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.

Male spondyloarthritis patients and those with longer disease duration have less severe disc degeneration: propensity score-matched comparison.

Objective: Using whole spine sagittal T2 MRI, we aimed to compare the severity and prevalence of disc degeneration (DD) in axial SpA patients vs the general population and to determine any association between spinal inflammation, structural changes, mobility and DD among SpA patients. Methods: Two prospectively collected cohorts of SpA patients (n = 411) and the general population (n = 2007) were recruited. Eventually, 967 participants from the populational cohort and 304 participants from the SpA cohort were analysed. Two hundred and nineteen matched pairs were generated by propensity score matching. Imaging parameters, including Pfirrmann grading, disc herniation, high-intensity zone, Schmorl's node, Modic change and anterior marrow change were studied and compared from C2/3 to L5/S1. DD was defined as Pfirrmann grade 4 or 5. Demographic factors, including age, sex and BMI, were collected. Multivariable linear regression was used to determine the association between spinal inflammation [Spondyloarthritis Research Consortium of Canada (SPARCC) spine MRI index], structural changes [modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)] and mobility (BASMI) with lumbar Pfirrmann score. Results: SpA patients had lower prevalence of DD (P < 0.001). The disease stage-stratified regression model showed that SPARCC spinal MRI index was associated with higher lumbar Pfirrmann scores in early disease (ß = 0.196, P = 0.044), whereas mSASSS was associated with lower lumbar Pfirrmann scores in later disease (ß = -0.138, P = 0.038). Males had higher mSASSS (P < 0.001) and lower odds of whole spine DD (odds ratio = 0.622, P = 0.028). Conclusion: SpA patients had lower DD severity than the general population. Males had higher mSASSSs, and increased mSASSS at later disease was associated with less severe DD.

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.

Directed Versus Nondirected Standing Postures in Adolescent Idiopathic Scoliosis: Its Impact on Curve Magnitude, Alignment, and Clinical Decision-Making.

STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the difference in major curve Cobb angle and alignment between directed and nondirected positioning for adolescent idiopathic scoliosis (AIS) and to evaluate implications on treatment decision-making. SUMMARY OF BACKGROUND DATA: Proper positioning of patients with spinal deformities is important for assessing usual functional posture in standing, so management strategies can be customized accordingly. Whether postural variability affects coronal and sagittal radiologic parameters and the impact of posture on management decisions remains unknown. PATIENTS AND METHODS: Patients with adolescent idiopathic scoliosis presenting for an initial consultation at a tertiary scoliosis clinic were recruited. They were asked to stand in two positions: passive, nondirected position; and directed position by the radiographer. Radiologic assessment included major and minor Cobb angle, coronal balance, spinopelvic parameters, sagittal balance, and alignment. Cobb angle difference >5° between directed and nondirected positioning was considered clinically impactful. Patients with or without such differences were compared. Overestimation or underestimation of the major curve (at 25° or 40°) by nondirected positioning were examined due to its relevance to bracing and surgical indications. RESULTS: This study included 198 patients, with 22.2% experiencing Cobb angle difference (>5°) between positioning. The major curve Cobb angle was smaller in nondirected than directed positioning (median difference: -6.0°, upper and lower quartile: -7.8, 5.8), especially for curves ≥30°. Patients with a Cobb angle difference had changes in shoulder balance ( P =0.007) when assuming a directed position. Nondirected positioning had 14.3% of major Cobb 25° underestimated and 8.8% overestimated, whereas 11.1% of curves >40° were underestimated. CONCLUSION: Strict adherence to a standardized radiographic protocol is mandatory for reproducing spine radiographs reliable for curve assessment, as a nondirected position demonstrates smaller Cobb angles. Postural variation may lead to overestimation, or underestimation, of the curve size which is relevant to both bracing and surgical decision-making. LEVEL OF EVIDENCE: Level-II.

Why Are Some Intervertebral Discs More Prone to Degeneration?: Insights Into Isolated Thoracic "Dysgeneration".

STUDY DESIGN: Prospective observational study. OBJECTIVE: To determine the prevalence of isolated thoracic degeneration on magnetic resonance imaging (MRI), demographic factors and imaging features, as well as the patient-reported quality of life outcomes associated with this condition. SUMMARY OF BACKGROUND DATA: Thoracic intervertebral discs are least susceptible to disc degeneration (DD) and may represent a manifestation of "dysgeneration." These discs may never be hydrated from the beginning and seem hypointense on MRI. PATIENTS AND METHODS: A population-based MRI study of 2007 volunteers was conducted. Each disc from C2/3 to L5/S1 was measured by Pfirrmann and Schneiderman grading. Disc herniation, Schmorl node (SN), high-intensity zones (HIZ), and Modic changes were studied. DD was defined by Pfirrmann 4 or 5. patient-reported quality of life scores, including a 36-item short-form questionnaire and visual analog scale for low back pain, were recorded. Subjects were divided into "isolated thoracic degeneration" (only thoracic segment) and "tandem thoracic degeneration" (thoracic with other segments). The association between imaging findings and isolated thoracic degeneration was determined using multivariate logistic regression. RESULTS: The mean age of the subjects was 50.0 ± 0.5 and 61.4% were females (n = 1232). Isolated thoracic degeneration was identified in 2.3% of the cohort. Factors associated with isolated thoracic degeneration included lower age, C6/7 HIZ, T8/9 HIZ, and T8/9 SN. Factors associated with tandem thoracic degeneration included L4/5 posterior bulging. The thoracic and lumbar tandem degeneration group demonstrated higher bodily pain, despite a lower visual analog scale, and a higher physical component score of the 36-item short form. CONCLUSIONS: Isolated thoracic degeneration demonstrated an earlier age of onset, mostly involving the mid-thoracic region (T5/6-T8/9), and in association with findings such as SN. Subjects with tandem thoracolumbar degeneration had less severe lumbar DD and low back pain as compared with those with isolated lumbar degeneration. This paints the picture of "dysgeneration" occurring in the thoracic and lumbar spine. LEVEL OF EVIDENCE: 1.

Can the proximal humeral ossification system (PHOS) effectively guide brace weaning in patients with adolescent idiopathic scoliosis?

PURPOSE: The proximal humeral epiphyses can be conveniently viewed in routine spine radiographs. This study aimed to investigate whether the proximal humeral epiphyseal ossification system (PHOS) can be used to determine the timing of brace weaning in adolescent idiopathic scoliosis (AIS), as assessed by the rate of curve progression after brace weaning. METHODS: A total of 107 patients with AIS who had weaned brace-wear at Risser Stage ≥  4, no bodily growth and post-menarche ≥  2 years between 7/2014 and 2/2016 were studied. Increase in major curve Cobb angle > 5° between weaning and 2-year follow-up was considered curve progression. Skeletal maturity was assessed using the PHOS, distal radius and ulna (DRU) classification, Risser and Sanders staging. Curve progression rate per maturity grading at weaning was examined. RESULTS: After brace-wear weaning, 12.1% of the patients experienced curve progression. Curve progression rate for weaning at PHOS Stage 5 was 0% for curves < 40°, and 20.0% for curves ≥ 40°. No curve progression occurred when weaning at PHOS Stage 5 with radius grade of 10 for curves ≥ 40°. Factors associated with curve progression were: Months post-menarche (p = 0.021), weaning Cobb angle (p = 0.002), curves < 40° versus ≥ 40° (p = 0.009), radius (p = 0.006) and ulna (p = 0.025) grades, and Sanders stages (p = 0.025), but not PHOS stages (p = 0.454). CONCLUSION: PHOS can be a useful maturity indicator for brace-wear weaning in AIS, with PHOS Stage 5 having no post-weaning curve progression in curves < 40°. For large curves ≥ 40°, PHOS Stage 5 is also effective in indicating the timing of weaning together with radius grade ≥ 10.

Propensity-matched Comparison Between Chronic Nonspecific Low Back Pain and Axial Spondyloarthritis: Impact on patient-perceived Quality of Life.

STUDY DESIGN: Prospective study. OBJECTIVE: To compare the burden between chronic nonspecific low back pain (LBP) and axial spondyloarthropathy (SpA). SUMMARY OF BACKGROUND DATA: Chronic nonspecific LBP and SpA are two debilitating yet different chronic musculoskeletal disorders. To compare their burden, propensity score matching is used to control for potential confounders and match the study subjects. MATERIALS AND METHODS: Two prospectively collected cohorts of LBP (n=269) and SpA (n=218) patients were studied. Outcomes included current LBP, 36-item Short Form Questionnaire, Oswestry Disability Index, EuroQol 5-dimension 5-level Questionnaire, and EuroQol Visual Analog Scale. With the inherent differences between the two types of patients, propensity score matching was performed for comparing the two groups. Baseline covariates of age, sex, education level, occupation, smoking, and drinking history were selected for the estimation of propensity scores for each subject with the logistic regression model. Significant independent variables for the outcome of current back pain were included in the multivariate logistic regressions. RESULTS: A total of 127 matched pairs were identified, with 254 patients. In the matched cohort, more patients with chronic LBP had current back pain (95.3%) as compared with SpA (71.7%). Patients with SpA were younger ( P <0.001), with more males ( P <0.001), and better educated ( P =0.001). There was less current back pain and higher nonsteroidal anti-inflammatory drug use ( P <0.001). Most SpA patients had lower Oswestry Disability Index than LBP patients and with low disease activity. Patients with LBP had worse outcome scores as compared with SpA patients given the same Visual Analog Scale. LBP patients had 8.6 times the odds (95% CI: 3.341-20.671; P <0.001) of experiencing current back pain compared with SpA patients. CONCLUSIONS: The disease activity of SpA patients is well controlled. However, patients with chronic LBP have worse pain severity, disability, and health-related quality of life. This has implications on resource utilization and the necessity of advancing LBP understanding and management. LEVEL OF EVIDENCE: Type I prognostic study.

Alternate In-Brace and Out-of-Brace Radiographs Are Recommended to Assess Brace Fitting and Curve Progression With Adolescent Idiopathic Scoliosis Follow-Up.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the prevalence of missed curve progression in patients with adolescent idiopathic scoliosis (AIS) undergoing brace treatment with only in-brace follow-up radiographs, and to provide recommendations on when in-brace and out-of-brace should be obtained during follow-up. METHODS: 133 patients who had documented clinically significant curve progression during brace treatment or only when an out-of-brace radiograph were studied. Of these, 95 patients (71.4%) had curve progression noted on in-brace radiographs while 38 patients (28.6%) showed curve progression only after brace removal. We analyzed differences in age, sex, curve types, Risser stage, months after menarche, standing out-of-brace Cobb angle, correction rate, and flexibility rate between the groups. Multivariate logistic regression was performed to determine factors contributing to curve progression missed during brace treatment. RESULTS: There were no differences in initial Cobb angle between out-of-brace and in-brace deterioration groups. However, the correction rate was higher (32.7% vs 25.0%; P = .004) in the in-brace deterioration group as compared to the out-of-brace deterioration group. A lower correction rate was more likely to result in out-of-brace deterioration (OR 0.970; P = .019). For thoracic curves, higher flexibility in the curves was more likely to result in out-of-brace deterioration (OR 1.055; P = .045). For double/triple curves, patients with in-brace deterioration had higher correction rate (OR 0.944; P = .034). CONCLUSIONS: Patients may develop curve progression despite good correction on in-brace radiographs. Those with higher flexibility and suboptimal brace fitting are at-risk. In-brace and out-of-brace radiographs should be taken alternately for brace treatment follow-up.

Curve Overcorrection Predicts Coronal Imbalance in Selective Thoracic Fusion in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective cohort Study. OBJECTIVES: To identify predictive factors for coronal imbalance after selective fusion in adolescent idiopathic scoliosis (AIS) with Lenke type 1 curves. METHODS: AIS patients with Lenke type 1 curve with A, B and C lumbar modifiers underwent selective thoracic fusion. The curve fulcrum flexibility and fulcrum bending correction index (FBCI) was studied. Coronal imbalance was defined as more than 2 cm of truncal shift or more than 2 cm list at two-year follow-up. RESULTS: A total of 301 patients were included in the study. Coronal imbalance at two-year follow-up was found in 38 patients (13%). At the preoperative stage, we found a significant difference in main curve flexibility with 66±15% in the balanced group and 60±15% in the imbalanced group (P = .032). At the immediate postoperative stage, mean curve correction was 71±13% vs 70±13% and mean FBCI was 112±29% vs 122±29% in the balance and unbalanced group, respectively (P = .031). Postoperative FBCI of more than 125% (third quartile) resulted in an odds ratio of 2.1 (95%CI:1.1-4.3) for coronal imbalance at two years (P=.031). No significant changes in fusion mass or LIV tilt was observed. CONCLUSIONS: A decreased preoperative flexibility and a higher FBCI was significantly associated with coronal imbalance. A high FBCI is an indication of a curve correction that exceeds the inherent flexibility of the spine, and our results add to a growing body of evidence that "overcorrection" of the main curve can lead to postoperative imbalance.

Predictive factors for successful non-operative treatment and achieving MCID improvement in health-related quality of life in adult spinal deformity.

BACKGROUND: Adult spinal deformity is a spectrum of degenerative spinal diseases with increasing prevalence and healthcare burden worldwide. Identification of patients who are more likely to improve through conservative management may reduce cost and potentially prevent surgery and its associated costs and complications. This study aims to identify predictive factors for MCID in improvement of ODI and SRS-22r questionnaires in patients with adult spinal deformity treated with conservative treatment. METHODS: A prospective, observational cohort study of 46 patients was conducted at a spine specialist clinic. Inclusion criteria were 30-80 years of age, diagnosis of neglected adolescent idiopathic scoliosis, de-novo scoliosis, degenerative spondylolisthesis, and sagittal plane deformities (thoracic hypokyphosis, lumbar hypolordosis), presenting with mechanical back pain with or without radicular leg pain. All patients received conservative management including medication and physiotherapy. Radiological and clinical parameters were measured at baseline and at 1-year follow-up. Primary outcomes were ODI and SRS-22r scores. Secondary outcomes were EQ-5D-5L scores and requiring spine surgery during conservative treatment. Predictors for MCID improvement in ODI and SRS-22r were identified using multivariate regressions and receiver operating characteristic (ROC) analyses. RESULTS: At baseline, patients who reached MCID in ODI and/or SRS-22r showed less comorbidities (diabetes mellitus, hypertension, ischemic heart disease, osteoarthritis, cancer), smaller range of lateral spinal flexion, larger trunk shift, larger pelvic incidence, a higher EQ-5D-5L anxiety/depression dimension score, a lower SRS-22r total score, and presence of spondylolisthesis. Lateral flexion range < 25 degrees, trunk shift > 14 mm, pelvic incidence > 50 degrees, EQ-5D-5L anxiety/depression dimension score > 1, and SRS-22r total score < 3.5 were the cut-off values generated by ROC analysis. CONCLUSIONS: Both radiological and clinical predictive factors for MCID improvement in health-related quality of life were identified. Future research should identify subgroups of patients who are responsive to specific conservative treatment modalities, so as to provide information for personalized medicine. LEVEL OF EVIDENCE: II.

Longitudinal comparison of direct medical cost, radiological and health-related quality of life treatment outcomes between traditional growing rods and magnetically controlled growing rods from preoperative to maturity.

BACKGROUND: Magnetically controlled growing rods (MCGR) have replaced traditional growing rods (TGR) in the past decade, however, a comparison of their direct costs and treatment outcomes based on real longitudinal data is lacking. This study aims to compare the direct cost and treatment outcomes between TGR and MCGR, whilst incorporating complications, reoperations and changes in health-related quality of life (HRQoL) throughout the entire treatment course. METHODS: Patients with early onset scoliosis (EOS) who underwent initial growing rod surgery between 2003 and 2016 at a tertiary scoliosis clinic were studied with longitudinal data. Accumulated direct medical costs were calculated based on the unit cost of surgeries of each TGR and MCGR, costs incurred for any rod exchange or remedial surgery for post-operative complication. Treatment outcomes were evaluated via: Patient's HRQoL using SRS-22r questionnaire, and radiological parameters (including major curve correction, spine length gains, spinal balance) throughout the treatment until maturity. RESULTS: A total of 27 EOS patients (16 MCGR, 11 TGR) were studied. Total direct cost of index surgery for MCGR was HKD$223,108 versus lower cost of HKD$135,184 for TGR (p < 0.001). At 2-3 years post-index surgery, accumulative total direct medical cost of MCGR and TGR became most comparable (TGR:MCGR ratio = 1.010) and had reached neutrality between the two groups since. Radiological parameters had no intergroup differences at maturity. For HRQoL, TGR group had shown the trend of less pain (domain score mean difference: 0.53, p = 0.024) post-index surgery and better self-appearance (domain score mean difference: 1.08, p = 0.017) before fusion. Higher satisfaction with treatment (domain score mean difference: 0.76, p = 0.029) was demonstrated by TGR patients at fusion/maturity. MCGR had negative (rs = -0.693) versus TGR's positive (rs = 0.989) correlations (p < 0.05) of cost and SRS-22r total scores at 2-3 years post-index surgery. CONCLUSIONS: From index surgery to maturity, TGR demonstrated better satisfaction with treatment by patients and comparable overall HRQoL with MCGR during the treatment course, as MCGR did not show apparent benefit despite less surgeries and cost neutrality between the two groups at 2-3 years post-index surgery.

Equipoise for Lateral Access Surgery.

OBJECTIVE: To investigate the use of lateral access surgery among surgeons from the Asia-Pacific region to determine equipoise for areas of contentious use. METHODS: A questionnaire was distributed to members of the Asia Pacific Spine Society. Surgeons were asked about their past experiences with lateral access surgery, including their advantages and disadvantages, specific surgical strategies, choices in implant-related factors, order of levels to operate on in multilevel reconstruction surgery, and postoperative complications. RESULTS: A total of 69 of 102 surgeons (67.6%) had performed lateral access surgery previously. In total, 56 participating surgeons (54.9%) agreed that anterior column reconstruction via lateral access is most of time superior to transforaminal lumbar interbody fusion and other techniques. Surgeons would consider laminectomy instead of indirect decompression in the presence of severe central or lateral recess stenosis, thickened ligamentum flavum, and facet joint hypertrophy. For the order of levels to operate on in multiple level reconstruction for deformity, where 1 stands for L3-L4 or higher, 2 stands for L4-L5, and 3 stands for L5-S1, 2-1-3 (28/95, 29.5%) was most common, followed by 1-2-3 (26/95, 27.4%), and 3-2-1 (21/95, 22.1%). CONCLUSIONS: Lateral access surgery is seeing greater use in the Asia-Pacific region, especially in upper middle- to high-income countries, whereas keenness of surgeons who practice in lower middle- to low-income countries can be improved by more training, resources, and reasonable cost. A high percentage of surgeons do not consider indirect decompression for spinal stenosis. There was no consensus on the order of levels in multiple level reconstruction for deformity.

Psychometric performance of proxy-reported EQ-5D youth version 5-level (EQ-5D-Y-5L) in comparison with three-level (EQ-5D-Y-3L) in children and adolescents with scoliosis.

OBJECTIVES: To assess the psychometric performance of proxy-reported EQ-5D-Y-5L (Y-5L) in comparisons with EQ-5D-Y-3L (Y-3L) administered by caregivers of patients with juvenile (JIS) or adolescent idiopathic scoliosis (AIS). METHODS: A consecutive sample of caregivers of JIS or AIS patients were recruited. Redistribution property, ceiling effects, and discriminative power were examined. Known-group validity was determined by examining their ability to detect differences across clinical known groups. Test-retest reliability was assessed using intraclass correlation coefficient (ICC) for EQ-VAS score and Gwet's agreement coefficient (GAC) and percentage agreement (PA) for dimension responses. Furthermore, subgroups were analyzed for comparing test-retest reliability. RESULTS: A total of 130 caregivers were involved in the study. Consistencies between proxy-reported Y-3L and Y-5L were very high for all dimensions (93.8-99.2%). The ceiling effect in the Y-5L was slightly reduced in four dimensions (AR: 0.8-2.3%) whereas increased in "Having pain/discomfort". Greater informativity was found in the Y-5L than the Y-3L. In known-group comparisons of curvature magnitude, curvature type, and treatment modality, Y-5L and Y-3L dimension scales showed hypothesized results. For example, more full-health responses were found in the mild Cobb angle group (Y-5L: 63.1%; Y-3L: 62.2%) than the severe Cobb angle group (Y-5L: 55.6%, Y-3L: 55.6%). EQ-VAS score exhibited low test-retest reliability (ICC: 0.41), whereas dimension scales of both instruments showed satisfactory test-retest reliability (GAC ≥ 0.7 and PA ≥ 70% for all). In most known groups, hard-to-observe dimensions were more reliable for proxy-reported Y-5L than Y-3L. CONCLUSION: Both the proxy-reported Y-5L and Y-3L are valid and reliable instruments for assessing the HRQoL of JIS or AIS patients.

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.

A Randomized Controlled Trial to Evaluate the Clinical Effectiveness of 3D-Printed Orthosis in the Management of Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To compare clinical effectiveness and quality of life (QoL) of the 3D-printed orthosis (3O) and conventional orthosis (CO) for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Using 3D printing technology to design and fabricate orthoses to manage AIS aiming to improve in-orthosis correction and patients' compliance that are considered essential factors of effective treatment. Clinical evaluation was conducted to study the effectiveness of this innovative method. METHODS: Thirty females with AIS who met the criteria (age 10-14, Cobb 20-40°, Risser sign 0-2, ≤12 months after menarche) were recruited. Subjects were randomly allocated to the 3O group (n = 15, age 12.4, Cobb 31.8°) and CO group (n = 15, age 12.0, Cobb 29.3°). All patients were prescribed for full-time wearing (23 hours/d) and follow-up every 4 to 6 months until bone maturity. Compliance was monitored by thermosensors, while QoL was assessed using three validated questionnaires. RESULTS: Comparable immediate in-orthosis correction was observed between 3O (-11.6°, P < 0.001) and CO groups (-12.9°, P < 0.001). In the QoL study via SRS-22r, the 3O group got worse results after 3 months in aspects of function, self-image, and mental health (-0.5, -0.6, -0.7, P < 0.05) while the CO group had worse results in aspects of self-image and mental health (-0.3, -0.3, P < 0.05). No significant difference was found in QoL assessments between groups. After 2 years of follow-up, 22 patients were analyzed with 4 dropouts in each group. Comparable angle reduction was observed in both groups (3O: -2.2°, P = 0.364; CO: -3.5°, P = 0.193). There was one subject (9.1%) in the 3O group while two subjects (18.2%) in the CO group had curve progression >5°. Daily wearing hours were 1.9 hours longer in the 3O group than the CO group (17.1 vs. 15.2 hours, P = 0.934). CONCLUSION: The 3O group could provide comparable clinical effects as compared with the CO group while patients with 3O showed similar compliance and QoL compared to those with CO.Level of Evidence: 1.

Prevalence and Definition of Multilevel Lumbar Developmental Spinal Stenosis.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To define multilevel lumbar developmental spinal stenosis (DSS) using a composite score model and to determine its prevalence. METHODS: This was a cohort study of 2385 openly recruited subjects with lumbosacral (L1-S1) MRIs. All subjects with previous spinal surgery or spinal deformities were excluded. The anteroposterior (AP) vertebral canal diameter was measured by two independent observers. Any associations between level-specific vertebral canal diameter and subject body habitus were analysed with non-parametric tests. Three or more stenotic levels, equivalent to a composite score of 3 or more, were considered as multilevel DSS. The median values of these subjects' AP canal diameters were used to construct the multilevel DSS values. Receiver operating characteristic analysis was utilized to determine the ability of these cut-off values to screen for DSS by presenting their area under curve, sensitivity and specificity. RESULTS: Subject body habitus was poorly correlated with AP vertebral canal diameter. Multilevel DSS was identified as L1<19 mm, L2<19 mm, L3<18 mm, L4<18 mm, L5<18 mm, S1<16 mm with 81%-96% sensitivity and 72%-91% specificity. The prevalence of multilevel DSS in this cohort was 7.3%. CONCLUSIONS: Utilizing a large homogeneous cohort, the prevalence of multilevel DSS is determined. Our cut-offs provide high diagnostic accuracy. Patients with multiple levels that fulfil these criteria may be at-risk of spinal canal compressions at multiple sites. LEVEL OF EVIDENCE: III.

Does the Use of Sanders Staging and Distal Radius and Ulna Classification Avoid Mismatches in Growth Assessment with Risser Staging Alone?

BACKGROUND: Although Risser stages are visible on the same radiograph of the spine, Risser staging is criticized for its insensitivity in estimating the remaining growth potential and its weak correlation with curve progression in patients with adolescent idiopathic scoliosis. Risser staging is frequently accompanied by other skeletal maturity indices to increase its precision for assessing pubertal growth. However, it remains unknown whether there is any discrepancy between various maturity parameters and the extent of this discrepancy when these indices are used concurrently to assess pubertal growth landmarks, which are important for the timing of brace initiation and weaning. QUESTIONS/PURPOSES: (1) What is the chronologic order of skeletal maturity grades based on the growth rate and curve progression rate in patients with adolescent idiopathic scoliosis? (2) What are the discrepancies among the grades of each maturity index for indicating the peak growth and start of the growth plateau, and how do these indices correspond to each other? (3) What is the effectiveness of Risser staging, Sanders staging, and the distal radius and ulna classification in assessing peak growth and the beginning of the growth plateau? METHODS: Between 2014 and 2017, a total of 13,536 patients diagnosed with adolescent idiopathic scoliosis were treated at our tertiary clinic. Of those, 3864 patients with a radiograph of the left hand and wrist and a posteroanterior radiograph of the spine at the same visits including initial presentation were considered potentially eligible for this study. Minimum follow-up was defined as 6 months from the first visit, and the follow-up duration was defined as 2 years since initial consultation. In all, 48% (1867 of 3864) of patients were eligible, of which 26% (485 of 1867) were excluded because they were prescribed bracing at the first consultation. These patients visited the subsequent clinics wearing the brace, which might have affected body height measurement. Six percent (117 of 1867) of eligible patients were also excluded as their major coronal Cobb angle reached the surgical threshold of 50° and had undergone surgery before skeletal maturity. Another 21% (387 of 1867) of patients were lost before minimum follow-up or had incomplete data, leaving 47% (878) for analysis. These 878 patients with 1139 skeletal maturity assessments were studied; 74% (648 of 878) were girls. Standing body height was measured in a standardized manner by a wall-mounted stadiometer. Several surgeons measured curve magnitude as per routine clinical consultation, skeletal maturity was measured according to the distal radius and ulna classification, and two raters measured Risser and Sanders stages. Reliability tests were performed with satisfaction. Data were collected for the included patients at multiple points when skeletal maturity was assessed, and only up to when brace wear started for those who eventually had bracing. The growth rate and curve progression rate were calculated by the change of body height and major coronal Cobb angle over the number of months elapsed between the initial visit and next follow-up. At each skeletal maturity grading, we examined the growth rate (in centimeters per month) and curve progression rate (in degrees per month) since the skeletal maturity assessment, as well as the mean age at which this maturity grading occurred. Each patient was then individually assessed for whether he or she was experiencing peak growth and the beginning of growth plateau at each timepoint by comparing the calculated growth rate with the previously defined peak growth rate of ≥ 0.7 cm per month and the beginning of growth plateau rate of ≤ 0.15 cm per month in this adolescent idiopathic scoliosis population. Among the timepoints at which the peak growth and the beginning of growth plateau occurred, the median maturity grade of each maturity index was identified as the benchmark grade for comparison between indices. We used the McNemar test to investigate whether pubertal growth landmarks were identified by specific maturity grades concurrently. We assessed the effectiveness of these skeletal maturity indices by the difference in proportions (%) between two benchmark grades in indicating peak growth and the growth plateau. RESULTS: For girls, the chronological order of maturity grades that indicated peak growth was the radius grade, ulna grade, Sanders stage, and Risser stage. Curve progression peaked between the age of 11.6 and 12.1 years at a similar timing by all maturity indices for girls but was inconsistent for boys. For both sexes, radius (R) grade 6, ulna (U) grade 5, Sanders stage (SS) 3, and Risser stage 0+ were the median grades for peak growth, whereas Risser stage 4, R8/9, U7/8, and SS6/7 indicated the beginning of the growth plateau. The largest discrepancy between maturity indices was represented by Risser stage 0+, which corresponded to six grades of the Sanders staging system (SS2 to SS7) and to R6 in only 41% (62 of 152) of girls in the whole cohort. Despite Risser stage 0+ corresponding to the wide range of Sanders and distal radius and ulna grades, none of the R6, U5, SS3, and Risser stage 0+ was found more effective than another grade in indicating the peak growth in girls. R6 most effectively indicated the peak growth in boys, and Risser stage 0+ was the least effective. For the beginning of the growth plateau in girls, SS6/7 was the most effective indicator, followed by U7/8. Risser stage 4 was the least effective because it indicated 29% (95% CI 21% to 36%; p < 0.001) fewer patients who reached the beginning of the growth plateau than did those with R8/9. Risser stage 4 also indicated 36% (95% CI 28% to 43%; p < 0.001) fewer patients who reached the beginning of the growth plateau than those indicated by U7/8, and it identified 39% fewer patients than SS6/7 (95% CI 32% to 47%; p < 0.001). For boys, similarly, R8/9, U7/8, and SS6/7 were all more effective than Risser stage 4 in identifying when the growth plateau began. CONCLUSION: Risser stage 0+ corresponds to a wide range of Sanders and distal radius and ulna grades. Risser stage 0+ is least effective in indicating the peak growth in boys, and Risser stage 4 is the least effective maturity grade for indicating when the growth plateau starts in both sexes. The concurrent use of R6 and SS3 can be useful for detecting the peak growth, and SS6/7 in conjunction with U7/8 is most effective in indicating the beginning of the growth plateau. Using a combination of specific grades of Sanders staging and the distal radius and ulna classification can indicate pubertal growth landmarks with reduced risk of underestimating or overestimating skeletal maturity. These findings may aid in refining clinical decision-making of brace initiation and weaning at a more precise timing. Among Risser stage 0, the appearance of R6, U5, and SS3 provide the most effective assessment of peak growth that can indicate the most effective bracing period within which curve progression occurs. For initiation of the growth plateau, Risser 4 is not useful, and SS6/7, R8/9 and U7/8 should be used instead. LEVEL OF EVIDENCE: Level III, diagnostic study.

Responsiveness of the EuroQoL 5-Dimension (EQ-5D) questionnaire in patients with spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) has a significant impact on patients' quality of life due to functional impairments. Generic health instruments like the EuroQoL 5-dimension (EQ-5D) is important for cost-utility analysis of health care interventions and calculation of quality-adjusted life-years. It has been validated in patients with SpA. However, its responsiveness property is unclear. Hence, the aim of study is to test the responsiveness properties of the EQ-5D health measure for Chinese patients with SpA. METHODS: Prospective and consecutive recruitment of 151 Chinese patients with SpA was conducted with follow-up assessments 6 months later. Demographic data including smoking and drinking habits, education level, income and occupation was collected. Disease-associated data including disease duration, presence of back pain, peripheral arthritis, dactylitis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease was also recorded. Questionnaires regarding disease activity and functional disability (BASDAI, BASFI, BASGI, BASMI, ASDAS), mental health (HADS) and the EQ-5D scores were recorded. Responsiveness was tested against the global rating of change scale (GRC) and changes in disease activity using BASDAI and ASDAS-CRP. RESULTS: A total of 113 (74.8%) patients completed the follow-up assessments. Most patients (61.6%) had low disease activity level with BASDAI <4 and 39.7% of patients had inactive disease by ASDAS-CRP. EQ-5D scores was well discriminated along with BASDAI and BASFI scores. EQ-5D scores also correlated well with HADS. The GRC was not able to discriminate adequately. No significant ceiling or floor effect was observed. CONCLUSIONS: EQ-5D demonstrates satisfactory responsiveness property for assessment of changes in SpA disease activity. LEVEL OF EVIDENCE: II.

The profile of the spinal column in subjects with lumbar developmental spinal stenosis.

AIMS: The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. METHODS: This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate. RESULTS: Axial AP vertebral canal diameter (p < 0.001), interpedicular distance (p < 0.001), AP dural sac diameter (p < 0.001), lamina angle (p < 0.001), and sagittal mid-vertebral body height (p < 0.001) were significantly different between those identified as having DSS and controls. Narrower interpedicular distance (OR 0.745 (95% CI 0.618 to 0.900); p = 0.002) and AP dural sac diameter (OR 0.506 (95% CI 0.400 to 0.641); p < 0.001) were associated with DSS. Lamina angle (OR 1.127 (95% CI 1.045 to 1.214); p = 0.002) and right facet joint angulation (OR 0.022 (95% CI 0.002 to 0.247); p = 0.002) were also associated with DSS. No association was observed between disc parameters and DSS. CONCLUSION: From this large-scale cohort, the canal size is found to be independent of body stature. Other than spinal canal dimensions, abnormal orientations of lamina angle and facet joint angulation may also be a result of developmental variations, leading to increased likelihood of DSS. Other skeletal parameters are spared. There was no relationship between DSS and soft tissue changes of the spinal column, which suggests that DSS is a unique result of bony maldevelopment. These findings require validation in other ethnicities and populations. Level of Evidence: I (diagnostic study) Cite this article: Bone Joint J 2021;103-B(4):725-733.