[Show abstract][Hide abstract] ABSTRACT: The secondary use of medical data to improve medical care is gaining much attention. We have analyzed electronic clinical pathways for improving the medical process. The analysis of clinical pathways so far has used statistics analysis models, however as issue remains that the order, and multistory spatial and time relations of the each factor could not be analyzed. We constructed an Outcome tree system that shows the greatest significant relation for each factor. The Hip replacement arthroplasty clinical pathway was analyzed by the system, and the outcome variance of the clinical pathway was visualized. The results indicate the path of patient's who have a long hospitalization stay and extracted four critical indicators.
[Show abstract][Hide abstract] ABSTRACT: In patients with degenerative meniscal tears, subclinical cartilage degeneration may be present even if gross morphological changes are not evident. The aim of this study was to detect occult cartilage degeneration using T1ρ MRI mapping in patients with meniscal tears without obvious radiographic osteoarthritis (OA).
A total of 22 subjects with degenerative meniscal tears in the early stages of osteoarthritis [Kellgren-Lawrence (KL) grade of 0-2] and 19 healthy subjects as the control group were examined. The femoral condyle was divided into four 30° wedges (-30°-0° anteriorly, 0°-30°, 30°-60° and 60°-90° posteriorly), and each area of cartilage was further divided into superficial and deep layers of equal thickness. The tibial side was divided into anterior and posterior areas with superficial and deep layers in each. The mean T1ρ values (ms) in each area were calculated.
On the femoral side, T1ρ values of the superficial and deep regions (-30°-0°, 0°-30° and 30°-60°) in the meniscal tear group were significantly higher than those in the control group [superficial (-30°-0°): 49.0 ± 4.0 (meniscal tear group) vs 45.1 ± 2.1 (control group), deep (-30°-0°): 45.2 ± 3.3 vs 39.5 ± 5.0, superficial (0°-30°): 54.5 ± 5.3 vs 47.4 ± 5.7, deep (0°-30°): 46.8 ± 4.0 vs 40.7 ± 6.3, superficial (30°-60°): 50.5 ± 3.1 vs 47.1 ± 5.7]. On the tibial side, the meniscal tear group had significantly higher T1ρ values superficially in both anterior and posterior regions compared with the control group [superficial (anterior): 52.0 ± 4.3 vs 46.7 ± 5.4, superficial (posterior): 53.1 ± 5.1 vs 46.0 ± 4.9]. Moreover, these significant differences were observed when comparing patients in the meniscal tear group with KL grades of 0 or 1 and the control group.
Our study suggested that early biochemical changes in cartilage associated with degenerative meniscal tears occur first in the superficial zones in areas of contact during slight flexion. Characterising the early relationship between cartilage degeneration and degenerative meniscal tears using T1ρ MRI mapping may be of clinical benefit and provide further evidence linking meniscal injury to OA.
[Show abstract][Hide abstract] ABSTRACT: CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPβ mediates the expression of receptor activator of nuclear factor-kappa-B ligand (RANKL) and drives osteoclast formation in primary fibroblast-like synoviocytes (FLS) from RA patients. The cooperation of C/EBPβ and activation transcription factor-4 (ATF4) in the regulation of the RANKL promoter was also investigated.
Immunofluorescence staining was performed for C/EBPβ, RANKL, and ATF4 in synovium from RA patients. Adenovirus expression vectors for two major isoforms, C/EBPβ-liver-enriched activator protein (LAP) and - liver-enriched inhibitory protein (LIP), or small interfering RNA for C/EBPβ, were used to manipulate C/EBPβ expression in RA-FLS. RA-FLS over-expressing C/EBPβ were co-cultured with peripheral blood mononuclear cells (PBMCs) to test osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. A promoter assay for RANKL, a chromatin immunoprecipitation (ChIP) assay and an immunoprecipitation (IP) assay were also performed.
Immunofluorescence staining showed colocalization of C/EBPβ, ATF4 and RANKL in RA synovium. Western blotting revealed the expression of C/EBPβ-LAP and -LIP in RA-FLS. Over-expression of either C/EBPβ-LAP or -LIP significantly increased the expression of RANKL mRNA, while C/EBPβ-LIP down-regulated osteoprotegerin (OPG) mRNA. The RANKL/OPG mRNA ratio was significantly increased by C/EBPβ-LIP over-expression. Knockdown of C/EBPβ with siRNA decreased the expression of RANKL mRNA. The number of TRAP-positive multinucleated cells was increased in co-cultures of PBMCs and FLS over-expressing either C/EBPβ-LAP or -LIP, but was more significant with LIP. C/EBPβ-LIP does not have a transactivation domain. However, promoter assays showed that C/EBPβ-LIP and ATF4 synergistically transactivate the RANKL promoter. ChIP and IP assays revealed the cooperative binding of C/EBPβ and ATF4 on the RANKL promoter.
We demonstrated that C/EBPβ, especially C/EBPβ-LIP in cooperation with ATF4, is involved in osteoclast formation by regulating RANKL expression in RA-FLS. These findings suggest that C/EBPβ plays a crucial role in bone destruction in RA joints.
[Show abstract][Hide abstract] ABSTRACT: Despite recent advancements in rheumatoid arthritis (RA) pharmacotherapy, surgeons still encounter severely damaged knees. The purpose of the present study was to analyze the mid-term clinical results of total knee arthroplasty (TKA) with metal block augmentation and stem extension.
A total of 26 knees in 21 patients who underwent primary TKA with metal block augmentation and stem extension were retrospectively reviewed. All patients with a mean age of 63 years had RA for a mean duration of 15 years. Functional and radiographic results as well as complications were evaluated at the mean follow-up period of 6 years after TKA. Eight knees were lost follow-up after the two-year evaluation.
Tibial bone defects with average depth of 19 mm were preoperatively recognized in all 26 knees. The postoperative joint line was reconstructed on average 11 mm above the fibular head using average thickness of 11 mm tibial inserts and 9 mm metal blocks with stem extension. Significant improvements (p < 0.05 for all comparisons) were observed postoperatively in maximum extension angle from -10° to -1°, range of motion from 101 ° to 115 °, and Knee Society Score (knee score/function score) from 35/18 to 90/64. Non-progressive radiolucent lines beneath the metal block and osteosclerotic changes around the medullary stem were found in 16 knees (62 %) and 14 knees (54 %), respectively. There was two failures (8 %): fragile supracondylar femur fractures and knee instability. No knees showed any radiographic implant loosening, dislocation, polyethylene insert breakage, peroneal palsy, or infection.
Primary TKA with metal block augmentation and stem extension could effectively restore function in RA patients with advanced forms of knee joint destruction, and be reliable and durable for a mean postoperative period of 6 years. Further study is needed to determine the long-term results of TKA using metal block augmentation and stem extension.
[Show abstract][Hide abstract] ABSTRACT: Background Undifferentiated pleomorphic sarcoma (UPS) is a heterogeneous tumor group, and little is known about molecular target therapy for UPS. Heat shock protein 90 (HSP90) is an expressed chaperone that refolds certain denatured proteins under stress conditions. One of these proteins is Akt. The disruption of Akt signaling plays an important role in tumor progression. The present study’s purpose was to analyze the HSP90 expression, Akt/mTOR pathway activation and the correlation between HSP90 expression and its pathway activation in UPS. Methods The status of HSP90 and the profiles of the Akt/ mTOR pathway were assessed by immunohistochemistry in 79 samples of UPS, and these data were compared with clinicopathological and histopathological findings. The expressions of indicated proteins were assessed by Western blotting in five frozen samples. After treating UPS cells with the HSP90 inhibitor, we assessed the antitumor effect of the inhibitor. Results Immunohistochemically, phosphorylated Akt (p-Akt), p-mTOR, p-S6RP and p-4EBP were positive in 57.3, 51.9, 54.5 and 57.1 % of the UPS samples, respectively. The expressions of those phosphorylated proteins were correlated with each other. HSP90 expression was elevated in 56.4 % of the samples and was correlated with p-Akt, p-mTOR and p-S6RP. The immunohistochemical results were confirmed by Western blotting. The HSP90 inhibitor led to decreased viability and invasiveness of the cells and inactivated the AKT/mTOR pathway in vitro. Conclusion Elevated expression of HSP90 is a poor-prognosis factor and is involved in the activation of the Akt/mTOR pathway in UPS. HSP90 inhibition is a potential treatment option for UPS.
BMC Cancer 12/2015; 15(1). DOI:10.1186/s12885-015-1830-8 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present the case of an 80-year-old man with a tumor recurrence on his right arm 6 years after initial treatment. The lateral aspect of the elbow joint, involving overlaying skin, muscles, tendons, joint capsule, lateral collateral ligament complex, the lateral 1/3 of the capitellum, and lateral epicondyle of humerus were excised in the tumor resection. Intraoperative assessment revealed multidirectional instability of the elbow, and joint stabilization was needed. Because the lateral epicondyle was resected, graft placement in an anatomical position was impossible to carry out. Therefore, non-anatomical reconstruction of lateral ulnar collateral ligament with palmaris longus tendon graft was performed. The skin was reconstructed using an antegrade pedicled radial forearm flap. For wrist extension reconstruction, the pronator quadratus tendon was transferred to the extensor carpi radialis brevis tendon. One year after the operation, elbow range of motion was 5–130°. The patient remains symptom free. The Mayo elbow performance score is good. The Musculoskeletal Tumor Society rating score is excellent. To our knowledge, this is the first report of an elbow lateral ulnar collateral ligament reconstruction after tumor resection.
Strategies in Trauma and Limb Reconstruction 11/2015; DOI:10.1007/s11751-015-0235-1
[Show abstract][Hide abstract] ABSTRACT: Leiomyosarcoma (LMS) of soft tissue is a sarcoma with smooth-muscle differentiation, and conventional chemotherapy does not improve its outcome. The application of novel antitumor agents and precise prognostication has been demanded. The expression of the protein Forkhead box M1 (FOXM1), a member of the FOX family, is considered an independent predictor of poor survival in many cancers and sarcomas. However, the expression status of FOXM1 in LMSs is poorly understood. The purposes of this study were to examine the correlation between the expression of FOXM1 and clinicopathologic or prognostic factors and to clarify the efficacy of FOXM1 target therapy in LMSs. We evaluated the immunohistochemical expressions of FOXM1 using 123 LMS tumor specimens. Univariate and multivariate survival analyses revealed that FOXM1 expression was associated with poor prognosis in LMS. An in vitro study was then conducted to examine the antitumor effect of a FOXM1 inhibitor (thiostrepton) and small interference RNA (siRNA) on a novel LMS cell line, TC616. We also assessed the efficacy of the combined use of doxorubicin and thiostrepton. Thiostrepton showed dose dependent antitumor activity and TC616 treated with the combination of thiostrepton and doxorubicin showed lower proliferation compared to those treated with either drug individually. FOXM1 interruption by siRNA decreased the cell proliferation and increased chemosensitivity. In conclusion, FOXM1 have a potential to be a therapeutic target for LMS. This article is protected by copyright. All rights reserved.
Cancer Science 11/2015; DOI:10.1111/cas.12846 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Corticosteroid-induced osteonecrosis of the femoral head (ONFH) often affects both femoral heads. Such bilateral ONFH cases are generally detected concurrently on magnetic resonance imaging (MRI). On the other hand, in unilateral cases, it is rare that contralateral ONFH is subsequently detected. We herein report a case in which bilateral ONFH was detected in both femoral heads by repeated MRI examination at an interval of 6 weeks.
A 34-year-old man with purpura nephritis was started on corticosteroid therapy with prednisolone at 30 mg/day. Eight months after the initiation of corticosteroid therapy, he complained of left hip pain with no antecedent triggering activity. MRI obtained 8.5 months after the initiation of corticosteroid therapy showed the findings of osteonecrosis of the left femoral head, while no abnormalities were detected in the right femoral head. On the second MRI obtained 10 months after the initiation of corticosteroid treatment, however, osteonecrosis of the right femoral head was newly detected without an increase of the corticosteroid dose.
This case may indicate that corticosteroid-induced bilateral ONFH do not always develop at the same time.
[Show abstract][Hide abstract] ABSTRACT: The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression.
[Show abstract][Hide abstract] ABSTRACT: Study design:
A computed tomography study.
To clarify the position of the aorta relative to the spine in patients with Lenke type 1 adolescent idiopathic scoliosis.
Summary of background data:
Several authors have examined the position of the aorta in patients with scoliosis. However, their analysis included several types of curve. There is a possibility that the position of the aorta differs according to the scoliosis curve type.
Thirty-eight patients with Lenke type 1 were analyzed. The angle (LtP-Ao angle) and distance (LtP-Ao distance) from the insertion point of the left pedicle screw to the aorta were measured from T4 through L2. The measured data were evaluated from four levels above to four levels below the apical vertebra. The difference between lumbar modifiers A and C was examined. Dangerous pedicles, which were defined as those in which the aorta entered the expected area based on the screw direction error and length, were counted from T10 to L2.
The aorta located posterolaterally and adjacent to the vertebra at the middle thoracic level, and anteromedially and distant at the thoracolumbar level. LtP-Ao angle was largest at one level above the apical vertebra, and LtP-Ao distance was shortest at two levels above. LtP-Ao angle of Lenke 1A was significantly larger than 1C from T11 to L2, and LtP-Ao distance of 1A was significantly shorter than 1C from T11 to L1. When the screw length was 40 mm and the direction error was within 10°, there were a large number of dangerous pedicles at T11, regardless of the lumbar modifier.
The direction error has a potential risk of injuring the aorta around the apical vertebra. The selection of screws of the proper length is necessary to avoid a breach of the anterior vertebral wall at thoracolumbar level, especially at T11.
Level of evidence:
[Show abstract][Hide abstract] ABSTRACT: The Akt/mTOR and MAPK pathways play important roles in modulating cellular function in response to extracellular signals, and they are known to be activated in certain kinds of sarcomas. Few investigations have examined these pathways in dedifferentiated liposarcoma (DDLS), in relation to clinicopathological features. Clinicopathological and immunohistochemical analyses were conducted using 99 DDLS specimens. An in vitro study was also conducted to examine the antitumor effects of an mTOR inhibitor and a MEK inhibitor on two DDLS cell lines. The clinicopathological analyses revealed that the AJCC staging was a significant prognostic factor for overall survival and that the tumor size, depth, and location were significant prognostic factors for event-free survival. Phosphorylated Akt (pAkt), pmTOR, pS6RP, p4E-BP1, pMEK, and pERK expressions were positive in 57.4, 52.4, 71.4, 57.1, 84.1, and 50.8 % of the dedifferentiated component of the 63 primary DDLSs. Positive staining for pmTOR was significantly more frequent in the dedifferentiated component than the well-differentiated component. A univariate prognostic analysis revealed that pmTOR expression was associated with poor prognosis in the tumors in the retroperitoneum/ventral body cavity. The mTOR and MEK inhibitors dose-dependently inhibited the cell proliferation of both DDLS cell lines and decreased the expression of downstream pS6RP and pERK, respectively. The combined use of the two inhibitors enhanced antiproliferative activity. In conclusion, the Akt/mTOR and MAPK pathways were activated in DDLS specimens, and the inhibition of these pathways decreased cell proliferation in DDLS cell lines. Our findings suggest that these pathways could be a therapeutic target for patients with DDLS.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
International Orthopaedics 10/2015; DOI:10.1007/s00264-015-3020-3 · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Level of evidence:
Level III, comparative case series.
[Show abstract][Hide abstract] ABSTRACT: Disaster has a negative impact on health conditions, especially on those of temporary housing residents. Health status has a close relationship with physical activity and performance. However, few reports have assessed physical performance among residents living in temporary housing. In this study, we compared physical capabilities between the elderly who evacuated to temporary housing and those who stayed in their own homes after the Great East Japan Earthquake.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The objective of this study was to investigate the common sites of subchondral insufficiency fractures of the femoral head (SIF) based on three-dimensional (3-D) reconstruction of MR images.
Materials and methods:
In 33 hips of 31 consecutive patients diagnosed with SIF, 3-D reconstruction of the bone, fracture, and acetabular edge was performed using MR images. These 3-D images were used to measure the fractured areas and clarify the positional relationship between the fracture and degree of acetabular coverage.
The fractured area in the anterior portion was significantly larger than in the posterior area. In 11 cases, the fractures contacted the acetabular edge and were distributed on the lateral portion. The indices of acetabular coverage (center-edge angle and acetabular head index) in these cases were less than the normal range. In the remaining 22 cases, the fractures were apart from the acetabular edge and distributed on the mediolateral centerline of the femoral head. The majority of these cases had normal acetabular coverage.
The common site of SIF is the anterior portion. In addition, two types of SIF are proposed: (1) Lateral type: the contact stress between the acetabular edge and lateral portion of the femoral head causes SIF based on the insufficient acetabular coverage, and (2) Central type: the contact stress between the acetabular surface and the mediolateral center of the femoral head causes SIF independent from the insufficiency of acetabular coverage. These findings may be useful for considering the treatment and prevention of SIF.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To assess the distributions of stress, strain, and fractured areas using a finite element model (FEM), and examine the osteoclastic activity histopathologically in osteonecrosis of the femoral head.
Three femoral heads were obtained during hip arthroplasty for femoral head osteonecrosis. One sample with a normal area, two samples with a non-sclerotic boundary without collapse (Type 1), two samples with a non-collapsed sclerotic boundary (Type 2), and two samples with a collapsed sclerotic boundary (Type 3) were collected from each femoral head for the FEM and histopathological analyses. FEM was performed using CT data, and the distributions of von Mises equivalent stress, octahedral shear stress, octahedral shear strain, and simulated fractured area were evaluated. Furthermore, the osteoclast count at the boundary was compared for each type.
In normal and Type 1 samples, the distributions of von Mises equivalent stress, octahedral shear stress, octahedral shear strain, and the fractured area were equally concentrated along the whole analytical range; however, in the Type 2 and 3 samples, they were concentrated along the thickened bone trabeculae at the boundary, which corresponded to the fractured area. Histopathologically, a significantly increased osteoclast number was observed only at the collapsed sclerotic boundary.
These results demonstrated that both shear stress and shear strain tend to be concentrated on thickened bone trabeculae at the boundary. Fracture analyses revealed that the boundary of sclerotic changes, which results from the repair process, may be the starting point of the fracture. Additionally, the osteoclastic activity increases after collapse.
Bone 09/2015; 81. DOI:10.1016/j.bone.2015.09.009 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We recently published a paper entitled "Anterior Border of the Tibia as a Landmark for Extramedullary Alignment Guide in Total Knee Arthroplasty for Varus Knees" in J.O.R. (29:919-924, 2011)(1) . The key finding was identifying consistent external bony landmarks that can be used for aligning extramedullary total knee arthroplasty (TKA) instruments with varus knees from an image-based anatomic study. A recent clinical study has also demonstrated the efficacy of the anterior border of the tibia as appropriate landmarks for the placement of extramedullary tibial guides(2) . This article is protected by copyright. All rights reserved.
Journal of Orthopaedic Research 09/2015; DOI:10.1002/jor.23052 · 2.99 Impact Factor