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Background Lipomatous tumors represent the most common type of soft tissue neoplasms. Mouse double minute 2 homolog (MDM2)/cyclin-dependent kinase 4 (CDK4) immunostaining is considered effective in differentiating between benign lipomas and intermediate malignant atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPSs). However, these tumors have traditionally been diagnosed histopathologically using hematoxylin and eosin-stained specimens, which is referred to here as morphological diagnosis. In this study, the accuracy of morphological diagnoses that had been made before MDM2/CDK4 immunostaining became available for distinguishing between lipoma and ALT/WDLPS was examined. Methods The study participants were 109 patients with a morphological diagnosis of lipoma (68 patients) or ALT/WDLPS (41 patients) who had undergone surgical resection of the tumor in our hospital between 2009 and 2012. Tissue samples from all patients were used for MDM2/CDK4 immunostaining and the confirmation of MDM2/CDK4 amplification by fluorescence in situ hybridization (FISH). Results Of the 41 patients with a morphological diagnosis of ALT/WDLPS, only 17 were positive for MDM2 FISH. In addition, one of the 68 patients with a morphological diagnosis of lipoma showed MDM2 amplification by FISH. When the definitive diagnosis of ALT/WDLPS was made by the positive results of MDM2 FISH, the sensitivity and specificity of morphological diagnosis were 41.5% and 98.5%, respectively. The sensitivity of MDM2 and CDK4 immunostaining was 55.6% and 40.0%, respectively, and their specificity was 87.0% and 84.6%, respectively. This indicates that the diagnostic accuracy of these immunostaining assays was not particularly high. The clinical features suggesting ALT/WDLPS were: patient age (older), maximum tumor diameter (large, cut-off value of 125 mm), tumor location (lower limb), and tumor depth (deep-seated). Conclusions Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS.

IntroductionSecond-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT.Materials and methodsStudy participants were 61 healthy Japanese women (31–70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed.ResultsTrabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength.ConclusionsTrabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

IntroductionRelationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed.Materials and methodsThe subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group.ResultsQUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60 years.QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60 years. No significant correlations were seen between QUS and biochemical markers.ConclusionsModerate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

Biofilms forming on the surface of biomaterials can cause intractable implant-related infections. Bacterial adherence and early biofilm formation are influenced by the type of biomaterial used and the physical characteristics of implant surface. In this in vitro research, we evaluated the ability of Staphylococcus epidermidis, the main pathogen in implant-related infections, to form biofilms on the surface of the solid orthopaedic biomaterials, oxidized zirconium-niobium alloy, cobalt-chromium-molybdenum alloy (Co-Cr-Mo), titanium alloy (Ti-6Al-4V), commercially pure titanium (cp-Ti) and stainless steel. A bacterial suspension of Staphylococcus epidermidis strain RP62A (ATCC35984) was added to the surface of specimens and incubated. The stained biofilms were imaged with a digital optical microscope and the biofilm coverage rate (BCR) was calculated. The total amount of biofilm was determined with the crystal violet assay and the number of viable cells in the biofilm was counted using the plate count method. The BCR of all the biomaterials rose in proportion to culture duration. After culturing for 2-4 hours, the BCR was similar for all materials. However, after culturing for 6 hours, the BCR for Co-Cr-Mo alloy was significantly lower than for Ti-6Al-4V, cp-Ti and stainless steel (P<0.05). The absorbance value determined in the crystal violet assay and the number of viable cells on Co-Cr-Mo were not significantly lower than for the other materials (P>0.05). These results suggest that surface properties, such as hydrophobicity or the low surface free energy of Co-Cr-Mo, may have some influence in inhibiting or delaying the two-dimensional expansion of biofilm on surfaces with a similar degree of smoothness.

PurposeTibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure.Methods11 knees with medial OA and a widened lateral joint were treated by TCVO (KL stage III: 6, IV: 5). In this procedure, by the L-shaped osteotomy from the medial side of the proximal tibia to the intercondylar eminence and the valgus correction, lateralization of the mechanical axis and reduction of the subluxated lateral joint are obtained with early postoperative weight-bearing. Before, 6 months, 1, and 5 years after the operation, a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), alignment of the lower extremity, and congruency and stability of the femorotibial joint were investigated.ResultsThe VAS improved from an average of 73 mm to 13 mm, and the total WOMAC score from 52 to 14 before to 5 years after the operation, respectively. The mechanical axis changed from 1 to 60%, and the FTA changed from 186° to 171°. The joint line convergence angle (JLCA) changed from 6° to 1°, and the angle difference of JLCA between varus and valgus stress improved from 8° to 4° after the procedure.ConclusionImprovements in pain and activities of daily living were observed by TCVO along with valgus correction of the lower extremity and stabilization of the femorotibial joint.

BackgroundKnee osteoarthritis (OA) gradually reduces knee function and limits activities of daily living with age. However, the progression of abnormal kinematics of the knee in knee OA is unclear.AimsThis study aimed to clarify the relationship between stage of knee OA and abnormal knee kinematics and to identify a strategy for prevention of knee OA.MethodsA total of 112 knees of 99 patients (45 men/54 women; 55.9 ± 18.2 years), comprising 28 (27/1) in Kellgren–Lawrence grade 0, 18 (8/10) in grade 1, 27 (2/25) in grade 2, 28 (6/22) in grade 3, and 11 (3/8) in grade 4, were enrolled in this cross-sectional study. In vivo knee kinematics was obtained using a three-dimensional-to-two-dimensional registration technique utilizing CT-based bone models and lateral fluoroscopy during knee extension–flexion in an upright sitting position and squatting.ResultsThe external rotation angle of the tibia relative to the femur was greater in grade 3/4 knees than in grade 0/1 knees and tibial posterior translation was greater in grade 3/4 knees than in grade 0–2 knees.DiscussionAge-related changes in muscle activity and joint instability are considered to be the cause of these abnormal kinematics.ConclusionsAs the stage of knee OA progresses, there was a tendency toward increasing tibial external rotation and tibial posterior translation during knee extension–flexion in sitting position and squatting. Prevention of the progress of the abnormal knee kinematics may prevent the progression of the knee OA.

Primary culture of skeletal muscle stem cells (MuSCs) is indispensable to study the dynamics of muscle regeneration and homeostasis. Here we describe the modified pre-plating method for isolating MuSCs in culture with greatly improved purity, yield, and procedure time. The protocol is based on the distinct adhesion characteristics of MuSCs. We reduced the procedure time to 2.5 days to obtain highly purified MuSCs through a newly employed re-plating step, which repeats incubation and cell-suspension. The re-plating step efficiently traps remaining fibroblastic cells, but not MuSCs, on a collagen-coated dish. Additionally, we confirmed that MuSCs can be isolated from small amounts of human/mouse muscle tissues, enabling us to perform experiments with amount-limited specimens. Thus, our method can be performed with basic laboratory equipment suitable for most facilities and without sophisticated MuSC handling techniques.

Background This study aimed to compare radiological features and short-term clinical outcomes between open-wedge high tibial osteotomy (OWHTO) and tibial condylar valgus osteotomy (TCVO), to provide information facilitating decision-making regarding those two procedures. Methods Twenty-seven cases involving 30 knees that had undergone OWHTO (HTO group) and eighteen cases involving 19 knees that had undergone TCVO (TCVO group) for medial compartment knee osteoarthritis (OA) were retrospectively evaluated. Patient characteristics, severity of knee OA, lower limb alignment, joint congruity and instability were measured from standing full-length leg and knee radiographs obtained before and 1 year after surgery. Range of motion in the knee joint was measured and Knee Injury and Osteoarthritis Outcome Score (KOOS) was obtained to evaluate clinical results preoperatively and 1 year postoperatively. Results Mean age was significantly higher in the TCVO group than in the HTO group. Radiological features in the TCVO group included greater frequencies of advanced knee OA, varus lower limb malalignment, higher joint line convergence angle, and varus-valgus joint instability compared to the HTO group before surgery. However, alignment of the lower limb and joint instability improved to comparable levels after surgery in both groups. Maximum flexion angles were significantly lower in the TCVO group than in the HTO group both pre- and postoperatively. Mean values in all KOOS subscales recovered similarly after surgery in both groups, although postoperative scores on three subscales (Symptom, Pain, and ADL) were lower in the TCVO group (Symptom: HTO, 79.0; TCVO, 67.5; Pain: HTO, 80.5; TCVO, 71.1; ADL: HTO, 86.9; TCVO, 78.0). Conclusions Both osteotomy procedures improved short-term clinical outcomes postoperatively. TCVO appears preferable in cases of advanced knee OA with incongruity and high varus-valgus joint instability. An appropriate choice of osteotomy procedure is important to obtain favorable clinical outcomes.

The purpose of this study was to establish an algorithm for measuring bone erosions at metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), to investigate the precision of measurements, and to assess longitudinal changes in bone erosions among patients with rheumatoid arthritis (RA). The 2nd and 3rd MCP joints were scanned at a voxel size of 60.7 μm using second-generation HR-pQCT. Bone erosions on MCP joints were identified using a semi-automated algorithm we developed, and each erosion parameter was measured. Measurement reproducibility was evaluated in 19 healthy subjects using intraclass correlation coefficients (ICCs) and root mean square percent coefficient of variance (RMS%CV). Finally, longitudinal changes in bone erosions over a period of 12 months were assessed in 26 patients with RA based on the calculated least significant change (LSC). Reproducibilities for measurement parameters regarding bone erosions with our algorithm were good (all ICCs ≥ 0.98; all RMS%CVs < 5%). No erosion parameters showed significant changes after 12 months of treatment in terms of median values in all erosions, while both progression and repair of erosions were observed individually (e.g., erosion volume: progression, 26% (+0.62 mm3); repair, 34% (-0.85 mm3); no change, 40%). The measurement algorithm developed for bone erosions at MCP joints showed good reproducibility. Both progression and repair of bone erosions were observed in patients with RA even after 12 months of appropriate treatment. Our algorithm may be useful to investigate the etiology of RA and assess drug efficacy.

Purpose To describe the indications for, and surgical technique of, tibial condylar valgus osteotomy (TCVO). Indications TCVO is commonly performed in patients with middle-to-end-stage medial unicompartmental osteoarthritis. Among the most important TCVO indication criteria are the types of tibial plateau shape. The convex-type (also called “pagoda-type”), with over a 5° joint line convergence angle on the standing X-ray, meets the indication criteria for TCVO. Surgical technique An L-shaped osteotomy is performed from the medial side of the proximal tibia to the lateral beak of the intercondylar eminence. The apex of the L-shaped osteotomy line is on the medial border of the patellar tendon insertion. Surgeons should note the direction of the chisel (during the osteotomy) to the intercondylar eminence following fluoroscopic guidance. The posterior cortical bone is cut under a lateral view observation, and the crossed-leg position is adopted to prevent injury to the popliteal blood vessels. The spreader should be positioned at the posterior cortical bone to avoid increasing the tibial slope. The locking plate reliably stabilizes the osteotomy and helps shorten the period of postoperative rehabilitation. Conclusions TCVO adjusts varus deformity alongside joint congruity. Accurate identification of indications and a detailed surgical plan would ensure effective correction and proper alignment. Additional osteotomies are recommended in case of under-correction of the varus limb deformity. TCVO is an effective intervention in patients with advanced knee osteoarthritis and lateral joint laxity with the pagoda-type tibial plateau shape.