Decrease in pelvic incidence after adult spinal deformity surgery is a predictive factor for progression of hip joint osteoarthritis.

BACKGROUND: This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment. METHODS: This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint. Spinopelvic alignment parameters were measured preoperatively and 1-month postoperatively and the changes (Δ) during this period were calculated. Patients were followed-up for ≥ 5 years and factors associated with KL grade progression at 5-years postoperatively were determined by logistic regression analysis. RESULTS: In the analysis with all cases, KL grade progressed in 23 joints. Logistic regression analysis revealed age (OR: 1.098, 95% CI: 1.007-1.198, p = 0.019), ARO (OR: 1.176, 95% CI: 1.01-1.37, p = 0.026), and Δ PI (OR: 0.791, 95% CI: 0.688-0.997, p < 0.001) as parameters significantly associated with KL grade progression. On the other hand, in the analysis limited to 185 cases with 1-month postoperative KL grade of 0, KL grade progressed in 13 joints. Logistic regression analysis revealed PI-LL (OR: 1.058, 95% CI: 1.001-1.117, p = 0.04), ΔPI (OR: 0.785, 95% CI: 0.649-0.951, p < 0.001), and ΔCobb (OR: 1.127, 95% CI: 1.012-1.253, p = 0.009) as parameters significantly associated with progression. CONCLUSIONS: Both the overall and limited analyzes of this study identified preoperative to postoperative change in PI as parameters affecting the hip osteoarthritis progression after spinal fusion surgery. Decrease in PI might represent preexisting sacroiliac joint laxity. Patients with this risk factor should be carefully followed for possible hip osteoarthritis progression.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

BACKGROUND: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images. METHODS: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations. RESULTS: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change. CONCLUSIONS: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

A patient and public involvement study to explore patient perspectives on the efficacy of treatments for pain and numbness derived from ossification of posterior longitudinal ligament of the spine.

BACKGROUND: Chronic pain and numbness are common complaints in patients with ossification of the posterior longitudinal ligament of the spine (OPLL). However, it is unclear whether the current treatments are effective in patients with OPLL in terms of improving pain and numbness. METHODS: A cross-sectional survey of patients with OPLL was conducted to determine patient satisfaction with surgery and drug therapy for pain and numbness, and its association with health-related quality of life. The survey was conducted by a patient association and its members, and anonymized data were analyzed by physicians. Comparisons between groups were made using T-tests or Kruskal-Wallis and Steel-Dwass tests, chi-square tests, and Fisher's exact tests. RESULTS: Data from 121 patients with OPLL (age 69 ± 11 years, 69 males; 43 females; and 7 unknown) who completed a mailed questionnaire were analyzed. Of the 93 patients with a history of surgery for OPLL, 24% and 18% reported much improvement in pain and numbness, respectively. After surgery, 42% and 48% reported some improvement, and 34% and 34% reported no improvement, respectively. Patients whose numbness did not improve with surgery had a significantly poorer health-related quality of life than those who did. Of the 78 patients who received medication, only 2% reported "much improvement," 64% reported "some improvement," and 31% reported "no improvement at all." Compared to patients with OPLL only in the cervical spine, those with diffuse-type OPLL showed poorer improvement in numbness after surgery and poorer quality of life. CONCLUSIONS: The majority of patients with OPLL belonging to the association were unsatisfied with surgery and pharmacotherapy in terms of pain and numbness improvement, indicating that there is an unmet medical need for more effective treatment for chronic pain and numbness in patients with OPLL.

Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Anterior fusion surgery with overcorrection in the treatment of adolescent idiopathic scoliosis with Lenke 1 AR curve type: how to achieve overcorrection and its effect on postoperative spinal alignment.

BACKGROUND: The efficacy of anterior fusion with overcorrection in the instrumented vertebra for Lenke 1 AR type curves has been reported, but how to achieve overcorrection and how overcorrection affects spinal alignment are unclear. The purpose of this study was to identify the factors that cause overcorrection, and to investigate how overcorrection affects postoperative spinal alignment in the surgical treatment of Lenke 1 AR type curves. METHODS: Patients who had anterior surgery for a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) type scoliosis and minimum 2-year follow-up were included. The radiographic data were measured at preoperative, postoperative 1 month, and final follow-up. The UIV-LIV Cobb angle was determined as the Cobb angle between the upper instrumented vertebra (UIV) and the lower instrumented vertebra (LIV), and a negative number for this angle was considered overcorrection. The screw angle was determined to be the sum of the angle formed by the screw axis and the lower and upper endplates in the LIV and UIV, respectively. The change (Δ) in the parameters from postoperative to final follow-up was calculated. The relationships between the UIV-LIV Cobb angle and other radiographic parameters were evaluated by linear regression analyses. RESULTS: Fourteen patients met the inclusion criteria. Their median age was 15.5 years, and the median follow-up period was 53.6 months. The median UIV-LIV Cobb angle was -1.4° at postoperative 1 month. The median screw angle was 4.7°, and overcorrection was achieved in 11 (79%) cases at postoperative 1 month. The screw angle (r2 = 0.42, p = 0.012) and Δ FDUV-CSVL (the deviation of the first distal uninstrumented vertebra from the central sacral vertical line, r2 = 0.53, p = 0.003) were significantly correlated with the UIV-LIV Cobb angle. CONCLUSIONS: Screw placement in the UIV and LIV not parallel to the endplate, but angled, was an effective method to facilitate overcorrection in the instrumented vertebrae. The results of the present study suggest that overcorrection could bring spontaneous improvement of coronal balance below the instrumented segment during the postoperative period.

Current status and future prospects of the Japanese orthopaedic association national registry (JOANR), Japan's first national registry of orthopaedic surgery.

The Japanese Orthopaedic Association National Registry (JOANR) is Japan's first national registry of orthopaedic surgery, which has been developed after having been selected for the Project for Developing a Database of Clinical Outcome approved by the Health Policy Bureau of the Ministry of Health, Labour and Welfare. Its architecture has two levels of registration, one being the basic items of surgical procedure, disease, information on surgeons, surgery-related information, and outcome, and the other being detailed items in the affiliated registries of partner medical associations. It has a number of features, including the facts that, because it handles medical data, which constitute special care-required personal information, data processing is conducted entirely in a cloud environment with the imposition of high-level data security measures; registration of the implant data required to assess implant performance has been automated via a bar code reader app; and the system structure enables flexible collaboration with the registries of partner associations. JOANR registration is a requirement for accreditation as a core institution or partner institution under the board certification system, and the total number of cases registered during the first year of operation (2020) was 899,421 registered by 2,247 institutions, providing real-world evidence concerning orthopaedic surgery.

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Thoracic kyphosis in light of lumbosacral alignment in thoracic adolescent idiopathic scoliosis: recognition of thoracic hypokyphosis and therapeutic implications.

BACKGROUND: The uniqueness of spinal sagittal alignment in thoracic adolescent idiopathic scoliosis (AIS), for example, the drastically smaller thoracic kyphosis seen in some patients, has been recognized but not yet fully understood. The purpose of this study was to clarify the characteristics of sagittal alignment of thoracic AIS and to determine the contributing factors. METHODS: Whole spine radiographs of 83 thoracic AIS patients (73 females) were analyzed. The measured radiographic parameters were the Cobb angle of thoracic scoliosis, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (C7 SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Additionally, max-LL, which was defined as the maximum lordosis angle from the S1 endplate, the inflection point between thoracic kyphosis and lumbar lordosis, and the SVA of the inflection point (IP SVA) were measured. The factors significantly related to a decrease in TK were assessed by stepwise logistic regression analysis. In addition, cluster analysis was performed to classify the global sagittal alignment. RESULTS: The significant factors for a decrease in TK were an increase in SS (p = 0.0003, [OR]: 1.16) and a decrease in max-LL (p = 0.0005, [OR]: 0.89). According to the cluster analysis, the global sagittal alignment was categorized into the following three types: Type 1 (low SS, low max-LL, n = 28); Type 2 (high SS, low max-LL, n = 22); and Type 3 (high SS, high max-LL, n = 33). CONCLUSIONS: In thoracic AIS, a decreased TK corresponded to an increased SS or a decreased max-LL. The sagittal alignment of thoracic AIS patients could be classified into three types based on SS and max-LL. One of these three types includes the unique sagittal profile of very small TK.

Guidelines for cadaver dissection in education and research of clinical medicine (The Japan Surgical Society and The Japanese Association of Anatomists).

This article translates the guidelines for cadaver surgical training (CST) published in 2012 by Japan Surgical Society (JSS) and Japanese Association of Anatomists from Japanese to English. These guidelines are based on Japanese laws and enable the usage of donated cadavers for CST and clinical research. The following are the conditions to implement the activities outlined in the guidelines. The aim is to improve medicine and to contribute to social welfare. Activities should only be carried out at medical or dental universities under the centralized control by the department of anatomy under the regulation of Japanese law. Upon the usage of cadavers, registered donors must provide a written informed-consent for their body to be used for CST and other activities of clinical medicine. Commercial use of cadavers and profit-based CST is strongly prohibited. Moreover, all the cadaver-related activities except for the commercial-based ones require the approval of the University's Institutional Review Board (IRB) before implementation. The expert committee organized at each university for the implementation of CST should summarize the implementation of the program and report the details of the training program, operating costs, and conflicts of interest to the CST Promotion Committee of JSS.

Prevalence and associated factors of primary elbow osteoarthritis in the Japanese general elderly population: a Japanese cohort survey randomly sampled from a basic resident registry.

BACKGROUND: The epidemiology of primary elbow osteoarthritis (PEOA) remains unknown. We aimed to evaluate the prevalence and associated factors of PEOA in a cross-sectional resident cohort from a municipal registry of a Japanese town. METHODS: A total of 415 residents over 50 years of age were randomly sampled from a Japanese town and were adjusted for age and gender. Those with diseases that could potentially cause a secondary osteoarthritis of the elbow were excluded. The remaining 318 subjects (150 men and 168 women) underwent bidirectional radiography of the elbow. Subjects were diagnosed with PEOA if one of their elbows was Kellgren-Lawrence (KL) grade 2 or greater. In addition, motion pain and tenderness at the elbow were examined by orthopedic surgeons. Associated factors for the PEOA were statistically analyzed. RESULTS: The prevalence of PEOA was 25.2% (male, 27.3%; female, 23.2%), and the prevalence of symptomatic PEOA was 0.9%. The age-stratified prevalence of PEOA was as follows: 50-59, 6.2% (male, 5.0%; female, 7.3%); 60-69, 15.4% (male, 17.5%; female, 13.7%); 70-79, 29.5% (male, 35.3%; female, 25.0%); and 80-89, 55.9% (male, 55.6%; female, 56.3%). Age and body mass index were revealed as associated factors that increased the prevalence of PEOA with KL grade 2 or greater. The use of vibrating tools was demonstrated as an independent associated factor that increased the prevalence of PEOA with KL grade 4 in addition to the 2 aforementioned factors. CONCLUSIONS: The prevalence of PEOA in Japanese subjects was 25.2% for those aged 50-89 years with a mean age of 69.2 years, most of which was asymptomatic OA without motion pain or tenderness at the elbow. Age and body mass index increased the prevalence of PEOA with KL grade 2 or greater. The prevalence of PEOA increased with age, but the disease was self-accommodated by most people.

Impact of background factors on outcomes of pharmacological therapy for chronic low back pain: A nationwide multicenter prospective study.

BACKGROUND: Chronic low back pain (CLBP) is a major cause of chronic pain with nociceptive, neuropathic or both pain components, and a leading cause of disability. The objectives of this study were to determine the impact of background factors including previous use of drugs on outcomes of pharmacological therapy for CLBP in a nationwide multicenter prospective study. METHODS: The subjects were 474 patients (male: 41.9%, median age: 73.0) with CLBP. Background factors that could influence outcomes after pharmacological treatment for 6 months were examined: age, gender, body mass index (BMI), duration of CLBP, osteoporosis, history of spinal surgery, history of malignant tumor, smoking habit, employment status (yes or no), exercise habit (frequency), number of live-in family members, having something to do for pleasure, Center for Epidemiologic Studies depression scale (CES-D) score, and medication at baseline. Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) for LBP, JOA Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire (RDQ), Short-form 8-item health survey (SF-8), and EQ-5D were used for evaluation at baseline and after 6 months. Multivariate linear regression models were used in statistical analysis. RESULTS: Drugs for neuropathic pain at baseline (p < 0.001), Tramacet® at baseline (p < 0.05), weak opioids at baseline (p < 0.05), older age (p < 0.001), long disease duration (p < 0.005), history of spinal surgery (p < 0.001), and smoking habit (p < 0.001) had significant negative effects on outcomes. Employment (p < 0.05), exercise habit (p < 0.05), and CED-D at baseline (p < 0.001) had positive effects on outcomes. CONCLUSIONS: This is the first study to identify significant prognostic factors for outcomes of pharmacological treatment of CLBP. The neuropathic pain component of CLBP at baseline is a major significant negative factor for most outcomes involving improved pain, activities of daily life, and quality of life. Treatment strategies developed with consideration of these factors may be advantageous for recovery from CLBP.

Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.

BACKGROUND: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. METHODS: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. RESULTS: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. CONCLUSIONS: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.

A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting millions of children. Since treatment and prognosis of AIS depend on curve progression, identifying factors related to AIS curve progression is important in its management. Although several genetic loci for AIS occurrence are reported, no locus for curve progression has been identified. To identify genes associated with AIS progression, we conducted a genome-wide association study followed by a replication study using a total of 2,543 AIS subjects who were evaluated for the curve progression. We identified a significantly associated locus on chromosome 11q14.1 (P = 1.98 × 10-9, odds ratio = 1.56). In silico and in vitro analyses identified a functional variant, rs35333564 in MIR4300HG, the host gene of a microRNA, MIR4300. The genomic region containing rs35333564 had enhancer activity, which was decreased in its risk allele. Our data suggest that decrease of MIR4300 is related to AIS progression.

Cost-effectiveness analysis of the pharmacological management of chronic low back pain with four leading drugs.

BACKGROUND: Chronic low back pain is a major health problem that has a substantial effect on people's quality of life and places a significant economic burden on healthcare systems. However, there has been little cost-effectiveness analysis of the treatments for it. Therefore, the purpose of this prospective observational study was to evaluate the cost-effectiveness of the pharmacological management of chronic low back pain. METHODS: A total of 474 patients received pharmacological management for chronic low back pain using four leading drugs for 6 months at 28 institutions in Japan. Outcome measures, including EQ-5D, the Japanese Orthopaedic Association (JOA) score, the JOA back pain evaluation questionnaire (BPEQ), the Roland-Morris Disability Questionnaire, the Medical Outcomes Study SF-8, and the visual analog scale, were investigated at baseline and every one month thereafter. The incremental cost-utility ratio (ICUR) was calculated as drug cost over the quality-adjusted life years. An economic estimation was performed from the perspective of a public healthcare payer in Japan. Stratified analysis based on patient characteristics was also performed to explore the characteristics that affect cost-effectiveness. RESULTS: The ICUR of pharmacological management for chronic low back pain was JPY 453,756. Stratified analysis based on patient characteristics suggested that the pharmacological treatments for patients with a history of spine surgery or cancer, low frequency of exercise, long disease period, low scores in lumbar spine dysfunction and gait disturbance of the JOA BPEQ, and low JOA score at baseline were not cost-effective. CONCLUSIONS: Pharmacological management for chronic low back pain is cost-effective from the reference willingness to pay. Further optimization based on patient characteristics is expected to contribute to the sustainable development of a universal insurance system in Japan.

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.

Isolated Coronal Shear Fracture of the Nonossified Humeral Trochlea in a 7-Year-Old Patient.

Coronal shear fractures of the nonossified humeral trochlea are extremely rare in skeletally immature children. This fracture is difficult to diagnose accurately on routine radiographs. In addition, the mechanism of injury and appropriate treatment methods are unknown. We present the case of a 7-year-old boy who sustained an isolated coronal shear fracture of the nonossified humeral trochlea. Internal fixation of the fracture was performed with 2 K-wires. Two and a half years after surgery, the patient had pain-free active range of motion of the elbow from 0° to 130° with full forearm rotation and magnetic resonance imaging showed healing of the chondral fragment of the trochlea. Hand surgeons should be aware of the possibility of this rare fracture in skeletally immature children. Magnetic resonance imaging and arthrography are helpful in establishing the correct diagnosis.

Osseointegration improves bone-implant interface of pedicle screws in the growing spine: a biomechanical and histological study using an in vivo immature porcine model.

PURPOSE: Implant failure is a frequent complication in corrective surgery for early onset scoliosis, since considerable forces are acting on small and fragile vertebrae. Osseointegration showing biomechanical and histological improvement in bone-implant interface (BII) after dental implant placement has been well investigated. However, there are no studies regarding osseointegration in immature vertebral bone. The purpose was to evaluate the timecourse of biomechanical and histological changes at BII after pedicle screw placement using in vivo immature porcine model. METHODS: Ten immature porcine were instrumented with titanium pedicle screws in the thoracic spine. After a 0-, 2-, 4-, and 6-month survival periods, the spines were harvested at the age of 12 months. Histological evaluation of BII was conducted by bone volume/tissue volume (BV/TV) and bone surface/implant surface (BS/IS) measurements. Bone mineral density (BMD) measurement and biomechanical testing of BII were done. RESULTS: Contact surface and bone volume around the screw threads were significantly increased over the time. BV/TV and BS/IS were improved with statistically significant differences between 0- and ≥4-month (p ≤ 0.001) periods. BMD in all subjects was determined to be the same (p ≥ 0.350). Pullout strength was also increased over time with significant differences between 0- and ≥2-month (p ≤ 0.011) periods. CONCLUSION: Improved stability at BII caused by osseointegration was confirmed by in vivo immature porcine model. A two-stage operation is proposed based on the osseointegration theory, in which an implant is installed in advance in the vertebrae at the first stage and deformity correction surgery is performed after sufficient stability is obtained by osseointegration at a later stage.

Multiple concave rib head resection improved correction rate of posterior spine fusion in treatment of adolescent idiopathic scoliosis.

BACKGROUND: Hybrid constructs have been widely used to surgically correct thoracic adolescent idiopathic scoliosis (AIS). To enhance the correction obtained with hybrid constructs, we perform concave rib head resection and convex costovertebral release as posterior release procedures. The objective of the study was to evaluate coronal and sagittal curve correction in patients with adolescent idiopathic scoliosis (AIS) treated with hybrid constructs combined with concave rib head resection and convex transverse process resection as posterior release procedures. METHODS: The records of 24 patients with Lenke type 1 or 2 AIS treated with hybrid constructs combined with posterior release procedures were retrospectively reviewed. The mean age at surgery was 14.3 years. The mean follow-up period was 33.0 months (range, 24-60 months). Radiographs were evaluated before surgery, immediately postoperatively, and at latest follow-up. RESULTS: The average preoperative Cobb angle of the main thoracic (MT) curve was 58.1 ± 12.6° (range, 45-88°). The MT curve was corrected to 12.8 ± 9.0° (range, 0-38°) immediately after surgery. At the latest follow-up, the average Cobb angle was 13.6 ± 9.9° (range, 0-44°; correction, 77.5 ± 14.0%). The average loss of coronal correction was 0.8°. The average preoperative flexibility of the MT curve was 54.6 ± 17.4%. The average Cincinnati correction index was 1.53 ± 0.48 at the latest follow-up. The average preoperative thoracic kyphosis (TK) was 13.7 ± 12.0° (range, -12-34°). Immediately after surgery, TK was corrected to 18.6 ± 5.9° (range, 10-29°). At the latest follow-up, TK measured 18.1 ± 6.5° (range, 6-32°). CONCLUSIONS: Hybrid instrumentation combined with concave rib head resection and convex transverse process resection as posterior release procedures achieved satisfactory coronal and sagittal curve correction with little loss of correction at 2-year follow-up.

A Japanese nationwide multicenter survey on perioperative complications of corrective fusion for elderly patients with adult spinal deformity.

BACKGROUND: Recently, corrective fusion surgery for patients with adult spinal deformity (ASD) has become common in Japan. This study aimed to clarify the status of surgeries for ASD in Japan, focusing on perioperative complications. A nationwide multicenter survey gathering information on surgically treated ASD patients was conducted by the committee for Adult Spinal Deformity of the Japanese Scoliosis Society. METHODS: This study was a review of retrospectively collected data from 18 spine scoliosis centers belonging to the Japanese Scoliosis Society. Patients who underwent corrective fusion surgery for ASD between 2011 and 2013 were included. Demographics, comorbidities, surgical data, and complications were investigated. RESULTS: A total of 1192 patients (mean age, 57.7 years) were included in this study. Of these, 611 patients were aged less than 65 years and 581 patients were aged 65 years or greater. The age distribution had two peaks, in the third and eighth decades. Deformities caused by degeneration represented 67% of the pathology in patients aged over 65 years; however, non-degenerative disease such as adult idiopathic scoliosis and syndromic or congenital deformity represented over 60% of pathology in patients aged less than 65 years. The iatrogenic deformity and reoperation rates were both less than 3%. The mean operation time and estimated blood loss were 370 min and 1642 ml, respectively. Major perioperative complications occurred in 160 patients (14.5%). The incidence of complications was significantly higher in patients aged over 65 years, including neurological deficits, hemorrhagic shock, hematoma, heart failure, and surgical site infection (p < 0.05). CONCLUSIONS: Older (aged over 65 years) ASD patients showed greater rates of deformity due to the occurrence of degeneration and vertebral fractures, as well as a higher incidence of peri-and postoperative complications. Efforts to reduce perioperative complications are therefore imperative, especially for elderly ASD patients in our aging society.