Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells.

Metastasis frequently targets bones, where cancer cells from the primary tumour migrate to the bone marrow, initiating new tumour growth. Not only is bone the most common site for metastasis, but it also often marks the first site of metastatic recurrence. Despite causing over 90% of cancer-related deaths, effective treatments for bone metastasis are lacking, with current approaches mainly focusing on palliative care. Circulating tumour cells (CTCs) are pivotal in metastasis, originating from primary tumours and circulating in the bloodstream. They facilitate metastasis through molecular interactions with the bone marrow environment, involving direct cell-to-cell contacts and signalling molecules. CTCs infiltrate the bone marrow, transforming into disseminated tumour cells (DTCs). While some DTCs remain dormant, others become activated, leading to metastatic growth. The presence of DTCs in the bone marrow strongly correlates with future bone and visceral metastases. Research on CTCs in peripheral blood has shed light on their release mechanisms, yet investigations into bone marrow DTCs have been limited. Challenges include the invasiveness of bone marrow aspiration and the rarity of DTCs, complicating their isolation. However, advancements in single-cell analysis have facilitated insights into these elusive cells. This review will summarize recent advancements in understanding bone marrow DTCs using single-cell analysis techniques.

Patient-perceived factors on treatment satisfaction in early onset scoliosis treated surgically with a minimum of ten years.

BACKGROUND: The prognosis of surgically treated subjects with early onset scoliosis (EOS) into adulthood has been lacking. We aimed to investigate the patients' perspectives on satisfaction with surgical treatment. METHODOLOGY: We included all surgical candidates with EOS who had undergone index spinal surgery for scoliosis correction between 2009 and 2013. The minimum duration of postoperative follow-up was 10 years at the time of survey completion. Three questionnaires were used in this study, comprising the revised Scoliosis Research Society questionnaire (SRS-22r), the Patient-Reported Outcomes Measurement Information System (PROMIS-29), and the World Health Organization Quality of Life (WHOQOL-BREF). Measures of treatment satisfaction were retrieved from SRS-22r. RESULTS: There were 29 participants who completed the survey, and thereby included in the study (i.e., a response rate of 43% and a dropout rate of 6%). Amongst them, 14, 11, and 4 individuals received posterior spinal fusion (PSF), magnetically controlled growing rods (MCGR), and traditional growing rods, respectively. The average duration after the index spinal surgery was 12.6 ± 2.2 years. Our findings revealed that self-image (across all treatment groups), sleep disruption (only in PSF), and social aspects (in both PSF and MCGR) were significantly worse when compared to the normative values. According to the multivariable linear regression model (R-square = 0.690, p < .001), an increase in SRS-22r mental health (p = .008) and PROMIS-29 social participation scores (p = .004) corresponded to 0.511 and 0.055 points increases in satisfaction. Every unit increase in PROMIS-29 fatigue (p = .043) and WHOQOL-BREF physical domain scores (p = .007) was in conjunction with 0.019 and 0.040 points decreases in satisfaction. SRS-22r self-image (p = .056) and WHOQOL-BREF environmental domain scores (p = .076) were included in the model but did not reach statistical significance. CONCLUSIONS: To improve the long term quality of life in surgical candidates with EOS, we demonstrated that mental health, social participation, fatigue, and physical health were significant factors associated with treatment satisfaction. Interestingly, demographic and radiographic parameters did not have a significant effect in our cohort.

Radiographic characterization of OPLL progression in patients receiving laminoplasty with a minimum of two-years follow-up.

Ossification of the posterior longitudinal ligament (OPLL) is a common cause of degenerative cervical myelopathy (DCM) in Asian populations. Characterization of OPLL progression following laminoplasty remains limited in the literature. 29 patients with OPLL received cervical laminoplasty and a minimum of 2-years follow-up. Clinical and radiological surveillance occurred at 3-months, 6-months, 12-months post-op and then at yearly intervals. Transverse (anteroposterior) diameter and sagittal length of OPLL in relation to their cervical vertebral level of localisation was assessed upon immediate post-op radiographs compared to those obtained at subsequent follow-up. OPLL progression was defined as an increase in transverse dimensions and/or length by ≥ 2 mm. The average period of clinical follow-up was 6.7 ± 3.3 years. Upon latest follow-up, 79% of patients demonstrated at least 2 mm of transverse or longitudinal progression of OPLL. This corresponded to 2-years and 5-year progression rates of 54% and 71% respectively. OPLL located over C5 demonstrated the greatest transverse progression rate at (0.24 ± 0.34 mm / year). The mean overall longitudinal progression rate was 1.61 ± 2.06 mm / year. No patients experienced neurological decline resulting from OPLL progression requiring revision decompression during the period of post-operative observation. Characterizing transverse and longitudinal progression by cervical level via radiographs has implications in surgical planning for OPLL and should be consolidated upon post-operative CT/MRI scans as well as larger sample sizes.

Increased lengthening frequency does not adversely affect the EOSQ scores in magnetically controlled growing rod surgeries in 133 subjects followed to final fusion.

PURPOSE: Magnetically Controlled Growing Rod (MCGR) allows frequent outpatient rod lengthening when treating Early Onset Scoliosis (EOS) patients. But there is lack of expert consensus on the optimal MCGR lengthening interval. EOS 24-Item Questionnaire (EOSQ) is validated for assessing health-related quality of life (HrQOL), family burden, and satisfaction. This is the first study assessing how MCGR lengthening intervals affects patient-perceived outcomes. METHODS: This is a multicentred cohort study with subjects recruited from 2012 to 2018 and followed till fusion. EOS subjects who underwent MCGR surgeries were grouped into high, medium or low lengthening interval subgroups based on 16 and 20 week cut-offs. Repeated measure analysis was performed on EOSQ's specified 12 domains. EOSQ results were taken: before index surgery, after index surgery, and prior to definitive treatment. Demographic, clinical and radiographic data were included in model adjustment. RESULTS: 133 subjects with mean follow-up of 3.5 (± 1.3) years were included, with 60 males and 73 females; 45 idiopathic, 23 congenital, 38 neuromuscular, and 27 syndromic patients. Mean Cobb angle at surgery was 67° (± 22°) with mean age of 8.3 (± 2.5) years. Between groups, clinical and radiographic parameters were comparable. Higher EOSQ scores in medium lengthening interval subgroup was present in fatigue (p = 0.019), emotion (p = 0.001), and parental impact (p = 0.049) domains, and overall score (p = 0.046). Trendline contrast between subgroups were present in general health (p = 0.006) and physical function (p = 0.025) domains. CONCLUSION: Patient-perceived outcome improvements appear similar between lengthening interval subgroups. All MCGR lengthening intervals were tolerated by patients and family, with no negative impact observed. LEVEL OF EVIDENCE: Prognostic Level III.

Immediate vs Gradual Brace Weaning Protocols in Adolescent Idiopathic Scoliosis: A Randomized Clinical Trial.

Importance: Lack of evidence and consensus for brace weaning protocol in adolescent idiopathic scoliosis (AIS) results in clinicians prescribing gradual weaning in the hope of avoiding curve deterioration after weaning. However, gradual weaning contributes to prolonged brace wear, which can affect spinal stiffness and health-related quality of life (HRQoL). Objective: To determine whether gradual weaning results in better curve magnitude and truncal balance maintenance after brace weaning vs immediate brace removal for patients with AIS. Design, Setting, and Participants: This was an open-labeled randomized clinical trial commenced in April 2017 with 24-month follow-up completed in January 2023. Outcome assessors were masked to weaning protocol assigned. The study took place at a territory-wide tertiary scoliosis clinic serving the largest number of referrals in the local population. Patients with AIS ready to wean off of brace wear were eligible (402 were screened; 33 were excluded [15 for <18 hours/day of brace-wear compliance before weaning, 11 were treated with Milwaukee brace, and 7 declined to participate]; and 369 were included), and those who were treated with a custom molded thoracolumbosacral orthosis and had reached skeletal maturity were consecutively recruited. Interventions: Patients were randomized to gradual weaning protocol (n = 176) with an additional 6 months of nighttime wear before completely stopping or immediate weaning protocol (n = 193) with immediate brace removal at recruitment. Main Outcomes and Measures: Changes in major curve Cobb angle and truncal balance from the time of weaning to 6-month, 12-month, and 24-month follow-up. HRQoL was also assessed using the refined Scoliosis Research Society 22-item and EuroQol 5-dimension questionnaires. Results: A total of 369 patients (mean [SD] age, 14.9 [1.1] years; 304 [83.4%] girls) were randomized with 284 (77.0%) completing 24-month longitudinal follow-up. Immediate and gradual weaning groups had no significant differences in change of major Cobb angle at postweaning 6-month (difference, -0.6°; 95% CI, -1.4 to 0.2; P = .17), 12-month (difference, -0.3°; 95% CI, -1.2 to 0.6; P = .47), and 24-month (difference, -0.3°; 95% CI, -1.2 to 0.7; P = .60) follow-up. The number of curve progression, nonprogression, and rebound cases were comparable (χ22 = 2.123; P = .35). Postweaning changes in truncal balance and HRQoL demonstrated no significant differences between groups. Conclusions: Gradual weaning did not demonstrate superiority to immediate weaning with predefined criteria of Cobb angle and truncal balance maintenance and HRQoL after brace weaning. Gradual and immediate weaning achieved very similar maintenance of brace outcomes in AIS. We therefore recommend the consideration of immediate brace weaning, which aims to benefit patients with earlier time for increased exercises and activity level. Trial Registration: ClinicalTrials.gov Identifier: NCT03329716.

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.

Gaussian random field-based characterization and reconstruction of cancellous bone microstructure considering the constraint of correlation structure.

The macro scale physical properties of cancellous bone materials are governed by the microstructural features, which is of great significance for the multi-scale research of cancellous bone and the inverse design of bone-mimicking materials. Therefore, it is essential to characterize the natural cancellous bone samples, and reconstruct the microstructures with the biomimetic osteointegration and mechanical properties. In this research, a novel approach for the characterization and reconstruction of cancellous bone was proposed, based on the medical image analysis and anisotropic three-dimensional Gaussian random field (GRF). The geometric similarity, i.e. the interface curvature distribution (ISD), was meticulously studied, which is important to the osteointegration ability. And the mechanical properties were validated by the stress-strain curves under the large compressive strain simulated by the smoothed particle hydrodynamic (SPH) method. In addition, the effects of the generation parameters of GRF-based biomimetic microstructures on the apparent properties were analyzed. The ISD results demonstrated that both GRF and micro-CT groups had the similar columnar morphological properties, while the latter had more hyperbolic features. And it was found that the GRF-based biomimetic microstructures and the natural bone samples based on micro-CT (MCT) had the similar failure mode. The concordance correlation coefficient between MCT and GRF pairs was 0.8685, with a Pearson ρ value of 0.8804, and significance level p<0.0001. The Bland-Altman LoA was 0.1647 MPa with 95 % (1.96SD) lower and upper bound value between -0.2892 and 0.6185 MPa. The two groups had almost the same elastic modulus with the mean absolute percentage error (MAPE) of 7.84 %. While the yield stress and total conversion energy of the GRF-based samples were lower than those of the natural bone samples, and the MAPE were 16.99 % and 16.27 %, respectively. Although it meant the lower structural efficiency, the huge design space of this approach and advanced 3D printing technology can provide great potential for the design of orthopedic implants.

Circulating Tumour Cells in the Prediction of Bone Metastasis.

Bone is the most common organ for the development of metastases in many primary tumours, including those of the breast, prostate and lung. In most cases, bone metastasis is incurable, and treatment is predominantly palliative. Much research has focused on the role of Circulating Tumour Cells (CTCs) in the mechanism of metastasis to the bone, and methods have been developed to isolate and count CTCs from peripheral blood. Several methods are currently being used in the study of CTCs, but only one, the CellSearchTM system has been approved by the United States Food and Drug Administration for clinical use. This review summarises the advantages and disadvantages, and outlines which clinical studies have used these methods. Studies have found that CTC numbers are predictive of bone metastasis in breast, prostate and lung cancer. Further work is required to incorporate information on CTCs into current staging systems to guide treatment in the prevention of tumour progression into bone.

"Am I different?" Coping and mental health among teenagers with adolescent idiopathic scoliosis: A qualitative study.

PURPOSE: To explore the stressors, coping strategies, and mental health of adolescents diagnosed with idiopathic scoliosis. DESIGN AND METHODS: This study adopted a descriptive qualitative study design. Twelve participants were recruited from a local non-government organization in Hong Kong. Semi-structured interviews were conducted to collect data. Verbatim transcriptions of interviews were coded and analyzed using thematic analysis. The guideline of the Consolidated Criteria for Reporting Qualitative Studies was used to report the findings. RESULTS: Five themes were identified: "Disease- and treatment-induced changes and stressors", "Cognitive assessment and personal perceptions", "Behavioral and emotional coping strategies", "Social interactions and social support", and "Deteriorating or thriving in psychological development and well-being". CONCLUSIONS: Adolescents with idiopathic scoliosis experienced a variety of physical and psychological stressors. It is imperative to prioritize efforts to promote adaptive coping and activate social support systems to achieve better outcomes in this population. PRACTICAL IMPLICATIONS: Healthcare providers should aim to comprehend the experiences of adolescents with idiopathic scoliosis for improved clinical interactions and holistic care. Future research should prioritize coping-based interventions, to enhance adaptive coping behaviors and the well-being of this population.

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.

Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.

Adolescent idiopathic scoliosis (AIS) is a twisting deformity of the spine that occurs during periods of rapid growth in children worldwide. Children with severe cases of AIS require surgery to stop it from getting worse, presenting a significant financial burden to health systems and families. Although AIS is known to cluster in families, its genetic causes and its inheritance pattern have remained elusive. Additionally, AIS is known to be more prevalent in females, a bias that has not been explained. Advances in techniques to study the genetics underlying diseases have revealed that certain variations that increase the risk of AIS affect cartilage and connective tissue. In humans, one such variation is near a gene called Pax1, and it is female-specific. The extracellular matrix is a network of proteins and other molecules in the space between cells that help connect tissues together, and it is particularly important in cartilage and other connective tissues. One of the main components of the extracellular matrix is collagen. Yu, Kanshour, Ushiki et al. hypothesized that changes in the extracellular matrix could affect the cartilage and connective tissues of the spine, leading to AIS. To show this, the scientists screened over 100,000 individuals and found that AIS is associated with variants in two genes coding for extracellular matrix proteins. One of these variants was found in a gene called Col11a1, which codes for one of the proteins that makes up collagen. To understand the relationship between Pax1 and Col11a1, Yu, Kanshour, Ushiki et al. genetically modified mice so that they would lack the Pax1 gene. In these mice, the activation of Col11a1 was reduced in the mouse spine. They also found that the form of Col11a1 associated with AIS could not suppress the activation of a gene called Mmp3 in mouse cartilage cells as effectively as unmutated Col11a1. Going one step further, the researchers found that lowering the levels of an estrogen receptor altered the activation patterns of Pax1, Col11a1, and Mmp3 in mouse cartilage cells. These findings suggest a possible mechanism for AIS, particularly in females. The findings of Yu, Kanshour, Ushiki et al. highlight that cartilage cells in the spine are particularly relevant in AIS. The results also point to specific molecules within the extracellular matrix as important for maintaining proper alignment in the spine when children are growing rapidly. This information may guide future therapies aimed at maintaining healthy spinal cells in adolescent children, particularly girls.

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.

Incidence of back pain from initial presentation to 3 years of follow-up in subjects with untreated adolescent idiopathic scoliosis.

BACKGROUND: Although back pain may be present in subjects with adolescent idiopathic scoliosis (AIS), its natural history is unknown. Therefore, this study evaluated the incidence of back pain in scoliotic adolescents longitudinally. METHODS: This retrospective analysis examined prospectively collected pain subscale data of the Scoliosis Research Society questionnaire between the initial presentation and up to 3 years of follow-up. Consecutive subjects with AIS aged 10-18 at baseline managed by observation within the study period were included. Study subjects with at least one time point of follow-up data were considered. Alternatively, a group with physiotherapy-treated was also included for comparison. RESULTS: We enrolled 428 subjects under observation. The incidence of back pain among study subjects was 14.7%, 18.8%, and 19.0% for the first year, second year, and third year of follow-up, respectively. Most experienced mild pain (1 out of 5 points) throughout the study. Neither incidence nor intensity of pain significantly differed between subjects under observation and received physiotherapy. Additionally, study subjects with a new onset of back pain had poorer function, self-image, and mental health scores than those without pain. CONCLUSION: We investigated the incidence of back pain longitudinally in subjects suffering from AIS. Further validation of the current results is warranted.

SpineHRformer: A Transformer-Based Deep Learning Model for Automatic Spine Deformity Assessment with Prospective Validation.

The Cobb angle (CA) serves as the principal method for assessing spinal deformity, but manual measurements of the CA are time-consuming and susceptible to inter- and intra-observer variability. While learning-based methods, such as SpineHRNet+, have demonstrated potential in automating CA measurement, their accuracy can be influenced by the severity of spinal deformity, image quality, relative position of rib and vertebrae, etc. Our aim is to create a reliable learning-based approach that provides consistent and highly accurate measurements of the CA from posteroanterior (PA) X-rays, surpassing the state-of-the-art method. To accomplish this, we introduce SpineHRformer, which identifies anatomical landmarks, including the vertices of endplates from the 7th cervical vertebra (C7) to the 5th lumbar vertebra (L5) and the end vertebrae with different output heads, enabling the calculation of CAs. Within our SpineHRformer, a backbone HRNet first extracts multi-scale features from the input X-ray, while transformer blocks extract local and global features from the HRNet outputs. Subsequently, an output head to generate heatmaps of the endplate landmarks or end vertebra landmarks facilitates the computation of CAs. We used a dataset of 1934 PA X-rays with diverse degrees of spinal deformity and image quality, following an 8:2 ratio to train and test the model. The experimental results indicate that SpineHRformer outperforms SpineHRNet+ in landmark detection (Mean Euclidean Distance: 2.47 pixels vs. 2.74 pixels), CA prediction (Pearson correlation coefficient: 0.86 vs. 0.83), and severity grading (sensitivity: normal-mild; 0.93 vs. 0.74, moderate; 0.74 vs. 0.77, severe; 0.74 vs. 0.7). Our approach demonstrates greater robustness and accuracy compared to SpineHRNet+, offering substantial potential for improving the efficiency and reliability of CA measurements in clinical settings.

Predicting Progression in Adolescent Idiopathic Scoliosis at the First Visit by Integrating 2D Imaging and 1D Clinical Information.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: The prediction of curve progression in patients with adolescent idiopathic scoliosis (AIS) remains an unresolved area in orthopedic surgery. To make a rapid meaningful prediction, easily accessible multi-dimensional data at the patient's first consultation should be used. Current studies use clinical growth parameters and numerical values extracted from radiographs to compile a predictive model, leaving out the radiographs themselves. Such practice inevitably wastes a lot of information. Thus, this study aims to create a neural network that can predict AIS progression among patients with curves indicated for bracing by integrating both one-dimensional (1D) clinical and two-dimensional (2D) radiological data collected at the patient's first visit in a fully automated manner. METHODS: 513 idiopathic scoliosis patients indicated for and managed with bracing orthosis were recruited. After exclusion, 463 patients were included in deep learning analysis. Processed first-visit growth parameters and posteroanterior radiographs are used as training inputs and the curve progression outcomes obtained in follow ups are used as binary training outputs. The CapsuleNet architecture was modified and trained accordingly to make a prediction. RESULTS: The final model achieved 90% sensitivity with an overall accuracy of 73.9% in the prediction of AIS in-brace curve progression by using first-visit multi-dimensional data, outperforming conventional convolutional neural networks. CONCLUSIONS: This first-ever multidimensional-input model shows promise in serving as a screening tool for AIS in-brace curve progression. The incorporation of such a model into routine AIS diagnostic pipeline can assist orthopedics clinicians in personalizing the most appropriate management for each patient.

Electromyographic Discrepancy in Paravertebral Muscle Activity Predicts Early Curve Progression of Untreated Adolescent Idiopathic Scoliosis.

STUDY DESIGN: This study adopted a prospective cohort study design. PURPOSE: This study aimed to examine electromyogram (EMG) discrepancy in paravertebral muscle activity and scoliosis progression, determine how vertebral morphology and EMG discrepancy evolve during scoliosis progression, and identify differences in EMG activity between individuals with and without adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: Higher EMG activity is observed in the convex side of scoliotic curves, but not in populations without scoliosis, suggesting that higher EMG activity is a causative factor for curve progression. METHODS: In this study, 267 matched pairs of AIS and controls were recruited. The participants underwent EMG measurements at their first presentation and did not receive any treatment for 6 months at which point they underwent EMG and radiographs. Early curve progression was defined as >5° in Cobb angle at 6 months. The root mean square of the EMG (rms-EMG) signal was recorded with the participants in sitting and back extension. The rms-EMG ratio at the upper end vertebrae, apical vertebrae (AV), and lower end vertebrae (LEV) of the major curve was calculated. RESULTS: The rms-EMG ratio in the scoliosis cohort was high compared with that in the controls (sitting: 1.2±0.3 vs. 1.0±0.1, p<0.01; back extension: 1.1±0.2 vs. 1.0±0.1, p<0.01). An AV rms-EMG ratio in back extension, with a cutoff threshold of ≥1.5 in the major thoracic curve and ≥1.3 in the major lumbar curve, was a risk factor for early curve progression after 6 months without treatment (odds ratio, 4.1; 95% confidence interval, 2.8-5.9; p<0.01). Increases in side deviation (SD) (distance between the AV and the central sacral line) were related to a higher rms-EMG ratio in LEV of the major thoracic curve (baseline: rs=0.2, p=0.03; 6 months: rs=0.3, p<0.01). CONCLUSIONS: An EMG discrepancy was detected in the scoliosis cohort, which was related to increases in SD in the major thoracic curve. The AV rms-EMG ratio in back extension was correlated with curve progression after 6 months of no treatment.

Impact of mental health components on the development of back pain in young adults with adolescent idiopathic scoliosis.

BACKGROUND: Back pain occurs commonly in adults and is multifactorial in nature. This study aimed to assess the prevalence and intensity of back pain during young adulthood in subjects with adolescent idiopathic scoliosis (AIS), as well as factors that may be associated with its prognosis. METHODS: Subjects with AIS aged 20-39 treated conservatively were included in this study. Patient-reported outcome measures in adulthood involved episodes of back pain, and scales of self-image, depression, anxiety, and stress. Additionally, pain, self-image, and mental health scores were retrieved at the first clinic consultation. Occurrence of back pain was defined as a numeric pain rating scale ≥ 6. RESULTS: 101 participants were enrolled. The prevalence of back pain in the lifetime, past 12 months, past 6 months, past 1 month, past 7 days, and past 24 h were 37%, 35%, 31%, 27%, 23%, and 20%, respectively. Male, self-image, and depression were significant associated factors for the development of back pain at all time points. Furthermore, the analyses of the initial presentation of participants have shown that participants with back pain in adulthood were characterised by poor self-image and mental health during their adolescence. CONCLUSION: The present study addressed the natural history of back pain in young adults with conservatively treated AIS. Psychological makeup has been shown to constitute the development of back pain and is strongly hinted as an early sign of having back pain in adulthood among subjects with AIS.

Surface electromyography (sEMG) biofeedback posture training improves the physical and mental health of early adolescents with mild scoliosis: A qualitative study.

Introduction: Asymmetry in paraspinal muscle activities is observed in adolescent idiopathic scoliosis and may be of value for predicting curve progression. We have reported the effects of the surface electromyography biofeedback posture training program in improving the symmetry of paraspinal muscle activities and reducing the curve progression of early adolescents with mild scoliosis. This study further explored their subjective experience of the training program on posture correction and health-related quality of life. Methods: Using purposive sampling, 13 early adolescents aged between 11 and 13 years with mild scoliosis participated in semi-structured in-depth interviews after completing 30 sessions of training. The data were recorded, transcribed, and coded using thematic analysis with NVivo 10. Significant statements and phrases were categorized into themes and subthemes. Results: As assessed by X-ray, five early adolescents showed at least a 5° Cobb angle reduction in spinal curvature, while eight showed no significant curve progression (a Cobb angle change under 5°). Several subthemes related to the benefits of the training program on the health-related quality of life were generated, namely (a) posture correction, (b) improvement in body appearance, (c) restoration of muscle relaxation, (d) reduction in bodily pain and fatigue, (e) enhancement of self-confidence/self-image, and (f) improvement in social functioning. Conclusions: Given its positive effects, the sEMG biofeedback posture training program has the potential to be an alternative early intervention for early adolescents with mild scoliosis. Further empirical studies need to be carried out to substantiate its effectiveness and evaluate the sustainability of its benefits over time.

Biomechanical Comparison of Different Surgical Approaches for the Treatment of Adjacent Segment Diseases after Primary Transforaminal Lumbar Interbody Fusion: A Finite Element Analysis.

BACKGROUND AND OBJECTIVE: Adjacent segment disease (ASD) is a well-known complication after interbody fusion. Revision surgery is necessary for symptomatic ASD to further decompress and fix the affected segment. However, no optimal construct is accepted as a standard in treating ASD. The purpose of this study was to compare the biomechanical effects of different surgical approaches for the treatment of ASD after primary transforaminal lumbar interbody fusion (TLIF). METHODS: A finite element model of the L1-S1 was conducted based on computed tomography scan images. The primary surgery model was developed with a single-level TLIF at L4-L5 segment. The revision surgical models were developed with anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), or TLIF at L3-L4 segment. The range of motion (ROM), intradiscal pressure (IDP), and the stress in cages were compared to investigate the biomechanical influences of different surgical approaches. RESULTS: The results indicated that all the three surgical approaches can stabilize the spinal segment by reducing the ROM at revision level. The ROM and IDP at adjacent segments of revision model of TLIF was greater than those of other revision models. While revision surgery with ALIF and LLIF had similar effects on the ROM and IDP of adjacent segments. Compared among all the surgical models, cage stress in revision model of TLIF was the maximum in extension and axial rotation. CONCLUSION: The IDP at adjacent segments and stress in cages of revision model of TLIF was greater than those of ALIF and LLIF. This may be that direct extension of the surgical segment in the same direction results in stress concentration.