Mid- to Long-Term Outcomes After Resection of Thoracic Dumbbell Tumors Managed by Laminectomy and Unilateral Total Facetectomy Without Instrumented Fusion.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To evaluate mid- to long-term surgical outcomes of thoracic dumbbell tumors managed by laminectomy and unilateral total facetectomy without instrumented fusion. METHODS: A total of 15 patients with thoracic dumbbell tumors who underwent primary resection by laminectomy and unilateral total facetectomy without spinal instrumented fusion between 2000 and 2015 were reviewed. Patient characteristics, surgical outcomes (including spinal alignment and stability), disc degeneration, pain, disability, and health-related quality of life were evaluated. Additionally, to analyze the impact of the affected levels on these outcomes, we divided the patients into 2 groups: a middle thoracic group and a thoracolumbar group. RESULTS: The mean duration of follow-up was 100.5 months (range, 36-190 months). The affected level was T3-T4 or below in all patients. Although the local kyphosis angle (8.1° to 12.7°), thoracic kyphosis angle (25.6° to 33.9°), and coronal Cobb angle (6.6° to 9.5°) significantly increased from preoperative to the final visit (P ≤ .02), no patient demonstrated spinal instability. From magnetic resonance imaging, no patient had a worse grade of disc degeneration in the affected level than those in the adjacent levels. The percentage of patients who presented with an Oswestry disability index ≤ 22% was 80%. Moreover, the surgical region did not adversely affect the outcomes. No patient required additional surgery due to spinal instability or deformity. CONCLUSIONS: Unilateral total facetectomy without fusion to resect thoracic dumbbell tumors caused neither spinal deformity nor instability requiring additional surgery at the mid- to long-term follow-up.

A modified minimally invasive surgery for thoracic pyogenic spondylitis: Percutaneous pedicle screw fixation in combination with a vertebral debridement in a separate posterolateral approach-A case report.

In this report, we present a successfully treated case of intractable thoracic pyogenic spondylitis using one-step curettage/bone grafting of spinal anterior segment and less-contaminated percutaneous spinal posterior fixation via separated posterior approaches, which was not compatible with conventional spinal instruments.

Differences in subtrochanteric and diaphyseal atypical femoral fractures in a super-aging prefectural area: YamaCAFe Study.

INTRODUCTION: Atypical femoral fractures (AFFs) have been correlated with long-term use of bisphosphonates (BPs), glucocorticoids (GCs), and femoral geometry. We investigated the incidence and characteristics of subtrochanteric (ST) and diaphyseal (DP) AFFs in all institutes in a super-aging prefectural area. MATERIALS AND METHODS: We performed a blinded analysis of radiographic data in 87 patients with 98 AFFs in all institutes in Yamagata prefectural area from 2009 to 2014. Among the 98 AFFs, 57 AFFs comprising 11 ST fractures in 9 patients and 46 DP fractures in 41 patients with adequate medical records and X-rays were surveyed for time to bone healing and geometry. RESULTS: Of the 87 patients, 67 received BPs/denosumab (77%) and 10 received GCs (11%). Surgery was performed in 94 AFFs. Among 4 AFFs with conservative therapy, 3 required additional surgery. In univariate regression analyses for ST group versus DP group, male-to-female ratio was 2/7 versus 1/40, mean age at fracture was 58.2 (37-75) versus 78 (60-89) years, rheumatic diseases affected 55.5% (5/9) versus 4.9% (2/41), femoral lateral bowing angle was 1.7 (0-6) versus 11.8 (0.8-24)°, GC usage was 67% (6/9) versus 4.9% (2/41), and bone healing time was 12.1 (6-20) versus 8.1 (3-38) months (p < 0.05). In multivariate analyses, higher male-to-female ratio, younger age, greater proportion affected by rheumatic diseases, and higher GC usage remained significant (p < 0.05). CONCLUSIONS: The incidence of AFFs in our prefectural area was 1.43 cases/100,000 persons/year. This study suggests that the onset of ST AFFs have greater correlation with the worse bone quality, vice versa, the onset of DP AFFs correlated with the bone geometry. The developmental mechanisms of AFFs may differ significantly between ST and DP fractures.

Chaperone-Mediated Autophagy after Spinal Cord Injury.

Autophagy is the degradation process of dysfunctional intracellular components and has a crucial function in various human diseases. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is a major route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect. The present study investigated the expression of lysosome-associated membrane protein type 2A (LAMP2A), which is the hallmark of CMA activity, in damaged neural tissue after spinal cord injury (SCI) in mice. The number of LAMP2A-expressing cells was significantly increased at the lesion following SCI. The increased number of LAMP2A-positive cells was observed from 24 h and peaked at 3 days after injury. A western blot analysis confirmed that the level of LAMP2A protein was significantly increased in the injured spinal cord compared with the uninjured cord. On double staining for LAMP2A and different neural cell type markers, the increased expression of LAMP2A was observed in neurons, astrocytes, oligodendrocytes, and microglia/macrophages following injury. An electron microscopic analysis showed that secondary lysosomes were increased in damaged neurons at the lesion site. Immunoelectron microscopy revealed that the gold particles with anti-LAMP2A antibody were frequently localized at the secondary lysosomes in the injured site. These findings indicated that CMA was clearly activated in damaged neural tissue after SCI. The activation of CMA may contribute to the elimination of intracellular aberrant proteins and exert a neuroprotective effect following SCI.

Low-energy extracorporeal shock wave therapy promotes BDNF expression and improves functional recovery after spinal cord injury in rats.

Low-energy extracorporeal shock wave therapy (ESWT) has been used to treat various human diseases. Previous studies have shown that low-energy ESWT promotes the release of various cell growth factors and trophic factors from the cells surrounding the target lesion. The aim of the current study was to determine whether the application of low-energy ESWT upregulates the expression of brain-derived neurotrophic factor (BDNF) and reduces neural tissue damage and functional impairment using a rat model of thoracic spinal cord contusion injury. We found that low-energy ESWT promoted BDNF expression in the damaged neural tissue. The expression of BDNF was increased in various neural cells at the lesion. Additionally, low-energy ESWT increased the area of spared white matter and the number of oligodendrocytes in the injured spinal cord compared with untreated control animals. There were more axonal fibers around the injured site after the application of low-energy ESWT than control. Importantly, low-energy ESWT improved the locomotor functions evaluated by both the BBB scale and ladder rung walking test in addition to the sensory function measured using a von Frey test. Moreover, the electrophysiological assessment confirmed that the conductivity of the central motor pathway in the injured spinal cord was restored by low-energy ESWT. These findings indicate that low-energy ESWT promotes BDNF expression at the lesion site and reduces the neural tissue damage and functional impairment following spinal cord injury. Our results support the potential application of low-energy ESWT as a novel therapeutic strategy for treating spinal cord injury.

B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury.

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

Assessment of the risk of low bone mineral density in premenopausal Japanese female patients with systemic lupus erythematosus.

BACKGROUND: The aim of this study was to assess the relationships between clinical parameters and bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE). METHODS: A total of female 136 SLE patients without menopause were retrospectively assessed to identify associations between age, disease duration, body mass index (BMI), glucocorticoid usage and disease activity and BMD based on the treatment with or without bisphosphonate. There were 71 patients treated with bisphosphonate (bisphosphonate group) and 65 patients without (non-bisphosphonate group). We evaluated the impact of age, disease duration, BMI, serologic SLE markers, glucocorticoid use on BMD of the anterior-posterior (AP) and lateral lumbar spine, total hip and femoral neck using univariate and multivariate linear regression analyses of both bisphosphonate and non-bisphosphonate groups. RESULTS: Multivariate linear regression analyses showed that in non-bisphosphonate group disease duration was negatively associated with BMD of AP spine and femoral neck, whereas in bisphosphonate group these negative associations were not present. However, multivariate linear regression analyses showed a significant relationship between BMI and BMD of the AP spine, femoral neck and total hip, regardless of bisphosphonate treatment. CONCLUSIONS: Bisphosphonate treatment eliminated the negative relationships between disease duration and the BMD of the spine and hip. AP spine and hip BMD in patients with SLE depend on BMI, regardless of bisphosphonate use. SLE serologic markers and glucocorticoid use were not negatively associated with generalized bone loss. SLE patients with low BMI have a high risk of generalized bone loss, and should be assessed and treated to prevent osteoporosis even before menopause.

The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.