Kazuya Oshima

Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation

Obesity is linked to a variety of metabolic disorders, such as insulin resistance and atherosclerosis. Dysregulated production of fat-derived secretory factors, adipocytokines, is partly responsible for obesity-linked metabolic disorders. However, the mechanistic role of obesity per se to adipocytokine dysregulation has not been fully elucidated. Here, we show that adipose tissue of obese mice is hypoxic and that local adipose tissue hypoxia dysregulates the production of adipocytokines. Tissue hypoxia was confirmed by an exogenous marker, pimonidazole, and by an elevated concentration of lactate, an endogenous marker. Moreover, local tissue hypoperfusion (measured by colored microspheres) was confirmed in adipose tissue of obese mice. Adiponectin mRNA expression was decreased, and mRNA of C/EBP homologous protein (CHOP), an endoplasmic reticulum (ER) stress–mediated protein, was significantly increased in adipose tissue of obese mice. In 3T3-L1 adipocytes, hypoxia dysregulated the expression of adipocytokines, such as adiponectin and plasminogen activator inhibitor type-1, and increased the mRNAs of ER stress marker genes, CHOP and GRP78 (glucose-regulated protein, 78 kD). Expression of CHOP attenuated adiponectin promoter activity, and RNA interference of CHOP partly reversed hypoxia-induced suppression of adiponectin mRNA expression in adipocytes. Hypoxia also increased instability of adiponectin mRNA. Our results suggest that hypoperfusion and hypoxia in adipose tissues underlie the dysregulated production of adipocytokines and metabolic syndrome in obesity.

Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice.

Adiponectin (APN) is a hormone released by adipose tissue with anti-inflammatory properties. The purpose of this study was to examine the therapeutic effects of systemic delivery of APN in murine arthritis model. Collagen-induced arthritis (CIA) was induced in male DBA1/J mice, and adenoviral vectors encoding human APN (Ad-APN) or beta-galactosidase (Ad-beta-gal) as control were injected either before or during arthritis progression. Systemic APN delivery at both time points significantly decreased clinical disease activity scores of CIA. In addition, APN treatment before arthritis progression significantly decreased histological scores of inflammation and cartilage damage, bone erosion, and mRNA levels of pro-inflammatory cytokines in the joints, without altering serum anti-collagen antibodies levels. Immunohistochemical staining showed significant inhibition of complement C1q and C3 deposition in the joints of Ad-APN infected CIA mice. These results provide novel evidence that systemic APN delivery prevents inflammation and joint destruction in murine arthritis model.

Acute Cervical Spinal Cord Injury Complicated by Preexisting Ossification of the Posterior Longitudinal Ligament : A Multicenter Study

Study Design. Retrospective multicenter study. Objective. To review the clinical characteristics of traumatic cervical spinal cord injury (SCI) associated with ossification of the posterior longitudinal ligament (OPLL). Summary of Background Data. Despite its potentially devastating consequences, there is a lack of information about acute cervical SCI complicated by OPLL. Methods. This study included consecutive patients with acute traumatic cervical SCI (Frankel A, B, and C) who were admitted within 48 hours of injury to 34 spine institutions across Japan. For analysis of neurologic outcome, patients who had completed at least a 6-month follow-up were included. Neurologic improvement was defined as at least one grade conversion in Frankel grade. Results. A total of 453 patients were identified (367 men, 86 women; mean age, 59 years). OPLL was found in 106 (23%) patients (87 men, 19 women; mean age, 66 years). Most of the patients with OPLL (94 of 106) were without bone injury, presenting with incomplete SCI. The prevalence of OPLL reached 34% in SCI without bone injury. The cause of SCI was predominantly falls (74%). Only 25% of the patients were aware of OPLL. Half of the OPLL patients reported gait disturbance before injury. Forty-eight (52%) OPLL patients without bone injury underwent surgery (median, 13.5 days after injury), mostly laminoplasty. Overall, no significant difference was noted in neurologic improvement between surgery group and conservative group. However, further stratification showed that surgery was associated with greater neurologic recovery in patients who had gait disturbance before injury (P = 0.04). Conclusion. Prevalence of OPLL among cervical SCI was alarmingly high, especially in those without bone injury. Most of cervical SCI associated with OPLL were incomplete, without bone injury, and caused predominantly by low-energy trauma. The majority of the patients were unaware of OPLL. Surgery produced better neurologic recovery in patients who had gait disturbance before injury.

Preservation of the nuchal ligament plays an important role in preventing unfavorable radiologic changes after laminoplasty.

Study Design Prospective study. Objective To examine whether preservation of the funicular section of the nuchal ligament attached to the C6 and C7 spinous processes could prevent unfavorable radiologic changes such as kyphotic deformity and destabilization at the C6/7 segment, and to investigate possible correlations between adverse radiologic changes and neurologic recovery or incidence of axial neck pain after laminoplasty in patients with cervical spondylotic myelopathy. Summary of Background Data Adverse radiologic changes after cervical laminoplasty have been reported to result from detachment of cervical extensor muscles. Methods Subjects comprised 37 patients who underwent modified C3-6 laminoplasty. Our procedure preserves the funicular section of the nuchal ligament attached to the C6 and/or C7 spinous processes in addition to all muscles attached to the C2 and C7 spinous processes and the subaxial deep extensor muscles on the hinged side. The funicular section of the ligament attached only to the C7 spinous process was preserved in 18 patients (C7 group). This funicular section attaching both to the C7 and C6 spinous processes was preserved in 19 patients (C6+7 group). Radiologic and clinical data were prospectively collected. Results Postoperative loss of lordosis and destabilization at the C6/7 segment were significantly reduced in the C6+7 group compared with the C7 group. As of final follow-up, neurologic recovery was significantly poorer in the 3 patients with kyphosis than in the 34 patients with straight spinal alignment or lordosis. Frequencies of axial pain showed no significant differences between groups. This value did not vary with the differences in sagittal alignment. Conclusions These results indicate that the preserved funicular section of the nuchal ligament attached both to the C6 and C7 spinous processes plays an important role in preventing undesirable radiologic changes after laminoplasty.

Repeated vertebrobasilar thromboembolism in a patient with severe upper cervical instability because of rheumatoid arthritis

BACKGROUND CONTEXT Although many reports have examined upper cervical rheumatoid arthritis (RA) and spinal cord disorders resulting from RA lesions, few cases of thromboembolic events in the vertebrobasilar system associated with RA lesions of the upper cervical spine have been reported. PURPOSE We encountered a rare case of repeated vertebrobasilar thromboembolism with severe upper cervical instability resulting from RA. Furthermore, we obtained clinical images of the vertebrobasilar system just before and after the first thromboembolic event. We thus present the case of a patient with RA who recovered without surgery from repeated vertebrobasilar thromboembolism that might have been caused by severe upper cervical instability. STUDY DESIGN Case report. METHODS A 59-year-old man with a 14-year history of RA experienced nuchal pain because of severe atlantoaxial and vertical subluxations. While awaiting surgery, he developed left Wallenberg syndrome because of occlusion in the left vertebral artery (VA). Five days later, he displayed impaired consciousness and symptoms of right Wallenberg syndrome. Emergency magnetic resonance angiography showed occlusion in the basilar artery. After thrombolytic therapy, he gradually recovered. RESULTS Because we presumed that the patients recurrent thrombus formation resulted from kinking of the right VA caused by severe instability of the upper cervical spine, we planned to treat him surgically despite his impaired consciousness and tracheostomy. However, the anesthesiologist would not approve surgery because the patient had high-risk conditions. The cervical spine was thus realigned and immobilized in a halo apparatus for 3 months to achieve stability. Now, more than 5 years after these events, the patient has experienced no more thromboembolic events and his condition has remained stable, without need for surgery. CONCLUSIONS Repeated vertebrobasilar thromboembolism in patients with RA may sometimes be caused by severe upper cervical instability that can be treated without surgery.

The utility of superficial abdominal reflex in the initial diagnosis of scoliosis: a retrospective review of clinical characteristics of scoliosis with syringomyelia

BackgroundWith increasing use of magnetic resonance imaging (MRI), underlying syringomyelia is increasingly found in patients with presumed idiopathic scoliosis. To determine the indications for MRI in the differential diagnosis of scoliosis, several clinical characteristics of syringomyelia have been reported. Neurological signs, particularly abnormal superficial abdominal reflex (SAR), are important in establishing the initial diagnosis of scoliosis. However, the prevalence of abnormal SAR in patients with scoliosis and the sensitivity of this sign in predicting syringomyelia are not well known. We aimed to determine the diagnostic utility of SAR and other characteristics of syringomyelia in patients with scoliosis.MethodsWe reviewed the medical records of 93 patients with scoliosis, 90 of whom underwent corrective surgery. All patients underwent MRI to determine the presence of syringomyelia. Mean age at surgery was 12.5 years. Abnormal SAR was defined as unilateral or bilateral absence or hyporeflexia of SAR. We calculated indices of diagnostic utility of abnormal SAR for non-idiopathic scoliosis and for syringomyelia. Abnormal SAR, left thoracic curve pattern, gender, and curve flexibility were compared between scoliosis with syringomyelia and idiopathic scoliosis. Logistic regression analysis was performed with the existence of syringomyelia as the dependent variable and curve flexibility as the independent variable.ResultsAbnormal SAR was observed in 20 patients (prevalence 22%). All 6 patients with myopathic scoliosis displayed bilateral absence of SAR. The sensitivity of abnormal SAR for non-idiopathic scoliosis was 38%, with 96% specificity, 90% PPV (positive predictive value), and 60% NPV (negative predictive value). Syringomyelia was identified in 9 of the 93 patients (9.7%); 8 of these had abnormal SAR. The sensitivity of abnormal SAR for syringomyelia in presumed idiopathic scoliosis was 89%, with 95% specificity, 80% PPV, and 98% NPV. Gender, abnormal neurological findings, and curve flexibility differed significantly between patients with syringomyelia and those with idiopathic scoliosis (P < 0.05). In the logistic regression model, the area under the receiver operating characteristic (ROC) curve was 0.79 and the cut-off value of curve flexibility for syringomyelia was 50% (P = 0.08).ConclusionAbnormal SAR was a useful indicator not only for syringomyelia, but also for myogenic scoliosis.

Radiofrequency ablation of osteoid osteoma using a three-dimensional navigation system

OBJECTIVE This study aimed to report the clinical outcomes for patients with osteoid osteoma (OO) treated by radiofrequency ablation (RFA) using a three-dimensional (3D) navigation system. METHODS We performed RFA using a 3D navigation system on 32 patients with clinically and radiologically diagnosed OO. This study included 25 males and 7 females with a median age of 20 years (range, 10-39 years). The median duration of follow-up was 18 months (range, 1-65 months). We investigated technical specifications, tumor localization, technical success, clinical success, biopsy success, complications, incomplete treatment, and recurrences. RESULTS Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one each in the fibula, scapula, patella, lumbar vertebra, and acetabula. All procedures were technically successful, and pain relief was achieved in all patients. However, local recurrence developed in one patient, needing additional RFA. The clinical success rate was 96.8%. Biopsy showed OO in 12 patients (37%). Complications occurred in three patients (9%), two cases of fractures and one of osteomyelitis. CONCLUSIONS A 3D navigation provides real-time imaging and enables us to set the RFA needle in the correct position, particularly in case of OO-aroused complex anatomical structures. Our initial results indicated that radiofrequency ablation using a 3D navigation system is feasible and safe for patients with OO.

Atypical femoral fracture associated with bone-modifying agent for bone metastasis of breast cancer: A report of two cases:

Atypical femoral fractures (AFFs) are recently observed as a complication of long-term bone-modifying agent (BMA; bisphosphonate or denosumab) therapy for bone metastases. We describe the cases of two women diagnosed with breast cancer who developed incomplete AFF associated with BMAs prescribed for bone metastases. Radiographs of their femurs revealed thickening of the lateral subtrochanteric cortex, and tomosynthesis revealed a visible fracture line in the thickened cortex. They were initially treated with conservative management; however, the incomplete fracture resulted in a complete fracture. These cases highlight two major implications. First, symptomatic incomplete AFF associated with BMAs prescribed for bone metastases should be treated with surgical prophylaxis, given the fact that fracture healing is expected to require a longer duration and an incomplete fracture might potentially progress to a complete fracture during long-term conservative management. Second, tomosynthesis is useful in identifying radiolucent fracture lines that are reliable predictors of fracture propagation.

Comparison of the Japanese Orthopaedic Association Score and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire Scores: Time-Dependent Changes in Patients with Cervical Spondylotic Myelopathy and Posterior Longitudinal Ligament

Study Design Prospective cohort study. Purpose To identify differences in time-dependent perioperative changes between the Japanese Orthopaedic Association (JOA) score and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) score in patients with cervical spondylotic myelopathy (CSM) and posterior longitudinal ligament (OPLL) who underwent cervical laminoplasty. Overview of Literature The JOA score does not take into consideration patient satisfaction or quality of life. Accordingly, the JOACMEQ was designed in 2007 as a patient-centered assessment tool. Methods We studied 21 patients who underwent cervical laminoplasty. We objectively evaluated the time-dependent changes in JOACMEQ scores and JOA scores for all patients before surgery and at 2 weeks, 3 months, 6 months, and 1 year after surgery. Results The average total JOA score and the recovery rate improved significantly after surgery in both groups, with a slightly better recovery rate in the OPLL group. Cervical spine function improved significantly in the CSM group but not in the OPLL group. Upper- and lower-extremity functions were more stable in the CSM group than in the OPLL group. The effectiveness rate of the JOACMEQ for measuring quality of life was quite low in both groups. In both groups, the Spearman contingency coefficients were dispersed widely except for upper- and lower-extremity function. Conclusions Scores for upper- and lower-extremity function on the JOACMEQ correlated well with JOA scores. Because the JOACMEQ can also assess cervical spine function and quality of life, factors that cannot be assessed by the JOA score alone, the JOACMEQ is a more comprehensive evaluation tool.

Primary osteosarcoma of the heart with long-term survival: A case report of laparoscopic resection of a metastatic sarcoma in the intestine

Primary cardiac tumors are uncommon and cardiac osteosarcoma is a rare disease. While complete surgical resection is considered to be the best treatment option for cardiac osteosarcomas, local and metastatic recurrences present challenges and indicate a poor prognosis. A combination of surgical resection with radio- and/or chemotherapy is a more effective course of treatment for osteosarcoma. In the present case, the patient underwent a complete resection of a primary cardiac osteosarcoma, and received chemotherapy and radiotherapy following local recurrence and metastasis to the bone post-operatively. Following these treatments, a rectal metastatic tumor was detected as causative of anemia. There is currently a lack of guidelines on the treatment of metastatic osteosarcomas in the intestine and there are few reports on rectal metastases. The present study described a laparoscopic resection of the osteosarcoma. The patient recovered without any complications and radiotherapy and chemotherapy were administered post-surgery to treat the bone metastases. The patient remained healthy at a follow-up examination, 61 months post surgery.