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

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

Impact of preoperative echocardiographic delay on timing of hip fracture surgery in elderly patients.

Objectives: Early surgery is recommended for hip fractures in elderly patients. This study was performed to evaluate factors contributing to delayed surgery and associated outcomes in a secondary hospital in Japan with a rehabilitation centre. Methods: We retrospectively reviewed the records of 895 patients aged >50 years [median age, 86 (81-91) years] treated for hip fractures at our institution from 2016 to 2020. We defined surgical delay as surgery performed >48 h after admission. We evaluated several risk factors for surgical delay and associated outcomes: mortality, length of hospital stay and walking status. Results: Binomial logistic regression analysis showed that several factors, including preoperative echocardiographic delay (odds ratio, 9.38; 95% confidence interval, 5.95-15.28), were risk factors for surgical delay. In the multiple regression analyses, surgical delay was a significant risk factor for a longer hospital stay (partial regression coefficient, 6.99; 95% confidence interval, 3.67-10.31). Conclusions: Our findings indicated that preoperative echocardiographic delay was one of the risk factors for surgical delay of hip fractures in elderly patients. Surgical delay was a risk factor for a longer hospital stay, including rehabilitation.

Association between bone mineral density, muscle volume, walking ability, and geriatric nutritional risk index in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Hemodialysis patients are at risk for bone loss and sarcopenia, characterized by reduced muscle mass and limited mobility/function. Osteoporosis and sarcopenia both increase the risk of hospitalization and death in affected individuals. Malnutrition also occurs as a complication of hemodialysis and has been identified as a risk factor for osteoporosis and sarcopenia. In this study, we examined the relationship between osteoporosis, muscle volume, walking ability, and malnutrition in hemodialysis patients. METHODS AND STUDY DESIGN: Forty-five hemodialysis patients were evaluated. Bone mineral density (BMD) and muscle volume were measured by dual-energy X-ray absorptiometry. Muscle volume and strength were evaluated using lean mass index (LMI), handgrip strength, and walking ability. The time required for a patient to walk 10 meters was measured to evaluate walking ability. The geriatric nutritional risk index (GNRI) was used to assess malnutrition. RESULTS: Multiple linear regression analysis showed that older age, female sex, lower LMI, and higher total type I procollagen N-terminal propeptide were correlated with lower BMD of lumbar spine. Higher age and lower LMI were correlated with lower BMD of the femoral neck. Female sex and lower GNRI were correlated with lower LMI. Longer duration of hemodialysis was correlated with lower walking ability. CONCLUSIONS: Our findings suggest that muscle preservation is required to maintain both lumbar spine and femoral neck BMD. Similarly, nutritional management is necessary to maintain BMD via preservation of muscle volume. Complementary nutritional therapies are needed to improve osteoporosis and sarcopenia in high-risk hemodialysis patients.

Association between Bone Mineral Density of Femoral Neck and Geriatric Nutritional Risk Index in Rheumatoid Arthritis Patients Treated with Biological Disease-Modifying Anti-Rheumatic Drugs.

Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti-rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its management remains a problem. The Geriatric Nutritional Risk Index (GNRI) evaluates the risk of malnutrition-related complications in elderly patients and has been shown to be a significant predictor of many diseases. We evaluated the correlation between GNRI and RA activity. In addition, risk factors for femoral neck bone loss were evaluated in RA patients treated with bDMARDs. We retrospectively examined the medical records of 146 patients with RA, collecting and recording the patients' demographic and clinical characteristics. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse correlations were observed between GNRI and disease duration, disease activity score-28 joint count serum C-reactive protein (CRP), simple disease activity index, modified health assessment questionnaire score and CRP. GNRI showed correlation with femoral neck BMD and femoral neck BMD ≤ 70% of young adult men (YAM). Multiple regression analysis showed that female sex, increased age and lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate binomial logistic regression analysis showed that female sex (odd ratio: 3.67) and lower GNRI (odd ratio: 0.87) were risk factors for BMD ≤ 70% of YAM. Because the GNRI is a simple method, it might be a simple predictor for RA activity and BMD status in RA patients. Complementary nutritional therapies might improve RA activity and osteoporosis in RA patients who have undergone treatment with bDMARDs.

Outcomes of Surface Replacement Proximal Interphalangeal Joint Arthroplasty Using the Self Locking Finger Joint Implant: Minimum Two Years Follow-up.

BACKGROUND: The Self Locking Finger Joint (SLFJ) implant is a new type of surface replacement implant. The purpose of this study was to evaluate midterm clinical outcomes of the proximal interphalangeal (PIP) arthroplasty with the SLFJ implant. METHODS: We retrospectively studied 26 PIP joint arthroplasties using the SLFJ implant in 17 patients with osteoarthritis or posttraumatic osteoarthritis. Preoperative and postoperative range of motion, grip strength and key pinch, radiographic findings, and complications were evaluated. The Disabilities of the Arm, Shoulder, and Hand (DASH) score, visual analog scale (VAS) score, course of pain, and patient satisfaction were obtained. RESULTS: The mean follow-up time was 44 months (range, 24-76 months). The average active PIP joint arc of motion improved from 36° before surgery to 44° after surgery. Grip strength and key pinch showed no statistical difference between preoperative and postoperative assessments. The average DASH score and VAS score improved from 40 to 15 and from 5 to 1, respectively. Overall patient satisfaction was 94%. Ninety percent of implants showed osteointegration, and there were no radiographic signs of migration and loosening. Three joints (12%) showed abnormal heterotopic bone formation. Four joints (15%) had secondary surgery-1 joint needing joint head and socket replacement and 3 joints needing contracture release. CONCLUSIONS: Our minimum 2 years of follow-up evaluation of the SLFJ implant PIP joint arthroplasty demonstrated good pain relief and good overall patient satisfaction while maintaining joint range of motion. The SLFJ implant showed good osteointegration. Further longer-term prospective studies with various types of currently available implants are needed.

Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs.

OBJECTIVE: Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients' variables to identify risk factors for least significant reduction of bone mineral density. RESULTS: Least significant reduction of lumbar spine bone mineral density (≤ - 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ - 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.

Giant Cell Tumor of the Distal Phalanx of the Fourth Toe: A Case Report.

Giant cell tumor of the bone is a benign, but locally aggressive, primary bone tumor of unknown origin. It most commonly occurs in the long bones and is only rarely found in the phalangeal bones, such as the distal phalanx of the foot. In our review of English-language published studies, only 4 other cases of giant cell tumor involving the distal phalangeal bone of the foot had been reported to date. We report a case of giant cell tumor arising in the distal phalanx of the fourth toe in a 28-year-old female. Although bisphosphonate therapy was administered, the tumor showed highly aggressive behavior with ulceration of the overlying skin, and the patient underwent phalangeal amputation 1.5 months after diagnosis.

Risk of low bone mineral density in patients with rheumatoid arthritis treated with biologics.

BACKGROUND: Osteoporosis is a complication of rheumatoid arthritis (RA). We identified risk factors for osteoporosis during treatment with biologics. METHODS: Femoral neck bone mineral density (BMD) was measured in 186 patients with biologics-treated RA. We compared the characteristics of those with BMD ≥70% of young adult mean (YAM) and those with BMD <70% of YAM, and undertook multivariable logistic regression analysis to identify risk factors for bone loss. RESULTS: Mean age and disease duration, the proportion of females, scores in the Modified Health Assessment Questionnaire and history of vertebral fracture were significantly greater in the BMD <70% of YAM group, but body mass index (BMI) was significantly lower in the BMD <70% of YAM group. There was no significant difference between the groups in terms of other biomarkers of RA activity, the proportion treated with methylprednisolone, or the duration or choice of biologics. The proportions of patients treated with anti-osteoporosis drugs and parathyroid hormone were significantly higher in the BMD <70% of YAM group. In the multivariable analysis, advanced age, female, longer disease duration, history of past thoracic or lumbar vertebral fracture, higher Steinbrocker classification and lower BMI were significant factors for BMD <70% of YAM. DISCUSSION: We identified risk factors for bone loss in patients with RA treated with biologics. Before suppression of disease activity by biologics, bone loss might already be advanced. CONCLUSIONS: We recommend that patients with RA who possess these risk factors be considered for earlier and more intense treatment to prevent bone loss, as well as addressing RA disease progression.

Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report.

We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi's syndrome. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249.

An investigation of the correlation between blood concentration of mizoribine and its efficacy in treatment of rheumatoid arthritis based on indices of drug survival and improvement in DAS28-CRP.

OBJECTIVES: The efficacy of mizoribine (MZR) in treatment of rheumatoid arthritis (RA) was retrospectively investigated in terms of drug survival, improvement in Disease Activity Score-28 (DAS28)-C-reactive protein (CRP), and blood MZR concentration obtained 3 h after dosing (MZR-C3). METHODS: To compare the efficacy of MZR administered via different regimens, the subjects were divided into 2 groups: those receiving a single dose of MZR at 100-150 mg every other day (group A) and those receiving 2 or 3 divided doses of the drug on consecutive days, which is the usual dosing method of the drug (group B). RESULTS: Group A had significantly higher MZR-C3 levels compared with group B, as well as significantly greater improvement in DAS28-CRP. Moreover, drug survival was significantly longer in group A. The primary regression equation suggested that the effective blood MZR concentration in RA treatment is MZR-C3 of 1.47 µg/mL or more. CONCLUSIONS: The results of the present study indicate that it is possible to increase the efficacy of MZR in a blood concentration-dependent manner, and also to control RA over a prolonged period, using single administration of MZR on alternate days at an increased dose.

Bilobular calcifying fibrous pseudotumor in soleus muscle: a case report.

INTRODUCTION: Calcifying fibrous pseudotumor is a rare benign soft-tissue lesion composed of fibrous tissue with abundant hyalinized collagen and dystrophic and often psammomatous calcifications. The cause of the disease is unclear but, usually, complete resection of the well-circumscribed tumor is sufficient to avoid recurrence of the disease. Here, we report an unusual case of this rare tumor that presented as two lobulated lesions in the calf muscle. CASE PRESENTATION: The patient was a 17-year-old Japanese girl who noted a hard mass in her left calf. Magnetic resonance imaging revealed two well-demarcated lobular masses in the soleus muscle, and the tumor was significantly enhanced by contrast medium. Preoperative differential diagnoses included soft-part tumors composed of fibrous tissue. However, making a definite diagnosis was impossible because a lobulated shape is rare for fibrous tumors. Biopsy demonstrated that the mass was a benign tumor composed of collagen-rich, hyalinized fibrosclerotic tissue. We performed marginal resection of the two nodules, including the fibrous tissue that connected them. Immunohistochemistry was positive for factor XIIIa and negative for anaplastic lymphoma kinase-1. These findings were helpful to distinguish calcifying fibrous pseudotumor from inflammatory myofibroblastic tumor. There was no sign of recurrence at 30 months after surgery. CONCLUSION: To the best of our knowledge, this is the first case of bilobular calcifying fibrous pseudotumor that developed in an extremity. As described in the previous literature, simple excision was sufficient for the treatment of calcifying fibrous pseudotumor with two lobules.

Clinical implications of determination of safe surgical margins by using a combination of CT and 18FDG-positron emission tomography in soft tissue sarcoma.

BACKGROUND: To determine safe surgical margins for soft tissue sarcoma, it is essential to perform a general evaluation of the extent of tumor, responses to auxiliary therapy, and other factors preoperatively using multiple types of diagnostic imaging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a tool for diagnostic imaging that has recently spread rapidly in clinical use. At present, the roles played by FDG-PET/CT in determination of margins for surgical resection of sarcoma are unclear. The present study was undertaken to explore the roles of FDG-PET/CT in determination of surgical margins for soft tissue sarcoma and to examine whether PET can serve as a standard means for setting the margins of surgical resection during reduced surgery. METHODS: The study involved 7 patients with sarcoma who underwent surgery in our department and in whom evaluation with FDG-PET/CT was possible. Sarcoma was histologically rated as MFH in 6 cases and leiomyosarcoma in 1 case. In all cases, sarcoma was superficial (T1a or T2a). The tumor border was defined by contrast-enhanced MRI, and SUVs were measured at intervals of 1 cm over a 5-cm long area from the tumor border. Mapping of viable tumor cells was carried out on whole-mount sections of resected tissue, and SUVs were compared with histopathological findings. RESULTS: Preoperative maximum SUVs (SUV-max) of the tumor averaged 11.7 (range: 3.8-22.1). Mean SUV-max was 2.2 (range: 0.3-3.8) at 1 cm from the tumor border, 1.1 (0.85-1.47) at 2 cm, 0.83 (0.65-1.15) at 3 cm, 0.7 (0.42-0.95) at 4 cm, and 0.64 (0.45-0.82) at 5 cm. When resected tissue was mapped, tumor cells were absent in the areas where SUV-max was below 1.0. CONCLUSIONS: Our findings suggest that a safe surgical margin free of viable tumor cells can be ensured if the SUV cut-off level is set at 1.0. FDG-PET/CT is promising as a diagnostic imaging technique for setting of safe minimal margins for surgical resection of soft tissue sarcoma.

Preventive effect of erythropoietin on spinal cord cell apoptosis following acute traumatic injury in rats.

STUDY DESIGN: Using a rat spinal cord injury (SCI) model, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), anti-active caspase-3 antibody staining, histological examination, and histochemical studies were used to examine the antiapoptotic effect of erythropoietin. OBJECTIVE: To evaluate in detail the antiapoptotic effect of erythropoietin following SCI. SUMMARY OF BACKGROUND DATA: Although some investigators have reported antiapoptotic effects of erythropoietin using the TUNEL method, it has not been determined whether erythropoietin can prevent both acute neuronal death and secondary injury. Therefore, we examined the temporal and spatial effects of erythropoietin using TUNEL and active caspase-3 following SCI. METHODS: An in vitro study used a cerebrocortical culture in which the antiapoptotic effect of erythropoietin was examined after N-methyl-D-aspartate treatment. Using an in vivo study, rats with SCI received erythropoietin intraperitoneally, and were examined histologically and immunohistochemically with TUNEL, active caspase-3, and cell markers between 6 hours and 7 days after injury. RESULTS: Cerebrocortical culture confirmed an antiapoptotic effect of erythropoietin. Erythropoietin treatment significantly decreased TUNEL-positive apoptotic neurons and oligodendrocytes as early as 6 hours after SCI in rats. This antiapoptotic effect was observed until 7 days after injury. In addition, erythropoietin treatment significantly decreased the number of active caspase-3 immunoreactive cells within the SCI. In the in vitro study, cerebrocortical culture confirmed an antiapoptotic effect of erythropoietin. CONCLUSIONS: These findings suggest that exogenous erythropoietin decreases the number of apoptotic cells observed between the very early and subchronic stages following traumatic SCI.

Changes in nitric oxide and expression of nitric oxide synthase in spinal cord after acute traumatic injury in rats.

The aim of this study was to observe the time course of NO production and NOS expression in the spinal cord following acute traumatic injury. Rat spinal cord was injured by extradural static weight-compression, which resulted in an incomplete transverse spinal cord lesion with paralysis of the lower extremities. Using this model, measurement of NO by microdialysis and Griess reaction and histological and immunohistochemical examinations using polyclonal antibodies to nNOS and iNOS were performed from immediately to 14 days after injury. In injured cord, the amount of NO markedly increased immediately after injury and gradually decreased between 1 and 12 h after injury. A second wave of increase in NO level was observed at 24 h and 3 days after injury. Histologically, hematomas and necrotic changes were observed after injury and demyelination of nerve fibers increased with time in the compressed segment. Immunohistochemically, the number of cells with expression of nNOS was increased immediately to 12 h after injury. Expression of iNOS was observed from 12 h to 3 days after injury. These findings suggested that the initial maximal increase of NO production might be caused mainly by nNOS and that the second wave of increase in NO might be due mainly to iNOS.