shaped cells with prolonged culture. By contrast, the tension-free group showed no organized cell arrangement or collagen fiber structure. Additionally, the tension-loaded group showed a significantly improved tendon-maturing score as compared with that for the tension-free group at week 8. Moreover, immunohistochemistry revealed tenascin C distribution with a parallel arrangement in the tensile-loading direction at week 8 in the tension-loaded group, which exhibited stronger scleraxis-staining intensity than that observed in the tension-free group at weeks 4 and 8. Conclusions: The NHDF-generated scaffold-free Bio-3D construct underwent remodeling and formed tendon-like structures under tensile culture in vitro..
29. Yoshihiro Matsumoto, Akira Matsunobu, Kenichi Kawaguchi, Mistumasa Hayashida, Keiichiro Iida, Hirokazu Saiwai, Seiji Okada, Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Shingo Baba, Satoshi Nomoto, Yasuharu Nakashima, Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas, International Journal of Clinical Oncology, 10.1007/s10147-019-01505-y, 2019.11, Purpose: To evaluate the clinical outcome of combination of carbon-ion radiotherapy with separation surgery (CIRT-SS) in patients with primary spinal/paraspinal sarcoma (PSPS) and epidural spinal cord compression (ESCC). Methods: CIRT-SS was performed in 11 consecutive patients. Patients treated in the primary and salvage settings were categorized into Group A (n = 8) and Group B (n = 3), respectively. Clinical results and imaging findings were collected, with a particular focus on ESCC grade, treatment-associated adverse events (AEs), and the locoregional control (LRC) rate and overall survival (OS). Results: The median follow-up period from the start of CIRT-SS was 25 months (7–57 months). ESCC was improved by SS in all cases. No patients exhibited radiation-induced myelopathy (RIM), but three developed Grade 3 vertebral compression fracture (VCF) during follow-up. Locoregional recurrences were observed in four patients [Group A: 1 (12.5%), Group B: 3 (100%)]. Over the entire follow-up period, three patients developed distant metastases and two patients died. The 2-year LRC rate and OS were 70% and 80%, respectively. Conclusion: CIRT-SS in the primary setting achieved acceptable LRC and OS without RIM in patients with PSPS and with ESCC. VCF was the most frequent AE associated with CIRT-SS..
30. Tetsuro Ushio, Ken Okazaki, Kanji Osaki, Yukihisa Takayama, Koji Sagiyama, Hideki Mizu-uchi, Satoshi Hamai, Yukio Akasaki, Hiroshi Honda, Yasuharu Nakashima, Degenerative changes in cartilage likely occur in the medial compartment after anterior cruciate ligament reconstruction, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-019-05468-5, 2019.11, Purpose: Magnetic resonance imaging with T1ρ mapping is used to quantify the amount of glycosaminoglycan in articular cartilage, which reflects early degenerative changes. The purposes of this study were to evaluate early degenerative changes in knees after anterior cruciate ligament (ACL) reconstruction by comparing T1ρ values before and 2 years after surgery and investigate whether surgical factors and clinical outcomes are related to differences in T1ρ values. Methods: Fifty patients who underwent unilateral primary ACL reconstruction were evaluated using T1ρ mapping before and 2 years after surgery. Three regions of interest (ROIs) were defined in the cartilage associated with the medial (M) and lateral (L) weight-bearing areas of the femoral condyle (FC) (anterior: MFC1 and LFC1, middle: MFC2 and LFC2, and posterior: MFC3 and LFC3). Two ROIs associated with the tibial plateau (T) were defined (anterior: MT1 and LT1, and posterior: MT2 and LT2). T1ρ values within the ROIs were measured before and 2 years after surgery and compared using the paired t test. Correlations between the difference in T1ρ values at these two time points and patient characteristics, presence of a cartilaginous lesion, graft type, and postoperative anteroposterior laxity were also evaluated using Pearson’s and Spearman’s correlation coefficients. Results: There was a significant increase in T1ρ before versus 2 years after surgery in the MT1, MT2, LFC1, and LT1 areas, and a significant decrease in the LFC3 and LT2 areas. There was a significant correlation between postoperative anterior-posterior laxity and a postoperative increase in T1ρ values in the MFC3 (r = 0.37, P = 0.013) and MT2 (r = 0.35, P = 0.021) areas. Increases in T1ρ values in the MFC2 area were negatively correlated with KOOS symptoms (ρ = − 0.349, P = 0.027) and quality of life (ρ = − 0.374, P = 0.017) subscale scores. Conclusion: Early degenerative changes in medial articular cartilage were observed with T1ρ mapping at 2 years after ACL reconstruction. Postoperative anterior-posterior laxity is correlated with an increase in T1ρ values in the posteromedial femur and tibia. An increase in T1ρ values in the central medial femoral condyle was associated with knee symptoms. Level of evidence: III..
31. Tetsuya Tachibana, Masanori Fujii, Kenji Kitamura, Tetsuro Nakamura, Yasuharu Nakashima, Does Acetabular Coverage Vary between the Supine and Standing Positions in Patients with Hip Dysplasia?, Clinical orthopaedics and related research, 10.1097/CORR.0000000000000898, 2019.11, BackgroundAlthough variation in physiologic pelvic tilt may affect acetabular version and coverage, postural change in pelvic tilt in patients with hip dysplasia who are candidates for hip preservation surgery has not been well characterized, and its clinical importance is unknown.Questions/purposesThe aim of this study was to determine (1) postural changes in sagittal pelvic tilt between the supine and standing positions; (2) postural changes in the acetabular orientation and coverage of the femoral head between the supine and standing positions; and (3) patient demographic and morphologic factors associated with sagittal pelvic tilt.MethodsBetween 2009 and 2016, 102 patients underwent pelvic osteotomy to treat hip dysplasia. All patients had supine and standing AP pelvic radiographs and pelvic CT images taken during their preoperative examination. Ninety-five patients with hip dysplasia (lateral center-edge angle < 20°) younger than 60 years old were included. Patients with advanced osteoarthritis, other hip disease, prior hip or spine surgery, femoral head deformity, or inadequate imaging were excluded. Sixty-five patients (64%) were eligible for participation in this retrospective study. Two board-certified orthopaedic surgeons (TT and MF) investigated sagittal pelvic tilt, spinopelvic parameters, and acetabular version and coverage using pelvic radiographs and CT images. Intra- and interobserver reliabilities, evaluated using the intraclass correlation coefficient (0.90 to 0.98, 0.93 to 0.99, and 0.87 to 0.96, respectively), were excellent. Demographic data (age, gender, and BMI) were collected by medical record review. Sagittal pelvic tilt was quantified as the angle formed by the anterior pelvic plane and a z-axis (anterior pelvic plane angle). Using a 2D-3D matching technique, we measured the change in sagittal pelvic tilt, acetabular version, and three-dimensional coverage between the supine and standing positions. We correlated sagittal pelvic tilt with demographic and CT measurement parameters using Pearson's or Spearman's correlation coefficients.ResultsAlthough functional pelvic tilt varied widely among individuals, the pelvis of patients with hip dysplasia tilted posteriorly from the supine to the standing position (mean APP angle 8° ± 6° versus 2° ± 7°; mean difference -6°; 95% CI, -7° to -5°; range -17° to 4.1°; p < 0.001; paired t-test).The pelvis tilted more than 5° posteriorly from the supine to the standing position in 39 patients (60%), and the change was greater than 10° in 12 (18%). In the latter subgroup of patients, the mean acetabular anteversion angle increased (22° ± 5° versus 27° ±5°; mean difference 5°; 95% CI, 4°-6°; p < 0.001) and the mean anterosuperior acetabular sector angle notably deceased from the supine to the standing position (91° ± 11° versus 77° ± 14°; mean difference -14°; 95% CI, -17° to -11°; p < 0.001; paired t-test). Postural change in pelvic tilt was not associated with any of the studied demographic or morphologic parameters, including patient age, gender, BMI, and acetabular version and coverage.ConclusionsOn average, the pelvis tilted posteriorly from the supine to the standing position in patients with hip dysplasia, resulting in increased acetabular version and decreased anterosuperior acetabular coverage in the standing position. Thus, assessment with a supine AP pelvic radiograph may overlook changes in acetabular version and coverage in weightbearing positions. We recommend assessing postural change in sagittal pelvic tilt when diagnosing hip dysplasia and planning hip preservation surgery. Further studies are needed to determine how postural changes in sagittal pelvic tilt affect the biomechanical environment of the hip and the clinical results of acetabular reorientation osteotomy. Level of EvidenceLevel IV, diagnostic study..
32. Ichiro Kurakazu, Yukio Akasaki, Mitsumasa Hayashida, Hidetoshi Tsushima, Norio Goto, Takuya Sueishi, Masakazu Toya, Masanari Kuwahara, Ken Okazaki, Tomas Duffy, Martin K. Lotz, Yasuharu Nakashima, FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor β1 signaling, Journal of Biological Chemistry, 10.1074/jbc.RA119.009409, 2019.11, The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor β1 (TGFβ1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFβ1/ SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sexdetermining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFβ1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9. To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNAby TGFβ1, andFOXO1bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cellcycle arrest during chondrogenic differentiation via TGFβ1 signaling..
33. Satoshi Baba, Yoshihiro Matsumoto, Kenichi Kawaguchi, Keiichiro Iida, Hirokazu Saiwai, Seiji Okada, Akira Matsunobu, Yoshiyuki Shioyama, Yasuharu Nakashima, Post-carbon-ion radiotherapy vertebral pathological fractures in upper cervical primary malignant spinal tumors treated by occipito-cervical fusion, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-019-03183-x, 2019.11, Purpose: To describe the characteristic features of post-carbon-ion radiotherapy (CIRT) vertebral pathological fractures (VPFs) in upper cervical primary malignant spinal tumors (PMSTs) treated by occipito-cervical (OC) fusion. Methods: OC fusion was performed for three consecutive patients with post-CIRT VPFs. The clinical results and imaging findings, including bone single-photon emission computed tomography (SPECT)/CT were prospectively collected. Results: No surgery-related wound complication and surgical site infection were noted. One patient experienced re-fracture and displacement of dens with the loosening of occipital screws and was treated by posterior revision surgery. At the final follow-up, all patients were alive without evidence of disease, and the solid OC fusion was confirmed. Bone SPECT/CT clearly revealed the effect of CIRT on bone turnover in the irradiated field. Conclusion: The OC fusion with autologous bone grafts was a reliable option for the treatment of post-CIRT VPCs in the patients with upper cervical PMSTs. In addition, evaluation of the bone turnover at the irradiated field by bone SPECT/CT would help surgeons select an effective plan of care, such as fusion level and postoperative care..
34. Takahiro Senju, Takamitsu Okada, Naohide Takeuchi, N. Kozono, Yoshitaka Nakanishi, Hidehiko Higaki, Takeshi Shimoto, Yasuharu Nakashima, Biomechanical analysis of four different medial row configurations of suture bridge rotator cuff repair, Clinical Biomechanics, 10.1016/j.clinbiomech.2019.07.015, 2019.10, Background: Rotator cuff tendon rupture after suture bridge repair occasionally occurs at the medial row, with remnant tendon tissue remaining at the footprint. While concentrated medial row stress is suspected to be involved in such tears, the optimal suture bridge technique remains controversial. Methods: This study aimed to investigate the construct strength provided by suture bridge techniques having four different medial row configurations using artificial materials (n = 10 per group): Group 1, four-hole (two stitches per hole) knotless suture bridge; Group 2, eight-hole (one stitch per hole) parallel knotless suture bridge; Group 3, eight-hole non-parallel knotless suture bridge; and Group 4, eight-hole knot-tying suture bridge. Each construct underwent cyclic loading from 5 to 30 N for 20 cycles, followed by tensile testing to failure. The ultimate failure load and linear stiffness were measured. Findings: Group 2 had the highest ultimate failure load (mean 160.54 N, SD 6.40) [Group 4 (mean 150.21 N, SD 9.76, p = 0.0138), Group 3 (mean 138.80 N, SD 7.18, p < 0.0001), and Group 1 (mean 129.35 N, SD 4.25, p < 0.0001)]. The linear stiffness of Group 2 (mean 9.32 N/mm, SD 0.25) and Group 4 (mean 9.72 N/mm, SD 0.40) was significantly higher (p = 0.0032) than that of Group 1 (mean 8.44 N/mm, SD 0.29) and Group 3 (mean 8.61 N/mm, SD 0.31). Interpretation: In conclusion, increasing the number of suture-passed holes, arranging the holes in parallel, and a knotless technique improved the failure load following suture bridge repair..
35. Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Itou, Yutaka Koga, Mikiko Hashisako, Yui Nozaki, Daisuke Kiyozawa, Daichi Kitahara, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Yoshifumi Matsushita, Fumiyoshi Fushimi, Kenichi Taguchi, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, Toru Iwaki, Yoshinao Oda, Clinicopathological review of solitary fibrous tumors
dedifferentiation is a major cause of patient death
, Virchows Archiv, 10.1007/s00428-019-02622-9, 2019.10, Solitary fibrous tumor (SFT) is a soft-tissue neoplasm of intermediate malignant potential, presenting a wide histopathological spectrum. Poorer prognosis of hemangiopericytoma of the central nervous system (CNS), hypoglycemic SFT, and dedifferentiation are well-known characters of SFT, but their clinical significance were not demonstrated enough by large-sized study. Here, the clinicopathological features of SFTs are reviewed and the relationship between genetics and clinicopathological features is examined using 145 SFT cases. All cases were STAT6 IHC-positive and/or NAB2-STAT6 fusion gene-positive. Tumor location was classified into three categories: 30 pleuropulmonary, 96 non-pleuropulmonary/non-central nervous system (CNS), and 18 CNS tumors. The tumor developed recurrence in 21 of 93 available cases (22.5%), metastasis in 11 of 93 (11.8%), and tumor death in 9 of 93 (9.6%). Hypoglycemia occurred in 2 primary tumors and 1 metastatic tumor among 63 reviewable cases, and dedifferentiation occurred in 10 cases (6.8%) including 6 primary tumors, 2 recurrent tumors, and 2 metastatic tumors. Recurrence was positively associated with CNS location (p = 0.0109) and hypoglycemia (p = 0.001); metastasis was positively associated with CNS location (p = 0.0231), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001), while metastasis was negatively correlated with pleural location (p = 0.0471). Tumor death was positively associated with male sex (p = 0.0154), larger size (p = 0.0455), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001). Multivariate analysis revealed independent statistical significance of dedifferentiation for overall survival (p = 0.0467). Exon variant of the fusion gene had no statistical correlation with clinical outcome. In conclusion, dedifferentiation is a major prognostic factor of SFT, and specific location such as cerebromeningeal and intra-abdominal site and hypoglycemia also had a high risk for unfavorable prognosis..
36. Jun ichi Fukushi, Hidetoshi Tsushima, Yoshihiro Matsumoto, Chikage Mitoma, Masutaka Furue, Hisaaki Miyahara, Yasuharu Nakashima, Influence of dioxin-related compounds on physical function in Yusho incident victims, Heliyon, 10.1016/j.heliyon.2019.e02702, 2019.10, Purpose: Few studies have examined the influence of dioxin-related compounds on human physical function, and existing results are inconsistent. In 1968, accidental human exposure to rice oil contaminated with dioxin-related compounds resulted in the development of Yusho oil disease in Japan. We aimed to determine whether the degree of exposure to dioxin-related compounds was associated with physical function in Yusho patients. Methods: In 2016, 65 men (average age: 65.7 years) and 77 women (average age: 64.7 years) participated in a nationwide health examination in Fukuoka prefecture. Functional reach, gait speed, hand grip strength, and toe grip strength were evaluated as part of physical function. The serum levels of polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls were measured using high-resolution gas chromatography and high-resolution mass spectrometry. We examined the association between physical function tests and serum toxic equivalency (TEQ) values. Results: A 10-fold increase in serum TEQ levels was negatively associated with functional reach (adjusted b = -4.07, p = 0.017) and hand grip strength (adjusted b = -2.20, p = 0.0245) in men. No association was observed between serum TEQ level and physical function in women. Conclusion: Our findings suggest that dioxin-related compounds have a negative influence on physical function in men. However, these findings should be interpreted carefully. Future studies examining additional data on musculoskeletal disorders are warranted..
37. Makoto Nakagawa, Fumihiko Nakatani, Hironori Matsunaga, Takahiko Seki, Makoto Endo, Yoko Ogawara, Yukino Machida, Takuo Katsumoto, Kazutsune Yamagata, Ayuna Hattori, Shuhei Fujita, Yukiko Aikawa, Takamasa Ishikawa, Tomoyoshi Soga, Akira Kawai, Hirokazu Chuman, Nobuhiko Yokoyama, Suguru Fukushima, Kenichiro Yahiro, Atsushi Kimura, Eijiro Shimada, Takeshi Hirose, Toshifumi Fujiwara, Nokitaka Setsu, Yoshihiro Matsumoto, Yukihide Iwamoto, Yasuharu Nakashima, Issay Kitabayashi, Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma, Oncogene, 10.1038/s41388-019-0929-9, 2019.10, Chondrosarcoma is the second most common malignant bone tumor. It is characterized by low vascularity and an abundant extracellular matrix, which confer these tumors resistance to chemotherapy and radiotherapy. There are currently no effective treatment options for relapsed or dedifferentiated chondrosarcoma, and new targeted therapies need to be identified. Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Mutant IDH inhibitors are therefore potential novel anticancer drugs in IDH mutant tumors. Here, we examined the efficacy of the inhibition of mutant IDH1 as an antitumor approach in chondrosarcoma cells in vitro and in vivo, and investigated the association between the IDH mutation and chondrosarcoma cells. DS-1001b, a novel, orally bioavailable, selective mutant IDH1 inhibitor, impaired the proliferation of chondrosarcoma cells with IDH1 mutations in vitro and in vivo, and decreased 2-HG levels. RNA-seq analysis showed that inhibition of mutant IDH1 promoted chondrocyte differentiation in the conventional chondrosarcoma L835 cell line and caused cell cycle arrest in the dedifferentiated JJ012 cell line. Mutant IDH1-mediated modulation of SOX9 and CDKN1C expression regulated chondrosarcoma tumor progression, and DS-1001b upregulated the expression of these genes via a common mechanism involving the demethylation of H3K9me3. DS-1001b treatment reversed the epigenetic changes caused by aberrant histone modifications. The present data strongly suggest that inhibition of mutant IDH1 is a promising therapeutic approach in chondrosarcoma, particularly for the treatment of relapsed or dedifferentiated chondrosarcoma..
38. Keisuke Komiyama, Jun ichi Fukushi, Goro Motomura, Satoshi Hamai, Satoshi Ikemura, Masanori Fujii, Yasuharu Nakashima, Does high hip centre affect dislocation after total hip arthroplasty for developmental dysplasia of the hip?, International Orthopaedics, 10.1007/s00264-018-4154-x, 2019.09, Background: To achieve sufficient socket coverage by the native bone, high placement of cementless acetabular cup is often required. We previously reported, using computer simulation, that higher hip centre improved the bone coverage but decreased the range of motion in total hip arthroplasty (THA) for patients with hip dysplasia. However, in a clinical setting, the correlation between the hip centre height and dislocation after primary THA is still unclear. We examined whether a high hip centre affects dislocation after THA. Methods: A total of 910 patients, with 1079 dysplastic hips, who underwent primary THA were retrospectively reviewed. The age at THA averaged 63.0 years and mean follow-up was 74.3 months. Vertical centre of rotation (V-COR) was defined as the distance from the head centre to the interteardrop line. Uni- and multivariate logistic regression models were applied to identify significant factors affecting dislocation. Results: Ten hips in nine patients (0.9%) had dislocation after THA. In univariate analysis, age at surgery and V-COR were significant risk factors for dislocation. Multivariate analysis identified advanced age at operation (odds ratio [OR] 1.8/5 years), Crowe classification (OR 15.6), V-COR (OR 3.1/5 mm), and femoral head size (OR 11.6) as independent risk factors for dislocation. Receiver operating characteristic curve analysis revealed the cutoff value of the V-COR for dislocation as 23.9 mm. Conclusions: A higher hip centre with the V-COR > 23.9 mm affected dislocation after THA for DDH. Our results would be useful for reconstruction of the hip centre, particularly with cementless acetabular cups..
39. Umito Kuwashima, Ken Okazaki, Kenyu Iwasaki, Yukio Akasaki, Hideya Kawamura, Hideki Mizu-uchi, Satoshi Hamai, Yasuharu Nakashima, Patient reported outcomes after high tibial osteotomy show comparable results at different ages in the mid-term to long-term follow-up, Journal of Orthopaedic Science, 10.1016/j.jos.2018.12.022, 2019.09, Background: Few studies have evaluated the impact of age on patient-reported outcomes in the long-term follow-up after high tibial valgus osteotomy (HTO). The purpose of this study is to assess the association between age at surgery and patient-reported clinical outcomes in the mid-term to long-term follow-up of HTO. Materials and methods: We mailed the 2011 Knee Society score (KSS) questionnaires to 234 consecutive patients (295 knees) who had undergone closing-wedge HTO, and 158 patients (202 knees, 68.5%) returned a completed questionnaire. The cohort was divided into two groups depending on the age at the time of surgery, and pairs matched the follow-up period and sex was created. The mean follow-up period was approximately 12 years. KSS scores at the final follow-up were compared between two groups using the Student t test and chi-square test, and the survival rates were calculated using Kaplan–Meier survival curves. Results: The symptom, satisfaction, and expectation scores were not significantly different between the ≤64-year-old patients and ≥65-year-old patients. The functional activities score was significantly lower in older patients than in younger patients. The overall survival rates of HTO were 99.1 ± 0.4% at 5 years, 94.4 ± 1.2% at 10 years, and 84.6 ± 2.7% at 15 years. There was no significant difference in the survival rate after HTO between the two groups divided by the age (p = 0.602). Conclusions: Pain relief and satisfaction after HTO in older patients were comparable to those in younger patients in the mid-term to long-term follow-up, although the functional activity was affected by age..
40. Atsushi Kimura, Yoshihiro Matsumoto, Yoshifumi Wakata, Akiko Oyamada, Masanobu Ohishi, Toshifumi Fujiwara, Ko Ikuta, Kuniyoshi Tsuchiya, Naohisa Tayama, Shinji Tomari, Hisaaki Miyahara, Takao Mae, Toshihiko Hara, Taichi Saito, Takeshi Arizono, Kozo Kaji, Taro Mawatari, Masami Fujiwara, Riku Sakimura, Kunichika Shin, Kenichi Ninomiya, Kazutoshi Nakaie, Yasuaki Antoku, Shoji Tokunaga, Naoki Nakashima, Yukihide Iwamoto, Yasuharu Nakashima, Predictive factors of mortality of patients with fragility hip fractures at 1 year after discharge
A multicenter, retrospective study in the northern Kyushu district of Japan
, Journal of Orthopaedic Surgery, 10.1177/2309499019866965, 2019.09, Purpose: Fragility hip fractures (FHFs) are associated with a high risk of mortality, but the relative contribution of various factors remains controversial. This study aimed to evaluate predictive factors of mortality at 1 year after discharge in Japan. Methods: A total of 497 patients aged 60 years or older who sustained FHFs during follow-up were included in this study. Expected variables were finally assessed using multivariable Cox proportional hazards models. Results: The 1-year mortality rate was 9.1% (95% confidence interval: 6.8–12.0%, n = 45). Log-rank test revealed that previous fractures (p = 0.003), Barthel index (BI) at discharge (p = 0.011), and place-to-discharge (p = 0.004) were significantly associated with mortality for male patients. Meanwhile, body mass index (BMI; p = 0.023), total Charlson comorbidity index (TCCI; p = 0.005), smoking (p = 0.007), length of hospital stay (LOS; p = 0.009), and BI (p = 0.004) were the counterparts for females. By multivariate analyses, previous vertebral fractures (hazard ratio (HR) 3.33; p = 0.044), and BI <30 (HR 5.42, p = 0.013) were the predictive variables of mortality for male patients. BMI <18.5 kg/m2 (HR 2.70, p = 0.023), TCCI ≥5 (HR 2.61, p = 0.032), smoking history (HR 3.59, p = 0.018), LOS <14 days (HR 13.9; p = 0.007), and BI <30 (HR 2.76; p = 0.049) were the counterparts for females. Conclusions: Previous vertebral fractures and BI <30 were the predictive variables of mortality for male patients, and BMI <18.5 kg/m2, TCCI ≥5, smoking history, LOS <14 days, and BI <30 were those for females. Decreased BI is one of the independent and preventable risk factors. A comprehensive therapeutic approach should be considered to prevent deterioration of activities of daily living and a higher risk of mortality..
41. Norio Goto, Ken Okazaki, Takenori Akiyama, Yukio Akasaki, Hideki Mizu-uchi, Satoshi Hamai, Shunsuke Nakamura, Yasuharu Nakashima, Alignment factors affecting the medial meniscus extrusion increases the risk of osteoarthritis development, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-018-5286-7, 2019.08, Purpose: Varus alignment is known as one of the major causes of medial compartment osteoarthritis (OA). Medial meniscus extrusion also plays a critical role in the in the development of OA. However, studies on the exact relationship between alignment parameters and medial meniscus extrusion are limited. Therefore, this study aimed to investigate this relationship in patients with knee OA. Methods: Based on a retrospective analysis of the outpatient magnetic resonance imaging (MRI) database, 190 knees were identified to be examined using weight-bearing, whole-leg radiographs and MRIs within 3 months from the first consultation. Subsequently, various parameters of lower leg alignment were measured, which affected the knee varus in radiographs. Finally, a statistical analysis was performed to assess the relationships between the OA grade, distance of medial meniscus extrusion (MME), and alignment parameters; hip–knee–ankle angle (HKAA), percentage of mechanical axis (% MA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA). The subjects were divided according to the presence or absence of MME (Group A: MME distance below 3 mm, Group B: MME distance 3 mm and above) to assess the differences in each alignment parameter correlated with MME distance between the groups. Results: MME distance significantly increased with OA grade progression. HKAA, % MA, MPTA, and JLCA significantly correlated with medial meniscus extrusion distance (r = − 0.21, − 0.23, − 0.16, 0.3, respectively). Multiple regression analysis of each significant alignment combined with age, sex, and body mass index revealed that HKAA, % MA, MPTA, and JLCA were significant independent factors of MME distance (P = 0.008, 0.0026, 0.011, 0.0001, respectively). These significant findings were reinforced in group B. In contrast, the correlation between alignment parameters and medial meniscus extrusion distance was not significant in group A. Conclusion: Varus alignment factors are related to MME distance especially in extruded meniscus knees, as the OA grade progressed. Therefore, the coexistence of varus alignment and MME can be the risk factors for OA progression. As the low MPTA was an independent alignment factor for generating varus alignment, patients with osteoarthritis of the knee with both, low MPTA and MME could be the appropriate candidates for early intervention by high tibial osteotomy. Level of evidence: III..
42. Masato Kiyohara, Satoshi Hamai, Daisuke Hara, Daisuke Fujiyoshi, Satoru Harada, Kenichi Kawaguchi, Yasuharu Nakashima, Do component position and muscle strength affect the cup-head translation during gait after total hip arthroplasty?, European Journal of Orthopaedic Surgery and Traumatology, 10.1007/s00590-019-02443-1, 2019.08, Introduction: This study examined whether the component position or muscle strength affects the cup-head translation under in vivo weight-bearing conditions after total hip arthroplasty (THA). We hypothesized that there was a correlation between the hip offset or abductor strength and cup-head translation during gait. Materials and methods: We prospectively evaluated 31 patients undergoing unilateral cementless primary THA. The cup height, cup/stem offset, and limb length discrepancy were measured on anterior–posterior bilateral hip radiographic images. The isometric muscle strength of the lower limbs was quantified using a handheld dynamometer. Continuous radiographic images were recorded during gait, and cup-head translation was analysed using a computer-assisted method. Results: The average cup height, cup/stem offset, and limb length discrepancy were − 3.8 ± 5.1 mm, 1.2 ± 5.2 mm/− 0.7 ± 7.7 mm, and − 2.1 ± 5.2 mm, respectively. The average hip abductor/flexor and knee extensor strength were 86% ± 18%/85% ± 17% and 88% ± 17% of the contralateral healthy hip, respectively. The average cup-head translation during swing phase of gait was − 0.003 ± 0.31 mm. Multiple regression analyses found no significant independent predictors of cup-head translation (p > 0.05). Conclusions: The component position or muscle strength did not significantly influence cup-head translation during gait after well-positioned primary THA..
43. Keisuke Komiyama, Satoshi Hamai, Satoru Ikebe, Kensei Yoshimoto, Hidehiko Higaki, Kyohei Shiomoto, Hirotaka Gondo, Daisuke Hara, Yifeng Wang, Yasuharu Nakashima, In vivo kinematic analysis of replaced hip during stationary cycling and computer simulation of optimal cup positioning against prosthetic impingement, Clinical Biomechanics, 10.1016/j.clinbiomech.2019.05.035, 2019.08, Background: Dynamic hip kinematics during stationary cycling after total hip arthroplasty (THA) have been unclear. Furthermore, no computer simulation of optimal cup position based on in vivo kinematics has yet been assessed. Methods: This study consisted of 7 patients who underwent unilateral primary THA for symptomatic osteoarthritis. Using a flat-panel X-ray detector, continuous radiographs were obtained during stationary cycling. We analyzed the three-dimensional replaced hip kinematics from the top to the bottom position of the crank using image-matching techniques and quantified minimum liner-to-stem neck distance. Simulation analyses with in vivo kinematics were performed to examine patient-specific optimal cup placement against prosthetic impingement. Findings: During stationary cycling, pelvis showed 27.1° of posterior tilt on average without significant change. Hip flexed by 59.4° and 19.3° on average at the top and bottom positions, respectively. Minimum liner-to-neck distance was 8.8 mm on average at the bottom position. Liner-to-neck, bone-to-bone, or bone-to-component impingement was not observed at any positions in any hips. Simulation analysis of cup placement showed that larger cup anteversion, inclination, and use of elevated liner significantly decreased the minimum distance between posterior liner and stem neck. Cup anteversion of more than 30° with elevated liner could cause posterior liner-to-neck impingement at bottom position. Interpretation: Stationary cycling after THA provides no excessive hip range of motion or liner-to-neck contact. Cup placement and use of elevated liner significantly influence the minimum liner-to-neck distance, in some cases simulating posterior prosthetic impingement..
44. Kenta Momii, Satoshi Hamai, Goro Motomura, Kensuke Kubota, Masato Kiyohara, Takuaki Yamamoto, Yasuharu Nakashima, Revascularization of the necrotic femoral head after traumatic open anterior hip dislocation in a child
A case report
, Journal of Medical Case Reports, 10.1186/s13256-019-2192-7, 2019.08, Introduction: Avascular necrosis of the femoral capital epiphysis is the most serious complication after traumatic dislocation of the hip in children. This case report discusses the localization and revascularization of the necrotic femoral head following rarely experienced traumatic open anterior hip dislocation in children. Case presentation: Our patient was an 11-year-old Japanese boy who had open anterior hip dislocation sustained in a traffic accident. Reduction of the hip joint was performed in an emergency operation, and he was evaluated using serial gadolinium-enhanced magnetic resonance imaging. T1-weighted magnetic resonance images showed two bands with low signal intensity in the femoral capital epiphysis on coronal and oblique axial planes, indicating the existence of avascular osteonecrosis of the femoral head. We observed gadolinium enhancement in the central region of the epiphysis, where the area between the two bands with low signal intensity was located. Serial assessment with enhanced magnetic resonance images during a non-weight-bearing period of 1.5 years after injury showed revascularization starting from the central region and converging toward the peripheral region. Although the patient had leg-length discrepancy due to the early epiphyseal closure, non-weight-bearing treatment for the avascular osteonecrosis of the femoral head achieved a favorable outcome without any hip joint dysfunction, pain, or sign of secondary osteoarthritic change within 4.5 years after injury. Conclusion: We confirmed the revascularization process of the necrotic lesion in the femoral capital epiphysis in an 11-year-old boy using serial gadolinium-enhanced magnetic resonance imaging. Conservative non-weight-bearing treatment achieved a favorable outcome..
45. Hiroyuki Hatanaka, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Takeshi Utsunomiya, Shoji Baba, Yasuharu Nakashima, Volume of hip synovitis detected on contrast-enhanced magnetic resonance imaging is associated with disease severity after collapse in osteonecrosis of the femoral head, Skeletal Radiology, 10.1007/s00256-019-3158-y, 2019.08, Objective: To evaluate the relationship between the volume of hip synovitis detected on contrast-enhanced magnetic resonance imaging (MRI) and the disease stage of osteonecrosis of the femoral head (ONFH). Materials and methods: Sixty-three consecutive hips in 40 ONFH patients were reviewed using contrast-enhanced MRI. Ten unaffected hips in 10 patients with unilateral ONFH were used as controls. Based on the Japanese Investigation Committee system, these hips were classified according to stage and type. The volume and location of hip synovitis were semi-quantitatively measured on contrast-enhanced MRI. Clinicoradiological factors were statistically analyzed to determine the relationship with the volume of hip synovitis. Results: The mean synovial volume was significantly larger in ONFH hips (8,020 ± 6,900 mm3) than in controls (910 ± 1,320 mm3; p = 0.001). The area of synovitis in the anterior portion of the hip joint was double (mean: 2.17 ± 1.77) that in the posterior portion. The volume of synovitis was small in pre-collapse-stage hips (stage 1: 680 ± 690 mm3, stage 2: 1,460 ± 1,200 mm3), but significantly larger in post-collapse-stage hips (stage 3A: 7,820 ± 4,490 mm3, stage 3B: 13,850 ± 7,110 mm3; p < 0.001). Multiple regression analysis showed that disease stage was the only factor related to hip synovitis. Conclusions: Our study suggests that hip synovitis in ONFH might occur after femoral head collapse and worsen with collapse progression, mainly in the anterior portion..
46. Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Takeaki Ishii, Makoto Nakagawa, Kenichiro Yahiro, Atsushi Kimura, Eijiro Shimada, Yasuharu Nakashima, Yoshihiro Matsumoto, Diagnosis and Management of Subcutaneous Soft Tissue Sarcoma, Current Treatment Options in Oncology, 10.1007/s11864-019-0656-z, 2019.07, The proper diagnosis and treatment planning for subcutaneous soft tissue sarcoma is very important. Soft tissue tumors can occur anywhere in the body, but if they occur subcutaneously, patients can easily notice a subcutaneous soft tissue mass. Therefore, it is possible to determine through recording, the growth speed of the mass, which is often difficult to obtain with deep-situated soft tissue masses. Palpation can also provide information about the firmness and mobility of the mass. Thus, history taking and physical examinations are informative for subcutaneous soft tissue tumors, compared to tumors that occur deeply. Because subcutaneous soft tissue tumors are easily recognized, they are often resected, without sufficient imaging analyses or thorough treatment planning. An operation performed based on such an inadequate preoperative plan is called a “whoops surgery.” In the case of “whoops surgeries,” subsequent radical surgery is required to remove additional areas, including hematomas that result from the initial surgery, that require a wider range of resection and soft tissue reconstruction. Therefore, as with deep-seated soft tissue tumors, it is important to conduct careful imaging examinations and make appropriate preoperative plans for subcutaneous soft tissue tumors. Subcutaneous soft tissue sarcomas often show an invasive pattern, and such tumors require a more careful assessment to prevent local recurrence after surgery. During surgery, it is necessary to remove the entire infiltration area along the fascia. Sometimes, an adequately wide excision is necessary, which is considered the minimum necessary procedure to eradicate the lesion. As noted above, clinicians who see patients with subcutaneous soft tissue tumors are encouraged to have sufficient knowledge and experience regarding the diagnosis and treatment. This article is intended for all doctors who deal with subcutaneous soft tissue tumors and focuses on essential points regarding their diagnosis and management..
47. Toshifumi Fujiwara, Kenjiro Fujimura, Satoshi Hamai, Satoshi Kamura, Yasuharu Nakashima, Hisaaki Miyahara, Mid-term clinical outcome of constrained condylar knee prosthesis for patients with rheumatoid arthritis, Modern Rheumatology, 10.1080/14397595.2018.1486954, 2019.07, Objectives: This study retrospectively investigated the mid-term outcome of Legacy constrained condylar knee (LCCK) prosthesis in patients with rheumatoid arthritis (RA) having severe varus/valgus deformity, instability, and/or bone loss. Methods: Between January 2000 and December 2015, LCCK prostheses had been performed in 32 knees of 25 patients with RA, and 23 knees of 17 patients of the postoperative follow-up minimum 2 years were analyzed in this study (Primary: 14 knees, Revision: 9 knees). The average of follow-up duration was 6.9 ± 2.7 years, all were female, and the average of age and RA duration at the surgery was 59.0 ± 9.5 years and 26.6 ± 13.5 years, respectively. Clinical result was analyzed by Knee Society Score (KSS) knee and function at preoperative time and final visit. Imaging outcome was investigated by femoral tibial angle (FTA), four component alignment angles, and radiolucent line at pre-/postoperative time. Results: KSS knee/function scores and radiographic FTAs were improved after operation. Radiolucent lines around components were seen in 17 knees (73.9%), of which only one knee (4.3%) has shown aseptic loosening. The seven-year Kaplan-Meier survivorship analysis resulted in 91.7%. Conclusion: LCCK prosthesis in RA patients was achieved to the excellent mid-term clinical and radiographic result..
48. Shingo Yoshizaki, Ken Kijima, Masamitsu Hara, Takeyuki Saito, Tetsuya Tamaru, Masatake Tanaka, Dai Jiro Konno, Yasuharu Nakashima, Seiji Okada, Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury, Journal of neuroinflammation, 10.1186/s12974-019-1536-y, 2019.07, Background: Spinal cord injury (SCI) is a catastrophic trauma accompanied by intralesional bleeding and neuroinflammation. Recently, there is increasing interest in tranexamic acid (TXA), an anti-fibrinolytic drug, which can reduce the bleeding volume after physical trauma. However, the efficacy of TXA on the pathology of SCI remains unknown. Methods: After producing a contusion SCI at the thoracic level of mice, TXA was intraperitoneally administered and the bleeding volume in the lesion area was quantified. Tissue damage was evaluated by immunohistochemical and gene expression analyses. Since heme is one of the degraded products of red blood cells (RBCs) and damage-associated molecular pattern molecules (DAMPs), we examined the influence of heme on the pathology of SCI. Functional recovery was assessed using the open field motor score, a foot print analysis, a grid walk test, and a novel kinematic analysis system. Statistical analyses were performed using Wilcoxon's rank-sum test, Dunnett's test, and an ANOVA with the Tukey-Kramer post-hoc test. Results: After SCI, the intralesional bleeding volume was correlated with the heme content and the demyelinated area at the lesion site, which were significantly reduced by the administration of TXA. In the injured spinal cord, toll-like receptor 4 (TLR4), which is a DAMP receptor, was predominantly expressed in microglial cells. Heme stimulation increased TLR4 and tumor necrosis factor (TNF) expression levels in primary microglial cells in a dose-dependent manner. Similarly to the in vitro experiments, the injection of non-lysed RBCs had little pathological influence on the spinal cord, whereas the injection of lysed RBCs or heme solution significantly upregulated the TLR4 and TNF expression in microglial cells. In TXA-treated SCI mice, the decreased expressions of TLR4 and TNF were observed at the lesion sites, accompanied by a significant reduction in the number of apoptotic cells and better functional recovery in comparison to saline-treated control mice. Conclusion: The administration of TXA ameliorated the intralesional cytotoxicity both by reducing the intralesional bleeding volume and preventing heme induction of the TLR4/TNF axis in the SCI lesion. Our findings suggest that TXA treatment may be a therapeutic option for acute-phase SCI..
49. Yuan Ma, Hideki Mizu-uchi, Tetsuro Ushio, Satoshi Hamai, Yukio Akasaki, Koji Murakami, Yasuharu Nakashima, Bony landmarks with tibial cutting surface are useful to avoid rotational mismatch in total knee arthroplasty, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-018-5052-x, 2019.05, Purpose: The purpose of this study was to define various anteroposterior axes of the tibial component as references and to evaluate their accuracy and variability using virtual surgery. It was hypothesized that (1) Akagi’s Line could result in high accuracy and low variability in varus osteoarthritic knees; (2) anteroposterior axes defined by using the tibial bony cutting surface as a landmark might be good substitutes for Akagi’s Line; and (3) extra-articular bony landmarks might influence the variability of the anteroposterior axis. Methods: Three-dimensional bone models were reconstructed from the preoperative computed tomography data of 111 osteoarthritic knees with varus deformities. Seven different anteroposterior axes of the tibial component were defined: Akagi’s Line, Axis MED, Axis 1/6MED, Axis 1/3MED, Axis of Oval Shape, Axis of Anterior Crest, and Axis Second Metatarsus. The rotational mismatch angle was measured between the tibial anteroposterior axis and the line perpendicular to the transepicondylar axis projected on the cutting surface (positive value: external rotation of the tibial anteroposterior axis). Results: The average rotational mismatch angles (referring to the projected anatomical/surgical epicondylar axes) were − 2.7° ± 5.8°/1.0° ± 6.0° (Akagi’s Line), − 4.2° ± 7.7°/− 0.5° ± 7.8°, 2.9° ± 7.2°/6.6° ± 7.2°, 9.8° ± 7.0°/13.5° ± 6.8° (Axis MED, Axis 1/6MED, Axis 1/3MED), − 5.1° ± 7.9°/− 1.4° ± 7.8° (Axis of Oval Shape), and 19.3 ± 9.5°/23.0° ± 9.6°, − 2.0° ± 11.3°/1.7° ± 11.4° (Axis Anterior Crest, Axis Second Metatarsus), respectively. Conclusions: Akagi’s Line provided the best accuracy and least variability in varus osteoarthritic knees. Axis 1/6MED and Axis MED are good substitutes for Akagi’s Line due to the difficulty of identifying the attachment site of the posterior cruciate ligament after the proximal tibia has been cut. Extra-articular bony landmarks should not be used for alignment due to their high variability. This study will aid surgeons in choosing the proper anteroposterior axis of the tibial component to reduce rotational mismatch and thus achieve good clinical knee outcomes. Levels of evidence: III..
50. Kazu Kobayakawa, Yasuyuki Ohkawa, Shingo Yoshizaki, Tetsuya Tamaru, Takeyuki Saito, Ken Kijima, Kazuya Yokota, Masamitsu Hara, Kensuke Kubota, Yoshihiro Matsumoto, Katsumi Harimaya, Keiko Ozato, Takahiro Masuda, Makoto Tsuda, Tomohiko Tamura, Kazuhide Inoue, V. Reggie Edgerton, Yukihide Iwamoto, Yasuharu Nakashima, Seiji Okada, Macrophage centripetal migration drives spontaneous healing process after spinal cord injury, Science Advances, 10.1126/sciadv.aav5086, 2019.05, Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury..
51. Tetsuro Ushio, Hideki Mizu-uchi, Ken Okazaki, Kazuki Miyama, Yukio Akasaki, Yuan Ma, Yasuharu Nakashima, Medial soft tissue contracture does not always exist in varus osteoarthritis knees in total knee arthroplasty, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-018-5276-9, 2019.05, Purpose: To evaluate preoperative soft tissue balance for total knee arthroplasty (TKA), varus/valgus stress radiographs has been used in previous studies. While the joint line of femur and tibia is almost parallel in healthy and postoperative knees, osteoarthritis (OA) knees exhibit articular cartilage wear that causes the joint line tilting even in a non-stress condition. Therefore, the exact angle of the joint line might mislead to understand the joint laxity in OA knees. The purpose of this study was to evaluate soft tissue balance in varus OA knees using preoperative stress radiographs under three different constant loads, taking the articular cartilage wear into consideration. Methods: One hundred and eighteen varus-deformed OA knees in 102 patients were investigated before primary TKA. Preoperative knee radiographs were obtained in the anteroposterior view with no stress (defined as the neutral condition) and with varus and valgus stresses (5, 10, and 15 kg) in extension. Two different types of joint line angle (JLA), the absolute JLA (an exact angle of joint line) and the relative JLA (the absolute JLA minus the JLA in the neutral condition), were compared for the same load with the paired t test. Results: The absolute JLA was 7.9 ± 1.2°/− 1.5 ± 2.2° under varus/valgus 15 kg stress, 6.7 ± 2.4°/− 0.3 ± 2.1° under varus/valgus 10 kg stress, and 4.7 ± 2.4°/1.1 ± 2.2° under varus/valgus 5 kg stress. Significant differences in the numerical values of the absolute JLA were observed between varus and valgus stresses for each load. The neutral JLA was 3.2 ± 2.0°. The relative JLA was 4.8 ± 2.1°/− 4.7 ± 1.8° under varus/valgus 15 kg stress, 3.5 ± 2.0°/− 3.5 ± 1.8° under varus/valgus 10 kg stress, and 1.5 ± 1.9°/− 2.1 ± 1.8° under varus/valgus 5 kg stress. No significant differences in the numerical values of the relative JLA were observed between varus and valgus stresses for each load. Conclusions: Consideration of cartilage wear allowed knee laxity to be evaluated more precisely in this study than in previous reports. It was shown that medial soft tissue contracture did not always exist, even in varus OA knees. Regarding clinical relevance, surgeons should be aware that underestimating medial soft tissue laxity due to reliance on the absolute JLA might lead to excessive medial tissue release and result in postoperative instability and lower patient satisfaction. Level of evidence: IV..
52. Hirokazu Saiwai, Seiji Okada, Ken ichi Kawaguchi, Takeyuki Saito, Mitsumasa Hayashida, Akinobu Matsushita, Yoshihiro Matsumoto, Yasuharu Nakashima, Prone position surgery for a professional sumo wrestler with thoracic ossification of the posterior longitudinal ligament resulting in intraoperative brachial plexus injury by hypertrophic pectoral muscles, Journal of Clinical Neuroscience, 10.1016/j.jocn.2019.01.047, 2019.05, Surgery in the prone position is associated with a variety of complications due to the positioning, including the widely recognized peripheral nerve compression injuries and brachial plexus neuropathy. Previous studies have reported that thin body habitus is a predisposing risk factor for the compressive peripheral nerve injuries due to the prone position surgery. However, prone-position-related brachial plexus injury in patients who are overweight due to hypertrophic muscles have never been reported. Here we report a case of a professional sumo wrestler with severe thoracic ossification of the posterior longitudinal ligament (OPLL). Thoracic OPLL was successfully treated by posterior spinal fusion and decompression surgery. Despite a preoperative simulation and intraoperative inspection of the patient's surgical positioning, he suffered from bilateral upper extremity paralysis immediately after the surgery. Postoperative axillary MRI image revealed a high-intensity area on both sides of his pectoral muscles and axillary fossa, which implied that the pectoral muscles between the ribs and chest pad were pushed out toward the axillary fossa, resulting in compressive brachial plexus injury. His upper extremity motor paralysis was fully recovered in 6 months, but he still has mild tingling sensation even after 12 months of his surgery. In conclusion, overweight patients with hypertrophic muscles pose a risk for brachial plexus entrapment injury by pectoral muscles during prone-position surgery, and therefore it would be more effective to use a wide chest pad to reduce the pressure on the pectoral muscles to prevent it from being pushed out toward the axillary fossa..
53. Kazuya Yokota, Takeshi Maeda, Osamu Kawano, Eiji Mori, Tsuneaki Takao, Hiroaki Sakai, Muneaki Masuda, Yuichiro Morishita, Tetsuo Hayashi, Kensuke Kubota, Yasuharu Nakashima, Progression of local kyphosis after conservative treatment for compressive cervical spine fracture with spinal cord injury, Journal of Orthopaedic Surgery and Research, 10.1186/s13018-019-1115-z, 2019.04, Introduction: Compressive-flexion type cervical spine fracture is typically accompanied by apparent dislocation of the facet joints, undesirable cervical alignment, and devastating neurological dysfunction, which provides strong rationale for rendering prompt operative treatment. However, the validity of conservative treatment for compressive-flexion cervical spine injury in cases with preserved congruity of the facet joints has yet to be elucidated. The purpose of this study is to evaluate the long-term outcome of cervical alignment following conservative treatment for compressive-flexion cervical spine injury with preserved congruity of the facet joints. Methods: A total of 662 patients who experienced spinal cord injury from 2007 to 2017 were included and underwent retrospective review in a single institute. Thirteen patients were identified as receiving conservative therapy following compressive-flexion cervical spine fractures with spinal cord injury. Clinical and radiological results were collected, including vertical fractures of the vertebral column, laminar fractures, progression of local kyphosis, and neurological status. The degree of the local cervical kyphosis was evaluated with two methods: the posterior tangent method and the endplate method. Results: All 13 patients were male, and the mean age at the time of injury was 28.4 years. The mean follow-up period was 3 years. Although none of the patients presented neurological deterioration after the injury, the degree of local kyphosis was increased at the time of final follow-up compared to what was observed at the time of injury. Patient age at the time of injury and concurrent vertical fracture of vertebral body could have been influencing factors for the progression of the kyphosis. While laminar fracture affected the kyphosis at the time of injury, it was not a strong influencing factor of the overall progression of local kyphosis. Conclusions: The conservative option for the compressive-flexion cervical injury allowed us to treat without exacerbating neurological symptoms as long as the facet joints are preserved. However, in terms of cervical alignment, surgical stabilization may have been desirable for these patients. Notably, the younger patients and the patients with vertical fracture of the cervical vertebral column in this type of injury required closer observation to help prevent the progression of local kyphosis..
54. Umito Kuwashima, Ryohei Takeuchi, Hiroyuki Ishikawa, Mikio Shioda, Yasuharu Nakashima, Steffen Schröter, Comparison of torsional changes in the tibia following a lateral closed or medial open wedge high tibial osteotomy, Knee, 10.1016/j.knee.2019.01.009, 2019.03, Objective: The aim of this study is to evaluate, by computed tomography (CT), whether different torsional changes occur in the tibia following a lateral closed wedge high tibial osteotomy (CWHTO) versus a medial open wedge high tibial osteotomy (OWHTO) procedure. It was hypothesized that the distal fragment of the tibia would show greater internal rotation after CWHTO. Methods: Thirty knees from 25 patients who underwent HTO were enrolled. Fifteen knees of 14 patients who underwent CWHTO and 15 knees of 11 patients who received OWHTO were match-paired. CT scans were taken before and three weeks after surgery. Rotational changes in the distal fragment of the tibia were assessed by measuring the tibial torsion angle (TTA). Results: The mean TTA in the CWHTO group pre-operatively and postoperatively was + 23.9° ± 7.8° and + 18.2° ± 7.0°, respectively. Internal rotation of the distal fragment of the tibia after CWHTO was − 5.7 ± 3.3° (P < 0.001). In the OWHTO group, the mean TTA pre-operatively and postoperatively was + 27.9° ± 6.9° and + 26.8 ± 7.7°, respectively, with no significant change in torsion observed (P > 0.05). Conclusions: The distal fragment of the tibia rotated internally after CWHTO but not after OWHTO. Level of evidence: Level III: case–control study..
55. Hiroyuki Hatanaka, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Takeshi Utsunomiya, Shoji Baba, Koichiro Kawano, Yasuharu Nakashima, Differences in magnetic resonance findings between symptomatic and asymptomatic pre-collapse osteonecrosis of the femoral head, European Journal of Radiology, 10.1016/j.ejrad.2019.01.002, 2019.03, Purpose: The purpose of this study was to assess the differences in magnetic resonance (MR) findings between the symptomatic and asymptomatic pre-collapse stage of osteonecrosis of the femoral head (ONFH). Materials and methods: This study reviewed 123 consecutive hips in 91 patients in the pre-collapse stage of ONFH based on plain radiographic findings. These 123 hips were divided into symptomatic and asymptomatic groups according to the pain domain score in the Harris hip score system. Bone marrow edema (BME), synovial fluid effusion, and subchondral fracture were evaluated using MR imaging. Odds ratios (ORs) were calculated between these three parameters and symptoms. The subsequent clinical course after MR examination was also assessed for each hip that could be followed more than 1 year. Results: Forty-six hips (37.4%) were categorized as symptomatic and 77 hips (62.6%) as asymptomatic. The prevalence of BME, synovial fluid effusion, and subchondral fracture were 87.0% (40/46), 80.4% (37/46), and 34.8% (16/46), respectively, in the symptomatic group, and 0%, 28.6% (22/77), and 0%, respectively, in the asymptomatic group, indicating significant differences between the two groups (p < 0.0001). Among these parameters, BME showed the highest OR with regard to the presence or absence of symptoms (BME, 965.8; joint effusion, 10.3; subchondral fracture, 83.9). Due to persistent pain and subsequent collapse, 30 of 35 (85.7%) symptomatic hips with BME subsequently underwent surgical treatment at a mean interval of 3.47 months after MR examination, while 25 of 66 (37.9%) asymptomatic hips without BME underwent surgical treatment at a mean interval of 20.7 months after MR examination. Conclusions: This study demonstrated that symptomatic pre-collapse ONFH diagnosed based on plain radiographic findings could be distinguished from asymptomatic pre-collapse ONFH by the presence of BME on MR imaging, and thus BME may be a sign of occult fracture..
56. Takamitsu Okada, Hidehiko Yuge, Takeshi Kamitani, Takahiro Senju, Naohide Takeuchi, Koji Sagiyama, Naoya Kozono, Yoshitaka Nakanishi, Hiroshi Honda, Yasuharu Nakashima, Evaluation of humeral head cartilage using magnetic resonance imaging T1 rho mapping for patients with small-to-medium rotator cuff tears
A pilot study
, Journal of Orthopaedic Science, 10.1016/j.jos.2018.10.002, 2019.03, Background: It is unclear whether smaller rotator cuff tears cause cartilage degeneration. This study was designed to detect early humeral head cartilage degeneration in patients with small-to-medium cuff tears using magnetic-resonance-imaging T1 rho mapping. Methods: Five male and 5 female volunteers without shoulder symptoms (control group) and 5 male and 5 female patients with small-to-medium (<3 cm) rotator cuff tears underwent 3.0-T magnetic resonance imaging of a single shoulder. T1 rho values of the humeral head cartilage were measured and analyzed. Results: The total mean T1 rho value was 40.4 ± 3.4 ms for the control group and 45.0 ± 5.3 ms for the patient group. In the control group, the T1 rho values in the inferior articular cartilage were significantly higher than those in the superior and middle articular cartilage. In the patient group, there was no significant difference between all regions. A comparison between the patient and control groups showed that the mean T1 rho values in the superior-to-middle articular cartilage were significantly higher for the patient group than for the control group. However, in the inferior articular cartilage, there was no significant difference between both groups. Conclusions: This study showed the possibility of early cartilage degenerative changes in the superior-to-middle humeral head articular cartilage of patients with small-to-medium rotator cuff tears..
57. Yuta Sakemi, Keisuke Komiyama, Kensei Yoshimoto, Kyohei Shiomoto, Miho Iwamoto, Yasuharu Nakashima, How does anteroposterior cup placement affect bone coverage and range of motion in primary total hip arthroplasty for hip dysplasia?, Journal of Orthopaedic Science, 10.1016/j.jos.2018.08.019, 2019.03, Background: Due to anterior bone defects, high and/or posterior placement of an acetabular cup is often required to achieve sufficient coverage in patients with hip dysplasia. We examined whether posterior cup placement affected the postoperative range of motion (ROM) in primary total hip arthroplasty (THA). Methods: Using computer software, bone coverage and ROM were examined in 32 patients with unilateral osteoarthritis of the hip with Crowe type II or III hip dysplasia. We determined the cup position to satisfy cup center-edge (Cup-CE) angle ≥0° and the required ROM. The cup was placed at the anatomic hip center and moved in 2-mm increments anteroposteriorly and 10-mm increments vertically. Results: At vertical anatomic hip center, less than 68.8% hips fulfilled Cup-CE ≥0° regardless of anteroposterior position. Significantly more hips at higher hip center with posterior cup placement achieved Cup-CE ≥0° than hips at vertical anatomic hip center, and 10 mm higher hip center was the most suitable for achieving bone coverage. However, posterior and superior cup placement significantly decreased the flexion and IR due to early bone impingement, whereas ER and extension were not affected. A smoothing spline curve demonstrated that more posterior cup placement than 4.8 mm and 3.6 mm did not satisfy the required ROM at 10 mm and 20 mm higher hip center, respectively. Conclusions: Posterosuperior cup placement gained more bone coverage but decreased the range of hip flexion and internal rotation. Consequently, posterosuperior cup placement did not satisfy the required ROM..
58. Yasuo Nakahara, Hiroshi Kitoh, Yasuharu Nakashima, Junya Toguchida, Nobuhiko Haga, Longitudinal study of the activities of daily living and quality of life in Japanese patients with fibrodysplasia ossificans progressiva, Disability and Rehabilitation, 10.1080/09638288.2017.1405083, 2019.03, Purpose: Fibrodysplasia ossificans progressiva is a rare congenital disorder that causes systemic heterotopic ossification, leading to systemic ankyloses and mobility losses. This study aimed to ascertain the natural history of fibrodysplasia ossificans progressiva. Methods: In addition to the medical history questionnaire, patients aged 16 years and older were asked to complete activities of daily living and quality of life surveys using the Barthel Index, MOS 36-Item Short-Form Health Survey, and Health Assessment Questionnaire. The surveys were conducted over a 4-years period. Results: Of the 15 participating patients, 13 reported swelling during the study period. The Barthel Index and Health Assessment Questionnaire surveys indicated a tendency for questionnaire items related to arm function to reflect early decreases in the activities of daily living. Decreases in activities of daily living functioning were closely related to decreases in the quality of life in physical function domains. Activities of daily living and quality of life were maintained at a similar level to baseline values over the study period (Barthel Index: p = 0.42, MOS 36-Item Short-Form Health Survey: p = 0.43, Health Assessment Questionnaire: p = 0.87). Conclusions: We obtained longitudinal information relating to natural history on fibrodysplasia ossificans progressiva patients.Implications for rehabilitation Fibrodysplasia ossificans progressiva is a rare congenital disease that causes heterotopic ossification of muscle tissue throughout the body, leading to systemic ankyloses and mobility losses. When the Barthel Index was high and the activities of daily living were relatively stable, the items on the Health Assessment Questionnaire that are related to arm function began to show impairment. Early focus on upper extremity function that includes the use of assistive devices during the period when a patient is still able to perform many activities of daily living is important. Although decreases in activities of daily living functioning were closely related to decreases in the quality of life in the physical function domains, the scores of the domains other than physical function were similar to the national standard score..
59. Yoshihiro Komohara, Hiroto Takeya, Nanako Wakigami, Natsuki Kusada, Hirofumi Bekki, Shin Ishihara, Motohiro Takeya, Yasuharu Nakashima, Yoshinao Oda, Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma, Medical Molecular Morphology, 10.1007/s00795-018-0201-3, 2019.03, Undifferentiated sarcoma (US) is a frequent soft tissue sarcoma. Although the 10-year survival rate is around 60%, advanced US is highly resistant to chemo/radiotherapy. The tumor microenvironment (TME) is closely associated with tumor progression. However, few studies of infiltrated immune cells in US have been published. In this study, we evaluated tumor-associated macrophages (TAMs) and CD8-positive cytotoxic T lymphocytes (CTLs) in 28 cases of US. Iba1, CD163, and CD204 were used as markers for TAMs. The density of CTLs was positively correlated with the density of TAMs. However, a negative correlation was seen between the density of CTLs and the percentage of CD204-positive TAMs. We found no significant association between the density of Iba1-/CD204-/CD8-positive cells and clinicopathological factors. No significant correlation between immune cell infiltration and clinical outcome was observed. Although we found no significant association between immune cells and clinicopathological factors, these findings may provide new insight into the characterization of immune cells in the TME of US..
60. Ken Kijima, Kensuke Kubota, Masamitsu Hara, Kazu Kobayakawa, Kazuya Yokota, Takeyuki Saito, Shingo Yoshizaki, Takeshi Maeda, Daijiro Konno, Yoshihiro Matsumoto, Yasuharu Nakashima, Seiji Okada, The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury, EBioMedicine, 10.1016/j.ebiom.2019.03.003, 2019.03, Background: Spinal cord injury (SCI) is a devastating disorder for which the accurate prediction of the functional prognosis is urgently needed. Due to the lack of reliable prediction methods, the acute evaluation of SCI severity and therapeutic intervention efficacy is extremely difficult, presenting major obstacles to the development of acute SCI treatment. We herein report a novel method for accurately predicting the functional prognosis using the acute-phase serum zinc concentration after SCI. Methods: We produced experimental animal SCI models with different prognoses and examined the relationship among the SCI severity, functional outcome, and acute-phase serum zinc concentration. We also examined whether we could predict the functional prognosis by evaluating the serum zinc concentration within 72 h after SCI in a human prospective study. Findings: In a mouse model, the acute serum zinc concentrations decreased in proportion to SCI severity and the serum zinc concentrations at 12 h after SCI accurately predicted the functional prognosis. We clarified the mechanism underlying this serum zinc proportional decrease, showing that activated monocytes took up zinc from blood-serum and then infiltrated the lesion area in a severity-dependent manner. A non-linear regression analysis of 38 SCI patients showed that the serum zinc concentrations in the acute-phase accurately predicted the long-term functional outcome (R 2 = 0·84) more accurately than any other previously reported acute-phase biomarkers. Interpretation: The acute-phase serum zinc concentration could be a useful biomarker for predicting the functional prognosis. This simple method will allow for more objective clinical trials and the development of patient-tailored treatment for SCI..
61. Yusuke Kohno, Yasuharu Nakashima, Masanori Fujii, Kyohei Shiomoto, Miho Iwamoto, Acetabular retroversion in dysplastic hips is associated with decreased 3D femoral head coverage independently from lateral center-edge angle, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-019-03277-6, 2019.01, Introduction: The clinical significance of acetabular retroversion in non-dysplastic hips can be explained as pincer-type femoroacetabular impingement (FAI), whereas that in dysplastic hips is not clarified because FAI normally poses little problems for dysplastic hips. We aimed to evaluate three-dimensional (3D) femoral head coverage in dysplastic hips with and without acetabular retroversion and to elucidate the role of acetabular retroversion on the 3D femoral head coverage. Materials and methods: We retrospectively investigated 93 hips in 93 patients (9 males and 84 females) that underwent periacetabular osteotomy for hip dysplasia. Dysplastic hips were divided into anteversion and retroversion groups according to their cranial anteversion, which was measured on the axial section 5 mm caudal to the acetabular roof. The 3D femoral head coverage was provided as a percentage of the acetabulum-covered surface area of the upper femoral hemisphere using a 3D preoperative planning software for total hip arthroplasty. Results: Of the 93 dysplastic hips, 15 hips (16%) were assigned to the retroversion group, which had significantly younger age at surgery (31.9 years versus 39.2 years; p = 0.033). The lateral center-edge angles were comparable between the groups (13.8° versus 12.9°; p = 0.68); however, the hips in the retroversion group had a trend of smaller 3D femoral head coverage than those in the anteversion group (59% versus 63%; p = 0.058). Multivariate analysis using two-way analysis of covariance showed that lateral center-edge angle (partial regression coefficient = 0.83; t value = 17.3; p < 0.001) and acetabular retroversion (partial regression coefficient = − 2.3; t value = − 4.9; p < 0.001) were independent factors that contributed to the 3D femoral head coverage. Conclusions: Acetabular retroversion in dysplastic hips was associated with decreased 3D femoral head coverage independently from lateral center-edge angle. The age at surgery in the retroversion group was significantly younger, suggesting a relationship between decreased 3D coverage and potentially earlier symptom onset..
62. Makoto Nakagawa, Shuhei Fujita, Takuo Katsumoto, Kazutsune Yamagata, Yoko Ogawara, Ayuna Hattori, Yuki Kagiyama, Daisuke Honma, Kazushi Araki, Tatsuya Inoue, Ayako Kato, Koichiro Inaki, Chisa Wada, Yoshimasa Ono, Masahide Yamamoto, Osamu Miura, Yasuharu Nakashima, Issay Kitabayashi, Dual inhibition of enhancer of zeste homolog 1/2 overactivates WNT signaling to deplete cancer stem cells in multiple myeloma, Cancer Science, 10.1111/cas.13840, 2019.01, Multiple myeloma (MM) is an incurable hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs as a result of a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells show cancer stem cell-like characteristics in MM; thus, targeting these cells is a promising strategy to completely cure this malignancy. Herein, we showed that SP cells expressed higher levels of enhancer of zeste homolog (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non-SP cells, suggesting that EZH1 as well as EZH2 contributes to the stemness maintenance of the MM cells and that targeting both EZH1/2 is potentially a significant therapeutic approach for eradicating myeloma stem cells. A novel orally bioavailable EZH1/2 dual inhibitor, OR-S1, effectively eradicated SP cells and had a greater antitumor effect than a selective EZH2 inhibitor in vitro and in vivo, including a unique patient-derived xenograft model. Moreover, long-term continuous dosing of OR-S1 completely cured mice bearing orthotopic xenografts. Additionally, PRC2 directly regulated WNT signaling in MM, and overactivation of this signaling induced by dual inhibition of EZH1/2 eradicated myeloma stem cells and negatively affected tumorigenesis, suggesting that repression of WNT signaling by PRC2 plays an important role in stemness maintenance of MM cells. Our results show the role of EZH1/2 in the maintenance of myeloma stem cells and provide a preclinical rationale for therapeutic application of OR-S1, leading to significant advances in the treatment of MM..
63. Keisuke Komiyama, Satoshi Hamai, Daisuke Hara, Satoru Ikebe, Yifeng Wang, Hirotaka Gondo, Hidehiko Higaki, Yasuharu Nakashima, Dynamic hip kinematics during recreational classical ballet and hula dance after total hip arthroplasty
Two case reports
, Journal of Medical Case Reports, 10.1186/s13256-018-1942-2, 2019.01, Background: The in vivo assessment of the three-dimensional kinematics of the hip during dance activities in patients after total hip arthroplasty has not been previously reported. We evaluated the replaced hip kinematics during recreational classical ballet and hula dance using radiographic-based image-matching techniques. Case presentation: A 58-year-old Japanese woman (patient 1; height, 157 cm; weight, 74.5 kg) and a 73-year-old Japanese woman (patient 2; height, 153 cm; weight, 48 kg) were still doing classical ballet and hula dance, respectively, after primary total hip arthroplasty. For ballet, there were gradual three-dimensional hip movements with 48° flexion, 36° abduction, and 49° external rotation in développé and 34° flexion, 29° abduction, and 43° external rotation in plié. For hula, there were small three-dimensional hip movements with 31° flexion, 15° adduction, and 11° external rotation in kao and 17° flexion, 11° adduction, and 11° external rotation in kaholo. No liner-to-neck contact was found in any dance activities. Conclusion: Both classical ballet and hula dance produced complex ranges of hip movements and activity-dependent kinematics. These kinematic data could be useful for recommending each patient with total hip arthroplasty to continue recreational dance activities..
64. Keiichiro Iida, Katsumi Harimaya, Kiyoshi Tarukado, Osamu Tono, Yoshihiro Matsumoto, Yasuharu Nakashima, Kyphosis progression after balloon kyphoplasty compared with conservative treatment, Asian Spine Journal, 10.31616/asj.2018.0329, 2019.01, Study Design: Retrospective cohort study (level of evidence: 4). Purpose: To demonstrate the effects of balloon kyphoplasty (BKP) on prevention of kyphosis progression. OverView of Literature: Kyphoplasty can correct local kyphosis (fractured vertebra), but its efficacy is attenuated by adjacent fracture and/or disc height reduction with endplate damage. With these attenuating factors incorporated, a comparison between BKP and conservative treatment is necessary to verify the effect of BKP on kyphosis correction. Methods: This study retrospectively analyzed 129 patients treated conservatively and 95 treated with BKP in our institution. The rate of new adjacent fracture occurrence was determined using Kaplan-Meier analysis. We examined the progression of local kyphosis in patients who underwent lateral X-ray after 1 year. Local kyphosis was measured as an angle between higher end plate of the vertebra above and lower end plate of the vertebra below the fractured vertebra. The comparison included 45 patients treated conservatively and 58 treated with BKP Results: The incidence of new adjacent fracture at 1 year was 7.3% in the conservative treatment group and 23.2% in the BKP group (p<0.001), while the progression of local kyphosis at 1 year was 5.7°±4.7° and 3.2°±4.6°, respectively (p=0.01). Relative to conservative treatment, local kyphosis did not progress after BKP, despite the higher incidence of adjacent fracture. Local kyphosis progressed in cases with adjacent fracture compared with those without adjacent fracture (6.0°±4.3° vs. 2.1°±4.3°, p=0.003), and fractured vertebral instability was found to be a risk factor for adjacent fracture in BKP. Conclusions: Compared with the conservative treatment, BKP suppressed the progression of local kyphosis. However, an adjacent fracture attenuated the BKP correction and was more frequently seen in patients with unstable vertebral fractures..
65. Masuo Hanada, Hideki Kadota, Sei Yoshida, Naohide Takeuchi, Takamitsu Okada, Yoshihiro Matsumoto, Yasuharu Nakashima, Large-defect Resurfacing
A comparison of skin graft results following sarcoma resection and traumatic injury repair
, Wounds, 2019.01, Introduction. Soft tissue sarcomas are rare neoplasms, and most plastic surgeons do not commonly resurface large tissue defects after a wide resection of these tumors. Objective. The purpose of this study is to elucidate the clinical results of large skin grafts after wide sarcoma resection by comparison with grafts for traumatic skin defects. Materials and Methods. A retrospective review was performed of patients who received skin grafts > 50 cm2 after traumatic injury or wide sarcoma resection from 2014 to 2016. Patient medical records were reviewed; graft take rate, graft loss, and days to complete epithelialization were compared between the 2 groups. Results. In the sarcoma group (n = 8), 5 grafts were partially lost; the sarcoma group mean graft take rate of 67.5% ± 30.0% was significantly lower than that of the trauma group (n = 7) at 99.6% ± 1.1%. The mean time to complete epithelialization from the skin graft placement in the sarcoma group was 113.3 ± 66.0 days, which was significantly longer than that of the trauma group (40.3 ± 38.0 days). Wounds located around the shoulder joint in 2 sarcoma group patients did not heal even after 300 days of conservative treatment; 1 required a secondary flap. Conclusions. The results of skin grafting for resurfacing large defects after sarcoma resection are inferior to those for traumatic injury repair. Skin grafts may fail because the blood supply for the wound bed is impaired during resection. Furthermore, due to the wound bed movement, epithelialization over muscles of the shoulder joint is difficult to achieve, and skin grafts in this region will likely fail..
66. Kazuya Yokota, Kensuke Kubota, Kazu Kobayakawa, Takeyuki Saito, Masamitsu Hara, Ken Kijima, Takeshi Maeda, Hiroyuki Katoh, Yasuyuki Ohkawa, Yasuharu Nakashima, Seiji Okada, Pathological changes of distal motor neurons after complete spinal cord injury, Molecular Brain, 10.1186/s13041-018-0422-3, 2019.01, Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury). Atrophic changes were widely observed in the injured spinal cord both rostral and caudal to the lesion, but the decrease in area was mainly in the white matter in the rostral spinal cord while both the white and gray matter decreased in the caudal spinal cord. The number of the motor neurons was maintained in the chronic phase of injury, but the number of presynaptic boutons decreased in the lumbar motor neurons caudal to the lesion. Using laser microdissection, to investigate gene expressions in motor neurons caudal to the lesion, we observed a decrease in the expressions of neuronal activity markers. However, we found that the synaptogenic potential of postsynapse molecules was maintained in the motor neurons after SCI with the expression of acetylcholine-related molecules actually higher after SCI. Collectively, our results show that the potential of synaptogenesis is maintained in the motor neurons caudal to the lesion, even though presynaptic input is decreased. Although researches into SCI concentrate their effort on the lesion epicenter, our findings suggest that the area caudal to the lesion could be an original therapeutic target for the chronically injured spinal cord..
67. Yukio Akasaki, Hideki Mizu-uchi, Satoshi Hamai, Hidetoshi Tsushima, Shinya Kawahara, Tomohiro Horikawa, Yasuharu Nakashima, Patient-specific prediction of joint line convergence angle after high tibial osteotomy using a whole-leg radiograph standing on lateral-wedge insole, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-019-05821-8, 2019.01, Purpose: To assess the usefulness of a whole-leg radiograph standing on lateral-wedge insole (LWI) for predicting the change in joint line convergence angle (JLCA) before vs. after high tibial osteotomy (HTO). Methods: Forty knees with medial osteoarthritis underwent open-wedge HTO. Pre-operatively, all patients had whole-leg radiographs taken in three different conditions: supine, standing, and standing on LWI inclined at 20°. A standing whole-leg radiograph was also obtained post-operatively. Radiological measurements including JLCA and percentage of mechanical axis (%MA) were compared. Using pre-operative radiographs, correction angles were calculated with the target %MA at 62.5%. Correlations between the difference in calculated correction angle among the three pre-operative conditions and the change in JLCA before vs. after HTO were assessed. Results: In the pre-operative standing conditions, the mean JLCA of 3.8° was significantly decreased to 3.2° using LWI, which did not differ from post-operative JLCA of 3.1°. Mean %MA significantly shifted laterally from 20.6 to 24.8% using LWI, and was strongly correlated with the change in JLCA (coefficient, 0.83). Calculated correction angles differed significantly among the three pre-operative conditions. The difference in calculated correction angle between standing with and without LWI was strongly correlated to the change in standing JLCA before vs. after HTO (coefficient, 0.73). Conclusion: Larger differences in calculated correction angles between pre-operative radiographs standing with and without LWI predicted larger changes in JLCA after HTO. Whole-leg radiograph standing on LWI is a promising modality for correct pre-operative planning considering patient-specific changes in JLCA before vs. after HTO. Level of evidence: IV..
68. Yu Matsushita, Satoshi Hamai, Ken Okazaki, Koji Murakami, Yuan Ma, Masato Kiyohara, Hideki Mizu-uchi, Yukio Akasaki, Yasuharu Nakashima, Recreational sports, workout and gym activities after total knee arthroplasty
Asian cohort study
, Journal of Orthopaedics, 10.1016/j.jor.2018.12.002, 2019.01, This study aimed to evaluate sports activities after total knee arthroplasty in an Asian cohort using 2011 Knee Society scoring system. The average scores for satisfaction and expectation about sports-related activities were 4.9 (61%) and 3.5 (70%), respectively. Most patients mainly opted for low-impact sports. Multivariate analysis showed that higher score of ‘standard activities’ and ‘walking & standing’ better range of motion, and older age were associated with higher scores of satisfaction and expectation about sports-related activities. In conclusion, improvement of activities of daily living could provide higher satisfaction and expectation about performing recreational sports, workout and gym activities..
69. Yasuharu Nakashima, Masakazu Kondo, Eisuke Shono, Takashi Ishinishi, Hiroshi Tsukamoto, Koji Kuroda, Akira Maeyama, Hiroshi Harada, Masayuki Maekawa, Takashi Shimauchi, Ryuji Nagamine, Hiroshi Jojima, Seiji Yoshizawa, Tomomi Tsuru, Takeshi Otsuka, Hisaaki Miyahara, Eiichi Suematsu, Ken Wada, Shigeru Yoshizawa, Yasushi Inoue, Takaaki Fukuda, Satoshi Ikemura, Akihisa Haraguchi, Suppression of joint destruction with subcutaneous tocilizumab for Japanese patients with rheumatoid arthritis in clinical practice, Modern Rheumatology, 10.1080/14397595.2019.1676369, 2019.01, Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting. Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI). Results: At baseline, the patients’ mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were naïve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to −0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified. Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period..
70. Mingjian Xu, Goro Motomura, Takeshi Utsunomiya, Satoshi Ikemura, Ryosuke Yamaguchi, Hiroyuki Hatanaka, Shoji Baba, Koichiro Kawano, Yasuharu Nakashima, Traumatic subchondral fracture of the femoral head occurring concurrently with contralateral acetabular fracture, Journal of Orthopaedic Science, 10.1016/j.jos.2019.05.016, 2019.01.
71. Hisakata Yamada, Tatsuhiko Ozawa, Hiroyuki Kishi, Seiji Okada, Yasuharu Nakashima, Atsushi Muraguchi, Yasunobu Yoshikai, Cutting edge
B cells expressing cyclic citrullinated peptide-specific antigen receptor are tolerized in normal conditions
, Journal of Immunology, 10.4049/jimmunol.1800826, 2018.12, Generation of neoantigens by citrullination is implicated in the production of anti-citrullinated protein Abs in rheumatoid arthritis, but citrullination is also a physiological process. To verify whether citrullin-specific B cells are immunologically ignorant or tolerant in normal conditions, transgenic (Tg) mice expressing IgM with the V region of an anti-cyclic citrullinated peptide (CCP) mAb cloned from a rheumatoid arthritis patient were generated. CCP-specific B cells developed in the anti-CCP IgM Tg mice with an alteration of bone marrow B cell fractions, and the number of mature B cells decreased compared with wild-type or the control anti-influenza nucleoprotein-specific IgM Tg mice. In addition, B cells in anti-CCP IgM Tg mice are functionally anergic. Thus, tolerance is induced in CCP-specific B cells in vivo, suggesting that the immune systems are naturally exposed to citrullinated Ags, and anti-CCP Ab production requires additional steps beyond the generation of neoantigens by citrullination..
72. Jun ichi Fukushi, Ichiro Kawano, Goro Motomura, Satoshi Hamai, Ken ichi Kawaguchi, Yasuharu Nakashima, Does hip center location affect the recovery of abductor moment after total hip arthroplasty?, Orthopaedics and Traumatology: Surgery and Research, 10.1016/j.otsr.2018.06.022, 2018.12, Background: In total hip arthroplasty (THA), placing the cup in an anatomic position is not always possible in case of deformities related to developmental dysplasia of the hip (DDH). Thus far, the influence of a hip center on the abductor moment after THA has not been clearly elucidated. Therefore, we performed a retrospective study to assess (1) how abductor muscle moment recovers postoperatively in THA and (2) whether acetabular cup position affects the recovery of abductor moment. Hypothesis: A high hip center affects the recovery of abductor moment of a dysplastic hip after THA. Patients and Methods: We evaluated 100 patients, who underwent unilateral primary THA, at 12 months postoperatively. The study included 86 women and 14 men, with a mean age of 65.5 ± 9.9 years (range, 40 to 86 years). Patients with secondary osteoarthritis due to DDH were included (Crowe 1: 76; Crowe 2: 15, Crowe 3:9, and Crowe 4: none). A cementless straight stem was implanted in all hips. Hip abductor moment was measured using a belt-stabilized hand-held dynamometer. The ratio of moment of the affected side to that of the contralateral side was calculated as moment ratio. The horizontal and vertical centers of rotation (H-COR and V-COR) (with respect to the inter teardrop line) and vertical shift (V-shift) (difference in V-COR between the affected hip and the contralateral normal hip) were determined. Results: At 6 and 12 months postoperatively, the abductor moment ratios were 95.1 and 94.7%, respectively. Significant negative correlation was observed between the postoperative abductor moment ratio and V-COR at 6 months postoperatively (r = −0.2436, p = 0.0238). Significant delay in the recovery of abductor moment ratio was observed in the groups with higher hip center (V-shift > 15 mm) (odds ratio = 12.7; 95% CI: 2.11–232.1, p = 0.0034) at 6 months postoperatively, which was fully recovered at 12 months postoperatively. Discussion: Superior placement of a hip center, more than 15 mm above the true hip center, delayed the recovery of abductor muscle moment after THA. Level of evidence: III, retrospective comparative study..
73. Takeshi Utsunomiya, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Kazuhiko Sonoda, Hiroyuki Hatanaka, Shoji Baba, Koichiro Kawano, Takuaki Yamamoto, Yasuharu Nakashima, Effects of sclerotic changes on stress concentration in early-stage osteonecrosis
A patient-specific, 3D finite element analysis
, Journal of Orthopaedic Research, 10.1002/jor.24124, 2018.12, Stress distribution remains unclear in early-stage osteonecrosis of the femoral head (ONFH). To clarify this issue, we generated patient-specific finite element models (FEMs) from 51 patients with ONFH. Patients’ hips were classified into three groups: ONFH without a sclerotic boundary (Stage 1, n = 6), ONFH with a sclerotic boundary (Stage 2, n = 10), and ONFH with both a sclerotic boundary and <2 mm collapse (Stage 3, n = 35). Four hips without ONFH were used as controls. Stress distribution in each FEM was compared with magnetic resonance imaging (MRI) and computed tomography (CT) results. Fifteen wholly resected femoral heads in Stage 3 hips were assessed by micro-CT. Furthermore, we histologically examined three Stage 2 femoral heads that subsequently developed subchondral fractures after FEM analyses. In all FEMs of both control and Stage 1 hip, stress was equally distributed on the femoral head surface. However, in all FEMs of both Stages 2 and 3 hips, stress was concentrated at the lateral boundary of the femoral head surface, corresponding to both a low-intensity band on T1-weighted MRI images and sclerotic changes on CT. On micro-CT, subchondral fractures consistently began at the lateral boundary with sclerotic changes, in which bone volume fraction was increased. Histology showed breakage of subchondral plates at the junction between necrotic and reparative zones. In early-stage ONFH, sclerotic changes caused stress concentration, which can trigger subchondral fractures at the lateral boundary. Clinical Significance: Our results will clarify the pathogenic mechanism of collapse in ONFH..
74. Naoya Kozono, Takamitsu Okada, Naohide Takeuchi, Satoshi Hamai, Hidehiko Higaki, Takeshi Shimoto, Satoru Ikebe, Hirotaka Gondo, Yoshitaka Nakanishi, Takahiro Senju, Yasuharu Nakashima, In vivo dynamic acromiohumeral distance in shoulders with rotator cuff tears, Clinical Biomechanics, 10.1016/j.clinbiomech.2018.07.017, 2018.12, Background: There are no previous studies on the acromiohumeral distance in shoulders with large-to-massive full-thickness rotator cuff tears. In this study, the acromiohumeral distance in rotator cuff tear and healthy shoulders was measured using 3D-to-2D model-to-image registration techniques. Methods: The dynamic glenohumeral kinematics during scapular plane abduction and axial rotation were analyzed in 11 rotator cuff tear patients and 10 healthy control subjects. Periodic radiographic images of scapular plane abduction and axial rotation were taken using a flat-panel radiograph image detector. Movements of the shoulder joint were assessed using radiographic images and computed tomography-derived digitally reconstructed radiographs. The acromiohumeral distance was defined as the shortest 3D distance between the acromion and the proximal humerus. Findings: For scapular plane abduction, the rotator cuff tear group had significantly smaller acromiohumeral distance than the control group at 15° 30° 45° 60° 75° 135° and 150° of humeral abduction (P < 0.05 at each measured angle). For axial rotation in the adducted position, the rotator cuff tear group had significantly smaller acromiohumeral distance than the control group at each point between −20° and 40° of glenohumeral external rotation (P < 0.05 at each measured angle). Interpretation: The minimum measured acromiohumeral distance was 0.9 mm in the rotator cuff tear shoulders and 2.1 mm in the healthy shoulders at 90° of scapular plane abduction. The findings are of clinical relevance because quantitative evaluation of the dynamic acromiohumeral distances in rotator cuff tear and healthy shoulders might provide important insight into subacromial impingement..
75. Naoyuki Fukuda, Masayuki Kanazawa, Kanji Tsuru, Akira Tsuchiya, Sunarso, Riki Toita, Yoshihide Mori, Yasuharu Nakashima, Kunio Ishikawa, Synergistic effect of surface phosphorylation and micro-roughness on enhanced osseointegration ability of poly(ether ether ketone) in the rabbit tibia, Scientific reports, 10.1038/s41598-018-35313-7, 2018.12, This study was aimed to investigate the osseointegration ability of poly(ether ether ketone) (PEEK) implants with modified surface roughness and/or surface chemistry. The roughened surface was prepared by a sandblast method, and the phosphate groups on the substrates were modified by a two-step chemical reaction. The in vitro osteogenic activity of rat mesenchymal stem cells (MSCs) on the developed substrates was assessed by measuring cell proliferation, alkaline phosphatase activity, osteocalcin expression, and bone-like nodule formation. Surface roughening alone did not improve MSC responses. However, phosphorylation of smooth substrates increased cell responses, which were further elevated in combination with surface roughening. Moreover, in a rabbit tibia implantation model, this combined surface modification significantly enhanced the bone-to-implant contact ratio and corresponding bone-to-implant bonding strength at 4 and 8 weeks post-implantation, whereas modification of surface roughness or surface chemistry alone did not. This study demonstrates that combination of surface roughness and chemical modification on PEEK significantly promotes cell responses and osseointegration ability in a synergistic manner both in vitro and in vivo. Therefore, this is a simple and promising technique for improving the poor osseointegration ability of PEEK-based orthopedic/dental implants..
76. Koji Murakami, Satoshi Hamai, Ken Okazaki, Yifeng Wang, Satoru Ikebe, Hidehiko Higaki, Takeshi Shimoto, Hideki Mizu-uchi, Yukio Akasaki, Yasuharu Nakashima, In vivo kinematics of gait in posterior-stabilized and bicruciate-stabilized total knee arthroplasties using image-matching techniques, International Orthopaedics, 10.1007/s00264-018-3921-z, 2018.11, Purpose: This study aimed to evaluate the effects of two types of total knee arthroplasty (TKA) designs: posterior-stabilized (PS) and bicruciate-stabilized (BCS) on in vivo kinematics during gait. Methods: Continuous X-ray images of the gait were taken using a flat panel detector for 23 PS and BCS TKAs. We analyzed the tibiofemoral implant flexion angle, anteroposterior (AP) translation, axial rotation, and anterior/posterior cam-post contact using image-matching techniques. Results: Double knee actions were demonstrated for the PS and BCS design (35 and 61%, respectively, p = 0.08). The tibiofemoral AP positions were significantly more posterior at peak extension (− 1.7 ± 2.2 and 1.0 ± 2.5 mm, respectively, p < 0.01) and anterior at peak flexion (1.3 ± 2.3 and − 0.8 ± 2.8 mm, respectively, p = 0.01) for the PS design than for the BCS design, with a significant difference in AP translation (3.0 ± 3.9 mm anterior and 1.7 ± 2.8 mm posterior, respectively, p < 0.01). Anterior/posterior tibial post contacts were found in 83/4% and 74/30% for the PS and BCS designs, respectively, with a significant difference in posterior contact (p = 0.72/0.04, respectively). Conclusion: The knee flexion pattern, tibiofemoral AP translation, axial rotation, and cam-post contact during gait varied, depending on the type of implant, the PS and BCS designs..
77. Yusuke Kubo, Goro Motomura, Satoshi Ikemura, Hiroyuki Hatanaka, Jun ichi Fukushi, Satoshi Hamai, Takuaki Yamamoto, Yasuharu Nakashima, Osteoclast-related markers in the hip joint fluid with subchondral insufficiency fracture of the femoral head, Journal of Orthopaedic Research, 10.1002/jor.24066, 2018.11, Similar to the radiological findings in rapidly destructive arthrosis of the hip joint (RDA), subchondral insufficiency fracture of the femoral head (SIF) can result in progressive femoral head collapse of unknown etiology. We thus examined the osteoclast activity of hip joint fluid in SIF with progressive collapse in comparison with that in RDA. Twenty-nine hip joint fluid samples were obtained intraoperatively with whole femoral heads from 12 SIF patients and 17 RDA patients. SIF cases were classified into subgroups based on the presence of ≥2 mm collapse on preoperative radiographs: SIF with progressive collapse (n = 5) and SIF without progressive collapse (n = 7). The levels of tartrate-resistant acid phosphatase (TRACP)-5b, interleukin-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were measured. The number of multinuclear giant cells at the subchondral region was histopathologically assessed using mid-coronal slice of each femoral head specimen. The median levels of all markers and the median number of multinuclear giant cells in SIF with progressive collapse were significantly higher than those in SIF without progressive collapse, while there were no significant differences in SIF with progressive collapse versus RDA. Regression analysis showed that the number of multinuclear giant cells was positively correlated with the level of TRACP-5b in joint fluid. The present study demonstrated the possible association of increased osteoclast activity with the existing condition of progressive collapse in SIF, which was quite similar to the findings in RDA, indicating that increased osteoclast activity may reflect the condition of progressive collapse in SIF as well as RDA..
78. Koji Murakami, Satoshi Hamai, Ken Okazaki, Satoru Ikebe, Hidehiko Higaki, Takeshi Shimoto, Yasuharu Nakashima, Preoperative tibial mechanical axis orientation and articular surface design influence on the coronal joint line orientation relative to the ground during gait after total knee arthroplasties, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-018-4899-1, 2018.11, Purpose: Neutral lower limb alignment does not necessarily produce a horizontal joint line after total knee arthroplasty (TKA). The orientation of the pre- and postoperative tibial mechanical axes (TMAs-G), tibial component, and joint line relative to the ground were evaluated. Methods: The study group included 46 knees, 23 posterior-stabilized (PS) and 23 bicruciate-stabilized (BCS) TKAs. Using whole-leg standing radiographs, the static orientation of the pre- and postoperative TMAs-G and the tibial component as well as the postoperative alignment were measured. Applying image-matching techniques, the dynamic coronal orientation of the tibial component and joint line over the stance phase of gait were analysed. The correlation between static and dynamic orientation of the tibial component and differences in the joint line between the PS and BCS TKAs were evaluated. Results: In standing, the postoperative TMA-G (0.8° ± 2.8°) and tibial component (1.5° ± 2.4°) were laterally tilted with a strong correlation. The preoperative lateral tilt of the TMA-G (7.9° ± 5.1°) was a significant predictor of the postoperative TMA-G. The lateral tilt of the tibial component increased to 5.1° ± 2.4° on dynamic analysis, and was moderately correlated to static orientation. The dynamic orientation of the joint line was smaller for the BCS (1.8° ± 2.4°) compared to the PS (5.5° ± 2.7°) TKA. Conclusion: Even with a mechanically well-aligned TKA, a lateral tilt of the tibial component was identified due to the lateral tilt of the postoperative TMA-G and the stance phase of gait. The BCS can better accommodate the residual lateral tilt of the joint line due to the 3° medial inclination of the joint surfaces of the implant. This study increases the awareness of surgeons regarding the possibility of the coronal joint line orientation to influence preoperative TMA-G and be accommodated by articular surface design, even in mechanically aligned TKA. Level of evidence: IV..
79. Satoshi Hamai, Yusuke Kohno, Daisuke Hara, Kyohei Shiomoto, Mio Akiyama, Jun Ichi Fukushi, Goro Motomura, Satoshi Ikemura, Masanori Fujii, Yasuharu Nakashima, Minimum 10-year clinical outcomes after periacetabular osteotomy for advanced osteoarthritis due to hip dysplasia, Orthopedics, 10.3928/01477447-20180806-04, 2018.09, The purpose of this study was to examine the minimum 10-year clinical outcomes, including patient-reported and functional outcomes, of periacetabular osteotomy in patients with advanced osteoarthritis. A total of 46 hips in 44 patients with advanced osteoarthritis who underwent periacetabular osteotomy between 1992 and 2006 were retrospectively reviewed. Mean age at surgery was 47.5 years, and mean follow-up was 16.9±4.7 years. Survivorship was determined using the Kaplan-Meier method, and the associated risk factors for the endpoint-conversion to total hip arthroplasty less than 15 years after surgery-were evaluated. The Oxford Hip Score and the University of California, Los Angeles activity score were evaluated at final follow-up. The survival rates at 15 and 20 years after surgery were 80% and 59%, respectively. Multivariate analysis indicated that body mass index greater than 24 kg/m2 (P=.034; odds ratio, 1.72) was significantly associated with the endpoint as an independent risk factor. For 32 hips of 31 patients with preserved native joints at final follow-up, the Oxford Hip Score and the University of California, Los Angeles score averaged 41±5 and 5.2±1.8, respectively, equivalent (P=.28 and P=.215, respectively) to the scores of 14 hips of 13 patients with conversion to total hip arthroplasty (38±8.7 and 5.8±1.4, respectively). The results of this mid-term study may be useful for surgical decision-making among patients with advanced osteoarthritis who want to preserve native hip joints..
80. Kimitaka Nakamura, Masanobu Ohishi, Tomoya Matsunobu, Yasuharu Nakashima, Akio Sakamoto, Akira Maekawa, Yoshinao Oda, Yukihide Iwamoto, Tumor-induced osteomalacia caused by a massive phosphaturic mesenchymal tumor of the acetabulum
A case report
, Modern Rheumatology, 10.3109/14397595.2016.1173322, 2018.09, We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO..
81. Masamitsu Hara, Kazuya Yokota, Takeyuki Saito, Kazu Kobayakawa, Ken Kijima, Shingo Yoshizaki, Ken Okazaki, Shigeo Yoshida, Yoshihiro Matsumoto, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada, Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury, The Journal of bone and joint surgery. American volume, 10.2106/JBJS.17.01230, 2018.08, BACKGROUND: Skeletal muscle injury (SMI) can cause physical disability due to insufficient recovery of the muscle. The development of muscle fibrosis after SMI has been widely regarded as a principal cause of this failure to recover. Periostin (Postn) exacerbates tissue fibrosis in various organs. We investigated whether Postn is involved in the pathophysiology after SMI. METHODS: Partial laceration injuries of the gastrocnemius were created in wild-type (WT) and Postn knockout (Postn) mice. We examined the expression of the Postn gene before and after SMI. Regeneration and fibrosis of skeletal muscle were evaluated by histological analyses, and recovery of muscle strength was measured by physiological testing. Immunohistochemistry was used to examine the number and proliferative potential of infiltrating fibroblasts in injured muscle. A trans-well migration assay was used to assess the migration capability of fibroblasts. Control immunoglobulin G (IgG) or Postn-neutralizing antibody (Postn-nAb) was injected into injured muscle at 7 and 14 days after injury (dpi). We evaluated the effects of Postn-nAb on muscle repair after SMI. RESULTS: The expression of Postn was dramatically upregulated after SMI. Compared with WT mice, Postn mice had improved muscle recovery and attenuated fibrosis as well as a significantly reduced number of infiltrating fibroblasts. The proliferative potential of these fibroblasts in WT and Postn mice was comparable at 14 dpi; however, the migration capability of fibroblasts was significantly enhanced in the presence of Postn (mean, 258%; 95% confidence interval, 183% to 334%). Moreover, the administration of Postn-nAb inhibited fibroblast infiltration and promoted muscle repair after SMI. CONCLUSIONS: Postn exacerbates fibrotic scar formation through the promotion of fibroblast migration into injured muscle after SMI. Treatment with Postn-nAb is effective for attenuating fibrosis and improving muscle recovery after SMI. CLINICAL RELEVANCE: Our findings may provide a potential therapeutic strategy to enhance muscle repair and functional recovery after SMI..
82. Keisuke Komiyama, Satoshi Hamai, Daisuke Hara, Satoru Ikebe, Hidehiko Higaki, Kensei Yoshimoto, Kyohei Shiomoto, Hirotaka Gondo, Yifeng Wang, Yasuharu Nakashima, Dynamic hip kinematics during squatting before and after total hip arthroplasty, Journal of Orthopaedic Surgery and Research, 10.1186/s13018-018-0873-3, 2018.07, Background: The difference in in vivo kinematics before and after total hip arthroplasty (THA) for the same subjects and the clearance between the liner and neck during squatting have been unclear. The purpose of the present study was to clarify (1) the changes in the in vivo kinematics between prosthetic hips and osteoarthritis hips of the same subjects and (2) the extent of the liner-to-neck clearance during squatting under weight-bearing conditions. Methods: This study consisted of 10 patients who underwent unilateral THA for symptomatic osteoarthritis. Using a flat-panel X-ray detector, we obtained continuous radiographs during squatting. We analyzed the hip joint's movements using three-dimensional-to-two-dimensional model-to-image registration techniques. We also quantified the minimum distance at maximum flexion and extension, and the minimum angle at maximum flexion between the liner and stem neck. Results: The maximum hip flexion angles post-THA (80.7° [range, 69.4-98.6°]) changed significantly compared with the pre-THA values (71.7° [range, 55.2°-91.2°]). The pelvic tilt angle (posterior +, anterior-) at the maximum hip flexion post-THA (10.4° [range, - 6.7° to 26.9°]) was significantly smaller than that at pre-THA (16.6° [range, - 3° to 40.3°]). The minimum anterior and posterior liner-to-neck distances averaged 10.9 and 8.0 mm, respectively, which was a significant difference. The minimum liner-to-neck angle at maximum flexion averaged 34.7° (range, 20.7°-46.3°). No liner-to-neck contact occurred in any of the hips. Conclusion: THA increased the range of hip joint motion and the pelvis tilted anteriorly more after than before THA, with sufficient liner-to-neck clearance during squatting. These data may be beneficial for advising patients after THA regarding postoperative activity restrictions in daily life..
83. Kensei Yoshimoto, Yasuharu Nakashima, Miyo Wakiyama, Daisuke Hara, Akihiro Nakamura, Mikio Iwamoto, Initial stability of a highly porous titanium cup in an acetabular bone defect model, Journal of Orthopaedic Science, 10.1016/j.jos.2018.03.007, 2018.07, Backgrounds: The purpose of this study was to quantify the initial stability of a highly porous titanium cup using an acetabular bone defect model. Methods: The maximum torque of a highly porous titanium cup, with a pore size of 640 μm and porosity of 60%, was measured using rotational and lever-out torque testing and compared to that of a titanium-sprayed cup. The bone models were prepared using a polyurethane foam block and had three levels of bone coverage: 100, 70, and 50%. Results: The highly porous titanium cup demonstrated significantly higher maximum torque than the titanium-sprayed cups in the three levels of bone defects. On rotational torque testing, it was found to be 1.5, 1.3, and 1.3 times stronger than the titanium-sprayed cups with 100, 70 and 50% bone coverage, respectively. Furthermore, it was found to be 2.2, 2.3, and 1.5 times stronger on lever-out testing than the titanium-sprayed cup. No breakage in the porous layers was noted during the testing. Conclusion: This study provides additional evidence of the initial stability of highly porous titanium cup, even in the presence of acetabular bone defects..
84. Akihisa Haraguchi, Hisakata Yamada, Masakazu Kondo, Ken Okazaki, Jun Ichi Fukushi, Akiko Oyamada, Yasunobu Yoshikai, Yasuharu Nakashima, Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA, Clinical and experimental rheumatology, 2018.07, RESULTS: Although IgM specific for citrullinated proteins was detected in some patients (11%), IgM molecules reactive to both citrullinated and non-citrullinated peptides were detected in a substantial number of patient samples (12%). IgM ACPA-positive reactions were associated with the presence of IgG ACPA and IgM RF. Surprisingly, protein G-mediated removal of IgG from the serum eliminated positivity for IgM ACPA, suggesting that IgG ACPA-IgM RF complex was being detected. This assumption was confirmed by the detection of IgM RF in the eluate of protein G beads and citrullinated peptide-conjugated beads.
CONCLUSIONS: In an attempt to detect IgM ACPA, we mostly revealed false positive reactions due to the presence of IgM molecules, which were not specific for citrullinated proteins, and IgG ACPA-IgM RF immune complex. The latter complex had been proposed to play a role in the pathogenesis of RA, and here, for the first time, we have demonstrated its presence in the sera of RA patients.
METHODS: IgM ACPA levels were determined in the serum of 176 RA patients by enzyme-linked immunosorbent assay, in which parameters of reactivity against citrullinated and non-citrullinated peptides were compared to ensure the specificity. Influence of IgM rheumatoid factor (RF) on IgM ACPA detection was examined by removing IgG, using protein G-conjugated beads, or by purifying ACPA, using citrullinated peptide-conjugated beads.
OBJECTIVES: Since the presence of IgM antibodies is a hallmark of ongoing immune response, we aimed to identify immunologically active rheumatoid arthritis (RA) patients by detecting IgM anti-citrullinated protein antibody (ACPA) levels..
85. Yusuke Kubo, Goro Motomura, Satoshi Ikemura, Kazuhiko Sonoda, Hiroyuki Hatanaka, Takeshi Utsunomiya, Shoji Baba, Yasuharu Nakashima, The effect of the anterior boundary of necrotic lesion on the occurrence of collapse in osteonecrosis of the femoral head, International Orthopaedics, 10.1007/s00264-018-3836-8, 2018.07, Purpose: The location of the necrotic lesion is one of the important factors for collapse in osteonecrosis of the femoral head (ONFH). The significance of anterior localization has been little studied. This study evaluated the effects of anterior boundary of a necrotic lesion on collapse. Methods: We reviewed the outcomes of 113 consecutive non-collapsed asymptomatic hips in 98 ONFH patients with mean follow-up of 4.7 years (2.0–11.8) after the initial magnetic resonance (MR) imaging. The presence or absence of collapse was investigated using follow-up radiographs. The location of the anterior boundary of a necrotic lesion was assessed using the anterior necrotic angle between the midline of the femoral neck shaft and the line passing from the femoral head centre to the anterior boundary on mid-oblique MR imaging. Multivariate analysis was performed to identify risk factors for collapse, and further analyses were executed according to the lateral boundary of the necrotic lesion. Results: During the follow-up period, collapse was confirmed in 61 hips (54.0%). Multivariate analysis revealed that the anterior necrotic angle was independently associated with collapse as well as the lateral boundary of the necrotic lesion. When the lateral boundary was located at the middle third of weight-bearing portion (32 hips), that was generally categorized as a low risk of collapse, all five cases with anterior necrotic angle ≥ 79° developed collapse, whereas only one of 27 cases (3.7%) with an anterior necrotic angle < 79° developed collapse (p < 0.0001). Conclusions: This study indicates that ONFH patients with anterior localization of a necrotic lesion can develop collapse even if the necrotic lesion is medially located..
86. Masaru Hada, Hideki Mizu-uchi, Ken Okazaki, Takao Kaneko, Koji Murakami, Yuan Ma, Satoshi Hamai, Yasuharu Nakashima, Bi-cruciate stabilized total knee arthroplasty can reduce the risk of knee instability associated with posterior tibial slope, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-017-4718-0, 2018.06, Purpose: The purpose of this study was to evaluate the relationship between posterior tibial slope and knee kinematics in bi-cruciate stabilized (BCS) total knee arthroplasty (TKA), which has not been previously reported. Methods: This computer simulation study evaluated Journey 2 BCS components (Smith & Nephew, Inc., Memphis, TN, USA) implanted in a female patient to simulate weight-bearing stair climbing. Knee kinematics, patellofemoral contact forces, and quadriceps forces during stair climbing (from 86° to 6° of flexion) were computed in the simulation. Six different posterior tibial slope angles (0°–10°) were simulated to evaluate the effect of posterior tibial slope on knee kinematics and forces. Results: At 65° of knee flexion, no anterior sliding of the tibial component occurred if the posterior tibial slope was less than 10°. Anterior contact between the anterior aspect of the tibial post- and the femoral component was observed if the posterior tibial slope was 6° or more. An increase of 10° in posterior tibial slope (relative to 0°) led to a 4.8% decrease in maximum patellofemoral contact force and a 1.2% decrease in maximum quadriceps force. Conclusion: BCS TKA has a wide acceptable range of posterior tibial slope for avoiding knee instability if the posterior tibial slope is less than 10°. Surgeons should prioritize avoiding adverse effects over trying to achieve positive effects such as decreasing patellofemoral contact force and quadriceps force by increasing posterior tibial slope. Our study helps surgeons determine the optimal posterior tibial slope during surgery with BCS TKA; posterior tibial slope should not exceed 10° in routine clinical practice..
87. Daisuke Shiraishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Toyohisa Iriki, Junko Tsuboki, Pan Cheng, Naomi Nakagata, Hiroshi Mizuta, Hirofumi Bekki, Yasuharu Nakashima, Yoshinao Oda, Motohiro Takeya, Yoshihiro Komohara, CD163 is required for protumoral activation of macrophages in human and murine sarcoma, Cancer Research, 10.1158/0008-5472.CAN-17-2011, 2018.06, Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here, we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histologic grade. We observed macrophage-induced tumor cell proliferation in cocultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison with wild-type (WT) mice. Coculture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison withWTmacrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL6 and CXCL2. Silencing of IL6 but not CXCL2 abrogated macrophageinduced proliferation ofMCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans. Significance: Macrophage CD163-mediated induction of IL6 promotes tumor development and progression in murine and human malignant tumors..
88. Koji Murakami, Satoshi Hamai, Ken Okazaki, Hirotaka Gondo, Yifeng Wang, Satoru Ikebe, Hidehiko Higaki, Takeshi Shimoto, Hideki Mizu-uchi, Yukio Akasaki, Yasuharu Nakashima, Knee kinematics in bi-cruciate stabilized total knee arthroplasty during squatting and stair-climbing activities, Journal of Orthopaedics, 10.1016/j.jor.2018.05.003, 2018.06, This study aimed to evaluate clinical outcomes and in vivo kinematics of bi-cruciate stabilized (BCS) total knee arthroplasty (TKA), using image-matching techniques. We analyzed tibiofemoral anteroposterior translation, axial rotation, and anterior/posterior cam-post contact for 22 BCS TKAs during squatting and stair-climbing. The functional activities on the 2011 Knee Society Score were significantly improved from 36 to 71. The tibiofemoral translation and axial rotation during squatting/stair-climbing were 16.1 mm/7.1 mm and 2.5° external/1.1° internal, respectively. Anterior/posterior cam-post contacts were observed during squatting (14%/96%) and stair-climbing (27%/96%). In conclusion, BCS TKA produced physiological sagittal plane kinematics during activities with favorable clinical outcomes..
89. Kenichi Kawaguchi, Katsumi Harimaya, Yoshihiro Matsumoto, Mitsumasa Hayashida, Seiji Okada, Keiichiro Iida, Go Kato, Kuniyoshi Tsuchiya, Toshio Doi, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima, Effect of cartilaginous endplates on extruded disc resorption in lumbar disc herniation, PloS one, 10.1371/journal.pone.0195946, 2018.04, Objective The aim of this study was to investigate the clinicopathologic features of lumbar disc herniation (LDH) with endplate degeneration and the association between cartilaginous fragments and inflammatory response to the herniated disc. Summary of background data LDH often involves hyaline cartilage fragments pulled from the vertebral endplates. Modic changes are closely associated with LDH that contains hyaline cartilage, and cartilaginous endplates seem to affect resorption of the herniated disc. Methods A total of 78 patients who underwent microscopic discectomy between 9 and 16 weeks after an occurrence of LDH were reviewed. Modic changes, disc degeneration, high-intensity zone, and vertebral corner defect were evaluated using magnetic resonance imaging (MRI). Histopathological observations of cartilaginous endplates and inflamed granulation tissue in the herniated disc were made. In cases with inflamed granulation tissue, neovascularization and macrophage infiltration were also evaluated using immunohistochemical analysis. Results Modic changes were observed in approximately one-third of the patients (26 cases: type 1, 7; type 2, 17; and type 3, 2). Cartilaginous endplates were observed in 32 cases (41%) and in the majority of cases with Modic changes compared with cases without Modic changes (65%, p = 0.001). Although inflamed granulation tissue was observed in 60 cases (77%), no significant differences were detected in patient age and the composition of the herniated material. Immunohistochemical analysis showed that fewer CD34-positive capillaries and CD68-positive cells were found in cases with cartilaginous fragments compared with those without cartilaginous fragments (p < 0.001). In addition, a higher immunoreactivity to CD34 and CD68 was found in herniated discs <25% of whose area was occupied by cartilaginous endplates compared with discs whose area was occupied at 25% or more (p < 0.001). Conclusion There is an association between LDH with endplate degeneration and cartilaginous herniation, with Modic type 2 predominating. Furthermore, neovascularization and macrophage infiltration, especially if the amount of cartilage is high, are likely to be less frequent in cartilaginous herniation, leading to failure in the spontaneous remission of clinical symptoms..
90. K. Murakami, S. Hamai, T. Moro-oka, K. Okazaki, H. Higaki, T. Shimoto, S. Ikebe, Y. Nakashima, Variable tibiofemoral articular contact stress in fixed-bearing total knee arthroplasties, Orthopaedics and Traumatology: Surgery and Research, 10.1016/j.otsr.2017.11.015, 2018.04, Background: Rotational allowance at the tibiofemoral joint would be required during deep flexion. However, the amount of flexion and rotation has not been investigated in modern total knee arthroplasty (TKA) designs. The present study aimed to determine the contact stress in five posterior-stabilized fixed-bearing TKA designs. Hypothesis: We hypothesized that the contact area and stresses at the tibiofemoral articular surfaces vary according to the type of implant design and tested condition. Materials and methods: The contact area and mean and peak contact stresses at the tibiofemoral articular surfaces were determined when a compressive load of 1200 N was applied to a NexGen LPS Flex, Scorpio NRG, Genesis II, PFC Sigma, and Foundation implant. Measurements were performed at 0° and 45° flexion with 0° 5° 10° and 15° rotation, and at 90° and 135° flexion with 0, 5° 10° 15° and 20° rotation. Results: The LPS Flex showed that the femoral component could not achieve 20° rotation at 135° flexion. The Scorpio NRG showed less than 20 MPa of contact stress at all conditions. The Genesis II showed higher contact stress than 20 MPa at 135° flexion with 20° rotation. The PFC Sigma showed that the femoral component could not achieve > 10° rotation at any flexion angle. The Foundation showed more than 20 MPa of contact stress at 90° flexion with 20° rotation and at 135° flexion with 10° 15° and 20° rotation. Discussion: Surgeons should be more aware of the variable contact conditions of the tibiofemoral articular surfaces in individual TKA designs. Level of evidence: Level IV, basic science study..
91. Kenyu Iwasaki, Takuaki Yamamoto, Goro Motomura, Kazuyuki Karasuyama, Kazuhiko Sonoda, Yusuke Kubo, Yasuharu Nakashima, Computed tomography findings of subchondral insufficiency fractures of the femoral head, Journal of Orthopaedics, 10.1016/j.jor.2018.01.044, 2018.03, Objectives: The objective of this study was to describe the appearance of Subchondral insufficiency fracture (SIF) by computed tomography (CT). Methods: Images of 52 consecutive patients diagnosed with SIF were retrospectively reviewed. CT was available for five patients (7 cases). Results: Corresponding to a low-intensity band on MR images, a radiolucent or sclerotic band was observed on CT images. Conclusion: The present study is the first to report CT findings of SIF. A radiolucent or sclerotic band was observed on CT images. The results of the present study provide useful information for diagnosis of SIF..
92. Hidetaka Yamamoto, Takeshi Iwasaki, Yuichi Yamada, Yoshihiro Matsumoto, Hiroshi Otsuka, Masato Yoshimoto, Kenichi Kohashi, Kenichi Taguchi, Ryohei Yokoyama, Yasuharu Nakashima, Yoshinao Oda, Diagnostic utility of histone H3.3 G34W, G34R, and G34V mutant-specific antibodies for giant cell tumors of bone, Human Pathology, 10.1016/j.humpath.2017.11.020, 2018.03, Giant cell tumors of bone (GCTBs) are characterized by mononuclear stromal cells and osteoclast-like giant cells; up to 95% have H3F3A gene mutation. The RANKL inhibitor denosumab, when used for the treatment of GCTB, leads to histological changes such as new bone formation and giant cell depletion. Here we assessed the diagnostic utility of immunohistochemical staining with the antibodies against histone H3.3 G34W, G34R and G34V mutant proteins for GCTB and other histologically similar bone and joint lesions. H3.3 G34W, G34R and G34V expressions were detected in mononuclear stromal cells in 47/51 (92%), 1/51 (2%) and 3/51 (6%) cases of primary GCTBs, respectively, in a mutually exclusive manner. All recurrent/metastatic GCTBs (n = 14), post-denosumab GCTBs (n = 8) and secondary malignant GCTBs (n = 2) were positive for H3.3 G34W. The immunohistochemical results were essentially correlated with the H3F3A genotype determined by mutation analysis. In post-denosumab GCTBs, H3.3 G34W expression was seen in immature bone-forming cells. H3.3 G34W, G34R and G34V were negative in 121/122 cases of non-GCTB, including chondroblastoma, osteosarcoma, primary aneurysmal bone cyst and other giant cell–rich lesions. The exception was a single case of undifferentiated high-grade pleomorphic sarcoma that was positive for H3.3 G34W, suggesting the possibility of sarcomatous overgrowth of primary malignant GCTB. Therefore, H3.3 G34W/R/V mutant-specific antibodies are useful surrogate markers for the H3F3A genotype and helpful for the diagnosis of GCTB and its variants. The expression of H3.3 G34W mutant protein in post-denosumab GCTB suggests that neoplastic stromal cells may play a role in new bone formation..
93. Hiroshi Otsuka, Kenichi Kohashi, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuichi Yamada, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda, Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors, Pathology Research and Practice, 10.1016/j.prp.2017.12.015, 2018.03, The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased..
94. Yasutaka Tashiro, Gian Andrea Lucidi, Tom Gale, Kanto Nagai, Elmar Herbst, James J. Irrgang, Yasuharu Nakashima, William Anderst, Freddie H. Fu, Anterior cruciate ligament tibial insertion site is elliptical or triangular shaped in healthy young adults
high-resolution 3-T MRI analysis
, Knee Surgery, Sports Traumatology, Arthroscopy, 10.1007/s00167-017-4607-6, 2018.02, Purpose: To clarify the morphology of anterior cruciate ligament (ACL) tibial insertion site in healthy young knees using high-resolution 3-T MRI. Methods: Subjects were 50 ACL-reconstructed patients with a mean age of 21.4 ± 6.8 years. The contralateral healthy knees were scanned using high-resolution 3-T MRI. The tibial insertion sites of the anteromedial (AM) and posterolateral (PL) bundle fibres, and the ACL attachment on the anterior horn of lateral meniscus (AHLM) were segmented from the MR images, and 3D models were reconstructed to evaluate the morphology. The shape of ACL footprint was qualitatively analysed, and the size of AM and PL attachments and AHLM overlapped area was measured digitally. Results: Tibial AM and PL bundles were clearly identified in 42 of 50 knees (84.0%). Morphology of the whole ACL tibial insertion site was elliptical in 23 knees (54.8%) and triangular in 19 knees (45.2%), but not classified as C-shape in any knees. However, the AM bundle attachment was of C-shape in 29 knees (69.0%) and band-like in 13 knees (31.0%). Overlap of ACL on AHLM was found in 26 knees (61.9%), and the size of the overlapped area was 4.8 ± 4.7% of the whole ACL insertion site. Conclusion: 3D morphology of the intact ACL tibial insertion site analysed by high-resolution 3-T MRI was elliptical or triangular in healthy young knees. However, the AM bundle insertion site was of C-shape or band-like. A small lateral portion of the ACL was overlapped with the AHLM. As for clinical relevance, these findings should be considered in order to reproduce the native ACL insertion site sufficiently. Level of evidence: III..
95. Yuichi Yamada, Izumi Kinoshita, Kohashi Kenichi, Hidetaka Yamamoto, Takeshi Iwasaki, Hiroshi Otsuka, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuki Kuma, Nokitaka Setsu, Yuki Koga, Yumi Honda, Takeshi Inoue, Hiroyuki Yanai, Kyoko Yamashita, Ichiro Ito, Mitsuru Takahashi, Shouichi Ohga, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda, Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant, Histopathology, 10.1111/his.13377, 2018.02, Aims: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by ‘smudgy/grungy’ calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. Methods and results: A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription–polymerase chain reaction (RT–PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT–PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. Conclusions: It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)–FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis..
96. Daisuke Hara, Satoshi Hamai, Keisuke Komiyama, Goro Motomura, Kyohei Shiomoto, Yasuharu Nakashima, Sports Participation in Patients After Total Hip Arthroplasty vs Periacetabular Osteotomy
A Propensity Score-Matched Asian Cohort Study
, Journal of Arthroplasty, 10.1016/j.arth.2017.08.035, 2018.02, Background: No studies have compared sports participation between total hip arthroplasty (THA) and periacetabular osteotomy (PAO) in matched Asian cohorts. We investigated sports participation and activity levels in Asian THA cohort, and compared them between THA and PAO cohorts. Methods: Multivariate analyses were applied to determine which factors were associated with postoperative sports participation and University of California-Los Angeles (UCLA) activity score in (1) 524 THA patients and (2) 487 acetabular dysplasia patients (295 THA patients and 192 PAO patients). In addition, postoperative sports participation and UCLA score were compared between 62 THA and 62 PAO patients after adjusting for baseline characteristics with propensity score matching. Results: Sports participation and UCLA score significantly increased after THA (P <.001 in both analyses). Preoperative sports participation was the factor most associated with both postoperative sports participation and UCLA score in both 524 THA patients and 487 acetabular dysplasia patients (P <.001 in all analyses). Multivariate analysis in 487 acetabular dysplasia patients demonstrated that THA, compared with PAO, was negatively associated with postoperative sports participation (P <.001), but not postoperative UCLA score (P =.22). THA patients showed significantly lower rate of postoperative sports participation (32.3% and 51.6%, respectively, P =.046), but not postoperative UCLA score (5.0 ± 1.6 and 5.2 ± 1.9, respectively, P =.47) compared with matched PAO patients. Conclusion: THA significantly increased both sports participation and activity levels. Both multivariate and propensity score-matched analyses showed that postoperative activity levels were comparable between THA and PAO cohorts..
97. Naoya Kozono, Takamitsu Okada, Naohide Takeuchi, Takeshi Shimoto, Hidehiko Higaki, Yasuharu Nakashima, A Biomechanical Comparison Between Asymmetric Pennington Technique and Conventional Core Suture Techniques
6-Strand Flexor Tendon Repair
, Journal of Hand Surgery, 10.1016/j.jhsa.2017.06.104, 2018.01, Purpose To evaluate the fatigue strength and gap sizes of the asymmetric Pennington technique compared with 2 conventional 6-strand core suture techniques: the triple-looped suture and the Yoshizu #1. Methods We recorded the fatigue strength (forces × cycles) and gap sizes of a 6-strand flexor tendon repair with different core suture techniques under cyclic loading in 30 porcine tendons. The asymmetric Pennington technique was performed with a Pennington repair of equal suture purchase in the 2 tendon stumps, with the 2 other Pennington repairs shifted by 3 mm, respectively, along the longitudinal axis of the tendon in relation to the first Pennington repair. The triple-looped suture technique was made with triple Tsuge sutures. The Yoshizu #1 technique was performed with a combined Pennington repair (using a double strand) and Tsuge suture. Results The asymmetric Pennington technique showed significantly greater fatigue strength and significantly smaller gaps in comparison to the triple-looped suture and Yoshizu #1 techniques. Conclusions This study demonstrated that the asymmetric Pennington technique generated increased fatigue strength and reduced gap sizes compared with 2 conventional 6-strand core suture techniques, the triple-looped suture and Yoshizu #1. Clinical relevance The asymmetric Pennington technique may permit an early active motion rehabilitation protocol similar to the triple-looped suture and Yoshizu #1 techniques..
98. Tetsuro Ushio, Ken Okazaki, Hideki Mizu-uchi, Satoshi Hamai, Yukio Akasaki, Yasuharu Nakashima, Anterior cruciate ligament reconstruction in a patient who has received systemic steroids for autoimmune disease, Asia-Pacific Journal of Sports Medicine, Arthroscopy, Rehabilitation and Technology, 10.1016/j.asmart.2017.11.003, 2018.01, Background An anterior cruciate ligament (ACL) reconstruction has become more common and the surgical morbidity has decreased, it has been performed not only in younger people to play sports but also middle-aged people, with satisfactory results. Therefore, some patients might have comorbidities for which they take medicines. Especially the medicines, such as systemic steroids, might influence the reconstructed ligament strength and durability. Case report A 49-year-old woman who was taking oral steroids for autoimmune hepatitis suffered a spontaneous ACL injury. She complained of unstable symptoms in the knee despite initial conservative treatment. Then, she was treated operatively with autologous hamstring tendon grafts. Three years postoperatively, her knee remained stable with 1.8 mm side-to-side difference on a Kneelax arthrometer and with 1.6 mm on anterior stress radiographs. There was no rerupture or instability. Conclusion The patient who had received systemic steroids for a long time recovered satisfactorily after the operation, with achievement of knee stability and possibility to prevent degenerative change in the knee joint. ACL reconstruction should be considered even in patients with such medication..
99. Seiji Okada, Masamitsu Hara, Kazu Kobayakawa, Yoshihiro Matsumoto, Yasuharu Nakashima, Astrocyte reactivity and astrogliosis after spinal cord injury, Neuroscience Research, 10.1016/j.neures.2017.10.004, 2018.01, After traumatic injuries of the central nervous system (CNS), including spinal cord injury (SCI), astrocytes surrounding the lesion become reactive and typically undergo hypertrophy and process extension. These reactive astrocytes migrate centripetally to the lesion epicenter and aid in the tissue repair process, however, they eventually become scar-forming astrocytes and form a glial scar which produces axonal growth inhibitors and prevents axonal regeneration. This sequential phenotypic change has long been considered to be unidirectional and irreversible; thus glial scarring is one of the main causes of the limited regenerative capability of the CNS. We recently demonstrated that the process of glial scar formation is regulated by environmental cues, such as fibrotic extracellular matrix material. In this review, we discuss the role and mechanism underlying glial scar formation after SCI as well as plasticity of astrogliosis, which helps to foster axonal regeneration and functional recovery after CNS injury..
100. Kenichiro Yahiro, Yoshihiro Matsumoto, Jun ichi Fukushi, Ken ichi Kawaguchi, Makoto Endo, Nokitaka Setsu, Keiichiro IIda, Suguru Fukushima, Makoto Nakagawa, Atsushi Kimura, Yoshinao Oda, Yasuharu Nakashima, Class III β-tubulin overexpression induces chemoresistance to eribulin in a leiomyosarcoma cell line, Analytical Cellular Pathology, 10.1155/2018/8987568, 2018.01, Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resistant leiomyosarcoma cell line to investigate the mechanism of resistance. The IC50 of eribulin was 125 times higher in the resistant cell line than in the parental cell line, and eribulin did not induce G2/M arrest in resistant cells. The resistant cell line showed increased expression of MDR1 transcript, but protein levels and functional analysis results were similar to the parental cell line. We found that class III β-tubulin (TUBB3) was overexpressed in the resistant cell line, and siRNA knockdown of TUBB3 partially recovered sensitivity to eribulin. TUBB3 expression in clinical samples varied, suggesting that TUBB3 has the potential to be a biomarker for selection of anticancer drugs and may be a target for overcoming resistance to eribulin..
101. Yoshihiro Matsumoto, Kenichi Kawaguchi, Jun ichi Fukushi, Makoto Endo, Nokitaka Setsu, Keiichiro Iida, Satoshi Baba, Hirokazu Saiwai, Akinobu Matsushita, Mitsumasa Hayashida, Seiji Okada, Yasuharu Nakashima, Clinical outcome and prognostic factors of malignant spinal dumbbell tumors, Spine Surgery and Related Research, 10.22603/ssrr.2018-0004, 2018.01, Introduction: To investigate the clinical outcome and prognostic factors of malignant spinal dumbbell tumors (m-SDTs). Methods: We retrospectively reviewed the clinical outcome of 22 consecutive cases of m-SDTs and analyzed the prognostic factors associated with worse outcome. Results: Nineteen of the 22 cases were managed with surgery (86%), and gross total resection (GTR) was achieved in four cases (21%). The duration of overall survival (OS) ranged from 3 to 140 months, with a median survival time of 15.3 months. The 5 year OS rate was 55.6%. In multivariate analysis, histological subtype (high-grade malignant peripheral nerve sheath tumor) (hazard ratio [HR] 14.9, p = 0.0191), GTR (HR 0.07, p = 0.0343), and presence of local recurrences (HR 11.2, p = 0.0479) were significant and independent predictors of OS. Conclusions: On the basis of clinical data, we propose that GTR and prevention of local recurrence may improve the clinical outcome of m-SDTs..
102. Miho Iwamoto, Yasuharu Nakashima, Tomoyuki Nakamura, Yusuke Kohno, Ryosuke Yamaguchi, Kazuyuki Takamura, Clinical outcomes of conservative treatment with a non-weight-bearing abduction brace for Legg–Calvé–Perthes disease, Journal of Orthopaedic Science, 10.1016/j.jos.2017.09.012, 2018.01, Background Treatment with a brace is the first choice as conservative treatment via the containment method for Legg–Calvé–Perthes disease (LCPD). The purpose of this study is to evaluate clinical outcomes and influential factors of conservative treatment with the non-weight-bearing abduction brace for LCPD. Methods One hundred thirty hips in 130 patients were examined in this study. The mean age at onset was 7.0 years (3.3–12.4 years) and the mean follow-up period was 8.4 years (4.1–17.6 years). The extent of necrosis and lateral collapse of the femoral head were evaluated using the Catterall classification and the lateral pillar classification, respectively. Radiological outcome was assessed as good (classes I and II), fair (III), and poor (IV), according to the modified Stulberg classification. Results Radiographic outcome at final follow-up was good in 82 hips (63%), fair in 40 hips (31%), and poor in 8 hips (6%). Multinomial logistic regression analysis showed that major influential factors for good outcomes were as follows: age at onset, lateral pillar classification, and Catterall classification. From the receiver operating characteristic curve, the cut-off value for age at onset was 8.4 years old to obtain good outcomes. Hips with Catterall group I and II and lateral pillar group A and B had significantly better results. Conclusion Patients younger than 8.4 years old at onset with lateral pillar group A or B or Catterall group I or II showed good outcomes with a non-weight-bearing abduction brace for LCPD. These results show that alternative treatment, such as surgery, may be another option for patients who are not included in the above groups..
103. Naoya Kozono, Takamitsu Okada, Naohide Takeuchi, Satoshi Hamai, Hidehiko Higaki, Takeshi Shimoto, Satoru Ikebe, Hirotaka Gondo, Yoshitaka Nakanishi, Takahiro Senju, Yasuharu Nakashima, Dynamic kinematics of the glenohumeral joint in shoulders with rotator cuff tears, Journal of Orthopaedic Surgery and Research, 10.1186/s13018-017-0709-6, 2018.01, Background: No clear trend has emerged from the literature regarding three-dimensional (3D) translations of the humerus relative to the scapula in shoulders with rotator cuff tears (RCTs). The purpose of this study was to evaluate the kinematics of RCT shoulders using 3D-to-two-dimensional (2D) model-to-image registration techniques. Methods: Dynamic glenohumeral kinematics during scapular plane abduction and axial rotation were analyzed in 11 RCT patients and 10 healthy control subjects. We measured the 3D kinematic parameters of glenohumeral joints using X-ray images and CT-derived digitally reconstructed radiographs. Results: For scapular plane abduction, the humeral head center was positioned significantly more medially in shoulders with RCTs than in controls at 135° of humeral abduction (p = 0.02; RCTs versus controls: - 0.9 ± 1.6 versus 0.3 ± 1.3 mm). There was no significant difference in the superior/inferior translation of the humeral head center (p = 0.99). For axial rotation in adducted position, the humeral head center was positioned significantly more anteriorly in shoulders with RCTs than in controls at - 30° of glenohumeral external rotation (p < 0.0001; RCTs versus controls: 3.0 ± 1.7 versus 0.3 ± 1.5 mm). Conclusions: This study revealed the kinematics of shoulders with large to massive full-thickness RCTs: the humeral head center showed a medial shift at the late phase of scapular plane full abduction, and an anterior shift at the internal rotation position during full axial rotation. The kinematic data in this study, which describe the patterns of movement of shoulders with large to massive full-thickness RCTs, provide valuable information for future studies investigating glenohumeral translations in other pathological conditions of the shoulder. For clinical relevance, quantitative assessment of the dynamic kinematics of shoulders with RCTs might be a therapeutic indicator for achieving functional restoration..
104. Yuan Ma, Hideki Mizu-uchi, Ken Okazaki, Tetsuro Ushio, Koji Murakami, Satoshi Hamai, Yukio Akasaki, Yasuharu Nakashima, Effects of tibial baseplate shape on rotational alignment in total knee arthroplasty
three-dimensional surgical simulation using osteoarthritis knees
, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-017-2828-2, 2018.01, Introduction: Placement of tibial component is expected to fulfill both maximum surface coverage and recommended anterior–posterior (AP) alignment in total knee arthroplasty (TKA). The purpose of this study is to evaluate the effect of the tibial baseplate shape on AP axis. Materials and methods: Virtual surgery of TKA was performed with three-dimensional bone models reconstructed from 77 osteoarthritis varus knees. Two differently designed tibial baseplates, symmetrically and anatomically, were set to the cut surface under posterior slopes of 0°, 3°, and 7°. The AP axes were defined by connecting the geometrical center of the cut surface with the medial edge (axis MED) and medial 1/3 (axis 1/3MED) of patella tendon attachment. We evaluated the overhang rates as well as the most fitting AP axis which passes through the geometric center. Results: Overhang rates when aligned to axis MED were 12–25% for the symmetrical-type group and 13–22% for the anatomical-type group. Overhang rates when aligned to axis 1/3MED were 42–48% for the symmetrical-type group and 3–7% for the anatomical-type group. The most fitting AP axis of tibial baseplate was located 2.5° external to axis MED for the symmetrical-type group and around 3.3° internal to axis 1/3MED for the anatomical-type group. Conclusions: Symmetrically or anatomically designed tibial baseplates have their own favored AP axis and specific performance on coverage. When aligned to axis 1/3MED, anatomically designed tibial baseplates will effectively lower the mismatch rates compared to a symmetrically designed tibial baseplate. Orthopaedic surgeons are expected to place the tibial components to the cut surface during TKA with full understanding of the features between different baseplate designs, AP axes, and posterior slopes for an ideal tibial rotational position..
105. Shoji Baba, Goro Motomura, Satoshi Ikemura, Kazuhiko Sonoda, Yusuke Kubo, Takeshi Utsunomiya, Hiroyuki Hatanaka, Yasuharu Nakashima, Femoral head fracture similar to slipped capital femoral epiphysis in an elderly woman with antecedent hip osteoarthritis after subchondral insufficiency fracture
A case report
, Journal of Orthopaedic Science, 10.1016/j.jos.2017.09.009, 2018.01.
106. Daisuke Abe, Satoshi Hamai, Ken Okazaki, Masato Yoshimoto, Takashi Komatsu, Yasuharu Nakashima, Inverted V-shaped high tibial osteotomy for severe tibia vara associated with Turner syndrome
A case report and review of literature
, International Journal of Surgery Case Reports, 10.1016/j.ijscr.2017.12.008, 2018.01, Introduction Severe cases of genu varum represent a major challenge in obtaining normal configuration of the proximal tibia and overall limb alignment. Presentation of case We performed inverted V-shaped high tibial osteotomy (HTO) by using a locking plate for recurrent severe bilateral tibia vara in a 15-year-old female patient with Turner syndrome. Preoperative medial proximal tibial angle (MPTA) and standing femorotibial angle (FTA) of the right/left legs were 67°/69° and 197°/203°, respectively. In order to obtain overall neutral alignment, the correction angle in the right/left knees was required to be 23°/32°. Preoperative planning demonstrated that inverted V-shaped HTO could provide sufficient correction angle with large bone stock and wide bony contact. A postoperative full-standing radiograph showed that the mechanical axes passed through the center of right/left knees with 87°/88° of MPTA. Discussion Inverted V-shaped HTO has advantages, as it requires a smaller amount of bone resection and smaller opening gap compared to the closing-wedge and opening-wedge osteotomies. Conclusion Inverted V-shaped HTO can be a useful surgical method to treat severe tibia vara in order to obtain adequate configuration of the proximal tibia and overall limb alignment..
107. Kensei Yoshimoto, Satoshi Hamai, Hidehiko Higaki, Hirotaka Gondo, Satoru Ikebe, Yasuharu Nakashima, Pre- and post-operative evaluation of pincer-type femoroacetabular impingement during squat using image-matching techniques
A case report
, International Journal of Surgery Case Reports, 10.1016/j.ijscr.2017.12.007, 2018.01, Introduction Although combined evaluation of hip joint kinematics and bone morphology is necessary for accurate assessment of femoroacetabular impingement (FAI), there are no report which evaluated hip kinematics of pincer-type FAI. Presentation of case The pre- and postoperative hip kinematics of a 46-year-old man, with a pincer-type FAI during squat were evaluated using image-matching techniques and the rim-neck distance was measured. Preoperative simulation of squatting was also performed using patient's bone models and healthy subject's kinematics data to detect the overlapping lesion between the acetabulum and the femur. Post-acetabuloplasty, right coxalgia during squat disappeared, and the Harris Hip Score improved from 79 to 92 at one year after surgery. Posterior pelvic tilt, femoral and hip flexion angle changed from 24.0°, 101.1°, and 70.8° to 23.3°, 92.6°, and 63.3°, respectively. The minimum rim-neck distance at maximum hip flexion improved from 1.8 mm to 7.3 mm. Discussion We could evaluate both of hip kinematics and morphology with image-matching techniques, and could visualize the clearance between the femoral head-neck junction and the acetabular rim. Conclusion Image-matching techniques were clinically useful to assist surgeons in detecting the location of the impingement and confirming resection of the pincer lesion post-operatively..
108. Satoshi Baba, Yoshihiro Matsumoto, Shinji Tomari, Takahiro Yasuhara, Hirokazu Saiwai, Akinobu Matsushita, Tatsuya Yufu, Mitsumasa Hayashida, Seiji Okada, Kenichi Kawaguchi, Kenichi Seo, Yasumasa Ito, Yasuharu Nakashima, Radiological examination of postoperative cervical alignment and stability in patients with dialysis-associated spondylosis excluding destructive spondyloarthropathy
Comparison with patients with cervical spondylotic myelopathy
, Spine Surgery and Related Research, 10.22603/ssrr.2017-0068, 2018.01, Introduction: Several reports have demonstrated the surgical treatment strategy for patients with dialysis-associated spondylosis in the cervical spine (CDAS) with destructive spondyloarthropathy (DSA). However, studies focusing on the clinical outcome of patients with CDAS without DSA remain scarce. We aimed to review the treatment strategy of patients with CDAS but without DSA. Methods: The clinical data and surgical records of consecutive patients with CDAS without DSA (n = 9; D-group) and cervical spondylotic myelopathy (CSM) (n = 30; C-group) who underwent modified double-door laminoplasty(DDL) were reviewed retrospectively. We investigated four radiologic factors in the pre-and postoperative periods that have been reported to be the risk factors for worsening of clinical symptoms in various studies and examined statistical comparison between the D and C groups. Results: In the D group, the pre- versus postoperative C2-C7 sagittal angles were not significantly different, and only two patients (22%) had kyphosis postoperatively. There was a significant difference in the pre- and postoperative C2-C7 angles in the two groups (P = 0.031). Regarding the change in segmental alignment, the local open angle increased at the C4/C5 level in the D group. Also there was a significant difference in the local angles between the two groups at C4/5 and C5/6 (P = 0.00038, and 0.037), suggesting that postoperative segmental mobility at C4/5 and C5/6 was higher in the D group than in the C group. Conclusions: In the present study, DDL in patients with CDAS without DSA did not adversely affect the postoperative alignment and stability compared with CSM patients with CSM. However, patients in the D group may have a chance to develop DSA change at the C4/5 level in the future, and careful long-term follow-up is warranted..
109. Kazuyuki Karasuyama, Goro Motomura, Satoshi Ikemura, Jun ichi Fukushi, Satoshi Hamai, Kazuhiko Sonoda, Yusuke Kubo, Takuaki Yamamoto, Yasuharu Nakashima, Risk factor analysis for postoperative complications requiring revision surgery after transtrochanteric rotational osteotomy for osteonecrosis of the femoral head, Journal of Orthopaedic Surgery and Research, 10.1186/s13018-018-0714-4, 2018.01, Background: This study investigated the risk factors for postoperative complications requiring revision surgery within 3 years after transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH). Methods: We reviewed 127 patients (147 hips) who underwent TRO (anterior or posterior rotational osteotomy) for ONFH between January 2002 and December 2014. Two patients were lost to follow-up, and five patients with progression of femoral head collapse requiring a salvage procedure such as total hip arthroplasty within 3 years after TRO were excluded. The better hip in patients treated bilaterally was also excluded (n = 20) to avoid duplication of patient demographics, leaving 120 hips (120 patients) for the analysis. We reviewed the medical records of each patient to screen for postoperative complications that required revision surgery within 3 years after surgery, recording the patient's age, sex, body mass index, surgical side, condition of the contralateral hip, previous alcohol intake, previous alcohol abuse, previous corticosteroid use, perioperative corticosteroid use, smoking status, preoperative stage and type of ONFH, preoperative activity level, and preoperative and final follow-up Japanese Orthopaedic Association scores. Differences between cases with and without complications were analyzed. Results: Eleven (9.2%) cases showed postoperative complications that required revision surgery. The most common complication was deep infection (n = 5), followed by nonunion of the greater trochanter (n = 3), nonunion of the intertrochanteric osteotomy site (n = 2), and femoral head fracture (n = 1). The multivariate analysis showed an independent association between previous alcohol abuse and postoperative complications (odds ratio, 13.5). Conclusion: A correlation might exist between alcohol abuse and complications following a TRO procedure..
110. Koichiro Kawano, Goro Motomura, Satoshi Ikemura, Yusuke Kubo, Hiroyuki Hatanaka, Takeshi Utsunomiya, Shoji Baba, Yasuharu Nakashima, Subchondral insufficiency fracture of the femoral head in an elderly woman with symptomatic osteoarthritis of the contralateral hip, Journal of Orthopaedic Science, 10.1016/j.jos.2018.02.001, 2018.01.
111. Teruaki Ono, Kiyoshi Tarukado, Osamu Tono, Katsumi Harimaya, Yuichiro Morishita, Yasuharu Nakashima, Toshio Doi, The morphological relationship between lumbosacral transitional vertebrae and lumbosacral pedicle asymmetry, Spine Surgery and Related Research, 10.22603/ssrr.2017-0012, 2018.01, Introduction: The clinical significance of lumbosacral transitional vertebrae (LSTV) has been reported. However, the association between LSTV and lumbosacral pedicle anatomical anomaly has not been investigated. We hypothesized that LSTV might be associated with lumbosacral anatomical anomaly. The purpose of this study was to examine the morphological association between LSTV and lumbosacral pedicle asymmetry (PA) using computed tomography (CT). Methods: A retrospective review of CT images of 347 lumbosacral degenerative disease patients was performed. We divided the subjects into two groups: the normal and LSTV groups. LSTV was classified based on Castellvi’s classification. PA was defined as a difference of more than 20° between the right and left angles of the pedicle. Results: Seventy out of 347 lumbosacral degenerative disease patients (20.17%) were diagnosed with LSTV. In the normal group, only a 0.54% incidence of PA was seen; however, with respect to the LSTV group, a 9.29% incidence of PA was seen. A significant difference in PA incidence was observed between the groups (p < 0.001). Type IIIa and Type IV in the LSTV group showed a statistically significant PA incidence rate (p = 0.004 and p = 0.039, respectively). Conclusions: Our study demonstrated that there was a significant difference in the incidence of PA between LSTV subjects and normal subjects. Moreover, the incidence of PA was significantly higher in LSTV subjects with severe anomaly. These results suggested that lumbosacral spine anomaly might have a close relationship with the incidence of PA and lumbosacral nerve root asymmetry. Therefore, morphological evaluation of the pedicle is important for preoperative surgical management, especially in cases using pedicle screws. This information could lower the incidence of pedicle screw malposition when pedicle screws are inserted at the lumbosacral spine..
112. Keiichiro Iida, Yoshihiro Matsumoto, Nokitaka Setsu, Katsumi Harimaya, Kenichi Kawaguchi, Mitsumasa Hayashida, Seiji Okada, Yasuharu Nakashima, The neurological outcome of radiotherapy versus surgery in patients with metastatic spinal cord compression presenting with myelopathy, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-017-2817-5, 2018.01, Purpose: While radiotherapy is generally an acceptable treatment for metastatic spinal cord compression, surgical intervention is controversial due to the invasiveness and diversity of diseases in the patients being considered. The ideal treatment, therefore, depends on the situation, and the most acute treatment possible is necessary in patients presenting with myelopathy. We compared the neurological outcomes between radiotherapy and surgery in patients with metastatic spinal cord compression presenting with myelopathy. Methods: A total 54 patients with metastatic spinal cord compression presenting with myelopathy treated in our institution between 2006 and 2016 were analyzed retrospectively. Twenty patients were selected by radiotherapy alone (radiation group), and 36 patients were selected by decompression and stabilization surgery with or without radiotherapy (surgery group). The neurological outcomes and complications were compared between the two treatment groups. Results: Seven patients initially in the radiation group underwent surgery because of a substantial decline in their motor strength during radiotherapy. One of the remaining 13 patients (8%) in the radiation group and 30 of the 34 patients (88%) in the surgery group showed improvement in their neurological symptoms (P < 0.01). One patient (8%) in the radiation group and 21 patients (62%) in the surgery group were ambulatory after treatment (P < 0.01). There were no major complications related to radiotherapy, but surgery-related complications occurred in 9 of 34 (26%) patients, and 6 (18%) patients needed reoperation. Conclusions: Surgical decompression and stabilization may be required to improve the neurological function in patients with metastatic spinal cord compression presenting with myelopathy. However, the high rate of complications associated with surgery should be taken into consideration..
113. Hirofumi Bekki, Katsumi Harimaya, Yoshihiro Matsumoto, Kenichi Kawaguchi, Mitsumasa Hayashida, Seiji Okada, Toshio Doi, Yasuharu Nakashima, Which side-bending X-ray position is better to evaluate the preoperative curve flexibility in adolescent idiopathic scoliosis patients, supine or prone?, Asian Spine Journal, 10.31616/ASJ.2018.12.4.632, 2018.01, Study Design: Prospective cohort study. Purpose: The present study aimed to evaluate the difference in the preoperative curve flexibility between the supine and prone positions in patients with adolescent idiopathic scoliosis (AIS). Overview of Literature: In AIS, a side-bending view is necessary to differentiate a structural curve from a nonstructural curve using the Lenke classification system. However, there are no published studies about which position, supine or prone, is more effective when evaluating preoperative curve flexibility using side-bending X-ray images in AIS patients. Methods: Radiographs were analyzed for 32 AIS patients (26 females, six males) who underwent posterior correction and fusion of their main thoracic (MT) curves. Cobb angles of MT, proximal thoracic (PT), and thoracolumbar/lumbar (TL/L) curves were measured preoperatively using upright, supine (anteroposterior and side-bending), and prone (posteroanterior and side-bending) X-rays. Results: The average Cobb angles of PT, MT, and TL/L curves on preoperative upright/supine/prone X-rays were 29.1°/26.7°/26.6°, 60.7°/48.5°/48.2°, and 41.0°/32.6°/33.1°, respectively. The average Cobb angles of PT, MT, and TL/L curves on supine/prone sidebending X-rays were 19.2°/20.3°, 36.3°/36.4°, and 13.9°/15.7°, respectively. The flexibility rates of PT, MT, and TL/L curves in supine/ prone positions were 35.3%/32.5%, 40.6%/40.2%, and 71.7%/68.2%, respectively. Comparing flexibility rates in the prone position with those in the supine position in each case, the average ratios of PT, MT, and TL/L curves were found to be 1.0, 1.0, and 0.9, respectively. There were no statistically significant differences between supine and prone side-bending X-ray measurements. However, the Lenke classification in six of 32 patients (18.8%) differed between supine and prone positions because the TL/L curve in the supine position was slightly more flexible than in the prone position. Conclusions: Supine side-bending films may be suitable for the evaluation of preoperative curve flexibility in AIS, especially for lumbar modifier C..
114. Yasutaka Tashiro, Ken Okazaki, Koji Murakami, Hirokazu Matsubara, Kanji Osaki, Yukihide Iwamoto, Yasuharu Nakashima, Anterolateral rotatory instability in vivo correlates tunnel position after anterior cruciate ligament reconstruction using bone-patellar tendon-bone graft, World Journal of Orthopaedics, 10.5312/wjo.v8.i12.913, 2017.12, AIM To quantitatively assess rotatory and anterior-posterior instability in vivo after anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BTB) autografts, and to clarify the influence of tunnel positions on the knee stability. METHODS Single-bundle ACL reconstruction with BTB autograft was performed on 50 patients with a mean age of 28 years using the trans-tibial (TT) (n = 20) and trans-portal (TP) (n = 30) techniques. Femoral and tibial tunnel positions were identified from the high-resolution 3D-CT bone models two weeks after surgery. Anterolateral rotatory translation was examined using a Slocum anterolateral rotatory instability test in open magnetic resonance imaging (MRI) 1.0-1.5 years after surgery, by measuring anterior tibial translation at the medial and lateral compartments on its sagittal images. Anterior-posterior stability was evaluated with a Kneelax3 arthrometer. RESULTS A total of 40 patients (80%) were finally followed up. Femoral tunnel positions were shallower (P < 0.01) and higher (P < 0.001), and tibial tunnel positions were more posterior (P <0.05) in the TT group compared with the TP group. Anterolateral rotatory translations in reconstructed knees were significantly correlated with the shallow femoral tunnel positions (R = 0.42, P < 0.01), and the rotatory translations were greater in the TT group (3.2 ± 1.6 mm) than in the TP group (2.0 ± 1.8 mm) (P < 0.05). Side-to-side differences of Kneelax3 arthrometer were 1.5 ± 1.3 mm in the TT, and 1.7 ± 1.6 mm in the TP group (N.S.). Lysholm scores, KOOS subscales and reinjury rate showed no difference between the two groups. CONCLUSION Anterolateral rotatory instability significantly correlated shallow femoral tunnel positions after ACL reconstruction using BTB autografts. Clinical outcomes, rotatory and anterior-posterior stability were overall satisfactory in both techniques, but the TT technique located femoral tunnels in shallower and higher positions, and tibial tunnels in more posterior positions than the TP technique, thus increased the anterolateral rotation. Anatomic ACL reconstruction with BTB autografts may restore knee function and stability..
115. Yuma Sakamoto, Takuaki Yamamoto, Nobuhiko Sugano, Daisuke Takahashi, Toshiyuki Watanabe, Takashi Atsumi, Junichi Nakamura, Yukiharu Hasegawa, Koichi Akashi, Ichiei Narita, Takeshi Miyamoto, Tsutomu Takeuchi, Katsunori Ikari, Koichi Amano, Atsuhiro Fujie, Toshikazu Kubo, Yoshifumi Tada, Ayumi Kaneuji, Hiroaki Nakamura, Tomoya Miyamura, Tamon Kabata, Ken Yamaji, Takahiro Okawa, Akihiro Sudo, Kenji Ohzono, Yoshiya Tanaka, Yuji Yasunaga, Shuichi Matsuda, Yuuki Imai, Yasuharu Nakashima, Goro Motomura, Satoshi Ikemura, Ryosuke Yamaguchi, Kazuyuki Karasuyama, Kazuhiko Sonoda, Takashi Nishii, Takashi Sakai, Masaki Takao, Tohru Irie, Tsuyoshi Asano, Norimasa Iwasaki, Tatsuya Atsumi, Satoshi Tamaoki, Ryosuke Nakanishi, Satoe Tanabe, Shunji Kishida, Shigeo Hagiwara, Taisuke Seki, Hiroshi Tsukamoto, Hiroaki Niiro, Yojiro Arinobu, Mitsuteru Akahoshi, Hiroshi Mitoma, Masahiro Ayano, Takeshi Kuroda, Yoshiaki Toyama, Atsushi Funayama, Hironari Hanaoka, Kunihiro Yamaoka, Yasushi Kawaguchi, Hisashi Yamanaka, Tetsuji Hosozawa, Shigeki Momohara, Kentaro Chino, Mikihiro Fujioka, Keichiro Ueshima, Masashi Ishida, Masazumi Saito, Shigeki Hayashi, Akira Ikegami, Toru Ichiseki, Shigekazu Mizokawa, Yoichi Ohta, Yoshitomo Kajino, Fumio Sekiya, Fujio Higuchi, Masahiro Hasegawa, Noriki Miyamoto, Shinichi Miyazaki, Toshio Yamaguchi, Wataru Ando, Kazuyoshi Saito, Kazuhisa Nakano, Yutaka Kuroda, Takuma Yamasaki, Masato Akiyama, Michiaki Kubo, Yoichiro Kamatani, Yukihide Iwamoto, Shiro Ikegawa, Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head, Scientific reports, 10.1038/s41598-017-14778-y, 2017.12, Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH..
116. Takeyuki Saito, Masamitsu Hara, Hiromi Kumamaru, Kazu Kobayakawa, Kazuya Yokota, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yoshihiro Matsumoto, Kenichi Kawaguchi, Mitsumasa Hayashida, Yutaka Inagaki, Keiichiro Shiba, Yasuharu Nakashima, Seiji Okada, Macrophage Infiltration Is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts, American Journal of Pathology, 10.1016/j.ajpath.2017.08.020, 2017.12, Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although previous studies have been performed on LF hypertrophy, its pathomechanisms have not been fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a microinjury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human. However, we found that macrophage depletion by injecting clodronate-containing liposomes counteracted LF hypertrophy even with microinjury. For identification of fibroblasts in the LF, we used collagen type I α2 linked to green fluorescent protein transgenic mice and selectively isolated green fluorescent protein–positive fibroblasts from the microinjured LF using laser microdissection. A quantitative RT-PCR on laser microdissection samples revealed that the gene expression of collagen markedly increased in the fibroblasts at the injured site with infiltrating macrophages compared with the uninjured location. These results suggested that macrophage infiltration was crucial for LF hypertrophy by stimulating collagen production in fibroblasts, providing better understanding of the pathophysiology of LF hypertrophy..
117. Masanori Fujii, Tetsuro Nakamura, Toshihiko Hara, Yasuharu Nakashima, Can the hip joint center be estimated from pelvic dimensions in dysplastic hips?, Journal of Orthopaedic Science, 10.1016/j.jos.2017.08.013, 2017.11, Background We aimed to determine correlations between the hip joint center position and pelvic dimensions and whether the three-dimensional position of the original hip joint center could be estimated from pelvic landmarks in dysplastic and normal hips. Methods We reviewed the pelvic CT scans of 70 patients (70 hips) with hip dysplasia. Seventy-seven normal hips were used as controls. The hip joint center coordinates (Cx, Cy, and Cz) and pelvic dimensions were measured with reference to the anterior pelvic plane coordinate system. Multiple regression formulas were used to estimate the original hip joint center. Results The hip center for both dysplastic and normal hip was highly correlated with the distance between the anterior superior iliac spine (ASIS) in the coronal plane (r = 0.76 and 0.84), the distance from the ASIS to the pubic tubercle in the sagittal plane (r = 0.81 and 0.76), and distance from the pubic tubercle to the most posterior point of the ischium on the transverse plane (r = 0.76 and 0.78). The hip joint center could be estimated within a 5-mm error for more than 80% of hips on their respective axes in both dysplastic and normal hips. Conclusions The three-dimensional position of the original hip joint center was correlated with pelvic dimensions, and can be estimated with substantial accuracy using pelvic landmarks as references. Although these results are preliminary, this estimation method may be useful for surgeons planning total hip arthroplasties..
118. K. Sonoda, G. Motomura, S. Ikemura, Y. Kubo, T. Yamamoto, Y. Nakashima, Effects of intertrochanteric osteotomy plane and preoperative femoral anteversion on the postoperative morphology of the proximal femur in transtrochanteric anterior rotational osteotomy
3D CT-based simulation study
, Orthopaedics and Traumatology: Surgery and Research, 10.1016/j.otsr.2017.06.012, 2017.11, Background Transtrochanteric anterior rotational osteotomy (ARO) is joint-preserving surgery for patients with osteonecrosis of the femoral head (ONFH). During ARO, femoral neck-shaft varus angulation by changing intertrochanteric osteotomy plane is often designed to obtain a sufficient postoperative intact ratio. However, the effect of intertrochanteric osteotomy plane on postoperative femoral anteversion has not been well examined. Therefore, we performed a simulation study of ARO to determine how intertrochanteric osteotomy plane and preoperative femoral anteversion affect both femoral neck-shaft varus angle and postoperative femoral anteversion. Hypothesis Both femoral neck-shaft varus angle and postoperative femoral anteversion are predicted by intertrochanteric osteotomy plane and preoperative femoral anteversion in ARO. Materials and methods Using CT-data obtained from 10 hips in 10 patients with ONFH, ARO was simulated. On anteroposterior view, basic intertrochanteric osteotomy line (AP-view line) was defined as the perpendicular line to the femoral neck axis. On lateral view, basic intertrochanteric osteotomy line (lateral-view line) made through the cut surface of greater trochanter was defined as the perpendicular line to the lateral axis of the femur. By changing either AP-view or lateral-view line, 49 ARO models/hip were produced, in which femoral neck-shaft varus angle and postoperative femoral anteversion were assessed. Results With increase in the vertically-inclined degree of AP-view line, both neck-shaft varus angle and postoperative femoral anteversion increased. With increase in the posteriorly-tilted degree of lateral-view line, neck-shaft varus angle increased, whereas postoperative femoral anteversion decreased. The approximation equations based on the multiple regression analyses were as follows: neck-shaft varus angle ≈ vertically-inclined degree of AP-view line × 0.9 + posteriorly-tilted degree of lateral-view line × 0.8 + preoperative femoral anteversion × 0.7; postoperative femoral anteversion ≈ vertically-inclined degree of AP-view line × 1.1 − posteriorly-tilted degree of lateral-view line × 0.8. Discussion The postoperative morphology of proximal femur was nearly defined by intertrochanteric osteotomy plane with preoperative femoral anteversion, which is useful for preoperative planning in terms of both achieving a sufficient postoperative intact ratio and maintaining femoral anteversion. Level of evidence Level IV case series without control group..
119. Norio Goto, Ken Okazaki, Yukio Akasaki, Kohei Ishihara, Koji Murakami, Kiyoshi Koyano, Yasunori Ayukawa, Noriyuki Yasunami, Tomohiro Masuzaki, Yasuharu Nakashima, Single intra-articular injection of fluvastatin-PLGA microspheres reduces cartilage degradation in rabbits with experimental osteoarthritis, Journal of Orthopaedic Research, 10.1002/jor.23562, 2017.11, Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA..
120. Umito Kuwashima, Hideki Mizu-uchi, Ken Okazaki, Satoshi Hamai, Yukio Akasaki, Koji Murakami, Yasuharu Nakashima, Three-dimensional analysis of accuracy of patient-matched instrumentation in total knee arthroplasty
Evaluation of intraoperative techniques and postoperative alignment
, Journal of Orthopaedic Science, 10.1016/j.jos.2017.08.010, 2017.11, Background It is questionable that the accuracies of patient-matched instrumentation (PMI) have been controversial, even though many surgeons follow manufacturers’ recommendations. The purpose of this study was to evaluate the accuracy of intraoperative procedures and the postoperative alignment of the femoral side using PMI with 3-dimensional (3D) analysis. Methods Eighteen knees that underwent total knee arthroplasty using MRI-based PMI were assessed. Intraoperative alignment and bone resection errors of the femoral side were evaluated with a CT-based navigation system. A conventional adjustable guide was used to compare cartilage data with that derived by PMI intraoperatively. Postoperative alignment was assessed using a 3D coordinate system with a computer-assisted design software. We also measured the postoperative alignments using conventional alignment guides with the 3D evaluation. Results Intraoperative coronal alignment with PMI was 90.9° ± 1.6°. Seventeen knees (94.4%) were within 3° of the optimal alignment. Intraoperative rotational alignment of the femoral guide position of PMI was 0.2° ± 1.6°compared with the adjustable guide, with 17 knees (94.4%) differing by 3° or less between the two methods. Maximum differences in coronal and rotation alignment before and after bone cutting were 2.0° and 2.8° respectively. Postoperative coronal and rotational alignments were 89.4° ± 1.8° and −1.1° ± 1.3° respectively. In both alignments, 94.4% of cases were within 3° of the optimal value. The PMI group had less outliers than conventional group in rotational alignment (p = 0.018). Conclusions Our 3D analysis provided evidence that PMI system resulted in reasonably satisfactory alignments both intraoperatively and postoperatively. Surgeons should be aware that certain surgical techniques including bone cutting, and the associated errors may affect postoperative alignment despite accurate PMI positioning..
121. Akiko Oyamada, Yoshihiro Matsumoto, Yoshifumi Wakata, Atsushi Kimura, Ko Ikuta, Kuniyoshi Tsuchiya, Naohisa Tayama, Shinji Tomari, Hisaaki Miyahara, Takao Mae, Hirokazu Shiraishi, Taichi Saito, Takeshi Arizono, Kozo Kaji, Taro Mawatari, Masami Fujiwara, Riku Sakimura, Kunichika Shin, Kenichi Ninomiya, Kazutoshi Nakaie, Yasuaki Antoku, Shoji Tokunaga, Naoki Nakashima, Yukihide Iwamoto, Yasuharu Nakashima, Characteristics of patients with fragility hip fractures in the northern Kyushu district in Japan
a multicenter prospective registry based on an electronic data capture system
, Journal of Bone and Mineral Metabolism, 10.1007/s00774-017-0869-9, 2017.10, Osteoporosis has become a worldwide public health problem, in part due to the fact that it increases the risk of fragility hip fractures (FHFs). The epidemiological assessment of FHFs is critical for their prevention; however, datasets for FHFs in Japan remain scarce. This was a multicenter, prospective, observational study in the northern district of Kyushu Island. Inclusion criteria were age > 60 years with a diagnosis of FHF and acquisition of clinical data by an electronic data capture system. Of 1294 registered patients, 1146 enrolled in the study. Nearly one third of patients (31.8%) had a history of previous fragility fractures. The percentage of patients receiving osteoporosis treatment on admission was 21.5%. Almost all patients underwent surgical treatment (99.1%), though fewer than 30% had surgery within 48 h after hospitalization. Bone mineral density (BMD) was evaluated during hospitalization in only 50.4% of patients. The rate of osteoporosis treatment increased from 21.5% on admission to 39.3% during hospitalization. The main reasons that prescribers did not administer osteoporosis treatment during hospitalization were forgetfulness (28.4%) and clinical judgment (13.6%). Age and female ratio were significantly higher in patients with previous FHFs than in those without. There was a significant difference in the rate of osteoporosis treatment or L-spine BMD values in patients with or without previous FHFs on admission. In conclusion, this study confirmed that the evaluation and treatment of osteoporosis and FHFs is still suboptimal in Japan, even in urban districts..
122. Daisuke Hara, Satoshi Hamai, Jun Ichi Fukushi, Ken Ichi Kawaguchi, Goro Motomura, Satoshi Ikemura, Keisuke Komiyama, Yasuharu Nakashima, Does Participation in Sports Affect Osteoarthritic Progression after Periacetabular Osteotomy?, American Journal of Sports Medicine, 10.1177/0363546517707942, 2017.09, Background: Periacetabular osteotomy (PAO) is an effective treatment for symptomatic acetabular dysplasia. However, whether postoperative participation in sports leads to progression of the Kellgren-Lawrence (KL) grade of osteoarthritis (OA) in these patients is unclear. Purpose: To investigate (1) participation in sports before and after PAO and (2) whether postoperative participation in sports leads to progression of the KL grade. Study Design: Case-control study; Level of evidence, 3. Methods: The authors retrospectively reviewed data on 161 patients (183 hips) who underwent PAO for symptomatic acetabular dysplasia with preoperative KL grade 1 or 2 between 1998 and 2011. The mean age at the time of surgery was 42.0 ± 10.9 years (range, 12-64 years), and the mean follow-up duration was 100 months (range, 13-180 months). Data included participation in sports, the University of California, Los Angeles (UCLA) activity scale score, age at the time of surgery, body mass index, follow-up duration, history of treatment for developmental hip dislocations, Merle d'Aubigné-Postel score, Oxford Hip Score, center-edge angle, and KL grade. Univariate and multivariate analyses were applied to determine which factors were associated with progression to KL grade 3 or 4 after PAO. Results: The number of patients who participated in sports significantly increased from 50 (31.1%) preoperatively to 89 (55.3%) postoperatively. The mean UCLA score significantly increased from 4.7 ± 2.1 preoperatively to 5.5 ± 2.0 postoperatively. The KL grade progressed to grade 3 or 4 in 16 hips, including 4 hips that underwent conversion to total hip arthroplasty. No significant differences were found in postoperative participation in sports (89 hips [53.3%] vs 11 hips [68.8%], respectively; P =.24) and the UCLA score (5.6 ± 2.0 vs 5.1 ± 2.0, respectively; P =.30) between hips with KL grade 1 or 2 and KL grade 3 or 4. A multivariate analysis revealed that no factors, including postoperative participation in sports, were significantly associated with progression to KL grade 3 or 4. Conclusion: Postoperative participation in sports after PAO did not significantly and negatively influence progression of the KL grade at midterm follow-up..
123. Naohide Takeuchi, Takao Mae, Jun ichi Fukushi, Nobuaki Tsukamoto, Hideki Mizu-uchi, Kenta Momii, Yasuharu Nakashima, Management of Intra-Articular Calcaneal Fractures
Clinical Results of Reduction Technique Using a Bone Spreader
, Journal of Foot and Ankle Surgery, 10.1053/j.jfas.2017.04.026, 2017.09, The purpose of the present study was to examine the clinical results of surgery for intra-articular calcaneal fractures using a calcaneal locking plate and a bone spreader as a reduction tool. Ten patients with intra-articular calcaneal fractures were treated. An extended lateral approach was used. The reduction of the intra-articular fragments of the posterior facet was temporarily held using a bone spreader and Kirschner wires. Internal fixation was achieved with a locking calcaneal plate. Böhler's angle and Preiss' angle were assessed on the day of injury and the day of the final follow-up examination. The step off and gap of the posterior facet were assessed on the day of injury and the first week after surgery. The functional outcome was evaluated using the American Orthopaedic Foot and Ankle Society ankle hindfoot scale score. The mean Böhler's angle ranged from 2.1° ± 11.0° to 30.4° ± 5.0° (p <.0001), the mean Preiss' angle ranged from 23.5° ± 4.5° to 15.5° ± 2.9° (p <.0001), the mean step off ranged from 4.0 ± 1.9 mm to 0.1 ± 0.2 mm (p =.0002), and the mean gap ranged from 2.6 ± 1.0 mm to 1.2 ± 0.6 mm (p =.0035). The mean American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale score was 89.2 (range 85 to 100) at a mean of 14.3 months after surgery. Our results suggest that a locking calcaneal plate can be used to restore and reduce an intra-articular calcaneal fracture and achieve good clinical results..
124. Takeshi Utsunomiya, Goro Motomura, Satoshi Ikemura, Satoshi Hamai, Jun ichi Fukushi, Yasuharu Nakashima, The Results of Total Hip Arthroplasty After Sugioka Transtrochanteric Anterior Rotational Osteotomy for Osteonecrosis, Journal of Arthroplasty, 10.1016/j.arth.2017.04.034, 2017.09, Background Since Sugioka transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) changes the morphology of the proximal femur, total hip arthroplasty (THA) after previous ARO is considered a technically demanding procedure. The purpose of this study was to compare the clinicoradiologic outcomes of THA after ARO with those of THA without any antecedent surgery for ONFH. Methods Twenty-four hips in 20 patients who underwent cementless THA after ARO (postosteotomy group) were retrospectively reviewed and compared with patients who underwent cementless THA without any antecedent surgery for ONFH during the same period (primary group). In the postosteotomy group, the mean duration from ARO to THA was 19.7 years. All patients were followed for at least 5 years (mean, 8.3 years; follow-up rate, 78.5%). A clinical assessment was performed preoperatively and at the latest follow-up using the Harris Hip Score. A radiographic examination was performed at 3 months after THA and at the latest follow-up. Results The Harris Hip Score at the latest follow-up in the postosteotomy group was equivalent to that in the primary group, but longer operation time and greater intraoperative blood loss were observed in the postosteotomy group. There were no significant differences in postoperative complications, including dislocation (2 hips in each group). The leg lengthening in the postosteotomy group tended to be longer. No hips showed implant malpositioning, loosening, or required any revision surgery. Conclusion The clinicoradiologic outcomes of THA after ARO are considered to be comparable with those of THA without any antecedent surgery for ONFH..
125. Kensei Yoshimoto, Satoshi Hamai, Hidehiko Higaki, Hirotaka Gondoh, Yasuharu Nakashima, Visualization of a cam-type femoroacetabular impingement while squatting using image-matching techniques
a case report
, Skeletal Radiology, 10.1007/s00256-017-2677-7, 2017.09, The in vivo assessment of the three-dimensional (3D) kinematics of the hip in patients with femoroacetabular impingement (FAI) under weight-bearing conditions has not been previously reported. We evaluated the pre- and postoperative hip kinematics of a 34-year-old man, with a cam-type FAI while squatting, using image-matching techniques with measurement of the rim-neck distance. Post-osteochondroplasty, the α-angle improved from 51.0° to 35.5° and the head-neck offset ratio from 0.04 to 0.23. Coxalgia during squatting disappeared, and the Harris Hip Score improved from 79 to 92 at 1 year post-surgery. Postoperative hip kinematic values (3.8° of posterior pelvic tilt and 101.2° of femoral flexion at 96.8° of maximum hip flexion) were similar to the preoperative values (2.9° of posterior pelvic tilt and 102.7° of femoral flexion at 98.8° of maximum hip flexion). Meanwhile, osteochondroplasty improved the minimum rim-neck distance at maximum hip flexion from 2.0 to 10.4 mm. In vivo 3D visualization of the clearance between the femoral head-neck junction and the acetabulum could assist surgeons in adequately identifying the location of impingement and confirming sufficient resection post-operatively..
126. Yusuke Kubo, Goro Motomura, Satoshi Ikemura, Kazuhiko Sonoda, Takuaki Yamamoto, Yasuharu Nakashima, Effect of collapse on the deformity of the femoral head–neck junction in osteonecrosis of the femoral head, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-017-2720-0, 2017.07, Introduction: The purpose of this study was to morphologically assess the effect of collapse on the deformity of the femoral head–neck junction in patients with nontraumatic osteonecrosis of the femoral head (ONFH). Materials and methods: From January 2005 through March 2016, magnetic resonance (MR) imaging including the oblique view was repeatedly performed before and after collapse in 24 hips of patients with ONFH (16 men, 8 women; mean age 43 years; range 23–68 years), that were the subjects of this study. The interval of MR imaging before and after collapse was 8.0 months (range 1–32 months). In addition, 82 asymptomatic hips in patients without ONFH as identified by MR imaging taken at the same duration were used as controls. The oblique MR image was used to measure the radiological parameters of the femoral head–neck junction, including the α-angle and head–neck offset ratio (HNOR). Results: The α-angle and HNOR after collapse (58.3° ± 10.0° and 0.138 ± 0.033, respectively) indicated significantly decreased anterior femoral head–neck offset compared with those before collapse (46.2° ± 5.7° and 0.178 ± 0.018, respectively; p < 0.0001). These parameters had a positive association with the depth of femoral head collapse (p < 0.0001 and p < 0.01, respectively). However, there were no significant differences in either the α-angle or HNOR between hips with ONFH before collapse and hips without ONFH. Conclusions: This study demonstrated that the decreased femoral head–neck offset observed in patients with ONFH was a consequence of collapse..
127. Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada, Interaction of reactive astrocytes with type i collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury, Nature medicine, 10.1038/nm.4354, 2017.07, Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin-N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte-type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury..
128. Akihisa Haraguchi, Yasuharu Nakashima, Hisaaki Miyahara, Yukio Esaki, Ken Okazaki, Jun-Ichi Fukushi, Go Hirata, Satoshi Ikemura, Satoshi Kamura, Koji Sakuraba, Kenjiro Fujimura, Yukio Akasaki, Hisakata Yamada, Minimum 10-year results of cementless total hip arthroplasty in patients with rheumatoid arthritis, Modern Rheumatology, 10.1080/14397595.2016.1256024, 2017.07, Objectives: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA. Methods: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan–Meier method, and the associated influencing factors were determined. Results: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals. Conclusions: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA..
129. Hisakata Yamada, Akihisa Haraguchi, Koji Sakuraba, Ken Okazaki, Jun Ichi Fukushi, Hideki Mizu-Uchi, Yukio Akasaki, Yukio Esaki, Satoshi Kamura, Kenjiro Fujimura, Masakazu Kondo, Hisaaki Miyahara, Yasuharu Nakashima, Yasunobu Yoshikai, Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis, RMD Open, 10.1136/rmdopen-2017-000487, 2017.07.
130. Yasutaka Tashiro, Tom Gale, Vani Sundaram, Kanto Nagai, James J. Irrgang, William Anderst, Yasuharu Nakashima, Scott Tashman, Freddie H. Fu, The graft bending angle can affect early graft healing after anterior cruciate ligament reconstruction
In vivo analysis with 2 years' follow-up
, American Journal of Sports Medicine, 10.1177/0363546517698676, 2017.07, Background: A high graft bending angle (GBA) after anterior cruciate ligament (ACL) reconstruction has been suggested to cause stress on the graft. Nevertheless, evidence about its effect on graft healing in vivo is limited. Hypothesis: The signal intensity on magnetic resonance imaging (MRI) would be higher in the proximal region of the ACL graft, and higher signals would be correlated to a higher GBA. Study Design: Descriptive laboratory study. Methods: Anatomic single-bundle ACL reconstruction was performed on 24 patients (mean age, 20 ± 4 years) using the transportal technique. A quadriceps tendon autograft with a bone plug was harvested. To evaluate graft healing, the signal/noise quotient (SNQ) was measured in 3 regions of interest (ROIs) of the proximal, midsubstance, and distal ACL graft using high-resolution MRI (0.45 × 0.45 × 0.70 mm), with decreased signals suggesting improved healing. Dynamic knee motion was examined during treadmill walking and running to assess the in vivo GBA. The GBA was calculated from the 3-dimensional angle between the graft and femoral tunnel vectors at each motion frame, based on tibiofemoral kinematics determined from dynamic stereo X-ray analysis. Graft healing and GBAs were assessed at 6 and 24 months postoperatively. Repeated-measures analysis of variance was used to compare the SNQ in the 3 ROIs at 2 time points. Pearson correlations were used to analyze the relationship between the SNQ and mean GBA during 0% to 15% of the gait cycle. Results: The SNQ of the ACL graft in the proximal region was significantly higher than in the midsubstance (P =.022) and distal regions (P <.001) at 6 months. The SNQ in the proximal region was highly correlated with the GBA during standing (R = 0.64, P <.001), walking (R = 0.65, P =.002), and running (R = 0.54, P =.015) but not in the other regions. At 24 months, signals in the proximal and midsubstance regions decreased significantly compared with 6 months (P <.001 and P =.008, respectively), with no difference across the graft area. Conclusion: The signal intensity was highest in the proximal region and lowest in the distal region of the reconstructed graft at 6 months postoperatively. A steep GBA was significantly correlated with high signal intensities of the proximal graft in this early period. A steep GBA may negatively affect proximal graft healing after ACL reconstruction..
131. Masayuki Kanazawa, Kanji Tsuru, Naoyuki Fukuda, Yuta Sakemi, Yasuharu Nakashima, Kunio Ishikawa, Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate dihydrate blocks for reconstruction of rabbit femoral and tibial defects, Journal of Materials Science: Materials in Medicine, 10.1007/s10856-017-5896-5, 2017.06, Abstract: This study aimed to evaluate in vivo behavior of a carbonate apatite (CO3Ap) block fabricated by compositional transformation via a dissolution–precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO4·2H2O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO3Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO3Ap was resorbed with increasing time after implantation and replaced with new bone. The CO3Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO3Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1−1.5 years. Hence, the CO3Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone..
132. Abdul Halim Abdullah, Mitsugu Todo, Yasuharu Nakashima, Prediction of damage formation in hip arthroplasties by finite element analysis using computed tomography images, Medical Engineering and Physics, 10.1016/j.medengphy.2017.03.006, 2017.06, Femoral bone fracture is one of the main causes for the failure of hip arthroplasties (HA). Being subjected to abrupt and high impact forces in daily activities may lead to complex loading configuration such as bending and sideway falls. The objective of this study is to predict the risk of femoral bone fractures in total hip arthroplasty (THA) and resurfacing hip arthroplasty (RHA). A computed tomography (CT) based on finite element analysis was conducted to demonstrate damage formation in a three dimensional model of HAs. The inhomogeneous model of femoral bone was constructed from a 79 year old female patient with hip osteoarthritis complication. Two different femoral components were modeled with titanium alloy and cobalt chromium and inserted into the femoral bones to present THA and RHA models respectively. The analysis included six configurations, which exhibited various loading and boundary conditions, including axial compression, torsion, lateral bending, stance and two types of falling configurations. The applied hip loadings were normalized to body weight (BW) and accumulated from 1 BW to 3 BW. Predictions of damage formation in the femoral models were discussed as the resulting tensile failure as well as the compressive yielding and failure elements. The results indicate that loading directions can forecast the pattern and location of fractures at varying magnitudes of loading. Lateral bending configuration experienced the highest damage formation in both THA and RHA models. Femoral neck and trochanteric regions were in a common location in the RHA model in most configurations, while the predicted fracture locations in THA differed as per the Vancouver classification..
133. Yasuharu Nakashima, Masanori Fujii, Yasuo Noguchi, Kenya Suenaga, Takuaki Yamamoto, Jun-Ichi Fukushi, goro motomura, Satoshi Hamai, Daisuke Hara, Yukihide Iwamoto, Arthroscopic validation of radiographic minimum joint space width associated with the subchondral bone exposure in symptomatic hip dysplasia, Modern Rheumatology, 10.1080/14397595.2016.1222663, 2017.05, Objective: The purpose of this study was to clarify the minimum joint space width (MJSW) that leads to subchondral bone exposure (SBE) in patients with hip dysplasia. Methods: We included 82 subjects (86 hips) who had hip dysplasia with center-edge angle less than 20° and who underwent periacetabular osteotomy combined with hip arthroscopy. The acetabular and femoral cartilages were divided into three regions: anterosuperior, superior, and posterosuperior; for each region, we analyzed the correlation between the incidence of SBE and the MJSW measured on plain radiographs. The disease stage was defined according to the Kellgren and Lawrence grades (KL grade). Results: SBE was found in 51 hips (59.3%) in total, involved the acetabulum in 49 hips (57.0%), and involved the femoral head in 26 hips (30.2%). SBE was more frequent in the acetabulum, with the highest incidence in the anterosuperior region, followed by the superior region. SBE was present in six hips (22.2%), 17 hips (56.7%), and 28 hips (96.5%), at KL-1, KL-2, and KL-3, respectively. MJSW of hips with SBE was significantly smaller than those without SBE (2.3 vs 4.0 mm, p < 0.001), and the cut-off value for MJSW that led to SBE was 3.7 mm (sensitivity: 0.902, 1–specificity: 0.343). SBE was present in 23.3% in patients with MJSW ≥3.7 mm, whereas 76.7% in those <3.7 mm. Conclusions: Cartilage degeneration is more advanced than would be predicted on plain radiographs. The cut-off value of MJSW for SBE was 3.7 mm in patients with symptomatic hip dysplasia..
134. Shoji Baba, Goro Motomura, Junichi Fukushi, Satoshi Ikemura, Kazuhiko Sonoda, Yusuke Kubo, Takeshi Utsunomiya, Hiroyuki Hatanaka, Yasuharu Nakashima, Osteonecrosis of the femoral head associated with pigmented villonodular synovitis, Rheumatology International, 10.1007/s00296-016-3624-y, 2017.05, A 23-year-old Japanese woman with no history of corticosteroid intake or alcohol abuse presented with a 10-month history of left hip pain without any antecedent trauma. An anteroposterior radiograph performed 10 months after the onset of pain showed slight joint space narrowing and bone erosions surrounded by sclerotic lesions in both the acetabular roof and femoral neck. Magnetic resonance images of the left hip showed a feature of osteonecrosis of the femoral head and a mass with villus proliferation extending from the posterior intertrochanteric area to the anteromedial aspect of the femoral neck. In addition, the left quadratus femoris muscle, which is generally located just above the nutrient vessels of the femoral head, was not detected. Based on these findings, the patient was diagnosed with osteonecrosis of the femoral head caused by impairment of the nutrient vessels from invasion of the pigmented villonodular synovitis. She underwent radical synovectomy of the left hip 16 months after the onset of pain, and her hip pain improved after the surgery..
135. Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun Ichi Fukushi, Tomoya Matsunobu, Ken Ichi Kawaguchi, Nokitaka Setsu, Keiichiro IIda, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima, Potential therapeutic target in malignant peripheral nerve sheath tumor, PloS one, 10.1371/journal.pone.0178064, 2017.05, Background Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear. Methods The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α.specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α. Results The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis. Conclusion Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs..
136. Kazuhiko Sonoda, Goro Motomura, Satoshi Kawanami, Yukihisa Takayama, Hiroshi Honda, Takuaki Yamamoto, Yasuharu Nakashima, Degeneration of articular cartilage in osteonecrosis of the femoral head begins at the necrotic region after collapse
a preliminary study using T1 rho MRI
, Skeletal Radiology, 10.1007/s00256-017-2567-z, 2017.04, Objective: The purpose of this study is to evaluate the role of collapse on the degeneration of articular cartilage in patients with osteonecrosis of the femoral head (ONFH). Materials and methods: Sixteen hips in 12 patients (four men, eight women; mean age, 34.8 years) with a history of systemic corticosteroid treatment were studied using T1 rho magnetic resonance imaging (MRI). Six hips had collapsed ONFH, five had non-collapsed ONFH, and five had no osteonecrosis (controls). Using oblique coronal images, we divided the articular surface of necrotic femoral heads into a region just above the necrotic bone (necrotic zone) and another above the living bone (living zone). T1 rho value was evaluated for each zone. Results: The mean T1 rho value in the necrotic zone was significantly higher in the collapsed ONFH group (48.4 ± 2.7 ms) than in the non-collapsed ONFH group (41.0 ± 0.9 ms). In the collapsed ONFH group, the mean T1 rho value was significantly higher in the necrotic zone (48.4 ± 2.7 ms) than in the living zone (43.5 ± 2.5 ms). In the non-collapsed ONFH group, there was no significant difference between the mean T1 rho values of the necrotic and living zones. In the collapsed ONFH group, the mean T1 rho value of the necrotic zone and the interval from pain onset to the MRI examination were positively correlated. Conclusions: The current T1 rho MRI study suggested that the degeneration of articular cartilage in ONFH begins at the necrotic region after collapse..
137. Naoya Kozono, Takamitsu Okada, Naohide Takeuchi, Takeshi Shimoto, Hidehiko Higaki, Yasuharu Nakashima, Effect of the Optimal Asymmetry on the Strength of Six-Strand Tendon Repair
An Ex Vivo Biomechanical Study
, Journal of Hand Surgery, 10.1016/j.jhsa.2017.01.015, 2017.04, Purpose To evaluate the mechanical properties of a 6-strand core suture repair with asymmetric purchase in the 2 tendon ends, in comparison with a repair with symmetric suture purchases. Methods Under cyclic loading of the tendons, we recorded the fatigue strength (Forces × Cycles) of a 6-strand flexor tendon repair with different symmetry in the lengths of suture purchase in 60 porcine tendons. The symmetric repair was made with 3 groups of parallel Kessler repairs of equal suture purchase (10 mm from the cut end) in the 2 tendon stumps. The asymmetric core suture repairs were then made with a Kessler repair of equal suture purchase (10 mm from the cut end) in the 2 tendon stumps, and shifting 2 other Kessler repairs by 1, 2, 3, 4, or 5 mm, respectively, along the longitudinal axis of the tendon in relation to the first (symmetric) Kessler repair. Results The core repairs with 2 mm or more asymmetry in suture purchases in 2 tendon ends showed significantly greater fatigue strength compared with those with symmetric suture placement. The core repairs with 3 mm or more asymmetry in suture purchases in 2 tendon ends showed significantly smaller gaps compared with those with symmetric suture placement. Conclusions The core repairs with 3 mm or more asymmetry in suture purchases in 2 tendon ends generated increased fatigue strength and reduced gap sizes compared with those with symmetric suture placement in an ex vivo porcine model. Clinical relevance An asymmetric core suture repair with 3 mm or more difference in purchase length may allow for earlier rehabilitation and reduce the risk of postoperative complications..
138. Y. Kubo, G. Motomura, S. Ikemura, K. Sonoda, T. Yamamoto, Y. Nakashima, Factors influencing progressive collapse of the transposed necrotic lesion after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head, Orthopaedics and Traumatology: Surgery and Research, 10.1016/j.otsr.2016.10.019, 2017.04, Background Transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) can preserve for a long-time collapsed femoral head. Progressive collapse of anteriorly-transposed necrotic lesion leads to secondary arthritic changes and clinical failure. Critical factors influencing collapse of the transposed necrotic lesion after ARO remain largely unknown. Therefore, we performed a retrospective study of ARO to determine: (1) if preoperative collapse influences collapse of the transposed necrotic area, (2) if any other factor may influence collapse of the transposed necrotic area. Hypothesis We hypothesized the degree of preoperative femoral head collapse influences progressive collapse of the transposed necrotic lesion after ARO. Materials and methods We reviewed 47 hips in 42 patients with ONFH treated with ARO between 2000 and 2005 with a mean follow-up of 11.4 years (10–14 years). The occurrence of progressive collapse of the transposed necrotic lesion after ARO was examined using lateral radiographs taken at least once every year after ARO. The following factors were statistically analyzed: age, sex, body mass index, Harris Hip Score (HHS), preoperative level of collapse, extent of the necrotic lesion and postoperative intact ratio (ratio of the transposed intact articular surface of the femoral head). Results Progressive collapse of the transposed necrotic lesion (progressive collapse group) was seen in 17 hips (36%) during a mean period of 1.8 years (0.5–3.7 years) after ARO, which has developed within 4 years in all cases. Preoperative level of collapse in the progressive collapse group (4.4 ± 1.4 mm) was significantly larger than that in the non-progressive collapse group (2.1 ± 1.0 mm), which was independently associated with progressive collapse of the transposed necrotic lesion in multivariate analysis (P < 0.0001) with cut off point of 2.98 mm. In univariate analysis, lower preoperative HHS, severe extent of the necrotic lesion and the lower postoperative intact ratio were also associated with progressive collapse of the transposed necrotic lesion, but were not associated as independent factors in multivariate analysis. Discussion The current study suggests that progressive collapse of the transposed necrotic lesion after ARO depends mainly on the preoperative level of collapse (cut-off point = 2.98 mm). Level of evidence IV; retrospective case series..
139. , Yuma Sakamoto, Takuaki Yamamoto, Noriko Miyake, Naomichi Matsumoto, Aritoshi Iida, Yasuharu Nakashima, Yukihide Iwamoto, Shiro Ikegawa, Screening of the COL2A1 mutation in idiopathic osteonecrosis of the femoral head, Journal of Orthopaedic Research, 10.1002/jor.23300, 2017.04, Idiopathic osteonecrosis of the femoral head (idiopathic ONFH) is an ischemic disorder resulting in necrosis of the subchondral bone of the femoral head. COL2A1 mutations, including c.3508G>A, have been reported to be involved in its etiology. However, the etiological role of COL2A1 mutations in idiopathic ONFH remains controversial, because the pathology of idiopathic ONFH is ischemic necrosis, not epiphyseal dysplasia usually seen in the diseases caused by COL2A1 mutations. The purpose of this study is to examine whether COL2A1 mutations have causal relation with idiopathic ONFH or not. We recruited 1,451 Japanese patients with idiopathic ONFH, including steroid-, alcohol-, and neither steroid nor alcohol-associated (neither-associated) ONFH. The diagnosis was based on the criteria of the Japanese Research Committee on idiopathic ONFH of the Ministry of Health, Labour and Welfare. By whole-exome sequencing, entire COL2A1 coding regions and flanking introns were analyzed in 49 neither-associated ONFH patients. In addition, the c.3508G>A mutation of COL2A1 was checked in all idiopathic ONFH patients using the invader assay. Whole-exome sequencing did not detect any COL2A1 mutations in the 49 patients. The c.3508G>A mutation was not found in any of the 1,451 patients. In conclusion, COL2A1 is unlikely to cause idiopathic ONFH. Epiphyseal dysplasia of the femoral head caused by COL2A1 mutations may radiographically mimic idiopathic ONFH. COL2A1 mutations should prompt clinical re-evaluation of the patient's phenotype..
140. Kanji Tsuru, Ayami Yoshimoto, Masayuki Kanazawa, Yuki Sugiura, Yasuharu Nakashima, Kunio Ishikawa, Fabrication of carbonate apatite block through a dissolution-precipitation reaction using calcium hydrogen phosphate dihydrate block as a precursor, Materials, 10.3390/ma10040374, 2017.03, Carbonate apatite (CO3Ap) block, which is a bone replacement used to repair defects, was fabricated through a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate (DCPD) block as a precursor. When the DCPD block was immersed in NaHCO3 or Na2CO3 solution at 80 °C, DCPD converted to CO3Ap within 3 days. β-Tricalcium phosphate was formed as an intermediate phase, and it was completely converted to CO3Ap within 2 weeks when the DCPD block was immersed in Na2CO3 solution. Although the crystal structures of the DCPD and CO3Ap blocks were different, the macroscopic structure was maintained during the compositional transformation through the dissolution-precipitation reaction. CO3Ap block fabricated in NaHCO3 or Na2CO3 solution contained 12.9 and 15.8 wt % carbonate, respectively. The diametral tensile strength of the CO3Ap block was 2 MPa, and the porosity was approximately 57% regardless of the carbonate solution. DCPD is a useful precursor for the fabrication of CO3Ap block..
141. K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima, Characterisation of osteophytes as an autologous bone graft source
An experimental study in vivo and in vitro
, Bone and Joint Research, 10.1302/2046-3758.62.BJR-2016-0199.R1, 2017.02, Objectives" Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods: Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intraperitoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative realtime polymerase chain reaction, and migration assays. Results: After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm2, sd 14660 versus 9421 μm2, sd 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion: We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts..
142. Kensei Yoshimoto, Yasuharu Nakashima, Shigeo Aota, Ayumi Kaneuji, Kiyokazu Fukui, Kazuo Hirakawa, Nariaki Nakura, Koichi Kinoshita, Masatoshi Naito, Yukihide Iwamoto, Re-dislocation after revision total hip arthroplasty for recurrent dislocation
a multicentre study
, International Orthopaedics, 10.1007/s00264-016-3127-1, 2017.02, Purpose: Although most case of dislocations after total hip arthroplasty (THA) can be managed with conservative treatment, recurrent dislocation may require surgical intervention. This multicentre study was conducted to evaluate the re-dislocation rate after revision THA for recurrent dislocation, and to determine the risk factors for re-dislocation. Methods: We retrospectively reviewed the 88 hips in 88 patients who underwent revision THA for recurrent dislocation at five institutions between 1995 and 2014. The mean patient age at surgery was 68.5 years and the mean follow-up period was 53.1 months. Multivariate logistic regression was performed to identify risk factors for re-dislocation. Results: Sixteen hips in 16 patients (18.2 %) re-dislocated at a mean of 25.5 months (range, 1–83 months) after revision THA. Multivariate analysis identified osteonecrosis of the femoral head (odds ratio [OR] = 5.62 vs. osteoarthritis) and a femoral head size < 32 mm (OR = 3.86) as independent risk factors for re-dislocation. Eight hips required additional revision THA for re-dislocation. Conclusion: The re-dislocation rate after revision THA for recurrent dislocation remains high, suggesting the need for prevention measures. We recommend the use of a femoral head size ≥ 32 mm..
143. Yoshihiro Matsumoto, Makoto Shinoto, Makoto Endo, Nokitaka Setsu, Keiichiro Iida, Jun Ichi Fukushi, Kenichi Kawaguchi, Seiji Okada, Hirofumi Bekki, Reiko Imai, Tadashi Kamada, Yoshiyuki Shioyama, Yasuharu Nakashima, Evaluation of risk factors for vertebral compression fracture after carbon-ion radiotherapy for primary spinal and paraspinal sarcoma, BioMed Research International, 10.1155/2017/9467402, 2017.01, Background and Purpose. Carbon-ion radiotherapy (C-ion RT) was effective therapy for inoperable spinal and paraspinal sarcomas. However, a significant adverse event following radiotherapies is vertebral compression fractures (VCFs). In this study, we investigated the incidence of and risk factors for post-C-ion RT VCFs in patients with spinal or paraspinal sarcomas. Material and Methods. Thirty consecutive patients with spinal or paraspinal sarcomas treated with C-ion RT were retrospectively reviewed. Various clinical parameters and the Spinal Instability Neoplastic Score (SINS) were used to evaluate the risk factors for post-C-ion RT VCFs. Results. The overall incidence of VCFs was 23% (median time: 7 months). Patients with VCFs showed a markedly higher SINS score (median value, 9 points) than those without VCF (5 points). The area under the receiver operating characteristic curve for the SINS score was 0.88, and the optimum SINS cut-off score was 8 points. The cumulative incidence of VCFs at 1 year was 9% for patients with a SINS score under 8 points, versus 80% for those with a SINS score of 8 points or higher (p<0.0001). Conclusions. In patients with a SINS score of 8 points or higher, referral to a spine surgeon for stabilization and multidisciplinary discussion is appropriate..
144. Takeyuki Saito, Kazuya Yokota, Kazu Kobayakawa, Masamitsu Hara, Kensuke Kubota, Katsumi Harimaya, Kenichi Kawaguchi, Mitsumasa Hayashida, Yoshihiro Matsumoto, Toshio Doi, Keiichiro Shiba, Yasuharu Nakashima, Seiji Okada, Experimental mouse model of lumbar ligamentum flavum hypertrophy, PloS one, 10.1371/journal.pone.0169717, 2017.01, Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production..
145. Yasuharu Nakashima, Hisaaki Miyahara, Masakazu Kondo, Takaaki Fukuda, Hiroshi Harada, Akihisa Haraguchi, Yasushi Inoue, Takashi Ishinishi, Masayuki Maekawa, Akira Maeyama, Munetoshi Nakashima, Eisuke Shono, Eiichi Suematsu, Takashi Shimauchi, Tomomi Tsuru, Hiroshi Tsukamoto, Shigeru Yoshizawa, Seiji Yoshizawa, Yukihide Iwamoto, Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid arthritis
Results from registered data analyses
, Modern Rheumatology, 10.3109/14397595.2016.1170958, 2017.01, Objective: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. Method: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. Results: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). Conclusions: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients..
146. Yusuke Kohno, Yasuharu Nakashima, Toshio Kitano, Taichi Irie, Atsushi Kita, Tomoyuki Nakamura, Hirosuke Endo, Yosuke Fujii, Takayuki Kuroda, Shigeru Mitani, Hiroshi Kitoh, Masaki Matsushita, Tadashi Hattori, Koji Iwata, Yukihide Iwamoto, Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study, Journal of Orthopaedic Science, 10.1016/j.jos.2016.08.012, 2017.01, Background An unstable slipped capital femoral epiphysis (SCFE) is associated with a high rate of avascular necrosis (AVN). The etiology of AVN seems to be multifactorial, although it is not thoroughly known. The aims of our study were to determine the rate of AVN after an unstable SCFE and to investigate the risk factors for AVN, specifically evaluating the notion of an “unsafe window”, during which medical interventions would increase the risk for AVN. Methods This retrospective multicenter study included 60 patients with an unstable SCFE diagnosed between 1985 and 2014. Timing of surgery was evaluated for three time periods, from acute onset of symptoms to surgery: period I, <24 h; period II, between 24 h and 7 days; and period III, >7 days. Multivariate logistic regression analysis was used to identify risk factors for AVN. Results Closed reduction and pinning was performed in 43 patients and in situ pinning in 17. Among these cases, 16 patients (27%) developed AVN. The rate of AVN was significantly higher in patients treated by closed reduction and pinning (15/43, 35%) than in those treated by in situ pinning (1/17, 5.9%) (p = 0.022). In patients treated by closed reduction and pinning, the incidence of AVN was 2/11 (18%) in period I, 10/13 (77%) in period II and 3/15 (20%) in period III, showing the significantly higher rate in period II (p = 0.002). The surgery provided in period II was identified as an independent risk factor for the development of AVN. Conclusions Our rate of AVN was 27% using two classical treatment methods. Time-to-surgery, between 24 h and 7 days, was independently associated with AVN, supporting the possible existence of an “unsafe window” in patients with unstable SCFE treated by closed reduction and pinning..
147. Takashi Hatano, Masanobu Ohishi, Goichi Yoshimoto, Moriyasu Yamauchi, Akira Maekawa, Hidetaka Yamamoto, Yoshinao Oda, Makoto Endo, Hirofumi Bekki, Tomoya Matsunobu, Yasuharu Nakashima, Ken Okazaki, Jun Ichi Fukushi, Akiko Oyamada, Yukihide Iwamoto, Methotrexate-related lymphoproliferative disorder presenting with severe swelling of the elbow joint, JBJS case connector, 10.2106/JBJS.CC.17.00002, 2017.01, Case: A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD. Conclusion: MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy..
148. Masanori Fujii, Yasuharu Nakashima, Tetsuro Nakamura, Yoshihiro Ito, Toshihiko Hara, Minimum lateral bone coverage required for securing fixation of cementless acetabular components in hip dysplasia, BioMed Research International, 10.1155/2017/4937151, 2017.01, Objectives. To determine the minimum lateral bone coverage required for securing stable fixation of the porous-coated acetabular components (cups) in hip dysplasia. Methods. In total, 215 primary total hip arthroplasties in 199 patients were reviewed. The average follow-up period was 49months (range: 24-77months).The lateral bone coverage of the cups was assessed by determining the cup center-edge (cup-CE) angle and the bone coverage index (BCI) from anteroposterior pelvic radiographs. Further, cup fixation was determined using the modified DeLee and Charnley classification system. Results. All cups were judged to show stable fixation by bone ingrowth. The cup-CE angle was less than 0° in 7 hips (3.3%) and the minimum cup-CE angle was-9.2° (BCI: 48.8%). Thin radiolucent lines were observed in 5 hips (2.3%), which were not associated with decreased lateral bone coverage. Loosening, osteolysis, dislocation, or revision was not observed in any of the cases during the follow-up period. Conclusion. A cup-CE angle greater than-10° (BCI > 50%) was acceptable for stable bony fixation of the cup. Considering possible errors in manual implantation, we recommend that the cup position be planned such that the cup-CE angle is greater than 0° (BCI > 60%)..
149. Abdul Halim Abdullah, Mitsugu Todo, Yasuharu Nakashima, Stress and damage formation analysis in hip arthroplasties using CT-based finite element method, Journal of Engineering and Applied Sciences, 10.3923/jeasci.2017.2715.2719, 2017.01, Femoral neck fractures and prosthesis loosening are several biomechanical concerns in promoting the long term stability of hip arthroplasties. External high impact loading due to sideway falls may contribute to the risk of femoral fractures and joint failures. The purpose of this study is to investigate the biomechanical effects of hip resurfacing and total hip arthroplasty on the resulting stress and damage formation. Four loading conditions are considered in the analysis to represent sideway falls at different configurations. Finite element analysis is performed using CT-based femoral bone model to predict the stress and damage formation in both arthroplasties. Stress shielding effects and potential of femoral fractures are observed in the cortical bone adjacent to the prosthesis. The results show that stress adaptation is predicted at both hip arthroplasties cases which lead to stress shielding problems especially in total hip arthroplasty. The variation of damage formation at trochanteric region suggested for femoral neck fractures and potential of implant loosening in both cases..
150. Hiroyuki Hatanaka, Goro Motomura, Satoshi Ikemura, Kazuhiko Sonoda, Yusuke Kubo, Takeshi Utsunomiya, Takuaki Yamamoto, Yasuharu Nakashima, Use of a long distally fixed intramedullary stem to treat a periprosthetic femoral fracture following total hip arthroplasty using a thrust plate hip prosthesis
A case report
, International Journal of Surgery Case Reports, 10.1016/j.ijscr.2017.06.010, 2017.01, Introduction The thrust plate hip prosthesis (TPP; Zimmer, Winterthur, Switzerland) is a hip prosthesis that is no longer in production. Few reports have focused on periprosthetic fractures following total hip arthroplasty (THA) with the use of a TPP. Presentation of case We report a 57-year-old woman with a periprosthetic femoral fracture 13 years after THA with the use of a TPP. A plain radiograph showed a displaced subtrochanteric fracture of the right femur just below the distal tip of the lateral plate without implant loosening. She underwent revision surgery with a long distally fixed intramedullary stem in conjunction with a plate and cable system. Three months after surgery, bone union was confirmed using radiography and the patient was clinically asymptomatic. Discussion We encountered three major problems while planning surgical treatment, these being, discontinuation of the TPP system, loss of proximal femoral cancellous bone, and difficulties with the type of subtrochanteric fracture. After considering these problems, we planned revision surgery using a long distally fixed intramedullary stem in conjunction with a plate and cable system. Conclusion This case shows that sufficient implant preparation based on precise preoperative planning is necessary to obtain good clinical results for the surgical treatment of periprosthetic femoral fractures following THA with the use of a TPP..
151. Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Tomoya Matsunobu, Ken-Ichi Kawaguchi, Nokitaka Setsu, Keiichiro IIda, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima, Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor, PLoS One, 10.1371/journal.pone.0178064, 2017, BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear.
METHODS: The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α.
RESULTS: The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis.
CONCLUSION: Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs..
152. Yoshihiro Matsumoto, Shingo Baba, Makoto Endo, Nokitaka Setsu, Keiichiro Iida, Jun-Ichi Fukushi, Kenichi Kawaguchi, Seiji Okada, Hirofumi Bekki, Takuro Isoda, Yoshiyuki Kitamura, Hiroshi Honda, Yasuharu Nakashima, Metabolic Tumor Volume by (18)F-FDG PET/CT Can Predict the Clinical Outcome of Primary Malignant Spine/Spinal Tumors, BioMed Research International, 10.1155/2017/8132676, 2017, BACKGROUND AND PURPOSE: Primary malignant spine/spinal tumors (PMSTs) are rare and life-threatening diseases. In this study, we demonstrated the advantage of volume-based (18)F-FDG PET/CT metabolic parameter, metabolic tumor volume (MTV), for assessing the aggressiveness of PMSTs.
MATERIALS AND METHODS: We retrospectively reviewed 27 patients with PMSTs and calculated SUVmax, MTV, and total lesion glycolysis (TLG) to compare their accuracy in predicting progression-free survival (PFS) and overall survival (OS) by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to compare the reliability of the metabolic parameters and various clinical factors.
RESULTS: MTV exhibited greater accuracy than SUVmax or TLG. The cut-off values for PFS and OS derived from the AUC data were MTV 45 ml and 83 ml and TLG 250 SUV⁎ml and 257 SUV⁎ml, respectively. MTV above cut-off value, but not TLG, was identified as significant prognostic factor for PFS by log-lank test (p = 0.04). In addition, MTV was the only significant predictive factors for PFS and OS in the multivariate analysis.
CONCLUSIONS: MTV was a more accurate predictor of PFS and OS in PMSTs compared to TLG or SUVmax and helped decision-making for guiding rational treatment options..
153. Yasuharu Nakashima, Takuaki Yamamoto, Jun ichi Fukushi, Goro Motomura, Satoshi Hamai, Yusuke Kohno, Yukihide Iwamoto, Transtrochanteric rotational osteotomy for avascular necrosis of the femoral head after unstable slipped capital femoral epiphysis
10-year clinical results
, Journal of Orthopaedic Science, 10.1016/j.jos.2016.06.014, 2016.11, Background Avascular necrosis of the femoral head (AVN) is the most serious complication after unstable slipped capital femoral epiphysis (SCFE), and is often unsalvageable. We report a minimum 10 years of clinical results for transtrochanteric rotational osteotomy of the femoral head (TRO) for AVN. Methods This study included 7 patients (7 hips) with a mean age at surgery of 13.3 years, and the follow-up period was 15.8 years. All patients had prior treatment via closed reduction and pinning of the unstable SCFE, and showed severely collapsed femoral heads. The direction of rotation was anterior in 3 hips and posterior in 4. The Merle d'Aubigné–Postel score (MDPS) was used for clinical assessment, and joint degeneration was assessed with the Kellgren and Lawrence classification (KL-grade). Results The spherical intact area of the femoral head was moved to the weight-bearing portion, and subluxation was corrected via rotation combined with intentional varus positioning. The mean MDPS improved from 10.3 points to 15.6 points at 5 years, and it was maintained at 15.0 points by 10 years; 3 hips were excellent, 1 was good, 2 were fair, and 1 showed poor outcomes. No patient experienced re-collapse after TRO or required conversion to hip replacement or arthrodesis. After 10 years, degenerative changes became evident over time, and 2 hips progressed to KL-4 with a decreased MDPS. Conclusions Although some joint degeneration is inevitable in the long-term, TRO is an effective salvage procedure for treating AVN after unstable SCFE..
154. Sachi Hasegawa, Teresa Victoria, Hülya Kayserili, Elaine Zackai, Gen Nishimura, Nobuhiko Haga, Yasuharu Nakashima, Osamu Miyazaki, Hiroshi Kitoh, Characteristic calcaneal ossification
an additional early radiographic finding in infants with fibrodysplasia ossificans progressiva
, Pediatric Radiology, 10.1007/s00247-016-3662-3, 2016.10, Background: We have clinically encountered children with fibrodysplasia ossificans progressiva who had abnormal calcaneal ossification. Objective: To evaluate whether calcaneal ossification variants are significant radiographic findings in children with fibrodysplasia ossificans progressiva. Materials and methods: Lateral feet radiographs in nine children who fulfilled the diagnostic criteria of fibrodysplasia ossificans progressiva were reviewed. The studies were obtained during infancy or early childhood. Results: Fourteen lateral foot radiographs of fibrodysplasia ossificans progressiva were available for this study (ages at examination: 1-104 months). Four children ages 2 months to 11 months showed double calcaneal ossification centers; 7 children had plantar calcaneal spurs that decreased in size with age. Overall, eight of nine children with fibrodysplasia ossificans progressiva demonstrated double calcaneal ossifications and/or plantar calcaneal spurs in infancy or childhood. Conclusion: Double calcaneal ossification centers in early infancy and plantar calcaneal spurs in childhood are frequently seen in children with fibrodysplasia ossificans progressiva and may be a useful radiologic indicator for early diagnosis..
155. Keisuke Komiyama, Yasuharu Nakashima, Masanobu Hirata, Daisuke Hara, Yusuke Kohno, Yukihide Iwamoto, Does High Hip Center Decrease Range of Motion in Total Hip Arthroplasty? A Computer Simulation Study, Journal of Arthroplasty, 10.1016/j.arth.2016.03.014, 2016.10, Background High placement of a cementless acetabular cup is often required to have sufficient bone coverage in hip dysplasia. We examined whether a high hip center decreases the postoperative range of motion (ROM) in total hip arthroplasty. Methods Using a computer software, ROM and bone coverage were examined in 32 patients with unilateral osteoarthritis of the hip with Crowe type II or III hip dysplasia. The cup was placed at the anatomic hip center and moved vertically in 5-mm increments. Vertical center of rotation (V-COR) was defined as the distance from the head center to the interteardrop line. The required ROM was defined as flexion  ≥110°, internal rotation (IR) at 90° flexion ≥30°, extension ≥30°, and external rotation ≥30°. We determined the V-COR to satisfy the required ROM and cup center-edge angle (Cup-CE) ≥0°. Results Only 40.6% of the patients satisfied Cup-CE ≥0° at the anatomic hip center. Bone coverage increased with the peak at 30, 35 mm of V-COR (90.6% satisfied Cup-CE ≥0°) and decreased at ≥40 mm. Higher V-COR resulted in lower range of flexion and IR, but increased the range of extension and external rotation. The cutoff value from the receiver-operating characteristic curve for both flexion and IR was a V-COR of 35 mm. Conclusion The higher hip center gained more bone coverage but decreased the range of hip flexion and IR. Acceptable V-COR in hip dysplasia was around 35 mm, about 20 mm above the true hip center, in terms of ROM..
156. Yusuke Kohno, Yasuharu Nakashima, Takashi Hatano, Mio Akiyama, Masanori Fujii, Daisuke Hara, Masayuki Kanazawa, Akihisa Haraguchi, Yukihide Iwamoto, High prevalence of cam deformity in dysplastic hips
A three-dimensional CT study
, Journal of Orthopaedic Research, 10.1002/jor.23147, 2016.09, Cam deformity could lead to suboptimal articulation by causing secondary femoroacetabular impingement after periacetabular osteotomy; however, the inherent femoral head-neck morphology in dysplastic hips and the effect of an additional osteoarthritic deformity have not been well described. We compared femoral head-neck morphology using three-dimensional imaging of normal and dysplastic hips in pre/early (Tönnis grade 0 and 1) and advanced stage osteoarthritis (Tönnis grade 2). Using computed tomography, we measured the circumferential α-angle and head-neck offset ratio in 68 dysplastic hips and 24 normal hips. Locations of the head-neck junction were represented by the clock position. In the pre/early group, the α-angle was significantly larger at the anterosuperior and inferior aspects (1, 2, and 5–7 o'clock) and head-neck offset ratio was smaller at the anterosuperior aspect (2 o'clock) than in the control group. The α-angle was significantly larger at the anterior aspects (1–4 o'clock) in the advanced group than in the pre/early group. The maximum α-angle was most commonly found at 2 o'clock (60%, 41/68 hips) in dysplastic hips. The prevalence of cam deformity (maximum α-angle >55°) was 4.2% (1/24 hips) in the control group, 22% (11/50 hips) in the pre/early group, and 50% (9/18 hips) in the advanced group. Cam deformity, inherent in the pre/early group, was found with relatively high frequency. The higher prevalence in the advanced group reflected degeneration-modified changes. When performing periacetabular osteotomy, preoperative radiographic assessments should include the femoral head-neck junction to prevent secondary femoroacetabular impingement, especially in patients with advanced stage osteoarthritis..
157. Masayuki Kanazawa, Yasuharu Nakashima, Takayuki Arai, Takahiro Ushijima, Masanobu Hirata, Daisuke Hara, Yukihide Iwamoto, Quantification of pelvic tilt and rotation by width/height ratio of obturator foramina on anteroposterior radiographs, HIP International, 10.5301/hipint.5000374, 2016.09, Objective: Compared to sagittal pelvic tilt, only a few studies have examined axial rotation on anteroposterior radiographs. We therefore quantified 3-D pelvic rotation using the width and height ratio of the obturator foramina under the various pelvic tilts. Methods: Using CT reconstructions of 10 healthy pelvises, anterior pelvic planes (APPs) were rotated by 20° in 5° increments on the axial plane with various degrees of sagittal pelvic tilt. The correlation between the pelvic rotation angle and the width ratio (WR) in the axial plane and the height/width ratio (H/W) in the sagittal plane were examined. Results: Axial pelvic rotation and WR showed a high linear correlation regardless of the sagittal tilt, with the correlation coefficient ranging from 0.93 to 0.98 in males and 0.87 to 0.95 in females. The angle that resulted in a WR of 1: 2 was approximately 13° in males and 18° in females. H/W also showed a linear regression with sagittal tilt. Axial rotation was determined by the following equation incorporating pelvic tilts; axial rotation (male: female) = (19.9: 24.2) + (2.1: 3.6) × Hright/Wright + (0.9: 1.5) × Hleft/Wleft - (23.2: 25.1) × WR. Conclusions: Pelvic tilt and rotation could be quantified by the equation using width and height ratios of the obturator foramina on a plain anteroposterior radiograph. Width and height ratios of the obturator foramina proved to be useful parameters in clinical practice for understanding pelvic rotation..
158. Masanobu Ohishi, Yasuharu Nakashima, Takuaki Yamamoto, Goro Motomura, Jun ichi Fukushi, Satoshi Hamai, Yusuke Kohno, Yukihide Iwamoto, Cementless total hip arthroplasty for patients previously treated with femoral osteotomy for hip dysplasia
the incidence of periprosthetic fracture
, International Orthopaedics, 10.1007/s00264-015-2992-3, 2016.08, Purpose: Femur deformities can make stem fixation difficult in total hip arthroplasty (THA). We report the clinical results of cementless THA using a press-fit stem in patients who had previously undergone femoral osteotomy for hip dysplasia. Methods: The subjects included 66 hips in 64 patients, with the mean follow-up period of 7.3 years. THA was performed at a mean period of 17.1 years after intertrochanteric femoral osteotomy. Valgus osteotomy was performed in 42 hips, and varus osteotomy in 24. Clinical results were evaluated by using the Merle d’Aubigne-Postel score. Implant survival was determined with revision as the end point, and any related complications were investigated. Results: The Merle d’Aubigne-Postel score improved from 9.4 to 16.1 at the final follow-up, without any implant loosening. However, periprosthetic femoral fractures were observed in four hips (6.0 %), one intra-operatively and three within three weeks after THA. Among these cases, three hips previously had varus osteotomy (12.5 %) and one hip had valgus osteotomy (2.3 %). Two hips were revised with full porous stems and circumferential wiring. The five and ten year cumulative survivorship rates were 97 % (range, 88.8–99.3 %) and 97 % (88.8–99.3 %), respectively. Conclusions: Although the use of a press-fit cementless stem yielded acceptable results in most of the patients, perioperative femoral fracture was a major complication especially in the patients previously treated with intertrochanteric varus osteotomy. Careful planning and implant selection could be emphasized for these cases..
159. Kensei Yoshimoto, Yasuharu Nakashima, Takuaki Yamamoto, Jun ichi Fukushi, Goro Motomura, Masanobu Ohishi, Satoshi Hamai, Yukihide Iwamoto, Dislocation and its recurrence after revision total hip arthroplasty, International Orthopaedics, 10.1007/s00264-015-3020-3, 2016.08, Purpose: Dislocation is a leading cause of failure after revision total hip arthroplasty (THA). This study was conducted to examine the risk factors for dislocation as well as their recurrence after revision THA. Methods: We retrospectively reviewed 178 revision THAs in 162 patients between 1998 and 2013. The mean patient age was 65.2 years at operation and the mean follow-up period was 6.7 years. Multivariate logistic regression was performed to identify risk factors for dislocation, and further comparison was made between patients with single and recurrent dislocations. Results: Sixteen hips in 15 patients (9.0 %) dislocated at a mean of 9.1 months (range, 0–83 months) after revision THA. Multivariate analysis identified advanced age (odds ratio [OR] = 2.94/10 years) and osteonecrosis of the femoral head (OR = 7.71) as the independent risk factors for any dislocations. Risk factors for recurrent dislocations, which were observed in eight hips (50 %), were later dislocations (≥4 months) and lower BMI. Conclusion: Dislocation is a serious problem after revision THA with multiple risk factors. Although our findings were limited to revision THAs done through posterolateral approach, recognition of these factors is helpful in patient education and surgical planning..
160. Masanori Fujii, Yasuharu Nakashima, Yasuo Noguchi, Takuaki Yamamoto, Goro Motomura, Satoshi Hamai, Yukihide Iwamoto, Factors Associated With Severity of Intra-articular Lesions in Patients With Severe Hip Dysplasia, Arthroscopy - Journal of Arthroscopic and Related Surgery, 10.1016/j.arthro.2016.01.060, 2016.08, Purpose To identify demographic and morphologic factors associated with the severity of intra-articular lesions in patients with severe hip dysplasia. Methods One hundred twenty-one patients (134 hips) with symptomatic hip dysplasia were retrospectively reviewed. The cartilage and labral lesions were scored according to the Outerbridge and the original classification systems, respectively. The association of the cartilage and labrum scores with patient demographics (age, gender, body mass index, bilateral hip dysplasia, and treatment history for developmental hip dislocation) and morphologic factors (the lateral center-edge angle, Sharp angle, acetabular index, acetabular head index, acetabular depth ratio, Shenton line disruption, roundness index of the femoral head, and femoral neck shaft angle) were determined using a multiple linear regression analysis. Results The cartilage and labral scores were significantly associated with radiographic osteoarthritis; however, these scores showed wide distribution among hips with equivalent degrees of radiographic osteoarthritis. Age (38.4 ± 12.8 years) (P <.001), lateral center-edge angle (0.2 ± 9.0°) (P =.014), acetabular head index (54.4 ± 9.1%) (P =.001), and the roundness index of the femoral head (55.6 ± 4.6%) (P =.022) were identified as independent factors associated with the cartilage score. Age (P <.001), having a medical history of developmental hip dislocation (P =.002), acetabular index (27.8 ± 6.8°) (P =.011), and the roundness index of the femoral head (P =.022) were identified as independent factors associated with the labral score. Conclusions Our findings suggest that the morphologic factors responsible for severe intra-articular lesions differ for cartilage degeneration and labral tears in patients with severe hip dysplasia. Decreased acetabular coverage of the femoral head was responsible for cartilage degeneration severity, whereas an increased acetabular index was responsible for labral tear severity. Level of Evidence Level III, diagnostic study..
161. Daisuke Hara, Yasuharu Nakashima, Satoshi Hamai, Hidehiko Higaki, Satoru Ikebe, Takeshi Shimoto, Kensei Yoshimoto, Yukihide Iwamoto, Dynamic Hip Kinematics during the Golf Swing after Total Hip Arthroplasty, American Journal of Sports Medicine, 10.1177/0363546516637179, 2016.07, Background: Although most surgeons allow their patients to play golf after total hip arthroplasty (THA), the effect on the implant during the golf swing is still unclear. Purpose: To evaluate hip kinematics during the golf swing after THA. Study Design: Descriptive laboratory study. Methods: Eleven hips in 9 patients who underwent primary THA were analyzed. All patients were right-handed recreational golfers, and these 11 hips included 6 right hips and 5 left hips. Periodic radiographic images of the golf swing were taken using a flat-panel x-ray detector. Movements of the hip joint and components were assessed using 3-dimensional-to-2-dimensional model-to-image registration techniques. Liner-to-neck contact and translation of the femoral head with respect to the acetabular cup (cup-head translation) were examined. Hip kinematics, orientation of components, and maximum cup-head translation were compared between patients with and without liner-to-neck contact. Results: On average, the golf swing produced approximately 50° of axial rotation in both lead and trail hips. Liner-to-neck contact was observed in 4 hips with elevated rim liners (2 lead hips and 2 trail hips) at maximum external rotation. Neither bone-to-bone nor bone-to-implant contact was observed at any phases of the golf swing in any of the hips. Four hips with liner-to-neck contact had significantly larger maximum external rotation (37.9° ± 7.0° vs 20.6° ± 9.9°, respectively; P =.01) and more cup anteversion (26.5° ± 6.1° vs 10.8° ± 8.9°, respectively; P =.01) than hips without liner-to-neck contact. No significant differences between hips with and without contact were found for cup inclination (42.0° ± 2.5° vs 38.1° ± 5.5°, respectively; P =.22), combined anteversion (45.3° ± 8.9° vs 51.4° ± 7.9°, respectively; P =.26), or maximum cup-head translation (1.3 ± 0.3 mm vs 1.5 ± 0.4 mm, respectively; P =.61). Conclusion: In this analysis, the golf swing did not produce excessive hip rotation or cup-head translation in any hips. However, liner-to-neck contact during the golf swing was observed in 36% of the hips, with unknown effects on the long-term results. Clinical Relevance: Golf is an admissible sport after THA because dynamic hip stability was observed. However, the implant position, especially cup anteversion and the use of elevated rim liners, promoted liner-to-neck contact..
162. Satoshi Hamai, Yasuharu Nakashima, Naohiko Mashima, Takuaki Yamamoto, Tomomi Kamada, Goro Motomura, Hiroshi Imai, Jun ichi Fukushi, Hiromasa Miura, Yukihide Iwamoto, Comparison of 10-year clinical wear of annealed and remelted highly cross-linked polyethylene
A propensity-matched cohort study
, Journal of the Mechanical Behavior of Biomedical Materials, 10.1016/j.jmbbm.2015.12.022, 2016.06, No previous studies comparing the clinical wear rates of the two different kinds of cross-linked ultra-high-molecular-weight polyethylene (XLPE), annealed and remelted, are available. We compared the creep and steady wear rates of 36 matched pairs (72 hips in total) adjusting for baseline characteristics with propensity score matching techniques. Zirconia femoral heads with 26-mm diameter were used in all cases. The femoral-head cup penetration was measured digitally on radiographs. Significantly greater creep ( p=0.006) was detected in the remelted (0.234 mm) than annealed (0.159 mm) XLPE. However, no significant difference ( p=0.19) was found between the steady wear rates (0.003 and 0.008 mm/year, respectively) of the annealed and remelted XLPE. Multiple regression analyses showed that remelted XLPE is significant independent variable ( p<0.001) that is positively associated with creep. However, the patient age and body weight, cup size, the liner thickness, cup inclination, follow-up periods, and postoperative Merle d'Aubigné hip score had no significant effects ( p>0.05) on the steady wear rates. No patients exhibited above the osteolysis threshold of 0.1 mm/year, progressive radiolucencies, osteolysis, or polyethylene fracture. This[U+3000]propensity-matched cohort study document no significant difference in wear resistant performances of annealed and remelted XLPE over an average period of 10 years..
163. Masayuki Kanazawa, Yasuharu Nakashima, Satoshi Hamai, Masanobu Hirata, Yukihide Iwamoto, Is a Stem Version on the Crosstable Lateral Radiograph Accurate in Total Hip Arthroplasty?, Journal of Arthroplasty, 10.1016/j.arth.2015.12.022, 2016.06, Background: In contrast to the acetabular cup version (CV), stem version (SV) measurement on the crosstable lateral radiograph has not been validated. We, therefore, investigated: (1) the difference of SV on the crosstable lateral radiograph from that measured using computed tomography data and (2) the reliability of SV measurement on the crosstable lateral radiograph. Methods: We examined the correlations of the crosstable-CV and crosstable-SV with true-CV (operative cup anteversion) and true-SV (neck version relative to the posterior condylar line) obtained using computed tomography data from 103 patients. We also produced the digital reconstructed crosstable lateral radiograph with adjusted hip flexion and rotation and defined SV on this image as the true-crosstable SV. Results: Significant positive correlations were noted between the crosstable-CV and true-CV, with a correlation coefficient of 0.79. In contrast, the correlation between the crosstable-SV and true-SV was very low (r = 0.30), with significantly higher deviation from the true-SV values when compared with the crosstable-CV (standard deviation, 11.6° vs 6.5°, P < .001). The true-crosstable SV was correlated with true-SV (r = 0.81); however, the average difference was 23.5° ± 8.9°. Conclusion: Crosstable-SV differed from true-SV in the measurement plane and did not correlate well with the true-SV, suggesting the unreliability of its measurements. Therefore, the crosstable-SV is not recommended for clinical use..
164. Taishi Sato, Yasuharu Nakashima, Keisuke Komiyama, Takuaki Yamamoto, Goro Motomura, Yukihide Iwamoto, The Absence of Hydroxyapatite Coating on Cementless Acetabular Components Does Not Affect Long-Term Survivorship in Total Hip Arthroplasty, Journal of Arthroplasty, 10.1016/j.arth.2015.11.034, 2016.06, Background: Hydroxyapatite (HA) has been applied to joint prostheses as a bioactive coating to prolong their durability. However, HA benefits for cup survival in total hip arthroplasty (THA) remain controversial. In this study, we compared the survival of cups with and without HA coating during a minimum follow-up of 18 years. Methods: In total, 183 THA cases in 163 patients were analyzed, including 73 cups with HA coating (HA+ group) and 110 without HA coating (HA- group); otherwise, the cups had identical titanium-sprayed rough surfaces and were fixed with screws. In both groups, the same conventional polyethylene liners were applied. Zirconia and alumina ceramic heads were used in the HA+ and HA- groups, respectively. We retrospectively analyzed cup survival based on cup revision for any reason or aseptic loosening as end points. Results: In total, 7 and 8 revisions were performed in the HA- and HA+ groups with survival rates of 86.3% and 90.1%, respectively. Among them, 3 cups in the HA- group and 1 cup in the HA+ group were revised for aseptic loosening in 20 years (survival rates 94.1% and 98.7%, respectively). No significant difference was detected in cup survival rates between the groups based on both end points. There were no stem revisions during the observation period. Conclusion: The results suggested that HA coating did not have either beneficial or adverse effects on the long-term cup survival in primary cementless THA..
165. Yasuharu Nakashima, Yuma Sakamoto, Gen Nishimura, Shiro Ikegawa, Yukihide Iwamoto, A novel type II collagen gene mutation in a family with spondyloepiphyseal dysplasia and extensive intrafamilial phenotypic diversity, Human Genome Variation, 10.1038/hgv.2016.7, 2016.05, The purpose of this study was to describe a family with spondyloepiphyseal dysplasia caused by a novel type II collagen gene (COL2A1) mutation and the family's phenotypic diversity. Clinical and radiographic examinations of skeletal dysplasia were conducted on seven affected family members across two generations. The entire coding region of COL2A1, including the flanking intron regions, was analyzed with PCR and direct sequencing. The stature of the subjects ranged from extremely short to within normal height range. Hip deformity and advanced osteoarthritis were noted in all the subjects, ranging from severe coxa plana to mild acetabular dysplasia. Atlantoaxial subluxation combined with a hypoplastic odontoid process was found in three of the subjects. Various degrees of platyspondyly were confirmed in all subjects. Genetically, a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala) was identified in all the affected family members; however, it was not present in the one unaffected family member tested. We described a family with spondyloepiphyseal dysplasia and a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala). Phenotypes were diverse even among individuals with the same mutation and within the same family..
166. Yasuharu Nakashima, Masanobu Ohishi, Ken Okazaki, Jun Ichi Fukushi, Akiko Oyamada, Daisuke Hara, Toshio Doi, Yukio Akasaki, Hisakata Yamada, Yukihide Iwamoto, Delayed diagnosis of ankylosing spondylitis in a Japanese population, Modern Rheumatology, 10.3109/14397595.2015.1088679, 2016.05, Objectives: This study was conducted to evaluate the period from symptom onset to diagnosis of ankylosing spondylitis (AS) in Japanese patients and to examine possible reasons for delayed diagnosis.Methods: Seventy-two consecutive patients with AS were studied. Diagnostic delay was defined as the gap between the first spondyloarthropathic symptom and diagnosis of AS according to the modified New York criteria.Results: The mean patient ages at disease onset and diagnosis were 25.6 ± 11.3 and 33.3 ± 13.2 years old, respectively, resulting in diagnostic delay of 6.7 years. The number of medical institutions to which patients were referred before diagnosis was 2.4, and orthopedic surgeons were most commonly visited (62%). Non-specific low back pain or lumbar spondylitis (33%) and degenerative arthritis (28%) were the primary diagnoses preceding that of AS. Absence of articular symptoms significantly correlated with diagnostic delay. The patients with disease onset on year 2000 or later had significantly shorter periods until diagnosis than those before 2000 (3.6 vs. 7.5 years).Conclusions: The present study showed a marked diagnostic delay among Japanese patients with AS. Although it has been improved, continuing medical education focusing on inflammatory back pain in adolescent is required for early diagnosis of AS..
167. Masayuki Kanazawa, Yasuharu Nakashima, Masanobu Ohishi, Satoshi Hamai, Goro Motomura, Takuaki Yamamoto, Jun Ichi Fukushi, Takahiro Ushijima, Daisuke Hara, Yukihide Iwamoto, Pelvic tilt and movement during total hip arthroplasty in the lateral decubitus position, Modern Rheumatology, 10.3109/14397595.2015.1092914, 2016.05, Objectives: Total hip arthroplasty (THA) is often performed in the lateral decubitus (lateral) position. In this position, the pelvis may have various degrees of tilt leading to implant malposition. We sought to quantify the pelvic tilt in lateral position and further pelvic movement during surgery.Methods: In 95 cases with primary THA, three-dimensional pelvic tilts were quantified by superimposing images reconstructed from CT data onto antero-posterior radiographs taken in lateral position at set-up and after cup placement. Pelvises were fixed with a device compressing anterior superior iliac spines and sacrum.Results: Various degrees of pelvic tilt occurred compared to the supine position; sagittal: -3.1° (-25.5° to 10.2°), axial: 3.9° (-8.4° to 17°), coronal: 0.9° (-11.9° to 13.2°). Absolute changes more than 5° were observed 43%, 47%, and 12% in the sagittal, axial, and coronal planes, respectively. The more preoperative posterior pelvic tilt resulted in the more change in the sagittal plane. Further pelvic movement of about 3° in three planes were observed ranging from -11° to 20° after cup placement.Conclusion: This study showed various pelvic tilt and movement during THA. As pelvic tilt directly alters the cup orientation, its changes should be well understood. Improved tools for positioning and holding the pelvis are required..
168. T. Yamamoto, G. Motomura, K. Karasuyama, Y. Nakashima, T. Doi, Y. Iwamoto, Results of the Sugioka transtrochanteric rotational osteotomy for osteonecrosis
Frequency and role of a defect of the quadratus femoris muscle in osteonecrosis progression
, Orthopaedics and Traumatology: Surgery and Research, 10.1016/j.otsr.2016.01.017, 2016.05, Background: During transtrochanteric rotational osteotomy (RO), it is important to preserve the posterior column artery (PCA), which is generally located in the adipose tissue underneath the quadratus femoris muscle (QF). If there is a defect in the QF, the risk of injuring the PCA, subsequently resulting in total necrosis of the femoral head, may increase. Therefore, we investigated: (1) the frequency of defects of the QF at the time of RO, and (2) clinical outcome of RO based upon a defect of the QF. Hypothesis: The presence of defects of the QF at the time of RO could be detected pre-operatively by magnetic resonance imaging. Methods: RO was performed in 124 hips between 2001 and 2010. In all, 95 of the hips were in male patients and 29 in female patients. The mean age was 45.4 years (range: 11-61 years) at the time of surgery and MRI was performed before RO in all cases. We retrospectively evaluated the progression of a collapse through 3 years after RO. Results: MRI showed a defect in the QF in four hips (3.2%) (2 males, 2 females), all of which were confirmed intra-operatively. Among the four patients, one (25%) underwent total hip arthroplasty because of varus deformity of the osteotomy site due to total necrosis of the femoral head 1 year after RO. The 120 hips with a normal QF showed no evidence of total necrosis or progression of necrosis of the femoral head, indicating that the presence of defects of the QF may increase the risk of poor survivorship of this procedure. Conclusions: Defects of the QF have been reported to occur in 1-2% of all patients, whereas in our study the incidence in ON was approximately 3%. In ON patients with QF defects, pre-operative MRI evaluation of the QF appears to be important when planning RO, followed by a carefully performed surgical procedure. Level of evidence: IV; retrospective case series without control group..
169. Jun Ichi Fukushi, Yasuharu Nakashima, Ken Okazaki, Hisakata Yamada, Taro Mawatari, Masanobu Ohishi, Akiko Oyamada, Yukio Akasaki, Yukihide Iwamoto, Outcome of joint-preserving arthroplasty for rheumatoid forefoot deformities, Foot and Ankle International, 10.1177/1071100715609981, 2016.03, Background: Along with the recent advances in the pharmacological management of rheumatoid arthritis, there is a trend toward the use of joint-preserving surgery in the treatment of rheumatoid forefoot deformities. However, the clinical outcomes of joint-preserving surgery for rheumatoid forefoot deformities have not been assessed in comparison to resection arthroplasty. Methods: We retrospectively evaluated 23 feet in 17 patients with rheumatoid forefoot deformities who underwent surgery between January 2010 and December 2013. The patients included 1 male (1 foot) and 16 females (22 feet), with a mean age of 62 years. The mean length of follow-up was 28 months. The patients were treated by 3 surgeons. One surgeon performed joint-preserving procedures (JP group) to the feet in which (1) no pain with motion existed, and (2) the range of motion in the first metatarsophalangeal (MTP) joint was greater than 30 degrees (n = 10); otherwise, resection arthroplasty with arthrodesis of the first MTP joint was performed (n = 3). The other surgeons performed resection arthroplasty in all cases (n = 10) (RA group, n = 13 in total). The clinical outcomes of the patients were evaluated using the Japanese Society for Surgery of the Foot (JSSF) hallux and lesser toe scales. Results: There were no significant differences in the preoperative total JSSF scores for either the hallux (54.5 and 61.4 points) or the lesser toe (45.2 and 57.4 points) between the RA and JP groups, respectively. Postoperatively, the total JSSF scores for both the hallux (79.4 and 88.2 points) and lesser toes (73.6 and 87.7 points) showed significant improvement in both the RA and JP groups, respectively; however, the JP group showed a greater postoperative improvement. The scores relating to the function category on the hallux scale and the alignment category on the lesser toe scale were significantly higher in the JP group. Conclusion: With regard to the function of the hallux and the alignment of the lesser toes, the joint-preserving procedures for rheumatoid forefoot deformities resulted in better clinical outcomes than resection arthroplasty..
170. Daisuke Hara, Yasuharu Nakashima, Taishi Sato, Masanobu Hirata, Masayuki Kanazawa, Yusuke Kohno, Kensei Yoshimoto, Yusuke Yoshihara, Akihiro Nakamura, Yumiko Nakao, Yukihide Iwamoto, Bone bonding strength of diamond-structured porous titanium-alloy implants manufactured using the electron beam-melting technique, Materials Science and Engineering C, 10.1016/j.msec.2015.11.025, 2016.02, The present study examined the bone bonding strength of diamond-structured porous titanium-alloy (Porous-Ti-alloy) manufactured using the electron beam-melting technique in comparison with fiber mesh-coated or rough-surfaced implants. Cylindrical implants with four different pore sizes (500, 640, 800, and 1000 μm) of Porous-Ti-alloy, titanium fiber mesh (FM), and surfaces roughened by titanium arc spray (Ti-spray) were implanted into the distal femur of rabbits. Bone bonding strength and histological bone ingrowth were evaluated at 4 and 12 weeks after implantation. The bone bonding strength of Porous-Ti-alloy implants (640 μm pore size) increased over time from 541.4 N at 4 weeks to 704.6 N at 12 weeks and was comparable to that of FM and Ti-spray implants at both weeks. No breakage of the porous structure after mechanical testing was found with Porous-Ti-alloy implants. Histological bone ingrowth that increased with implantation time occurred along the inner structure of Porous-Ti-alloy implants. There was no difference in bone ingrowth in Porous-Ti-alloy implants with pore sizes among 500, 640, and 800 μm; however, less bone ingrowth was observed with the 1000 μm pore size. These results indicated Porous-Ti-alloy implants with pore size under 800 μm provided biologically active and mechanically stable surface for implant fixation to bone, and had potential advantages for weight bearing orthopedic implants such as acetabular cups..
171. Daisuke Hara, Yasuharu Nakashima, Satoshi Hamai, Hidehiko Higaki, Satoru Ikebe, Takeshi Shimoto, Kensei Yoshimoto, Yukihide Iwamoto, Dynamic hip kinematics in patients with hip osteoarthritis during weight-bearing activities, Clinical Biomechanics, 10.1016/j.clinbiomech.2015.11.019, 2016.02, Background There is an interest in quantifying the hip kinematics of patients with end-stage hip disorders before total hip arthroplasty. The purpose of the present study was to obtain dynamic hip kinematics under four different conditions, including deep flexion and rotation, in patients with osteoarthritis of the hip. Methods Continuous X-ray images were obtained in 14 patients during gait, chair-rising, squatting, and twisting, using a flat panel X-ray detector. These patients received computed tomography scan to generate virtual digitally reconstructed radiographs. The density-based digitally reconstructed radiographs were then compared with the serial X-ray images acquired using image correlations. These 3D-to-2D model-to-image registration techniques determined the 3D positions and orientations of the pelvis and femur during the movement cycle of each activity. Findings For gait, chair-rising, and squatting, the maximum hip flexion angles averaged 22°, 64°, and 68°, respectively. The pelvis was tilted anteriorly by an average of around 7° during the full gait cycle. For chair-rising and squatting, the maximum absolute values of anterior/posterior pelvic tilt averaged 8°/17° and 6°/18°, respectively. Hip flexion showed maximum flexion angle on the way of movement due to further anterior pelvic tilt during both chair-rising and squatting. For twisting, the maximum absolute values of internal/external hip rotation averaged 3°/13°. Interpretation Patients with hip osteoarthritis prior to total hip arthroplasty demonstrated the limited ranges of coordinated motion of the pelvis, femur, and hip joint during each activity, especially in deeply flexed and rotated postures..
172. Jun ichi Fukushi, Shoji Tokunaga, Yasuharu Nakashima, Goro Motomura, Chikage Mitoma, Hiroshi Uchi, Masutaka Furue, Yukihide Iwamoto, Effects of dioxin-related compounds on bone mineral density in patients affected by the Yusho incident, Chemosphere, 10.1016/j.chemosphere.2015.11.091, 2016.02, Exposure to dioxin-related compounds results in many adverse health effects. Several studies have examined the effects of dioxin-related compounds on human bone metabolism with inconsistent results. In Japan in 1968, accidental human exposure to rice oil contaminated with dioxin-related compounds led to the development of Yusho oil disease. The aim of this study was to determine whether exposure to dioxin-related compounds was associated with bone mineral density in Yusho patients. In 2010, 262 women and 227 men underwent dual-energy X-ray absorptiometry bone scans as part of the nationwide Yusho health examination. Serum levels of polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls were measured using high-resolution gas chromatography and high-resolution mass spectrometry. When adjusted for prefecture, 1,2,3,4,7,8-HxCDD and 2,3,7,8-TCDF were significantly positively associated with Z-scores in men. No congeners were positively associated with Z-scores in women. After adjustment for prefecture and body mass index, one congener, 1,2,3,4,6,7,8-HpCDD, was negatively associated with Z-scores in women. In contrast, no congeners remained significant in men after adjusting for body mass index. This may suggest that 1,2,3,4,6,7,8-HpCDD has a negative effect on bone mineral density in women; however, the findings should be interpreted carefully, because no increase in the serum level of this congener was observed in patients with Yusho disease..
173. Hiroki Kobayashi, Yasuharu Nakashima, Takuaki Yamamoto, goro motomura, Masayuki Kanazawa, Kenji Takagishi, Yukihide Iwamoto, Late Anterior Dislocation Due to Posterior Pelvic Tilt in Total Hip Arthroplasty, The open orthopaedics journal, 10.2174/1874325001610010206, 2016.01, BACKGROUND: Excessive pelvic tilt may be one of the factors leading to instability in total hip arthroplasty (THA), even when the acetabular cup is placed properly. To our knowledge, only a few studies have described late anterior dislocation due to posterior pelvic tilt. We present 3 cases with late anterior dislocations possibly due to posterior pelvic tilt.
CASES PRESENTATIONS: Case-1: An 84-years-old woman fell and presented with an anterior dislocation 12-years after THA. Her pelvis had tilted to approximately 30° posteriorly in a supine position. After conservative treatment, she presented with 10 recurrent anterior dislocations. She had thoracolumbar kyphosis due to multiple compression fractures. Revision with anterior placement of an elevated liner and a 32-mm head corrected the dislocation, and no further dislocations occurred. Case-2: A 78-years-old woman fell and presented with an anterior dislocation 4-years after THA. Her posterior pelvic tilt had increased 23° due to a lumbar compression fracture. Revision by decreasing the cup anteversion was performed, but recurrent posterior dislocations occurred. Owing to her worsened general condition, further treatment was abandoned. Case-3: A 79-years-old woman twisted her body and presented an anterior dislocation 3-years after THA. After manual reduction and conservative treatment, the dislocation recurred. Her posterior pelvic tilt had increased 16°.
CONCLUSION: Although minor trauma triggered the anterior instability in these patients, the underlying pathomechanism existed in the progressive pelvic posterior tilt due to thoracolumbar kyphosis. As longer life expectancy as well as implant survivorship is predicted, attention must be paid to the change of pelvic tilt in elderly patients..
174. Yusuke Kubo, Masanobu Ohishi, Yasuharu Nakashima, Ken Okazaki, Jun ichi Fukushi, Akiko Oyamada, Yukihide Iwamoto, Efficacy and Safety of Infliximab for Ankylosing Spondylitis in Japanese Patients
A Retrospective Study of 11 Cases
, Fukuoka igaku zasshi = Hukuoka acta medica, 2015.12, PURPOSE: Tumor necrosis factor inhibitors (TNFi) such as infliximab (IFX) and adalimumab have been shown to be efficacious not only for rheumatoid arthritis but also for Ankylosing Spondylitis (AS). However, only a limited number of reports regarding the effect of TNFi on AS in Japanese population have been published.
MATERIALS AND METHODS: We retrospectively evaluated all 11 patients (8 males and 3 females) with AS who were treated with IFX.
RESULTS: After a mean follow-up period of 19 months, the mean BASDAI decreased from 4.7 ± 2.2 to 1.7 ± 1.2 and the serum CRP level decreased from 1.62 ± 1.94 mg/dl to 0.23 ± 0.45 mg/dl. There was no case of serious infection or anaphylaxis.
CONCLUSIONS: Our results indicate that IFX is efficacious and safe for AS in Japanese patients..
175. Yongseung Lee, Goro Motomura, Takuaki Yamamoto, Yasuharu Nakashima, Masanobu Ohishi, Satoshi Hamai, Kunio Iura, Yukihide Iwamoto, Rapidly destructive arthrosis of the hip joint in a young adult with systemic lupus erythematosus, Rheumatology International, 10.1007/s00296-015-3304-3, 2015.10, A 37-year-old female had been treated with corticosteroids for systemic lupus erythematosus clinically diagnosed at age 10. She suddenly had right hip pain without any antecedent trauma. Four months after the onset of pain, she visited her primary care physician. On magnetic resonance imaging, joint space narrowing at the weight-bearing area was already seen with bone marrow edematous lesions in both the femoral head and acetabulum. She was treated non-operatively; however, her pain continued to worsen in severity. Thirteen months after the onset of pain, she was referred to our hospital. A plain radiograph showed subluxation of the collapsed femoral head accompanied by destruction of the acetabular rim. Because of her severe intractable pain, she underwent total hip arthroplasty 1 month after her first visit. Histological examination of the resected femoral head revealed pseudogranulomatous lesions along with prominent callus formation, suggesting rapid destruction of the femoral head..
176. Kensei Yoshimoto, Yasuharu Nakashima, Akihiro Nakamura, Taro Mawatari, Mitsugu Todo, Daisuke Hara, Yukihide Iwamoto, Neck fracture of femoral stems with a sharp slot at the neck
biomechanical analysis
, Journal of Orthopaedic Science, 10.1007/s00776-015-0745-1, 2015.09, Background: Fracture of the femoral stem in total hip arthroplasty (THA) is a rare complication. We have encountered 2 cases of neck fractures of the femoral stem occurring 9 and 12 years after THA. Morphological and biomechanical analysis were performed to investigate the mechanism of these fractures. Method: A titanium alloy femoral stem having a slot with sharp corners (R = 0.2 mm) at the neck had been implanted in both cases. Fracture surfaces were examined by use of scanning electron microscopy (SEM). Stress concentration was simulated by using a finite element method (FEM) to compare slots with sharp (R = 0.2 mm) and smooth (R = 2 mm) corners. Results: Study of the retrieved stems revealed that neck fractures had occurred at the distal end of the slot in both cases. SEM revealed numerous fine fissures extending from the anterolateral edge, striations on the middle of the fracture surface, and dimples on the posteromedial surface, suggesting that the fractures had occurred from the anterolateral aspect toward the posteromedial aspect because of metallic fatigue. FEM analysis showed that mechanical stress was concentrated at the distal and anterolateral corners of the slot. Under 3500-N loading force, the stress at the sharp corner was 556 MPa, which was approximately twofold that at the smooth corner and exceeded the fatigue strength of titanium alloy. Conclusion: These findings showed that the sharp corner of slot increased stress concentrations at the anterolateral aspect and led to the neck fractures..
177. Kazuhiko Sonoda, Takuaki Yamamoto, Goro Motomura, Yasuharu Nakashima, Ryosuke Yamaguchi, Yukihide Iwamoto, Outcome of transtrochanteric rotational osteotomy for posttraumatic osteonecrosis of the femoral head with a mean follow-up of 12.3 years, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-015-2282-y, 2015.09, Introduction: This study examined the outcomes of applying transtrochanteric rotational osteotomy (TRO) for posttraumatic osteonecrosis of the femoral head (ON). Patients and Methods: We retrospectively reviewed 28 hips in 28 patients (male, n = 17; female n = 11) with a mean age of 34.8 years (12–61 years) at the time of TRO. Transtrochanteric anterior rotational osteotomy (ARO) was used when the lesion was localized on the anterior aspect of the femoral head, and transtrochanteric posterior rotational osteotomy (PRO) was indicated in patients with lesions limited to the posterior aspect of the femoral head. The mean follow-up period was 12.3 years (5.0–21.3 years). We investigated the patients’ clinical and radiological factors, including age, sex, body mass index, preoperative Harris Hip Score (HHS), type of antecedent trauma, preoperative stage, and postoperative intact ratio (the ratio of the intact articular surface of the femoral head to the weight-bearing surface of the acetabulum). We divided the patients into a hip-survival group and a conversion-to-total hip arthroplasty (THA) group and then compared these factors between the two groups. Results: At the final follow-up, 22 hips had survived with a mean HHS of 85.8. The remaining six hips underwent THA at a mean of 10.2 years after TRO. The preoperative stage was correlated with hip survival. Furthermore, the postoperative intact ratio was significantly lower in the conversion-to-THA group. Based on the receiver operating characteristic curve, a ratio of less than 33.6 % was found to be associated with the need to convert to THA. Conclusions: TRO to correct posttraumatic ON resulted in favorable midterm results. The possible risk factors for conversion to THA were an advanced preoperative stage and a postoperative intact ratio of less than 33.6 %..
178. Toru Ishibashi, Miki Ichikawa, Bunpei Sato, Shinji Shibata, Yuichi Hara, Yuji Naritomi, Ken Okazaki, Yasuharu Nakashima, Yukihide Iwamoto, Samon Koyanagi, Hiroshi Hara, Tetsuhiko Nagao, Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen
A report of three cases
, Molecular medicine reports, 10.3892/mmr.2015.3707, 2015.08, Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis..
179. Mio Akiyama, Taro Mawatari, Yasuharu Nakashima, Hisaaki Miyahara, Hisakata Yamada, Ken Okazaki, Jun Ichi Fukushi, Masakazu Kondo, Junji Kishimoto, Chinami Hashimura, Yukihide Iwamoto, Prevalence of dyslipidemia in Japanese patients with rheumatoid arthritis and effects of atorvastatin treatment, Clinical Rheumatology, 10.1007/s10067-015-3049-0, 2015.08, Few studies have examined dyslipidemia in patients with rheumatoid arthritis (RA), especially in Japanese cohorts. The aims of this study were to investigate the lipid profiles of RA patients, to assess the relationships between lipid profiles and RA activity and treatment, and to elucidate the effects of HMG-CoA reductase inhibitors (statins) in Japanese patients with RA. A multicenter observational study was conducted in 488 patients with RA. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels, and RA activity as assessed by disease activity score 28 (DAS28), and treatment for RA were analyzed retrospectively. In statin-treated patients, drug efficacy was also analyzed. The prevalence of hyper LDL-C, hyper TG, and hypo HDL-C were 29.3, 24.2, and 10.2 %, respectively, and the overall prevalence of dyslipidemia was 56.5 %. The level of HDL-C was inversely correlated with DAS28. Patients treated with low-dose glucocorticoids showed significantly higher levels of HDL-C and lower TC/HDL-C ratios compared with patients not receiving glucocorticoid treatment. Conversely, patients treated with biologic agents showed significantly higher levels of LDL-C, lower levels of HDL-C, and higher TC/HDL-C ratios. Atorvastatin significantly improved lipid profiles after a few months of treatment. The prevalence of dyslipidemia in Japanese patients with RA is higher than that in the non-RA population. Our result suggests that controlling RA disease activity might improve lipid profiles and eventually lower cardiovascular risk. Low-dose atorvastatin was effective for treatment of dyslipidemia in RA patients but had no apparent effect on RA disease activity..
180. Yasuharu Nakashima, CORR Insights ®
How are Dysplastic Hips Different? A Three-dimensional CT Study
, Clinical orthopaedics and related research, 10.1007/s11999-015-4165-5, 2015.05.
181. Yusuke Kohno, Yasuharu Nakashima, Mio Akiyama, Masanori Fujii, Yukihide Iwamoto, Does Native Combined Anteversion Influence Pain Onset in Patients With Dysplastic Hips?, Clinical orthopaedics and related research, 10.1007/s11999-015-4373-z, 2015.05, Background: Combined anteversion is the sum of femoral and acetabular anteversion and represents their morphological relationship in the axial plane. Few studies have investigated the native combined anteversion in patients with symptomatic dysplastic hips. Questions/purposes: We hypothesized the following: (1) dysplastic hips have two distinct populations, which differ from each other and from normal hips in their combined anteversion; and (2) these populations differ clinically in terms of correlation between age of onset of symptoms and amount of anteversion. Methods: We measured radiographic parameters by CT of 100 dysplastic hips in 76 patients who were symptomatic enough to undergo periacetabular osteotomy and of 50 normal hips in 44 patients who had CT scans as part of preparation for computer-navigated TKAs; these patients had no visible hip arthritis or dysplasia and no hip symptoms. Dysplastic hips were divided into the anteversion (83 hips) and retroversion groups (17 hips) based on acetabular version. Age at pain onset was determined from their medical charts. Results: Combined anteversion in the anteversion group was greater than that in the retroversion and control groups: 47° ± 12°, 30° ± 16°, and 36° ± 9°, respectively. In the anteversion group, combined anteversion (r = −0.49; 95% confidence interval [CI], −0.66 to −0.27; p < 0.001) and femoral anteversion (r = −0.41; 95% CI, −0.60 to −0.19; p < 0.001) were associated with an earlier age at pain onset; however, no such relationships were observed in the retroversion group. After controlling for relevant potential confounding variables, we found that combined anteversion (hazard ratio [HR], 1.04; 95% CI, 1.01–1.07; p = 0.006) and Sharp angle (HR, 1.10; 95% CI, 1.02–1.17; p = 0.008) were associated with an earlier age of pain onset in the anteversion group. Conclusions: These results suggest that not only lateral coverage of the femoral head, but also axial joint morphology is important for the development of pain in the anteversion group. Optimal combined anteversion should be considered during periacetabular osteotomy. Level of Evidence: Level IV, prognostic study..
182. Yasuharu Nakashima, CORR Insights®: How are Dysplastic Hips Different? A Three-dimensional CT Study., Clin Orthop Relat Res, 2015.04.
183. Kazuyuki Karasuyama, Takuaki Yamamoto, Goro Motomura, Yasuharu Nakashima, Akio Sakamoto, Ryosuke Yamaguchi, Yukihide Iwamoto, Osteonecrosis of the femoral head with collapsed medial lesion, Clinical Medicine Insights: Case Reports, 10.4137/CCRep.S18171, 2014.09, A 60-year-old female experienced the gradual onset of left hip pain without any triggering event. Radiographs showed vertical sclerosis in the center of the femoral head and the lesion inside the boundary demonstrated diffuse bony sclerosis. No collapse was observed at the weight-bearing portion on radiograph. However, computed tomography showed a subchondral collapse at the medial lesion. On T2-weighted magnetic resonance imaging, the necrotic lesion showed diffuse high-intensity signals that indicated a prominent repair process. Bone biopsy diagnosed osteonecrosis with associated prominent appositional bone and vascular granulation tissue..
184. Yasuharu Nakashima, Masakazu Kondo, Hisaaki Miyahara, Yukihide Iwamoto, Drug delivery options to increase patient adherence and satisfaction in the management of rheumatoid arthritis - Focus on subcutaneous tocilizumab, Drug Design, Development and Therapy, 10.2147/DDDT.S52099, 2014.07, Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease associated with joint destruction. Tocilizumab (TCZ) is a humanized monoclonal anti-interleukin-6 receptor antibody that was initially developed for use as an intravenous (IV) infusion. Previous studies have shown that TCZ-IV is an important treatment option in patients with moderate-to-severe RA. A subcutaneous (SC) formulation of 162 mg TCZ that was recently developed and approved provides an additional treatment option for RA patients. In the present review, we provide an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC doses of 162 mg every 2 weeks (q2w) or weekly (qw) were selected based on pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw regimen consistently showed a more rapid effect in terms of C-reactive protein normalization. Randomized controlled studies showed that TCZ-SC monotherapy or combined with disease-modifying antirheumatic drugs demonstrated comparable efficacy to TCZ-IV in patients who were both biologic-naïve and refractory to tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well-tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse events, and their incidence was comparable with that seen with TCZ-IV. An injection site reaction was seen in approximately 10% of patients who received the subcutaneous formulation. In conclusion, although clinical results are still limited, the currently available evidence suggests that TCZ-SC is a promising treatment for moderate-to-severe RA, both as monotherapy and combination therapy. More data is needed to determine the optimal dosing schedule..
185. Masanobu Hirata, Yasuharu Nakashima, Takashi Itokawa, Masanobu Ohishi, Taishi Sato, Mio Akiyama, Daisuke Hara, Yukihide Iwamoto, Influencing factors for the increased stem version compared to the native femur in cementless total hip arthroplasty, International Orthopaedics, 10.1007/s00264-014-2289-y, 2014.07, Purpose: Stem version is not always equivalent to femoral neck version (native version) in cementless total hip arthroplasty (THA). We therefore examined the discrepancy of version between the native femoral neck and stem using pre- and postoperative computed tomography (CT), the level of the femur where the canal version most closely fit the stem version, and the factors influencing version discrepancy between the native femoral neck and stem. Methods: A total of 122 hips in 122 patients who underwent primary THA using a metaphyseal-fit stem through the postero-lateral approach were included. Pre- and postoperative CT images were utilized to measure native and stem version, and the version of the femoral canal at four levels relative to the lesser trochanter. Results: The mean native and stem versions were 28.1±11. 0° and 38.0±11.2°, respectively, revealing increased stem version with a mean difference of 9.8° (p<0.0001). A total of 84 hips (68.9 %) revealed an increase in version greater than 5°. Femoral canal version at the level of the lesser trochanter most closely approximated that of stem version. Among the factors analysed, both univariate and multivariate analysis showed that greater degrees of native version and anterior stem tilt significantly reduced the version discrepancy between the native femoral neck and stem version. Conclusions: Since a cementless stem has little version adjustability in the femoral canal, these findings are useful for surgeons in preoperative planning and to achieve proper component placement in THA..
186. Yasuharu Nakashima, Drug delivery options to increase patient adherence and satisfaction in the management of rheumatoid arthritis - focus on subcutaneous tocilizumab., Drug Des Devel Ther, 2014.05.
187. Masanobu Ohishi, Hisaaki Miyahara, Masakazu Kondo, Yasuharu Nakashima, Kazumasa Terada, Yukio Esaki, Nobuo Kobara, Katsumi Harimaya, Yoshihiro Matsumoto, Yukihide Iwamoto, Characteristics of lumbar scoliosis in patients with rheumatoid arthritis, Journal of Orthopaedic Surgery and Research, 10.1186/1749-799X-9-30, 2014.04, Background: Although a substantial percentage of patients with rheumatoid arthritis (RA) experience low back pain, the characteristics of lumbar spine pathology in RA patients has been poorly investigated. In our institutions, lumbar spine radiographs indicated scoliosis in 26 patients. The present study aimed to clarify the characteristics of lumbar scoliosis in RA patients. Methods: This is a retrospective study of 26 RA patients with lumbar scoliosis. Patient characteristics such as disease duration, disease stage and class according to Steinbrocker's classification, and medication for RA and osteoporosis were reviewed. Radiologic evaluation of scoliosis was performed at two different time points by measuring Cobb angles. The progression of scoliosis per year was calculated by dividing the change in Cobb angles by the number of years. Apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at the first observation were also measured. The correlation between different factors and changes in the Cobb angles per year was analyzed. Results: Majority of the patients had a long disease duration and were classified as stage 3 or 4 according to Steinbrocker's classification. During the observation period, most patients were treated with glucocorticoids. Unlike the previous studies on degenerative scoliosis, apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at initial observation were not significantly related to the progression of scoliosis. Initial Cobb angles were inversely related to the progression of scoliosis. Patients who were treated with bisphosphonates showed slower progression of scoliosis. Conclusions: Our results indicate that the characteristics of lumbar scoliosis in RA patients differ from those of degenerative lumbar scoliosis. Bone fragility due to the long disease duration, poor control of disease activity, and osteoporosis is possibly related to its progression..
188. Yusuke Kohno, Yasuharu Nakashima, Toshio Kitano, Tomoyuki Nakamura, Kazuyuki Takamura, Mio Akiyama, Daisuke Hara, Takuaki Yamamoto, Goro Motomura, Masanobu Ohishi, Satoshi Hamai, Iwamoto Yukihide, Subclinical bilateral involvement of the hip in patients with slipped capital femoral epiphysis - A multicentre study, International Orthopaedics, 10.1007/s00264-013-2131-y, 2014.03, Purpose: This study was conducted to assess the posterior inclination of the contralateral femoral epiphysis in patients with unilateral slipped capital femoral epiphysis (SCFE). Methods: The posterior sloping angle (PSA) was measured using lateral radiographs in 67 patients with a unilateral SCFE and in 41 age-matched normal controls. A symptomatic epiphyseal slip was defined as the development of SCFE. Results: The contralateral PSA in SCFE patients was more widely distributed and significantly larger compared to controls (15.0°vs. 9.0°, p < 0.0001). Forty-seven hips (70.1 %) had a PSA of greater than 12.8°, which was +2SD of the control hips. Of the 65 hips excluding the two cases with prophylactic pinning, 11 hips (16.9 %) eventually developed a contralateral SCFE during adolescence and their PSA at the initial visit was significantly larger compared to patients without a contralateral SCFE (18.0°vs. 14.3°, p < 0.005) with a cutoff value of 19°. Conclusions: These findings suggested the possibility of bilateral hip involvement in SCFE patients. Hips with greater degrees of PSA (> 19°) are likely to become symptomatic..
189. Mio Akiyama, Yasuharu Nakashima, Masanobu Oishi, Taishi Sato, Masanobu Hirata, Daisuke Hara, Yukihide Iwamoto, Risk factors for acetabular retroversion in developmental dysplasia of the hip
Does the Pemberton osteotomy contribute?
, Journal of Orthopaedic Science, 10.1007/s00776-013-0473-3, 2014.01, Background: The purpose of this study was to investigate residual acetabular retroversion after skeletal maturity in patients with Pemberton osteotomy. Patients and methods: We compared 40 hips in 36 patients treated with a Pemberton osteotomy (Pemberton group) and 30 hips in 26 patients treated only with a Pavlik harness (Rb group) for developmental dysplasia of the hip. The average age at operation in the Pemberton group was 94.5 months and the follow-up duration was 151.8 months. Radiographic parameters included the acetabular index (α angle) and the center-edge angle of Wiberg, preoperatively and at skeletal maturity. We examined the crossover sign (COS) at the latest follow-up as a sign of acetabular retroversion (AR). We compared the parameters between the two groups and examined the risk factors for acetabular retroversion using a multivariate Cox model. Result: A COS (+) was significantly more frequent in the Pemberton group compared to the Rb group [15 hips (37.5%) vs 3 hips (10%); p = 0.0077]. In the Pemberton group, the average age at operation in COS (+) hips was significantly older than that in COS (-) hips (126.9 vs 72.8 months; p = 0.0005). The preoperative α angle did not vary between hips with and without COS; however, the postoperative α angle was significantly smaller in COS (+) hips. A multiple logistic regression analysis for prediction of COS (+) showed that the age at operation and the amount change of α angle were significant predictors for COS (+) hips. The cut-off of the age at operation was 7 years and 9 months old. Conclusions: AR was present in 37.5% of the hips in the Pemberton group after skeletal maturity. Remodeling of acetabular version was observed in younger patients; however, hips in older patients (>8 years) at the time of operation and greater degrees of correction tended to result in AR..
190. Keiichiro Iida, Satoshi Hamai, Takuaki Yamamoto, Yasuharu Nakashima, Goro Motomura, Masanobu Ohishi, Kazuyuki Karasuyama, Yukihide Iwamoto, Subchondral fracture of the femoral head after acetabular fracture
A case report
, Journal of Medical Case Reports, 10.1186/1752-1947-8-447, 2014.01, Introduction: Preventing post-traumatic osteoarthritis is a challenging problem following acetabular fracture. Progressive osteoarthritis is considered to be caused by an irregular articular surface of the acetabular roof or cartilage injury, but little is known about the pathogenesis of collapse of the femoral head after acetabular fracture. We report a case of post-traumatic osteoarthritis after acetabular fracture in which subchondral fracture of the femoral head contributed to the progressive collapse of the femoral head and osteoarthritis. To the best of our knowledge, there has been no previous report of subchondral fracture of the femoral head after acetabular fracture. Case presentation: A 58-year-old Japanese man fell from a ladder. He was diagnosed with a left acetabular fracture, which was managed conservatively. He developed left coxalgia six months after injury and was seen at our institution one year after the onset of pain. The left acetabular fracture had fused, but his left femoral head had collapsed. The images at the time of injury showed a fracture of the acetabular roof, and an approximately 2mm step-off existed in the articular surface. Retrospective evaluation of the plain radiographs and computed tomography images showed that his femoral head had progressively collapsed. Our patient underwent total hip arthroplasty. Histopathologic findings demonstrated that the collapse of his femoral head was caused by a subchondral fracture of his femoral head. Conclusion: Our experience with this case indicates that in addition to post-traumatic osteonecrosis, subchondral fracture may need to be considered in cases with progressive collapse of the femoral head after acetabular fracture..
191. Daisuke Hara, Yasuharu Nakashima, Satoshi Hamai, Hidehiko Higaki, Satoru Ikebe, Takeshi Shimoto, Masanobu Hirata, Masayuki Kanazawa, Yusuke Kohno, Yukihide Iwamoto, Kinematic analysis of healthy hips during weight-bearing activities by 3D-to-2D model-to-image registration technique, BioMed Research International, 10.1155/2014/457573, 2014, Dynamic hip kinematics during weight-bearing activities were analyzed for six healthy subjects. Continuous X-ray images of gait, chair-rising, squatting, and twisting were taken using a flat panel X-ray detector. Digitally reconstructed radiographic images were used for 3D-to-2D model-to-image registration technique. The root-mean-square errors associated with tracking the pelvis and femur were less than 0.3 mm and 0.3° for translations and rotations. For gait, chair-rising, and squatting, the maximum hip flexion angles averaged 29.6°, 81.3°, and 102.4°, respectively. The pelvis was tilted anteriorly around 4.4° on average during full gait cycle. For chair-rising and squatting, the maximum absolute value of anterior/posterior pelvic tilt averaged 12.4°/11.7° and 10.7°/10.8°, respectively. Hip flexion peaked on the way of movement due to further anterior pelvic tilt during both chair-rising and squatting. For twisting, the maximum absolute value of hip internal/external rotation averaged 29.2°/30.7°. This study revealed activity dependent kinematics of healthy hip joints with coordinated pelvic and femoral dynamic movements. Kinematics' data during activities of daily living may provide important insight as to the evaluating kinematics of pathological and reconstructed hips..
192. Satoshi Ikemura, Takuaki Yamamoto, Goro Motomura, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, Erratum
The utility of clinical features for distinguishing subchondral insufficiency fracture from osteonecrosis of the femoral head (Archives of Orthopaedic and Trauma Surgery (DOI 10.1007/s00402-013-1847-x)
, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-013-1863-x, 2013.12.
193. Daisuke Hara, Yasuharu Nakashima, Takuaki Yamamoto, Shinshichiro Higashihara, Mitsugu Todo, Masanobu Hirata, Mio Akiyama, Yukihide Iwamoto, Late failure of annealed highly cross-linked polyethylene acetabular liner, Journal of the Mechanical Behavior of Biomedical Materials, 10.1016/j.jmbbm.2013.08.003, 2013.12, Highly cross-linked polyethylene (HXPE) in total hip arthroplasty (THA) has been shown to significantly decrease wear rates compared with conventional polyethylene (CPE). However, crosslinking, thermal treatment and oxidation can decrease the mechanical properties of PE, and several cases of fracture of remelted HXPE liners were reported. We present, for the first time, unexpected failures of THA with the use of annealed HXPE liners in two patients occurring at 7 and 8 years after operation. Operative findings revealed dislocated liners from the metal shell and a fracture of the superior rim at the rim-dome junction in both liners. Scanning electron microscopy showed that the cracks initiated at the rim and propagated toward the articular surface. Both liners showed generally a low amount of oxidation (less than 1.00) at the articular surface and low wear rates; however, oxidation at the rim was relatively higher (mean 1.55). These findings suggested that decreased mechanical properties at the rim-dome junction due to cross-linking, annealing and oxidation might have been caused breakage of the HXPE liners after a long implantation time, although the annealed HXPE achieved low degree of wear..
194. Mio Akiyama, Yasuharu Nakashima, Toshio Kitano, Tomoyuki Nakamura, Kazuyuki Takamura, Yusuke Kohno, Takuaki Yamamoto, Goro Motomura, Masanobu Ohishi, Satoshi Hamai, Yukihide Iwamoto, Remodelling of femoral head-neck junction in slipped capital femoral epiphysis
A multicentre study
, International Orthopaedics, 10.1007/s00264-013-2047-6, 2013.12, Purpose: We examined the remodelling of the femoral head-neck junction in patients with slipped capital femoral epiphysis (SCFE) and the frequency of residual cam deformities. Methods: We reviewed 69 hips in 56 patients with stable SCFE who had undergone in situ pinning. Mean age at slip was 11.7 years and the follow-up period 63.4 months. Cam deformity was evaluated using the anterior offset alpha (α) angle and head-neck offset ratio (HNOR). Results: The average α angle and HNOR significantly improved from 76.2 to 51.3 and 0.086 to 0.135, respectively; 25 hips (36.2 %) still had an α angle greater than 50, and 32 hips (46.4 %) had an HNOR of under 0.145. A multivariate analysis selected age at onset and slip angle as risk factors for cam deformity, with cutoff values 11.1 years and 21.0, respectively. Conclusions: Although most hips had remodelling of the head-neck junction, 29.4 % had residual cam deformities that may be susceptible to femoroacetabular impingement..
195. Satoshi Ikemura, Takuaki Yamamoto, Goro Motomura, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, The utility of clinical features for distinguishing subchondral insufficiency fracture from osteonecrosis of the femoral head, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-013-1847-x, 2013.12, Purpose: Subchondral insufficiency fractures of the femoral head (SIF) need to be differentiated from osteonecrosis of the femoral head (ON), since these two conditions have several overlapping characteristics especially in their radiological findings. The purpose of this study was to determine the useful clinical features for differentiating SIF from ON. Methods: This study reviewed 44 consecutive patients, aged 60 years or older with a radiological evidence of subchondral collapse of the femoral head. According to the histopathological diagnosis, 22 patients were grouped as SIF and 22 patients as ON. A 2 × 2 contingency table analysis was used to obtain the odd ratios (ORs) for SIF compared to ON. Results: The age, proportion of females, the rate of a history of either corticosteroid intake or alcohol abuse, and the presence of vertebral compression fracture in subchondral insufficiency fracture were significantly higher than those with osteonecrosis (p = 0.0001, 0.0212, 0.0001, and 0.0040, respectively). ORs for SIF were 12.01 [95 % confidence intervals (CI) 1.35-106.80] and 7.29 (95 % CI 1.91-27.86), if the patient were female and 70 years of age or older, respectively. In addition, OR for SIF was extremely high (OR 56.01, 95 % CI 6.12-512.87) compared to ON, if the patients have a history of either corticosteroid intake or alcohol abuse. Conclusion: The results of this study indicate that osteoporotic elderly women without any history of corticosteroid intake or alcohol abuse need to first be considered to have subchondral insufficiency fracture when radiographs show a collapse of the femoral head..
196. Masanobu Hirata, Yasuharu Nakashima, Masanobu Ohishi, Satoshi Hamai, Daisuke Hara, Yukihide Iwamoto, Surgeon error in performing intraoperative estimation of stem anteversion in cementless total hip arthroplasty, Journal of Arthroplasty, 10.1016/j.arth.2013.03.006, 2013.10, To examine the accuracy of intraoperative estimation of stem anteversion in total hip arthroplasty (THA), we compared the intraoperatively estimated stem anteversion (estimated prosthetic anteversion) to stem anteversion measured by postoperative computed tomography (true anteversion) in 73 hips in 73 patients. Estimated prosthetic anteversion was significantly greater than true anteversion by 5.8°, and the mean absolute value of surgeon error was 7.3° ranging from 11° underestimation to 25° overestimation. Surgeons tended to overestimate when the true anteversion was smaller. A multivariate analysis showed that advanced knee osteoarthritis significantly increased surgeon error. These results indicated that estimated prosthetic anteversion was generally larger than true anteversion and that the grade of knee osteoarthritis affected the degree of surgeon error..
197. Ikuo Wada, Eisuke Sakuma, Takanobu Otsuka, Kenjiro Wakabayashi, Kinya Ito, Osamu Horiuchi, Yoshimi Asagai, Makoto Kamegaya, Eiji Goto, Shinichi Satsuma, Daisuke Kobayashi, Susumu Saito, Mayuki Taketa, Kazuharu Takikawa, Yasuharu Nakashima, Tadashi Hattori, Shigeru Mitani, Akifusa Wada, The Pavlik harness in the treatment of developmentally dislocated hips
Results of Japanese multicenter studies in 1994 and 2008
, Journal of Orthopaedic Science, 10.1007/s00776-013-0432-z, 2013.09, Background: It has already been more than 50 years since the Pavlik harness was introduced in Japan, and today the Pavlik harness is widely recognized as the standard initial treatment modality for developmental dysplasia of the hip. We performed a multicenter nationwide questionnaire study concerning the results of Pavlik harness treatment twice in 1994 and 2008. Methods: In 1994 and in 2008, we sent questionnaires to 12 institutes in Japan specializing mainly in pediatric orthopedics. We compare the results of these two studies and discuss differences in reduction rates, incidence of avascular necrosis in the femoral epiphysis and the percentage of joints with acceptable morphology (Severin grade I + II/total) at skeletal maturity. We statistically assessed these results to see whether there were changes in the treatment outcomes over this 14-year period. Results: Reduction of the dislocated hips was obtained by the Pavlik harness in 80.2 % (1990/2481 hips; 1994) and 81.9 % (1248/1523 hips; 2008). The incidences of avascular necrosis of the proximal femoral epiphysis in the dysplastic hips were 14.3 % (119/835 hips; 1994) and 11.5 % (76/663 hips; 2008). The type of avascular necrosis in hips from the 2008 study was determined according to the classification of Kalamchi and MacEwen: 24/69 hips (34.8 %) were classified as group I; 20/69 hips (29.0 %) as group II; 11/69 hips (15.9 %) as group Ill; 14/69 hips (20.3 %) as group IV. The percentages of hips with acceptable outcomes at skeletal maturity discerned from Severin X-ray changes (grade I + II/total) were 72.3 % (604/835 hips; 1994) and 77.7 % (488/628 hips; 2008). Conclusion: Reduction rates and the incidence of avascular necrosis in 2008 were statistically similar to the results in 1994. The rate of acceptable outcome (Severin grade I + II/total) in 2008 was statistically higher than that of 1994..
198. Takashi Itokawa, Yasuharu Nakashima, Takuaki Yamamoto, Goro Motomura, Masanobu Ohishi, Satoshi Hamai, Mio Akiyama, Masanobu Hirata, Daisuke Hara, Yukihide Iwamoto, Late dislocation is associated with recurrence after total hip arthroplasty, International Orthopaedics, 10.1007/s00264-013-1921-6, 2013.08, Purpose: This study was conducted to examine the risk factors for recurrent dislocation after total hip arthroplasty (THA) and test the hypothesis that late dislocations are associated with recurrence. Methods: A total of 1,250 hips in 1,017 patients were retrospectively reviewed. All operations were performed through the posterolateral approach with posterior soft tissue repair. An early or late dislocation was defined as a dislocation occurring before or after one year postoperatively, respectively. Results: Dislocation occurred in 36 hips (2.9 %) and 20 of them experienced recurrence. Recurrent dislocations were observed in ten out of 25 hips (40.0 %) with early dislocation; however, ten out of 11 hips (90.9 %) with late dislocation experienced recurrence (p = 0.0046). Multivariate analysis revealed that late dislocation was significantly associated with recurrence with odds ratio of 5.94 per year. Seven in 20 hips with recurrent dislocation required surgical treatment. Conclusion: Late dislocation significantly contributed to the development of recurrent dislocations..
199. Yasuharu Nakashima, Naohiko Mashima, Hiroshi Imai, Naoto Mitsugi, Naoya Taki, Yuichi Mochida, Ichiro Owan, Kaoru Arakaki, Takuaki Yamamoto, Taro Mawatari, Goro Motomura, Masanobu Ohishi, Toshio Doi, Masayuki Kanazawa, Yukihide Iwamoto, Clinical and radiographic evaluation of total hip arthroplasties using porous tantalum modular acetabular components
5-year follow-up of clinical trial
, Modern Rheumatology, 10.1007/s10165-012-0618-9, 2013.01, Objectives: Porous tantalum is a biomaterial newly applied for artificial joints. We present here 5-years follow-up report of a multicenter clinical trial of total hip arthroplasties (THA) with porous tantalum modular acetabular component (modular PTC). Methods: Study participants received 82 hips in 79 cases, with 61.2 months follow-up on average. Age at operation was 60.9 years. Clinical results were evaluated using Merle d'Aubigne Postel score. Presence of implant loosening, periacetabular radiolucency, osteolysis, and gap filling were examined for radiographic results. Results: Merle d'Aubigne Postel score improved from 10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year, with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm; however, all showed bone filling within 12 months. PTC with oversized reaming was significantly less likely to have a gap. No implant failure was noted related to modularity. Resulting survival rate of modular PTC was 100% at 5 years. Conclusions: Modular PTC showed excellent results at 5-years of follow-up. Some hips showed periacetabular gaps, which were filled with bone within 1 year. Further follow-up was needed to determine long-term efficacy..
200. Yasutaka Tashiro, Yasuharu Nakashima, Ken Okazaki, Taro Mawatari, Jun-Ichi Fukushi, Masanobu Ohishi, Akiko Oyamada, Hisakata Yamada, Yukihide Iwamoto, Effects of adalimumab administration in bio-naïve and bio-switch rheumatoid arthritis patients in daily clinical practice
two-year results from single center.
, Fukuoka igaku zasshi = Hukuoka acta medica, 2013.01, To investigate the impact of adalimumab on the biologic-naive (bio-naïve) and bio-switch rheumatoid arthritis (RA) patients, and to clarify the appropriate indications for adalimumab treatment. The retention rate, efficacy and safety of adalimumab in twenty-one RA patients were analyzed. Fourteen of the patients were bio-naive and seven were bio-switched from other biologics. Concomitant methotrexate was used in 85% of the bio-naive and 71% of the bio-switch patients. The radiographic findings before and after the 1 year and the two years treatment were also surveyed. In the bio-naive group, 63% of patients continued adalimumab for 2 years, and remission was achieved in approximately 50% of patients. The mean 28-joint Disease Activity Scores improved from 5.2 to 2.6. Radiographically, the joint damage did not progress in either erosions or joint space narrowing. In the bio-switch group, the retention rate was 29%, and only patients who were switched from infliximab showed responses to the treatment. Herpes zoster requiring hospitalization occurred in two cases and injection site reactions were noted in other two cases. Adalimumab combined with methotrexate would be a useful first choice biologic regimen in bio-naïve RA patients. As a second biologic, adalimumab could be useful only when treatments are switched from infliximab..
201. Jun Ichi Fukushi, Yasuharu Nakashima, Yukihide Iwamoto, Osteitis pubis ameliorated after tooth extraction
A case report
, Clinical Rheumatology, 10.1007/s10067-010-1451-1, 2013.01, Osteitis pubis is a non-infective inflammation of the symphysis pubis, which is known to be associated with trauma, athletic exertion, urological or gynecological surgery, or with rheumatic conditions such as seronegative spondyloarthropathies. In this report, we describe a case of osteitis pubis whose symptoms were completely ameliorated following tooth extraction attributable to periodontitis. A 57-year-old female patient developed osteitis pubis, presenting with pain in the groin area with an elevated Creactive protein (CRP; 4.4 mg/dl) and radiological erosive changes in symphysis pubis. Prednisolone (5 mg/day) and etodolac were prescribed, but the patient's symptoms improved only partially and remained persistent. One year from the patient's first visit, three teeth were extracted due to severe chronic periodontitis, which she had been suffering from for years. Soon after the above tooth extraction, her symptoms appeared completely resolved, and the patient's CRP was decreased to nearly normal levels in 4 weeks. Human leukocyte antigen (HLA)-typing analysis revealed a positive result for HLA-A11, A24, and B54. Because HLA-B54 cross-reacts with HLA-B27, the patient's osteitis pubis was considered to be a form of reactive arthritis associated with periodontitis..
202. Taishi Sato, Yasuharu Nakashima, Mio Akiyama, Takuaki Yamamoto, Taro Mawatari, Takashi Itokawa, Masanobu Ohishi, Goro Motomura, Masanobu Hirata, Yukihide Iwamoto, Wear resistant performance of highly cross-linked and annealed ultra-high molecular weight polyethylene against ceramic heads in total hip arthroplasty, Journal of Orthopaedic Research, 10.1002/jor.22148, 2012.12, The purpose of this study was to examine the effects of ceramic femoral head material, size, and implantation periods on the wear of annealed, cross-linked ultra-high molecular weight polyethylene (UHMWPE) (XLPE) in total hip arthroplasty compared to non-cross-linked conventional UHMWPE (CPE). XLPE was fabricated by cross-linking with 60 kGy irradiation and annealing. Femoral heads made from zirconia and alumina ceramics and cobalt-chrome (CoCr) of 22 or 26 mm diameter were used. In this retrospective cohort study, the femoral head penetration into the cup was measured digitally on radiographs of 367 hips with XLPE and 64 hips with CPE. The average follow-up periods were 6.3 and 11.9 years, respectively. Both XLPE creep and wear rates were significantly lower than those of CPE (0.19 mm vs. 0.44 mm, 0.0001 mm/year vs. 0.09 mm/year, respectively). Zirconia displayed increased wear rates compared to alumina in CPE; however, there was no difference among head materials in XLPE (0.0008, 0.00007, and -0.009 mm/year for zirconia, alumina, and CoCr, respectively). Neither head size or implantation period impacted XLPE wear. In contrast to CPE, XLPE displayed low wear rates surpassing the effects of varying femoral head material, size, implantation period, and patient demographics. Further follow-up is required to determine the long-term clinical performance of the annealed XLPE..
203. Mio Akiyama, Yasuharu Nakashima, Masanori Fujii, Taishi Sato, Takuaki Yamamoto, Taro Mawatari, Goro Motomura, Shuichi Matsuda, Yukihide Iwamoto, Femoral anteversion is correlated with acetabular version and coverage in Asian women with anterior and global deficient subgroups of hip dysplasia
A CT study
, Skeletal Radiology, 10.1007/s00256-012-1368-7, 2012.11, Objective: Morphological correlation between the acetabulum and femur at the hip joint is still controversial. We tested the hypothesis that femoral anteversion correlates with acetabular version and coverage in patientswith developmental dysplasia of the hip (DDH). Materials and methods: Using pelvic computed tomography (CT) images of 79 hips in 49 Asian women with DDH and 49 normal hips, we measured femoral anteversion, the axial and vertical acetabular version and the acetabular sector angle (ASA) to demarcate femoral head coverage. Depending on the location of the acetabular bone defect, dysplastic hips were divided into three subgroups: the anterior, global and posterior deficiency groups. We performed a comparative analysis between dysplastic and normal hips using the Wilcoxon rank sum test, and a relative analysis between femoral anteversion and acetabular measurements in dysplastic hips using Pearson's correlation coefficient. Results: The amount of femoral anteversion in dysplastic hips was greater and more variable than in normal hips (p<0.0001, p00.0277 respectively). Femoral anteversion in dysplastic hips correlated significantly with acetabular anteversion in the groups with anterior and global deficiency subgroups (p<0.05, r00.2990, p<0.05, r00.451 respectively), but not with the posterior deficiency subgroup. Femoral anteversion also correlated with vertical acetabular version. When acetabular coverage was examined, significant correlations were noted between femoral anteversion and anterior and superior coverage, but not with posterior coverage. These correlations were not observed in normal hips. Conclusions: Our results showed significantly greater and more variable femoral anteversion in DDH, and a significant correlation between femoral anteversion and acetabular version and coverage in DDH with anterior and global acetabular bone deficiency..
204. Makoto Hamasaki, Yoshinobu Hashizume, Yoshinori Yamada, Tomohiko Katayama, Hirohiko Hohjoh, Noemi Fusaki, Yasuharu Nakashima, Hirokazu Furuya, Nobuhiko Haga, Yoichiro Takami, Takumi Era, Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming and maintenance
Mechanisms of reprogramming and strategy for drug identification
, STEM CELLS, 10.1002/stem.1221, 2012.11, Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by progressive ossification of soft tissues. FOP is caused by mutations in activin receptor-like kinase 2 (ALK2) that cause its constitutive activation and result in dysregulation of BMP signaling. Here, we show that generation of induced pluripotent stem cells (iPSCs) from FOP-derived skin fibroblasts is repressed because of incomplete reprogramming and inhibition of iPSC maintenance. This repression was mostly overcome by specific suppression of ALK2 expression and treatment with an ALK2 inhibitor, indicating that the inhibition of iPSC generation and maintenance observed in FOP-derived skin fibroblasts results from constitutive activation of ALK2. Using this system, we identified an ALK2 inhibitor as a potential candidate for future drug development. This study highlights the potential of the inhibited production and maintenance of iPSCs seen in diseases as a useful phenotype not only for studying the molecular mechanisms underlying iPS reprogramming but also for identifying drug candidates for future therapies..
205. Masanori Fujii, Yasuharu Nakashima, Taishi Sato, Mio Akiyama, Yukihide Iwamoto, Acetabular tilt correlates with acetabular version and coverage in hip dysplasia hip, Clinical orthopaedics and related research, 10.1007/s11999-012-2370-z, 2012.10, Background: The rotational position of the acetabulum to the pelvis (acetabular tilt) may influence acetabular version and coverage of the femoral head. To date, the pathologic significance of acetabular tilt in hip dysplasia is unknown. Questions/Purposes: We determined whether acetabular tilt in hip dysplasia is different from that in normal hips and whether this correlates with acetabular version and coverage. Methods: We measured the acetabular tilt angle on the lateral view of three-dimensional pelvic CT images of 40 patients (72 hips) with hip dysplasia. Forty normal hips from 40 patients were used as controls. The acetabular sector angle was measured as an index for acetabular coverage of the femoral head. Results: The mean acetabular tilt angle was increased in dysplastic hips compared with controls. In dysplastic hips, a posteriorly rotated acetabulum (increased acetabular tilt) was associated with increased acetabular anteversion and with decreased anterior and anterosuperior acetabular coverage. No correlation was found in controls. In dysplastic hips with a posterior acetabular deficiency, the acetabulum was rotated anteriorly (decreased acetabular tilt) compared with hips with anterior and lateral deficiencies. Conclusions: We observed a correlation between the rotational position of the acetabulum in the pelvis with acetabular version and coverage in hip dysplasia. Our observations confirmed anterior rotation of the acetabular fragment during periacetabular osteotomies is an anatomically reasonable maneuver for hips with anterolateral acetabular deficiencies, while the maneuver can exacerbate posterior coverage and should be avoided in hips with a posterior acetabular deficiency. Level of Evidence: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence..
206. Hidetoshi Tsushima, Ken Okazaki, Yukihisa Takayama, Masamitsu Hatakenaka, Hiroshi Honda, Toshiaki Izawa, Yasuharu Nakashima, Hisakata Yamada, Yukihide Iwamoto, Evaluation of cartilage degradation in arthritis using T1q magnetic resonance imaging mapping, Rheumatology International, 10.1007/s00296-011-2140-3, 2012.09, T1q magnetic resonance imaging (MRI) can be used to map proteoglycan (PG) loss in cartilage. Here, we used T1q MRI to map cartilage degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). Tissue samples were obtained from five RA patients and 14 OA patients following total knee arthroplasty (TKA). Three parameters were measured: First, macroscopic grading of cartilage sample tissues was performed on a 5-grade scale (G0: normal, G1: swelling, G2: superficial fibrillation, G3: deep fibrillation, G4: subchondral bone exposure). Second, semi-quantitative values of PG were assessed by measuring the optical density of Safranin-O-stained paraffin sections that had been digitally photographed. Third, cartilage was divided into superficial and deep layers and the T1q values were quantified. T1q values of OA and RA in the superficial layers showed significant differences between groups (G0/1 and G0/2 for OA; G0/2 and G1/2 for RA). In the deep layers, T1q values of OA and RA also differed significantly between groups. In both the superficial and deep layers, there was a significant correlation between the mean T1q values and macroscopic grading (P\0.01 for OA, P\0.001 for RA). We found a negative correlation between the score of Safranin-O staining and T1q values (r = -0.61 for OA, r = -0.79 for RA). In addition, RA subjects had significantly higher T1q values than OA subjects of similar morphologic grade. In conclusion, T1q MRI is able to detect and map the early stages of cartilage degradation in OA and RA. This method is reliable and useful for the evaluation of macromolecular changes in arthritic cartilage..
207. Garida Zhao, Takuaki Yamamoto, Satoshi Ikemura, Goro Motomura, Kenyu Iwasaki, Ryosuke Yamaguchi, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, Clinico-radiological factors affecting the joint space narrowing after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head, Journal of Orthopaedic Science, 10.1007/s00776-012-0238-4, 2012.07, Purpose The purpose of this study was to investigate the factors that affect the joint space narrowing after transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH). Methods We reviewed 39 cases (43 hips) of ONFH in patients who underwent ARO between 2000 and 2004. Their mean age was 42 years (23-61) at the time of surgery. The mean follow-up period was 7.3 years (3-10). The following clinical and radiological factors were investigated: the preoperative stage, localization and extent of the necrotic lesion, and the postoperative intact ratio (transposed intact articular surface of the femoral head to the weight-bearing surface of the acetabulum). The 43 hips were divided into two groups: a joint space narrowing (JSN) group and a non-joint space narrowing (non-JSN) group. Results Thirty-seven hips (86 %) were categorized as non-JSN and six (14 %) as having JSN. The preoperative Japanese Orthopaedic Association score was significantly higher in the non-JSN group than in the JSN group (P = 0.01). In the non-JSN group, the rate of early stage disease was significantly higher than in the JSN group (P = 0.03). The postoperative intact ratio was significantly higher in the non-JSN group than in the JSN group (P = 0.002). A multivariate analysis revealed that the postoperative intact ratio was an independent predictor of the progression of joint space narrowing after ARO, and the cutoff point was 39.2 %. Conclusion The results of this study suggest that the postoperative intact ratio is one of factors determining the progression of joint space narrowing after ARO and that an approximately 40 % or higher postoperative intact ratio is recommended to prevent joint space narrowing..
208. Shinya Kawahara, Yasuharu Nakashima, Hiroshi Oketani, Akifusa Wada, Masanori Fujii, Takuaki Yamamoto, Taro Mawatari, Goro Motomura, Taishi Sato, Mio Akiyama, Toshio Fujii, Kazuyuki Takamura, Yukihide Iwamoto, High prevalence of acetabular retroversion in both affected and unaffected hips after Legg-Calvé-Perthes disease, Journal of Orthopaedic Science, 10.1007/s00776-012-0213-0, 2012.05, Background Acetabular retroversion is observed in hips after various pediatric hip diseases. This study sought to examine the frequency of acetabular retroversion in both affected and unaffected hips after Legg-Calvé- Perthes disease and its correlation with the prominence of the ischial spine. Methods We retrospectively investigated the version and morphological features of the acetabulum using pelvic radiographs after Legg-Calvé-Perthes disease (107 affected hips treated non-operatively and 72 unaffected hips from the contralateral side). The diagnosis of acetabular retroversion was made based on the presence of a positive cross-over sign on anteroposterior pelvic radiographs. The correlation between the presence of a positive cross-over sign and modified Stulberg classes, the onset age of Legg-Calvé-Perthes disease, radiographic parameters for acetabular dysplasia and the prominence of the ischial spine were examined. Results The prevalence of a positive cross-over sign was 49.5 % (45 of 91 hips) in affected hips and 45.8 % (33 of 72 hips) in unaffected hips. Hips with a positive cross-over sign were significantly coexistent bilaterally. The prevalence of prominence of the ischial spine in the positive cross-over sign group was 71.4 % in the affected side and 81.8 % in the unaffected side, indicating a significant correlation between the cross-over sign and the prominence of the ischial spine in both affected and unaffected hips. The positive cross-over sign did not have any correlation with the parameters for acetabular dysplasia and the onset age, however, had a significant correlation with the severity of the femoral head deformity. Conclusions High prevalence of acetabular retroversion in both affected and unaffected hips after Legg-Calvé-Perthes disease was demonstrated. Symmetric acetabular deformity and the coexistence of prominence of the ischial spine suggested the effects of the Legg-Calvé-Perthes disease lesions on the skeletal development of the whole pelvis. Further follow-up is needed to clarify the pathological significance of acetabular retroversion after Legg-Calvé-Perthes disease..
209. Goro Motomura, Takuaki Yamamoto, Yasuharu Nakashima, Ryosuke Yamaguchi, Taro Mawatari, Yukihide Iwamoto, Midterm results of transtrochanteric anterior rotational osteotomy combined with shelf acetabuloplasty for osteonecrosis with acetabular dysplasia
A preliminary report
, Journal of Orthopaedic Science, 10.1007/s00776-012-0205-0, 2012.05, Background Transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head should be performed to obtain [34% of the ratio of transposed intact posterior articular surface to the acetabular weight-bearing area. Therefore, the presence of acetabular dysplasia is unfavorable in obtaining this ratio. Between 1999 and 2005, we performed the modified Spitzy shelf acetabuloplasty combined with anterior rotational osteotomy for three patients (four hips) with acetabular dysplasia. In this study, we retrospectively evaluated the midterm results of this combined surgery. Methods and results Patients comprised one man and two women with a mean age of 29 years at the time of surgery. Mean follow-up was 7.5 years. The average preoperative Harris hip score of 65.5 points increased to an average of 79.3 points at the latest follow-up. None of the hips required conversion to total hip arthroplasty during the follow-up periods. The average postoperative intact ratio without a shelf procedure was 23%, and with a shelf procedure, this ratio increased to be 58%. As a result, collapse progression was not observed in any of the four hips. Conclusions Our results suggest that anterior rotational osteotomy combined with shelf acetabuloplasty may be a surgical option for osteonecrosis of the femoral head with acetabular dysplasia. Further studies with a larger patient population are necessary to clarify appropriate indications and limitations of this combined surgery..
210. K. Iwasaki, Takuaki Yamamoto, G. Motomura, S. Ikemura, T. Mawatari, Y. Nakashima, Y. Iwamoto, Prognostic factors associated with a subchondral insufficiency fracture of the femoral head, British Journal of Radiology, 10.1259/bjr/44936440, 2012.03, Objective: The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF). Methods: Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singh's index, were documented. The morphological characteristics of the low-intensity band on T 1 weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre). Results: Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values. Conclusion: These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF..
211. M. Fujii, Y. Nakashima, Y. Noguchi, T. Yamamoto, T. Mawatari, G. Motomura, Y. Iwamoto, Effect of intra-articular lesions on the outcome of periacetabular osteotomy in patients with symptomatic hip dysplasia, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.93B11.27314, 2011.11, In order to clarify how intra-articular lesions influence the survival of a periacetabular osteotomy in patients with dysplasia of the hip, we performed an observational study of 121 patients (121 hips) who underwent a transposition osteotomy of the acetabulum combined with an arthroscopy. Their mean age was 40.2 years (13 to 64) and the mean follow-up was 9.9 years (2 to 18). Labral and cartilage degeneration tended to originate from the anterosuperior part of the acetabulum, followed by the femoral side. In all, eight hips (6.6%) had post-operative progression to Kellgren-Lawrence grade 4 changes, and these hips were associated with the following factors: moderate osteoarthritis, decreased width of the joint space, joint incongruity, and advanced intra-articular lesions (subchondral bone exposure in the cartilage and a full-thickness labral tear). Multivariate analysis indicated subchondral bone exposure on the femoral head as an independent risk factor for progression of osteoarthritis (p = 0.003). In hips with early stage osteoarthritis, femoral subchondral bone exposure was a risk factor for progression of the grade of osteoarthritis. Although the outcome of transposition osteotomy of the acetabulum was satisfactory, post-operative progression of osteoarthritis occurred at a high rate in hips with advanced intra-articular lesions, particularly in those where the degenerative process had reached the point of femoral subchondral bone exposure..
212. Yasuharu Nakashima, Hideaki Kubota, Takuaki Yamamoto, Taro Mawatari, goro motomura, Yukihide Iwamoto, Transtrochanteric rotational osteotomy for late-onset Legg-Calve-Perthes disease, Journal of Pediatric Orthopaedics, 10.1097/BPO.0b013e318223b4f3, 2011.09, Background: The pathology of late-onset Legg-Calve-Perthes disease (LCPD) is similar to that of avascular necrosis of the femoral head in adult and is associated with poorer prognosis of the hip. The optimal treatment for this condition is still controversial. The purpose of this study was to evaluate the long-term clinical results of the transtrochanteric rotational osteotomy for the patients with LCPD onset at more than 9 years of age. Methods: Individuals included 14 hips in 13 cases with the mean age at onset of the disease and operation of 10 years 9 months and 12 years. Average follow-up periods were 12 years. All cases were resistant to the conservative treatments and did not have our indications for varus osteotomy. Clinical results were evaluated using Merle d'Aubigne Postel score and the modified Stulberg criteria. Results: Average Merle d'Aubigne Postel score at the final follow-up was 16.2 points ranging from 12 to 18 points. All patients did not have additional treatment except nail removal. Stulberg class II, III, and IV were obtained in 5, 2, and 7 hips, respectively. More spherical femoral head was obtained in patients with less head involvement and more bone preservation or new bone formation at posterior pillar. Three hips showed slight narrowing of joint space without severe osteoarthritic changes. Conclusions: Transtrochanteric rotational osteotomy is an effective procedure to salvage the hips of the late-onset LCPD. Amount of head involvement, posterior and lateral pillar had influences on the surgical outcomes..
213. Kenyu Iwasaki, Takuaki Yamamoto, Goro Motomura, Taro Mawatari, Yasuharu Nakashima, Yukihide Iwamoto, Subchondral insufficiency fracture of the femoral head in young adults, Clinical Imaging, 10.1016/j.clinimag.2010.05.005, 2011.05, A subchondral insufficiency fracture of the femoral head (SIF) is generally observed in elderly women. In addition, SIF has been reported to occur in young military trainees, which are considered to be due to a fatigue stress fracture. This report reviewed five cases of SIF in young adults without any history of overexertion or antecedent trauma. The clinical findings, time to the initial radiograph, time to the initial magnetic resonance imaging (MRI), and follow-up period were investigated. Radiographs and MRI were obtained in both hips. Bone mineral density and bone scintigram were performed. Measurements of a bone mineral density indicated presence of osteopenia in three patients. MRI disclosed a discontinuous irregular-shaped low-intensity band surrounded by bone marrow edema in all cases. After conservative treatments, one patient's condition resolved, while four patients underwent femoral head collapse resulting in surgical treatment. In these four patients, the diagnosis of SIF was histologically confirmed. In addition, the histological findings showed thin disconnected bone trabeculae, thus indicating the presence of some degree of osteopenia. These patients were considered to demonstrate an insufficiency fracture rather than a fatigue stress fracture based on both clinical findings and histological findings. SIF needs to be considered in patients presenting with hip pain even in young cases..
214. Satoshi Ohte, Masashi Shin, Hiroki Sasanuma, Katsumi Yoneyama, Masumi Akita, Kenji Ikebuchi, Eijiro Jimi, Yuichi Maruki, Masaru Matsuoka, Akira Namba, Hiroshi Tomoda, Yasushi Okazaki, Akira Ohtake, Hiromi Oda, Ichiro Owan, Tetsuya Yoda, Hirokazu Furuya, Jyunji Kamizono, Hiroshi Kitoh, Yasuharu Nakashima, Takafumi Susami, Nobuhiko Haga, Tetsuo Komori, Takenobu Katagiri, A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2011.03.001, 2011.04, Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. Constitutively activated mutants of a bone morphogenetic protein (BMP) receptor, ALK2, have been identified in patients with FOP. Recently, a novel ALK2 mutation, L196P, was found in the most benign case of FOP reported thus far. In the present study, we examined the biological activities of ALK2(L196P) in vitro. Over-expression of ALK2(L196P) induced BMP-specific activities, including the suppression of myogenesis, the induction of alkaline phosphatase activity, increased BMP-specific luciferase reporter activity, and increased phosphorylation of Smad1/5 but not Erk1/2 or p38. The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP. ALK2(L196P) was equally or more resistant to inhibitors in comparison to ALK2(R206H). These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in patients with this mutation..
215. G. Motomura, T. Yamamoto, R. Yamaguchi, S. Ikemura, Y. Nakashima, T. Mawatari, Y. Iwamoto, Morphological analysis of collapsed regions in osteonecrosis of the femoral head, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.93B225476, 2011.02, In order to investigate the mechanisms of collapse in osteonecrosis of the femoral head, we examined which part of the femoral head was the key point of a collapse and whether a collapsed region was associated with the size of the necrotic lesion. Using 30 consecutive surgically removed femoral heads we retrospectively analysed whole serial cut sections, specimen photographs, specimen radiographs and histological sections. In all of the femoral heads, collapse consistently involved a fracture at the lateral boundary of the necrotic lesion. Histologically, the fractures occurred at the junction between the thickened trabeculae of the reparative zone and the necrotic bone trabeculae. When the medial boundary of the necrotic lesion was located lateral to the fovea of the femoral head, 18 of 19 femoral heads collapsed in the subchondral region. By contrast, when the medial boundary was located medial to the fovea, collapse in the subchondral region was observed in four of 11 femoral heads (p = 0.0011). We found that collapse began at the lateral boundary of the necrotic lesion and that the size of the necrotic lesion seemed to contribute to its distribution..
216. Akinobu Matsushita, Yasuharu Nakashima, Masanori Fujii, Taishi Sato, Yukihide Iwamoto, Modular necks improve the range of hip motion in cases with excessively anteverted or retroverted femurs in THA, Clinical orthopaedics and related research, 10.1007/s11999-010-1385-6, 2010.12, Background: Anteversion of an acetabular component often is difficult to ascertain in patients with THA in whom excessively anteverted or retroverted femurs may result in limited ROM or risk of dislocation. Restriction of motion, however, is determined by the combination of version of both components. Questions/purposes: We therefore determined the combined anteversion values that provide adequate ROM. We varied acetabular version by differing implantations and varied femoral version with modular necks. Methods: ROM was tested by changing cup anteversion after setting the femoral version to 20° or 60° anteversion or 20° retroversion. The angle of the modular neck was adjusted in 11 increments of 5° each. Range of internal rotation (IR) at 90° flexion, external rotation (ER) at 0° extension, and flexion (Flex) were measured when any impingement occurred before dislocation. We defined a required ROM as having 40° IR, 30° ER, and 110° Flex. Results: At 60° anteversion, ER was less than 10° even when the acetabular component was set at 10° retroversion because of posterior impingement. When a modular neck with 25° retroversion was used, ER improved to greater than 30°. At 20° retroversion, IR was 31° even when the acetabular component was opened to 35° anteversion. IR improved to 34° and 40° with 20° and 25° anteverted modular necks, respectively. Conclusions and Clinical Relevance: In cases with excessive femoral anteversion or retroversion, the required ROM could not be achieved by simply changing the version of acetabular components. The adjustment of femoral versions using the modular necks allowed additional improvement of ROM..
217. Yasuharu Nakashima, Nobuhiko Haga, Hiroshi Kitoh, Junji Kamizono, Koji Tozawa, Takenobu Katagiri, Takafumi Susami, Jun Ichi Fukushi, Yukihide Iwamoto, Deformity of the great toe in fibrodysplasia ossificans progressiva, Journal of Orthopaedic Science, 10.1007/s00776-010-1542-5, 2010.11, Background: As invasive medical procedures can induce permanent heterotopic ossification in fibrodysplasia ossificans progressiva (FOP), caution should be exercised in clinical practice. The present study was conducted to examine the characteristics of the great toe deformity in patients with FOP, which may lead to an early diagnosis of this condition. Methods: The subjects consisted of 31 feet from 16 FOP patients (8 males, 8 females) with an average age of 17.3 years (range 1-47 years) at the time of this study. Gross and radiographic findings, including the hallux valgus angles (HVA), intermetatarsal angles (IMA), and the deformity of the proximal phalanx and metatarsal bone, were examined. Results: Of the 31 feet, 29 (93.5%) showed several degrees of great toe deformity. A shortened great toe was the typical gross finding and was observed in 20 feet (64.5%). The mean HVA and IMA were 19.7° and 8.5°, respectively; and 22 (71.0%) feet satisfied the radiographic definition of hallux valgus (HVA ≥ 20° or IMA ≥ 10°). The proximal phalanx was consistently shortened but morphologically dissimilar from case to case. The metatarsal bone was also shortened and sharpened to the medial side, deviating the proximal phalanx laterally from the metatarsal axis. Fusion between the distal and proximal phalanx occurred with advancing age. Only two feet in one patient showed no obvious deformity of the great toe. Conclusions: A shortened great toe and hallux valgus were frequently found in patients with FOP. Shortening and sharpening of the proximal phalanx and metatarsal bone consistently existed and contributed to the great toe deformity. These findings were thought to exist from birth and may be a key to an early diagnosis..
218. Takenobu Katagiri, Jyunji Kamizono, Yasuharu Nakashima, Hiroshi Kitoh, Takafumi Susami, Nobuhiko Haga, [Cytokines in bone diseases. BMP signaling and fibrodysplasia ossificans progressiva]., Clinical calcium, 2010.10, Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic bone formation in skeletal muscle tissue. In 2007, FOP was authorized as one of the Intractable Disorders by the Ministry of Health, Labour and Welfare of Japan. The Research Committee on FOP is working on the molecular mechanisms underlying heterotopic bone formation and the development of new treatments for FOP..
219. Yasuharu Nakashima, Masakazu Kondo, Hiroshi Harada, Takahiko Horiuchi, Takashi Ishinishi, Hiroshi Jojima, Koji Kuroda, Hisaaki Miyahara, Ryuji Nagamine, Hitoshi Nakashima, Takeshi Otsuka, Isao Saikawa, Eisuke Shono, Eiichi Suematsu, Tomomi Tsuru, Ken Wada, Yukihide Iwamoto, Clinical evaluation of tocilizumab for patients with active rheumatoid arthritis refractory to anti-TNF biologics
tocilizumab in combination with methotrexate.
, Modern rheumatology / the Japan Rheumatism Association, 10.1007/s10165-010-0290-x, 2010.08, We retrospectively observed the clinical efficacy and safety of tocilizumab (TCZ) in 74 patients with rheumatoid arthritis (RA) at 13 hospitals, without any restrictions on disease duration or stage, treatment history, and other influencing factors. TCZ was infused by the approved method, and disease activity was evaluated every 4 weeks until week 24 using a joint disease activity score (DAS28). Remission and treatment response were categorised using European League Against Rheumatism (EULAR) definitions. We also analysed the impact of previous treatment with other biologics and of concomitant methotrexate (MTX) therapy on the efficacy of TCZ. At week 24, the DAS28 had improved from 5.5 to 2.7 and the EULAR remission rate was 55.2%. Good and moderate responses according to the EULAR criteria were obtained in 61 and 36% of the patients, respectively. The biologic-naïve group had a significantly better DAS28 (2.1 vs. 2.8) and a significantly higher "good" response rate (86% vs. 54%) than the biologic-exposed group. Although the TCZ + MTX treatment group and the TCZ monotherapy group had a good response rate of 71 and 48%, respectively, the difference was not significant. Based on these results, we conclude that TCZ is able to significantly alleviate disease symptoms in a wide range of patients with RA in a normal clinical context..
220. Jun Ichi Fukushi, Yasuharu Nakashima, Yukihide Iwamoto, Gynecomastia associated with low-dose methotrexate therapy for rheumatoid arthritis ameliorated by folate supplement, Rheumatology International, 10.1007/s00296-009-1062-9, 2010.08, A 62-year-old male with a 10-year history of seropositive rheumatoid arthritis (RA) developed gynecomastia 8 months after beginning oral low-dose methotrexate (MTX) therapy. Two months after folate supplementation, the gynecomastia symptoms improved. Gynecomastia associated with low-dose MTX is a rare occurrence, with only nine cases previously reported in the literature. This is the first report showing folate supplementation to be effective against gynecomastia following low-dose MTX. Although it occurs infrequently, gynecomastia associated with low-dose MTX therapy should be considered in male patients with RA..
221. Satoshi Ikemura, Takuaki Yamamoto, Goro Motomura, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, MRI evaluation of collapsed femoral heads in patients 60 years old or older
Differentiation of subchondral insufficiency fracture from osteonecrosis of the femoral head
, American Journal of Roentgenology, 10.2214/AJR.09.3271, 2010.07, OBJECTIVE. The purpose of this article is to verify the hypothesis that osteonecrosis and subchondral insufficiency fracture of the femoral head can be differentiated on the basis of their appearance on MRI. SUBJECTS AND METHODS. Between May 1998 and February 2009, we reviewed 30 consecutive hips in 30 patients, 60 years old or older at the time of onset of hip pain, with radiologic evidence of subchondral collapse of the femoral head and with both MR images and histologic results available. Both clinical and radiologic appearances were investigated. The patients were divided into two groups according to the shape of low-intensity bands on T1-weighted images. The first group showed concavity of the articular surface, which is characteristic of osteonecrosis, and the second group showed an irregular convexity of the articular surface, which is characteristic of subchondral insufficiency fracture. RESULTS. Sixteen hips (53.3%) showed evidence of osteonecrosis, and 14 (46.7%) showed evidence of subchondral insufficiency fracture, which was consistent with the corresponding histopathologic diagnoses. In all cases of osteonecrosis, the patient had a history of either corticosteroid intake or alcohol abuse. Among patients with subchondral insufficiency fracture, the proportion of women was significantly higher than that among patients with osteonecrosis. A crescent sign (subchondral fracture) was present radiographically in about half of all cases in both groups. CONCLUSION. The results of the present study suggest that the shape of the low-intensity band on MRI is useful for the differentiating subchondral insufficiency fracture from osteonecrosis. In addition, among osteoporotic elderly women without any history of corticosteroid intake or alcohol abuse, a diagnosis of subchondral insufficiency fracture should be considered..
222. G. Motomura, T. Yamamoto, K. Suenaga, Y. Nakashima, T. Mawatari, S. Ikemura, Y. Iwamoto, Long-term outcome of transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head in patients with systemic lupus erythematosus, Lupus, 10.1177/0961203310361896, 2010.06, This study sought to examine the long-term outcomes of transtrochanteric anterior rotational osteotomy (ARO) as treatment for osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Twenty-one patients (33 hips), aged 20-40 years, underwent ARO between 1980 and 1988. We examined 16 patients (25 hips), a 76% follow-up rate. A Kaplan-Meier curve was used for survivorship analysis. Patients with surviving hips were evaluated by the modified Oxford hip score and Short Form 36 (SF-36). Twelve hips in eight patients had survived at the final follow-up. The average length of hip survival was 24.6 years (range: 20.1-27.2 years). Three patients (six hips) had died of unrelated causes without any subsequent operation. Based on Kaplan-Meier analysis with the endpoint defined as the need for a subsequent operation, the hip survival rate at 25 years was 73.7% (95% confidence interval, ±19.8%). Based on classification by the modified Oxford hip score, five hips were classified as excellent, two hips were good, and the remaining five hips were fair. The average SF-36 summary score for the physical and mental components was 38.7 and 47.2 points, respectively. The physical component summary scores for three patients exceeded the normal level of the Japanese population..
223. G. Zhao, T. Yamamoto, S. Ikemura, G. Motomura, T. Mawatari, Y. Nakashima, Y. Iwamoto, Radiological outcome analysis of transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head at a mean follow-up of 12.4 years, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.92B6.23621, 2010.06, We investigated the factors related to the radiological outcome of a transtrochanteric curved varus osteotomy in patients with osteonecrosis of the hip. We reviewed 73 hips in 62 patients with a mean follow-up of 12.4 years (5 to 31.1). There were 28 men and 34 women, with a mean age of 33.3 years (15 to 68) at the time of surgery. The 73 hips were divided into two groups according to their radiological findings: group 1 showed progression of collapse and/or joint-space narrowing; group 2 had neither progressive collapse nor joint-space narrowing. Both of these factors and the radiological outcomes were analysed by a stepwise discriminant analysis. A total of 12 hips were categorised as group 1 and 61 as group 2. Both the post-operative intact ratio and the localisation of the necrotic lesion correlated with the radiological outcome. The cut-off point of the postoperative intact ratio to prevent the progression of collapse was 33.6%, and the cut-off point to prevent both the progression of collapse and joint-space narrowing was 41.9%. The results of this study indicate that a post-operative intact ratio of 33.0% is necessary if a satisfactory outcome is to be achieved after this varus osteotomy..
224. Masanori Fujii, Yasuharu Nakashima, Takuaki Yamamoto, Taro Mawatari, Goro Motomura, Akinobu Matsushita, Shuichi Matsuda, Seiya Jingushi, Yukihide Iwamoto, Acetabular retroversion in developmental dysplasia of the hip, Journal of Bone and Joint Surgery - Series A, 10.2106/JBJS.I.00046, 2010.04, Background: Patients with developmental dysplasia of the hip are prone to the development of degenerative changes in the affected hip. The aim of this study was to evaluate the prevalence, morphological features, and clinical relevance of acetabular retroversion in these patients. Methods: We investigated the version and morphological features of the acetabulum using pelvic radiographs and computed tomography images of ninety-six hips in fifty-nine patients with developmental dysplasia of the hip. A diagnosis of acetabular retroversion was based on the presence of a positive cross-over sign on the pelvic radiograph. Using computed tomography images, we determined the acetabular anteversion angle at various levels in the axial plane. The acetabular sector angle served as an indicator of acetabular coverage of the femoral head. We evaluated the association between acetabular version and the patient's age at the onset of pain. Fifty normal hips were examined as controls. Results: Weobserved acetabular retroversion in 18% (seventeen) of the ninety-six hips in the patients with developmental dysplasia of the hip. The mean acetabular anteversion angle in the hips with acetabular retroversion was significantly smaller, at all levels, than that in the hips with acetabular anteversion; this tendency was more evident at proximal levels. There was significantly less posterior and posterosuperior coverage in the hips with acetabular retroversion than in those with acetabular anteversion, but superior acetabular coverage did not differ between the groups. Multivariate analysis showed that the onset of pain occurred at a significantly earlier age in patients with acetabular retroversion (27.9 years) than in those with acetabular anteversion (40.5 years), regardless of the severity of the dysplasia (p = 0.003). Conclusions: In patients with developmental dysplasia of the hip, acetabular retroversion results from relatively deficient coverage by the posterior portion of the acetabulum. Developmental dysplasia with acetabular retroversion is associated with an earlier onset of pain than is developmental dysplasia with anteversion, suggesting a correlation between deficiency of the posterior acetabular wall and the earlier onset of pain. Level of Evidence: Prognostic Level IV. See Instructions to Authors for a complete description of levels of evidence..
225. Garida Zhao, Takuaki Yamamoto, Satoshi Ikemura, Yasuharu Nakashima, Taro Mawatari, Goro Motomura, Yukihide Iwamoto, A histopathological evaluation of a concave-shaped low-intensity band on T1-weighted MR images in a subchondral insufficiency fracture of the femoral head, Skeletal Radiology, 10.1007/s00256-009-0750-6, 2010.02, A 73-year-old female suffered from right hip pain without any history of antecedent trauma. The initial radiograph showed a slight narrowing of the joint space in the right hip. The patient was treated by non-weight bearing for 5 weeks. Radiographs obtained 3 months after the onset of pain showed the progression of both the joint-space narrowing and subchondral collapse at the superior portion. T1-weighted MR (magnetic resonance) images obtained 3 months after the onset revealed an irregular-shaped lowintensity area just beneath the articular cartilage as well as a low-intensity band, which was concave to the articular surface. A total hip replacement was performed. A histopathological examination revealed fracture callus and granulation tissue in the subchondral area. This subchondral fractured area was surrounded by vascular rich granulation tissue and fibrous tissue, which corresponded to the concave-shaped low-intensity band observed on the T1- weighted image..
226. Yuka Otera, Seiichi Morokuma, Yasuo Yumoto, Satoshi Hojo, Takako Gotoh, Toshiro Hara, Yasuhiro Ushijima, Yasuharu Nakashima, Kiyomi Tsukimori, Norio Wake, Prenatal three-dimensional images of proximal focal femoral deficiency produced by helical computed tomography, Fetal Diagnosis and Therapy, 10.1159/000235884, 2009.09, Introduction: Proximal focal femoral deficiency (PFFD) is a rare skeletal disorder characterized by failure in development of the subtrochanteric region of the femoral shaft, with varying degrees of shortening of the proximal femur. Objective: To investigate the potential of helical computed tomography as a prenatal diagnostic tool for bony abnormalities. Case: A 37-year-old Japanese woman was referred to our hospital at 32 weeks of gestation for the evaluation of fetal growth restriction with short femurs. An ultrasound examination revealed the fetus to have short femurs bilaterally with normal echogenicity, and a normal facial profile. Assessment by 3D CT confirmed the absence of the femoral heads bilaterally and also revealed bilateral hip dislocations and oligodactyly of the right hand. The baby was delivered by cesarean section at 37 weeks of gestation, whereupon the diagnosis of PFFD was confirmed. Conclusion: Helical CT is a useful prenatal diagnostic alternative for bony abnormalities that is superior to the conventional sonographic approach..
227. Kenyu Iwasaki, Takuaki Yamamoto, Yasuharu Nakashima, Taro Mawatari, Goro Motomura, Satoshi Ikemura, Yukihide Iwamoto, Subchondral insufficiency fracture of the femoral head after liver transplantation, Skeletal Radiology, 10.1007/s00256-009-0706-x, 2009.09, A 53-year-old woman developed a subchondral insufficiency fracture of the right femoral head after undergoing a liver transplantation. Radiographs obtained at her first visit demonstrated a slight subchondral collapse in the superolateral portion of the femoral head. Magnetic resonance imaging (MRI) disclosed an irregular, discontinuous, low-intensity band on the T1-weighted image. After 7 months of conservative treatment, the hip pain and the radiograph abnormalities had both disappeared. On the follow-up T1-weighted MR image obtained 17 months after the onset, the band of low signal intensity was not obvious. A subchondral insufficiency fracture is one of the diagnoses to be considered in patients presenting with hip pain after a liver transplantation..
228. Akinobu Matsushita, Yasuharu Nakashima, Seiya Jingushi, Takuaki Yamamoto, Akio Kuraoka, Yukihide Iwamoto, Effects of the Femoral Offset and the Head Size on the Safe Range of Motion in Total Hip Arthroplasty, Journal of Arthroplasty, 10.1016/j.arth.2008.02.008, 2009.06, The purpose of this study was to quantify the effects of femoral offset and head size on range of motion (ROM) after total hip arthroplasty. Modular prostheses were implanted into 11 cadaveric hips using a posterolateral approach and tested for ROM with 3 different offsets and 5 different femoral head sizes. Increasing the femoral offset to 4 and 8 mm resulted in 21.1° and 26.7° of improved flexion, and 13.7° and 21.2° of improved internal rotation, respectively. The ROM improved in a head size-dependent manner primarily because of increasing the jumping distance of the femoral head rather than delaying any impingement. In contrast, the effectiveness of femoral offset was driven by delayed osseous impingement..
229. Atsushi Matsuo, Seiya Jingushi, Yasuharu Nakashima, Takuaki Yamamoto, Taro Mawatari, Yasuo Noguchi, Toshihide Shuto, Yukihide Iwamoto, Transposition osteotomy of the acetabulum for advanced-stage osteoarthritis of the hips, Journal of Orthopaedic Science, 10.1007/s00776-009-1327-x, 2009.05, Background: Transposition osteotomy of the acetabulum (TOA) was the first periacetabular osteotomy in which the acetabulum was transposed with articular cartilage. TOA improves coverage of the femoral head and joint congruity. The purpose of this study was to investigate whether TOA is an appropriate option for treating osteoarthritis of the hips at the advanced stage by comparing it with matched control hips at the early stage. Methods: Between 1998 and 2001, TOA was performed in 104 hips of 98 patients. Altogether, 16 of 17 hips (94%) with osteoarthritis at the advanced stage were examined and compared with 37 matched control hips at the early stage. The mean age at the operation was 48 years (38-56 years), and the mean follow-up period was 88 months (65-107 months). Results: TOA corrected the acetabular dysplasia and significantly improved containment of the femoral head. Clinical scores were also significantly improved in both groups. In the advanced osteoarthritis cases, there was a tendency for abduction congruity before transposition osteotomy of the acetabulum to reflect the clinical outcome. Conclusions: TOA is a promising treatment option for advanced osteoarthritis of the hips as well as for patients at an early stage when preoperative radiographs show good congruity or containment of the joint..
230. Satoshi Ikemura, Takuaki Yamamoto, Yasuharu Nakashima, Taro Mawatari, Goro Motomura, Yukihide Iwamoto, Transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head in patients 20 years or younger, Journal of Pediatric Orthopaedics, 10.1097/BPO.0b013e31819bc746, 2009.04, BACKGROUND:: For young patients with osteonecrosis of the femoral head, especially those younger than 20 years, a joint-preserving operation may be one of the surgical treatment options to be considered. We investigated the clinical and radiological results of transtrochanteric anterior rotational osteotomy for the treatment of osteonecrosis of the femoral head in patients 20 years or younger. METHODS:: Between 1976 and 2001, a transtrochanteric anterior rotational osteotomy was performed in 28 hips of 23 patients aged 20years or younger with osteonecrosis of the femoral head. Among them, 27 hips of 22 patients with a minimum follow-up duration of 2years were investigated (follow-up rate, 96.4%). They included 7males and 15 females with a mean age of 16 years at the time of surgery. The mean follow-up period was 14.7 years (range, 2.0-31.7 years). The clinical assessment was made based on the Merle d'Aubigné-Postel score. The postoperative intact ratio, joint-space narrowing, and progression of collapse were all investigated radiographically. RESULTS:: Two (7.4%) of the 27 hips required total hip arthroplasty because of restrictions in the range of motion, whereas the original hip joints in 25 (92.6%) of the 27 hips were preserved at the time of final follow-up. The mean preoperative Merle d'Aubigné-Postel score was 10.4 points, which improved to 15.9 points at the final follow-up (P < 0.0001). The mean postoperative intact ratio was 49.8% (range, 30-100). Five (18.5%) of the 27 hips had a progressive joint-space narrowing, but progression of the collapse was not observed in anyhips. CONCLUSIONS:: Transtrochanteric anterior rotational osteotomy appears to be a useful joint-preserving operation for patients younger than 20years..
231. Toru Fukuda, Masakazu Kohda, Kazuhiro Kanomata, Junya Nojima, Atsushi Nakamura, Jyunji Kamizono, Yasuo Noguchi, Kiyofumi Iwakiri, Takeo Kondo, Junichi Kurose, Ken Ichi Endo, Takeshi Awakura, Junichi Fukushi, Yasuharu Nakashima, Tomohiro Chiyonobu, Akira Kawara, Yoshihiro Nishida, Ikuo Wada, Masumi Akita, Tetsuo Komori, Konosuke Nakayama, Akira Nanba, Yuichi Maruki, Tetsuya Yoda, Hiroshi Tomoda, Paul B. Yu, Frederick S. Kaplan, Kohei Miyazono, Masaru Matsuoka, Kenji Ikebuchi, Akira Ohtake, Hiromi Oda, Eijiro Jimi, Ichiro Owan, Yasushi Okazaki, Takenobu Katagiri, Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva, Journal of Biological Chemistry, 10.1074/jbc.M801681200, 2009.03, Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and by progressive heterotopic bone formation in muscle tissue. Recently, a mutation involving a single amino acid substitution in a bone morphogenetic protein (BMP) type I receptor, ALK2, was identified in patients with FOP. We report here that the identical mutation, R206H, was observed in 19 Japanese patients with sporadic FOP. This mutant receptor, ALK2(R206H), activates BMP signaling without ligand binding. Moreover, expression of Smad1 and Smad5 was up-regulated in response to muscular injury. ALK2(R206H) with Smad1 or Smad5 induced osteoblastic differentiation that could be inhibited by Smad7 or dorsomorphin. Taken together, these findings suggest that the heterotopic bone formation in FOP may be induced by a constitutively activated BMP receptor signaling through Smad1 or Smad5. Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP..
232. Masanori Fujii, Yasuharu Nakashima, Seiya Jingushi, Takuaki Yamamoto, Yasuo Noguchi, Eiji Suenaga, Yukihide Iwamoto, Intraarticular findings in symptomatic developmental dysplasia of the hip, Journal of Pediatric Orthopaedics, 10.1097/BPO.0b013e318190a0be, 2009.01, BACKGROUND: The purpose of this study was to examine intraarticular pathology in patients younger than 20 years with symptomatic developmental dysplasia of the hip. METHODS: We performed hip arthroscopy during corrective osteotomy in 23 hips in 22 patients. All patients were female, and the average age at operation was 16.4 years. Eighteen hips were in a prearthritic stage, and 5 hips were in an early stage. The presence and location of cartilage degeneration and labral tears were evaluated. Second-look arthroscopy was performed in 13 hips in 12 patients. RESULTS: Fourteen hips (77.8%) in the prearthritic stage had cartilage degeneration. Cartilage lesions were more frequent in the acetabulum than in the femoral head (72.2% vs 16.7%). Sixty-one percent of acetabular lesions were located at the anterosuperior area. Labral tears were observed in 77.8% of hips in prearthritic stages located at the anterosuperior (72.2%) and superior (44.4%) areas. The degree of cartilage and labral lesions in the early stage was more severe than in the prearthritic stage. On second-look arthroscopy, there were no changes in the state of the cartilage and labrum in the majority (84.6%) of hips. CONCLUSIONS: The incidence of intraarticular lesions in developmental dysplasia of the hip was high, even in the prearthritic stage. These lesions tended to originate in the anterosuperior area of the acetabulum and were generally progressive. LEVEL OF EVIDENCE: Therapeutic study, level IV..
233. Taro Mawatari, Hiromasa Miura, Satoshi Hamai, Toshihide Shuto, Yasuharu Nakashima, Ken Okazaki, Naoko Kinukawa, Shuji Sakai, Paul F. Hoffmann, Yukihide Iwamoto, Tony M. Keaveny, Vertebral strength changes in rheumatoid arthritis patients treated with alendronate, as assessed by finite element analysis of clinical computed tomography scans
A prospective randomized clinical trial
, Arthritis and rheumatism, 10.1002/art.23988, 2008.11, Objective. Finite element analysis of clinical computed tomography (CT) scans provides a noninvasive means of assessing vertebral strength that is superior to dual x-ray absorptiometry (DXA)-measured areal bone mineral density. The present study was undertaken to compare strength changes, measured using this newer method, in rheumatoid arthritis (RA) patients who were treated with alendronate (ALN) versus those who were not. Methods. Thirty female RA patients without radiologic signs of L3 compression fractures or a history of osteoporosis medication were enrolled in a prospective randomized clinical trial. Patients were randomly assigned to the ALN group (5 mg orally, once daily) or the control group not receiving antiresorptive treatment. All patients were evaluated by DXA and quantitative CT at baseline and reevaluated after a mean of 12.2 months. Nonlinear finite element analysis was performed on the CT scans (n = 29 available for analysis) to compute an estimate of vertebral compressive strength and to assess strength changes associated with changes in the trabecular compartment and the outer 2 mm of bone (peripheral compartment). Results. On average, vertebral strength was significantly decreased from baseline in the control group (n = 15) (median change -10.6%; P = 0.008) but was maintained in the ALN group (n = 14) (median change +0.4%; P = 0.55), with a significant difference between the 2 groups (P < 0.01). Strength decreased more rapidly within the trabecular bone, and ALN treatment was much more effective in the peripheral than the trabecular compartment. Conclusion. Our results indicate that patients with RA can lose a substantial amount of vertebral strength over a relatively short period of time, and this loss can be prevented by ALN, primarily via its positive effect on the outer 2 mm of vertebral bone..
234. H. Yamada, Y. Nakashima, K. Okazaki, T. Mawatari, J. I. Fukushi, N. Kaibara, A. Hori, Y. Iwamoto, Y. Yoshikai, Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis, Annals of the Rheumatic Diseases, 10.1136/ard.2007.080341, 2008.09, Objectives: Recent animal studies have revealed critical roles of interleukin (IL)17, which is produced by a newly identified subset of helper T cells, Th17 cells, in the development of autoimmune diseases including arthritis. However, in human rheumatoid arthritis (RA), detailed characteristics and the prevalence of Th17 cells are unclear. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 123 patients with RA and 28 healthy controls. Mononuclear cells were also prepared from synovial membrane or synovial fluid of 12 patients with RA. ILI7 (IL17A) positive T cells were identified by a flow cytometer after ex vivo stimulation with phorbol myristate acetate and ionomycin. Disease activity was assessed with the 28-joint Disease Activity Score (DAS28). Results: IL17 positive cells were detected in CD45RO+ CD4 T cells. Most IL17 positive T cells produced neither interferon (IFN)γ nor IL4, but tumour necrosis factor (TNF)α similar to murine Th17 cells. The frequency of Th17 cells was neither increased in RA nor correlated with DAS28. Unexpectedly, the frequency of Th17 cells was significantly decreased in the joints compared with PBMC of the same patients with RA, whereas Th1 cells were more abundant in the joints than in PBMC. Conclusions: We could not obtain evidence that positively supports predominance of Th17 cells in RA. Further careful investigation is necessary before clinical application of IL17-targeting therapy..
235. N. Kaibara, H. Yamada, T. Shuto, Y. Nakashima, K. Okazaki, H. Miyahara, Y. Esaki, G. Hirata, Y. Iwamoto, Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis, Histopathology, 10.1111/j.1365-2559.2008.03050.x, 2008.06, Aims: To clarify the histological and biological features of tenosynovitis accompanying rheumatoid arthritis (RA). Methods and results: Synovial tissue was obtained from the wrist joint and extensor tendon of the digits of six RA patients and the sections were examined by haematoxylin and eosin staining and immunohistochemical analysis. RA tenosynovitis exhibited the typical histological features of RA joint synovitis, including hyperplasia of the synovial lining and infiltration of leucocytes, largely CD4+ T cells and CD68+ macrophages. Notably, there was a significant correlation in the number of CD4+ T cells and CD68+ macrophages between the tenosynovium and joint synovium in each individual. Real-time reverse transcriptase-polymerase chain reaction analysis revealed similar mRNA expression patterns of various inflammatory mediators in tenosynovitis and joint synovitis. It was also observed that synovial fibroblasts isolated from the tenosynovium behaved in a manner similar to those isolated from the joint synovium with regard to proliferation and the production of inflammatory mediators. Conclusions: The histopathological features of RA tenosynovitis were indistinguishable from those of joint synovitis. Therefore, it is suggested that the ongoing inflammation is driven by similar mechanisms in the tenosynovium and joint synovium and that RA is probably a tissue-specific disease which targets systemic synovial tissues..
236. Satoshi Ikemura, Takuaki Yamamoto, Seiya Jingushi, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, Recurrent transient osteoporosis of the hip, European Journal of Radiology Extra, 10.1016/j.ejrex.2008.03.002, 2008.05, A 49-year-old woman had suffered from a left hip pain. Radiographs showed a focal loss of radiodensity in the left femoral head and neck, and magnetic resonance imaging revealed a bone marrow edema in the femoral head. She was diagnosed as transient osteoporosis of the hip and was treated conservatively. Three years later, right hip pain occurred. Based on the imaging appearances, she was diagnosed as transient osteoporosis of the hip in the right and was treated conservatively. Five years after the onset of right hip pain, she suffered from a recurrent right hip pain. Imaging findings were similar to those obtained 5 years before. Five months after the onset of pain, both hip pain and imaging abnormalities disappeared by the same treatments as the previous episodes. This case was considered to have recurrent transient osteoporosis of the hip..
237. Seiya Jingushi, Hideki Mizuuchi, Yasuharu Nakashima, Takuaki Yamamoto, Taro Mawatari, Yukihide Iwamoto, Computed Tomography-Based Navigation to Determine the Socket Location in Total Hip Arthroplasty of an Osteoarthritis Hip With a Large Leg Length Discrepancy due to Severe Acetabular Dysplasia, Journal of Arthroplasty, 10.1016/j.arth.2007.04.022, 2007.10, For osteoarthritis hips due to severe acetabular dysplasia such as Crowe type 3 or 4, placement of the socket is a difficult procedure in total hip arthroplasty. Because the acetabular bone stock is poor, suitable location for the socket is very limited with respect to achieving good coverage with the host bone. A 51-year-old woman who had an osteoarthritis hip with a large leg length discrepancy due to severe acetabular dysplasia required total hip arthroplasty. The purpose of the total hip arthroplasty was to improve the hip disorder as well as to reduce the leg length discrepancy to achieve good gait function. We present technical solutions to aid the surgeons in placing the acetabular socket at the proper location by using computed tomography-based navigation system..
238. Hisakata Yamada, Nobutaka Kaibara, Shinji Okano, Takeshi Maeda, Toshihide Shuto, Yasuharu Nakashima, Ken Okazaki, Yukihide Iwamoto, Interleukin-15 selectively expands CD57+CD28-CD4+ T cells, which are increased in active rheumatoid arthritis, Clinical Immunology, 10.1016/j.clim.2007.06.001, 2007.09, Proinflammatory cytokines as well as CD4+ T cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recently, an increase of CD57+ or CD28-CD4+ T cells was demonstrated in RA, although the mechanism of the increase of these T cells is unclear. In this study, we first examined the relationship between CD57+CD4+ T cells and CD28-CD4+ T cells and found CD57+CD28-CD4+ T cells, but neither CD57+CD28+ nor CD57-CD28+ cells, expanded in the peripheral blood of active RA. In vitro experiments revealed that CD57+CD28-CD4+ T cells selectively expanded in response to IL-15. Furthermore IL-15-stimulated CD57+CD28-CD4+ T cells induced TNF-α production from monocytes. These results suggest that CD57+CD28-CD4+ T cells are involved in the pathogenesis of RA by responding to IL-15..
239. S. Ikemura, Taku Yamamoto, S. Jingushi, Y. Nakashima, T. Mawatari, Y. Iwamoto, Leg-length discrepancy after transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.89B6.18499, 2007.06, Transtrochanteric curved varus osteotomy was designed to avoid some of the disadvantages of varus wedge osteotomy, such as post-operative leg-length discrepancy. In this retrospective study we investigated the leg-length discrepancy and clinical outcome after transtrochanteric curved varus osteotomy undertaken in patients with osteonecrosis of the femoral head. Between January 1993 and March 2004, this osteotomy was performed in 42 hips of 36 patients with osteonecrosis of the femoral head. There were 15 males and 21 females with a mean age at surgery of 34 years (15 to 68). The mean follow-up was 5.9 years (2.0 to 12.5). The mean pre-operative Harris hip score was 64.0 (43 to 85) points, which improved to a mean of 88.7 (58 to 100) points at final follow-up. The mean varus angulation post-operatively was 25° (12° to 38°) and the post-operative mean leg-length discrepancy was 13 mm (4 to 25). The post-operative leg-length discrepancy showed a strong correlation with varus angulation (Pearson's correlation coefficient; r = 0.9530, p < 0.0001), which may be useful for predicting the leg-length discrepancy which can occur even after transtrochanteric curved varus osteotomy..
240. Takuaki Yamamoto, Yasuharu Nakashima, Toshihide Shuto, Seiya Jingushi, Yukihide Iwamoto, Subchondral insufficiency fracture of the femoral head in younger adults, Skeletal Radiology, 10.1007/s00256-006-0178-1, 2007.06, We report two cases of subchondral insufficiency fracture of the femoral head observed in younger adults without any history of overexertion. In both cases, MRI revealed an irregular, discontinuous low-intensity band on the T1-weighted images. Both patients were treated operatively, and histological examination confirmed the diagnosis of subchondral fracture. A diagnosis of subchondral insufficiency fracture needs to be put in as one of the diagnoses in younger patients with a hip pain..
241. Satoshi Ikemura, Takuaki Yamamoto, Seiya Jingushi, Yasuharu Nakashima, Taro Mawatari, Yukihide Iwamoto, Use of a screw and plate system for a transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head, Journal of Orthopaedic Science, 10.1007/s00776-007-1123-4, 2007.05, Background. We originally used two or three large cancellous screws for a transtrochanteric rotational osteotomy for osteonecrosis. Since January 2002, a screw and plate system (K-MAX Adjustable Angle Hip Screw) has been used to obtain more rigid fixation at the site of osteotomies. We investigated the clinical and radiological results of a transtrochanteric anterior rotational osteotomy. Methods. Between January 2000 and December 2001, a transtrochanteric anterior rotational osteotomy with large cancellous screws was performed in 25 hips of 22 patients, and between January 2002 and March 2005, the K-MAX Adjustable Angle Hip Screw was used in 44 hips of 40 patients for treatment of osteonecrosis of the femoral head. Japanese Orthopaedic Association (JOA) score, postoperative management, and radiographic appearances were investigated. Results. The mean preoperative JOA score was 60.8 ± 12.1 points in the large cancellous screw group and 61.5 ± 14.4 points in the K-MAX Adjustable Angle Hip Screw group. This improved to 86.1 ± 13.3 points in the large cancellous screw group and 88.7 ± 6.6 points in the K-MAX Adjustable Angle Hip Screw group at the final follow-up. Intentional varus angulations were obtained in 15 of 25 hips in the large cancellous screw group and in 36 of 44 hips in the K-MAX Adjustable Angle Hip Screw group. Altogether, 23 of 25 (92.0%) cases with large cancellous screws started partial weight-bearing 7 weeks after the operation, and 43 of 44 (97.7%) cases with the K-MAX Adjustable Angle Hip Screw started 5 weeks after the operation. Conclusions. The K-MAX Adjustable Angle Hip Screw produced clinical results similar to those with the large cancellous screws. In addition, partial weight-bearing could be started 2 weeks earlier after a transtrochanteric anterior rotational osteotomy with the K-MAX Adjustable Angle Hip Screw..
242. Tetsuo Hayashi, Seiya Jingushi, Toshihide Shuto, Yasuharu Nakashima, Takuaki Yamamoto, Yukihide Iwamoto, The accuracy of socket orientation using a pelvic fixation device for total hip arthroplasty with the patient in the lateral decubitus position in comparison to the vacuum bag fixation method., Fukuoka igaku zasshi = Hukuoka acta medica, 2007.01, BACKGROUND: In our department, a vacuum bag with two lateral boards used to be utilized in order to maintain patients in the lateral decubitus position during THA. However, we recently changed this modality to a three-point fixation device for the pelvis in order to accurately control the position of the acetabular socket. The purpose of this study was to retrospectively compare the orientation of the acetabular socket when THA was carried out using two different positioning methods. METHODS: Group 1 consisted of 66 hips that underwent THA in 1997 using a vacuum bag, which became rigid with suction. Group 2 consisted of 42 hips that were treated in 2000 using a three-point fixation device for the pelvis. This device was designed to able to rigidly fix the bilateral anterior superior iliac spines and the sacrum. Before fixation with the device, the angle between the line aligning the anterior-superior iliac spines and the vertical plane in the lateral decubitus position was measured as the lateral pelvic tilt. The orientation of the fixed acetabular socket was evaluated based on postoperative radiographs. RESULTS: The average absolute value from 45 degrees in the abduction angle was significantly lower in group 2 than that in group 1 (p < 0.01). In 18% of the cases in group 1, the anteversion angle was over 30 degrees. In contrast, no such cases were observed in group 2. Postoperative dislocation occurred in six cases (9%) in group 1. In contrast, it only occurred in one case (2%) in group 2. CONCLUSIONS: The positioning method using the pelvic fixation device enabled surgeons to more accurately control the position of the sockets during THA comparison to using the vacuum bag. The positioning of the patient is therefore suggested to be an important first step in successfully performing THA procedures..
243. Goro Motomura, Takuaki Yamamoto, Yasuharu Nakashima, Toshihide Shuto, Seiya Jingushi, Yukihide Iwamoto, Outcome of the Contralateral Hip in Rapidly Destructive Arthrosis After Total Hip Arthroplasty. A Preliminary Report, Journal of Arthroplasty, 10.1016/j.arth.2005.08.007, 2006.10, We investigated the outcome of the contralateral hip in patients with rapidly destructive arthrosis of the hip after total hip arthroplasty. Twenty-four patients were included, and the mean duration of radiographic follow-up was 7.0 years (range, 3.8-17.8 years). To assess the capable parameters for predicting the development of osteoarthritis, we evaluated the receiver operating characteristic curves. Three (12.5%) of 24 patients developed osteoarthritis and underwent total hip arthroplasty within 3.8 to 6.5 years. In these 3 patients, both the acetabular-head index and the center-edge angle were significantly lower than those in patients without osteoarthritis (P < .005). Based on the receiver operating characteristic curves, both an acetabular-head index of less than 72% and a center-edge angle of less than 16° were considered to be associated with the development of osteoarthritis..
244. Kenjiro Nishida, Takuaki Yamamoto, Goro Motomura, Toshihide Shuto, Yasuharu Nakashima, Seiya Jingushi, Yukihide Iwamoto, Early MRI findings of the acetabulum and femoral head in a dysplastic hip resulting in a rapid destruction of the hip joint, Archives of Orthopaedic and Trauma Surgery, 10.1007/s00402-005-0053-x, 2005.10, We documented a case of rapidly destructive arthrosis of the hip joint (RDA), in whom abnormal findings were observed not only in the femoral head but also in the acetabulum on magnetic resonance images (MRI) in the early stage. Radiographs made 1 month after the onset of pain showed a slight narrowing of the joint space. MRI obtained 2 months after the onset detected small foci of low signal intensity in the subchondral area of the femoral head on the T1-weighted images, and a linear pattern of high signal intensity in the lateral side of the acetabulum on the T2-weighted images. During the 17-month follow-up period, this case eventually underwent massive destruction of the femoral head as well as the acetabulum..
245. Satoshi Ikemura, Takuaki Yamamoto, Yasuharu Nakashima, Toshihide Shuto, Seiya Jingushi, Yukihide Iwamoto, Bilateral subchondral insufficiency fracture of the femoral head after renal transplantation
A case report
, Arthritis and rheumatism, 10.1002/art.20994, 2005.04, This report describes the case of a 47-year-old woman who was found to have subchondral insufficiency fractures in both femoral heads after renal transplantation. Initially, plain radiographs showed no obvious changes, but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low-intensity band on the T1-weighted image of both hips. The patient was treated non surgically. Ten months after onset, the pain in both hips disappeared, and plain radiographs and MRI showed no abnormalities. Subchondral insufficiency fracture should be considered in the diagnosis of patients who have hip pain after renal transplantation..
246. Hiroshi Yagi, Kotaro Fukushima, Shoji Satoh, Yasuharu Nakashima, Masahiro Nozaki, Hitoo Nakano, Postpartum retroperitoneal fasciitis
A case report and review of literature
, American Journal of Perinatology, 10.1055/s-2005-861573, 2005.02, We present a case of a postpartum female with iliopsoas fasciitis in the puerperium. Two days after a spontaneous vaginal delivery at 38 weeks without any complications, the patient complained of pain in the left thigh and hip, associated with a temperature of 38° C. Consequently, she could not walk 4 days after delivery and her body temperature had increased to 39°C. Extreme left flank pain and tenderness in the left pelvic wall were prominent, whereas the tenderness in the pelvis was moderate. Magnetic resonance imaging led us to diagnose iliopsoas fasciitis. This was complicated by sepsis but improved after a protracted antibiotic treatment without any surgical intervention. A literature review revealed that serious complications, including sepsis or permanent functional disturbance, could arise although retroperitoneal fasciitis and/or abscesses are very rare after vaginal delivery. Iliopsoas fasciitis could be considered when patients complain of extreme pain in the pelvic wall, sacroiliac joint region, or thigh-symptoms that are uncommon in uncomplicated endometritis..
247. Taro Mawatari, Hiromasa Miura, Tsutomu Kawano, Satoshi Hamai, Nobuaki Tsukamoto, Toshihide Shuto, Yasuharu Nakashima, Yukihide Iwamoto, Hidehiko Higaki, Kosaku Kurata, Shuji Sakai, Bone quantity and quality to its mechanical integrity, Clinical calcium, 2004.04, Bone strength is made up of quantity (mass, mineralization), geometry (anatomy, micro architecture, collagen structure), and turnover/damage accumulation. While most of the mechanical behavior can be explained by measures of porosity, several additional descriptors of the geometry have been proposed for better predictions of fracture risk. This review introduces various aspects of these relationships between bone quantity and quality to its mechanical integrity..
248. Mayuki Taketa, Toshio Fujii, Hideaki Kubota, Yasuharu Nakashima, Yasuo Noguchi, Yukihide Iwamoto, Correlation between center-edge angle and acetabulum-head index in developmental dysplasia of the hip with avascular necrosis of the femoral head, Journal of Pediatric Orthopaedics Part B, 10.1097/00009957-200305000-00009, 2003.05, In order to clarify the relationship between the center-edge angle and the acetabulum-head index, we reviewed 97 hips in 86 patients suffering from developmental dysplasia of the hip. We measured the center edge angle and the acetabulum-head index, and evaluated avascular necrosis of the femoral head according to Kalamchi classification. The center-edge angle correlated highly with the acetabulum-head index in non-avascular necrosis, and in Kalamchi groups I and II, but not in Kalamchi groups III and IV. Because of difficulties in measurement, it is possible that the center-edge angle does not precisely indicate acetabular coverage of developmental dysplasia of the hip with avascular necrosis..
249. Doo Hoon Sun, Michael C.D. Trindade, Yasuharu Nakashima, William J. Maloney, Stuart B. Goodman, David J. Schurman, R. Lane Smith, Human serum opsonization of orthopedic biomaterial particles
Protein-binding and monocyte/macrophage activation in vitro
, Journal of Biomedical Materials Research - Part A, 10.1002/jbm.a.10477, 2003.05, Wear particles generated after total joint arthroplasty activate monocyte/macrophages and incite formation of a granulomatous periprosthetic tissue associated with bone loss and implant loosening. This study tested the hypothesis that selective opsonization of orthopedic implant biomaterial wear particles by human serum proteins influences monocyte/macrophage activation. Serum protein binding to metallic, polymeric, and ceramic particles was determined by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual proteins bound to particles were subsequently identified using two-dimensional SDS-PAGE, microsequencing techniques, and SWISS-PROT analysis. Effects of selective protein opsonization on particle-induced monocyte/macrophage activation were assessed by quantification of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha release. Results from one-dimensional gel analyses revealed distinct serum protein-binding patterns specific for each material tested. Two-dimensional gel analysis together with amino acid sequencing of the prominent protein species confirmed the presence of albumin and alpha-1-antitrypsin bound to all particles tested. In contrast to the metallic particles, apolipoprotein was a major species associated with polymeric particles. Opsonization of PMMA particles with purified preparations of each of the identified proteins showed that albumin significantly enhanced particle-induced monocyte/macrophage activation. These data confirm orthopedic biomaterial specific binding of human serum proteins and demonstrate that albumin exacerbates particle-induced monocyte/macrophage activation. Alterations in the chemical and surface properties of orthopedic biomaterials to modulate protein interactions may improve implant longevity..
250. Akio Sakamoto, Ryuji Nagamine, Takeshi Maeda, Takeshi Shuto, Go Hirata, Yasuharu Nakashima, Shuichi Matsuda, Yukihide Iwamoto, Multicentric reticulohistiocytosis with hydrarthrosis in both knee joints
Disease stabilization with synovectomy, and medication with a steroid and low-dose methotrexate
, Modern Rheumatology, 10.1007/s101650200026, 2002.08, Multicentric reticulohistiocytosis is a rare systemic disease characterized by the infiltration of histiocytes and multinucleated giant cells with cutaneous nodules, and severe destructive arthritis. It is commonly the peripheral joints which are affected, and therefore symptoms in large joints have not been fully investigated. We describe the case of a 44-year-old woman with multicentric reticulohistiocytosis, who was suffering from swelling in both knee joints and cutaneous nodules, in addition to arthritis in the elbow, hip, and peripheral joints. Magnetic resonance imaging of both knee joints showed hydrarthrosis associated with a tumor-like overgrowth of synovial tissue. These symptoms were reduced following a resection of the synovial tissue and subsequent medication with prednisone and low-dose methotrexate. It should be noted that swelling in the knee joints can be one of the symptoms caused by multicentric reticulohistiocytosis, in addition to cutaneous nodules and arthritis in the peripheral joints. Resection of synovial tissue, and medication with prednisone and low-dose methotrexate were effective in the present case..
251. Eiji Suenaga, Yasuo Noguchi, Seiya Jingushi, Toshihide Shuto, Yasuharu Nakashima, Keita Miyanishi, Yukihide Iwamoto, Relationship between the maximum flexion-internal rotation test and the torn acetabular labrum of a dysplastic hip, Journal of Orthopaedic Science, 10.1007/s776-002-8409-8, 2002.01, To determine the relationship between pain at flexion-rotation and the status of a labral tear in patients with dysplastic hips, physical examination maneuvers and hip arthroscopy were carried out in 59 patients with dysplastic osteoarthritis (5 men and 54 women; mean age, 41 years; range, 16 to 64 years). Between January 1998 and June 2000, these patients underwent 60 hip arthroscopies at Kyushu University Hospital. All hip joints arthroscoped demonstrated incomplete or complete detaching tears of the acetabular labrum in one portion of the weight-bearing area. Twenty-three patients (39%) experienced pain during the maximum flexion-internal rotation test; 16 patients (27%) showed a positive result for the maximum flexion-external rotation test. There was no statistically significant relationship between the results of the maximum flexion-external rotation test and the arthroscopic findings of labral tears. A positive maximum flexion-internal rotation test result, however, correlated well with incomplete detaching tears in the posterosuperior portion of the acetabular labrum. In contrast, a complete detaching tear of the posterosuperior labrum was associated with a negative maximum flexion-internal rotation test result. The maximum flexion-internal rotation test is useful for assessing the magnitude of a labral tear in the posterosuperior portion of the acetabular labrum in dysplastic hips..
252. Michael C.D. Trindade, Martin Lind, Yasuharu Nakashima, Doohoon Sun, Stuart B. Goodman, David J. Schurman, R. Lane Smith, Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-α release by human monocyte/macrophages in vitro, Biomaterials, 10.1016/S0142-9612(00)00376-8, 2001.08, Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-α, and prostaglandin E2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 μm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-α release by the cells following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-α at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-α release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-α release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-α release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α in response to PMMA particle challenge in vitro..
253. Keita Miyanishi, Takuaki Yamamoto, Yasuharu Nakashima, Toshihide Shuto, Seiya Jingushi, Yasuo Noguchi, Yukihide Iwamoto, Subchondral changes in transient osteoporosis of the hip, Skeletal Radiology, 10.1007/s002560100350, 2001.05, Objective. To review the subchondral changes on MR imaging in transient osteoporosis of the hip (TOH) and to consider the pathophysiology. Design and patients. MR images of 12 hips of 11 consecutive patients with TOH were retrospectively studied. The diagnoses of TOH were confirmed on the basis of previously published criteria, including decreased bone density of the femoral head and/or neck on radiographs, bone marrow edema (BME) pattern on MR images, spontaneous resolution of the symptoms and a return to normal radiodensity. Results. All 12 hips showed a BME pattern in the femoral head and/or neck. Linear patterns of very low signal intensity were identified on T1-weighted images in the subchondral area within the diffuse low signal intensity area in all 12 hips. On T2-weighted images, a low signal intensity line was observed in the corresponding area in eight hips only. These linear patterns were thought to represent subchondral fracture lines. Conclusions. The presence of a subchondral fracture may be important when considering the pathophysiology of TOH..
254. H. Kubota, Y. Noguchi, K. Urabe, T. Itokawa, Y. Nakashima, Y. Iwamoto, Flexor digitorum longus accessorius in the club foot of an infant with Nager syndrome, Archives of Orthopaedic and Trauma Surgery, 10.1007/s004020000167, 2001.02, The case of a male infant is reported who had club foot on the right side and pes adductus on the left side in combination with acrofacial dysostosis; he also demonstrated preaxial anomalies of the upper limbs indicative of Nager syndrome. In addition, an unusual aberrant muscle was discovered during surgical correction of the right club foot..
255. R. Nagamine, T. Maeda, T. Shuto, Yasuharu Nakashima, G. Hirata, Y. Iwamoto, Menopausal syndrome in female patients with rheumatoid arthritis, Modern Rheumatology, 10.3109/s101650170009, 2001.01, This study was performed to assess the relationship between joint symptoms in rheumatoid arthritis (RA) and symptoms in menopausal syndrome. Detailed analyses of the clinical course, laboratory data, joint symptoms, and symptoms of menopausal syndrome were performed for five patients with stage I and monocyclic-type RA. The age when joint symptoms first appeared coincided with the age of menopause in all patients, and the mean age was 51.0 years. The mean period from menopause to this study was 5.4 years. All patients showed more than six menopausal syndrome symptoms. Two patients were confirmed gynecologically to have definite menopausal syndrome, and accordingly hormone replacement therapy (HRT) was given. In one patient, the polyarthralgia disappeared after she received HRT. All the American College of Rheumatology (ACR) criteria, with the exception of subcutaneous nodules, can be explained as symptoms related to estrogen deficiency in menopausal syndrome because estrogen regulates the production of inflammatory cytokines such as IL-1, IL-6, and TNFα, and these cytokines are produced in greater abundance in conditions of estrogen deficiency. Estrogen deficiency at the menopause influences joint symptoms and inflammatory parameters in rheumatoid arthritis. Estrogen deficiency in menopausal syndrome may induce joint symptoms resembling RA..
256. S. Jingushi, Y. Noguchi, T. Shuto, T. Nakashima, Y. Iwamoto, A device for removal of femoral distal cement plug during hip revision arthroplasty
A high-powered drill equipped with a centralizer
, Journal of Arthroplasty, 10.1016/S0883-5403(00)90374-7, 2000.01, A removal procedure of a femoral cement mantle in hip revision arthroplasty has a risk of causing perforation or fracture, especially when removing a well-fixed distal cement plug. A high-powered drill equipped with a centralizer was developed to remove the distal cement plug safely. Using the drill equipped with a centralizer, the cement plug was removed well enough to insert a new component without causing perforation during the operation..
257. R. Nagamine, Y. Hanada, M. Kondo, S. Fukumoto, T. Shuto, Y. Nakashima, G. Hirata, A. Katayama, Y. Iwamoto, Quantification of bone volume on radiographs using NIH Image, Modern Rheumatology, 10.3109/s101650070006, 2000.01, We attempted to quantify periarticular bone atrophy from radiographs of the proximal phalanx in patients with rheumatoid arthritis (RA) by means of the National Institutes of Health (NIH) Image computer program. The degree of brightness or darkness in four squares, each 20 × 20 pixels, in the right third proximal phalanx was measured using NIH Image, and the mean value of the 400 pixels was defined as the brightness/darkness index (BDI). The BDI was used to express bone volume. The BDI value was set at zero for an area of complete darkness and at 255 for an area of maximum brightness. The mean coefficient of variation in our hospital was 2.28%. The BDI was measured in 54 RA patients and 146 normal volunteers. The mean BDI at the midpoint of the diaphysis was 100 in RA patients and 176 in normal volunteers, while at the medial side of the proximal end it was 75 and 145, respectively. The difference between normal volunteers and RA patients was greatest in younger people. In some young RA patients, the BDI was significantly low at the medial side of the proximal end, clearly demonstrating periarticular bone atrophy. Periarticular bone atrophy can be quantified using the NIH Image computer program..
258. M. Lind, M. C.D. Trindade, Y. Nakashima, D. J. Schurman, S. B. Goodman, R. L. Smith, Chemotaxis and activation of particle-challenged human monocytes in response to monocyte migration inhibitory factor and C-C chemokines, Journal of Biomedical Materials Research, 10.1002/(SICI)1097-4636(1999)48:3<246::AID-JBM7>3.0.CO;2-X, 1999.06, Cytokines that regulate monocyte migration were found in membrane tissue surrounding loosened prosthetic implants. Monocyte migration inhibition factor (MIF) is able to inhibit macrophage migration. Monocyte chemoattractant protein (MCP) and macrophage inflammatory protein (MIP) are potent macrophage chemoattractants. These cytokines may be expressed as part of the foreign body response to prosthetic particulate debris. Chemotaxis analysis and macrophage activation experiments were performed to determine the effects of MIF, MCP-1, and MIP-1α on macrophage migration and activation in vitro. We demonstrated that MIF had its maximal migration inhibitory effect for unchallenged and particle challenged macrophages at 1 ng/mL. MCP- 1 and MIP-1α stimulated macrophage chemotaxis maximally at 1 to 10 ng/mL. Dose-response studies with MIF, MCP-1, and MIP-1α demonstrated that these cytokines did not modulate activation of unchallenged or particle challenged macrophages as evaluated by IL-6 and TNF-α release. However, these cytokines do not appear to affect macrophage release of proinflammatory mediators in vitro..
259. Yasuharu Nakashima, Doo Hoon Sun, Michael C.D. Trindade, William J. Maloney, Stuart B. Goodman, David J. Schurman, Lane R. Smith, Signaling pathways for tumor necrosis factor-α and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro, Journal of Bone and Joint Surgery - Series A, 10.2106/00004623-199905000-00002, 1999.05, Background: Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signaling pathways involved in particle- mediated release of cytokines. Methods: Macrophages were isolated from mononuclear leukocytes obtained from healthy human donors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes collected at revision total joint arthroplasties and then enzymatically prepared. The experimental protocols included examination of the effects of the inhibition of phagocytosis and the binding of antibodies to macrophage complement receptors on particle-induced macrophage activation. The release of the proinflammatory cytokines TNF-α (tumor necrosis factor-alpha) and IL- 6 (interleukin-6) was used to assess macrophage activation. The signaling pathways involved in the induction of cytokine release were analyzed by identification of phosphorylated proteins with use of the Western blot technique and by translocation of the transcription factors nuclear factor- kappa B (NF-κB) and nuclear factor-interleukin-6 (NF-IL-6) into the nuclear protein fraction with use of electrophoretic mobility shift assays. The role of serine/threonine and tyrosine kinase pathways in the activation of nuclear factors and the release of cytokines was examined with use of selective pharmacological agents. Results: Exposure of macrophages to titanium-alloy particles in vitro for forty-eight hours resulted in a fortyfold increase in the release of TNF-α and a sevenfold increase in the release of IL-6 (p < 0.01). Phagocytosis of particles occurred in approximately 73 percent of the macrophages within one hour of exposure. Pretreatment of the macrophages with cytochalasin B reduced phagocytosis by 95 percent but did not reduce the release of TNF-α or IL-6. Thus, phagocytosis of particles was not necessary for induction of the release of TNF-α or IL-6 in the cultured macrophages. Ligation of the macrophage CD11b/CD18 receptors by integrin-specific antibodies also increased the release of TNF-α and IL-6. Antibodies to CD11b/CD18 receptors (macrophage Mac-1 receptors) reduced phagocytosis of particles by 50 percent (p < 0.05). (The CD11b/CD18 macrophage receptor is the macrophage receptor for the complement component CR3bi. The CD11b/CD18 macrophage receptor can also bind to ICAM-1 and ICAM-2. CD is the abbreviation for cluster of differentiation, and ICAM is the abbreviation for intercellular adhesion molecule.) Inhibition of phagocytosis was not accompanied by a decrease in the release of TNF-α and IL-6. Blocking RNA synthesis with actinomycin D or preventing protein synthesis with cycloheximide abolished or decreased particle-induced release of TNF-α and IL-6 from the macrophages. Macrophage release of TNF-α and IL-6 in response to particles coincided with increased tyrosine phosphorylation and mitogen- activated protein kinase activation. Inhibition of tyrosine and serine/threonine kinase activity decreased the particle-induced release of cytokines. Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-κB and NF-IL-6. Inhibition of particle phagocytosis did not block activation of the transcription factors. However, inhibition of tyrosine and serine/threonine kinase activity decreased the activation of NF-κB and NF-IL-6. Conclusions: These data suggest that particle-induced macrophage release of TNF-α and IL-6 does not require phagocytosis but is dependent on tyrosine and serine/threonine kinase activity culminating in activation of the transcription factors NF-κB and NF-IL-6. Clinical Relevance: Retrieval studies have documented numerous macrophages in association with particulate debris in granulomatous tissue surrounding failed total joint replacements. However, the molecular basis on which wear particles induce macrophage expression of proinflammatory cytokines and bone-resorbing factors remains unclear. This in vitro study showed that particles incite the release of proinflammatory cytokines from macrophages in the absence of phagocytosis. These results imply that contact of wear particles with macrophage cell-surface membrane proteins, such as the complement receptor CD11b/CD18, is sufficient signal for release of proinflammatory cytokines. The data further suggest that release of proinflammatory cytokines follows transmission of a membrane recognition event through intracellular signaling pathways that effect gene activation and protein synthesis. Therefore, these data indicate that a reduction in the formation of wear particles can be expected to improve the outcome after total joint arthroplasty by decreasing macrophage activation..
260. Y. Nakashima, D. H. Sun, M. C.D. Trindade, L. E. Chun, Y. Song, S. B. Goodman, D. J. Schurman, W. J. Maloney, R. L. Smith, Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.81B1.8884, 1999.01, Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PRIMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PRIMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty..
261. Michael C.D. Trindade, Yasuharu Nakashima, Martin Lind, Doo Hoon Sun, Stuart B. Goodman, William J. Maloney, David J. Schurman, R. Lane Smith, Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro, Journal of Orthopaedic Research, 10.1002/jor.1100170602, 1999.01, The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin- 4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocytemacrophage colony- stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1 beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte- macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particleinduced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators..
262. William J. Maloney, Doo Hoon Sun, Yasuharu Nakashima, Ron James, R. Lane Smith, Effects of serum protein opsonization on cytokine release by titanium- alloy particles, Journal of Biomedical Materials Research, 10.1002/(SICI)1097-4636(19980905)41:3<371::AID-JBM5>3.0.CO;2-9, 1998.09, This study tested whether macrophages respond differently to retrieved titanium-alloy particles than they do to machined titanium-alloy particles and assessed whether pretreatment of machined titanium-alloy particles with human serum would influence macrophage activation and cytokine release in vitro. Human monocyte/macrophages were isolated from normal healthy donors and exposed to increasing concentrations of machined and retrieved titanium- alloy particles. The profile of cytokine release was determined by commercially available ELISA kits. Machined titanium-alloy particles were opsonized with human serum and added to macrophage cultures. Serum protein binding was confirmed by SDS-PAGE analysis. The results showed that machined titanium-alloy particles and retrieved titanium-alloy particles stimulate a similar level of cytokine release when tested at comparable concentrations. Opsonization of the machined particles with human serum increased the macrophage release of cytokines in the first 12 h after exposure compared to nonopsonized particles. At 24 h, the opsonized particles stimulated significantly higher levels of cytokine release, but only at the greatest particle concentrations. This study demonstrates that machined titanium alloy induces a metabolic response in macrophages similar to that of titanium- alloy particles retrieved from failed total hip arthroplasty. In addition, these data show that serum protein binding to orthopedic biomaterial debris alters the macrophage reaction to the particles..
263. Yasuharu Nakashima, Doo Hoon Sun, W. J. Maloney, Stuart B. Goodman, David J. Schurman, R. Lane Smith, Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro, Journal of Bone and Joint Surgery - Series B, 10.1302/0301-620X.80B4.8374, 1998.07, We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 μm in size. Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle. Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues..