Is quality of life after surgery for adolescent idiopathic scoliosis affected by the presence of a concomitant low-grade isthmic spondylolisthesis non-surgically treated? A retrospective cohort study.

PURPOSE: The HRQoL after surgery for adolescent idiopathic scoliosis (AIS) is not affected by the presence of concomitant isthmic spondylolisthesis non-surgically treated. Improvement in QoL after surgery was similar for AIS patients with and without concomitant spondylolisthesis. The purpose is to compare preoperative and postoperative Health-Related Quality of Life (HRQoL) scores in operated AIS patients with and without concomitant isthmic spondylolisthesis. METHODS: A retrospective study of a prospective cohort of 464 individuals undergoing AIS surgery between 2008 and 2018 was performed. All patients undergoing surgery for AIS with a minimum 2-year follow-up were included. We excluded patients with prior or concomitant surgery for spondylolisthesis. HRQoL scores were measured using the SRS-22 questionnaire. Comparisons were performed between AIS patients with versus without concomitant spondylolisthesis treated non-surgically. RESULTS: AIS surgery was performed for 36 patients (15.2 ± 2.5 y.o) with concomitant isthmic spondylolisthesis, and 428 patients (15.5 ± 2.4 y.o) without concomitant spondylolisthesis. The two groups were similar in terms of age, sex, preoperative and postoperative Cobb angles. Preoperative and postoperative HRQoL scores were similar between the two groups. HRQoL improved significantly for all domains in both groups, except for pain in patients with spondylolisthesis. There was no need for surgical treatment of the spondylolisthesis and no slip progression during the follow-up duration after AIS surgery. CONCLUSION: Patients undergoing surgical treatment of AIS with non-surgical management of a concomitant isthmic grade I spondylolisthesis can expect improvement in HRQoL scores, similar to that observed in patients without concomitant spondylolisthesis.

Predicting lowest hemoglobin level and risk of blood transfusion in spinal fusion surgery for adolescent idiopathic scoliosis.

PURPOSE: The aim of this study was to evaluate the factors associated with timing of lowest hemoglobin (Hb) level and the need for postoperative blood transfusion in posterior spinal fusion for adolescent idiopathic scoliosis. METHODS: We conducted a retrospective review of all adolescent scoliosis patients undergoing posterior spinal fusion at our institution, 2002-2014. Surgery consisted of segmental pedicle screw fixation using multi-level pedicle screws. Blood-saving techniques were used in all patients. Data included Cobb angle, pre- and postoperative Hb levels, preoperative autologous blood donation (PABD), surgery duration, and allogeneic or autologous transfusion. We used linear and logistic regressions for statistical analysis. RESULTS: There were 456 patients (402 female, 54 male), mean age 16 ± 5 years. Lowest Hb was observed on postoperative Days 2 (32.2%) and 3 (33.3%); 45.1% of postoperative transfusions occurred on Day 2. One hundred and eighty-eight (41%) patients who provided PABD had significantly lower preoperative Hb and received more transfusions intraoperatively (22.6% vs. 5.2%) and postoperatively (20% vs. 6.3%) than others. Probability of transfusion increased 49.6 (95% CI 17.40-141.37) times with preoperative Hb < 11 g/dL as compared to preoperative Hb > 14 g/dL. Probability of transfusion increased 4.3- and 9.8-fold when surgery duration exceeded 5 and 6 h, respectively. Probability of transfusion increased 3.3- and 5.3-fold with Cobb angle > 70° and 80°, respectively. CONCLUSIONS: We identified clear patient-specific perioperative parameters that affect risk of perioperative blood transfusion, including Cobb angle, PABD and preoperative Hb. Hb measurement beyond postoperative Day 3 is considered unnecessary unless clinically indicated. These slides can be retrieved under Electronic Supplementary Material.

The importance of proximal femoral angle on sagittal balance and quality of life in children and adolescents with high-grade lumbosacral spondylolisthesis.

PURPOSE: Previous studies did not specifically assess the influence of proximal femoral angle (PFA) on sagittal balance in high-grade spondylolisthesis (HGS). In addition, the relationship between PFA and quality of life (QOL) remains unknown. This study determines if increased PFA is associated with decreased QOL and sagittal balance in lumbosacral HGS. METHODS: This retrospective case-control study was performed on a cohort of 56 normal subjects and 42 patients with HGS. Initially, PFA was measured twice by 3 raters in a random subset of 30 subjects (15 normal and 15 HGS) to determine the intrarater and interrater reliability of the measurement technique. PFA was then measured for all subjects. For the 42 patients with HGS, QOL was assessed from the SRS-22 questionnaire, in addition to the evaluation of the spino-pelvic balance. RESULTS: The intrarater and interrater intraclass correlation coefficients for the measurement of PFA were, respectively, 0.951 and 0.958, suggesting excellent reliability. PFA was significantly higher in HGS patients (8.3° ± 6.7°; range - 5° to 24°) when compared to normal subjects (3.0° ± 3.1°; range - 6° to 10°). The PFA in HGS was 5.6° ± 5.6° (range - 5° to 18°), 8.9° ± 6.7° (range - 2° to 24°), and 14.0° ± 6.0° (range 7°-23°) in type 4 (balanced pelvis), type 5 (unbalanced pelvis/balanced spine), and type 6 (unbalanced pelvis and spine) subjects, respectively. There were, respectively, 23.5% (4/17), 26.3% (5/19), and 83.3% (5/6) of HGS patients with abnormal PFA ≥ 10° in type 4, type 5, and type 6 subgroups. Increased PFA in HGS patients was related with deteriorating self-image, pain, function and total SRS-22 score, as well as with increasing pelvic tilt and decreasing sacral slope. CONCLUSION: A PFA ≥ 10° is proposed as a criterion to define abnormal PFA. PFA was increased in HGS and increased along with deteriorating sagittal balance and QOL. PFA is a clinically relevant parameter of sagittal balance, and can be useful in the evaluation and management of patients with HGS.

Normal sagittal parameters of global spinal balance in children and adolescents: a prospective study of 646 asymptomatic subjects.

PURPOSE: To document values for parameters of global spinal balance in asymptomatic children and adolescents. METHODS: Multicenter prospective study of normal sagittal global spinal balance in Caucasian children and adolescents. Spinosacral angle (SSA), spinal tilt (ST), and C7 translation ratio were evaluated in 646 asymptomatic children and adolescents (276 males and 370 females). RESULTS: Mean and standard deviation for SSA, ST, and C7 translation ratio were, respectively 132.1° ± 8.3°, 93.2° ± 4.6° and -0.7 ± 8.3. Mean ± 2 standard deviations were, respectively 116°-149° for SSA and 84°-102° for ST. C7 plumbline was behind the HA (hip axis) in 78 % of subjects. Correlations between global balance and age were small (-0.17 ≤ r ≤ 0.19). CONCLUSION: Asymptomatic children and adolescents tend to stand with a stable global balance, and 95 % have an SSA and ST between 116° and 149° and 85°-102°, respectively. C7 plumbline in front of the HA is not necessarily associated with a spinal pathology.

Automated design of nighttime braces for adolescent idiopathic scoliosis with global shape optimization using a patient-specific finite element model.

Adolescent idiopathic scoliosis is a complex three-dimensional deformity of the spine, the moderate forms of which require treatment with an orthopedic brace. Existing brace design approaches rely mainly on empirical manual processes, vary considerably depending on the training and expertise of the orthotist, and do not always guarantee biomechanical effectiveness. To address these issues, we propose a new automated design method for creating bespoke nighttime braces requiring virtually no user input in the process. From standard biplanar radiographs and a surface topography torso scan, a personalized finite element model of the patient is created to simulate bracing and the resulting spine growth over the treatment period. Then, the topography of an automatically generated brace is modified and simulated over hundreds of iterations by a clinically driven optimization algorithm aiming to improve brace immediate and long-term effectiveness while respecting safety thresholds. This method was clinically tested on 17 patients prospectively recruited. The optimized braces showed a highly effective immediate correction of the thoracic and lumbar curves (70% and 90% respectively), with no modifications needed to fit the braces onto the patients. In addition, the simulated lumbar lordosis and thoracic apical rotation were improved by 5° ± 3° and 2° ± 3° respectively. Our approach distinguishes from traditional brace design as it relies solely on biomechanically validated models of the patient's digital twin and a design strategy that is entirely abstracted from empirical knowledge. It provides clinicians with an efficient way to create effective braces without relying on lengthy manual processes and variable orthotist expertise to ensure a proper correction of scoliosis.

Optimized braces for the treatment of adolescent idiopathic scoliosis: A study protocol of a prospective randomised controlled trial.

INTRODUCTION: Adolescent Idiopathic Scoliosis (AIS) is a 3D deformity of the spine that affects 3% of the adolescent population. Conservative treatments like bracing aim to halt the progression of the curve to the surgical threshold. Computer-aided design and manufacturing (CAD/CAM) methods for brace design and manufacturing are becoming increasingly used. Linked to CAD/CAM and 3D radiographic reconstruction techniques, we developed a finite element model (FEM) enabling to simulate the brace effectiveness before its fabrication, as well as a semi-automatic design processes. The objective of this randomized controlled trial is to compare and validate such FEM semi-automatic algorithm used to design nighttime Providence-type braces. METHODS AND ANALYSIS: Fifty-eight patients with AIS aged between 10 to 16-years and skeletally immature will be recruited. At the delivery stage, all patients will receive both a Providence-type brace optimized by the semi-automatic algorithm leveraging a patient-specific FEM (Test) and a conventional Providence-type brace (Control), both designed using CAD/CAM methods. Biplanar radiographs will be taken for each patient with both braces in a randomized crossover approach to evaluate immediate correction. Patients will then be randomized to keep either the Test or Control brace as prescribed with a renewal if necessary, and will be followed over two years. The primary outcome will be the change in Cobb angle of the main curve after two years. Secondary outcomes will be brace failure rate, quality of life (QoL) and immediate in-brace correction. This is a single-centre study, double-blinded (participant and outcome assessor) randomized controlled trial (RCT). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05001568.

Clinical and radiological outcomes of gradual reduction and circumferential fusion of high-grade spondylolisthesis in adolescents: a prospective cohort study of 29 young patients.

AIM: The objective of this study was to evaluate the safety and efficacy of a novel technique of formal reduction and circumferential fusion for pediatric high-grade spondylolisthesis (HGS). PURPOSE: The safety and efficacy of formal reduction for high-grade spondylolisthesis (HGS) has never been thoroughly examined. This study reports the outcomes of 29 children with HGS who underwent a procedure of gradual reduction and circumferential fusion. METHODS: 29 children (13 males, 16 females) were recruited between 2006 and 2010. Radiographic measurements (including % of slip, lumbosacral angle-LSA, pelvic incidence-PI, pelvic tilt-PT, sacral slope-SS, and proximal femoral angle-PFA) and quality of life assessment (SRS-22 questionnaire) were prospectively obtained at baseline and at the last post-operative follow-up (> 2 years post-op). Radiological measurements were used to classify patients according to the Spine Deformity Study Group (SDSG) classification. RESULTS: Mean baseline slip % was 69.9 ± 16.5%. There were 13 patients with a balanced pelvic (SDSG Type 4) and 16 with an unbalanced pelvis (SDSG Type 5 and 6). On average, a reduction of 45.5 ± 15.3% (range 20-86%) was achieved safely with no major complication. In particular, of the 29 patients, only 3 had a L5 radiculopathy postoperatively that was self-resolved at follow-up. From a radiological standpoint, we observed a mean improvement of LSA from 80.3 ± 17.9° to 91.7 ± 13.6°. We also observed a statistically significant improvement in global HRQOL, and in the function and body image domains. CONCLUSION: This prospective study suggests that formal reduction of HGS followed by circumferential fusion is safe when using a standardized surgical technique based on gradual reduction. Performing this intervention could also help improve QOL in some patients.

A modified position for optimized skeletal maturity assessment of AIS patients and its impact on 3D spinal and pelvic parameters.

PURPOSE: A hands-on-wall (HOW) position for low-dose stereoradiography of adolescent idiopathic scoliosis (AIS) patients would allow for skeletal maturity assessment of the hand and wrist. Our aims were twofold: confirm the reliability and validity of skeletal maturity assessment using the HOW radiographs and compare the spinal and pelvic 3D parameters to those of standard hands-on-cheeks (HOC) stereoradiographs. METHODS: Seventy AIS patients underwent two successive stereoradiographs and a standard hand and wrist radiograph on the same day. Patients were randomly assigned to begin with HOW and follow with HOC, or vice versa. Raters assessed digital skeletal age (DSA), Sanders Simplified Skeletal Maturity (SSMS) and Thumb Ossification Composite Index (TOCI). 3D reconstructions of the spine and pelvis bones were performed for each stereoradiograph to measure nine clinically relevant spinal and pelvic 3D parameters. RESULTS: Inter-rater and intra-rater reliabilities were excellent for DSA, SSMS and TOCI with both standard radiographs and HOW (ICC > 0.95). Strong correlation was found between ratings of both imaging types (ICC > 0.95). In the 3D reconstructions, kyphosis and sacral slope were slightly decreased in the HOW position, but within the clinical margin of error. All other parameters did not differ significantly between positions (p < 0.05). CONCLUSION: The results suggest that HOW stereoradiographs allow clinicians to assess skeletal maturity of the hand and wrist with adequate reliability and validity. We recommend that scoliosis clinics adopt the HOW position to assess skeletal maturity because there is no significant clinical impact on the spinal and pelvic evaluation, and on radiation exposure, cost or time.

COVID-19 significantly impacted initial consultation for idiopathic scoliosis.

INTRODUCTION: Since the outbreak of the COVID-19 pandemic, reduction of social activities and rapid adoption of telemedicine, decreasing face-to-face encounters seems to have negatively affected the timely Idiopathic Scoliosis (IS) referral with a spine specialist. We aim to document the progression of IS curves during COVID-19 pandemic reflected by the late presentation of patients at the initial visit with higher Cobb angles and to evaluate its influence on health-related quality of life scores. MATERIALS AND METHODS: All IS patients scheduled for surgery between April 2019 and September 2021 were recruited in a prospective cohort study. The patients were divided into five cohorts of 6 month duration each according to their booking date: 2 periods before the 1st COVID-19 wave, one period during and two periods afterwards. In each cohort, patients were divided into 3: those who were scheduled for posterior spinal fusion (PSF) at 1st visit, those booked for vertebral body tethering (VBT) at 1st visit, and those scheduled for surgery but who have failed brace treatment. Variables included age, gender, Risser grade and preoperative SRS-22 scores. Chi2 and ANOVA tests were used for comparison. RESULTS: 173 patients were analyzed. 33 patients (13.1 ± 3 y.o.) were scheduled between Apr and Sept 2019; 38 (13.1 y.o. ± 2) between Oct 2019 and Mar 2020; 31 (13.4 ± 3 y.o.) between Apr and Sept 2020; 30 (14.3 ± 2 y.o.) between Sept 2020 and Mar 2021; and 41 patients (13.8 ± 2 y.o.) between Apr and Sept 2021. Non-statistically significant differences were found between periods before, during or after the COVID-19 first wave regarding patients' age, gender, Risser grade and SRS-22 scores. Average Cobb angles of patients at their 1st visit after the beginning of the COVID-19 pandemic were significantly higher than those before COVID-19 (52.2° ± 7° and 56.6° ± 13° vs 47.8° ± 12° and 45.2° ± 13°; p = 0.0001). More patients were booked for PSF (p < 0.0000) through the five evaluated periods, while the indication of VBT or surgery in patients previously braced progressively decreased. CONCLUSION: Patients presented at the scoliosis clinic for the 1st time after the 1st COVID-19 wave with significantly larger Cobb angles, and likely contributed to an increased proportion of PSF, as the potential window for bracing or VBT was missed due to a delayed consultation.

Pre-operative parameters influencing vertebral body tethering outcomes: patient's characteristics play an important role in determining the outcomes at a minimum of 2 years post-op.

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 Chi2 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 (r2 = 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.

Differential Regulation of POC5 by ERα in Human Normal and Scoliotic Cells.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 (POC5) was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify POC5 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the POC5 gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant POC5A429V AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of POC5, which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the POC5 promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.

Cross-cultural French-Canadian adaptation and psychometric assessment of the Italian Spine Youth Quality of Life (ISYQOL) questionnaire.

BACKGROUND CONTEXT: Idiopathic scoliosis (IS) can significantly alter the quality of life of adolescents. Some of the available questionnaires in French measuring the quality of life in this population show weak psychometric properties. The newly developed Italian Spine Youth Quality of Life (ISYQOL) questionnaire promises better properties. PURPOSE: To provide a French-Canadian version of the ISYQOL and to verify its psychometric characteristics. STUDY DESIGN: Prospective validation of a cross-cultural adaptation of the ISYQOL questionnaire. PATIENT SAMPLE: A total of 111 participants with idiopathic scoliosis (77.5% female, 10-18 years old, mean Cobb angle=28°) were included in the study. OUTCOME MEASURE: The French-Canadian version of the Italian Spine Youth Quality of Life (ISYQOL-F) questionnaire. MATERIALS AND METHODS: The ISYQOL was translated into French using a forward-backward approach. We then verified the understanding of the translated items with two scoliosis experts and 10 adolescents. Afterward, 111 adolescents with IS were recruited by convenience at the scoliosis clinic and they completed the ISYQOL on three occasions (before seeing the specialist, 1 week, and 2 weeks after). Cronbach's alpha, intra-class (ICC), and Pearson correlation coefficients were used to respectively determine internal consistency, test-retest reliability, and concurrent validity with the SRS-22r and SF-12. The standard error of measurement (SEM) and 95% confidence minimal detectable change (MDC95) were also calculated. The ceiling effect was quantified as the percentage of participants who scored the maximum on ISYQOL-F. RESULTS: The ISYQOL-F showed good internal consistency with a Cronbach alpha of 0.81 and 0.85 respectively for items 1-13 (n=55; ISYQOL-F mean score ± SD = 63.9±13.5) and 1-20 (n=56; ISYQOL-F mean score ± SD=60.7±10.3). Test-retest reliability was excellent (ICC3,1=0.94). The SEM is 3.1 and the MDC95 is 8.6. Correlations between ISYQOL-F and SRS-22r and between ISYQOL-F and SF-12 were moderate for total scores (r=0.56 and 0.50 respectively, p<.001), but low for each domain (between 0.20 and 0.48, p<.05). No significant ceiling effects were observed for ISYQOL-F (≤2.5%). In contrast, ceiling effects ranged from 3.6% to 30.6% for SRS-22r and 0%-68.5% for SF-12. CONCLUSIONS: The internal consistency and reliability of ISYQOL-F are good. The total score correlates moderately with the SRS-22r and SF-12. Unlike SRS-22r, the ISYQOL-F does not appear to have a ceiling effect. The ISYQOL-F may thus be suitable to assess quality of life in a population of French-Canadian adolescents with IS.

3D Radiological Outcomes and Quality of Life of Patients With Moderate Idiopathic Scoliosis Treated With Anterior Vertebral Growth Modulation Versus Bracing: Two-Year Follow-up.

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.

A Dangerous Curve: Impact of the COVID-19 Pandemic on Brace Treatment in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Observational Cohort study. OBJECTIVES: We aim to document the abandon and irregular compliance rate towards brace treatment during the COVID-19 pandemic and its impact on AIS progression. METHODS: We reviewed a database of AIS patients recruited between March and September 2020. We included AIS patients under brace treatment according to SRS criteria. The patients were divided in 2 cohorts: those with self-reported Good-Compliance (GC) to treatment and those who had a Bad-Compliance (BC). Data analysis included biometric and radiographic data at first visit and last follow-up and percentage of progression. Unpaired student-t tests and Chi2 were used for comparison. RESULTS: 152 patients met inclusion criteria. 89 patients (age:12.1y.o.±1.4) reported good adherence to treatment, while 63 patients (age:12.7y.o.±1.8) were not compliant. Within the BC group, 18 patients reported irregular brace wear, while 45 had completely abandoned treatment (abandon rate of 29%). The GC cohort started treatment with a mean main thoracic (MT) curve of 26° and finished with 27°. The mean difference between measurements was +.65°±7.5; mean progression rate was -4.6%. However, the BC cohort started with a mean MT curve of 27° and finished with 32°, with a mean increase of +5°±8 and a mean progression rate of -13%. The differences between the 2 cohorts were statistically significant (P = .0002). Six patients from the BC group progressed and were offered surgery. CONCLUSION: The abandon rate of brace treatment in AIS significantly increased during the first wave of COVID-19 pandemic. Patients who voluntarily discontinued treatment had significant increases in curve progression and surgical indication rates. LEVEL OF EVIDENCE: III.

Biomechanical Effects of Thoracolumbosacral Orthosis Design Features on 3D Correction in Adolescent Idiopathic Scoliosis: A Comprehensive Multicenter Study.

STUDY DESIGN: Multicenter numerical study. OBJECTIVE: To biomechanically analyze and compare various passive correction features of braces, designed by several centers with diverse practices, for three-dimensional (3D) correction of adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: A wide variety of brace designs exist, but their biomechanical effectiveness is not clearly understood. Many studies have reported brace treatment correction potential with various degrees of control, making the objective comparison of correction mechanisms difficult. A Finite Element Model simulating the immediate in-brace corrective effects has been developed and allows to comprehensively assess the biomechanics of different brace designs. METHODS: Expert clinical teams (one orthotist and one orthopedist) from six centers in five countries participated in the study. For six scoliosis cases with different curve types respecting SRS criteria, the teams designed two braces according to their treatment protocol. Finite Element Model simulations were performed to compute immediate in-brace 3D correction and skin-to-brace pressures. All braces were randomized and labeled according to 21 design features derived from Society on Scoliosis Orthopaedic and Rehabilitation Treatment proposed descriptors, including positioning of pressure points, orientation of push vectors, and sagittal design. Simulated in brace 3D corrections were compared for each design feature class using ANOVAs and linear regressions (significance P ≤ 0.05). RESULTS: Seventy-two braces were tested, with significant variety in the design approaches. Pressure points at the apical vertebra level corrected the main thoracic curve better than more caudal locations. Braces with ventral support flattened the lumbar lordosis. Lateral and ventral skin-to-brace pressures were correlated with changes in thoracolumbar/lumbar Cobb and lumbar lordosis (r =- 0.53, r = - 0.54). Upper straps positioned above T10 corrected the main thoracic Cobb better than those placed lower. CONCLUSIONS: The corrective features of various scoliosis braces were objectively compared in a systematic approach with minimal biases and variability in test parameters, providing a better biomechanical understanding of individual passive mechanisms' contribution to 3D correction.

Braces Designed Using CAD/CAM Combined or Not With Finite Element Modeling Lead to Effective Treatment and Quality of Life After 2 Years: A Randomized Controlled Trial.

STUDY DESIGN: Single-center prospective randomized controlled trial. OBJECTIVE: The aim of this study was to assess the computer-aided design/manufacturing (CAD/CAM) brace design approach, with and without added finite element modeling (FEM) simulations, after 2 years in terms of clinical outcomes, 3D correction, compliance, and quality of life (QoL). SUMMARY OF BACKGROUND DATA: .: Previous studies demonstrated that braces designed using a combination of CAD/CAM and FEM induced promising in-brace corrections, were lighter, thinner, and covered less trunk surface. Yet, their long-term impact on treatment quality has not been evaluated. METHODS: One-hundred twenty adolescent idiopathic scoliosis patients were recruited following Scoliosis Research Society standardized criteria for brace treatment; 61 patients in the first subgroup (CAD) were given braces designed using CAD/CAM; 59 in the second subgroup (CAD-FEM) received braces additionally simulated and refined using a patient-specific FEM built from 3D reconstructions of the spine, rib cage and pelvis. Main thoracic (MT) and thoraco-lumbar/lumbar (TL/L) Cobb angles, sagittal curves, and apical rotations were compared at the initial visit and after 2 years. Patient compliance and QoL were tracked respectively by using embedded temperature sensors and SRS-22r questionnaires. RESULTS: Forty-four patients with CAD-FEM braces and 50 with CAD braces completed the study. Average in-brace correction was 9° MT (8° CAD-FEM, 10° CAD, P = 0.054) and 12° TL/L (same for both subgroups, P = 0.91). Out-of-brace 2-year progression from initial deformity was <4° for all 3D measurements. Sixty-six percent of all cases (30 CAD-FEM, 35 CAD) met the ≤5° curve progression criterion, 83% (38 CAD-FEM, 43 CAD) stayed <45°, and 6% (5 CAD-FEM, 1 CAD) underwent fusion surgery. 3D correction, compliance, and QoL were not significantly different between both subgroups (P > 0.05). CONCLUSION: After 2 years, patients with braces designed using CAD/CAM with/without FEM had satisfying clinical outcomes (compared to the BrAIST study), 3D corrections, compliance and QoL. A more comprehensive optimization of brace treatment remains to be accomplished. LEVEL OF EVIDENCE: 2.

Prevalence of POC5 Coding Variants in French-Canadian and British AIS Cohort.

Adolescent idiopathic scoliosis (AIS) is a complex common disorder of multifactorial etiology defined by a deviation of the spine in three dimensions that affects approximately 2% to 4% of adolescents. Risk factors include other affected family members, suggesting a genetic component to the disease. The POC5 gene was identified as one of the first ciliary candidate genes for AIS, as three variants were identified in large families with multiple members affected with idiopathic scoliosis. To assess the prevalence of p.(A429V), p.(A446T), and p.(A455P) POC5 variants in patients with AIS, we used next-generation sequencing in our cohort of French-Canadian and British families and sporadic cases. Our study highlighted a prevalence of 13% for POC5 variants, 7.5% for p.(A429V), and 6.4% for p.(A446T). These results suggest a higher prevalence of the aforementioned POC5 coding variants in patients with AIS compared to the general population.

Automatic bone maturity grading from EOS radiographs in Adolescent Idiopathic Scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a deformation of the spine and it is routinely diagnosed using posteroanterior and lateral radiographs. The Risser sign used in skeletal maturity assessment is commonly accepted in AIS patient's management. However, the Risser sign is subject to inter-observer variability and it relies mainly on the observation of ossification on the iliac crests. This study proposes a new machine-learning-based approach for Risser sign skeletal maturity assessment using EOS radiographs. Regions of interest including right and left humeral heads; left and right femoral heads; and pelvis are extracted from the radiographs. First, a total of 24 image features is extracted from EOS radiographs using a ResNet101-type convolutional neural network (CNN), pre-trained from the ImageNet database. Then, a support vector machine (SVM) algorithm is used for the final Risser sign classification. The experimental results demonstrate an overall accuracy of 84%, 78%, and 80% respectively for iliac crests, humeral heads, and femoral heads. Class activation maps using Grad-CAM were also investigated to understand the features of our model. In conclusion, our machine learning approach is promising to incorporate a large number of image features for different regions of interest to improve Risser grading for skeletal maturity. Automatic classification could contribute to the management of AIS patients.

Towards a new 3D classification for adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective analysis of consecutive cases. OBJECTIVES: To identify clinically relevant three-dimensional (3D) sub-groups for adolescent idiopathic scoliosis (AIS). Classifications for AIS are developed to assist surgeons in surgical planning and therapeutic management. However, current systems are based on two-dimensional (2D) parameters that do not completely describe the 3D deformity. Hence, variations in surgical results based on pre-operative 2D classifications may be attributed to the lack of 3D description. METHODS: Subjects from a multicenter database of AIS patients were included in this study. All patients had bi-planar radiographs and 3D reconstruction of the entire spine. A clustering algorithm based on fuzzy c-means was utilized to identify sub-groups based on the following ten parameters measured on 3D reconstructions of the spine: Cobb angle, orientation of the plane of maximum curvature of the proximal thoracic, mid-thoracic (MT) and thoracolumbar (TLL) levels, axial rotation of the apical vertebra of the MT and TLL segments, T4-T12 thoracic kyphosis, and L1-S1 lumbar lordosis. Da Vinci views were also generated and analyzed for each patient in the study. A panel of four experienced spine surgeons from the SRS 3D Scoliosis Committee reviewed and evaluated each group to determine if cluster groups were clinically distinct from each other. RESULTS: The clustering algorithm was able to detect 11 sub-groups. The population size for each cluster varied from 11 to 290. Statistically significant differences were seen between the parameters for each group. Four spine surgeons reviewed the three most representative cases of each group and unanimously agreed that each cluster group represents a sub-group that was not defined in current classifications. CONCLUSIONS: This study presents a new method of classifying AIS based on a fuzzy clustering algorithm using parameters describing the 3D characteristics of the deformity. Further clinical validation is needed to confirm the usefulness of this classification system. LEVEL OF EVIDENCE: IV.

CFTR knockdown stimulates lipid synthesis and transport in intestinal Caco-2/15 cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel highly expressed in epithelial cells of the gastrointestinal tract. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease characterized by pancreatic insufficiency, fat malabsorption, and steatorrhea. Despite the administration of pancreatic enzymes to normalize malabsorption, CF patients still experienced lipid fecal loss, nutritional deficiencies, and abnormalities in serum lipid profile, suggesting the presence of intrinsic defects in the intestinal handling of nutrients. The objective of the present study was to assess the impact of CFTR gene knockdown on intracellular lipid metabolism of the intestinal Caco-2/15 cell line. Partial CFTR gene inactivation led to cellular lipid accretion of phospholipids, triglycerides, and cholesteryl esters. Likewise, secretion of these lipid fractions was significantly increased following CFTR gene manipulation. As expected from these findings, the output of triglyceride-rich lipoproteins showed the same increasing pattern. Investigation of the mechanisms underlying these changes revealed that CFTR knockdown resulted in raised levels of apolipoproteins in cells and media and microsomal transfer protein activity, two important factors for the efficient assembly and secretion of lipoproteins. Similarly, scrutiny of the enzymatic monoacylglycerol acyltransferase and diacylglycerol acyltransferase, which exhibit dynamic function in triacylglycerol resynthesis and chylomicron formation in enterocytes, revealed a significant augmentation in their activity. Conversely, cholesterol uptake mediated by Niemann-Pick C1 like 1, Scavenger Receptor Class B Type I, and ATP-binding cassette G8 remains unaffected by genetic modification of CFTR. Collectively, these results highlight the role played by CFTR in intestinal handling of lipids and may suggest that factors other than defective CFTR are responsible for the abnormal intracellular events leading to fat malabsorption in CF patients.