Genetic variant of MIR4300HG is associated with progression of adolescent idiopathic scoliosis in a Chinese population

Abstract Background A recent genome-wide association study identified a susceptible locus in MIR4300HG gene that was associated with curve progression of adolescent idiopathic scoliosis (AIS) in the Japanese population. However, the association between the gene and curve progression in other populations remains unclear. Methods A cohort of 1952 AIS patients and 2495 healthy controls were included in the case-control analysis. In the case-only analysis, 747 patients were assigned to the progression group and 520 patients were assigned to the non-progression group, respectively. Rs35333564 was genotyped for all the subjects. Paraspinal muscles of 76 patients were collected for the analysis of gene expression. Chi-square test and ANOVA test were used for the intergroup comparison. Pearson correlation analysis was performed to investigate the relationship between the gene expression and curve magnitude. Results Variant rs35333564 was significantly associated with the curve severity of AIS (p = 0.025), but not the development of AIS (p = 0.418). Genotype GG was indicated by remarkably lower expression of MIR4300 (p = 0.020) which was significantly correlated with curve magnitude (p = 0.010). As a predicted target gene of MIR4300, the expression of CRTC1 was negatively correlated with MIR4300 expression (p = 0.012, r = −0.287) and positively correlated with curve severity (p = 0.025, r = 0.257). Conclusions The association between rs35333564 and curve progression was successfully replicated in a Chinese AIS population. CRTC1 may be the target gene of MIR4300 that plays a role in the curve progression of AIS.

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Supine flexibility predicts curve progression for patients with adolescent idiopathic scoliosis undergoing underarm bracing

The Bone & Joint Journal ◽

10.1302/0301-620x.102b2.bjj-2019-0916.r1 ◽

2020 ◽

Vol 102-B (2) ◽

pp. 254-260 ◽

Cited By ~ 4

Author(s):

Jason P. Y. Cheung ◽

Prudence W. H. Cheung

Keyword(s):

Adolescent Idiopathic Scoliosis ◽

Idiopathic Scoliosis ◽

Regression Model ◽

Cobb Angle ◽

Characteristic Curve ◽

Absolute Error ◽

Curve Progression ◽

Curve Magnitude ◽

Spine Radiograph ◽

Whole Spine

Aims The aim of this study was to assess whether supine flexibility predicts the likelihood of curve progression in patients with adolescent idiopathic scoliosis (AIS) undergoing brace treatment. Methods This was a retrospective analysis of patients with AIS prescribed with an underarm brace between September 2008 to April 2013 and followed up until 18 years of age or required surgery. Patients with structural proximal curves that preclude underarm bracing, those who were lost to follow-up, and those who had poor compliance to bracing (<16 hours a day) were excluded. The major curve Cobb angle, curve type, and location were measured on the pre-brace standing posteroanterior (PA) radiograph, supine whole spine radiograph, initial in-brace standing PA radiograph, and the post-brace weaning standing PA radiograph. Validation of the previous in-brace Cobb angle regression model was performed. The outcome of curve progression post-bracing was tested using a logistic regression model. The supine flexibility cut-off for curve progression was analyzed with receiver operating characteristic curve. Results A total of 586 patients with mean age of 12.6 years (SD 1.2) remained for analysis after exclusion. The baseline Cobb angle was similar for thoracic major curves (31.6° (SD 3.8°)) and lumbar major curves (30.3° (SD 3.7°)). Curve progression was more common in the thoracic curves than lumbar curves with mean final Cobb angles of 40.5° (SD 12.5°) and 31.8° (SD 9.8°) respectively. This dataset matched the prediction model for in-brace Cobb angle with less mean absolute error in thoracic curves (0.61) as compared to lumbar curves (1.04). Reduced age and Risser stage, thoracic curves, increased pre-brace Cobb angle, and reduced correction and flexibility rates predicted increased likelihood of curve progression. Flexibility rate of more than 28% has likelihood of preventing curve progression with bracing. Conclusion Supine radiographs provide satisfactory prediction for in-brace correction and post-bracing curve magnitude. The flexibility of the curve is a guide to determine the likelihood for brace success. Cite this article: Bone Joint J 2020;102-B(2):254–260.

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Influence of curve morphology and location on the efficacy of rigid conservative treatment in patients with adolescent idiopathic scoliosis

The Bone & Joint Journal ◽

10.1302/0301-620x.103b2.bjj-2020-1113.r2 ◽

2021 ◽

Vol 103-B (2) ◽

pp. 373-381

Author(s):

Patrick Strube ◽

Maria Gunold ◽

Tanja Müller ◽

Mario Leimert ◽

André Sachse ◽

...

Keyword(s):

Adolescent Idiopathic Scoliosis ◽

Conservative Treatment ◽

Idiopathic Scoliosis ◽

Treatment Failure ◽

Univariate Analysis ◽

Curve Progression ◽

Curve Correction ◽

Major Curve ◽

Apical Rotation ◽

Curve Magnitude

Aims The aim of the present study was to answer the question whether curve morphology and location have an influence on rigid conservative treatment in patients with adolescent idiopathic scoliosis (AIS). Methods We retrospectively analyzed AIS in 127 patients with single and double curves who had been treated with a Chêneau brace and physiotherapeutic specific exercises (B-PSE). The inclusion criteria were the presence of structural major curves ≥ 20° and < 50° (Risser stage 0 to 2) at the time when B-PSE was initiated. The patients were divided into two groups according to the outcome of treatment: failure (curve progression to ≥ 45° or surgery) and success (curve progression < 45° and no surgery). The main curve type (MCT), curve magnitude, and length (overall, above and below the apex), apical rotation, initial curve correction, flexibility, and derotation by the brace were compared between the two groups. Results In univariate analysis treatment failure depended significantly on: 1) MCT (p = 0.008); 2) the apical rotation of the major curve before (p = 0.007) and during brace treatment (p < 0.001); 3) the initial and in-brace Cobb angles of the major (p = 0.001 and p < 0.001, respectively) and minor curves (p = 0.015 and p = 0.002); 4) major curve flexibility (p = 0.005) and the in-brace curve correction rates (major p = 0.008, minor p = 0.034); and 5) the length of the major curve (LoC) above (p < 0.001) and below (p = 0.002) the apex. Furthermore, MCT (p = 0.043, p = 0.129, and p = 0.017 in MCT comparisons), LoC (upper length p = 0.003, lower length p = 0.005), and in-brace Cobb angles (major p = 0.002, minor p = 0.027) were significant in binary logistic regression analysis. Conclusion Curve size, location, and morphology were found to influence the outcome of rigid conservative treatment of AIS. These findings may improve future brace design and patient selection for conservative treatment. Cite this article: Bone Joint J 2021;103-B(2):373–381.

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

Asian Spine Journal ◽

10.4184/asj.2018.12.2.202 ◽

2018 ◽

Vol 12 (2) ◽

pp. 202-213 ◽

Cited By ~ 10

Author(s):

Jason Pui Yin Cheung ◽

Prudence Wing Hang Cheung ◽

Dino Samartzis ◽

Keith Dip-Kei Luk

Keyword(s):

Adolescent Idiopathic Scoliosis ◽

Idiopathic Scoliosis ◽

Cobb Angle ◽

Distal Radius ◽

Skeletal Maturity ◽

Curve Progression ◽

Close Monitoring ◽

Skeletally Immature ◽

Increased Risk ◽

Curve Magnitude

<sec><title>Study Design</title>Prospective study.</sec><sec><title>Purpose</title>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.</sec><sec><title>Overview of Literature</title>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.</sec><sec><title>Methods</title>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.</sec><sec><title>Results</title>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°).</sec><sec><title>Conclusions</title>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.</sec>

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Should L3 be selected as the lowest instrumented vertebra in patients with Lenke type 5C adolescent idiopathic scoliosis whose lowest end vertebra is L4?

Journal of Neurosurgery Spine ◽

10.3171/2020.11.spine201807 ◽

2021 ◽

pp. 1-10

Author(s):

Tomohiro Banno ◽

Yu Yamato ◽

Hiroki Oba ◽

Tetsuro Ohba ◽

Tomohiko Hasegawa ◽

...

Keyword(s):

Adolescent Idiopathic Scoliosis ◽

Idiopathic Scoliosis ◽

Curve Progression ◽

Global Alignment ◽

Fusion Surgery ◽

Radiographic Outcomes ◽

Lowest Instrumented Vertebra ◽

Upper Instrumented Vertebra ◽

Coronal Decompensation

OBJECTIVE L3 is most often selected as the lowest instrumented vertebra (LIV) to conserve mobile segments in fusion surgery; however, in cases with the lowest end vertebra (LEV) at L4, LIV selection as L3 could have a potential risk of correction loss and coronal decompensation. This study aimed to compare the clinical and radiographic outcomes depending on the LEV in adolescent idiopathic scoliosis (AIS) patients with Lenke type 5C curves. METHODS Data from 49 AIS patients with Lenke type 5C curves who underwent selective thoracolumbar/lumbar (TL/L) fusion to L3 as the LIV were retrospectively analyzed. The patients were classified according to their LEVs into L3 and L4 groups. In the L4 group, subanalysis was performed according to the upper instrumented vertebra (UIV) level toward the upper end vertebra (UEV and 1 level above the UEV [UEV+1] subgroups). Radiographic parameters and clinical outcomes were compared between these groups. RESULTS Among 49 patients, 32 and 17 were in the L3 and L4 groups, respectively. The L4 group showed a lower TL/L curve correction rate and a higher subjacent disc angle postoperatively than the L3 group. Although no intergroup difference was observed in coronal balance (CB), the L4 group showed a significantly higher main thoracic (MT) and TL/L curve progression during the postoperative follow-up period than the L3 group. In the L4 group, the UEV+1 subgroup showed a higher absolute value of CB at 2 years than the UEV subgroup. CONCLUSIONS In Lenke type 5C AIS patients with posterior selective TL/L fusion to L3 as the LIV, patients with their LEVs at L4 showed postoperative MT and TL/L curve progression; however, no significant differences were observed in global alignment and clinical outcome.

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