Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Instrumentation failure following pediatric spine deformity growth-sparing surgery using traditional growing rods or vertical expandable prosthetic titanium ribs.

BACKGROUND: Instrumentation failure (IF) is a major complication associated with growth-sparing surgery for pediatric spinal deformities; however, studies focusing on IF following each surgical procedure are lacking. We aimed to evaluate the incidence, timing, and rates of unplanned return to the operating room (UPROR) associated with IF following each surgical procedure in growth-sparing surgeries using traditional growing rods (TGRs) and vertical expandable prosthetic titanium ribs (VEPTRs). METHODS: We reviewed 1,139 surgical procedures documented in a Japanese multicenter database from 2015 to 2017. Of these, 544 TGR and 455 VEPTR procedures were included for evaluation on a per-surgery basis. IF was defined as the occurrence of an implant-related complication requiring revision surgery. RESULTS: The surgery-based incidences of IF requiring revision surgery in the TGR and VEPTR groups were 4.3% and 4.0%, respectively, with no significant intergroup difference. Remarkably, there was a negative correlation between IF incidence per surgical procedure and the number of lengthening surgeries in both groups. In addition, rod breakage in the TGR group and anchor-related complications in the VEPTR group tended to occur relatively early in the treatment course. The surgery-based rates of UPROR due to IF in the TGR and VEPTR groups were 2.0% and 1.5%, respectively, showing no statistically significant difference. CONCLUSIONS: We found that IF, such as anchor related-complications and rod breakage, occurs more frequently earlier in the course of lengthening surgeries. This finding may help in patient counseling and highlights the importance of close postoperative follow-up to detect IF and improve outcomes.

Analysis of the relationship between spinal alignment and retrocrural space area in adult spinal deformity surgery: Potential risk factors for acute celiac artery compression syndrome.

PURPOSE: This study was designed to reveal the association between spinal parameters and RCS area in patients with adult spinal deformities treated with spinal correction surgery. We hypothesized that reduction of the retrocrural space (RCS) area is related to thoracolumbar alignment, which may cause acute celiac artery compression syndrome (ACACS). METHODS: Eighty-nine patients (age: 68.4 ± 7.6 years; sex: 7 male/82 female) with ASD treated by spinal correction surgery were enrolled. Preoperative and postoperative spinal parameters were measured, and the differences between these parameters were calculated. Postoperative T12 translation was measured and RCS area was evaluated using reconstructed computed tomography. The change of RCS area after surgery was defined as ΔRCS. Patients were divided into increased and decreased RCS groups by the ΔRCS value, and spinal parameters were compared between groups. The correlation between spinal parameters and ΔRCS was calculated. RESULTS: The patients in the decreased RCS group had greater anterior T12 translation than those in the increased RCS group (p < 0.001). T12 translation was significantly correlated with ΔRCS (ß = -0.31, p = 0.017). There were no correlations between ΔRCS and other spinal parameters. CONCLUSION: Thoracolumbar alignment was associated with RCS area. Consistent with the hypothesis, overcorrection of the thoracolumbar junction was associated with reduced RCS area and might be one risk factor for ACACS.

Long-term changes in bone mineral density following adolescent idiopathic scoliosis surgery: a minimum 34-year follow-up.

PURPOSE: To investigate longitudinal changes in bone mineral density (BMD) in middle-aged female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS). METHODS: The study subjects were 229 female patients who were diagnosed with AIS and underwent spinal fusion between 1968 and 1988. A two-step survey study was conducted on 19 female AIS patients. BMD, Z-scores, T-scores, and the prevalence of osteoporosis and osteopenia were compared between the initial (2014-2016) and second (2022) surveys. Correlations between the annual changes in Z-scores and T-scores with radiographic parameters, body mass index (BMI), and the number of remaining mobile discs were analyzed. RESULTS: BMD decreased significantly from the initial (0.802 ± 0.120 g/cm2) to the second survey (0.631 ± 0.101 g/cm2; p < 0.001). Z-scores decreased from 0.12 ± 1.09 to - 0.14 ± 1.04, while T-scores decreased significantly from - 0.70 ± 1.07 to - 1.77 ± 1.11 (p < 0.001). The prevalence of osteopenia and osteoporosis increased significantly from 36.8% to 89.5% (p = 0.002), but the increase in osteoporosis alone was not statistically significant (5.3% to 26.3%; p = 0.180). Moderate negative correlations were found between annual changes in Z-scores and both main thoracic (MT) curve (r = - 0.539; p = 0.017) and lumbar curve (r = - 0.410; p = 0.081). The annual change in T-scores showed a moderate negative correlation with the MT curve (r = - 0.411; p = 0.081). CONCLUSION: Significant reductions in BMD and an increased prevalence of osteopenia and osteoporosis were observed in middle-aged female AIS patients who had undergone spinal fusion. The decline in Z-scores in patients with AIS suggested that there was an accelerated loss of BMD compared with the general population. Larger residual curves could pose an added osteoporosis risk. Further research is needed to understand if the onset of osteoporosis in AIS patients is attributable to the condition itself or the surgical intervention.

Risk factors for vertebral bridging in residual adolescent idiopathic scoliosis with thoracolumbar/lumbar curves.

BACKGROUND: Although vertebral bridging in residual adolescent idiopathic scoliosis (AIS) can make corrective surgery more complicated, no study has investigated the risk factors. The purpose of this research was to determine risk factors for vertebral bridging in individuals with residual AIS with thoracolumbar/lumbar (TL/L) curves. METHODS: Forty-two pre-operative patients with residual AIS and TL/L curves (3 males, 39 females: age 41.9 ± 18.0 years) were divided into bridging (n = 17) and non-bridging (n = 25) groups. All patients were 20 years or older with a diagnosis of AIS in adolescence. The bridging group consisted of patients with third or more degree bridging by the Nathan classification. RESULTS: There were significant differences in age, absolute value of apical vertebral translation (AVT), C7 translation, and L3,4 tilt between groups. There was no significant difference in TL/L Cobb angle. Multivariate analyses and ROC curves demonstrated that older age was a significant risk factor for vertebral bridging (odds ratio [OR]: 1.08; 95% confidence interval: 1.02-1.14; P = 0.004), with a cutoff value of 38.0 years old. CONCLUSIONS: This study indicates that patients >38 years old are at risk for vertebral bridging in residual AIS. Because of the higher risk of vertebral bridging and other degenerative changes, residual AIS patients about 40 years of age are at a critical point for treatment strategy. Because appropriate surgical time should not be missed, regular follow-up is required even after 30 years of age, especially if the patient with residual AIS has a large TL/L curve indicated for surgery.

Associated factors and effects of coronal vertebral wedging angle in thoracic adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) causes vertebral wedging, but associated factors and the impact of vertebral wedging are still unknown. We investigated associated factors and effects of vertebral wedging in AIS using computed tomography (CT). METHODS: Preoperative patients (n = 245) with Lenke types-1 and 2 were included. Vertebral wedging, lordosis, and rotation of the apical vertebra were measured by preoperative CT. Skeletal maturity and radiographic global alignment parameters were evaluated. Multiple regression analysis was performed on associated factors for vertebral wedging. Side-bending radiographs were evaluated using multiple regression analysis to calculate the percentage of reduction of Cobb angles to determine curve flexibility. RESULTS: The mean vertebral wedging angle was 6.8 ± 3.1°. Vertebral wedging angle was positively correlated with proximal thoracic (r = 0.40), main thoracic (r = 0.54), and thoracolumbar/lumbar curves (r = 0.38). By multiple regression, the central sacral vertical line (p = 0.039), sagittal vertical axis (p = 0.049), main thoracic curve (p = 0.008), and thoracolumbar/lumbar curve (p = 0.001) were significant factors for vertebral wedging. In traction and side-bending radiographs there were positive correlations between curve rigidity and the vertebral wedging angle (r = 0.60, r = 0.59, respectively). By multiple regression, thoracic kyphosis (p < 0.001), lumbar lordosis (p = 0.013), sacral slope (p = 0.006), vertebral wedging angle (p = 0.003), and vertebral rotation (p = 0.002) were significant factors for curve flexibility. CONCLUSIONS: Vertebral wedging angle was found to be highly correlated to coronal Cobb angle, with larger vertebral wedging indicating less flexibility.

Risk factors for celiac artery and superior mesenteric artery stenosis in preoperative lumbar and thoracolumbar spinal surgery patients.

BACKGROUND: Ischemic necrosis of the abdominal organs caused by compression of the celiac artery (CA) and superior mesenteric artery (SMA) by the median arcuate ligament (MAL) after correction surgery has been recognized as acute celiac artery compression syndrome (ACACS). Here, using contrast-enhanced computed tomographic (CT) images, we sought to determine the prevalence and degree of CA and SMA stenosis in spinal patients preoperatively, and the risk factors associated with the stenosis. METHODS: We retrospectively examined contrast-enhanced abdominal CT of 90 patients with preoperative lumbar degenerative disease, lumbar burst fracture, or adult spinal deformity. The trunks of the CA and SMA were detected using three-dimensional reconstructed CT. To investigate their degree of stenosis, we determined the ratio of the narrowest diameter of the stenotic segment to the distal normal lumen's diameter. Patients with a degree of stenosis ≥35% were defined as being in the group with stenosis and the remainder as in the group without. To determine the risk factors for stenosis of these arteries, the relationship between the stenosis and CA and SMA calcification or the median arcuate ligament (MAL) crossing the proximal portion of the celiac axis (MAL overlap) was also investigated. RESULTS: The average degree of stenosis of the CA trunk was 12.1% ± 13.9% and that for the SMA trunk was 8.5% ± 8.8%. There were 8 patients (8.9%) in the group with CA stenosis and 2 patients (2.2%) in the group with SMA stenosis. The number of patients in the group with CA stenosis was significantly greater than the number with MAL overlap or CA calcification (P < 0.05). DISCUSSION: The prevalence of CA or SMA stenosis was 11.2% of preoperative patients due to undergo thoracolumbar fusion surgery. Calcifications of the CA trunk and MAL overlap are risk factors for CA stenosis.

Prevalence of pleural injury in an extrapleural approach to adolescent idiopathic scoliosis and association of pleural injury with postoperative respiratory function.

BACKGROUND: The prevalence of pleural injury during surgery for adolescent idiopathic scoliosis using an extrapleural approach and the association of pleural injury with postoperative pulmonary function remain unclear. We sought to determine the prevalence of pleural injury associated with an extrapleural approach to adolescent idiopathic scoliosis, and to determine any difference in respiratory function between patients with or without pleural injury. METHODS: Data from consecutive patients with scoliosis of the thoracolumbar/lumbar spine who underwent anterior spinal fusion using an extrapleural approach were assessed in this retrospective study. We had diagnosed and treated pleural injury according to our algorithm. Pre- and postoperative values of pulmonary function tests and postoperative change rates were compared between patients with and without pleural injury. FVC, %FVC, FEV1.0, and FEV1.0% were evaluated from pulmonary function tests. RESULTS: We included data from 51 patients with adolescent idiopathic scoliosis (45 female and 6 male) with a mean age of 17.2 ± 3.5 years in this retrospective study. The group with pleural injury comprised 31 patients and the group without 20. Therefore, the prevalence of pleural injury during an extrapleural approach was 61%. We found no significant differences in preoperative FVC, %FVC, FEV1.0, and FEV1.0% between the groups. We found no significant differences in FVC, %FVC, FEV1.0, and FEV1.0% between the groups at 3 months or 1 year postoperatively. Furthermore, we found no significant differences in the postoperative change ratio of FVC, %FVC, FEV1.0, and FEV1.0% between the groups. CONCLUSION: The prevalence of pleural injury associated with an extrapleural approach to scoliosis was 61%. Pleural injury was not associated with a decrease in postoperative pulmonary function in patients with scoliosis treated using an extrapleural approach.

Efficacy of lateral lumbar interbody fusion combined with posterior spinal fusion compared with three-column osteotomy for adult spinal deformity with severe lumbar sagittal deformity.

PURPOSE: The clinical and radiological results of adult spinal deformity (ASD) patients with a severe lumbar sagittal deformity undergoing multilevel lateral lumbar interbody fusion (LLIF) + posterior spinal fusion (PSF) were compared to patients undergoing three-column osteotomy (3CO). METHODS: We defined severe lumbar sagittal deformity as fulcrum backward bending (FBB) pelvic incidence minus lumbar lordosis (PI-LL) ≧ 20 degrees. A total of twenty-five patients with an ASD were enrolled between 2013 and 2018. Fifteen patients were in the LLIF + PSF group, and ten patients were in the 3CO group. We evaluated patient demographics, clinical outcomes, and radiographic parameters such as the Cobb angle and spinopelvic parameters from standing X-ray films in each group. RESULTS: The LLIF + PSF group had a significantly shorter follow-up time than the 3CO group. Postoperatively, the LLIF + PSF group had significantly lower PI-LL and a shorter sagittal vertical axis than the 3CO group. Postoperative PI-LL changes in the LLIF + PSF group were significantly smaller than those in the 3CO group. There were no differences in other patient demographics, radiographic parameters, or clinical outcomes between the groups. CONCLUSION: Multilevel LLIF + PSF improved the PI-LL and SVA more than did 3CO for ASD patients with severe lumbar sagittal deformity. This indicated that the multilevel LLIF with open PSF can provide good clinical outcomes even in cases with severe lumbar sagittal deformity such as large FBB PI-LL in which 3CO techniques usually are needed.

What factor induces stress in patients with AIS under brace treatment? Analysis of a specific factor using exploratory factor analysis.

BACKGROUND: Stress from brace treatment in patients with adolescent idiopathic scoliosis (AIS) can deteriorate their quality of life. A Japanese version of the Bad Sobernheim Stress Questionnaire-Brace (JBSSQ-brace) was developed to assess the stress from brace treatment for Japanese patients with AIS. However, the specific factors causing stress under brace treatment have remained unknown. METHOD: We enrolled 69 consecutive Japanese patients with AIS. Stress from brace treatment was assessed by JBSSQ-brace and Scoliosis Research Society-22 (SRS-22) instruments. The correlations of JBSSQ-brace with SRS-22 score, patient demographics and Cobb angle were analyzed by Spearman's rank correlation. Exploratory factor analysis was used to determine the psychological factor causing stress from brace treatment. RESULTS: JBSSQ-brace score was correlated with total score of SRS-22, self-image and mental health domain, but not age, degree of curvature, or other domains of the SRS-22. Factor analysis detected one underlying factor, which was more related to Questions 4 or 5 with the factor loadings of 0.8 than Questions 1 or 6 with loadings of 0.65. CONCLUSION: Stress from brace treatment was not associated with age, spinal curve severity, pain, or satisfaction of treatment. Exploratory factor analysis suggested "anxious feeling about how we are perceived by others" induces the stress from brace treatment in Japanese patients with AIS.

Anchor type at upper instrumented vertebra and postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis.

PURPOSE: To clarify the impact of anchor type at upper instrumented vertebra (UIV) on postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion. METHODS: Subjects were 81 patients with Lenke type 1 AIS who underwent posterior spinal fusion between 2004 and 2013. Twenty-five patients agreed to participate in the study. We divided the patients into two groups: Hook group (15 patients with hooks at UIV who underwent surgery between 2004 and 2011) and PS group (ten patients with pedicle screws at UIV who underwent surgery between 2012 and 2013). To evaluate shoulder balance, first thoracic vertebra tilt angle (T1 tilt), clavicle angle (CA), and radiographic shoulder height (RSH) were measured. RESULTS: There were no significant differences in preoperative T1 tilt, CA, or RSH between the both groups. The postoperative 1-week, 2-year, and most recently observed T1 tilts were significantly smaller in the Hook group than in the PS group. There were no significant differences in postoperative 1-week, 2-year, and most recently observed CAs between the two groups. Although there were no significant differences in 1-week postoperative RSH between the groups, the 2-year postoperative RSH was significantly smaller in the Hook group than in the PS group. The most recently observed RSH tended to be smaller in the Hook group than in the PS group, but the difference was not significant. CONCLUSIONS: In the PS group, poor shoulder balance remained over the long term. The hooks at UIV adjusted postoperative shoulder balance.

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.

Comparison of Early Definitive Fusion and Traditional Growing Rods in Early-onset Dystrophic Scoliosis in Neurofibromatosis Type 1: A Preliminary Report.

BACKGROUND: Early definitive spinal fusion (EF) has been widely recommended to avoid spinal deformity progression for early-onset scoliosis (EOS) with neurofibromatosis type 1 (NF-1). In contrast, growing rod (GR) procedure has recently been recommended for EOS associated with the dystrophic type NF-1. However, no studies have compared the surgical outcomes between EF and GR procedure for EOS with NF-1. The purpose of this study was to compare the surgical outcomes of EF versus GR for early onset and dystrophic scoliosis with NF-1. METHODS: This was a retrospective multicenter study; 26 EOS patients with dystrophic type of NF-1 who underwent EF (16 patients) or GR (10 patients) were investigated. We compared age at first surgery, fused levels, total number of surgeries, coronal major curve, complication rates, spinal height (T1-T12 and T1-S1 length), and forced vital capacity between the 2 groups. RESULTS: The mean age at first surgery was 7.3 years in the EF and 5.8 years in the GR (P<0.05). The mean follow-up period was 12.8 and 10.5 years, respectively. The 2 groups did not show significant differences in preoperative major Cobb angle (75.1 vs. 83.1 degrees), complication rate (53% vs. 60%), and increase rate of T1-T12 (20.0% vs. 30.4%). However, significant differences (P<0.05) were recognized in fusion segments (13.9 vs. 15.8), total numbers of surgery (2.6 vs. 10.1), correction rate of major curve (59.0% vs. 40.6%), increase rate of T1-S1 (19.0% vs. 33.9%), body height at final follow-up (151 vs. 142 cm), and forced vital capacity at final follow-up (2.23 vs. 1.46 L). CONCLUSIONS: Early fusion is still a viable option for progressive EOS with dystrophic type of NF-1 even in the growth-friendly era. Surgeons should consider the best procedure for each patient taking into account the severity of dystrophic change when treating EOS with NF-1. LEVEL OF EVIDENCE: Level IV.

Clinical application of intraoperative O-arm navigation in reverse shoulder arthroplasty.

BACKGROUND: Inaccurate fixation and positioning of the glenoid component using conventional techniques are problematic in reversed shoulder arthroplasty (RSA). Our objective was to investigate the accuracy of O-arm navigation of the glenoid component in RSA. METHODS: This retrospective case-control study comprised 2 groups of 25 patients who underwent reversed shoulder arthroplasty with or without intraoperative O-arm navigation. The intraoperative goal was to place the component neutrally in the glenoid in the axial plane and 10° inferiorly tilted in the scapular plane. Glenoid version angle and inclination were measured by computed tomography obtained preoperatively and a year postoperatively. Operative time, intraoperative bleeding, and the presence of postoperative complications were recorded. RESULTS: Compared with the ideal, the range of error for version was 7.3° (SD 3.6°) in the control group and 5.6° (SD 3.6°) in the navigated group (P = 0.278), and the range of error for inclination was 18.3° (SD 11.7°) in the control group and 4.9° (SD 3.8°) in the navigated group (P = 0.0004). The mean operative time was 164.6 (SD 21.2) min in the control group and 192.0 (SD 16.2) min in the navigated group (P = 0.001). The mean intraoperative bleeding was 201.0 (SD 37.0) mL in the control group and 185.3 (SD 35.6) mL in the navigated group (P = 0.300). There were no complications reported related to the intraoperative O-arm navigation. CONCLUSION: O-arm navigation may be a useful tool for the placement with inferior tilt of the glenoid procedure in reversed shoulder arthroplasty.

Patients majoring in a healthcare field after scoliosis surgery: Comparison with the national census in Japan.

BACKGROUND: Although scoliosis surgery early in life may affect the career choice of the patient in favor of a healthcare field, no study has analyzed this relationship. We investigated the career paths of patients after scoliosis surgery. METHODS: A total of 212 patients with scoliosis who underwent corrective surgery at 12-17 years of age were mailed a questionnaire, of whom 98 (mean age at survey: 21.0 ± 1.7, years) responded. Choice of study major was determined by the same questions used in the Japanese national census. RESULTS: Of the 98 patients, 35% chose a career in healthcare compared with 11% of the general population of the same age, based on the national census. Healthcare was the most popular career choice of patients, whereas it ranked fourth according to the national census. Furthermore, 87% of patients reported that their decision to pursue a healthcare-related career was affected by their own medical experiences. Among the healthcare-related occupations, nursing ranked first, accounting for 35% of all healthcare professions chosen by the patients. Compared with patients who chose a non-healthcare career, those choosing a healthcare career decided on their study major at a significantly lower age. CONCLUSIONS: One-third of patients with scoliosis who underwent spine surgery chose a career in a healthcare field. Furthermore, an earlier age at the time of making a career decision was a significant factor associated with choosing a healthcare career. These findings suggest that the patients' experiences in the hospital positively affected their future career paths.

Automated classification of hip fractures using deep convolutional neural networks with orthopedic surgeon-level accuracy: ensemble decision-making with antero-posterior and lateral radiographs.

Background and purpose - Deep-learning approaches based on convolutional neural networks (CNNs) are gaining interest in the medical imaging field. We evaluated the diagnostic performance of a CNN to discriminate femoral neck fractures, trochanteric fractures, and non-fracture using antero-posterior (AP) and lateral hip radiographs. Patients and methods - 1,703 plain hip AP radiographs and 1,220 plain hip lateral radiographs were included in the total dataset. 150 images each of the AP and lateral views were separated out and the remainder of the dataset was used for training. The CNN made the diagnosis based on: (1) AP radiographs alone, (2) lateral radiographs alone, or (3) both AP and lateral radiographs combined. The diagnostic performance of the CNN was measured by the accuracy, recall, precision, and F1 score. We further compared the CNN's performance with that of orthopedic surgeons. Results - The average accuracy, recall, precision, and F1 score of the CNN based on both anteroposterior and lateral radiographs were 0.98, 0.98, 0.98, and 0.98, respectively. The accuracy of the CNN was comparable to, or statistically significantly better than, that of the orthopedic surgeons regardless of radiographic view used. In the CNN model, the accuracy of the diagnosis based on both views was significantly better than the lateral view alone and tended to be better than the AP view alone. Interpretation - The CNN exhibited comparable or superior performance to that of orthopedic surgeons to discriminate femoral neck fractures, trochanteric fractures, and non-fracture using both AP and lateral hip radiographs.

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.

Japanese adaptation of the Bad Sobernheim Stress Questionnaire-Brace for patients with adolescent idiopathic scoliosis.

BACKGROUND: Patients with adolescent idiopathic scoliosis (AIS) under brace treatment perceive stress, not only from scoliosis, but from wearing the brace itself. The Bad Sobernheim Stress Questionnaire-Brace (BSSQbrace) was developed to assess the level of psychological stress induced by brace treatment for AIS. However, a Japanese version of BSSQbrace had not yet been developed. METHODS: We developed a Japanese adaptation of the Bad Sobernheim Stress Questionnaire-Brace (JBSSQ-brace) through a guideline-based process to adapt assessment of the psychological effect of brace treatment for AIS in Japanese patients. We administered the JBSSQ-brace to 71 patients with AIS under brace treatment in our clinic. Internal consistency and reproducibility were analyzed using Cronbach's alpha and a test-retest method. RESULTS: We included 44 patients that responded adequately. JBSSQ-brace achieved excellent internal consistency (Cronbach's alpha = 0.84 for the first questionnaire, and 0.87 for the second) and substantial reproducibility (interclass correlation coefficient = 0.75). The average score for JBSSQ-brace was 16.5 and 16.8, and almost 40% of AIS patients felt a moderate-to-high stress from brace treatment. CONCLUSIONS: JBSSQ-brace is an effective instrument with which to evaluate the stress level from brace treatment in Japanese patients with AIS.

MRI evaluation of dural sac enlargement by interspinous process spacers in patients with lumbar spinal stenosis: Does it play a role in the long term?

BACKGROUND: To investigate dural sac enlargements and spinal alignments in patients who underwent indirect decompression with interspinous spacers. METHODS: The subjects were 20 patients who underwent indirect decompression using an interspinous spacer (X-STOP) without laminectomy. Of these 20 patients, 1 patient underwent implant removal surgery 1 month after X-STOP surgery and two patients dropped out. Ultimately, 17 patients were included in this study. MRI and X-ray images were investigated before surgery, 1 week after surgery, 3 months after surgery, and 2 years after surgery. RESULTS: On MRI, the mean cross-sectional areas of the dural sac were 52.7 mm2 before surgery, 73.2 mm2 1 week after surgery, 62.4 mm2 3 months after surgery, and 58.3 mm2 2 years after surgery. There was a significant 37% increase at 1 week postoperatively compared with that before surgery, but there were no significant differences between 3 months postoperatively and 2 years postoperatively. The disc angle in an extension posture was significantly decreased at 1 week after surgery compared with that before surgery, but there were no significant differences between before surgery, 3 months after surgery, and 2 years after surgery. CONCLUSIONS: The interspinous process spacer increased the dural sac area by 37% 1 week after surgery, but the enlargement was not maintained at 3 months or 2 years after surgery. The use of interspinous process spacers produced an enlargement of the dural sac by limiting extension of the stenotic level only. However, its effect diminished 2 years after surgery.

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.