Functional Adaptation of the Fibrocartilage and Bony Trabeculae at the Attachment Sites of the Anterior Cruciate Ligament.

The direct insertion of an enthesis is composed of uncalcified fibrocartilage (FC) and calcified FC, believed to function as buffers for multidirectional forces applied to the ligament. This study was performed to investigate the relationship between the FC thickness and bony trabecular orientation of the anterior cruciate ligament (ACL) on both the femoral and tibial sides. Six cadavers were examined (age at death: 73-92 years). Both femoral and tibial insertions of the ACL were harvested and used to make 0.5 mm interval semi-serial sections. Microdigital images were taken and used to measure the maximum thickness of both the uncalcified FC and Calcified FC. Two-dimensional discrete Fourier analysis was also performed to determine the orientation angle and orientation intensity of bony trabeculae directly under the FC. The mean thicknesses of the uncalcified FC at the femoral and tibial insertions were 0.98 mm and 0.49 mm, respectively. The mean thicknesses of the calcified FC were 0.47 mm and 0.38 mm, respectively. There was a significant difference in the uncalcified FC thickness, but not in the calcified FC thickness. The bony trabeculae showed a prominent orientation parallel to the ACL fiber on both sides, but it was more intense on the tibial side than on the femoral side. The trabecular orientation was prominent in the proximal-posterior part of the femoral side and in the anteromedial part of the tibial side, suggesting that mechanical stress is greater in these parts. The dominant bony trabecular angle was 69.0° on the femoral side and 59.8° on the tibial side when the tidemark was set at 0°. These findings suggest that the femoral side receives multidirectional stresses, while relatively unidirectional stress is loaded on the tibial side. Furthermore, stress is considered to be greater in the proximal-posterior part of the femoral insertion and in the anteromedial part of the tibial insertion. At the time of ACL reconstruction, attention should be paid to assign a robust portion of the graft to the posterior part of the femoral insertion and anteromedial part of the tibial insertion. Clin. Anat., 33:988-996, 2020. © 2019 Wiley Periodicals, Inc.

The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial.

BACKGROUND: An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids. OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients. METHODS: Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward. RESULTS: In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%. CONCLUSIONS: Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.

Quality of life of patients with osteonecrosis of the femoral head: a multicentre study.

PURPOSE: Quality-of-life (QOL) assessments in patients with osteonecrosis of the femoral head (ONFH) have rarely been reported. This multicentre study aimed to elucidate the relationship between disease severity, including necrotic lesion type and radiological staging, and QOL, as well as between patients' characteristics and QOL. METHODS: Two hundred seventy-four patients with ONFH (108 females, 166 males; median age, 46 years) were asked to complete self-assessment QOL questionnaires including the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire, Oxford Hip Score, and SF-12v2. RESULTS: Patients with large necrotic lesion type or collapsed ONFH had low QOL scores. Among patients with non-collapsed lesions, patients with alcohol-associated ONFH had lower QOL scores than those with steroid-associated ONFH, those with bilateral ONFH had lower mental scores, and male patients had worse social condition scores. Among patients with collapsed lesions, middle-aged patients exhibited lower mental QOL, and a strong correlation was observed between social activity and mental health. CONCLUSION: Collapsed ONFH was associated with low QOL scores. Among patients with non-collapsed lesions, alcohol-associated ONFH, bilateral disease, and male sex were linked to low QOL scores.

Restoration of proximal periprosthetic bone loss by denosumab in cementless total hip arthroplasty.

Denosumab contributed to the restoration of proximal periprosthetic bone loss around the femoral stem that were measured using a DEXA, especially in zone 7, at 1 year after cementless THA in elderly osteoporotic patients. INTRODUCTION: Although bone quality is an important issue in elderly osteoporotic patients who underwent total hip arthroplasty (THA) with a cementless stem, periprosthetic bone mineral density (BMD) in the proximal femur has been reported to be decreased by 15-40% postoperatively. Some authors have examined the use of several types of bisphosphonates to prevent decreases in BMD in the proximal femur after cementless THA; however, few reports have demonstrated success in restoring BMD in the proximal medial femoral bone, such as zone 7. METHODS: We conducted prospective study comparing patients who underwent cementless THA administered with denosumab (10 patients) and without denosumab (10 patients). BMD around the femoral stem were measured using a DEXA immediately after surgery, and at 6 months and at 1 year after surgery. No difference was found between the two groups referred to the patient's demographic data. RESULTS: We found that denosumab displayed definitive effects in increasing the % change in periprosthetic BMD at zone 7 by an average of 7.3% in patients with cementless THA, compared to control group who were given only vitamin D. CONCLUSION: Denosumab is one of a number of anti-osteoporotic agents to have a definitive effect on the restoration of proximal periprosthetic bone loss, especially in zone 7, after cementless THA. Denosumab contributed to the restoration of decreased periprosthetic BMD to normal levels. As the decrease in BMD in the proximal femur after THA is considered to be apparent at 6-12 months after surgery, it is believed that prevention of the deterioration of bone quality is important in the proximal femur immediately after cementless THA for elderly female patients with osteoporosis.

Three-dimensional orientation of the acetabulum.

This study was designed specifically to determine the normal acetabular orientation and femoral head covering, and whether these are affected by age or sex. Computed tomographic images of normal Japanese hip joints were used (males 60, females 60; mean age 48.3 years, range 15-79 years). Male and female age profiles were matched. The reconstructed 3-D pelvic images were aligned in the anatomical pelvic coordinate system. The acetabular orientation angles and femoral covering angles were measured in the sagittal, coronal, and horizontal planes. In the sagittal plane, the acetabular orientation angle was operative anteversion (O-av), and the femoral covering angles were the anterior and posterior center-edge angles (ACE and PCE). In the coronal plane, they were the Sharp angle (SA) and the lateral center-edge angle (LCE). In the horizontal plane, they were anatomical anteversion (A-av) and the anterior and posterior sector angles (ASA and PSA). The O-av, SA, and A-av were smaller in the male than the female acetabulum (P < 0.01). SA in both males and females was inversely correlated with age (P < 0.01). Both male PCE and PSA were significantly smaller than those of females, while male ASA was larger than female ASA (P < 0.05). The male acetabulum is directed further outward and downward than the female one. However, this does not indicate that the male acetabulum covers the femoral head more, because there is no significant sex difference in the LCE. Femoral coverage is more posteriorly biased in females than in males owing to pelvic inclination. Clin. Anat. 30:753-760, 2017. © 2017Wiley Periodicals, Inc.

Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats.

Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.

Prognostic impact of CD109 expression in myxofibrosarcoma.

BACKGROUND: CD109, a TGF-ß co-receptor, is reported to be preferentially expressed during the early stages of tumorigenesis in several carcinoma types. Myxofibrosarcoma is one of the most common soft-tissue sarcomas found in elderly patients. This study aimed to elucidate the impact of CD109 expression in myxofibrosarcoma on prognosis and recurrence. METHODS: Immunohistochemical staining for CD109 was performed on archival specimens from 37 patients. The Fisher exact test was used to evaluate association between CD109 expression and other clinicopathological features. Survival analysis was performed using Kaplan-Meier curves, and the prognostic significance was evaluated using the log-rank test. Multivariate analysis of factors was performed using Cox regression analysis. RESULTS: CD109 overexpression was significantly associated with surgical stage and distant metastasis (P = 0.00499, and 0.011, respectively). The frequency of CD109 overexpression was approximately 10% and CD109 overexpression was significantly associated with decreased overall survival (P = 0.004). Five-year overall survival rates 77% and 0% for CD109-negative and CD109-positive patients, respectively. In multivariate analysis, CD109 overexpression was the only independent risk factor for poor outcome (P = 0.02; hazard ratio, 10.64; 95% confidence interval, 1.47-76.91). CONCLUSIONS: Immunohistochemical CD109 expression in myxofibrosarcoma was associated with poor prognosis.

Ultrastructure of the three anterior cruciate ligament bundles.

The anterior cruciate ligament (ACL) can be morphologically separated into not only two, but three bundles: the anteromedial-medial bundle (AM-MB), the anteromedial-lateral bundle (AM-LB), and the posterolateral bundle (PLB). Our hypothesis was that the three bundles differ in their microstructures. The purpose of this study was to clarify the microstructural differences among the three bundles. The normal ACLs of six fresh frozen cadavers were harvested. After the AM-MB, AM-LB, and PLB were identified, their fibril structures were analyzed using a transmission electron microscope. The fibril orientation, distribution pattern, and the mass average diameter of the fibrils (MAD) were compared among the AM-MBs, AM-LBs, and PLBs. The AM-MB and AM-LB fibrils were arranged mostly in the longitudinal direction, while the PLB fibrils were not aligned in a uniform direction. The fibril diameter distribution pattern of AM-MBs showed a bi-modal pattern due to the existence of small-diameter (30-40 nm) and large-diameter fibrils (70-80 nm), while that of the AM-LBs and PLBs had a unimodal pattern with one prominent high peak at a diameter of 50-60 nm. The mean MAD of the AM-MBs (83.2 - 11.2 nm) was significantly larger than that of the PLBs (66.8 - 7.7 nm), while it showed no significant difference compared to that of the AM-LBs (77.6 - 12.3 nm). The three ACL bundles have different ultrastructures. The AM-MB predominantly includes thick, uni-directionally oriented fibrils like tendons, while the PLB consists of thinner, multi-directionally oriented fibrils. The AM-LB shows an intermediate structure between the AM-MB and the PLB.

Nationwide investigation into adverse tissue reactions to metal debris after metal-on-metal total hip arthroplasty in Japan.

BACKGROUND: Adverse reactions to metal debris (ARMD) after receiving metal-on-metal (MoM) hip implants is a recent concern. However, no epidemiologic study has examined ARMD for MoM hip implants in Japan. The purposes of this study were to research the incidence of ARMD and to identify poorly performing MoM hip implants in Japan. METHODS: From 2000 to 2011, 7 companies provided 23,226 MoM implants in Japan. A questionnaire regarding ARMD was sent to 101 hospitals at which 62% of the 23,226 MoM implants had been used. RESULTS: Replies to the questionnaire were received from 82 hospitals. In these hospitals, surface hip replacement types (SRs) were used in 606 hips and stemmed types were used in 12,961 hips. ARMD were reported in 3 hips (0.5%) with SRs and 160 hips (1.2%) with stemmed types. ARMD in the 3 hips with SRs were asymptomatic and no revisions were performed. Among AMRD with stemmed implants, revision was performed in 83 hips and excision of an ARMD lesion was performed in 3 hips. The remaining 74 hips were asymptomatic and careful follow-up was continued. A significant difference in reoperation rate was evident between SRs (0%) and stemmed types (0.7%). Incidences of ARMD were significantly higher with Ultamet (P = 0.005), Conserve (P < 0.001), and Cormet (P < 0.001) MoM bearing couples than with Metasul bearings. CONCLUSIONS: The incidence of ARMD in large surgical volume hospitals in Japan from 2000 to 2011 was estimated to be 0.5% with SRs and 1.2% with stemmed types. The reoperation rate was significantly higher with stemmed types than with SRs. Three brands of MoM stemmed implants were identified as showing a higher incidence of ARMD.

The Accuracy of Cup Placement in Total Hip Arthroplasty (THA) Using an Augmented Reality-Based Navigation System.

Background AR HIP Navigation System® (AR-navi; Zimmer-Biomet, Warsaw, IN) is a portable navigation system employing augmented reality via a smartphone app, which was developed in Japan. We retrospectively analyzed the accuracy of cup placement in total hip arthroplasty (THA) using AR-navi, to investigate whether obesity is associated with an absolute value error in cup placement angle. Methods We retrospectively analyzed 45 hips in 43 patients who underwent THA using AR-navi (AR-navi group) and compared them with 45 hips in 45 patients who underwent THA using alignment rods (conventional group). Results The mean absolute error of cup placement (AR-navi group vs. conventional group) was found to be 2.60° (±2.11) in radiographic inclination (RI) for the AR-navi group and 4.61° (±3.28) for the conventional group, which indicates significant difference in the AR-navi group compared to that in the conventional group (p = 0.0036). The mean absolute error of radiographic anteversion (RA) was 3.57° (±3.36) for the AR-navi group and 3.87° (±2.97) for the conventional group (p = 0.4732). The mean absolute error of RI was 2.36° (±2.24) in the obese group and 3.16° (±2.03) in the nonobese group, and the mean absolute error of RA was 4.08° (±4.51) and 3.16° (±2.05) in the obese and nonobese groups, respectively. Conclusions Cup placement accuracy for THA using AR-navi was 2.60 ± 2.11° for RI and 3.87 ± 2.97° for RA. Compared to THA using the conventional method, the RI installation error was significantly improved with AR Navi. There was no significant difference in the mean absolute error of RI and RA among the obese and nonobese groups.

Specific pelvic shape in patients with developmental dysplasia of the hip on 3D morphometric homologous model analysis.

PURPOSE: To clarify the morphological factors of the pelvis in patients with developmental dysplasia of the hip (DDH), three-dimensional (3D) pelvic morphology was analyzed using a template-fitting technique. METHODS: Three-dimensional pelvic data of 50 patients with DDH (DDH group) and 3D pelvic data of 50 patients without obvious pelvic deformity (Normal group) were used. All patients were female. A template model was created by averaging the normal pelvises into a symmetrical and isotropic mesh. Next, 100 homologous models were generated by fitting the pelvic data of each group of patients to the template model. Principal component analysis was performed on the coordinates of each vertex (15,235 vertices) of the pelvic homologous model. In addition, a receiver-operating characteristic (ROC) curve was calculated from the sensitivity of DDH positivity for each principal component, and principal components for which the area under the curve was significantly large were extracted (p<0.05). Finally, which components of the pelvic morphology frequently seen in DDH patients are related to these extracted principal components was evaluated. RESULTS: The first, third, and sixth principal components showed significantly larger areas under the ROC curves. The morphology indicated by the first principal component was associated with a decrease in coxal inclination in both the coronal and horizontal planes. The third principal component was related to the sacral inclination in the sagittal plane. The sixth principal component was associated with narrowing of the superior part of the pelvis. CONCLUSION: The most important factor in the difference between normal and DDH pelvises was the change in the coxal angle in both the coronal and horizontal planes. That is, in the anterior and superior views, the normal pelvis is a triangle, whereas in DDH, it was more like a quadrilateral.

Joint instability in patients with borderline developmental dysplasia of the hip.

BACKGROUND: The treatment strategy for developmental dysplasia of the hip is determined based on the lateral center-edge angle. Nonetheless, an evaluation of joint instability may be important in determining the treatment strategy. This study classified the displacement patterns of the femoral head center during hip abduction. METHODS: Ten patients with borderline developmental dysplasia of the hip, 10 patients with developmental dysplasia of the hip, and 10 patients with normal hips were analyzed. Image matching was performed using X-ray images of hip abduction with a three-dimensional hip model. The displacement of the femoral head center and its trajectory length were measured. A cluster analysis was conducted to classify the displacement pattern of the femoral head center, and trajectory lengths were compared. FINDINGS: Displacement was classified into three patterns: medialization, hinge abduction, and centering. Patients with borderline developmental hip dysplasia exhibited all three patterns. Almost all patients with developmental dysplasia of the hip showed medialization and hinge abduction, whereas all normal patients had the centering type. The mean trajectory length indices for the medialization and hinge abduction types were significantly longer than those for the centering type (P = 0.01 and P = 0.016, respectively). INTERPRETATION: Borderline developmental dysplasia of the hip is a heterogeneous condition characterized by varying hip instability levels. Our findings suggest that uniform evaluation based on the lateral center-edge angle is inappropriate and that joint instability must be evaluated in each patient with borderline developmental dysplasia of the hip.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

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

Experimental rat model for alcohol-induced osteonecrosis of the femoral head.

Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1-24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.

High risk of osteonecrosis of the femoral head in autoimmune disease patients showing no immediate increase in hepatic enzyme under steroid therapy.

Aim of the study is to determine the relationship between liver function and the incidence of ONF after steroid therapy in AID patients. The present study investigated 58 AID patients who had received high-dose systemic steroid therapy to determine whether a correlation exists between parameters of hepatic function and steroid-induced ONF at the precise time-point when steroid-induced ONF develops. The patients were divided into two groups on the basis of MRI findings: ONF (n = 31) and non-ONF (n = 27). The ONF group showed no increase in AST, ALT, or LDH within 4 weeks after the commencement of steroid therapy. By contrast, the non-ONF group showed an immediate and significant increase in all of these parameters. In the ONF group, hepatic steatosis and elevated triglyceride levels were also observed. Following 4 weeks of steroid therapy, there were no significant differences in biochemical data between two groups. Patients showing no immediate increase in ALT and AST in response to steroid therapy were at high risk of ONF. These findings provide important insights into the pathogenesis of steroid-induced ONF and may facilitate the development of prevention strategies in patients with AID.

The suppression of TRIM21 and the accumulation of IFN-α play crucial roles in the pathogenesis of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH), the pathogenesis of which remains unclear, has been observed in autoimmune disease patients treated with corticosteroids. Recently, it has been shown that anti-tripartite motif-containing 21 (TRIM21) autoantibodies, which are often present in patients with systemic lupus erythematosis and Sjögren's syndrome, inhibit the E3 ligase activity of TRIM21. TRIM21 negatively regulates nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) 3 and 7, three downstream transcription factors, via toll-like receptor 4 signaling. The aim of this study was to clarify the role of TRIM21 in the pathogenesis of ONFH using an animal model. Male Wistar rats were injected with lipopolysaccharide (LPS) twice and with methylprednisolone (MPSL) or saline three times. N-acetyl cysteine (NAC) was administered either concurrently with MPSL or once daily for the 3 days following the last MPSL injection. The incidence of ONFH in the MPSL group was 23.5%. Co-treatment of NAC and MPSL increased the incidence of ONFH to 55.6%. MPSL treatment decreased the activity of NF-κB in the liver and significantly increased the activity of both IRF3 and IRF7. No significant differences were observed in the activity of any of these three transcription factors between the MPSL and the co-treatment groups. In the femoral head, co-treatment with NAC and MPSL significantly decreased the expression of TRIM21 at 3 h and significantly increased the expression of interferon (IFN)-α at 24 h when compared with the MPSL group. IFN-α is known to induce cell death. These findings suggest that the suppression of TRIM21 in the femoral head causes an accumulation of IFN-α, which in turn leads to the development of ONFH. In conclusion, the suppression of TRIM21 resulting from altered NF-κB and IRF homeostasis accelerates the ONFH in rats treated with corticosteroids following LPS administration.

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group.

In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Weight bearing does not contribute to the development of osteonecrosis of the femoral head.

The hip joint is one of the major structures in the human body and the resultant force acting through the hip joint is 300% of body weight. Therefore, weight bearing, as a cause of ischaemia, may contribute to the development of non-traumatic osteonecrosis of the femoral head (ONFH). However, it remains unclear whether weight bearing is related to the development of non-traumatic ONFH. Therefore the aim of this study was to clarify the role of weight bearing in the development of non-traumatic ONFH. Non-weight-bearing (NWB) rats were tail suspended to prevent any weight coming to bear on the hindlimbs from day 1 to the time of sacrifice. The weight-bearing (WB) group rats were also housed individually, although without tail suspension. All rats were injected with lipopolysaccharide and methylprednisolone to promote the development of non-traumatic ONFH. All animals were sacrificed three weeks after the final methylprednisolone injection. Histopathological analysis was performed. Osteonecrosis of the femoral head was observed not only in the NWB but also in the WB rats; however, no osteonecrosis of the humeral head was observed in either group. We confirmed that non-traumatic ONFH developed in NWB rats, suggesting that weight bearing does not contribute to the development of non-traumatic ONFH in rats.

Diagnosis of prosthetic joint infection at the hip using the standard uptake value of three-phase 99mTc-hydroxymethylene diphosphonate SPECT/CT.

PURPOSE: To retrospectively investigate whether the standard uptake value (SUV) of 99mTc-bone single-photon emission computed tomography (SPECT)/CT could be useful for predicting prosthetic joint infection (PJI) at the hip. PATIENTS AND METHODS: We analyzed the cases of 37 patients with a suspected PJI at the hip who underwent 99mTc-bone SPECT/CT and surgical intervention with pathological and bacterial examinations. We divided the cases into those with and those without a causative bacterium detected in a surgical specimen, i.e., the positive bacterial culture (PBC) group (n = 17) and negative bacterial culture (NBC) group (n = 20). Cases with neutrophilic infiltration of surgical specimen comprised the positive neutrophilic infiltration (PINF) group (n = 18) and those without INF comprised the non-neutrophilic infiltration (NINF) group (n = 19). Quantitative analyses were performed using maximum SUVs and peak SUVs of blood-pool (BP) phase images (SUVmaxBP and SUVpeakBP) and late (LT)-phase images (SUVmaxLT and SUVpeakLT). RESULTS: Regarding the bacterial cultures, there were significant differences between the PBC and NBC groups in SUVmaxBP (5.26 ± 1.49 vs. 4.21 ± 1.15, respectively; p = 0.019), SUVpeakBP (4.89 ± 1.32 vs. 3.87 ± 1.06, p = 0.012), SUVmaxLT (16.10 ± 6.36 vs. 11.67 ± 4.95, p = 0.026), and SUVpeakLT (14.58 ± 5.83 vs. 10.49 ± 4.31 p = 0.036). Regarding neutrophilic infiltration, there were significant differences between the PINF and NINF groups in SUVmaxBP (5.18 ± 1.48 vs. 4.24 ± 1.19, p = 0.047) and SUVpeakBP (4.78 ± 1.32 vs. 3.92 ± 1.10, p = 0.043). CONCLUSION: An SUV analysis of 99mTc-bone SPECT/CT is a useful method to differentiate a PJI at the hip from non-infection.