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In recent years, advances in pharmacotherapy for rheumatoid arthritis (RA) have dramatically improved the control of disease activity. However, a significant number of patients still develop forefoot deformity. The purpose of this study was to investigate the results of more than 20 years' follow-up of metatarsal neck shortening oblique osteotomy (SOO) for forefoot deformity in patients with RA.The metatarsal neck SOO was performed on 163 feet in 108 patients between January 1985 and December 1996 in the authors' hospital. For the patients, who met the survey criteria, an observational study was performed clinically and radiologically at the baseline and at more than 20 years after surgery.A retrospective cohort study was conducted on 36 feet in 22 patients, all of whom were female, and the mean age at surgery was 45.6 (35.0-63.0) years old. The follow-up period was 25.1 (21.0-31.0) years. The presence of painful callosities in the surgically treated feet without revised surgeries decreased from 32 feet (100%) to 4 feet (12.5%) at the last follow-up with mild pain that did not cause any footwear problems. Re-osteotomy at the metatarsal of the lessor toe was performed on four feet in two patients. Radiologically, among 128 toes without revised surgeries, 85% were able to have the joint space preserved, and 89% maintained a pain-free condition without any recurrence of deformity. The mean total Japanese Society for Surgery for the Foot (JSSF) RA foot and ankle score was 64.0/100, and the visual analogue scale (VAS) of overall satisfaction was 62 (0: dissatisfied, 100: highly satisfied). The overall satisfaction had a positive correlation with calcaneal pitch and negative correlation with joint space narrowing at the talocrural joint.Metatarsal neck SOO appeared to be effective for patients with RA. The deformity was corrected and retained for a long time.

Background This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). Methods Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. Results Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80–8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3–4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. Conclusions Although GD had relatively mild toxicity, the regimen—as administered in this study—should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. Clinical trial registration jRCTs031180003.

Contact infection is a common route of respiratory infections, including that caused by severe acute respiratory syndrome coronavirus 2. Monitoring of viral contamination of environmental surfaces is critical for implementing appropriate hygiene measures and reducing the risk of viral transmission. We assessed the novel utility of the salivary amylase test on environmental surfaces for monitoring the viral contamination risk. An assay based on the principle of immunochromatography was used to detect amylase. Contamination of plastic substrates with amylase and viral genes over time showed similar patterns under laboratory conditions. Moreover, amylase was detected on the surfaces surrounding individuals who performed behaviors (e.g., coughing and sneezing) that spread droplets. Accordingly, detection of amylase might indicate the presence of viral genes in cases where droplets from infected individuals were retained on surfaces. Environmental surfaces (n = 186) located in public facilities were investigated and amylase was highly detected in the food courts (66.7−75.0%) and washbasins of hotel guest rooms (100%). However, no correlation was observed between the adenosine triphosphate level (a marker of hygiene control) and the sites positive for amylase. Our research provide a method revealing sites of viral contamination and lead to the establishment of an appropriate infection control system.

Background/aim Advanced undifferentiated pleomorphic sarcoma (UPS) has a poor prognosis and there are few treatments that can improve overall survival. Recently, Rapalink-1, a third-generation mammalian target of rapamycin (mTOR) kinase inhibitor, has been developed and shown to be effective against other tumours. However, mTOR inhibitors have been shown to induce autophagy and resistance to anti-cancer drugs. This study aimed to investigate the antitumor effects of Rapalink-1 with an autophagy inhibitor. Materials and methods The antitumor effect of Rapalink-1 and/or hydroxychloroquine in three UPS cell lines was examined via cell viability analysis, western blotting, flow cytometry and immunofluorescence. Results Rapalink-1 decreased cell proliferation and inhibited the PI3K/mTOR pathway. Combined treatment with Rapalink-1 and hydroxychloroquine enhanced the antitumor effect compared to treatment with Rapalink-1 alone by blocking the autophagy-inducing effect of mTOR inhibitors. Conclusion Combined treatment with Rapalink-1 and hydroxychloroquine may be used as a potential therapeutic agent against UPS.

Background: Total hip arthroplasty after osteotomy is more technically challenging than primary total hip arthroplasty, especially with regards to cup placement. This is due to bone morphological abnormalities caused by acetabular bone loss and osteophyte formation. This study aimed to investigate the clinical and radiological outcomes of total hip arthroplasty after rotational acetabular osteotomy compared with primary total hip arthroplasty, focusing mainly on acetabular deformity and cup position. Methods: The study included 22 hips that had undergone rotational acetabular osteotomy and 22 hips in an age and sex-matched control group in total hip arthroplasties performed between 2005 and 2020. We analyzed cup abduction and anteversion angle, lateral, anterior, and posterior cup center-edge angle, hip joint center position, femoral anteversion angle, and presence of acetabular defect using postoperative radiography and computed tomography. Operative results and clinical evaluations were also analyzed.Results: The clinical evaluation showed that the postoperative range of motion was lower in total hip arthroplasty after rotational acetabular osteotomy than in primary total hip arthroplasty. The lateral cup center-edge angle was significantly higher and the posterior cup center-edge angle was significantly lower in the total hip arthroplasty after rotational acetabular osteotomy, suggesting a posterior bone defect existed in the acetablum. In total hip arthroplasty after rotational acetabular osteotomy, the hip joint center was located significantly superior and lateral to the primary total hip arthroplasty.Conclusions: In total hip arthroplasty after rotational acetabular osteotomy, the cup tended to be placed in the superior and lateral positions, where there was more bone volume. The deformity of the acetabulum and the high hip center should be considered for treatment success because they may cause cup instability, limited range of motion, and impingement.

Objective We aimed to identify the risk factors and clinical outcomes for post-laminectomy fracture around the isthmus, which can cause back pain or radiculopathy. Methods We performed a retrospective cohort study involving all patients who underwent laminectomy splitting the spinous process for lumbar spinal stenosis between 2010 and 2014. The primary outcome measure was post-laminectomy fracture around the isthmus. Clinical outcomes were evaluated based on reoperation rate. To evaluate risk factors for fracture, the following parameters were collected: (1) patient characteristics and concomitant diabetes mellitus, (2) lumbar scoliosis and sagittal alignment parameters, and (3) surgical data, such as rate of total laminectomy. Logistic regression analysis was performed to identify the independent risk factors for post-laminectomy fracture. Results Twelve of the 92 patients suffered a post-laminectomy fracture around the isthmus. Logistic regression analysis revealed that diabetes mellitus (odds ratio [OR]: 15.41; 95% confidence interval [CI]: 2.93–80.98; P = 0.001), L4 total laminectomy (OR: 14.68; 95% CI: 1.51–142.76; P = 0.021), and lumbar scoliosis (OR: 5.72; 95% CI: 1.16–28.21; P = 0.032) were independent risk factors. The fracture group included 2 patients (16.7%) who required reoperation at the decompression level for recurrent leg pain, whereas the non-fracture group included 2 (2.5%) who underwent reoperation at a level different from the index procedure. Conclusions Post-laminectomy fractures around the isthmus were significantly associated with scoliosis, diabetes mellitus, and total laminectomy at L4. Total laminectomy at L4 is best avoided to reduce the risk of post-laminectomy fracture in patients with scoliosis or diabetes mellitus.

Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

Background The Masquelet method has become increasingly popular for the treatment of bone defects in recent years. In this method, an induced membrane (IM) with abundant blood circulation, stem cells, and osteogenesis-promoting factors is formed by implanting bone cement during the first surgery. This IM stimulates bone formation in the bone defect after implantation of the bone graft during the second surgery. However, the Masquelet method requires two surgeries and thus a longer treatment period. In the present study, we investigated whether bone defects could be reconstructed in a single surgery by introducing a vascular bundle into the bone defect as an alternative to the IM, in addition to bone grafting. Methods Thirty-six 12-week-old female Sprague-Dawley rats were used. After creating a 5-mm long bone defect in the femur, a mixture of autologous and artificial bone was grafted into the defect, and a saphenous arteriovenous vascular bundle was introduced. The animals were divided into three groups: the control group (bone defect only), the BG group (bone grafting only), and the BG + V group (bone grafting + vascular bundle introduction). After surgery, radiological and histological evaluations were performed to assess osteogenesis and angiogenesis in bone defects. Results In the BG + V group, significant bone formation was observed in the bone defect on radiological and histological evaluations, and the amount of bone formation was significantly higher than that in the other two groups. Furthermore, cortical bone continuity was observed in many specimens in the BG + V group. On histological evaluation, the number of blood vessels was also significantly higher in the BG + V group than in the other two groups. Conclusion Our results suggest that the introduction of a vascular bundle in addition to bone grafting can promote bone formation in bone defects and allow for complete bone defect reconstruction in a single surgery.

Background: Two-stage revision surgery using antibiotic-loaded acryl bone cement (ALAC) is an effective treatment for periprosthetic joint infection (PJI) after hip arthroplasty. However, ALAC has been reported to release different amounts of antibacterial agents, depending on the type of bone cement used. No previous study has examined patient outcomes based on the polymerization temperature of the bone cement used. This study aimed to compare the outcomes of patients who underwent a two-stage revision surgery using ALAC for PJI, stratified by the polymerization temperature of the bone cement used.Methods: This study involved 23 joints in 23 patients treated with ALAC between 1993 and 2019. They were classified into normal (control group, n=12) and low polymerization temperature (L group, n=11) groups, respectively. Patient outcomes were compared between the groups.Results: In both groups, the infection subsiding rate was 100%. The success rate of revision surgery at the 2-year follow-up was 82.6%. There was no difference between the groups in mean age, time to infection onset, patient general condition, presence of fistulas, or methicillin-resistant Staphylococcus aureus infection. However, the infection required less time to subside, and fewer beads or spacers were used in the L group than in the control group. The success rate of revision surgery was 66.7% and 100% in the control and L groups, respectively.Conclusions: In the present study, two-stage revision surgery with ALAC in PJI was associated with a shorter infection subsidence period and fewer surgeries in the group treated with bone cement of low polymerization temperature than in the control group. The use of bone cement of low polymerization temperature in ALAC is an effective treatment option for PJI.

The use of volar locking plates (VLPs) for distal radius fractures has remarkably improved clinical outcomes; however, there are some reports of delayed recovery of grip strength. Since January 2019, we have been conducting an early and proactive grip strength training program (EGTP). In this program, 20 minutes of grip strength training-using a gripper with a load of 0.7 kg-was initiated from 2 weeks after surgery; the load was then gradually increased. From 6 weeks postsurgery, daily home grip strength training was performed using a gripper with a load of 5 kg, provided to the patient.We investigated whether the introduction of the EGTP could lead to earlier recovery of grip strength. We also examined whether the EGTP caused postoperative correction loss at the fractured site, or contributed to the early improvement of wrist function.Thirty-nine patients who underwent surgery using VLPs for distal radius fractures were included in this study; 20 followed the EGTP (EGTP group) and 19 patients did not (NGTP group). For these patients, grip strength and range of motion of the wrist joint were evaluated both 3 and 6 months postoperatively. The Quick Disabilities of the Arm, Shoulder, and Hand (qDASH) scores were also evaluated 6 months postoperatively. Additionally, corrective losses of radial inclination (RI), palmar tilt (PT), and ulnar variance (UV)-occurring from immediately postsurgery to 6 months after surgery-were evaluated.At both 3 and 6 months postoperatively, the grip strength of the EGTP group was significantly higher than that of the NGTP group. Regarding range of motion, only palmar flexion was significantly improved in the EGTP group at 3 months postoperatively. Conversely, no differences in corrective losses of RI, PT, and UV, or in qDASH scores, were observed between the two groups.The results of this study suggest that the EGTP can provide early recovery of grip strength and palmar flexion of the wrist without causing corrective loss at the fracture site.

Background : Fitting a femoral prosthesis in a transfemoral amputee with a very short amputation stump is challenging. This case report aimed to introduce an effective and simple method that can preserve the residual limb length by the implantation of antibiotic-loaded bone cement for the treatment of a patient with femoral periprosthetic infection Case : A 30-year-old man who had osteosarcoma at the age of 13 years underwent transfemoral amputation 17 years after the initial surgery because of periprosthetic infection. Antibiotic-loaded bone cement was inserted into the infected bone marrow to control the residual infection and to preserve the stump length. The infection resolved, and the patient regained functional gait using a femoral prosthesis. Discussion : This case report demonstrates the usefulness of antibiotic-loaded cement in preserving the length of residual limbs and for femoral prosthesis fitting after periprosthetic infection. Maintaining the residual bone length is crucial in amputees for the functional fitting of femoral prostheses. The use of antibiotic-loaded bone cement has potential as a simple and useful surgical option in amputees after periprosthetic infection.

Background Spontaneous spinal epidural hematoma (SSEH) is a spinal emergency that requires early diagnosis and decompression surgery. Here, we report a case of SSEH that was difficult to differentiate from pigmented villonodular synovitis (PVS) because of combined facet joint destruction and that required gross total resection, a procedure not typically indicated for SSEH. Case Description A 58-year-old woman complained of sudden-onset walk disturbance after backache without any traumatic episode. Physical examination revealed motor paralysis in the leg. Moreover, extensive destruction of the L4/5 right facet joint and an epidural mass continuing from the facet was observed. The epidural mass showed heterogeneous intensity in magnetic resonance imaging, suggesting different stages of bleeding. These hemorrhagic changes combined with the facet joint destruction suggested PVS, and preoperative and intraoperative pathologic examinations could not rule out PVS. After surgical treatment of PVS, the lesion in the articular process was resected and decompression was performed. The pathologic diagnosis was hematoma with bone necrosis in the articular process, without neoplastic finding suggesting PVS. Conclusions SSEH could be combined with facet joint destruction composed of bone necrosis. Awareness of SSEH with facet joint destruction can facilitate early diagnosis and appropriate surgical treatment.

Subchondral insufficiency fractures of the femoral head are generally considered to be osteoporosis-related fragility fractures. There have been reports of microfractures being found in subchondral bone on pathological examination. However, the mechanism of these microfractures is not known. In this report, we describe a patient with osteogenesis imperfecta who developed a subchondral insufficiency fracture of the femoral head after a fall that had resulted in a subcapital femoral neck fracture. Bipolar hemiarthroplasty was performed, and bone at the femoral head and neck was sampled for pathophysiological examination. Hematoxylin and eosin staining revealed microfractures and microcallus in the subchondral bone in the femoral head, indicating healing of a subchondral insufficiency fracture before the subcapital femoral neck fracture. Moreover, decreased bone volume and accumulated microdamage were observed in the subchondral bone but not in the cancellous bone in the femoral neck. These findings suggest that subchondral insufficiency fracture of the femoral head is a stress fracture caused by accumulation of microdamage in fragile subchondral bone.

Weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. However, the effect of weekly teriparatide on cortical bone has not been clarified. This study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. Female monkeys, aged 9 to 15 years, were divided into four groups: (1) SHAM group, (2) ovariectomized group (OVX group), (3) OVX with 1.2 μg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 μg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein, and lumbar vertebrae were analyzed with histomorphometry and compressive mechanical tests. Following ovariectomy, we found reductions in the anterior cortical shell area of the vertebrae and reductions in nearly all of the tested vertebral mechanical properties. Weekly teriparatide significantly preserved the anterior cortical shell area and the energy absorption capacity of the lumbar vertebrae in a dose-dependent manner. Multiple regression analyses indicated that improved mechanical properties were more associated with the increased anterior cortical shell area rather than the cancellous bone volume. The intracortical structure of the Haversian canals was also preserved following teriparatide treatment after ovariectomy. These findings suggest the importance of the cortical shell as a therapeutic target in the treatment of osteoporosis. Weekly teriparatide treatment increases the compressive mechanical strength of the lumbar vertebrae by thickening the anterior cortical shell.

Background/aim We previously showed that the use of autophagy inhibitors in combination with chemotherapy can enhance anticancer effects in sarcoma cell lines. In this study, we investigated the combined effect of the autophagy inhibitor chloroquine and the mTOR inhibitor rapamycin on MG63 osteosarcoma cells. Materials and methods Effects of chloroquine and/or rapamycin on cell proliferation were assessed by WST-1 assays. Effects of chloroquine and/or rapamycin on the mTOR pathway components, autophagy, and apoptosis were investigated by western blot, flow cytometry, and fluorescence microscopy using immunocytochemical staining of LC3 and Annexin V-FITC/propidium iodide. Results Rapamycin suppressed cell growth and inhibited the mTOR pathway. Rapamycin promoted autophagy by blocking the mTOR pathway, and chloroquine enhanced apoptosis by blocking autophagy. Conclusion Chloroquine enhances the effects of rapamycin in inducing apoptosis via autophagy inhibition in MG63 cells. Thus, the combined therapy of chloroquine and rapamycin may be a potent treatment for osteosarcoma.

Highlights • Intra-nodular fasciitis is very rare and there are only two reported cases of intra-articular nodular fasciitis in the elbow joint. • It is difficult to diagnose preoperatively, so a clear diagnosis can be obtained only after excisional biopsy. • As local recurrence has not occurred in previously reported cases, we think that arthroscopic resection is suitable for treatment of this disease., Introduction Nodular fasciitis is a benign myofibroblastic proliferation arising from the fascia. Until now, there have been only two reported cases of intra-articular nodular fasciitis in the elbow joint. Presentation of case We report a case of a 19-year-old woman with a 3-month history of pain in the left elbow. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) showed an intra-articular lobulated mass on the anterior portion of the elbow joint, with accompanying effusion. The patient subsequently underwent arthroscopic excision of the mass. Histologically, intra-articular nodular fasciitis was the final diagnosis. At the most recent follow-up, 20 months after surgery, the patient had no subjective symptoms, including pain. The final MRI findings showed no tumor recurrence. Discussion As nodular fasciitis is not generally known to arise within a joint, the occurrence at such anatomical locations may lead to a misdiagnosis. Intra-articular nodular fasciitis is rarely encountered, and therefore, is not usually considered during the clinical investigation of joint symptoms. Conclusion Preoperative diagnosis was difficult in this case because of nonspecific preoperative clinical findings. Although histological examination is necessary to establish a diagnosis, we recommend that intra-articular nodular fasciitis should be included in the differential diagnosis of intra-articular mass lesions.

In the surgical management of Dupuytren contracture (DC), Y-V plasty (YV) and Z-plasty (ZP) are techniques often used for skin extension. However, achieving sufficient skin extension with these procedures alone is often difficult. Therefore, we addressed this issue with an adjunctive digito-lateral flap (DLF) and report the clinical results of the surgery using a DLF in addition to YV and ZP. Fifteen patients with DC (15 affected fingers) underwent partial fasciectomy using a DLF in addition to YV or ZP, and early active finger extension training was performed immediately after the operation. The flap survival rate, preoperative and postoperative extension angle, Tonkin contracture improvement (TCI) rate, and Tubiana staging grades were evaluated. The contracture sites were at 4 proximal interphalangeal (PIP) and 3 metacarpophalangeal (MP) joints of the little finger and 4 PIP and MP joints each of the ring and little fingers. All the flaps survived, and the extension angle improved at the final observation from a preoperative mean of -45° to -3° and -55° to 5° for the PIP and MP joints, respectively. One patient with PIP joint contracture treated in the early stage of the study experienced a persistent 5° limitation of extension, even though the TCI rate was satisfactory (91.9%) and the outcome was "good." Full extension of the joints was achieved in 15 patients, in whom the TCI rate was 100% and the outcome was "very good." This technique was able to solve 3 important steps to achieve full extension: intraoperatively, wound closure, and rehabilitation. We attained and maintained long-term full extension intraoperatively and immediately after surgery and obtained very good treatment results, as shown in this study. In conclusion, highly favorable clinical outcomes were achieved through the combination of a DLF with YV and ZP. Skin extension with a DLF is a useful surgical technique for DC.

Background Massive bone defects after wide resection of malignant bone tumors or a serious injury require treatment using vascularized bone grafts. Although cadaveric bone allografts combined with vascularized bone autografts are currently thought to be ideal in terms of size and durability, this treatment requires the scarification of healthy bone tissue. In a previous study, we attempted to improve this situation by prefabricating a vascularized bone allograft in recipient rats. In this study, we added vascular endothelial growth factor (VEGF)-containing hydroxyapatite/collagen composite (HAp/Col) to a prefabricated vascularized bone allograft to stimulate angiogenesis, which is known to be important for bone formation. Materials and Methods Sprague Dawley rats (n = 50) were used as donors and Wistar rats (n = 50) as recipients. All rats were 9 weeks old. The recipient rats were divided into five groups according to the use of vascular bundles, HAp/Col, and an additive substance (VEGF). The bone allografts collected from the donors were transplanted into the thigh region of the recipients, and a saphenous vein and 10 μg HAp/Col with VEGF were inserted into the bone allografts through the slit. After 4 weeks, the transplanted bone allografts were harvested, and histologic and genetic evaluations were performed in relation to bone formation and resorption. Results The results showed that, compared with the control group, the implantation of the vascular bundles and VEGF-containing HAp/Col significantly stimulated angiogenesis and bone formation in the rats with the bone allografts. However, histological and genetic evaluations of bone resorption revealed that resorption was not observed in any group. Conclusion These results suggest that VEGF-containing HAp/Col effectively stimulates angiogenesis and bone formation, but not bone resorption, in prefabricated vascularized bone allografts. This method could therefore become a useful tool for treating large bone defects.

Introduction: Sneathia sanguinegens(S sanguinegens) is a gram-negative rod-shaped bacterium mostly reported to cause a perinatal infection, and there are no reports of S sanguinegens in prosthetic joint infection (PJI). The purpose of this report is to describe a very rare case of PJI after total hip arthroplasty (THA) caused by S sanguinegens. Patient concerns: A 79-year-old woman presented with right coxalgia, inability to walk, and a fever of 39°C. She had undergone THA 28 years earlier for osteoarthritis of the hip. Diagnoses: The diagnosis was acute late-onset PJI, because blood tests revealed marked inflammatory reaction and computed tomography showed an abscess at the right hip joint; synovial fluid analysis resulted in detection of a gram-negative bacillus. Intervention: Surgical debridement with retention of the implant and antibiotic therapy was performed. Outcomes: One month after surgery, polymerase chain reaction (PCR) assay showed that the pathogen was 99.9% likely to be S sanguinegens. There has been no recurrence of infection or loosening of the implant in the 2 years since her surgery. Lessons: PCR should facilitate detection of previously unknown pathogens and potentially novel bacterial species.

Background We have developed a prefabricated vascularized allo-bone graft (PVAG) by implanting the saphenous vascular bundles of recipient rats into transplanted donor bones in a flow-through manner. We previously demonstrated that the angiogenetic and bone formative abilities of the PVAG are stimulated by the addition of a basic fibroblast growth factor (bFGF)-containing hydroxyapatite/collagen (HAp/Col). This study aimed to demonstrate that the bone union ability of the PVAG is similarly stimulated by the bFGF-containing HAp/Col composite. Methods Sprague-Dawley donor rats (n = 32) and Wistar recipient rats (n = 32) were used in this study. The PVAG was fixed to the femur of the recipient rat using K-wire (dimeter: 0.7 mm) pinning, followed by suturing with a 4–0 nylon suture. Recipients were divided into four groups: with or without vascular bundles, and with or without bFGF-containing HAp/Col. Rats were sacrificed 6 weeks after transplantation, and bone union, bone resorption, and angiogenesis were radiologically and histologically evaluated. Results Radiological analysis revealed a significant increase in callus formation and union rate, while histological analysis showed a significant increase in bone formation and angiogenesis in the group treated with both vascular bundles and bFGF. Bone resorption did not significantly increase in any of the evaluated groups. Conclusion Osteogenic cells, osteoconductive scaffolds, growth factors, and mechanical environment are known to be important factors in the process of fracture healing. The PVAG developed herein contains osteogenic cells, osteoconductive scaffolds, and growth factors. In addition, the PVAG is rigidly fixed to the fracture site, providing a stable mechanical environment. Together, these four factors contributed to a good bone union. Furthermore, this method did not promote bone resorption. Thus, the addition of a vascular bundle and bFGF-containing HAp/Col makes it possible to create an ideal vascularized allo-bone graft for the reconstruction of massive bone defects.

The effect of teriparatide treatment on microdamage accumulation has yet to be examined in animal studies. The purpose of this study was to investigate the effect of once-weekly teriparatide treatment on bone microdamage accumulation and the relationship between microdamage parameters and bone mass, architecture, turnover, and collagen cross-linking in the lumbar vertebral trabecular bone of ovariectomized (OVX) cynomolgus monkeys. Female monkeys were divided into four groups (n = 18-20 per group): (1) SHAM group, (2) OVX group, (3) OVX with 1.2 µg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 µg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein for histomorphometry. L3 and L7 lumbar vertebrae were harvested and analyzed for differences in histomorphometry, microdamage, and collagen cross-linking. The iliac crest was also analyzed for differences in bone turnover. In the OVX group, cancellous bone mass was reduced and microdamage accumulation was increased as compared with the SHAM control. Once-weekly teriparatide at both doses prevented the decrease in bone mass and increase in microdamage accumulation, and improved the distribution of collagen cross-linkage types. Regression analyses indicated that decreased microdamage accumulation was associated with reduced non-enzymatic cross-link pentosidine rather than increased cancellous bone mass or enzymatic cross-links. These findings suggest that once-weekly teriparatide treatment decreases microdamage accumulation by recovering the balance in collagen cross-links.

To investigate the correlation between mineral formation and enhanced expressions of some proteins using undecalcified frozen bone sections. Histological studies have revealed that some proteins, such as BMP2, BMPR1A, and Connexin 43, are expressed in and around sites of ectopic ossification. However, the relationship between the expressed proteins considered to be associated with the ossification and mineral formation in vivo is not clear. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1)-mutant spinal hyperostotic TWY mice and ICR mice as controls were euthanized after calcein labeling, and undecalcified frozen sections were obtained from the middle thoracic spine. Intervertebral disc areas were examined histologically and by measuring calcein-labeled areas and areas showing immunoreactivity for BMP2, BMPR1A, and Connexin 43. Calcein-labeled areas, indicating mineralization in the ectopic mineralization sites, were significantly larger in the mutant mice than in controls. The expression of Connexin 43 was elevated in the annulus fibrosus. Increases in the calcein-labeled areas was not correlated with increases in the areas showing immunoreactivity for Connexin 43 in the annulus fibrosus. There was no statistical correlation between enhanced immunohistochemical expression and elevated calcein-labeled areas. By applying the morphometrical analysis method using undecalcified frozen sections to ENPP1-mutant mice, quantitative evaluation of the mineralization and proteins expressed in the surrounding area in the same animal became possible.

Background/aim Selective heat shock protein 90 (Hsp90) inhibitor SNX-2112 exhibits antitumor activity in multiple cancer cell types. Here, the antitumor activity of SNX-2112 in Nara-H cells was analyzed. Materials and methods Antitumor activity of SNX-2112 was assessed using a cell proliferation assay. We also examined the signalling pathways involved in SNX-2112-mediated autophagy and apoptosis of Nara-H cells by western blot and morphological analyses. Results Cell proliferation assays demonstrated that SNX-2112 inhibited Nara-H cell growth. Western blotting revealed that SNX-2112 induced apoptosis and autophagy, inhibited mammalian target of rapamycin (mTOR) phosphorylation, and suppressed the mitogen-activated protein kinase (MAPK) signalling pathway. Morphological analysis confirmed that SNX-2112 induced autophagy and apoptosis. Conclusion SNX-2112 induced autophagy and apoptosis of Nara-H cells by inhibiting mTOR and MAPK pathways. Our results support developing SNX-2112 to treat human soft tissue sarcomas.

Background The Japanese Orthopaedic Association (JOA) has been surveying approximately 3000 orthopedic surgery hospitals and clinics with inpatient facilities nationwide to collect information on atypical femoral fractures (AFFs) and patient characteristics since 2010. The present study aims to examine radiographic images and clarify the relationship between radiographic and patient characteristics of patients with AFF and treatment status. Methods The study involved 1996 facilities certified as clinical training sites by the JOA and 912 clinics with inpatient facilities affiliated with the Japanese Clinical Orthopaedic Association (JCOA). Additional clinical data collection and radiographic image review were performed in patients aged 35 years or older who met the American Society for Bone and Mineral Research (ASBMR) case definition for AFF and received treatment at participating facilities registered with JOA in 2013. Radiographic images were evaluated in accordance with the ASBMR case definition. Results Radiographic images of 304 fractures in 304 patients were collected. Among them, 230 fractures were determined to be AFFs. The fracture site was the proximal third in 70 AFFs (30.4%), middle third in 157 AFFs (68.3%), and distal third in 3 AFFs (1.3%). Among patients with AFFs, 173 (75.2%) were treated with bisphosphonates (BPs) and 45 patients (19.6%) were not (unknown in 12 patients). Duration of use was three years or longer in 103 patients (59.5%) and between one and three years in 24 patients (13.9%). Radiographic beaking was observed in 149 fractures (86.1%) in patients treated with BPs and 17 fractures (37.8%) in patients who were not treated with BPs (odds ratio 11.3, 95% CI 5.7–22.3). Conclusions Radiographic beaking was observed more frequently in patients treated with BPs than in patients not treated with BPs.

Background A nationwide survey of hip fractures by the Japanese Orthopaedic Association (JOA) from 1998 to 2008 found a drastic increase in incidence. The aims of this study were to elucidate the status of hip fractures from 2009 to 2014 and to survey the causes for delayed surgery. Methods A tally of all hip fractures that occurred in patients from 2009 to 2014 was conducted in hospitals authorized by the JOA or in clinics with inpatient facilities of the Japanese Clinical Orthopaedic Association (JCOA). A survey of the causes for delay in surgery was conducted at 849 sites and 526 sites participated. Results A total of 488,759 hip fractures were registered. Increases in incidence from 2009 to 2014 were prominent in the 90–94-year-old age group among women and the 85–89-year-old age group among men. More trochanteric fractures than neck fractures occurred; however, the neck/trochanter ratio increased over time. The mean duration of preoperative hospital stay was 4.8 and 4.5 days, and the mean duration of hospitalization was 40.5 and 36.8 days in 2009 and 2014, respectively. There were significant differences between patients who waited for surgery up to 3 days and those who waited longer than 3 days in date of hospitalization, fracture type, comorbidities, anticoagulant use, surgical procedure, type of physician who administered anesthesia, type of anesthesia, and operating room schedule. Physicians in charge of each patient who waited for surgery for more than 3 days most frequently cited difficulties in securing operating rooms as the cause for delayed surgery. Conclusion A drastic increase occurred in the number of patients with hip fractures with time in Japan. One problem in the treatment of hip fractures is the long waiting time from hospitalization to surgery resulting from difficulties in securing operating rooms.

We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy. We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research. We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p

Highlights • The occurrence of CA-MRSA osteomyelitis in adults is uncommonly reported. • CA-MRSA often produce Panton-Valentine leucocidin. • CA-MRSA osteomyelitis involving the long bones has a propensity to mimic malignant bone tumors. • Appropriate identification of the organism and detection of the presence of PVL will help to more rapidly provide adequate treatment and improve the prognosis., Introduction Most community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections affect skin or soft tissues, while invasive and life-threatening illnesses including osteomyelitis are less common. CA-MRSA infections occur especially in the pediatric age group, while the occurrence of CA-MRSA osteomyelitis in adults is uncommonly reported. Presentation of cases A rare case of acute osteomyelitis of the femur caused by Panton-Valentine leukocidin (PVL)-positive CA-MRSA in a 37-year-old man in good health is presented. A pure bone biopsy revealed extensive inflammation, suggestive of acute osteomyelitis, with no evidence of neoplasm, and PVL-positive MRSA was isolated from the culture. Antibiotic treatment, with 6 weeks of intravenous vancomycin and 4 weeks of clindamycin, followed by 2 weeks of oral linezolid, was given, and 2 years after treatment completion, there has been no relapse of infection. Conclusion This case strongly suggests that we need to be aware of CA-MRSA osteomyelitis, which requires a high level of suspicion, prompt diagnosis, and appropriate antibiotic treatment.

Fracture of a femoral component after modern unicompartmental knee arthroplasty is very rare. Although this is not the first case on this subject, no study has reported insufficient crimping as the cause of femoral component loosening that led to breakage of a metallic component. A 69-year-old man underwent medial unicompartmental knee arthroplasty for right medial knee osteoarthritis. His early postoperative course was good; however, the 1-year postoperative radiograph showed an apparent radiolucent line around the femoral component, and he occasionally had right knee pain. However, he had been followed up conservatively because he had been doing well even while doing heavy agricultural work. At 8 years after surgery, because breakage of the femoral component was found, revision surgery was performed using bicruciate-retaining total knee arthroplasty. The removed fractured femoral component revealed a thick cement mantle detached from the bone surface. The postoperative course of the patient after the revision surgery was excellent. We suggest that the causes of femoral component breakage include early implant loosening caused by uneven cement crimping of the femoral component to the bone and excessive loading stress as a result of heavy labour.

Rationale: Multicentric carpotarsal osteolysis (MCTO) is a rare hereditary disease caused by mutations in MafB, a negative regulator of osteoclastogenesis. Patient concerns: A 20-year-old, Japanese woman with scoliosis visited our institute for treatment. Scoliosis was apparent since she was 12 years old, but she had not sought treatment until the age of 19. Medical examination showed a typical facial appearance associated with a small forehead and hypotelorism; shortening of the fingers of both hands and both upper limbs was observed, in addition to clubfoot. No café au lait spots or mental retardation were observed. On the other hand, the trunk showed evidence of an irregular waistline and a rib hump that obviously suggested scoliosis. Neurological deficit was not observed. Spirometry showed decreased forced vital capacity (FVC). Although proteinuria was observed, renal dysfunction and hypertension were not seen. The major curve of scoliosis was 82° (MC, Th7–L2; Th11 apical vertebra), and the upper curve was 77° (UC, Th1-6; Th3 apical vertebra). In a recumbent-traction position, the major curve was 54° and the upper curve was 56°. The pelvic incidence minus lumbar lordosis (PI–LL) angle was

We report the clinical results and problems of combined administration of rifampicin, ethambutol, and clarithromycin (REC) for the treatment of Mycobacterium avium complex (MAC) infection of the hand (hand MAC). Participants included 7 patients with hand MAC. After resection of the infected lesion, REC was prescribed for 12 months. For these patients, the site of infection, clinical course after initiation of REC, adverse drug effects (ADEs), and incidence of recurrence were evaluated. Sites of infection were the flexor tenosynovium in 5 patients, extensor tenosynovium in 1 patient, and both flexor and extensor tenosynovium in 1 patient. ADEs of REC occurred in 5 patients, and included visual disturbance caused by ethambutol in 2 patients, liver function abnormality caused by rifampicin in 2 patients, and fever with diarrhea caused by rifampicin in 1 patient. For 2 of these 5 patients, desensitization therapy was applied and REC was able to be reinstated. In the remaining 3 patients, the causative drugs were discontinued and levofloxacin, a new quinolone, was administered. Complete healing was achieved in 5 patients, and recurrence was observed in 2 patients. These 2 patients with recurrence included 1 patient in whom REC was completed and 1 patient in whom REC therapy was modified due to ADE. REC provided relatively good clinical results as a treatment for hand MAC. However, recurrences were observed even after the completion of REC and the use of an alternative drug. Optimal duration of REC and appropriate alternative drugs need to be identified in the future.

Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood-brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi-quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833-837, 2016. © 2016 Wiley Periodicals, Inc.

In end-stage osteoarthritis (OA) of the hip, the effect of bone metabolism with and without cartilage is unclear. In this study, we aimed to investigate histomorphology and microdamage in the subchondral bone of the femoral head in areas with and without articular cartilage in patients with end-stage OA. Nineteen femoral heads were evaluated in 10 women who underwent total hip arthroplasty for OA and in nine cadaveric controls (CNT). Chondral thickness and subchondral bone plate thickness (SBP.Th) were measured in 5-mm-wide areas where cartilage was lost (area A) or preserved (area B) in OA and in corresponding areas in the load-bearing portion of the femoral head in the CNT. Histomorphometry and microdamage in 5 × 5-mm areas of cancellous bone were assessed. SBP.Th and bone volume were significantly greater in area A than in area B or in the CNT. Osteoid volume was significantly greater in area A than in area B or in the CNT. There was no significant difference in eroded surface between area A and CNT. Microcrack density was significantly greater in area A than in area B or in the CNT. Although accumulation of microdamage was caused by concentration of stress on the subchondral bone in the cartilage loss area in end-stage OA, remodeling for microdamage repairing mechanism was not enhanced. It was considered that the subchondral cancellous bone volume was increased because of modeling, not remodeling, by stress concentration due to articular cartilage loss.

The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy. Although it remains under debate whether chemotherapy-induced autophagy in tumor cells is a protective response or is invoked to promote cell death, recent studies indicate that autophagy is a self-defense mechanism of cancer cells that are subjected to antitumor agents and that blocking autophagy can trigger apoptosis. The aim of this study was to examine the effects of rapamycin, an mTOR inhibitor, on MG63 osteosarcoma cells. We further examined whether the combination of rapamycin and the small molecule inhibitor of autophagy Spautin-1 (specific and potent autophagy inhibitor-1) enhanced the rapamycin-induced apoptosis in MG63 cells. We examined the effects of rapamycin treatment on cell proliferation, phosphorylation of mTOR pathway components, and autophagy by western blot analysis. Furthermore, we examined the effects of rapamycin with or without Spautin-1 on the induction of apoptosis by western blot analysis and immunohistochemical staining. We found that rapamycin inhibited cell proliferation and decreased the phosphorylation of mTOR pathway components in MG63 cells. Rapamycin induced the apoptosis of MG63 cells, and this apoptosis was enhanced by Spautin-1. It was considered that Spautin-1 suppressed the protective mechanism induced by rapamycin in tumor cells and induced apoptosis. Therefore, the combination of an mTOR inhibitor and an autophagy inhibitor may be effective in the treatment of osteosarcoma because it effectively induces the apoptotic pathway.

Introduction. Tumoral calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (CPPDCD), also known as tophaceous calcium pyrophosphate deposition disease (CPDD), is a tumorlike lesion, and it should be distinguished from usual CPDD that causes severe joint inflammation and arthralgia. A case of tumoral CPPDCD of the wrist joint that required differentiation from synovial osteochondromatosis is described.Case Presentation. The patient was a 78-year-old woman with a 5-year history of nodular lesions at the right wrist that had gradually increased in size. An excisional biopsy and a histological examination of the excised nodular lesions by hematoxylin and eosin (H&E) staining were performed, demonstrating numerous polarizable, rhabdoid, and rectangular crystals, surrounded by fibroblasts, macrophages, and foreign body-type giant cells, consistent with tumoral CPPDCD.Conclusion. Tumoral CPPDCD, especially at the wrist joint, is rare, and, to the best of our knowledge, only 2 articles have been published. This case seems to need further follow-up for recurrence, because tumoral CPPDCD may recur after complete or incomplete surgical excision.