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Purpose Extreme lateral interbody fusion provides minimally invasive treatment of spinal deformity, but complications including nerve and psoas muscle injury have been noted. To avoid nerve injury, mini-open anterior retroperitoneal lumbar interbody fusion methods using an approach between the aorta and psoas, such as oblique lumbar interbody fusion (OLIF) have been applied. OLIF with percutaneous pedicle screws without posterior decompression can indirectly decompress the spinal canal in lumbar degenerated spondylolisthesis. In the current study, we examined the radiographic and clinical efficacy of OLIF for lumbar degenerated spondylolisthesis. Methods We assessed 20 patients with lumbar degenerated spondylolisthesis who underwent OLIF and percutaneous pedicle screw fixation without posterior laminectomy. MR and CT images and clinical symptoms were evaluated before and 6 months after surgery. Cross sections of the spinal canal were evaluated with MRI, and disk height, cross-sectional areas of intervertebral foramina, and degree of upper vertebral slip were evaluated with CT. Clinical symptoms including low back pain, leg pain, and lower extremity numbness were evaluated using a visual analog scale and the Oswestry Disability Index before and 6 months after surgery. Results After surgery, significant increases in axial and sagittal spinal canal diameter (12 and 32 %), spinal canal area (19 %), disk height (61 %), and intervertebral foramen areas (21 % on the right side, 39 % on the left), and significant decrease of upper vertebral slip (−9 %) were found ( P  < 0.05). Low back pain, leg pain, and lower extremity numbness were significantly reduced compared with before surgery ( P  < 0.05). Conclusions Significant improvements in disk height and spinal canal area were found after surgery. Bulging of disks was reduced through correction, and stretching the yellow ligament may have decompressed the spinal canal. Lumbar anterolateral fusion without laminectomy may be useful for lumbar spondylolisthesis with back and leg symptoms.

Bone metastasis commonly causes severe pain. Nerve growth factor (NGF) contributes to pain, and promotes the production of pain-associated neuropeptides, such as calcitonin gene-related peptide (CGRP), from sensory nerve endings. We hypothesized that breast cancer cells have NGF levels that promote axonal growth from dorsal root ganglia (DRGs) neurons, and increase their CGRP production associated with pain from spinal metastases. Expression of NGF by the cultured rat breast adenocarcinoma cell line CRL-1666 was determined using an enzyme-linked immunosorbent assay (ELISA). We constructed a rat model of spinal metastasis by implanting CRL-1666 into L6 vertebrae and determined the change in CGRP expression in DRG neurons innervating vertebrae immunohistochemically. NGF was expressed by CRL-1666. When DRG cells were co-cultured with CRL-1666, there were more CGRP-ir neurons and with a greater average length of axon growth than in cultures without CRL-1666 (p<0.05). In the rat model of metastasis, there were more CGRP-ir DRG neurons innervating vertebra treated with CRL-1666 than in vertebrae from sham surgery control rats (p<0.05). NGF from breast cancer may mediate spinal bone pain from metastasis via axonal growth and up-regulation of pain-associated neuropeptides.

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, we had previously performed quantitative trait locus (QTL) analysis, using (SM/J×SMXA-5)F2 intercross mice, and identified Fl1sa on chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver. Furthermore, isoamyl acetate-hydrolyzing esterase 1 homolog (Iah1) was selected as the most likely candidate gene for Fl1sa. Iah1 gene expression in fatty liver-resistant A/J-12SM mice was significantly higher than in fatty liver-susceptible A/J mice. These data indicated that the Iah1 gene might be associated with fatty liver development. However, the function of murine Iah1 remains unknown. Therefore, in this study, we created Iah1 knockout (KO) mice with two different backgrounds [C57BL/6N (B6) and A/J-12SM (A12)] to investigate the relationship between Iah1 and liver lipid accumulation. Liver triglyceride accumulation in Iah1-KO mice of B6 or A12 background did not differ from their respective Iah1-wild type mice under a high-fat diet. These results indicated that loss of Iah1 did not contribute to fatty liver. On the other hands, adipose tissue dysfunction causes lipid accumulation in ectopic tissues (liver, skeletal muscle, and pancreas). To investigate the effect of Iah1 deficiency on white adipose tissue, we performed DNA microarray analysis of epididymal fat in Iah1-KO mice of A12 background. This result showed that Iah1 deficiency might decrease adipokines Sfrp4 and Metrnl gene expression in epididymal fat. This study demonstrated that Iah1 deficiency did not cause liver lipid accumulation and that Iah1 was not a suitable candidate gene for Fl1sa.

Background Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. Methods Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. Results The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively ( p  < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period ( p  < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires ( p  < 0.05). Conclusions The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Background Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. Method Six-week-old male C57BR/J mice were used ( n  = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4–L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted. Results On gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p  < 0.05). Conclusions MIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee.

Introduction Interleukin-6 (IL-6) is thought to play a crucial role in the radicular pain caused by lumbar spinal stenosis. However, efficacy of inhibition of IL-6 for sciatica in patients with lumbar spinal stenosis has not been clarified. The purpose of the current study was to examine the effect of the anti-IL-6 receptor monoclonal antibody, tocilizumab, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. Methods Sixty patients with low back and radicular leg pain caused by spinal stenosis were investigated. In 30 patients, we infiltrated 2.0 mL of lidocaine and 80 mg of tocilizumab onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone were used in 30 patients. Low back pain, leg pain, and leg numbness were evaluated during 1 month after spinal nerve infiltration. Results Infiltration of tocilizumab was more effective than dexamethasone for leg pain (3 days, 1, 2, and 4 weeks), low back pain (3 days, 1, 2 and 4 weeks), and leg numbness (3 days, 1 and 2 weeks). No adverse event was observed in either group. Conclusion Our results indicate that the epidural administration of an anti-IL-6 receptor monoclonal antibody, tocilizumab, onto the spinal nerve produced reduction of radicular leg pain, numbness, and low back pain without adverse event. IL-6 may be one of the inducers of pain caused by spinal stenosis in humans.

Background Age-related sarcopenia can cause various forms of physical disabilities. We investigated how sarcopenia affects degenerative lumbar scoliosis (DLS) and lumbar spinal canal stenosis (LSCS). Methods Subjects comprised 40 elderly women (mean age 74 years) with spinal disease whose chief complaints were low back pain and lower limb pain. They included 15 cases of DLS (mean 74.8 years) and 25 cases of LSCS (mean age 72.9 years). We performed whole-body dual-energy X-ray absorptiometry (DXA) to analyze body composition, including appendicular and trunk skeletal muscle mass index (SMI; lean mass (kg)/height (m) 2 ) and bone mineral density (BMD). A diagnostic criterion for sarcopenia was an appendicular SMI <5.46. To check spinal alignment, lumbar scoliosis (LS), sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and vertebral rotational angle (VRA) were measured. Clinical symptoms were determined from the Japanese Orthopedic Association scores, low back pain visual analog scale, and Roland-Morris Disability Questionnaire (RDQ). Criteria for DLS were lumbar scoliosis >10° and a sagittal vertical axis (SVA) >50 mm. Sarcopenia prevalence, correlations between spinal alignment, BMD, and clinical symptoms with appendicular and trunk SMIs, and correlation between spinal alignment and clinical symptoms were investigated. Results DLS cases had significantly lower body weight, BMI, lean mass arm, and total lean mass than LSCS cases. Sarcopenia prevalence rates were 4/25 cases (16%) in LSCS and 7/15 cases (46.6%) in DLS, revealing a high prevalence in DLS. Appendicular SMIs were DLS 5.61 and LSCS 6.13 ( p  < 0.05), and trunk SMIs were DLS 6.91 and LSCS 7.61 ( p  < 0.01) showing DLS to have significantly lower values than LSCS. Spinal alignment correlations revealed the appendicular SMI was negatively correlated with PT ( p  < 0.05) and the trunk SMI was found to have a significant negative correlation with SVA, PT, LS, and VRA ( p  < 0.05). The trunk SMI was found to have a significant positive correlation with BMD ( p  < 0.05). As for clinical symptoms, RDQ was negatively correlated with appendicular SMI and positively correlated with PT ( P  < 0.05). Conclusions Sarcopenia complications were noted in 16% of LSCS patients and a much higher percentage, or 46.6%, of DLS patients. Appendicular and trunk SMIs were both lower in DLS, suggesting that sarcopenia may be involved in scoliosis. The appendicular skeletal muscle was related to posterior pelvic tilt, while the trunk muscle affected stooped posture, posterior pelvic tilt, lumbar scoliosis, and vertebral rotation. Decreases in trunk muscle mass were also associated with osteoporosis. Moreover, RDQ had a negative correlation with appendicular skeletal muscle mass and a positive correlation with PT, suggesting that sarcopenia may be associated with low back pain as a result of posterior pelvic tilt. Our research reveals for the first time how sarcopenia is involved in spinal deformations, suggesting decreases in pelvic/lumbar support structures such as trunk and appendicular muscle mass may be involved in the progression of spinal deformities and increased low back pain.

Cadaver surgical training (CST), which ensures medical safety by improving the skills of surgeons, is popular overseas. However, training involves ethical issues given the use of cadavers. In 2012, the Japan Surgical Society and the Japanese Association of Anatomists compiled and opened the “Guidelines for Cadaver Dissection in Education and Research of Clinical Medicine (Guideline 2012)” to the public. This has allowed Japan to conduct CST or research under the regulations of Postmortem Examination and Corpse Preservation Act and the Body Donation Act. However, its dissemination has been sluggish. The Clinical Anatomy Lab (CAL), established in 2010 at Chiba University, is a facility for conducting CST and research. In the 11 years since its inception, 250 programs have been implemented. Orthopedics had the most implemented in the clinical field, with 120 (48%), followed by emergency and critical care medicine with 27 (10.8%), and neurological surgery with 27 (10. 8%). Based on the purpose of the training, the most common objective for the programs (approximately 83%) was education. Further, the highest number of programs was recorded in 2018 (34) and participants in 2017 (631). The implementation of CST requires more than just guiding surgeons to a dissection practice room. There are several methods of preserving cadavers to make them suitable for CST. For various surgical simulations, an operating table is more suitable than a dissection table. The current paper provides information on how to implement CST in universities that have so far only worked on anatomy education for medical students.

Prospective case series. To examine the clinical efficacy of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion (OLIF) for degenerated lumbar spinal kyphoscoliosis. The existing surgical procedures for the treatment of spinal kyphotic deformity, including Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection procedures, are invasive in nature. Extreme lateral interbody fusion to provide less invasive treatment of the deformity has been reported, but complications including spinal nerve and psoas muscle injury have been noted. In the current study, we examined the clinical efficacy and complications of OLIF for degenerated lumbar spinal kyphoscoliosis. Twelve patients with degenerated lumbar spinal kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with open pedicle screws or percutaneous pedicle screws, without real-time monitoring by electromyography. Visual analog scale score and Oswestry disability index were evaluated before and 12 months after surgery, and fusion rate at OLIF cage, correction of the deformity, total blood loss, and surgical complications were also evaluated. Pain scores significantly improved after surgery (p<0.05). Fusion rate was found to be 90%, balance parameters also improved after surgery (p<0.05), and average total blood loss was less than 350 mL. There was no spinal nerve, major vessel, peritoneal, or urinary injury, or breakage of instrumentation. OLIF surgery for degenerated lumbar spinal kyphoscoliosis is less invasive than other procedures and good surgical results were produced without major complications.

Background This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. Methods Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. Results The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase ( Dnmt 3a ), ten–eleven translocation ( Tet ) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. Conclusions The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.