Electrophilic compounds are a newly recognized class of redox-active neuroprotective compounds with electron deficient, electrophilic carbon centers that react with specific cysteine residues on ...targeted proteins via thiol (S-)alkylation. Although plants produce a variety of physiologically active electrophilic compounds, the detailed mechanism of action of these compounds remains unknown. Catechol ring-containing compounds have attracted attention because they become electrophilic quinones upon oxidation, although they are not themselves electrophilic. In this study, we focused on the neuroprotective effects of one such compound, carnosic acid (CA), found in the herb rosemary obtained from Rosmarinus officinalis. We found that CA activates the Keap1/Nrf2 transcriptional pathway by binding to specific Keap1 cysteine residues, thus protecting neurons from oxidative stress and excitotoxicity. In cerebrocortical cultures, CA-biotin accumulates in non-neuronal cells at low concentrations and in neurons at higher concentrations. We present evidence that both the neuronal and non-neuronal distribution of CA may contribute to its neuroprotective effect. Furthermore, CA translocates into the brain, increases the level of reduced glutathione in vivo, and protects the brain against middle cerebral artery ischemia/reperfusion, suggesting that CA may represent a new type of neuroprotective electrophilic compound.
Introduction: Spinal muscular atrophy (SMA) is defined as a neuromuscular disorder induced by progressive weakness of the skeletal muscle and is usually accompanied by progressive spinal deformity ...including scoliosis. The newly developed Nusinersen, which is the first approved drug worldwide for SMA, requires accurate intrathecal injection, which is sometimes difficult in patients with severe spinal deformity.Technical Note: For an accurate intrathecal approach in patients who have spinal fusion surgery to treat neuromuscular scoliosis, we have combined an L3 laminectomy with spinal correction and fusion surgery. Here, we review four cases of SMA in patients who underwent the additional L3 laminectomy during surgery to treat spinal scoliosis. A successful intrathecal approach was made using fluoroscopic guidance in all four patients, who were then administered with Nusinersen.Conclusions: Our findings show that additional lumbar laminectomy during surgery for spinal scoliosis has effectively allowed for intrathecal injection of Nusinersen.
Introduction: Intraoperative hypothermia is associated with perioperative complications such as blood loss and wound infection. Thus, perioperative heat retention methods to prevent perioperative ...hypothermia such as providing a warmed blanket and active patients' warming are important. Although major surgery and pediatric patient age are noted as risk factors, only a few studies focus on hypothermia as an intraoperative complication in pediatric scoliosis surgery. The aim of this study is to investigate the incidence of intraoperative hypothermia in pediatric scoliosis surgery and the associated preoperative risk factors.Methods: We retrospectively reviewed the records of pediatric patients who underwent posterior spinal fusion at a single institution between 2015 and 2019. We recorded the background data, perioperative data, lowest recorded core temperature, and perioperative complications. Patients were divided into those whose temperature decreased below 36°C (Group H) and those who maintained a temperature of 36°C or greater (Group N) during surgery. We compared the two groups and performed multivariate analysis to identify preoperative risk factors for intraoperative hypothermia.Results: A total of 103 patients underwent posterior spinal fusion; 56 for adolescent idiopathic scoliosis and 47 for neuromuscular scoliosis. Hypothermia was observed in 40 patients (38.8%). Group H had more non-adolescent idiopathic scoliosis (AIS) patients, lower mean body mass index, greater mean blood loss, greater number of fused vertebrae, larger preoperative Cobb angle, and lower initial core body temperature (immediately after induction of anesthesia). On multivariate analysis, a diagnosis of neuromuscular scoliosis, a lower body mass index, and a lower initial core body temperature were identified as independent risk factors for intraoperative hypothermia.Conclusions: The incidence of hypothermia in pediatric posterior scoliosis surgery is 38.8%. Diagnosis of non-AIS, lower body mass index, and lower core body temperature at the time of anesthesia induction are preoperative risk factors for intraoperative hypothermia.
Abstract
Background
Recently, Oblique lumbar interbody fusion (OLIF) is commonly indicated to correct the sagittal and coronal alignment in adult spinal deformity (ASD). Endplate fracture during ...surgery is a major complication of OLIF, but the detailed location of fracture in vertebral endplate in ASD has not yet been determined. We sought to determine the incidence and location of endplate fracture and subsidence of the OLIF cage in ASD surgery, and its association with fusion status and alignment.
Methods
We analyzed 75 levels in 27 patients were analyzed using multiplanar CT to detect the endplate fracture immediately after surgery and subsidence at 1 year postoperatively. The prevalence was compared between anterior and posterior, approach and non-approach sides, and concave and convex side. Their association with fusion status, local and global alignment, and complication was also investigated.
Results
Endplate fracture was observed in 64 levels (85.3%) in all 27 patients, and the incidence was significantly higher in the posterior area compared with the anterior area (85.3 vs. 68.0%,
p
=0.02) of affected vertebra in the sagittal plane. In the coronal plane, there was no significant difference in incidence between left (approach) and right (non-approach) sides (77.3 and 81.3%, respectively), or concave and convex sides (69.4 and 79.6%) of wedged vertebra. By contrast, cage subsidence at 1 year postoperatively was noted in 14/75 levels (18.7%), but was not associated with endplate fracture. Fusion status, local and global alignment, and complications were not associated with endplate fracture or subsidence.
Conclusion
Endplate fracture during OLIF procedure in ASD cases is barely avoidable, possibly induced by the corrective maneuver with ideal rod counter and cantilever force, but is less associated with subsequent cage subsidence, fusion status, and sustainment of corrected alignment in long fusion surgery performed even for elderly patients.
Low back pain (LBP) is a major public health problem that adversely affects the quality of life (QOL) of workers. The etiology of LBP is considered to be multi-factorial with individual, physical, ...and psychosocial factors contributing to its development and persistence. Although prevention of LBP in workers in the workplace is very important, only a small number of studies have assessed the risk factors and epidemiology of LBP among Japanese factory workers who stand as part of their job. This cross-sectional study investigated the prevalence of LBP in 691 factory employees who conducted their work while standing. Health-related QOL was evaluated using the Roland-Morris Disability Questionnaire (RDQ) to quantify the severity of LBP with the aim of identifying risk factors for LBP among workers who stand as part of their work in an electronics manufacturing company. We observed that the prevalence of LBP lasting for at least 48 hours within a week was 20.0% among participants, with female employees and those with a prior history of LBP having a significantly increased risk of developing LBP. The distribution of the RDQ score showed a negative regression curve among the employees, which was different from the normal distribution pattern reported previously in Japanese patients with LBP. These findings suggest that prolonged standing among factory workers poses an increased risk for LBP.
Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and ...axial loading contribute to discogenic LBP's pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (-) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (-) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.
Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and ...characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.
Objective Although secondary lymphedema is a common complication after surgical and radiation therapy for cancer, the treatment options for lymphedema remain limited and largely ineffective. We thus ...studied the effect of extracorporeal shock wave therapy on promoting lymphangiogenesis and improving secondary lymphedema. Methods A rabbit ear model of lymphedema was created by disruption of lymphatic vessels. Two weeks after surgery, the lymphedematous ear was treated with or without low-energy shock waves (0.09 mJ/mm2 , 200 shots), three times per week for 4 weeks. Results Western blot analysis showed that the expression of vascular endothelial growth factor (VEGF)-C (1.23-fold, P < .05) and VEGF receptor 3 (VEGFR3; 1.53-fold, P < .05) was significantly increased in the ears treated with shock wave than in the untreated lymphedematous ears. Compared with the control group, shock wave treatment led to a significant decrease in the thickness of lymphedematous ears (3.80 ± 0.25 mm vs 4.54 ± 0.18 mm, P < .05). Immunohistochemistry for VEGFR3 showed the density of lymphatic vessels was significantly increased by shock wave treatment ( P < .05). Conclusion Extracorporeal shock wave therapy promotes lymphangiogenesis and ameliorates secondary lymphedema, suggesting that extracorporeal shock wave therapy may be a novel, feasible, effective, and noninvasive treatment for lymphedema.
Multiple human and animal studies suggest that the upregulation of inflammatory cytokines and other pain‐related molecules in degenerated or injured intervertebral discs (IVDs) may cause discogenic ...low back pain (LBP). We previously reported that macrophages in injured IVD in mice produced inflammatory cytokines, but not other pain‐related molecules. CD14 is a monocyte marker expressed mainly by macrophages. The aim of the current study was to evaluate the role of CD14‐positive cells in inflammatory cytokine and pain‐related molecule expression in human degenerated IVD. IVD samples were harvested from 14 patients, including 10 with lumbar spinal stenosis, four with adult spinal deformity, and one with lumbar disc herniation during spinal interbody fusion surgery. Harvested IVD‐derived mononuclear cells were obtained and CD14‐positive (+) and CD14‐negative (−) cells were separated using CD14 antibody and streptavidin‐labeled magnetic beads. Inflammatory cytokines messenger RNA (mRNA) in the CD14(+) and CD14(−) cells, including tumor necrosis factor ɑ (TNFA), in, terleukin‐1β (IL1B) and IL6, were determined using quantitative polymerase chain reaction (qPCR) and their expression levels were compared. To evaluate factors controlling the regulation of pain‐related molecules mRNA expression, cultured CD14(−) and CD14(+) cells from IVDs were stimulated with recombinant human TNF‐ɑ and IL‐1β and levels of pain‐related molecules, including calcitonin gene‐related peptide (CGRP) and nerve growth factor (NGF) were determined using qPCR. Levels of TNFA, IL1B, IL6, and NGF in CD14(+) cells were significantly increased compared with those in CD14(−) cells (TNFA, p = 0.006; IL1B, p = .017; IL6, p = .010; NGF, p = .027). Following TNFA stimulation, NGF levels were significantly increased in CD14(−) and CD14(+) cells (CD14(−), p = .003; CD14(+), p < .001) and CGRP was significantly increased in CD14(−) IVD cells (p = .040). Following IL1B stimulation, NGF levels were significantly increased in CD14(−) cells (p = .004). CD14(+) cells had higher TNFA, IL1B, IL6, and NGF expressions than CD14(−) cells in human degenerated IVDs. Additionally, TNFA stimulation promoted the upregulation of NGF and CGRP in CD14(−) cells. These findings suggested that CD14(+) cells directly and indirectly contributed to inflammatory cytokine and pain‐related molecule expression in human degenerated IVD. CD14(+) cells might be important in the pathological mechanism of chronic discogenic LBP in humans.
We evaluated the role of CD14‐positive cells in inflammatory cytokine and pain‐related molecule expression in human degenerated intervertebral discs (IVDs). CD14(+) cells directly and indirectly contributed to inflammatory cytokine and pain‐related molecule expression in human degenerated IVD. CD14(+) cells might be important in the pathological mechanism of chronic discogenic low back pain (LBP) in humans.
Introduction: Patients with spinal muscular atrophy (SMA) usually have progressive scoliosis. Although fusion of the sacrum or pelvis has been recommended for correcting pelvic obliquity (PO), the ...procedure is invasive. This study determined as to whether performing instrumentation to the fifth lumbar vertebra (L5) is safe and effective for scoliosis in patients with SMA.Methods: Twelve patients with SMA underwent posterior spinal fusion and stopping instrumentation at the L5 level. We evaluated age at surgery, the duration of surgery, blood loss, complications, preoperative and postoperative Cobb angles, and PO.Results: The mean age at surgery was 11.4 years; the mean duration of surgery was 319 minutes, and the mean blood loss was 1170 mL. The Cobb angle improved from 97.3° to 39.1° at 1 month postoperatively (correction rate, 60.9%) and to 42.3° at the final follow-up. PO was corrected from 27.8° to 13.1° at 1 month postoperatively (correction rate, 51.7%) and to 19.8° at the final follow-up. No complications were reported. All patients showed improvement in low back pain, with reduced difficulty while sitting. However, >10% correction loss of PO was observed in 6 patients with high preoperative PO.Conclusions: The correction rate of scoliosis in SMA patients with posterior spinal fusion and instrumentation to the L5 level was acceptable, and no complications occurred. Scoliosis associated with SMA was more rigid and severer than scoliosis associated with Duchenne muscular dystrophy. Correction rates of the Cobb angle and PO in SMA patients with instrumentation to L5 were similar to those in SMA patients with instrumentation to the sacrum or pelvis. Correction loss of PO was greater in patients with high preoperative PO than in those with low preoperative PO. Instrumentation and fusion to L5 for scoliosis in patients with SMA seems safe and effective, except in cases of high preoperative PO.
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