Oxidative stress has been reported to be involved in numerous human diseases, including musculoskeletal disorders such as osteoarthritis. However, the interaction between intervertebral disc (IVD) degeneration and oxidative stress is not well understood. The purpose of the present study was to elucidate the contribution of oxidative stress to IVD degeneration and the efficacy of antioxidant treatment for degenerative discs. The expression level of an oxidative stress marker, nitrotyrosine, was assessed by immunohistochemistry and Western blotting. For evaluating intracellular reactive oxygen species (ROS) levels and oxidative stress in rat annulus fibrosus (AF) cells, flow cytometry and luciferase assay with an OKD48 construct were performed. The grade of IVD degeneration was assessed by magnetic resonance imaging and histological analysis. A high frequency of nitrotyrosine-positive cells was observed in rat and human degenerative discs. mRNA expression of catabolic factors such as tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), and cyclooxygenase-2 (COX-2) was significantly induced by treatment with H2O2 or buthionine sulfoximine, whereas that of aggrecan, an important chondrogenic proteoglycan, was reduced in a dose-dependent manner. Treatment with mitogen-activated protein kinase (MAPK) inhibitors blocked the inductive effect of excessive ROS on COX-2 mRNA expression. Western blotting confirmed the phosphorylation of MAPKs in H2O2 and BSO-treated AF cells. Conversely, we showed that TNF-α induced oxidative stress with increased intracellular ROS levels in AF cells. Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated the catabolic effect of excessive ROS and TNF-alpha in vitro. Finally, we showed that oral administration of NAC prevented IVD degeneration in rat degenerative model. A positive feedback loop was formed between excessive ROS and TNF-alpha in AF cells. Thus, oxidative stress contributes to the progression of IVD degeneration and NAC can be a therapeutic option for IVD degeneration.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

Study Design.: Retrospective review of surgically treated 481 adult patients with spinal disorders. Objective.: The aim of this study was to elucidate the effect of frailty and comorbidities on postoperative health-related quality of life (HRQoL) and complication rates. Summary of Background Data.: Elective surgeries for spinal disorders not only improve clinical outcomes but also have high complication rates. Methods.: We retrospectively reviewed the results of consecutive elective spine surgeries for 156 adult spinal deformities (ASDs: 65 ± 9 years), 152 degenerative spondylolisthesis (DS: 64 ± 10 years), or 173 lumbar spinal canal stenosis (LSCS: 71 ± 9 years) with follow-up of at least 2 years. Modified Frailty Index (mFI) and Charlson Comorbidity Index (CCI) were determined from baseline demographics. We compared the prevalence and the influence of mFI and CCI on postoperative outcomes and complication rates. Results.: The mFI and CCI were significantly worse in ASD than in others (mFI: ASD 0.09 ± 0.12, DS 0.06 ± 0.06, LSCS 0.04 ± 0.05, P < 0.01. CCI: ASD 2.1 ± 1.6, DS 1.4 ± 0.7, LSCS 1.6 ± 0.9, P < 0.01). Postoperative HRQoL deteriorated as mFI worsened in ASD (nofrail: Oswestry Disability Index [ODI] 26 ± 11, Scoliosis Research Society Questionnaire [SRS] 3.7 ± 0.7; prefrail: ODI 32 ± 12, SRS 3.6 ± 0.6; frail: ODI 42 ± 15, SRS 3.2 ± 0.7). In DS and LSCS, however, SF-36 physical component score and mental component score improved regardless of mFI and CCI. The 2-year major complications rate increased with frailty (36%, 58%, and 81%) in ASD, but not in others. Conclusion.: ASDs were more frail and had more comorbidities than the other populations. In ASD, postsurgical outcomes and complication rates deteriorated as frailty and CCI increased, whereas surgery produced favorable outcomes and acceptable complication rates in DS and LSCS regardless of frailty and CCI. Careful patient selection and treatment of comorbidities before surgery may decrease complications and improve outcomes for the surgical treatment of ASD. Level of Evidence: 4

Posterior spinal fusion for adolescent idiopathic scoliosis is one of the most invasive surgical procedures performed in children and adolescents. Because of the extensive surgical incision and massive tissue trauma, posterior spinal fusion causes severe postoperative pain. Intravenous patient-controlled analgesia with opioids has been the mainstay of postoperative pain management in these patients. However, the use of systemic opioids is sometimes limited by opioid-related side effects, resulting in poor analgesia. To improve pain management while reducing opioid consumption and opioid-related complications, concurrent use of analgesics and analgesic modalities with different mechanisms of action seems to be rational. The efficacy of intrathecal opioids and nonsteroidal anti-inflammatory drugs as components of multimodal analgesia in scoliosis surgery has been well established. However, there is either controversy or insufficient evidence regarding the use of other analgesic methods, such as continuous ketamine infusion, perioperative oral gabapentin, acetaminophen, continuous wound infiltration of local anesthetics, a single dose of systemic dexamethasone, and lidocaine infusion in this patient population. Moreover, appropriate combinations of analgesics have not been established. The aim of this literature review is to provide detailed information of each analgesic technique so that clinicians can make appropriate choices regarding pain management in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion.

The use of artificial intelligence (AI) as a tool supporting the diagnosis and treatment of spinal diseases is eagerly anticipated. In the field of diagnostic imaging, the possible application of AI includes diagnostic support for diseases requiring highly specialized expertise, such as trauma in children, scoliosis, symptomatic diseases, and spinal cord tumors. Moiré topography, which describes the 3-dimensional surface of the trunk with band patterns, has been used to screen students for scoliosis, but the interpretation of the band patterns can be ambiguous. Thus, we created a scoliosis screening system that estimates spinal alignment, the Cobb angle, and vertebral rotation from moiré images. In our system, a convolutional neural network (CNN) estimates the positions of 12 thoracic and 5 lumbar vertebrae, 17 spinous processes, and the vertebral rotation angle of each vertebra. We used this information to estimate the Cobb angle. The mean absolute error (MAE) of the estimated vertebral positions was 3.6 pixels (~5.4 mm) per person. T1 and L5 had smaller MAEs than the other levels. The MAE per person between the Cobb angle measured by doctors and the estimated Cobb angle was 3.42°. The MAE was 4.38° in normal spines, 3.13° in spines with a slight deformity, and 2.74° in spines with a mild to severe deformity. The MAE of the angle of vertebral rotation was 2.9°±1.4°, and was smaller when the deformity was milder. The proposed method of estimating the Cobb angle and AVR from moiré images using a CNN is expected to enhance the accuracy of scoliosis screening.