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OBJECTIVE Issues with spinopelvic fixation for adult spinal deformity (ASD) include loss of the physiological mobility of the entire lumbar spine, perioperative complications, and medical costs. Little is known about the factors associated with successful short fusion for ASD. The authors evaluated radiographic and clinical outcomes after shorter fusion for different subtypes of ASD at 2 years postoperatively and examined factors associated with successful short fusion. METHODS This was a single-center study of 37 patients who underwent short fusion and a minimum 2 years of follow-up for ASD in which lumbar kyphosis was the main deformity. The exclusion criteria were 1) age < 40 years, 2) previous lumbar vertebral fracture, 3) severe osteoporosis, 4) T10–L2 kyphosis > 20°, 5) scoliotic deformity with an upper end vertebra (UEV) above T12, and 6) concomitant Parkinson’s disease or neurological disease. The surgical procedures, radiographic course, and Oswestry Disability Index (ODI) were assessed, and correlations between radiographic parameters and postoperative ODI at 2 years were analyzed. RESULTS A mean of 3.5 levels were fused. The mean radiographic parameters preoperatively, at 2 weeks, and at 2 years, respectively, were as follows: coronal Cobb angle: 22.9°, 11.5°, and 12.6°; lumbar lordosis (LL): 12.9°, 35.8°, and 32.2°; pelvic incidence (PI) minus LL: 35.5°, 14.7°, and 19.2°; pelvic tilt: 29.4°, 23.1°, and 25.0°; and sagittal vertical axis 85.3, 36.7, and 59.2 mm. Abnormal proximal junctional kyphosis occurred in 8 cases. Revision surgery was performed to extend the length of fusion from a lower thoracic vertebra to the pelvis in 2 cases. The mean ODI scores preoperatively and at 2 years were 50.7% and 24.1%, respectively. Patient age, number of fused intervertebral segments, and radiographic parameters were analyzed by the stepwise method to identify factors contributing to the ODI score at 2 years, preoperative PI, and sagittal vertical axis at 2 years. On receiver operating characteristic curve analysis of the minimal clinically important difference of ODI (15%) and preoperative PI, the cutoff value of the preoperative PI was 47° (area under the curve 0.75). CONCLUSIONS In terms of subtypes of ASD in which lumbar kyphosis is the main deformity, if the PI is < 47°, then the use of short fusion preserving mobile intervertebral segments can produce adequate LL for the PI, improving both postoperative global spinal alignment and quality of life.

OBJECTIVEFacet cysts may represent a sign of intrinsic facet disease and instability, increasing the importance of less-invasive approaches that limit tissue dissection and improve visualization. The authors developed an intraoperative cyst-dyeing technique, involving the injection of indigo carmine from the facet joint into the cyst, as an adjunct during decompression. This study aimed to evaluate the clinical outcomes and perioperative complication rates of microendoscopic spinal decompression for lumbar spinal stenosis (LSS) and lumbar foraminal stenosis (LFS), caused by facet cysts and to elucidate the efficacy of the cyst-dyeing method in microendoscopic surgery for facet cysts.METHODSForty-eight consecutive patients who underwent surgical treatment with microendoscopic decompression for symptomatic LSS or LFS caused by facet cysts from 2011 to 2018 were reviewed. These patients were divided into two groups: a group that did not receive dye (N), with the patients undergoing surgery from April 2011 to May 2015; and a group that received dye (D), with patients undergoing surgery from June 2015 to March 2018. The authors evaluated the operative time, blood loss, perioperative complications, visual analog scale scores for low-back and leg pain, and Japanese Orthopaedic Association scores. Surgical outcome was evaluated 2 years postoperatively and was compared between groups D and N.RESULTSThe clinical outcomes were generally excellent or good. Group N consisted of 36 patients and group D of 12 patients. Comparing the clinical results, it was found that the cyst-dyeing method reduced the perioperative complication rate, including reduction in dural tears to 0%, and shortened the average operative time by approximately 40 minutes.CONCLUSIONSIn this study, the authors demonstrated that the clinical outcomes of microendoscopic spinal decompression in patients with LSS or LFS caused by facet-joint cysts are generally favorable. Additionally, the adjunctive cyst-dyeing method effectively delineated the cystic and dural boundaries, facilitating safer and more effective cyst separation and neural decompression. Microendoscopic surgery combined with this novel facet cyst-dyeing method is a safe and effective minimally invasive technique for facet-joint cysts.

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.

Aim Dravet syndrome (DS) is characterized by high epilepsy-related premature mortality with a markedly young age at death, however, autopsy report of sudden unexpected death with DS has been fewer than expected. Methods We report two autopsy cases with sudden unexpected death from DS. Case 1 was a 13-year-old male who drowned in a bathtub, and Case 2 was a 3-year-old female who died while sleeping. In Case 1, the blood concentration of the anticonvulsant, valproic acid, was below the recommended therapeutic range. Neuropathological investigation and genetic analysis of 402 cardiovascular disease-related and 146 epilepsy-related genes by next generation sequencing were applied. Results No significant neuronal loss with gliosis was observed in the brain of either patient. Although possible mild malformations of cortical development were found in both, the degree thereof was similar to that of age-matched controls. Genetic analysis identified a novel variant in SCN1A intron 23 (c.4477-3T > C) in Case 1 that falls outside of the minor splicing consensus sequence. In vitro splicing functional assays with minigene constructs revealed that this intronic variant leads to a 2-bp insertion immediately before exon 24 that results in protein truncation. Similarly, a novel de novo missense mutation of unknown significance, SCN1A_Arg187Pro, was identified in Case 2. In both cases, we also identified cardiomyopathy-related variants classified as likely pathogenic; however, the effect of these variants at death was minimal because there was an absence of pathological change indicating inherited cardiomyopathy. Conclusion The present cases emphasize the need for multifaceted examination of DS cases so as to obtain a definitive autopsy diagnosis and to explore the mechanism of sudden unexpected death.

Background and Study Aims Surgical treatment options for lumbar spinal stenosis (LSS) based on adjacent segment disease (ASD) after spinal fusion typically involve decompression, with or without fusion, of the adjacent segment. The clinical benefits of microendoscopic decompression for LSS based on ASD have not yet been fully elucidated. We aimed to investigate the clinical results of microendoscopic spinal decompression surgery for LSS based on ASD. Patients and Methods From 2011 to 2014, consecutive patients who underwent microendoscopic spinal decompression without fusion for LSS based on ASD were enrolled. Data of 32 patients (17 men and 15 women, with a mean age of 70.5 years) were reviewed. Japanese Orthopaedic Association score and low back pain/leg pain visual analog scale score were utilized to measure neurologic and axial pain outcomes, respectively. Additionally, after the surgeries, we analyzed the magnetic resonance imaging (MRI), computed tomography (CT) scans, or radiographs to identify any new instabilities of the decompressed segments or progression of ASD adjacent to the decompressed segments. Results The Japanese Orthopaedic Association recovery rate at the 5-year postoperative visit was 49.2%. The visual analog scale scores for low back pain and leg pain were significantly improved. The minimum clinically important difference for leg pain (decrease by ≥24 mm) and clinically important difference for low back pain (decrease by ≥38 mm) were achieved in 84% (27/32) and 72% (23/32) of cases, respectively. Regarding new instability after microendoscopic decompression, no cases had apparent spinal instability at the decompression segment and adjacent segment to the decompressed segment. Conclusions Microendoscopic spinal decompression is an effective treatment alternative for patients with LSS caused by ASD. The ability to perform neural decompression while maintaining key stabilizing structures minimizes subsequent clinical instability. The substantial clinical and economic benefits of this approach may make it a favorable alternative to performing concurrent fusion in many patients.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS., Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.

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 males, 168 females) 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%); 80-89, 55.9% (male, 55.6%; female, 56.3%). Age and body mass index (BMI) 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 two aforementioned factors. Conclusions The prevalence of PEOA in Japanese subjects was 25.2% for those aged 50-89 with a mean age of 69.2 years, most of which were asymptomatic OA without motion pain or tenderness at the elbow. Age and BMI 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. Level of Evidence Level III; Cross-Sectional Design; Epidemiology Study

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., Koda et al. present the results of a randomized phase 3 trial comparing granulocyte colony-stimulating factor versus placebo in patients with acute spinal cord injury. While the primary endpoint was not met, a sub-analysis revealed a trend towards superior efficacy of G-CSF versus placebo in an elderly population.

Background Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5–1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown. Methods We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole‐exome sequencing. Results We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease‐causing variants were identified in other patients, however. LFNG encodes a GlcNAc‐transferase. The LFNG variants showed loss of their enzyme function. Conclusions A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS.

Study design Retrospective review of North American and Japanese adult spinal deformity (ASD) database. Objective To investigate the ethnical differences in radiographic parameters and Scoliosis Research Society (SRS)-22 between North American and Japanese ASD. Summary of background data Previous comparison study between North American and Japanese ASD patients has revealed Japanese patients had marked pelvic tilt deformity and had lower Oswestry Disability Index scores corresponding to established thresholds of radiographic deformity. However, the subjects of the previous study included relatively younger ASD patients (above 18 y) of idiopathic origin. Materials and methods Total 282 ASD patients older than 50 years, 211 patients from North America (United States) and 71 patients from Japan (JP), with minimum 2-year follow-up postoperatively were included in the study. Radiologic parameters were compared at the baseline and at 2-year follow-up. SRS-22 score was used for the comparison of clinical outcome. Results At baseline, Japan showed significantly worse sagittal alignment such as smaller lumbar lordosis (LL), larger pelvic incidence (PI), and larger sagittal vertical axis than United States. However, Japan had significantly fewer levels fused than United States (US, 12.66±4.6; JP, 8.49±2.7). At 2 years after the surgery, Japan still had significantly worse residual sagittal deformity. Comparison of SRS-22 scores revealed Japan had better pain but worse functional domain scores at baseline which improved to comparable levels to the United States at 2 years. Self-image and mental health scores in Japan were significantly worse both at baseline and at 2 years. Analysis of factors affecting SRS-22 satisfaction score at 2 years revealed that previous spinal fusion surgery in the United States and LL, PI-LL, and sagittal vertical axis at 2 years in Japan had significant correlation. Conclusions These similarities and discrepancies may be influenced by the cultural or lifestyle differences between both nations and should be considered when interpreting the results of ASD studies among different ethnicities.

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.

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.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.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.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.

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.

Saffold virus (SAFV) is a novel human cardiovirus that was identified in 2007. Recently, SAFV has been isolated from nasal and stool specimens of infants presenting with respiratory and gastrointestinal symptoms and from cerebrospinal fluid (CSF) specimens of children with central nervous system infection. However, little is known regarding clinical characteristics of SAFV in children.We reviewed 5412 specimens from the database of the infectious agents surveillance system in Niigata prefecture, Japan, between January 2006 and December 2013, and identified SAFV-infected patients. Subsequently, we retrospectively reviewed their medical records and evaluated their clinical characteristics.We identified 9 SAFV-infected patients (median age: 5 years; range: 2-16 years). Seven patients were diagnosed with pharyngitis, one with meningitis and one with fever of unknown origin. Dominant symptoms were high fever, appetite loss and headache. The median duration of the fevers was 2 days in patients with pharyngitis; however, the patient with meningitis remained febrile for 5 days. All blood tests available in this case series revealed leukocytosis with a predominance of neutrophils. CSF profiles showed mild lymphocytic pleocytosis. All patients recovered fully without complications.A few clinical characteristics of SAFV infection were clarified, including high fever of short duration in patients with pharyngitis, and neutrophil-dominant leukocytosis. The clinical course and CSF profiles of a case of meningitis were similar to those of other aseptic meningitis. SAFV needs to be included in the differential diagnosis of pharyngitis or meningitis when commonly identified viruses are not identified in such patients.

A man in his 30s, who had undergone retrocolic Billroth II reconstruction for perforated duodenal ulcer, presented with watery diarrhea for 2 years and suspected fatty liver. He was referred to our hospital for management of chronic diarrhea, weight loss, hepatopathy and hypoalbuminemia. Initial upper and lower gastrointestinal endoscopies were negative. Since a small bowel lesion was suspected, peroral single-balloon enteroscopy was performed, which identified feces-like residue near the Billroth II anastomotic site and a connection to the colon separate from the afferent and efferent loops. Transanal single-balloon enteroscopy identified a fistula between the gastrojejunal anastomosis and transverse colon, with the scope reaching the stomach transanally. Barium enema confirmed flow of contrast medium from the transverse colon through the fistula to the anastomotic site, allowing the diagnosis of gastrojejunocolic fistula. Liver biopsy showed relatively severe steatohepatitis (Brunt's classification: stage 2-3, grade 3). Resection of the anastomotic site and partial transverse colectomy were performed to remove the fistula, followed by Roux-en-Y reconstruction. Postoperatively, watery diarrhea resolved and the stools became normal. Hepatopathy and hypoproteinemia improved. One year later, liver biopsy showed marked improvement of steatosis. This case demonstrated marked improvement of both diarrhea/nutritional status and steatohepatitis after treatment of gastrojejunocolic fistula, suggesting that the fistula caused non-alcoholic steatohepatitis.

Adult spinal deformity (ASD) classification showing that ideal pelvic incidence minus lumbar lordosis (PI-LL) value is within 10° has been received widely. But no study has focused on the optimum level of PI-LL value that reflects wide variety in PI among patients. This study was conducted to determine the optimum PI-LL value specific to an individual’s PI in postoperative ASD patients. 48 postoperative ASD patients were recruited. Spino-pelvic parameters and Oswestry Disability Index (ODI) were measured at the final follow-up. Factors associated with good clinical results were determined by stepwise multiple regression model using the ODI. The patients with ODI under the 75th percentile cutoff were designated into the “good” health related quality of life (HRQOL) group. In this group, the relationship between the PI-LL and PI was assessed by regression analysis. Multiple regression analysis revealed PI-LL as significant parameters associated with ODI. Thirty-six patients with an ODI

Objectives It is controversial whether to stop the fusion at L5 or S1 in adult spinal deformity (ASD) surgery. Our hypothesis is that we can stop long fusion at L5 for selected patients with less severe disability and less complex deformity. Aim was to compare minimum 5-year outcomes between ASD patients with fusion to L5 versus S1. Patients and methods Consecutive 40 patients (≥50 years of age) with ASD underwent spinal fusion from lower thoracic spine to L5 or S1 between 2008 and 2011. 33 patients (82.5 %) had a minimum 5-year follow-up. Lower instrumented vertebra (LIV) was L5 in 12 patients (L5 group) and S1 in 21 (S1 group). Clinical and radiographical parameters were compared between L5 and S1 group. Results There were statistically significant differences between two groups (L5 vs S1) in %male (50 % vs 14 %), %type-N of SRS-Schwab classification (83 % vs 38 %), preop ODI (40.5 vs 56), correction loss of LL (11˚ vs 3˚), final TK (32˚ vs 50˚), correction loss of TK (-1˚ vs 17˚), final improvement of PT (3˚ vs 10˚), final improvement of PI-LL (26˚ vs 39˚), PJK (8% vs 48 %), and revision surgery rate (50 % vs 14 %). Causes of revision surgery in L5 group were distal junctional failure in 5 patients and foraminal stenosis at L5-S1 in 1. All of them underwent additional spinal fusion to the sacrum. Whereas, causes of revision surgery in S1 group were rod fracture in 2 patients and proximal junctional failure in 1. Conclusion Although fusion to L5 was conducted for selected ASD patients with less severe disability (better ODI) and less complex deformity (type N), 50 % of the patients required additional fusion to the pelvis. Decision making to stop the long fusion at L5 for ASD patients ≥50 years of age should be made with careful considerations.

Case-only study.The aim of this study was to confirm the association of rs11190870 with adolescent idiopathic scoliosis (AIS) severity in Japanese patients with AIS.Although the association of rs11190870 with AIS susceptibility is replicated in multiple ethnics, the association of rs11190870 with curve severity is controversial. Since the previous studies are of small, we performed a replication study using far larger number of patients than previous studies.A total of 1860 Japanese patients with AIS who had reached skeletal maturity or undergone surgical fusion were included in the study. We evaluated the association between rs11190870 and AIS progression for the entire group, and then for patients grouped according to a severe curve (a Cobb angle of ≥40°) or mild curve (a Cobb angle30°). Because braces could affect the results of the present study, patients in the mild-curve group were divided according to whether or not they had worn a brace. We then evaluated associations between rs11190870 genotype and curve severity in these groups.The mean Cobb angles were 54.8° ± 12.1° in the severe-curve group and 24.4° ± 4.0° in the mild-curve group. The difference in rs11190870 risk-allele frequency between the severe- and mild-curve groups was evaluated. No significant differences were observed. We then examined the association of rs11190870 risk-allele frequency between patients in the mild- and severe-curve groups using the χ test for three models, and found a marginal association between rs11190870 and curve severity in the dominant model (P = 0.035, odds ratio = 1.51).We found no association between rs11190870 and curve severity using the criteria of previous study. However, we found a marginal association between rs11190870 and curve severity. Large-scale replication studies that consider skeletal maturity and brace history, including replication studies in other ethnic groups, would be helpful for clarifying the association.4.

STUDY DESIGN Retrospective review of adult spinal deformity patients in a multiethnic database. OBJECTIVE To investigate the role of ethnicity on recruitment of compensatory mechanisms for sagittal spinal deformity. SUMMARY OF BACKGROUND DATA While the impacts of age, sex, and pelvic morphology on the ability to compensate for sagittal malalignment have been investigated, the role of ethnicity in compensatory mechanism recruitment is poorly understood. METHODS Patients from USA (85% Caucasian) >25 y/o were propensity matched by age, sex, and pelvic incidence with patients from Korea and Japan. Only primary patients or those with existing fusion below T12 were retained for analysis. Groups were subclassified by deformity severity (aligned: sagittal vertical axis (SVA) 100 mm). Radiographic measurements including pelvic retroversion, thoracic kyphosis, loss of lumbar lordosis (PI minus LL), cervical lordosis, and cervical SVA were compared between the groups. RESULTS There were 288 patients (96 each in USA, KOR, JPN), with similar age (64-67 yr) and PI (49-53°). USA had smaller pelvic incidence minus lumbar lordosis in every alignment group (P

Aim To analyse the effects of thyroid hormones on β-cell function and glucose metabolism in people with prediabetes who are euthyroid. Methods A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of β-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic β-cell function. Results In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic β-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of β-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. Conclusions Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.

Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli infection and hemolytic-uremic syndrome (HUS). We employed an antibody array that simultaneously detects 174 serum cytokines. We identified five serum biomarkers, namely insulin growth factor-binding protein-2, angiopoietin-2, soluble interleukin-6 receptor, soluble tumor necrosis factor receptor type II, and matrix metalloprotease protein-3 whose levels increased with the development of HUS. Furthermore, the levels of these cytokines were significantly increased in severe HUS compared with mild HUS. These cytokines might play an important role in the pathogenesis of HUS and may also be used to predict the severity of HUS.

Objective Kakkonto, a Japanese herbal medicine, is frequently used to treat the common cold not only with a physician's prescription, but also in self-medication situations. This study aimed to examine whether Kakkonto prevents the aggravation of cold symptoms if taken at an early stage of illness compared with a well-selected Western-style multiple cold medicine. Methods This study was a multicenter, active drug-controlled, randomized trial. Adults 18 to 65 years of age who felt a touch of cold symptoms and visited 15 outpatient healthcare facilities within 48 hours of symptoms onset were enrolled. The participants were randomly assigned to two groups: one treated with Kakkonto (Kakkonto Extract-A, 6 g/day) (n=209) and one treated with a Western-style multiple cold medicine (Pabron Gold-A, 3.6 g/day) (n=198) for at most four days. The primary outcome of this study was the aggravation of cold, nasal, throat or bronchial symptoms, scored as moderate or severe and lasting for at least two days within five days after entry into the study. Results Among the 410 enrollees, 340 (168 in the Kakkonto group and 172 in the Pabron group) were included in the analyses. The proportion of participants whose colds were aggravated was 22.6% in the Kakkonto group and 25.0% in the Pabron group (p=0.66). The overall severity of the cold symptoms was not significantly different between the groups. No harmful adverse events occurred in either group. Conclusion Kakkonto did not significantly prevent the progression of cold symptoms, even when prescribed at an early stage of the disease.

Background Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. Objective We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. Methods We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. Results There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. Conclusion The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure.

Congenital occlusion of the left main coronary trunk is a life-threatening abnormality, and its optimal management remains controversial. This report describes a case of successful patch angioplasty with auto-pulmonary artery for a 12-year-old boy with congenital left main trunk occlusion. We divided the main pulmonary artery, harvested a pulmonary artery wall strip, and performed patch angioplasty of the occluded left main trunk ostium. We were able to clearly expose the left main trunk behind the pulmonary artery because the obstruction was divided for the patch material. The postoperative course was uneventful, and coronary angiography at 4 months after surgery showed excellent patency of the left main trunk. The auto-pulmonary arterial wall was easy to handle during angioplasty, and its favorable durability has been established both in the Ross procedures and in an arterial switch procedure. Therefore, we conclude that patch angioplasty using a piece of the pulmonary arterial wall represents a good alternative to conventional coronary artery bypass grafting.

STUDY DESIGN A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). OBJECTIVE To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them. METHODS We recruited 2117 patients with AIS with a Cobb angle of 10° or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40° or greater were included in the progression group, and those whose scoliotic curves were less than 30° and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype. RESULTS We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.

The association of socioeconomic status (SES) with nutrients intakes attracts public attention worldwide. In the current study, we examined the associations of SES with dietary salt intake and health outcomes in general Japanese workers (2,266) who participated in this Japanese occupational cohort. SES was assessed by a self-administered questionnaire. Dietary intakes were assessed with a validated, brief, self-administered diet history questionnaire (BDHQ). Multiple linear regression and stratified analysis were used to evaluate the associations of salt intake with the confounding factors. Education levels and household incomes were significantly associated with salt intake, as well as blood pressures (P < 0.05). After adjusting for age, sex and total energy intake, both years of education and household income significantly affect the salt intake (for education, β = −0.031, P = 0.040; for household income, β = −0.046, P = 0.003). SES factors also affect the risk of hypertension, those subjects with higher levels of education or income had lower risk to become hypertensive (ORs for education was 0.904, P < 0.001; ORs for income was 0.956, P = 0.032). Our results show that SES is an independent determinant of salt intake and blood pressure, in order to lower the risk of hypertension, the efforts to narrow the social status gaps should be considered by the health policy-makers.

The association of socioeconomic status (SES) with nutrient intake attracts public attention worldwide. In the current study, we examined the associations of SES with dietary intake of folate and health outcomes in general Japanese workers. This Japanese occupational cohort consisted off 2266 workers. SES was assessed by a self-administered questionnaire. Intakes of all nutrients were assessed with a validated, brief and self-administered diet history questionnaire (BDHQ). The degree of depressive symptoms was measured by the validated Japanese version of the K6 scale. Multiple linear regression and stratified analysis were used to evaluate the associations of intake with the confounding factors. Path analysis was conducted to describe the impacts of intake on health outcomes. Education levels and household incomes were significantly associated with intake of folate and depression scales (p &lt, 0.05). After adjusting for age, sex and total energy intake, years of education significantly affect the folate intake (β = 0.117, p &lt, 0.001). The structural equation model (SEM) shows that the indirect effect of folate intake is statistically significant and strong (p &lt, 0.05, 56% of direct effect) in the pathway of education level to depression scale. Our study shows both education and income are significantly associated with depression scales in Japanese workers, and the effort to increase the folate intake may alleviate the harms of social disparities on mental health.

The identification of risk factors for depression is necessary for the primary prevention of depression. The aim of this study is to determine whether self-efficacy (SE) is associated with onset of depression among workers. Medical expenditure records of 1,803 workers, who were clerks, system engineers, researchers, and service and sales workers in a software development company, were analyzed. Gender, age, job post, marital status, working hours, and SE were measured at baseline. Participants were divided according to quartiles of SE points. Risk ratios for undergoing a medical consultation due to depression were calculated using a multivariable Cox proportional hazards model. Of the 1,803 participants, 58 underwent medical consultation due to depression during a mean of 1.8 years of follow-up. Compared with the lowest quartile (Q1) of SE, adjusted hazard ratios (HR) were 0.65 (95%CI 0.34-1.25) for Q2, 0.49 (0.24-1.00) for Q3, and 0.40 (0.18-0.88) for Q4. In men, adjusted HRs were 0.87 (0.41-1.86) for Q2, 0.61 (0.26-1.41) for Q3, and 0.37 (0.14-0.98) for Q4. In women, no significant association was found. The present study suggests that low SE is a risk factor for onset of depression among male Japanese workers.

Objective To evaluate parents’ knowledge regarding foreign body aspiration (FBA) and determine the factors that are associated with lack of knowledge. Methods An 8-item questionnaire regarding knowledge of FBA was developed and distributed at regular check-ups for children younger than 24 months old. Results Out of the 1766 questionnaires distributed, 1603 were recovered and most of them (1539) were answered by mothers. After omitting 49 questionnaires with incomplete data, 1490 questionnaires answered by mothers were analyzed. Only 4.3% [95% CI 3.3–5.3] of mothers did not recognize a small toy as a cause of FBA, while 20.2% [95% CI 18.2–22.2] did not know that peanuts and other nuts can be causes of FBA, and 48.1% [95% CI 45.5–50.6] did not know that they should not give peanuts to a child younger than 3 years old. Regarding clinical signs, 27.7% [95% CI 25.4–30.0] and 41.8% [95% CI 39.3–44.3] of mothers did not know that sudden choking and sudden coughing were symptoms suggesting FBA, respectively. Being a mother with a child younger than 12 months old and being a mother with a first child were independent risk factors for lack of knowledge about FBA, regardless of the age of the mother. Conclusions A substantial number of mothers lack knowledge regarding FBA. To prevent FBA and to make timely diagnoses, parents, especially mothers with children younger than 12 months old and mothers with a first child should be given adequate information.

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.

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 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.

Shiro Ikegawa and colleagues identify common variants near LBX1 associated with adolescent idiopathic scoliosis. LBX1 encodes a homeobox protein expressed in the dorsal spinal cord and skeletal muscle that may contribute to scoliosis risk by altering somatosensory function. Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2–3% of school-age children worldwide1. Genetic factors have been implicated in its etiology2. Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 × 10−19; odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis.

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752.

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.

OBJECTIVE An association of the C-857T polymorphism of the tumor necrosis factor-α (TNF-α) gene promoter region with LDL cholesterol levels has been reported. This study was designed to evaluate the relationship between the TNF-α-C-857T polymorphism and LDL cholesterol levels according to statin treatment in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS DNA was obtained from 322 Japanese subjects (160 male and 162 female) with type 2 diabetes, and TNF-α-C-857T polymorphisms were determined by direct sequencing. Serum LDL cholesterol was measured by a direct method. RESULTS Although serum LDL cholesterol levels were significantly higher in the T carriers (C/T + T/T) than in the non–T carriers (C/C) (3.14 ± 0.86 vs. 2.89 ± 0.75 mmol/l, P < 0.05), there was no difference in LDL cholesterol levels between the non–T carriers and the T carriers in statin-untreated subjects (2.87 ± 0.73 vs. 2.89 ± 0.76 mmol/l, NS), whereas in statin-treated subjects, LDL cholesterol levels were significantly higher in the T carriers than in the non–T carriers (3.43 ± 0.89 vs. 2.90 ± 0.78 mmol/l, P = 0.0007). There were no differences in HDL cholesterol and triglyceride levels between the non–T carriers and the T carriers in both statin-treated and -untreated subjects. The percent decrease in LDL cholesterol levels after administration of statins was significantly smaller in the T carriers compared with the non–T carriers (27.6 vs. 36.4%, P = 0.031). CONCLUSIONS The mutant allele of the C-857T promoter polymorphism of the TNF-α gene may predispose to resistance to the LDL cholesterol–lowering effect of statins and could be one of the markers used to predict the efficacy of statins.

Repeated or chronic stress is known to produce structural and functional changes in the rat brain, and in particular, alter the response of the hypothalamic -- pituitary -- adrenal (HPA) axis to subsequent new stress. Occlusal disharmony via placement of acryl cap on the lower incisors of rats is perceived as chronic stress. To determine the response of the HPA axis to subsequent new stress in rats with occlusal disharmony, we measured plasma corticosterone levels in these rats after subjecting them to new stress. Plasma corticosterone levels in rats with and without incisal cap increased and reached a peak 30 min after exposure to the new stress. However, a later decrease in plasma corticosterone levels from peak levels was found in rats with incisal cap compared with rats without incisal cap. This finding suggests that occlusal disharmony alters the response of the HPA axis to subsequent new stress.

Tau protein levels in cerebrospinal fluid (CSF) and serum are elevated in patients with various central nervous system diseases. We investigated whether serum tau protein levels are useful for predicting and assessing disease activity of acute encephalopathy (AE) in enterohemorrhagic Escherichia coli (EHEC) O111-induced hemolytic uremic syndrome (HUS; EHEC encephalopathy). Serum samples were obtained from 14 patients with EHEC O111/HUS, 20 patients with non-EHEC-related AE, and 20 age- and sex-matched healthy controls. CSF samples were obtained from 2 patients with EHEC encephalopathy and 20 patients with non-EHEC-related AE. Tau protein levels and levels of several proinflammatory cytokines were quantified by enzyme-linked immunosorbent assays. Results were compared with the clinical features of EHEC encephalopathy, including magnetic resonance image (MRI) findings. Serum tau levels in patients with EHEC encephalopathy were significantly elevated compared with those in patients with EHEC O111/HUS without encephalopathy, patients with non-EHEC-related AE, and healthy controls. The ratio of CSF tau levels to serum tau levels was >1.0 in all patients with non-EHEC-related AE but

Improving knowledge and beliefs about mental health (or mental health literacy [MHL]) may promote appropriate help-seeking by adolescents who are suffering from mental health problems. We developed a concise, school-staff-led MHL program and examined its effects.The participants comprised 118 grade-9 students (61 boys and 57 girls). The program consisted of two 50-min sessions, and was given by a schoolteacher. The effects of the program were evaluated before, immediately after and 3 months after the program, using a self-report questionnaire.Knowledge of mental health/illnesses and desirable behavior for help-seeking were significantly improved immediately after (post-test, P 0.001, and P 0.001, respectively) and 3 months after the program (3-month follow up, P 0.001 and P 0.001, respectively), compared with the test before the delivery of the program (pre-test, Wilcoxon signed rank test). Proportions of the correct diagnoses of vignette cases of major depression and schizophrenia were significantly (P 0.001) elevated from 38.3% and 19.1% (pre-test) to 94.7% and 93.6% (post-test), and 91.5% and 86.2% (3-month follow up). Intentions to seek help and to provide peers with help with mental health problems were also significantly (P 0.001) elevated at post-test and at 3 months compared with the pre-test.A concise, school-staff-led program may have a significant effect on the improvement of MHL in secondary school students.

OBJECTIVE Several studies have reported favorable results of posterolateral fusion (PLF) with pedicle screw systems (PSs) for isthmic spondylolisthesis. However, the best indication and limitations of this method still remain unclear. The present study aimed to analyze the radiological risk factors of pseudoarthrosis and/or instrumentation failure after PLF with PSs in isthmic spondylolisthesis, and to determine the limitations of this method. METHODS The study group comprised of 101 patients with isthmic spondylolisthesis who underwent PLF with PSs. Follow-up was performed for more than 5 years. Statistical analyses with multivariate logistic regression models were used to identify risk factors of pseudoarthrosis and/or instrument failures associated with PLF with PSs. RESULTS Average follow-up was 8 years. Fusion rate was 95%. There were instrument breakage in 6 patients, and pseudoarthrosis in 5. Statistical analysis with a logistic regression model revealed that preoperative % disc height (odds ratio: 3.60 per 10%, P

Study design Retrospective comparative study of the postoperative subsidence of two interbody devices following posterior or transforaminal lumbar interbody fusion (PLIF/TLIF) for degenerative spondylolisthesis of the lumbar spine. Objective To assess certain radiograph characteristics of PLIF/TLIF using two interbody fusion devices at L4-L5. Summary of background data PLIF can achieve spinal stabilization with vertebral body support and direct neural decompression. Although various interbody devices have been used in PLIF procedures, no radiographic studies have compared the load-bearing capabilities of open box and fenestrated tube interbody cages. Methods Seventy-five patients who underwent one-level PLIF in the L4-L5 [corrected] segment for degenerative spondylolisthesis were retrospectively reviewed with a minimum 2-year follow-up. Fenestrated tube (Group FT: n = 30 [corrected]) or open box (Group OB: n = 45 [corrected]) cages were used for the PLIF procedure. The following radiographic parameters were evaluated to compare the load-bearing capabilities: disc space height (DH); percent increase and decrease of disc height (% IDH and % DDH, respectively); and percent coverage of the cage on the endplate (% CC). Results There were no significant differences in the baseline data, including age, segmental instability and osteoporotic status, between the two groups. Anterior %IDH and % CC were significantly higher in Group OB than in Group FT (% IDH: 69.4% vs. 57.3%; % OC: 24.5% vs. 12.9%), and anterior and posterior % DDH were significantly higher in Group FT than in Group OB (anterior: -2.9% vs. -.1%; posterior: -6.6% vs. -.3%). Although the restored DH gradually reduced over time in both groups, significant reduction to the preoperative level only occurred in Group FT. Conclusions The load-bearing capabilities of the open box cage are superior to those of the fenestrated tube cage. Since there were no significant differences between the baseline status of the two groups, the larger cross-sectional area and stable framework design of the open box cage appears to bring about a greater load-bearing capability. Therefore, the open box cage seems to be biomechanically more advantageous as an interbody device for PLIF than the fenestrated tube cage.

Object There are no published reports of unilateral transforaminal lumbar interbody fusion (TLIF) in which two Brantigan I/F cages were placed per level through a single portal to achieve bilateral anterior-column support. The authors describe such a surgical technique and evaluate the clinical outcomes of this procedure. Methods Data obtained in 86 (93.5%) of the first 92 consecutive patients who underwent the procedure were retrospectively reviewed; the minimum follow-up duration was 2 years. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scoring system. Disc height, disc angle, cage positioning in the axial plane, and fusion status were radiographically evaluated. The mean follow-up period was 33.8 months. The mean improvement in the JOA score was 77.2%. Fusion was successful in 93% of the cases. According to the Farfan method, the mean anterior and posterior disc heights increased from 20.2 and 16.9% preoperatively to 35.9 and 22.7% at follow up, respectively (p < 0.01). The mean disc angle increased from 4.8° preoperatively to 7.5° at last follow-up examination (p < 0.01). Two cages were correctly placed to achieve bilateral anterior-column support in greater than 85% of the cases. The following complications occurred: hardware migration in two patients and deep infection cured by intravenous antibiotic therapy in one patient. Conclusions Unilateral TLIF involving the placement of two Brantigan cages per level led to good clinical results. Two Brantigan cages were adequately placed via a single portal, and reliable bilateral anterior-column support was achieved. Although the less invasive unilateral approach was used, the outcomes were as good as those in many reported series of posterior lumbar interbody fusion in which the Brantigan cages were placed via the bilateral approach.

We measured liver fat content by 3-Tesla magnetic resonance spectroscopy (MRS) in 34 non- to mild obese Japanese subjects with type 2 diabetes, who were not complicated with any liver diseases including clinical fatty liver (liver/spleen ratio of computed tomography [CT] < 0.9) and were not being treated with oral hypoglycemic agents, insulin, or lipid-lowering agents, and analyzed the relationship between liver fat content and body composition and plasma metabolite. The liver fat content is significantly correlated with variables relating to obesity (body mass index [BMI], body weight, fat mass, waist to hip ratio, visceral fat area, subcutaneous fat area, and serum triglyceride), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR]), adipocytokines (serum plasminogen activator inhibitor-1 [PAI-1] and leptin), and serum cholinesterase, but not CT liver/spleen ratio, which is correlated only with fasting plasma glucose, BMI, and HOMA-IR. Multiple regression analysis revealed that the liver fat content is independently associated with serum PAI-1 level (p < 0.001) and BMI (p < 0.05), but not visceral fat area. MRS is a more sensitive method for quantifying liver fat content than CT in type 2 diabetic subjects with non- to mild obesity and without clinical fatty liver.

Background: Exposure of phosphatidylserine (PS) on apoptotic cells is known to result in the enhanced recognition of apoptotic cells by phagocytes. By the inclusion of PS in the lipid component of liposomes, increased liposome immune adjuvant activity was expected. Methods: In the present study, two different liposome preparations containing either PS, i.e. PS-liposome, or phosphatidylcholine (PC), i.e. PC-liposome, were made, and macrophage recognition, processing, and antigen presentation of surface-coupled liposomal antigen were compared. Results: When ovalbumin-liposome conjugates were added to a culture of macrophages, enhanced recognition and processing of ovalbumin by the macrophages were observed by the inclusion of PS in the liposomes. The results correlated well with those regarding macrophage antigen presentation of liposome-coupled ovalbumin. Furthermore, in vivo immunization in mice with ovalbumin-liposome conjugates made with PS-liposomes induced a significantly higher level of anti-ovalbumin IgG antibody production than was induced by ovalbumin-liposome conjugates made with PC-liposomes. IgE-selective unresponsiveness was induced by ovalbumin-liposome conjugates regardless of the lipid components of liposomes. Conclusions: These results suggest that the inclusion of PS in liposomes enhances recognition and processing of surface-coupled liposomal antigen by macrophages, and increases liposome immune adjuvant activity.

The Japan Spine Research Society carried out a nationwide survey on complications of the spine, enrolling a total of 16 157 patients who had undergone spine surgery in 196 institutes in the 1-year period from January to December 2001. Diseases, surgical procedures, and complications were surveyed in detail. Forty-nine percent of patients were aged 60 years or older, which was remarkably increased in comparison with the percentage reported by the 1994 survey (37.3%). The number of cases with degenerative spinal diseases comprised 78.2% of the total number of spine surgery cases. The percentage of patients with stenosis was the greatest (38.5%), reflecting the increase in the elderly population undergoing spine surgery. Spinal instrumentation was used with 5497 patients (34.0%). The frequency of its use was much greater than that reported in 1994 (27.0%). The pedicle screw was the most frequently used instrument (54.6%). The use of spinal instrumentation greatly increased for spinal deformity, trauma, and tumors. Posterior lumbar interbody fusion has been increasingly used in cases of lumbar degenerative disease. Complications of spinal surgery were reported in 1383 patients (8.6%). The incidence of complications associated with instrumentation surgery was 12.1%, being twice as much as that associated with noninstrumentation surgery (6.8%).

Several studies have suggested that there is frontal dysfunction in subjects with posttraumatic stress disorder (PTSD). We investigated the relationship between alterations of the hemodynamic response of the prefrontal cortex during a cognitive task (verbal fluency task; VFT) and memory function measured using the Wechsler Memory Scale-Revised (WMS-R). The subjects were victims of the Tokyo Subway Sarin attack with ( n =8) or without ( n =26) PTSD. Hemodynamic response in the prefrontal cortex was measured using a 24-channel near-infrared spectroscopy (NIRS) system. Subjects with PTSD had a significantly smaller response of oxygenated hemoglobin and total hemoglobin during the VFT compared with those without PTSD, although there was no significant difference in performance on the VFT. Subjects with PTSD had significantly lower scores on attention and concentration in the WMS-R, which was positively correlated with the increase of total hemoglobin during the VFT. The ‘frontal dysfunction' observed in subjects with PTSD may be a secondary phenomenon to reduced attentional capacity.

A retrospective, multicenter study.To identify risk factors for proximal junctional kyphosis (PJK) when treating early-onset scoliosis (EOS) with dual-rod growing-rod (GR) procedure.The risk factors for PJK associated with GR treatment for EOS have not been adequately studied.We evaluated clinical and radiographic results from 88 patients with EOS who underwent dual-rod GR surgery in 12 spine centers in Japan. The mean age at the time of the initial surgery was 6.5±2.2 years (range, 1.5-9.8 y), and the mean follow-up period was 3.9±2.6 years (range, 2.0-12.0 y). Risk factors for PJK were analyzed by binomial multiple logistic regression analysis. The potential factors analyzed were sex, etiology, age, the number of rod-lengthening procedures, coronal and sagittal parameters on radiographs, the type of foundation (pedicle screws or hooks), the uppermost level of the proximal foundation, and the lowermost level of the distal foundation.PJK developed in 23 patients (26%); in 19 of these, the proximal foundation became dislodged following PJK. Binomial multiple logistic regression analysis identified the following significant independent risk factors for PJK: a lower instrumented vertebra at or cranial to L3 [odds ratio (OR), 3.32], a proximal thoracic scoliosis of ≥40 degrees (OR, 2.95), and a main thoracic kyphosis of ≥60 degrees (OR, 5.08).The significant independent risk factors for PJK during dual-rod GR treatment for EOS were a lower instrumented vertebra at or cranial to L3, a proximal thoracic scoliosis of ≥40 degrees, and a main thoracic kyphosis of ≥60 degrees.

OBJECTIVE Oxidative stress has been implicated in the development of coronary artery calcification (CAC). However, there are few reports on this issue in Japanese patients with diabetes. In this study, we examined the association of the CAC score (CACS) with oxidative stress markers. METHODS The study subjects were 163 Japanese patients with type 2 diabetes (75 men and 88 women). The CACS (Agatston unit: AU) was measured by multi-detector computed tomography (MDCT), and the oxidative stress markers, such as the urinary 8-isoprostane and 8-hydroxydeoxyguanosine (8-OHdG) and serum malondialdehyde (MDA)-LDL cholesterol were measured. The relationships between CACS and oxidative stress markers were statistically analyzed. RESULTS Compared with the CACS 0-400 AU group (n=132), the age, duration of diabetes, urinary 8-isoprostane levels, serum MDA-LDL-C/LDL-C and maximum intima media thickness (IMT) were higher, and body mass index and HbA1c level were lower, in the CACS >400 AU group (n=31). The multiple logistic regression analysis showed that a CAC >400 AU was independently associated with the urinary 8-isoprostane (>median) (OR=2.54, 95% CI=1.03-6.32, p=0.044), MDA-LDL-C/LDL-C (>median) (OR=2.62, 95% CI=1.07-6.40, p=0.035) and HbA1c (>median) (OR=0.32, CI=0.12-0.87, p

BackgroundBackgroundIn 2007, the Japanese orthopaedic association back pain evaluation questionnaire (JOABPEQ) wasestablished to overcome the limitations of the original JOA scoring system developed in 1986. Although this new selfadministered questionnaire is a more accurate outcome measure for evaluating patients with low back pain, physicians were unable to as certain the exact status of a patientat a single time point because of a lack of reference values.This study aimed to establish the reference values of JOABPEQ in different age and gender groups using data obtained from healthy volunteers.MethodsThis study was conducted in 21 university hospitals and affiliated hospitals from October 2012 to July2013. The JOABPEQ includes 25 questions that yield five domains to evaluate individuals with low back pain from five different perspectives. A total of 1,456 healthy volunteers (719 men, 737 women; age range, 20–89 years) answered the questionnaire. The differences in scores according to age and gender were examined by non-parametric tests.ResultsThe JOABPEQ scores significantly decreased with age in the domains of lumbar spine dysfunction, gaitdisturbance, and social life dysfunction. In these three domains, the median scores approached the 100 possible points in individuals aged 20–70 for both genders. However,the median scores for lumbar spine dysfunction and social life dysfunction decreased to 83.0 and 65.0–78.0 points, respectively, in individuals in their 80s and 70–80 s,respectively; and the scores for gait disturbance decreased to 93.0 and 71.0 points for males and females in their 80 s. Overall, the median scores for pain-related and psychological disorders were 100 and 60.0–72.0 points, respectively.ConclusionsThe reference values for JOABPEQ according to age and gender were established herein. Patientswith low back pain should be evaluated with this new selfadministered questionnaire taking these reference values into account.

Objective: To elucidate the clinical and radiologic features and analyze factors associated with neurologic outcomes of encephalopathy secondary to Shiga toxin–producing Escherichia coli (STEC) O111. Methods: We reviewed medical records and neuroimaging in 22 patients with neurologic symptoms among 86 with STEC O111 infection. Results: Twenty-one (6 males and 15 females, 10 children and 11 adults) of the 22 patients were diagnosed with encephalopathy. All patients with encephalopathy also presented with hemolytic-uremic syndrome. Five patients died, from day 1 to 6 months (days 1–5 in 4 patients), due to progressive encephalopathy with severe cerebral edema observed in neuroimaging (4 patients). Fifteen of the 16 surviving patients clinically recovered completely. Statistical analysis revealed differences between patients with poor (n = 6) and good (n = 15) outcomes in the interval from hemolytic-uremic syndrome presentation to encephalopathy, creatinine levels, and the methylprednisolone administration ratio. Conclusion: We note a high incidence of encephalopathy in the Toyama STEC O111 outbreak. All fatal cases resulted from progressive encephalopathy. Methylprednisolone pulse therapy represents a possible therapeutic choice. Classification of evidence: This study provides Class III evidence that methylprednisolone pulse therapy increases the probability of a good outcome for patients with encephalopathy associated with STEC O111.