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PurposeLateral interbody fusion and posterior percutaneous pedicle screw (LIF-PPS) fixation has been performed in two-stage positioning. The aim of this study was to investigate the surgical outcomes of simultaneous single-position LIF-PPS fixation using O-arm-based navigation.MethodsOverall, 102 consecutive subjects underwent indirect decompression surgery for spondylolisthesis with LIF-PPS fixation. Fifty-one subjects underwent surgery with repositioning, and 51 in the right lateral decubitus position. We compared these two groups in terms of the surgery time, occupancy time in the operating room, intraoperative blood loss, Japanese Orthopaedic Association (JOA) score, local lordosis acquisition in postoperative radiographs, and accuracy of screw insertion using postoperative CT scans.ResultsIn the single-position group, surgery time, occupancy time of the operating room, and estimated blood loss were 93.3 ± 19.3 min (vs. the repositioning group: 121.0 ± 37.1 min; p <  0.001), 176.3 ± 36.4 min (vs. 272.4 ± 42.7 min; p < 0.001), and 93.4 ± 78.8 ml (vs. 40.9 ± 28.7 ml; p < 0.001), respectively. The JOA scores (pre-/postoperative) were 15.1 ± 3.0/24.4 ± 2.8 (p < 0.001) for the single-position group and 15.1 ± 4.0/24.8 ± 3.0 (p < 0.001) for the repositioning group. The rate of misplacement was 1.8% versus 4.0%, respectively (p = 0.267), and the lordosis acquisition was 4.2° ± 4.1° versus 4.4° ± 3.2°, respectively (p = 0.516).ConclusionsSingle-position surgery exhibited comparable clinical outcomes and local lordosis acquisition with conventional repositioning LIF-PPS fixation. This single-position minimally invasive technique reduces the occupancy time of the operating room and workforce requirements.Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

PurposeThere are few epidemiological studies of spinal surgery in Asia and none in Japan. The goal of this study was to review spine surgeries performed in our group between 2004 and 2015 in a cross-sectional study, with a focus on the effects of the superaging society on the characteristics and trends of spinal surgeries.MethodsA retrospective review was performed for all 45,831 spinal surgeries conducted between 2004 and 2015 and recorded in our prospective multicenter database.ResultsDuring the study period, there was a significant increase in annual spine surgeries (p < 0.05). The proportion of elderly patients (aged ≥ 70) also increased, and the mean age at the time of surgery significantly increased from 54.6 years in 2004 to 63.7 years in 2015 (p < 0.05). Regarding the etiology, there were significant increases in degenerative disease (p < 0.01) and osteoporotic vertebral fracture, and a significant decrease in rheumatic spondylosis from 2004 to 2015 (p < 0.01). Instrumentation surgery increased over time, with the performance of MIS, BKP and LLIF as new procedures in recent years (p < 0.01). The mean reoperation rate was 2.0% and this rate did not change significantly over time, although the rate of reoperation due to surgical site infection significantly increased from 0.9 to 1.5% (p < 0.05).ConclusionsOur data showed marked increases in the number of spine surgeries, the age of patients, and the number of surgeries for degenerative diseases. This large-scale study provides indicators for planning the future development of spine surgery and for treatment of spinal diseases in daily practice.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19–91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1–93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan–Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.

Metabolic dysfunction in chondrocytes drives the pro-catabolic phenotype associated with osteoarthritic cartilage. In this study, substitution of galactose for glucose in culture media was used to promote a renewed dependence on mitochondrial respiration and oxidative phosphorylation. Galactose replacement alone blocked enhanced usage of the glycolysis pathway by IL1β-activated chondrocytes as detected by real-time changes in the rates of proton acidification of the medium and changes in oxygen consumption. The change in mitochondrial activity due to galactose was visualized as a rescue of mitochondrial membrane potential but not an alteration in the number of mitochondria. Galactose-replacement reversed other markers of dysfunctional mitochondrial metabolism, including blocking the production of reactive oxygen species, nitric oxide, and the synthesis of inducible nitric oxide synthase. Of more clinical relevance, galactose-substitution blocked downstream functional features associated with osteoarthritis, including enhanced levels of MMP13 mRNA, MMP13 protein, and the degradative loss of proteoglycan from intact cartilage explants. Blocking baseline and IL1β-enhanced MMP13 by galactose-replacement in human osteoarthritic chondrocyte cultures inversely paralleled increases in markers associated with mitochondrial recovery, phospho-AMPK, and PGC1α. Comparisons were made between galactose replacement and the glycolysis inhibitor 2-deoxyglucose. Targeting intermediary metabolism may provide a novel approach to osteoarthritis care.

SummaryThe aim of this study is to investigate the effect of bisphosphonate (BP) on mortality after osteoporotic vertebral fracture (OVF). BP medication (hazard ratios = 0.593; 95%CI: 0.361–0.976) was significantly associated with reduced all-cause mortality after OVF.PurposeOsteoporotic vertebral fracture (OVF) is the most common type of fragility fracture. Bisphosphonate (BP) medication was suggested to have positive effects on both fracture prevention and recovery outcomes. The aim of this study is to investigate the effect of BP on mortality after OVF.MethodsThis cohort study involved 535 patients (170 males and 365 females), aged ≥ 65 years (mean age: 82.6 ± 7.0 years, mean follow-up periods: 33.0 ± 25.8 months) who were hospitalized after OVF from January 2011 to December 2019 at a public hospital. Patients treated with PTH (parathyroid hormone), PTH or PTHrp analogues, denosumab, and selective estrogen receptor modulators were excluded. Kaplan–Meier survival curves on mortality of patients with OVF with and without BP treatment were prepared, and log-rank tests were performed. Cox proportional hazards model was used to identify factors associated with mortality after OVF.ResultsThis study included 163 (30.5%) patients treated with BP. Kaplan–Meier survival curves showed that the mortality rate after OVF was significantly lower in patients treated with BP (P < 0.001). Cox proportional hazards model showed that older age (hazard ratios [HR] = 1.066; 95%CI:1.035–1.103), male sex (HR = 2.248; 95%CI:1.427–3.542), malnutrition (geriatric nutritional risk index < 92) (HR = 1.691; 95%CI:1.005–2.846), BP medication (HR = 0.593; 95%CI: 0.361–0.976), and Japanese Orthopaedic Association score at discharge (HR = 0.941; 95%CI: 0.892–0.993) were significantly associated with all-cause mortality after OVF.ConclusionsBP medication is beneficial not only for fracture prevention but also for mortality after OVF.

Transient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca 2+ signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV4 activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.

Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.

Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity.

Background Voriconazole-induced periostitis is predominantly reported in adults, with pediatric cases being exceedingly rare. Case presentation This report describes an 8-year-old boy with voriconazole-induced periostitis presenting with finger pain and nodules, initially suspected to be bone tumors. The patient had been on voriconazole for two years and seven months to treat Aspergillus pneumonia and had been hospitalized for six months due to chronic graft-versus-host disease following hematopoietic stem cell transplantation and total body irradiation for severe congenital neutropenia. The patient presented with a five-month history of pain and a one-month history of a mass in the middle finger of his right hand. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the distal ulna. Differential diagnoses included benign bone-forming tumors, such as osteochondroma post-total body irradiation, and bizarre parosteal osteochondromatous proliferation. The diagnosis of voriconazole-induced periostitis was confirmed as new sites of periostitis became apparent during the disease course. Conclusions Voriconazole-induced periostitis should be considered, even in pediatric patients, when multiple nodular periosteal reactions are observed in immunosuppressed patients undergoing long-term voriconazole therapy.