New Paradigms of Radiotherapy for Bone Metastasis

Proper care of patients with bone metastasis requires interdisciplinary treatments. Radiotherapy (RT) plays a central role in the management of painful bone metastasis. External beam RT can provide rapid successful palliation of painful bone metastasis in 50–80% of patients, is associated with very few adverse effects and leads to complete pain relief at the treated site in up to one‐third of patients. Intensity‐modulated RT (IMRT) or stereotactic body RT (SBRT) enables the delivery of higher doses to the target tumor while minimizing the dose to adjacent organs. Reirradiation using IMRT or SBRT is a valuable option for the management of bone metastases. A multidisciplinary team, especially one consisting of a spinal surgeon and rehabilitation physician, is particularly useful for treating patients with spinal bone metastases characterized by spinal instability. Rehabilitation intervention which increases the physical activity level and prevents deconditioning is important. Future developments in surgical procedures and RT will likely improve the management protocols for bone metastases and technology to reduce metal artifacts in radiation planning might improve the efficacy and safety of combination therapy

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS

Autophagy and mTOR signaling during intervertebral disc aging and degeneration

Degenerative disc disease is a highly prevalent, global health problem that represents the primary cause of back pain and is associated with neurological disorders, including radiculopathy, myelopathy, and paralysis, resulting in worker disability and socioeconomic burdens. The intervertebral disc is the largest avascular organ in the body, and degeneration is suspected to be linked to nutritional deficiencies. Autophagy, the process through which cells self-digest and recycle damaged components, is an important cell survival mechanism under stress conditions, especially nutrient deprivation. Autophagy is negatively controlled by the mammalian target of rapamycin (mTOR) signaling pathway. mTOR is a serine/threonine kinase that detects nutrient availability to trigger the activation of cell growth and protein synthesis pathways. Thus, resident disc cells may utilize autophagy and mTOR signaling to cope with harsh low-nutrient conditions, such as low glucose, low oxygen, and low pH. We performed rabbit and human disc cell and tissue studies to elucidate the involvement and roles played by autophagy and mTOR signaling in the intervertebral disc. In vitro serum and nutrient deprivation studies resulted in decreased disc cell proliferation and metabolic activity and increased apoptosis and senescence, in addition to increased autophagy. The selective RNA interference-mediated and pharmacological inhibition of mTOR complex 1 (mTORC1) was protective against inflammation-induced disc cellular apoptosis, senescence, and extracellular matrix catabolism, through the induction of autophagy and the activation of the Akt-signaling network. Although temsirolimus, a rapamycin derivative with improved water solubility, was the most effective mTORC1 inhibitor tested, dual mTOR inhibitors, capable of blocking multiple mTOR complexes, did not rescue disc cells. In vivo, high levels of mTOR-signaling molecule expression and phosphorylation were observed in human intermediately degenerated discs and decreased with age. A mechanistic understanding of autophagy and mTOR signaling can provide a basis for the development of biological therapies to treat degenerative disc disease