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The study of the molecular changes occurring in pinealectomized chickens revealed an increased production of Factor P in paraspinal muscles of scoliotic chickens. This prompted us to investigate the involvement of Factor P, a multifunctional cytokine, in AIS pathomechanism. A group of 159 consecutive patients with AIS were compared with 35 healthy control subjects without any family antecedent for scoliosis and 70 asymptomatic offspring, born from at least one scoliotic parent, and who are considered at risk of developing a scoliosis. Plasma Factor P and soluble Factor P receptor (sFPR) levels were measured by enzyme-linked immunosorbent assays. Mean plasma Factor P concentrations in patients with AIS were significantly higher (p-value <0.001) in patients with AIS having a Cobb's angle >45° (1152.55±378.48 ng/mL) than AIS patients with a Cobb's angle <45° (749.77±313.18 ng/mL) or in healthy controls (561.47±150.77 ng/mL). Diagnostic sensitivity and specificity of Factor P for AIS was 84.4 percent and 90.6 percent respectively (cut-off value ≥800 ng/mL). Interestingly, 49.2% of asymptomatic children at risk had Factor P values higher than 800 ng/mL (mean value of 1019.61±424.13 ng/mL) as opposed to only 8.6% for the controls indicating that elevated plasma Factor P levels precede AIS onset. There were no significant differences in mean plasma sFPR levels between all groups. Our clinical data suggest that elevated plasma Factor P concentration could be a useful marker for diagnosis of AIS and prognosis of curve progression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to determine preoperative predictors of good radiographic outcomes in VBT patients at a minimum 2-year follow-up., Methods: From a single-center dataset, we reviewed patients who underwent VBT from January 2014 to November 2018. Data analysis included age, gender, Risser grade and biometric data. Radiographically, maximum Cobb angle, C-DAR and apical vertebral and disc wedging were measured preop and at a minimum 2-year follow-up. Patients were divided into two cohorts following two different outcome measures: (1) vertebral growth modulation, those patients that growth modulated or corrected ≥ 5° and those who did not; and (2) Maximum Cobb angle at 2 years, < and ≥ 40°. Student T and Chi 2 tests were used for comparison and a multiple linear correlation test was implemented between statistically significant variables., Results: 79 patients were recruited. 26 patients (33%) did growth modulate their spine at 2-year follow-up. These patients were significantly younger, and more skeletally immature with less height (147 cm vs 155 cm; p < 0.0001), weight (38 kg vs. 45 kg; p = 0.0009) and BMI (17 vs 18.8; p = 0.0229) as those who did not. Multiple linear regression model with these variables resulted in a moderate correlation (r 2  = 0.234). 67 patients (85%) finished at a 2-year follow-up with a maximum Cobb angle < 40°. These patients were also younger and skeletally immature. We found significant differences in outcome 2 regarding the average preoperative maximum Cobb angle (48.5° ± 9.5 vs. 59.1° ± 10), average C-DAR (7 ± 1.5 vs. 8.5 ± 2.1), average apical vertebral wedging (6.5° vs. 8.3°), average vertebral/disc wedging ratio (1.5 vs. 2.4) and the average immediate postoperative Cobb angle (25° vs. 38°). These variables predicted a 36% of the variation in final Cobb angle measurement at a 2-year follow-up (r2 = 0.362)., Conclusion: Curve severity determined by a preoperative C-DAR, preoperative Cobb angles and immediate postoperative Cobb angle are significantly related to curves < 40° at a minimum 2-year follow-up, while the potential to growth modulate the spine is more dependent on skeletal maturity, lower body weight and lower BMI. These patients' characteristics should be considered preoperatively., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)

Study Design: Observational cohort study., Objective: To test the hypothesis that anterior vertebral body growth modulation (AVBGM) achieves 3D deformity correction after 2-year follow-up while brace treatment limits curve progression for moderate idiopathic scoliosis (30-50°)., Summary of Background Data: For idiopathic scoliosis, bracing and AVBGM have overlapping indications in skeletally immature patients with moderate scoliosis curve angles, creating a grey zone in clinical practice between them. The relative 3D deformity control performance over a 2-year period between these fusionless treatments is still uncertain., Methods: A retrospective review of a prospective idiopathic scoliosis patients database, recruited between 2013 and 2018 was performed. Inclusion criteria were skeletally immature patients (Risser 0-2), with Cobb angles between 30° and 50° and a 2-year follow-up after bracing or AVBGM. 3D radiological parameters and health related quality of life (HRQoL) scores were evaluated. Unpaired t test was used., Results: Thirty nine patients (12.7 ± 1.3 y.o.) with Cobb angles more than or equal to 30° treated with brace and 41 patients (11.8 ± 1.2 y.o.) with presenting Cobb angles less than or equal to 50° who received AVBGM were reviewed. The statistical analysis of 3D deformity measurements showed that at 2-year follow-up, only the 3D spine length and both sides apical vertebral heights changed significantly with brace treatment. While AVBGM treatment achieved statistically significant correction differences in thoracic and lumbar Cobb angles, TrueKyphosis, 3D spine length, and selective left apical vertebral height ( P < 0.05). 35% of brace patients had a curve progression of more than 5° at final follow-up while it was 0% for AVBGM. HRQoL assessment showed no statistically significant differences between pre and post SRS-22 total scores for each group ( P > 0.05)., Conclusion: Even though these two cohorts are not fully comparable, bracing seems to control progression for a significant portion of patients with moderate scoliosis curves, while AVBGM significantly corrected and maintained 3D deformity parameters at 2-year follow-up., Competing Interests: Authors M.P.D., M.R.B., I.T., C.B., N.C., and S.B. declare that they have no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective case series., Objective: Determine the efficacy of anterior vertebral body tethering (AVBT) in skeletally immature patients., Summary of Background Data: The value of AVBT is currently unclear given the paucity of available data., Methods: Consecutive skeletally immature patients with idiopathic scoliosis were treated with AVBT between 2012 and 2018 by one of two surgeons working at two independent centers and followed up for >2 years. Data were collected prospectively and supplemented retrospectively where necessary. Outcomes were measured preoperatively, at first erect radiograph (FE), 1-year postoperatively and at most recent follow up (FU)., Results: One hundred twelve patients underwent 116 primary tethering procedures (108 thoracic and eight lumbar tethers). Four patients had primary tethering of both lumbar and thoracic curves. At surgery mean age was 12.7 ± 1.4 years (8.2-16.7) and Risser 0.5 ± 0.9 (0-3). Follow up was mean 37 ± 9 months (15-64). Preoperative mean coronal Cobb angle of the 130 tethered curves was 50.8° ± 10.2 (31-81) and corrected significantly to 26.6° ± 10.1 (-3-61) at FE radiograph (P < 0.001). Further significant improvement was seen from FE to 1-year, to mean 23.1° ± 12.4 (-37-57) (P < 0.001). There was a small but significant increase between 1-year and FU to 25.7° ± 16.3 (-32-58) (P < 0.001), which appeared to reflect tether breakage. Untethered minor curves were corrected from 31.0° ± 9.5 (3-57) to 20.3° ± 10.3 (0-52) at FU (P < 0.001). Rib hump was corrected from 14.1 ± 4.8 (0-26) to 8.8° ± 5.4 (0-22) at FU (P < 0.01). Twenty-five patients (22%) had 28 complications. Fifteen patients (13%) requiring 18 revision operations including six completed and one awaited fusions., Conclusion: AVBT of immature cases is associated with satisfactory deformity correction in the majority of cases. However, complication and revision rates suggest the need for improved implants and patient selection. Long-term follow-up remains crucial to establish the true efficacy of this procedure.Level of Evidence: 3., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Recent studies showed that finite element model (FEM) combined to CAD/CAM improves the design of braces for the conservative treatment of adolescent idiopathic scoliosis (AIS), using 2D measurements from in-brace radiographs. We aim to assess the immediate effectiveness on curve correction in all three planes of braces designed using CAD/CAM and numerical simulation compared to braces designed with CAD/CAM only., Methods: SRS standardized criteria for bracing were followed to recruit 48 AIS patients who were randomized into two groups. For both groups, 3D reconstructions of the spine and patient's torso, respectively built from bi-planar radiographs and surface topography, were obtained and braces were designed using the CAD/CAM approach. For the test group, 3D reconstructions of the spine and patient's torso were additionally used to generate a personalized FEM to simulate and iteratively improve the brace design with the objective of curve correction maximization in three planes and brace material minimization., Results: For the control group (CtrlBraces), average Cobb angle prior to bracing was 29° (thoracic, T) and 25° (lumbar, L) with the planes of maximal curvature (PMC) respectively oriented at 63° and 57° on average with respect to the sagittal plane. Average apical axial rotation prior to bracing was 7° (T) and 9° (L). For the test group (FEMBraces), initial Cobb angles were 33° (T) and 28° (L) with the PMC at 68° (T) and 56° (L) and average apical axial rotation prior to bracing at 9° (T and L). On average, FEMBraces were 50% thinner and had 20% less covering surface than CtrlBraces while reducing T and L curves by 47 and 48%, respectively, compared to 25 and 26% for CtrlBraces. FEMBraces corrected apical axial rotation by 46% compared to 30% for CtrlBraces., Conclusion: The combination of numerical simulation and CAD/CAM approach allowed designing more efficient braces in all three planes, with the advantages of being lighter than standard CAD/CAM braces. Bracing in AIS may be improved in 3D by the use of this simulation platform. This study is ongoing to recruit more cases and to analyze the long-term effect of bracing., Trial Registration: ClinicalTrials.gov, NCT02285621.

Study Design: Cohort study., Objectives: To assess breast asymmetry (BA) directly with 3D surface imaging and to validate it using MRI values from a cohort of 30 patients with significant adolescent idiopathic scoliosis (AIS). Also, to study the influence of posture (prone vs standing) on BA using the automated method on both modalities., Summary of Background Data: BA is a common concern in young female patients with AIS. In a previous study using MRI, we found that the majority of patients with significant AIS experienced BA of up to 21% in addition to their chest wall deformity. MRI is costly and not always readily available. 3D surface topography, which offers fast and reliable breast acquisitions without radiation or distortion of the body surface, is an alternative method in the clinical setting., Methods: Thirty patients with AIS were enrolled in the study on the basis of their thoracic curvature, skeletal and breast maturity, without regard to their perception of their BA. Each patient underwent two imaging studies of their torso: a 3D trunk surface topography and a breast MRI. An automated breast volume measuring method was proposed using a program developed with Matlab programming., Results: Strong correlations were obtained when comparing the proposed method to the MRI on the left breast volumes (LBV) (r = 0.747), the right breast volumes (RBV) (r = 0.805) and the BA (r = 0.614). Using the same method on both imaging modalities also yielded strong correlation coefficients on the LBV (r = 0.896), the RBV (r = 0.939) and the BA (r = 0.709)., Conclusions: The proposed 3D body surface automated measurement technique is feasible clinically and correlates very well with breast volumes measured using MRI. Additionally, breast volumes remain comparable despite being measured in different body positions (standing and prone) in a young cohort of AIS patients., Level of Evidence: Level IV., (Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Study Design: This is a prospective case-control study., Objective: The objective of this study was to compare 3-dimensional (3D) morphological parameters of the spine at the first visit between a nonprogressive (NP) and a progressive (P) group of immature adolescent idiopathic scoliosis (AIS)., Summary of Background Data: Prediction of curve progression remains challenging in AIS at the first visit. Prediction of progression is based on curve type, curve magnitude, and skeletal or chronological age., Methods: A prospective cohort of 133 AIS was followed from skeletal immaturity to maturity (mean, 37 mo). The first group was made up of patients with AIS with a minimum 6-degree progression of the major curve between the first and last follow-up (P) (n = 53) and the second group was composed of patients with NP who reached maturity with less than 6-degree progression (n = 81). Computerized measurements were taken on reconstructed 3-dimensional (3D) spine radiographs of the first visit. There were 6 categories of measurements: angle of plane of maximum curvature, Cobb angles (kyphosis, lordosis), 3D wedging (apical vertebra, apical disks), rotation (upper and lower junctional vertebra, apical vertebra, and thoracolumbar junction), torsion, and slenderness (height/width ratio). t tests were also conducted., Results: There was no statistical difference between the 2 groups for age and initial Cobb angle. P presented significant hypokyphosis, and parameters related to rotation presented significant statistical differences between NP and P (plane of maximal curvature, torsion, and apical axial rotation). Depth slenderness also presented statistical differences., Conclusion: This study confirms that even at the initial visit, 3D morphological differences exist between P and NP AIS. It supports the use of 3D reconstructions of the spine in the initial evaluation of AIS to help predict outcome.

Background: Routine screening of scoliosis is a controversial subject and screening efforts vary greatly around the world., Methods: Consensus was sought among an international group of experts (seven spine surgeons and one clinical epidemiologist) using a modified Delphi approach. The consensus achieved was based on careful analysis of a recent critical review of the literature on scoliosis screening, performed using a conceptual framework of analysis focusing on five main dimensions: technical, clinical, program, cost and treatment effectiveness., Findings: A consensus was obtained in all five dimensions of analysis, resulting in 10 statements and recommendations. In summary, there is scientific evidence to support the value of scoliosis screening with respect to technical efficacy, clinical, program and treatment effectiveness, but there insufficient evidence to make a statement with respect to cost effectiveness. Scoliosis screening should be aimed at identifying suspected cases of scoliosis that will be referred for diagnostic evaluation and confirmed, or ruled out, with a clinically significant scoliosis. The scoliometer is currently the best tool available for scoliosis screening and there is moderate evidence to recommend referral with values between 5 degrees and 7 degrees. There is moderate evidence that scoliosis screening allows for detection and referral of patients at an earlier stage of the clinical course, and there is low evidence suggesting that scoliosis patients detected by screening are less likely to need surgery than those who did not have screening. There is strong evidence to support treatment by bracing., Interpretation: This information statement by an expert panel supports scoliosis screening in 4 of the 5 domains studied, using a framework of analysis which includes all of the World Health Organisation criteria for a valid screening procedure.

Background: Literature on scoliosis screening is vast, however because of the observational nature of available data and methodological flaws, data interpretation is often complex, leading to incomplete and sometimes, somewhat misleading conclusions. The need to propose a set of methods for critical appraisal of the literature about scoliosis screening, a comprehensive summary and rating of the available evidence appeared essential., Methods: To address these gaps, the study aims were: i) To propose a framework for the assessment of published studies on scoliosis screening effectiveness; ii) To suggest specific questions to be answered on screening effectiveness instead of trying to reach a global position for or against the programs; iii) To contextualize the knowledge through expert panel consultation and meaningful recommendations. The general methodological approach proceeds through the following steps: Elaboration of the conceptual framework; Formulation of the review questions; Identification of the criteria for the review; Selection of the studies; Critical assessment of the studies; Results synthesis; Formulation and grading of recommendations in response to the questions. This plan follows at best GRADE Group (Grades of Recommendation, Assessment, Development and Evaluation) requirements for systematic reviews, assessing quality of evidence and grading the strength of recommendations., Conclusions: In this article, the methods developed in support of this work are presented since they may be of some interest for similar reviews in scoliosis and orthopaedic fields.

Study Design: A cell-based assay was developed to identify asymptomatic children at risk of developing idiopathic scoliosis (IS) and to stratify IS patients at an earlier stage in order to better predict their clinical outcome. Clinical validation of this assay was performed by testing IS patients at different stages, healthy control subjects, and asymptomatic offspring, born from at least one scoliotic parent, who are considered at risk of developing this disorder., Objective: Our goal was to develop and validate a clinical test for IS using cellular dielectric spectroscopy (CDS) and peripheral blood mononuclear cells (PBMCs)., Summary of Background Data: We have previously demonstrated the occurrence of a melatonin signaling dysfunction in osteoblasts obtained from severely affected IS patients using a cAMP assay. This led us to stratify IS patients into 3 functional subgroups., Methods: A group of 44 patients with IS was compared with 42 healthy control subjects and 31 asymptomatic at-risk children. PBMCs were obtained after centrifugation on a Ficoll-gradient. Melatonin signal transduction was measured by CDS in the presence of varying concentrations of melatonin or iodomelatonin., Results: Osteoblasts from distinct functional subgroups were retested using CDS, allowing their classification into the same functional subgroups with both ligands as initially demonstrated using a cAMP assay. Clinical data obtained with CDS and PBMCs showed 100% specificity and 100% sensitivity because melatonin signaling impairment was observed only in IS patients and not in healthy controls. Assessment of the risk of developing a scoliosis in asymptomatic children was determined by CDS in 33% of asymptomatic children at risk, which was confirmed clinically within 24 months., Conclusion: This cell-based assay can serve as a presymptomatic screening test to identify asymptomatic children at risk of developing IS and may be used to improve stratification of patients, which in turn allow clinicians to predict their clinical outcome. Moreover, this functional blood test is advantageous because it can be performed without prior knowledge of specifically mutated genes causing IS.

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis that affects a significant number of young teenagers, mainly females (0.2-6 % of the population). Historically, several hypothesis were postulated to explain the aetiology of AIS, including genetic factors, biochemical factors, mechanics, neurological, muscular factors and hormonal factors. The neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS has generated great interest. This hypothesis stems from the fact that experimental pinealectomy in chicken, and more recently in rats maintained in a bipedal mode, produces a scoliosis. The biological relevance of melatonin in idiopathic scoliosis is controversial since no significant decrease in circulating melatonin level has been observed in a majority of studies. Analysis of melatonin signal transduction in musculoskeletal tissues of AIS patients demonstrated for the first time a defect occurring in a cell autonomous manner in different cell types isolated from AIS patients suffering of the most severe form of that disease. These results have led to a classification of AIS patients in three different functional groups depending on their response to melatonin, suggesting that the cause of AIS involves several genes. Molecular analysis showed that melatonin signaling dysfunction is triggered by an increased phosphorylation of Gi proteins inactivating their function. This discovery has led to development of a first scoliosis screening assay. This test, using blood sample, is currently in clinical validation process in Canada and could be used for screening children at high risk of developing AIS.