Factors affecting stress shielding and osteolysis after reverse shoulder arthroplasty: A multicenter study in a Japanese population.

BACKGROUND: Stress shielding and osteolysis around the humeral stem after reverse shoulder arthroplasty causes loosening and periprosthetic fractures and reduces bone stock during revision surgery. In Japanese patients, who have relatively small bodies, different characteristics may exist regarding the occurrence of these changes compared with the characteristics of Westerners, who have relatively larger frames. The purpose of this multicenter study was to investigate the incidence and clarify the predictors of stress shielding and osteolysis in Japanese individuals who underwent reverse shoulder arthroplasty. METHODS: The occurrence of stress shielding and osteolysis was investigated in 135 shoulders that had undergone reverse shoulder arthroplasty at least 2 years prior in five Japanese hospitals. During post-surgical follow-up, which was conducted every 3 months, the locations of the stress shielding occurrences, such as cortical thinning and osteopenia (which primarily occurred in zones 1, 2, and 7, where 1 is the greater tuberosity and 7 is the calcar part), spot weld, and condensation lines, were recorded. Cases without any abnormal findings on radiographs obtained up to ≥2 years after surgery were regarded as having no abnormalities. Finally, the predictors of cortical thinning and proximal humeral osteolysis were assessed using univariate and multivariate regression analyses. RESULTS: Cortical thinning and osteopenia occurred in 68 shoulders, a condensation line occurred in 37 shoulders, and spot weld occurred in 23 shoulders. In particular, greater tuberosity and calcar osteolysis occurred in 40 and 47 shoulders, respectively. Long stem, cementless stem, and a larger proximal filling ratio were independent predictors of cortical thinning and osteopenia, whereas a cementless stem, larger metaphysis diameter, and a larger proximal filling ratio were associated with proximal humeral osteolysis. CONCLUSIONS: The predictors of stress shielding and osteolysis included the use of long stems, cementless stems, larger proximal filling ratios, and larger metaphysis diameters. LEVEL OF EVIDENCE: retrospective comparative study (Level III).

Preoperative radiographic features of trochanteric fractures irreducible by closed reduction.

INTRODUCTION: The aim of this study was to clarify the relationship between the preoperative radiographic classification of trochanteric fractures and the success/failure of closed reduction. Identification of irreducible fractures would be important to proceed promptly to direct reduction. PATIENTS AND METHODS: Our retrospective analysis included 141 trochanteric fractures, in 122 women and 17 men, with a mean age of 85.7 years (range, 45-101 years). Evans' classification of trochanteric fractures, as modified by Jensen, and the lateral view classification were used, based on preoperative plain radiographs and computed tomography images. Features predictive of irreducible fractures were identified. RESULTS: Among the 141 fractures, 16 (11.3%) were irreducible by closed reduction. The position of the proximal fragment, relative to the shaft on lateral view, and the fracture pattern of the lesser and greater trochanters were predictive of the feasibility of obtaining a successful closed reduction. These criteria identified success/failure of closed reduction in 99.3% of cases. CONCLUSION: Our findings should be useful for identifying patients in whom closed reduction would be suitable and for avoiding ineffectual manipulation in unsuitable patients.

Clinical application of 3D printing technology to the surgical treatment of atlantoaxial subluxation in small breed dogs.

Atlantoaxial instability (AAI)/subluxation commonly occurs in small breed dogs. Ventral stabilization techniques using screws and/or pins and a plate or, more commonly, polymethylmethacrylate are considered to provide the most favorable outcome. However, the implantation of screws of sufficient sizes for long-term stability becomes challenging in toy breed dogs (e.g. <2 kg). We herein report the application of 3D printing technology to implant trajectory planning and implant designing for the surgical management of AAI in 18 dogs. The use of our patient-specific drill guide templates resulted in overall mean screw corridor deviations of less than 1 mm in the atlas and axis, which contributed to avoiding iatrogenic injury to the surrounding structures. The patient-specific titanium plate was effective for stabilizing the AA joint and provided clinical benefits to 83.3% of cases (15/18). Implant failure requiring revision surgery occurred in only one case, and the cause appeared to be related to the suboptimal screw-plate interface. Although further modifications are needed, our study demonstrated the potential of 3D printing technology to be effectively applied to spinal stabilization surgeries for small breed dogs, allowing for the accurate placement of screws and minimizing peri- and postoperative complications, particularly at anatomical locations at which screw corridors are narrow and technically demanding.

Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation.

OBJECTIVES: MicroRNAs, a class of noncoding RNAs, play roles in human diseases. MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis. The purpose of this study was to analyze the expression pattern of miR-223 in rheumatoid arthritis (RA) synovium and examine the suppression of osteoclastogenesis from human peripheral blood mononuclear cells (PBMC) by overexpression of miR-223. METHODS: Expression of miR-223 in synovium from RA patients was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and section in situ hybridization. MiR-223 was overexpressed in an osteoclastogenesis coculture system with PBMC and RA synovial fibroblast. At 3 weeks after transfection of double-stranded miR-223, the formation of tartrate-resistant acid phosphatase (TRAP)-stained multinucleated cells was analyzed to evaluate the inhibitory effect of miR-223 on osteoclastogenesis. RESULTS: MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium. MiR-223 was expressed in the superficial and sublining layers, and macrophages, monocytes, and CD4 T cells also expressed miR-223. The number of TRAP-positive multinucleated cells was significantly decreased by overexpression of miR-223 in a dose-dependent manner. The expression of osteoclastogenesis marker genes was significantly down-regulated by miR-223 overexpression. CONCLUSION: MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients.

Rotator cuff regeneration using a bioabsorbable material with bone marrow-derived mesenchymal stem cells in a rabbit model.

BACKGROUND: Rotator cuff regeneration using tissue engineering techniques is a challenging treatment in elderly patients with irreparable rotator cuff tears. HYPOTHESIS: A polyglycolic acid sheet scaffold with seeded mesenchymal stem cells (MSCs) may enhance the expression of type I collagen products and increase the mechanical strength of the regenerated tendon in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: A surgically created defect of infraspinatus tendons of rabbits was reconstructed with 2 different materials, a polyglycolic acid (PGA) sheet alone (PGA group) (n = 34) and a PGA sheet seeded with autologously cultured MSCs (MSC group) (n = 34). The authors created a tendon defect model without embedding any graft as the control model (control group) (n = 34). The rabbits were sacrificed at 4, 8, and 16 weeks after the operation and then were histologically evaluated. The rabbits were also biomechanically evaluated by measuring the ultimate failure loads and Young's modulus at 4 and 16 weeks following implantation. RESULTS: In the MSC group, the fibrocartilage layers and Sharpey fibers were found regularly in the insertion site at 8 weeks compared with the PGA group. In control group, thin membranes with many fibroblasts arranged in an irregular pattern linked the end of the torn cuff to the bone without any Sharpey fibers and type I collagen. A large volume of type I collagen was found in comparison with type III collagen at 16 weeks in the MSC group, whereas type III collagen was more prevalent than type I in the PGA group. The tendon maturing score in the MSC group had higher values than the PGA and control groups at 8 and 16 weeks (mean values were 21.0 ± 0.89, 24.0 ± 2.53 in the MSC group; 16.7 ± 2.25, 21.3 ± 2.42 in the PGA group; and 10.2 ± 0.98, 12.2 ± 1.72 in the control group, respectively) (P < .05). The results of the mechanical analysis revealed that the regenerated tendons in the MSC group had better tensile strength than in the PGA and control groups at 16 weeks (mean values were 3.04 ± 0.54 in the MSC group, 2.38 ± 0.63 in the PGA group, and 1.58 ± 0.13 in the control group) (P < .05). CONCLUSION: Bone marrow-derived MSCs were able to regenerate tendon-bone insertions and the tendon belly, including the production of type I collagen, and increased the mechanical strength of the regenerated rotator cuff tendon. CLINICAL RELEVANCE: Rotator cuff regeneration using MSCs is a promising treatment for massive rotator cuff defects.

The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis.

OBJECTIVE: MicroRNA, a class of noncoding RNA, play a role in human diseases. MicroRNA-146a (miR-146a) is a negative regulator of immune and inflammatory responses, and is strongly expressed in rheumatoid arthritis (RA) synovium and peripheral blood mononuclear cells (PBMCs). This study was undertaken to examine whether miR-146a expression inhibits osteoclastogenesis, and whether administration of miR-146a prevents joint destruction in mice with collagen-induced arthritis (CIA). METHODS: PBMCs from healthy volunteers were isolated and seeded in culture plates. The following day, double-stranded miR-146a was transfected and cultured in the presence of macrophage colony-stimulating factor and either tumor necrosis factor α or RANKL. After 3 weeks, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were counted. Three days after miR-146a culture, the expression of c-Jun, nuclear factor of activated T cells c1 (NF-ATc1), PU.1, and TRAP was evaluated by quantitative reverse transcriptase-polymerase chain reaction. After the onset of distinct arthritis in mice with CIA, double-stranded miR-146a or nonspecific double-stranded RNA was administered twice by intravenous injection. Radiographic and histologic examinations were performed at 4 weeks. RESULTS: The number of TRAP-positive multinucleated cells in human PBMCs was significantly reduced by miR-146a in a dose-dependent manner. The expression of c-Jun, NF-ATc1, PU.1, and TRAP in PBMCs was significantly down-regulated by miR-146a. Administration of miR-146a prevented joint destruction in mice with CIA, although it did not completely ameliorate inflammation. CONCLUSION: Our findings indicate that expression of miR-146a inhibits osteoclastogenesis and that administration of double-stranded miR-146a prevents joint destruction in arthritic mice. Administration of miR-146a has potential as a novel therapeutic target for bone destruction in RA.

A mini-review: microRNA in arthritis.

MicroRNA (miRNA) is a class of noncoding RNA that exhibits tissue- or developmental stage-specific expression patterns and negatively regulates gene expression. MiRNAs play an important role in human diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). OA is characterized by the progressive destruction of articular cartilage, and several miRNAs exhibit altered expression, playing a role in regulating gene expression in OA pathogenesis, especially in catabolic factors such as matrix metalloproteinases (MMP) and aggrecanases. RA is an autoimmune disease that is characterized by irreversible joint destruction due to chronic synovial inflammation. MiRNAs play an important role in inflammatory response, synovial cell proliferation, and production of MMPs in RA synovial tissues. The expression level of several miRNAs in peripheral blood mononuclear cells correlates with RA disease activity. Recently, therapeutic trials aimed at targeting miRNA in vivo have been conducted. Targeting miRNA will enable a new advanced strategy toward arthritis treatment.

The effect of an external magnetic force on cell adhesion and proliferation of magnetically labeled mesenchymal stem cells.

BACKGROUND: As the strategy for tissue regeneration using mesenchymal stem cells (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in the target area. To accumulate MSCs effectively, we developed a novel technique for a magnetic targeting system with magnetically labeled MSCs and an external magnetic force. In this study, we examined the effect of an external magnetic force on magnetically labeled MSCs in terms of cell adhesion and proliferation. METHODS: Magnetically labeled MSCs were plated at the bottom of an insert under the influence of an external magnetic force for 1 hour. Then the inserts were turned upside down for between 1 and 24 hours, and the number of MSCs which had fallen from the membrane was counted. The gene expression of MSCs affected magnetic force was analyzed with microarray. In the control group, the same procedure was done without the external magnetic force. RESULTS: At 1 hour after the inserts were turned upside down, the average number of fallen MSCs in the magnetic group was significantly smaller than that in the control group, indicating enhanced cell adhesion. At 24 hours, the average number of fallen MSCs in the magnetic group was also significantly smaller than that in control group. In the magnetic group, integrin alpha2, alpha6, beta3 BP, intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1) were upregulated. At 1, 2 and 3 weeks after incubation, there was no statistical significant difference in the numbers of MSCs in the magnetic group and control group. CONCLUSIONS: The results indicate that an external magnetic force for 1 hour enhances cell adhesion of MSCs. Moreover, there is no difference in cell proliferation after using an external magnetic force on magnetically labeled MSCs.

Induction of apoptosis in the synovium of mice with autoantibody-mediated arthritis by the intraarticular injection of double-stranded MicroRNA-15a.

OBJECTIVE: MicroRNA is a family of noncoding RNAs that exhibit tissue-specific or developmental stage-specific expression patterns and are associated with human diseases. MicroRNA-15a (miR-15a) is reported to induce cell apoptosis by negatively regulating the expression of Bcl-2, which suppresses the apoptotic processes. The purpose of this study was to investigate whether double-stranded miR-15a administered by intraarticular injection could be taken up by cells and could induce Bcl-2 dysfunction and cell apoptosis in the synovium of arthritic mice in vivo. METHODS: Autoantibody-mediated arthritis was induced in male DBA/1J mice. In the experimental group, double-stranded miR-15a labeled with FAM-atelocollagen complex was injected into the knee joint. In the control group, control small interfering RNA-atelocollagen complex was injected into the knee joint. Synovial expression of miR-15a was analyzed by quantitative polymerase chain reaction, FAM by fluorescence microscopy, Bcl-2 by Western blotting, and Bcl-2 and caspase 3 by immunohistochemistry. RESULTS: The expression of miR-15a in the synovium of the experimental group was significantly higher than that in the control group. Green fluorescence emission of FAM was observed in the synovium of the experimental group. Bcl-2 protein was down-regulated and the expression of caspase 3 was increased as compared with that in the control group. CONCLUSION: These results indicate that the induction of cell apoptosis after intraarticular injection of double-stranded miR-15a occurs through inhibition of the translation of Bcl-2 protein in arthritic synovium.

Low-grade myofibroblastic sarcoma of the palm.

We report here a case of an unusual spindle cell tumour of the palm with myofibroblastic differentiation, which was surgically excised. Histologically and immunohistochemically, it was a low-grade myofibroblastic sarcoma. After 25 months follow-up the patient is well and free of recurrence.

Tendon-bone insertion repair and regeneration using polyglycolic acid sheet in the rabbit rotator cuff injury model.

BACKGROUND: The quality of tendons has considerable limitations regarding torn rotator cuff tendons. Tissue-engineering techniques using a biodegradable scaffold offer potential alternatives for recreating a valid tendon-to-bone interface. HYPOTHESIS: A polyglycolic acid (PGA) sheet could facilitate the regeneration of the rotator cuff tendon insertion in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: An implant consisting of a PGA sheet, a rapidly absorbable material, was used to replace a completely resected infra-spinatus tendon insertion in 33 adult Japanese white rabbits. The contralateral infraspinatus tendon was replaced by poly-L-lactate-epsilon-caprolactone (PLC), a slowly absorbable material, by the same methods based on the results of the pilot study. Histological comparisons were made at 4, 8, and 16 weeks, and mechanical evaluations were performed at 4 and 16 weeks in both groups. Unrepaired defects were created in a control group. RESULTS: In the control group, the rotator cuff defects were covered with thin fibrous membranes with many fibroblasts arranged in an irregular pattern. In the PLC group, some chondrocytes were seen in the tendon insertion; however, these were not arranged along the long axis for a 16-week period. In the PGA group, a well-arranged fibrocartilage layer could be found in the regenerated tendon insertions; however, these tendon insertions were mainly regenerated by type III collagen. In mechanical examinations, the PGA group had significantly higher values in the maximum failure load, tensile strength, and Young's modulus for the 4-week and 16-week periods. These 3 categories statistically improved from 4 to 16 weeks postoperatively in both groups except for the Young's modulus in the PGA group (E = 5.66 at 4 weeks to 5.53 at 16 weeks). CONCLUSION: The PGA sheet scaffold material allows for tendon insertion regeneration with a fibrocartilage layer but displays mechanical properties inferior to those of the normal tendon in an animal model. CLINICAL RELEVANCE: The PGA sheet represent a possible alternative scaffold material for tendon regeneration in rotator cuff repair.

Mutism after evacuation of acute subdural hematoma of the posterior fossa.

CASE REPORT: A 7-year-old boy was involved in a road traffic accident. A computed tomography scan revealed an acute subdural hematoma (ASDH) of the posterior fossa, traumatic subarachnoid hemorrhage, and distortion of the brain stem. Removal of the ASDH was completed 3.5 h after injury. After extubation, the patient rapidly recovered consciousness. He was able to follow commands, although he did not speak. He began to utter 14 days after the injury. His speech became normal 39 days after injury. A magnetic resonance imaging scan revealed a post-contusional change in the right cerebellum and an ischemic lesion in the pons. DISCUSSION: Immediate removal of the hematoma is the only therapy for patients with ASDH of the posterior fossa. Although any lesions of the dentate nucleus, red nucleus, thalamus, cerebral cortex, and pons, all of which are involved in this case, are able to cause mutism, his mutism was primarily caused by the severe ASDH of the posterior fossa. The transient nature of this syndrome suggests that the cause of the mutism is trauma-related edema and/or transient ischemia of these structures.

A marked exophthalmos and corneal ulceration caused by delayed massive expansion of a subgaleal hematoma.

CASE REPORT: A 12-year-old girl had the hair on the right side of her head pulled during a quarrel, after which a subgaleal hematoma (SGH) developed over her right cranium. The subcutaneous swelling progressed to the forehead, and a marked exophthalmos then developed on the left side. The bilateral, liquefied SGH was removed surgically, and two drainage catheters connected to a vacuum-drain pump were introduced. After the surgery, the SGH disappeared. The liquefied hematoma was aspirated by puncturing the superolateral portion of the left orbit. Thereafter, the left exophthalmos rapidly disappeared. A chemical analysis of the SGH revealed that it contained extremely low levels of fibrinogen and platelets, and high levels of fibrinogen and fibrin degradation products, suggesting that secondary fibrinolysis had occurred in the subgaleal space. DISCUSSION AND CONCLUSION: Subgaleal hematomas are usually treated conservatively. However, closed observation is necessary, and if increased expansion is seen, aspiration with a closed drainage system should be considered.

Resistance exercise training reduces plasma endothelin-1 concentration in healthy young humans.

Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent vasoconstrictor and proliferative activity in vascular smooth muscle cells, and therefore has been implicated in regulation of vascular tonus and progression of atherosclerosis. We recently demonstrated that the plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans and healthy older humans. However, it is unclear whether the production of ET-1 is altered by resistance exercise training. We measured the plasma ET-1 concentration before and after resistance exercise training in healthy young humans. Six healthy young men (26 +/- 1 years old) performed 8 weeks of resistance exercise training (3 days/week). There were no significant differences in body composition, blood pressure, heart rate, and maximal oxygen consumption before and after resistance exercise training. The girths of the arm and thigh significantly increased after resistance exercise training. The maximal muscle powers in the arm and leg increased after resistance exercise training. After resistance exercise training, the plasma concentration of ET-1 significantly decreased. The present study suggested that resistance exercise training, as well as aerobic exercise training, reduces the plasma ET-1 concentration in healthy young humans, and that this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system.