Semi-automatic method for pre-surgery scoliosis classification on X-ray images using Bending Asymmetry Index.

PURPOSE: Bending Asymmetry Index (BAI) has been proposed to characterize the types of scoliotic curve in three-dimensional ultrasound imaging. Scolioscan has demonstrated its validity and reliability in scoliosis assessment with manual assessment-based X-ray imaging. The objective of this study is to investigate the ultrasound-derived BAI method to X-ray imaging of scoliosis, with supplementary information provided for the pre-surgery planning. METHODS: About 30 pre-surgery scoliosis subjects (9 males and 21 females; Cobb: 50.9 ± 19.7°, range 18°-115°) were investigated retrospectively. Each subject underwent three-posture X-ray scanning supine on a plain mattress on the same day. BAI is an indicator to distinguish structural or non-structural curves through the spine flexibility information obtained from lateral bending spinal profiles. BAI was calculated semi-automatically with manual annotation of vertebral centroids and pelvis level inclination adjustment. BAI classification was validated with the scoliotic curve type and traditional Lenke classification using side-bending Cobb angle measurement (S-Cobb). RESULTS: 82 curves from 30 pre-surgery scoliosis patients were included. The correlation coefficient was R2 = 0.730 (p < 0.05) between BAI and S-Cobb. In terms of scoliotic curve type classification, all curves were correctly classified; out of 30 subjects, 1 case was confirmed as misclassified when applying to Lenke classification earlier, thus has been adjusted. CONCLUSION: BAI method has demonstrated its inter-modality versatility in X-ray imaging application. The curve type classification and the pre-surgery Lenke classification both indicated promising performances upon the exploratory dataset. A fully-automated of BAI measurement is surely an interesting direction to continue our endeavor. Deep learning on the vertebral-level segmentation should be involved in further study.

Decreased cortical bone density and mechanical strength with associated elevated bone turnover markers at peri-pubertal peak height velocity: a cross-sectional and longitudinal cohort study of 396 girls with adolescent idiopathic scoliosis.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

A Decade in Review after Idiopathic Scoliosis Was First Called a Complex Trait-A Tribute to the Late Dr. Yves Cotrel for His Support in Studies of Etiology of Scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.

Lower WNT16 expression in patients with adolescent idiopathic scoliosis - potential link to lower bone mass in AIS?

Adolescent Idiopathic Scoliosis (AIS) occurs during pubertal rapid growth period and is closely associated with low bone mass. The underlying mechanisms for systemic low bone mass in AIS remains unclear. Wnt signalling pathway is one of the important pathways regulating bone metabolism and influencing bone strength, its family member Wnt16 associates with lower bone mineral density (BMD) in late adulthood, and plays key regulatory role in determining cortical bone quality in adult mice. Our randomized control trial have reported vitamin D (VitD) supplementation significantly improved bone mass and reduced the risk of curve progression in AIS. A case-control study and animal study were employed to answer if WNT16 is associated with the abnormal bone quality in AIS and if the effect of VitD supplementation is associated with Wnt16, respectively. A cohort of 161 AIS and control female subjects were recruited for measurement of anthropometric parameters, bone qualities, and circulating Wnt16 level. In animal study, WT and Wnt16 gKO mice were both subjected to special VitD diet from week 4 and terminated at week 7 and 10 for samples harvesting. AIS showed significantly lower BMD, circulating WNT16 level, and elevated serum level of type I procollagen N-terminal propeptide. Wnt16 gKO mice demonstrated lower cortical bone density compared with WT mice from week 7 of age and Wnt16 gKO were less prone to cortical bone loss induced by high dosage VitD diet. Further study on the biological role of WNT16 and crosstalk with VitD metabolism on bone qualities is warranted which might shed light on prognostic gene of osteopenia and new perspectives for potential target to prevent curve progression.

A six years longitudinal cohort study on the changes in bone density and bone quality up to peak bone mass in adolescent idiopathic scoliosis (AIS) with and without 2 years of Calcium and Vit-D supplementation.

Adolescent idiopathic scoliosis (AIS) is associated with osteopenia which could persist into adulthood affecting attainment of Peak Bone Mass thus resulting in osteoporosis in late adulthood. We previously reported a randomized double-blinded placebo-controlled trial(the Cal study) showing significant bone health improvement with 2-year calcium(Ca)+Vit-D supplementation for AIS girls. This study addressed the important issue whether bone health improvement from the initial 2-year Ca+Vit-D supplementation could persist as subjects approached towards Peak Bone Mass at 6-year ie after 4-year of supplement discontinuation. This was an extension of the Cal study on AIS girls (11-14 years old, mean age=12.9 years, Tanner stage

Role of differentially expressed LBX1 in Adolescent Idiopathic Scoliosis (AIS) paraspinal muscle phenotypes and muscle-bone crosstalk through modulating myoblasts.

AIS is three-dimensional spinal deformity with unclear etiopathogenesis. LBX1 is so far the only multi-centers validated AIS predisposing gene. The imbalance of posterior paraspinal muscles is an important factor in AIS etiopathogenesis. It is poorly understood how LBX1 contributes to the abnormal paraspinal muscles and onset/progression of AIS. We aimed to evaluate the expression of LBX1 in paraspinal muscles at the concave and convex side in AIS, and whether alternation of LBX1 expression could affect myoblastsactivities and potentially influence muscle-bone interaction via myokines expression. Paraspinal muscles from AIS and age- and curvature-matched congenital scoliosis (CS) patients were collected for fiber types analysis. Biopsies were also subjected to qPCR to validate expression of myogenic markers, selected myokines and LBX1. Human skeletal muscle myoblast (HSMM) was used for LBX1 loss-of-function study in vitro. Muscle fiber types analysis showed type I and type IIX/IIAX fibers proportion were significantly different between AIS concave and convex but not in two sides of CS. LBX1, myogenic markers and one myokine were significantly imbalanced in AIS but not in CS. Loss-of-function study showed knockdown of LBX1 could inhibit myogenic markers expression and myokines as well. This study provides new insight into the association between imbalanced paraspinal muscle and potential muscle-bone crosstalk in AIS patients and the biological function of predisposing gene LBX1. Further investigation with appropriate animal models is warranted to explore if asymmetric expression of LBX1 could result in distinct muscle phenotypes and bone qualities thus affect the progression of spine curvature in AIS.

Age- and gender-related normative value of whole-body sagittal alignment based on 584 asymptomatic Chinese adult population from age 20 to 89.

To establish the age- and sex-related normative values of sagittal alignment in asymptomatic Chinese adults, and to investigate the changes and possible associated compensation mechanisms across age groups. 584 asymptomatic Chinese adults aged 20-89 years were recruited. Subjects were grouped according to age and gender. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Sagittal parameters between gender in different age groups were compared via independent t test. Pearson correlation analysis was used to demonstrate relationships between parameters. Thoracic kyphosis (TK) increased steadily while lumbar lordosis decreased gradually in both genders. Pelvic tilt (PT) in male is greater than in female across all age groups with age related gradual increase. There were significant differences between male and female from 20s to 60s in terms of knee flexion angle (KA) and ankle dorsiflexion angle (AA), but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK. This study comprehensively presented the normative sagittal alignment based on a large asymptomatic population, which could serve as an age- and gender-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involve more pelvic and lower limb mechanisms for elderly people.

Morphological changes of intervertebral disc in relation with curve severity of patients with Adolescent Idiopathic Scoliosis - a T2-weighted MRI study.

The purpose of this study was to evaluate the morphological changes of intervertebral discs (IVD) and vertebral bodies (VB) in AIS girls according to the subgroups with different curve severity by magnetic resonance imaging (MRI). This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were evaluated on volumetric images. One-way ANOVA with Bonferroni correction was used. There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. On top of coronal wedging of VB and IVD, there was significantly reduced volume of IVD and NP in severe-AIS patients, despite T2 signal of IVD was preserved. The current findings indicate that early mechanical effects on the discs and vertebrae in adolescent scoliotic spine is evident on quantitative imaging. Importantly, these patients may be vulnerable to disc degeneration if no operative treatment is prescribed.

Is ultrasound accurate for radiation-free quantitative assessment of spinal curvatures in patients with idiopathic scoliosis - a systematic review and meta-analysis.

Despite application of ultrasound for quantitative measurement of spinal curvatures has been reported with various studies, a systematic review for such is lacking. This systematic review aimed to evaluate (1) reliability of ultrasound; (2) validity of ultrasound using radiographic measurement as gold standard in idiopathic scoliosis patients; and (3) the use of various anatomical landmarks for measurement of spinal curvatures. MEDLINE, EMBASE, CINAHL, and CENTRAL databases were searched. QUADAS-2 quality assessment tool was adopted. Reliability of ultrasound in terms of intra-class correlation coefficient was recorded. Pearson correlation coefficients between ultrasound and radiographic measurements were extracted for meta-analysis. Subgroup analyses based on ultrasound measurement protocols of spinous process (SP), transverse processes (TP) and center of lamina (COL) were conducted. Eleven articles reporting 18 correlation analyses on 766 subjects were eligible for meta-analysis. The mean inter-rater reliability of ultrasound measurement was 0.87±0.07. Pooled correlation for all studies was 0.918 (95% CI: 0.868-0.949), exhibiting substantial heterogeneity (I2=90.50%, p<0.001). Subgroup analyses showed that pooled correlations were 0.887 for COL method (comprising 356 subjects); 0.924 for SP method (255 subjects); and 0.941 for TP method (117 subjects); all with notable heterogeneity (I2>90%, p<0.001). The overall risk of bias was rated moderate; yet publication bias was noted. Evidences showed that ultrasound was a promising non-invasive method with satisfactory validity and reliability for measuring coronal curvatures utilizing the SP, TP or COL methods. Further development of three-dimensional ultrasound towards scoliosis assessment will facilitate its translational application for managing scoliosis.

Using ultrasound for screening scoliosis to reduce unnecessary radiographic radiation - a prospective diagnostic accuracy study on 442 schoolchildren.

Scoliosis screening is important for timely initiation of brace treatment to mitigate curve progression in skeletally immature children. Scoliosis screening programs frequently include the protocol of referring children screened positive with Scoliometer and Moiré Topography for confirmatory standard radiography. Despite being highly sensitive (88%) for detecting those who require specialist referral, the screening program was found to have more than 50% false positive rate that leads to unnecessary radiation exposure. Radiation-free ultrasound has been reported to be reliable for quantitative assessment of scoliosis curves. The aim of this prospective diagnostic accuracy study was to determine the accuracy of ultrasound in determining the referral status for children initially screened positive for scoliosis. 442 schoolchildren with a mean Cobb angle of 14.0 ± 6.6° were recruited. Using x-ray as the gold standard, the sensitivity and specificity of ultrasound in predicting the correct referral status were 92.3% and 51.6% respectively. ROC curve analysis revealed an area under curve of 0.735 for ultrasound alone and 0.832 for ultrasound plus scoliometer measurement. The finding provided strong evidences on the accuracy of ultrasound in determining the referral status that could result in more than 50% reduction of unnecessary radiation exposure for children undergoing scoliosis screening.

Feasibility and effects of 6-month home-based digitally supported E-Fit program utilizing high-intensity interval exercises in girls with adolescent idiopathic scoliosis: a randomized controlled pilot study.

Adolescent idiopathic scoliosis (AIS) patients have lower physical activities when compared with healthy controls, and are associated with lower bone mineral density (BMD), muscle strength and poorer quality of life (QoL). We aimed to assess the feasibility and effects of 6-month home-based digitally supported E-Fit comprised of high-intensity interval exercises for AIS patients. 40 AIS girls aged 11-14 were randomly assigned to E-Fit or control group. E-Fit group participated in an online 6-month home-based exercise program. At baseline, 6-months and 12-months follow-up, BMD using dual-energy X-ray absorptiometry, muscle functions, physical activity using Modified Baecke Questionnaire (MBQ), and QoL using Scoliosis Research Society-22 (SRS-22r) and feedback questionnaire were investigated. 14 in E-Fit and 16 in control group completed the study. Both groups had similar baseline characteristics. At 6-months, E-Fit group showed better improvement and significant interaction effect in left femoral neck bone mineral content (p=0.021) and isometric curl up test (p=0.04). Left arm lean mass showed better improvement between 6-months and 12-months follow-up (p=0.046) and whole-body areal BMD had significant interaction effect at 12-months follow-up (p=0.077). Improvement on self-image, work and sports participation were noted in E-Fit group across time. 70% of E-Fit participants were positive towards domestic application via online platform. E-Fit showed some benefits on bone health, muscle functions, physical activity and QoL measures. Current study indicated some potential physical and psychological benefits of E-Fit for AIS girls. E-Fit was feasible to conduct online at home and might have value of promoting exercise habits among relatively inactive AIS girls.

Association of serum 25(OH)Vit-D levels with risk of pediatric fractures: a systematic review and meta-analysis.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Sequential spine-hand radiography for assessing skeletal maturity with low radiation EOS imaging system for bracing treatment recommendation in adolescent idiopathic scoliosis: a feasibility and validity study.

PURPOSE: The EOS-imaging system is increasingly adopted for clinical follow-up in scoliosis with the advantages of simultaneous biplanar imaging of the spine in an erect position. Skeletal maturity assessment using a hand radiograph is an essential adjunct to spinal radiography in scoliosis follow-up. This study aims at testing the feasibility and validity of a newly proposed EOS workflow with sequential spine-hand radiography for skeletal maturity assessment and bracing recommendation. METHODS: EOS spine-hand radiographs from patients with diagnosis of idiopathic scoliosis, including both sexes and an age range of ten to 14 years, were scored using the Thumb Ossification Composite Index (TOCI), Sanders and Risser methods. Intraclass correlation coefficients (ICCs) were calculated for inter/intraobserver agreement and were tested with Cronbach's alpha values. RESULTS: In all, 60 EOS-spine hand radiographs selected from subjects with diagnosis of adolescent idiopathic scoliosis (AIS), including 32 male patients (mean age 11.53 years; 10 to 14) and 28 female patients (mean age 11.50 years; 10 to 13) who underwent sequential spine-hand low dose EOS imaging were generated for analysis. The overall interobserver (ICC = 0.997) and intraobserver agreement (α > 0.9) demonstrated excellent agreement for TOCI staging; ICC > 0.994 for both TOCI and Sanders staging comparing traditional digital versus EOS hand radiography; ICC ≥ 0.841 for agreement on bracing recommendation among TOCI versus the Risser and Sanders system. CONCLUSION: With the proposed new EOS workflow it was feasible to produce high image quality for skeletal maturity assessment with excellent reliability and validity to inform consistent bracing recommendation in AIS. The workflow is applicable for busy daily clinic settings in tertiary scoliosis centres with reduced time cost, improved efficiency and throughput of the radiology department. LEVEL OF EVIDENCE: III.

Antibiotic management of acute pharyngitis in primary care.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.