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.

Using the Proximal Femur Maturity Index at Brace Initiation for Adolescent Idiopathic Scoliosis Predicts Curve Progression Risk.

BACKGROUND: The Proximal Femur Maturity Index (PFMI) can be used to assess skeletal maturity on existing whole-spine radiographs without additional radiation. However, the relationship between the PFMI at the initiation of bracing for adolescent idiopathic scoliosis (AIS) and subsequent curve progression remains unknown. This study aimed to investigate the relationship between the PFMI and curve progression, and the predictability of risks to adulthood curve progression and surgical thresholds based on the PFMI grade at brace initiation. METHODS: This was a prospective study of 202 patients with AIS who were prescribed underarm bracing according to the Scoliosis Research Society criteria and had good brace-wear compliance. The patients were followed from brace initiation until complete skeletal maturity. Longitudinal data on the coronal Cobb angle and skeletal maturity assessments using Risser staging, Sanders staging, the distal radius and ulna classification, and the PFMI were collected. Each patient was assessed on whether the major curve progressed to ≥40° (adulthood deterioration) and ≥50° (the surgical threshold). Logistic regressions were used to predict probabilities of curve progression to the 2 thresholds, adjusted for factors that were significant in univariate analyses. RESULTS: The PFMI correlated with the other skeletal maturity indices (r s [Spearman rank correlation] = 0.60 to 0.72, p < 0.001 for all). The pre-brace PFMI grade correlated with progression to ≥40° (r rb [rank-biserial correlation] = -0.30, p < 0.001) and to ≥50° (r rb = -0.20, p = 0.005). Based on regression models (p < 0.001) adjusted for the pre-brace major Cobb angle and curve type, brace initiation at PFMI grades 2 and 3 for a curve of ≥30° had predicted risks of 30% (95% confidence interval [CI], 4% to 55%) and 12% (95% CI, 7% to 17%), respectively, for progression to the surgical threshold. Brace initiation at PFMI grade 5 had 0% progression risk. CONCLUSIONS: The PFMI can be used for predicting curve progression and prognosticating brace outcomes in AIS. Patients with brace initiation at PFMI grade 4 for a curve of <30° or at grade 5 were unlikely to progress to the adulthood deterioration or surgical threshold. In comparison, skeletally immature patients initiating bracing at a PFMI grade of ≤3 for a major curve of ≥30° had a higher risk of progression despite compliant brace wear. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.

The Utility of a Novel Proximal Femur Maturity Index for Staging Skeletal Growth in Patients with Idiopathic Scoliosis.

BACKGROUND: For growing patients, it is ideal to have a growth plate visible in routine radiographs for skeletal maturity assessment without additional radiation. The proximal femoral epiphyseal ossification is in proximity to the spine; however, whether it can be used for assessing a patient's growth status remains unknown. METHODS: Two hundred and twenty sets of radiographs of the spine and the left hand and wrist of patients with idiopathic scoliosis were assessed for skeletal maturity and reliability testing. Risser staging, Sanders staging (SS), distal radius and ulna (DRU) classification, the proximal humeral ossification system (PHOS), and the novel proximal femur maturity index (PFMI) were used. The PFMI was newly developed on the basis of the radiographic appearances of the femoral head, greater trochanter, and triradiate cartilage. It consists of 7 grades (0 to 6) associated with increasing skeletal maturity. The PFMI was evaluated through its relationship with pubertal growth (i.e., the rate of changes of standing and sitting body height [BH] and arm span [AS]) and with established skeletal maturity indices. Longitudinal growth data and 780 corresponding spine radiographs were assessed to detect peak growth using receiver operating characteristic (ROC) curve analysis. RESULTS: The PFMI was found to be correlated with chronological age (τ b = 0.522), growth rates based on standing BH (τ b = -0.303), and AS (τ b = -0.266) (p < 0.001 for all). The largest growth rate occurred at PFMI grade 3, with mean standing BH growth rates (and standard deviations) of 0.79 ± 0.44 cm/month for girls and 1.06 ± 0.67 cm/mo for boys. Growth rates of 0.12 ± 0.23 cm/mo (girls) and 0 ± 0 cm/mo (boys) occurred at PFMI grade 6, indicating growth cessation. Strong correlations were found between PFMI gradings and Risser staging (τ b = 0.743 and 0.774 for girls and boys), Sanders staging (τ b = 0.722 and 0.736, respectively), and radius (τ b = 0.792 and 0.820) and ulnar gradings (τ b = 0.777 and 0.821), and moderate correlations were found with PHOS stages (τ b = 0.613 and 0.675) (p < 0.001 for all). PFMI gradings corresponded to as young as SS1, R4, U1, and PHOS stage 1. Fair to excellent interrater and intrarater reliabilities were observed. PFMI grade 3 was most prevalent and predictive for peak growth based on ROC results. CONCLUSIONS: The PFMI demonstrated clear pubertal growth phases with satisfactory reliability. Grade 3 indicates peak growth and grade 6 indicates growth cessation. CLINICAL RELEVANCE: The use of PFMI can benefit patients by avoiding additional radiation in skeletal maturity assessment and can impact current clinical protocol of patient visits. PFMI gradings had strong correlations with SS, DRU gradings, and Risser staging, and they cross-referenced to their established grades at peak growth and growth cessation. PFMI may aid in clinical decision making.

Multidisciplinary programme for rehabilitation of chronic low back pain - factors predicting successful return to work.

BACKGROUND: There are no clear indicators for predicting return to work for patients with chronic low back pain (LBP). We aim to report the outcomes of a 14-week multidisciplinary programme targeting patients with chronic LBP who failed conventional physiotherapy to provide functional rehabilitation. Also, this study will identify factors predicting successful return to work (RTW). METHODS: A collected cohort of patients with chronic LBP was consecutively enrolled into the programme from 1996 to 2014. All recruited patients failed to RTW despite at least 3 months of conservative treatment. Patient underwent weekly multidisciplinary sessions with physiotherapists, occupational therapists and clinical psychologists. Patient perceived function was considered the primary outcome of the programme. Patients were assessed for their sitting, standing and walking tolerance. Oswestry Disability Index (ODI) and Spinal Function Sort Score (SFSS) were used to assess patient perceived disability. RESULTS: One hundred and fifty-eight patients were recruited. After the programme, statistically significant improvement was found in ODI (47.5 to 45.0, p = 0.01) and SFSS (98.0 to 109.5, p <  0.001). There was statistically significant improvement (p <  0.01) in sitting, standing, walking tolerance and straight leg raise tests. 47.4% of the patients were able to meet their work demand. Multivariate logistic regression model (R2 = 59.5%, χ2 (9) = 85.640, p <  0.001) demonstrated that lower initial job demand level and higher patient-perceived back function correlated with greater likelihood of returning to work. CONCLUSION: The results of this study may support the use of this multidisciplinary programme to improve patient function and return to work.

Proper positioning of mice for Cobb angle radiographic measurements.

BACKGROUND: There is no recommended standard for positioning of a mouse for radiographic assessment of the spine. This is necessary to have reproducible radiographic data and avoid false positive results. The objective of this study was to investigate the impact of various postures on Cobb angle measurements and to set up a positioning standard for imaging mouse spines. METHODS: This study was conducted in three parts. Firstly, we identified the problem of lack of posture standardization for radiographs. We collected 77 C57BL/6 J mice for spine radiographs and found a scoliosis prevalence of 28.6% with large variations in curve magnitude. Secondly, 24 C57BL/6 J mice underwent 4 consecutive weekly radiographs and observed high variations (relative standard deviation: 125.3%) between radiographs. Thirdly, we collected another 82 C57BL/6 J mice and designed 14 different postures that could take place during imaging. These postures were related to curling of the limbs, and head, pelvic and tail tilting. RESULTS: The results showed that head and pelvic tilting significantly affects the curve magnitude with effect size (Glass's delta) over 1.50. Avoiding these incorrect positions during radiographs is warranted. The standard recommended posture for mouse imaging entails positioning the snout, interorbital space, neck and whole spine in one line, and with the limbs placed symmetrical to the trunk, whilst avoiding stretching the body of the mouse. CONCLUSIONS: Our work exemplified the importance of standard protocol during imaging when using an animal model in the scoliosis study. We recommend utilizing this standard in studying various disorders of the spine to avoid technical causes for the appearance of a curve.

An insight of how multiple skeletal maturity indices can be used for growth assessment: relationship between the simplified olecranon, simplified digital, and distal radius and ulna classifications.

This cross-sectional study aims to investigate the relationship between the simplified olecranon, simplified digital, and distal radius and ulna (DRU) classifications, and whether they can aid in more comprehensive maturity assessment together. Left hand and wrist and lateral elbow radiographs from pediatric patients were assessed using the three skeletal maturity indices. The association between maturity indices was investigated using Goodman and Kruskal's gamma, and by mapping of individual grades based on chronological age. Specific maturity grades, at which peak height velocity (PHV) occurs as previously identified, were based upon to explore how the three systems interact. A total of 114 patients (63.2% girls) were studied. Correlations and associations between the three maturity parameters were significant (all at P < 0.001). Mapping revealed uneven spans and coverage of different periods by each index. Olecranon stage 1 coincided with R3 (for girls), R4 (for boys), U3, and SS1. Olecranon stage 5 occurred as early as R7, U6, and SS4. Upon elbow fusion, the simplified digital (SS5-SS8) and DRU (R8-R11 and U7-U9) classifications can be used for assessment until maturity. The inter-relationship of the simplified hand, wrist, and olecranon methods indicates their combined use. DRU grades can be used in growth periods which are less well covered. Prepubertal and growth acceleration phase of pubertal growth spurt can best be assessed by both the simplified olecranon (stages 1-3) and DRU classifications (R1-R5 and U1-U4). All three indices are required during PHV. For post-PHV, DRU (R8-R11 and U7-U9) and simplified digital method (SS5-SS8) complement each other for assessment until skeletal maturity.

Failure mechanisms of pedicle screws and cortical screws fixation under large displacement: A biomechanical and microstructural study based on a clinical case scenario.

STUDY DESIGN: Cadaveric biomechanical with imaging analysis. OBJECTIVE: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. SUMMARY OF BACKGROUND DATA: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. METHODS: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. RESULTS: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. CONCLUSIONS: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

When Should We Wean Bracing for Adolescent Idiopathic Scoliosis?

BACKGROUND: Current brace weaning criteria for adolescents with idiopathic scoliosis (AIS) are not well defined. Risser Stage 4, ≥ 2 years since the onset of menarche, and no further increase in body height over 6 months are considered justifications for stopping bracing. However, despite adherence to such standards, curve progression still occurs in some patients, and so better criteria for brace discontinuation are needed. QUESTIONS/PURPOSES: (1) Is no change in height measurements over 6 months and Risser Stage 4 sufficient for initiating brace weaning? (2) What is the association between larger curves (45°) at brace weaning and the progression risk? (3) Are a more advanced Risser stage, Sanders stage, or distal radius and ulna classification associated with a decreased risk of curve progression? (4) When should we wean patients with AIS off bracing to reduce the time for brace wear while limiting the risk of postweaning curve progression? METHODS: All AIS patients who were weaned off their braces from June 2014 to March 2016 were prospectively recruited and followed up for at least 2 years after weaning. A total of 144 patients were recruited with mean followup of 36 ± 21 months. No patients were lost to followup. Patients were referred for brace weaning based on the following criteria: they were Risser Stage 4, did not grow in height in the past 6 months of followup, and were at least 2 years postmenarche. Skeletal maturity was assessed with Risser staging, Sanders staging, and the distal radius and ulna classification. Curve progression was determined as any > 5° increase in the Cobb angle between two measurements from any subsequent six monthly followup visits. All radiographic measurements were performed by spine surgeons independently as part of their routine consultations and without knowledge of this study. Statistical analyses included an intergroup comparison of patients with and without curve progression, binomial stepwise logistic regression analysis, odds ratios (ORs) with their 95% confidence intervals (CIs), and a risk-ratio calculation. A reasonable protective maturity stage would generate an OR < 1. RESULTS: Among patients braced until they had no change in height for 6 months, were 2 years postmenarche for girls, and Risser Stage 4, 29% experienced curve progression after brace weaning. Large curves (≥ 45°) were associated with greater curve progression (OR, 5.0; 95% CI, 1.7-14.8; p = 0.002) as an independent risk factor. Patients weaned at Sanders Stage 7 (OR, 4.7; 95% CI, 2.1-10.7; p < 0.001), radius Grade 9 (OR, 3.9; 95% CI, 1.75-8.51; p = 0.001), and ulna Grade 7 (OR, 3.1; 95% CI, 1.27-7.38; p = 0.013) were more likely to experience curve progression. The earliest maturity indices with a reasonable protective association were Sanders Stage 8 (OR, 0.21; 95% CI, 0.09-0.48; p < 0.001), and radius Grade 10 (OR, 0.42; 95% CI, 0.19-0.97; p = 0.042) with ulna Grade 9 (no patients with curve progression). CONCLUSION: Brace weaning indications using Risser staging are inadequate. Curve progression is expected in patients with large curves, irrespective of maturity status. Bone age measurement by either Sanders staging or the distal radius and ulna classification provides clearer guidelines for brace weaning, resulting in the least postweaning curve progression. Weaning in patients with Sanders Stage 8 and radius Grade 10/ulna Grade 9 provides the earliest and most protective timepoints for initiating brace weaning. LEVEL OF EVIDENCE: Level II, prognostic study.

The relevance of high-intensity zones in degenerative disc disease.

PURPOSE: The purpose of this study was to review the current understanding of high-intensity zones (HIZ) in the lumbar spine with particular attention to its imaging phenotype and clinical relevance. METHODS: A review was conducted of studies related to HIZ. Particular attention was made to imaging phenotypes and classification, and its relationship with discogenic low back pain (LBP). RESULTS: The most current classification system of HIZ is based on location (anterior and posterior), morphology (round, fissure, vertical, rim, or giant types), and its appearance on both T1- and T2-weighted magnetic resonance imaging (MRI). HIZ are commonly manifested with disc degeneration. Hence, both conditions share similar risk factors such as the effect of frequent and prolonged disc loading. The clinical significance of HIZ however is not conclusive. Provocative discography is not sensitive (~ 70%) for eliciting a concordant pain response. Population-based studies have conflicting results regarding the prevalence (14-63%) of HIZ and its correlation with LBP. CONCLUSIONS: HIZ are likely a risk factor for discogenic LBP. However, its etiology and pathophysiology are not well understood. Some clinical studies suggest a link between its occurrence and LBP. However, the results are not consistent as a result of studies which are underpowered and based on heterogeneous study populations, lacking control groups, and without standardized imaging phenotypes. HIZ may be an important pain biomarker that should be further studied. With more modern MRI technology and a detailed classification system, future large-scale population studies will improve our knowledge on its role in the disc degeneration cascade and development of LBP.

Fulcrum flexibility of the main curve predicts postoperative shoulder imbalance in selective thoracic fusion of adolescent idiopathic scoliosis.

PURPOSE: To identify preoperative predictors for postoperative shoulder imbalance (PSI) after corrective surgery of adolescent idiopathic scoliosis (AIS) and using the fulcrum-bending radiograph to assess flexibility. METHODS: A consecutive surgical cohort of AIS patients undergoing selective thoracic fusion with alternate-level pedicle screw fixation was prospectively studied. Preoperative anteroposterior, lateral and fulcrum-bending radiographs were analysed. Postoperatively, a minimum of 2 years clinical and imaging follow-up was performed of all patients. PSI was defined as a radiographic shoulder height difference of more than 20 mm. RESULTS: A total of 80 patients were included, and 14 patients (18%) were confirmed with PSI at final follow-up. The flexibility of MT curve was an independent risk factor for PSI (odds ratio (OR) = 3.3 per 10% decrease, 95% confidence interval (CI) 1.6-8.2). Twenty-seven patients had a preoperative MT flexibility of < 55% (OR = 11.5, 95% CI 2.8-46.2). Postoperative T1 tilt was significantly higher in the PSI group (p < 0.001), and a T1 tilt of more than 9° resulted in 7.2 times higher odds of developing PSI (95% CI 2.0-26.0). Fulcrum-bending correction index (FBCI) was significantly higher in the PSI group at final follow-up, and 25 patients had a final postoperative MT FBCI above 120% (OR = 8.5 (95% CI 2.3-31.0). CONCLUSIONS: A low preoperative curve flexibility is a significant predictor for PSI. The surgical strategy should consider proximal fusion in presence of low-flexibility MT curves and consider less aggressive MT curve correction. Achieving a level T1 should be a main priority during intraoperative correction and may require fusion of the PT curve. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.

A Wearable Detector for Simultaneous Finger Joint Motion Measurement.

This paper presents a wearable and stretchable detector for simultaneous finger joint motion measurement, providing the feasible technical solutions to solve the problems existing in the current devices. The sensor array installed in the detector consists of 14 custom-made bending sensors and an inertial measurement unit with high accuracy. The glove support for a sensor array, which is made of three silicone materials with different elasticity, not only overcomes the drawbacks of cloth support, but also addresses the compatibility between the stretch substrate and the inelastic sensing components. Besides, two-section electrical connection avoids the problems caused by the external wires in traditional solutions to enhance the durability of glove. The experiment results indicated that the wearable detector offers a good user experience by exerting a small force on fingers. The device also shows a strong durability as it worked properly after tens of thousands of bending. The measurement tests on a single sensor demonstrated that two kinds of sensors are both with high accuracy. Besides, the hand goniometric system has an excellent performance in terms of hand motion detection. The measurement error of the device in subjects with different hand sizes is within a reasonable range. The good properties of the sensory detector allow it to be applied in clinical applications.

APSS-ASJ Best Clinical Research Award: Predictability of Curve Progression in Adolescent Idiopathic Scoliosis Using the Distal Radius and Ulna Classification.

STUDY DESIGN: Prospective study. PURPOSE: To determine the risk of clinically significant curve progression in adolescent idiopathic scoliosis (AIS) based on the initial Cobb angle and to test the utility of the distal radius and ulna (DRU) classification in predicting these outcomes. OVERVIEW OF LITERATURE: Determining the remaining growth potential in AIS patients is necessary for predicting prognosis and initiating treatment. Limiting the maturity Cobb angle to <40° and <50° reduces the risk of adulthood progression and need for surgery, respectively. The risk of curve progression is the greatest with skeletally immature patients and thus warrants close monitoring or early intervention. Many parameters exist for measuring the skeletal maturity status in AIS patients, but the DRU classification has been shown to be superior in predicting peak growth and growth cessation. However, its predictive capabilities for curve progression are unknown. METHODS: Totally, 513 AIS patients who presented with Risser 0-3 were followed until either skeletal maturity or the need for surgery, with a minimum 2-year follow-up period. Outcomes of 40° and 50° were used for probability analysis based on the cut-offs of adulthood progression risk and surgical threshold, respectively. RESULTS: At the R6/U5 grade, most curves (probability of ≥48.1%-55.5%) beyond a Cobb angle of 25° progressed to the 40° threshold. For curves of ≥35°, there was a high risk of unfavorable outcomes, regardless of skeletal maturity. Most patients with the R9 grade did not progress, regardless of the initial curve magnitude (probability of 0% to reach the 50° threshold for an initial Cobb angle of ≥35°). CONCLUSIONS: This large-scale study illustrates the utility of the DRU classification for predicting curve progression and how it may effectively guide the timing of surgery. Bracing may be indicated for skeletally immature patients at an initial Cobb angle of 25°, and those with a scoliosis ≥35° are at an increased risk of an unfavorable outcome, despite being near skeletal maturity.

Curve Progression in Adolescent Idiopathic Scoliosis Does Not Match Skeletal Growth.

BACKGROUND: Determining the peak growth velocity of a patient with adolescent idiopathic scoliosis (AIS) is important for timely treatment to prevent curve progression. It is important to be able to predict when the curve-progression risk is greatest to maximize the benefits of any intervention for AIS. The distal radius and ulna (DRU) classification has been shown to accurately predict skeletal growth. However, its utility in predicting curve progression and the rate of progression in AIS is unknown. QUESTIONS/PURPOSES: (1) What is the relationship between radius and ulna grades to growth rate (body height and arm span) and curve progression rate? (2) When does peak curve progression occur in relation to peak growth rate as measured by months and by DRU grades? (3) How many months and how many DRU grades elapse between peak curve progression and plateau? METHODS: This was a retrospective analysis of a longitudinally maintained dataset of growth and Cobb angle data of patients with AIS who presented with Risser Stages 0 to 3 and were followed to maturity at Risser Stage 5 at a single institute with territory-wide school screening service. From June 2014 to March 2016, a total of 513 patients with AIS fulfilled study inclusion criteria. Of these, 195 were treated with bracing at the initial presentation and were excluded. A total of 318 patients with AIS (74% girls) with a mean age of 12 ± 1.5 years were studied. For analysis, only data from initial presentation to commencement of intervention were recorded. Data for patients during the period of bracing or after surgery were not used for analysis to eliminate potential interventional confounders. Of these 318 patients, 192 were observed, 119 were braced, and seven underwent surgery. Therefore 192 patients (60.4%) who were observed were followed up until skeletal maturity at Risser Stage 5; no patients were lost to followup. The mean curve magnitude at baseline was 21.6 ± 4.8. Mean followup before commencing intervention or skeletal maturity was 4.3 ± 2.3 years. Standing body height, arm span, curve magnitude, Risser stage, and DRU classification were studied. A subgroup analysis of 83 patients inclusive of acceleration, peak, and deceleration progression phases for growth and curve progression was studied to determine any time lag between growth and curve progression. Results were described in mean ± SD. RESULTS: There was positive correlation between growth rate and curve progression rate for body height (r = 0.26; p < 0.001) and arm span (r = 0.26; p < 0.001). Peak growth for body height occurred at radius grade (R) 6 (0.56 ± 0.29 cm/month) and ulna grade (U) 4 (0.65 ± 0.31 cm/month); peak change in arm span occurred at R5 (0.67 ± 0.33 cm/month) and U3 (0.67 ± 0.22 cm/month); and peak curve progression matched with R7 (0.80 ± 0.89 cm/month) and U5 (0.84 ± 0.78 cm/month). Subgroup analysis confirmed that peak curve progression lagged behind peak growth rate by approximately 7 months or one DRU grade. The mean time elapsed between the peak curve progression rate and the plateau phase at R9 U7 was approximately 16 months, corresponding to two DRU grades. CONCLUSIONS: By using a standard skeletal maturity parameter in the DRU classification, this study showed that the maximal curve progression occurs after the peak growth spurt, suggesting that the curve should be monitored closely even after peak growth. In addition, the period of potential curve continuing progression extends nearly 1.5 years beyond the peak growth phase until skeletal maturity. Future studies may evaluate whether by observing the trend of growth and curve progression rates, we can improve the outcomes of interventions like bracing for AIS. LEVEL OF EVIDENCE: Level II, prognostic study.

A randomized double-blinded clinical trial to evaluate the safety and efficacy of a novel superelastic nickel-titanium spinal rod in adolescent idiopathic scoliosis: 5-year follow-up.

PURPOSE: To evaluate the safety and efficacy of a superelastic shape-memory alloy (SNT) rod used in the treatment of adolescent idiopathic scoliosis (AIS). METHODS: AIS Patients with Lenke 1 curves undergoing fusion surgery were randomized (1:1) at the time of surgery to receive either the SNT or a conventional titanium alloy (CTA) rod. Radiographs were obtained preoperatively and postoperatively up to 5 years of follow-up. Parameters assessed included coronal and sagittal Cobb angles, and overall truncal and shoulder balance. Sagittal profiles were subcategorized into Types A (<20°), B (20-40°), and C (>40°). RESULTS: Twenty-four patients with mean age of 15 years were recruited. A total of 87.0% of subjects were followed up till postoperative 5 years, but all patients had minimum 2 years of follow-up. The fulcrum-bending correction index for the SNT group was 113% at postoperative day 4 and 127% at half-year, while the CTA group was 112% at postoperative day 4 and only 106% at half-year. In terms of sagittal profile, the SNT group moved toward type B profile at half-year follow-up with a mean correction of 7.6°, while no significant change was observed in the CTA group (-0.7°). Nickel levels remained normal, and there were no complications. CONCLUSIONS: This is the first randomized clinical trial of a novel SNT rod for treating patients with AIS, noting it to be safe and has potential to gradually correct scoliosis over time. This study serves as a pilot and platform to properly power future large-scale studies to demonstrate efficacy and superiority.

Managing the Pediatric Spine: Growth Assessment.

Management of pediatric spinal deformities requires an accurate prediction of growth spurts to allow for timely initiation of treatment and prevention of curve progression. Determining remaining growth potential is also important for avoiding prolonged unnecessary treatment, e.g. bracing for patients nearing skeletal maturity. Many clinical and radiological growth parameters have been developed to aid clinicians in growth prediction. Of these, several commonly used measures such as height and arm span growth trends, timing of menarche, and the Risser sign are mostly retrospective and lack strong predictive utility. Bone age assessments, such as digital skeletal age and the distal radius and ulna classification, are more accurate parameters, but further research is required to determine interethnic variations and develop their role in management decisions.

Mapping the SRS-22r questionnaire onto the EQ-5D-5L utility score in patients with adolescent idiopathic scoliosis.

This is a prospective study to establish prediction models that map the refined Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ-5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients. Comparison of treatment outcomes in AIS can be determined by cost-utility analysis. However, the mainstay spine-specific health-related quality of life outcome measure, the SRS-22r questionnaire does not provide utility assessment. In this study, AIS patients were prospectively recruited to complete both the EQ-5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares regression was undertaken to develop mapping models, which the validity and robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D-5L utility scores were regressed on demographics, Cobb angle, curve types, treatment modalities, and five domains of the SRS-22r questionnaire. Three models were developed using stepwise selection method. EQ-5D-5L scores were regressed on 1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and interaction terms, and 3) as per 2 plus demographic and clinical characteristics. Model goodness-of-fit was assessed using R-square, adjusted R-square, and information criteria; whereas the predictive performance was evaluated using root mean square error (RMSE), mean absolute error (MAE), and the proportion of absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and 'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%). Three models demonstrated an acceptance predictive performance in error analysis applying 10-fold cross-validation to three models where RMSE and MAE were between 0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore recommended out of three mapping models established in this paper. To our knowledge, this is the first study to map a spine-specific health-related quality of life measure onto EQ-5D-5L for AIS patients. With the consideration and incorporation of demographic and clinical characteristics, over 60% variance explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L utility scores from existing SRS-22r data for health economic appraisal of different treatment options.

Predictive factors for neurological deterioration after surgical decompression for thoracic ossified yellow ligament.

PURPOSE: To investigate the rate and predictive factors of post-operative neurological deterioration in ossified yellow ligament (OYL) surgery. METHODS: A retrospective review was conducted for all patients with thoracic OYL causing myelopathy requiring surgical decompression from January 1998 to December 2012. Clinical parameters under study included clinical presentation, distribution of OYL, pre-operative walking score, pre- and post-operative neurological status, status of intra-operative neurophysiological monitoring, and modified Japanese Orthopaedic Association (mJOA) score. Any complications were also recorded. All outcomes were measured at post-operative 1 week and at 2 years. RESULTS: A total of 26 patients were included in this study. Most patients (92.3%) had Frankel grade D pre-operatively. The rate of neurological deterioration was 15.4% and was correlated with the presence of dural tear, extra-dural hematoma and spinal cord injury. Pre-operative walking score was prognostic of patients' walking ability in the post-operative period. Intra-operative monitoring of Somatosensory Evoked Potentials (SSEP) was found to be useful for monitoring spinal cord injury in OYL surgery, with a positive predictive value of 100% and a negative predictive value of 92.3%. The false negative rate of a SSEP signal drop was only 7.7% CONCLUSIONS: This is the first study exploring risk factors for post-operative neurological deterioration after surgery for thoracic OYL. The rate of neurological deficit is not small and prognostic factors for poor outcome include poor pre-operative walking score, presence of intra-operative dural tear, extra-dural hematoma and spinal cord injury, and intra-operative drop of SSEP signal.

A Machine Learning-based Surface Electromyography Topography Evaluation for Prognostic Prediction of Functional Restoration Rehabilitation in Chronic Low Back Pain.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to investigate the feasibility and applicability of support vector machine (SVM) algorithm in classifying patients with LBP who would obtain satisfactory or unsatisfactory progress after the functional restoration rehabilitation program. SUMMARY OF BACKGROUND DATA: Dynamic surface electromyography (SEMG) topography has demonstrated the potential use in predicting the prognosis of functional restoration rehabilitation for patients with low back pain (LBP). However, processing from raw SEMG topography to make prediction is not easy to clinicians. METHODS: A total of 30 patients with nonspecific LBP were recruited and divided into "responding" and "non-responding" group according to the change of Visual analog pain rating scale and Oswestry Disability Index. Each patient received a 12-week functional restoration rehabilitation program. A normal database was calculated from a control group from 48 healthy participants. Root-mean-square difference (RMSD) was extracted from the recorded dynamic SEMG topography during symmetrical and asymmetrical trunk-movement. SVM and cross-validation were applied to the prediction based on the optimized features selected by the sequential floating forward selection (SFFS) algorithm. RESULTS: RMSD feature parameters following rehabilitation in the "responding" group showed a significant difference (P < 0.05) with the one in the "nonresponding" group. The SVM classifier with Quadratic kernel based on SFFS-selected features showed the best prediction performance (accuracy: 96.67%, sensitivity: 100%, specificity: 93.75%, average area under curve [AUC]: 0.8925) comparing with linear kernel (accuracy: 80.00%, sensitivity: 85.71%, specificity: 75.00%, average AUC: 0.7825), polynomial kernel (accuracy: 93.33%, sensitivity: 92.86%, specificity: 93.75%, average AUC: 0.9675), and radial basis function (RBF) kernel (accuracy: 86.67%, sensitivity: 85.71%, specificity: 87.50%, average AUC: 0.7900). CONCLUSION: The use of SVM-based classifier of SEMG topography can be applied to identify the patient responding to functional restoration rehabilitation, which will help the healthcare worker to improve the efficiency of LBP rehabilitation. LEVEL OF EVIDENCE: 3.

Preventing Fusion Mass Shift Avoids Postoperative Distal Curve Adding-on in Adolescent Idiopathic Scoliosis.

BACKGROUND: Surgery for adolescent idiopathic scoliosis (AIS) is only complete after achieving fusion to maintain the correction obtained intraoperatively. The instrumented or fused segments can be referred to as the "fusion mass". In patients with AIS, the ideal fusion mass strategy has been established based on fulcrum-bending radiographs for main thoracic curves. Ideally, the fusion mass should achieve parallel endplates of the upper and lower instrumented vertebra and correct any "shift" for truncal balance. Distal adding-on is an important element to consider in AIS surgery. This phenomenon represents a progressive increase in the number of vertebrae included distally in the primary curvature and it should be avoided as it is associated with unsatisfactory cosmesis and an increased risk of revision surgery. However, it remains unknown whether any fusion mass shift, or shift in the fusion mass or instrumented segments, affects global spinal balance and distal adding-on after curve correction surgery in patients with AIS. QUESTIONS/PURPOSES: (1) To investigate the relationship among postoperative fusion mass shift, global balance, and distal adding-on phenomenon in patients with AIS; and (2) to identify a cutoff value of fusion mass shift that will lead to distal adding-on. METHODS: This was a retrospective study of patients with AIS from a single institution. Between 2006 and 2011 we performed 69 selective thoracic fusions for patients with main thoracic AIS. All patients were evaluated preoperatively and at 2 years postoperatively. The Cobb angle between the cranial and caudal endplates of the fusion mass and the coronal shift between them, which was defined as "fusion mass shift", were measured. Patients with a fusion mass Cobb angle greater than 20° were excluded to specifically determine the effect of fusion mass shift on distal adding-on phenomenon. Fusion mass shift was empirically set as 20 mm for analysis. Therefore, of the 69 patients who underwent selective thoracic fusion, only 52 with a fusion mass Cobb angle of 20° or less were recruited for study. We defined patients with a fusion mass shift of 20 mm or less as the balanced group and those with a fusion mass shift greater than 20 mm as the unbalanced group. A receiver operating characteristic (ROC) curve was used to determine the cutoff point of fusion mass shift for adding-on. RESULTS: Of the 52 patients studied, fusion mass shift (> 20 mm) was noted in 11 (21%), and six of those patients had distal adding-on at final followup. Although global spinal balance did not differ significantly between patients with or without fusion mass shift, the occurrence of adding-on phenomenon was significantly higher in the unbalanced group (55% (six of 11 patients), odds ratio [OR], 8.6; 95% CI, 2-39; p < 0.002) than the balanced group (12% [five of 41 patients]). Based on the ROC curve analysis, a fusion mass shift more than 18 mm was observed as the cutoff point for distal adding-on phenomenon (area under the curve, 0.70; 95% CI, 0.5-0.9; likelihood ratio, 5.0; sensitivity, 0.64; specificity, 0.73; positive predictive value, 39% [seven of 18 patients]; negative predictive value, 88% [30 of 34 patients]; OR, 4.8; 95% CI, 1-20; p = 0.02). CONCLUSIONS: Our study illustrates the substantial utility of the fulcrum-bending radiograph in determining fusion levels that can avoid fusion mass shift; thereby, underlining its importance in designing personalized surgical strategies for patients with scoliosis. Preoperatively, determining fusion levels by fulcrum-bending radiographs to avoid residual fusion mass shift is imperative. Intraoperatively, any fusion mass shift should be corrected to avoid distal adding-on, reoperation, and elevated healthcare costs. LEVEL OF EVIDENCE: Level II, prognostic study.