Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.

Surgical treatment of neuromuscular Early Onset Scoliosis with a bilateral posterior one-way rod compared to the Spring Distraction System: study protocol for a limited-efficacy Randomized Controlled Trial (BiPOWR).

BACKGROUND: Early Onset Scoliosis (EOS) is a progressive spinal deformity in children, and a potentially life-threatening disease. "Growth-friendly" surgical techniques aim to control the deformity, while allowing the spine and trunk to maintain growth. Current "growth-friendly" systems such as the traditional growing rod (TGR) and magnetically controlled growing rod (MCGR) have limitations that reduce their efficacy and cost-effectiveness. Recently, two "growth-friendly" systems have been developed that mitigate many of these limitations, the Spring Distraction System (SDS) and the One Way Self-Expanding Rod (OWSER). The purpose of the multicenter BiPOWR trial is to investigate, describe and compare the 1-year limited-efficacy and -safety of both strategies in the treatment of neuromuscular EOS. METHODS: After informed consent, 28 neuromuscular EOS patients will be randomized to receive either the SDS or the OWSER. Patients and caregivers will be blinded to allocation until after surgery. Primary outcomes will be maintenance of coronal curve correction and the occurrence of serious adverse events. In addition, spinal growth, implant lengthening, and perioperative findings are recorded systematically. At each follow-up moment, the Early Onset Scoliosis Questionnaire (EOSQ-24) will be used to assess health-related quality of life. All outcomes will be compared between groups. DISCUSSION: The BiPOWR trial is the first randomized controlled trial that compares two specific "growth-friendly" implants in a specified EOS population. It will determine the 1-year limited-efficacy and safety of the SDS and OWSER implants. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04021784 (13-06-2019). CCMO registry: NL64018.041.17 (06-05-2019).

Methodological aspects of a randomized within-patient concurrent controlled design for clinical trials in spine surgery.

INTRODUCTION: Randomized controlled trials are considered the highest level of evidence, but their feasibility in the surgical field is severely hampered by methodological and practical issues. Concurrent comparison between the experimental and control conditions within the same patient can be an effective strategy to mitigate some of these challenges and improve generalizability, mainly by the elimination of between-patient variability and reduction of the required sample size. This article aims (1) to describe the methodological aspects of a randomized within-patient controlled trial and (2) to quantify the added value of this design, based on a recently completed randomized within-patient controlled trial on bone grafts in instrumented lumbar posterolateral spinal fusion. METHODS: Boundary conditions for the application of the randomized within-patient controlled trial design were identified. Between-patient variability was quantified by the intraclass correlation coefficient and concordance in the primary fusion outcome. Sample size, study duration and costs were compared with a classic randomized controlled trial design. RESULTS: Boundary conditions include the concurrent application of the experimental and control conditions to identical but physically separated sites. Moreover, the outcome of interest should be local, uncorrelated and independently assessable. The spinal fusion outcomes within a patient were found to be more similar than between different patients (intraclass correlation coefficient 32% and concordance 64%), demonstrating a clear effect of patient-related factors. The randomized within-patient controlled trial design allowed a reduction of the sample size to one-third of a parallel-group randomized controlled trial, thereby halving the trial duration and costs. CONCLUSION: When suitable, the randomized within-patient controlled trial is an efficient design that provides a solution to some of the considerable challenges of a classic randomized controlled trial in (spine) surgery. This design holds specific promise for efficacy studies of non-active bone grafts in instrumented posterolateral fusion surgery.

The role of the femoral component orientation on dislocations in THA: a systematic review.

INTRODUCTION: Dislocation remains a major complication in total hip arthroplasty (THA), in which femoral component orientation is considered a key parameter. New imaging modalities and definitions on femoral component orientation have been introduced, describing orientation in different planes. This study aims to systematically review the relevance of the different orientation parameters on implant stability. METHODS: A systematic review was performed according to the PRISMA guidelines to identify articles in the PubMed and EMBASE databases that study the relation between any femoral component orientation parameters and implant stability in primary THA. RESULTS: After screening for inclusion and exclusion criteria and quality assessment, nine articles were included. Definitions to describe the femoral component orientation and methodologies to assess its relevance for implant stability differed greatly, with lack of consensus. Seven retrospective case-control studies reported on the relevance of the transversal plane orientation: Low femoral- or low combined femoral and acetabular anteversion was statistical significantly related with more posterior dislocations, and high femoral- or combined femoral and acetabular anteversion with anterior dislocations in two studies. There were insufficient data on sagittal and coronal component orientation in relation to implant stability. CONCLUSION: Because of incomparable definitions, limited quality and heterogeneity in methodology of the included studies, there is only weak evidence that the degree of transverse component version is related with implant stability in primary THA. Recommendations about the optimal orientation of the femoral component in all three anatomical planes cannot be provided. Future studies should uniformly define the three-dimensional orientation of the femoral component and systematically describe implant stability.

Osteoarticular allograft reconstruction after distal radius tumor resection: Reoperation and patient reported outcomes.

BACKGROUND: The aims of this study are to evaluate the rate of wrist joint preservation, allograft retention, factors associated with reoperation and to report the patient reported outcomes after osteoarticular allograft reconstruction of the distal radius. METHODS: Retrospective chart review identified 33 patients who underwent distal radius resection followed by osteoarticular allograft reconstruction, including 27 giant cell tumors and 6 primary malignancies. Ten patients with a preserved wrist joint completed the QuickDASH, PROMIS-CA physical function, and Toronto extremity salvage score (TESS) at a median of 13 years postoperatively. RESULTS: The allograft retention rate was 89%, and an allograft fracture predisposed to conversion to wrist arthrodesis. The reoperation rate was 55% and 36% underwent wrist arthrodesis at a median of 4.2 years following index surgery. The use of locking plate fixation was associated with lower reoperation and allograft fracture rates. Patients reported a median QuickDASH of 10.2 (range: 0-52.3), a mean PROMIS physical function of 57.8 (range: 38.9-64.5) and the median TESS was 95.5 (range: 67.0-98.4). CONCLUSION: Osteoarticular allograft reconstruction results in acceptable long-term patient reported outcomes, despite a high revision rate. Allograft fixation with locking plates seems to reduce the number of reoperations and allograft fractures, along with reduction in wrist arthrodesis rates.

Specific sagittal alignment patterns are already present in mild adolescent idiopathic scoliosis.

PURPOSE: The complex three-dimensional spinal deformity in AIS consists of rotated, lordotic apical areas and neutral junctional zones that modify the spine's sagittal profile. Recently, three specific patterns of thoracic sagittal 'malalignment' were described for severe AIS. The aim of this study is to define whether specific patterns of pathological sagittal alignment are already present in mild AIS. METHODS: Lateral spinal radiographs of 192 mild (10°-20°) and 253 severe (> 45°) AIS patients and 156 controls were derived from an international consortium. Kyphosis characteristics (T4-T12 thoracic kyphosis, T10-L2 angle, C7 slope, location of the apex of kyphosis and of the inflection point) and sagittal curve types according to Abelin-Genevois were systematically compared between the three cohorts. RESULTS: Even in mild thoracic AIS, already 49% of the curves presented sagittal malalignment, mostly thoracic hypokyphosis, whereas only 13% of the (thoraco) lumbar curves and 6% of the nonscoliosis adolescents were hypokyphotic. In severe AIS, 63% had a sagittal malalignment. Hypokyphosis + thoracolumbar kyphosis occurred more frequently in high-PI and primary lumbar curves, whereas cervicothoracic kyphosis occurred more in double thoracic curves. CONCLUSIONS: Pathological sagittal patterns are often already present in curves 10°-20°, whereas those are rare in non-scoliotic adolescents. This suggests that sagittal 'malalignment' patterns are an integral part of the early pathogenesis of AIS.

Comparison of different strategies on three-dimensional correction of AIS: which plane will suffer?

PURPOSE: There are distinct differences in strategy amongst experienced surgeons from different 'scoliosis schools' around the world. This study aims to test the hypothesis that, due to the 3-D nature of AIS, different strategies can lead to different coronal, axial and sagittal curve correction. METHODS: Consecutive patients who underwent posterior scoliosis surgery for primary thoracic AIS were compared between three major scoliosis centres (n = 193). Patients were treated according to the local surgical expertise: Two centres perform primarily an axial apical derotation manoeuvre (centre 1: high implant density, convex rod first, centre 2: low implant density, concave rod first), whereas centre 3 performs posteromedial apical translation without active derotation. Pre- and postoperative shape of the main thoracic curve was analyzed using coronal curve angle, apical rotation and sagittal alignment parameters (pelvic incidence and tilt, T1-T12, T4-T12 and T10-L2 regional kyphosis angles, C7 slope and the level of the inflection point). In addition, the proximal junctional angle at follow-up was compared. RESULTS: Pre-operative coronal curve magnitudes were similar between the 3 cohorts and improved 75%, 70% and 59%, from pre- to postoperative, respectively (P < 0.001). The strategy of centres 1 and 2 leads to significantly more apical derotation. Despite similar postoperative T4-T12 kyphosis, the strategy in centre 1 led to more thoracolumbar lordosis and in centre 2 to a higher inflection point as compared to centre 3. Proximal junctional angle was higher in centres 1 and 2 (P < 0.001) at final follow-up. CONCLUSION: Curve correction by derotation may lead to thoracolumbar lordosis and therefore higher risk for proximal junctional kyphosis. Focus on sagittal plane by posteromedial translation, however, results in more residual coronal and axial deformity.

The potential of spring distraction to dynamically correct complex spinal deformities in the growing child.

PURPOSE: Current treatment of progressive early onset scoliosis involves growth-friendly instrumentation if conservative treatment fails. These implants guide growth by passive sliding or repeated lengthenings. None of these techniques provide dynamic correction after implantation. We developed the spring distraction system (SDS), by using one or multiple compressed springs positioned around a standard sliding rod, to provide active continuous distraction of the spine to stimulate growth and further correction. The purpose of this study was to determine feasibility and proof of concept of the SDS. METHODS: We developed a versatile, dynamic spring distraction system for patients who would benefit from active continuous distraction. This prospective case series evaluates four patients with exceptional and progressive congenital spine deformities. RESULTS: Four patients had a mean age of 6.8 years at surgery with a mean follow-up of 36 months (range 25-45). The mean progressive thoracic lordosis, which was the reason for initiating surgical treatment in two patients, changed from 32° lordosis preoperatively to 1° kyphosis post-operatively. During follow-up, this further improved to 32° thoracic kyphosis. In the two other patients, with cervicothorcacic scoliosis, the main coronal curve improved from 79° pre-operatively to 56° post-operatively and further improved to 42°. The mean T1-S1 spine growth during follow-up for all patients was 1.3 cm/year. There was one reoperation because of skin problems and no device-failures. CONCLUSION: These early results show the feasibility and the proof of concept of spring-based distraction as a dynamic growth-enhancing system with the potential of further correction of the deformity after implantation.

The role of sagittal pelvic morphology in the development of adult degenerative scoliosis.

PURPOSE: Pelvic morphology dictates the alignment and biomechanics of the spine. Recent observations in different types of adolescent idiopathic scoliosis indicate that individual pelvic morphology is related to the spinal levels in which scoliosis develops: primary lumbar adolescent scoliosis is associated with a higher pelvic incidence (PI) than thoracic scoliosis and non-scoliotic controls. We hypothesize that adult degenerative scoliosis (ADS) of the lumbar spine follows the same mechanical principles and is associated with a high PI. METHODS: This study used an existing CT-scan database, 101 ADS patients were sex and age matched to 101 controls. The PI was measured by two observers with multi-planar reconstruction, perpendicular to the hip-axis according to a previously validated technique. RESULTS: The PI was 54.1° ± 10.8° in ADS patients and 47.7° ± 10.8° in non-scoliotic controls (p < 0.001). The median ADS curve apex was the disc L2-3 and median curve length was 4 vertebral levels. The mean supine Cobb angle was 21° ± 8° (ranged 10°-47°). There was no significant correlation between PI and the apex level (p = 0.883), the curve length (p = 0.418) or the Cobb angle (p = 0.518). CONCLUSIONS: ADS normally develops de novo in the lumbar spine of patients with a higher PI than controls, similar to primary lumbar adolescent idiopathic scoliosis. This suggests a shared mechanical basis of both deformities. Pelvic morphology dictates spinal sagittal alignment, which determines the segments of the spine that are prone to develop scoliosis.

Cross-validation of ultrasound imaging in adolescent idiopathic scoliosis.

PURPOSE: Adolescent idiopathic scoliosis (AIS) patients are exposed to 9-10 times more radiation and a fivefold increased lifetime cancer risk. Radiation-free imaging alternatives are needed. Ultrasound imaging of spinal curvature was shown to be accurate, however, systematically underestimating the Cobb angle. The purpose of this study is to create and cross-validate an equation that calculates the expected Cobb angle using ultrasound spinal measurements of AIS patients. METHODS: Seventy AIS patients with upright radiography and spinal ultrasound were split randomly in a 4:1 ratio to the equation creation (n = 54) or validation (n = 16) group. Ultrasound angles based on the spinous processes shadows were measured automatically by the ultrasound system (Scolioscan, Telefield, Hong Kong). For thoracic and lumbar curves separately, the equation: expected Cobb angle = regression coefficient × ultrasound angle, was created and subsequently cross-validated in the validation group. RESULTS: Linear regression analysis between ultrasound angles and radiographic Cobb angles (thoracic: R2 = 0.968, lumbar: R2 = 0.923, p < 0.001) in the creation group resulted in the equations: thoracic Cobb angle = 1.43 × ultrasound angle and lumbar Cobb angle = 1.23 × ultrasound angle. With these equations, expected Cobb angles in the validation group were calculated and showed an excellent correlation with the radiographic Cobb angles (thoracic: R2 = 0.959, lumbar: R2 = 0.936, p < 0.001). The mean absolute differences were 6.5°-7.3°. Bland-Altman plots showed good accuracy and no proportional bias. CONCLUSION: The equations from ultrasound measurements to Cobb angles were valid and accurate. This supports the implementation of ultrasound imaging, possibly leading to less frequent radiography and reducing ionizing radiation in AIS patients.

The Effect of Functional Pelvic Tilt on the Three-Dimensional Acetabular Cup Orientation in Total Hip Arthroplasty Dislocations.

BACKGROUND: Anterior and posterior pelvic tilt appears to play a role in total hip arthroplasty (THA) stability. When changing from the standing to the sitting position, the pelvis typically rotates posteriorly while the hips flex and this affects the femoro-acetabular positions. This case-control study compares changes in 3-D acetabular cup orientation during functional pelvic tilt between posterior THA dislocations vs stable THAs. METHODS: Standing and sitting 3-D cup orientation was compared between fifteen posterior dislocations vs 233 prospectively followed stable THAs. 3-D cup orientation was calculated using previously validated trigonometric algorithms on biplanar radiographs. Those algorithms combine the angles in the three anatomical planes (coronal inclination, transverse version, and sagittal ante-inclination) in the standing position with the change in sagittal pelvic tilt from standing to sitting to calculate the 3-D orientation in the sitting position. RESULTS: The standing cup orientation of the dislocated THAs was only characterized by a lower coronal inclination (P = .039). Compared with the controls, from standing to sitting, they showed less posterior pelvic tilt (P < .001). This led to a significant lower coronal inclination (P < .001) and sagittal ante-inclination (P < .001) in the sitting position but similar transverse version (P = .366). CONCLUSIONS: Comparing posterior THA dislocations to stable THAs, there is a lower increase of all three orientation angles from standing to sitting. This leads to a decreased sitting coronal inclination and sagittal ante-inclination which may lead to an increased risk of impingement ensued by THA instability. By contrast, the transverse version was not significantly different in both positions. This confirms the importance of biplanar data on functional cup orientation. LEVEL OF EVIDENCE: Diagnostic, Level III.

A roadmap to surgery in osteogenesis imperfecta: results of an international collaboration of patient organizations and interdisciplinary care teams.

Background and purpose - Involvement of patient organizations is steadily increasing in guidelines for treatment of various diseases and conditions for better care from the patient's viewpoint and better comparability of outcomes. For this reason, the Osteogenesis Imperfecta Federation Europe and the Care4BrittleBones Foundation convened an interdisciplinary task force of 3 members from patient organizations and 12 healthcare professionals from recognized centers for interdisciplinary care for children and adults with osteogenesis imperfecta (OI) to develop guidelines for a basic roadmap to surgery in OI.Methods - All information from 9 telephone conferences, expert consultations, and face-to-face meetings during the International Conference for Quality of Life for Osteogenesis Imperfecta 2019 was used by the task force to define themes and associated recommendations.Results - Consensus on recommendations was reached within 4 themes: the interdisciplinary approach, the surgical decision-making conversation, surgical technique guidelines for OI, and the feedback loop after surgery.Interpretation - The basic guidelines of this roadmap for the interdisciplinary approach to surgical care in children and adults with OI is expected to improve standardization of clinical practice and comparability of outcomes across treatment centers.

Deep learning-based MR-to-CT synthesis: The influence of varying gradient echo-based MR images as input channels.

PURPOSE: To study the influence of gradient echo-based contrasts as input channels to a 3D patch-based neural network trained for synthetic CT (sCT) generation in canine and human populations. METHODS: Magnetic resonance images and CT scans of human and canine pelvic regions were acquired and paired using nonrigid registration. Magnitude MR images and Dixon reconstructed water, fat, in-phase and opposed-phase images were obtained from a single T1 -weighted multi-echo gradient-echo acquisition. From this set, 6 input configurations were defined, each containing 1 to 4 MR images regarded as input channels. For each configuration, a UNet-derived deep learning model was trained for synthetic CT generation. Reconstructed Hounsfield unit maps were evaluated with peak SNR, mean absolute error, and mean error. Dice similarity coefficient and surface distance maps assessed the geometric fidelity of bones. Repeatability was estimated by replicating the training up to 10 times. RESULTS: Seventeen canines and 23 human subjects were included in the study. Performance and repeatability of single-channel models were dependent on the TE-related water-fat interference with variations of up to 17% in mean absolute error, and variations of up to 28% specifically in bones. Repeatability, Dice similarity coefficient, and mean absolute error were statistically significantly better in multichannel models with mean absolute error ranging from 33 to 40 Hounsfield units in humans and from 35 to 47 Hounsfield units in canines. CONCLUSION: Significant differences in performance and robustness of deep learning models for synthetic CT generation were observed depending on the input. In-phase images outperformed opposed-phase images, and Dixon reconstructed multichannel inputs outperformed single-channel inputs.

Giant Cell Tumors of the Upper Extremity: Predictors of Recurrence.

PURPOSE: Giant cell tumors (GCT) of the distal radius are thought to be more aggressive than in other locations. Therefore, the aim of this study was to investigate factors associated with recurrence of GCTs in the upper extremity. METHODS: We retrospectively identified 82 patients who underwent primary surgical treatment for an upper extremity GCT. Tumors were located in the radius (n = 47), humerus (n = 17), ulna (n = 9), and hand (n = 9). Treatment consisted of either wide resection or amputation or intralesional resection with or without adjuvants. A multivariable logistic regression was performed including tumor grade, type of surgery, and tumor location, from which the percentage of contribution to the model of each variable was calculated. RESULTS: The recurrence rate after intralesional resection was 48%; after wide resection or amputation, it was 12%. Two patients developed a pulmonary metastasis (2.4%). In multivariable analysis, intralesional resection was independently associated with recurrence. Intralesional resection had a 77% contribution to predict recurrence and the distal radius location had a 16% contribution in the predictive model. CONCLUSIONS: As expected, intralesional resection was the strongest independent predictor of recurrence after surgical treatment for GCT. The distal radius location contributed to the prediction of giant cell tumor recurrence to a lesser extent. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Changes in the Position of the Junctional Vertebrae After Posterior Spinal Fusion in Adolescent Idiopathic Scoliosis: Implication in Risk Assessment of Proximal Junctional Kyphosis Development.

BACKGROUND: The development of proximal junctional kyphosis (PJK) after posterior spinal fusion in adolescent idiopathic scoliosis is a major problem. Changes in the global sagittal parameters as they relate to PJK have been reported after surgery, however, the relationships between the changes in the upper-instrumented vertebra (UIV) during and after surgery as they relate to development of PJK have not been quantified. We hypothesize that the compensatory changes in the unfused segments of the spine over time are correlated with the surgically induced changes in the UIV position. METHODS: Sixty adolescent idiopathic scoliosis patients (with at least 1-year follow-up) who underwent posterior spinal surgery were included retrospectively. Global spinal parameters were calculated using 3-dimensional models of the spine, additional parameters [proximal junctional kyphosis angle (PJKA), cervical lordosis angle] were measured manually before surgery and at 3 postoperative follow-ups. The 3-dimensional position of the vertebral body centroids was calculated for T1, UIV, and lower-instrumented vertebra at all timepoints. The sagittal position of T1, UIV, and lower-instrumented vertebra were correlated to the cervical lordosis, PJKA, lumbar lordosis, and pelvic tilt. RESULTS: The position of T1 and UIV were significantly more anterior at first erect for patients who developed PJK. The posterior shift of UIV at the most recent follow-up as compared with the preoperative position was significant in both the PJK and non-PJK cohort. A larger anterior shift in UIV at first erect correlated with a larger T1 and UIV posterior shift at the most recent follow-up. At the most recent follow-up, a more posterior position of the UIV correlated with a larger angle of PJKA (P<0.05). CONCLUSION: Both a larger anterior shift of UIV between preoperative and first erect and a more posterior position of UIV at the most recent follow-up was correlated with a higher PJKA. A larger anterior shift in the position of the UIV after surgery was associated with a higher posterior shift of UIV at the last follow-up. The surgically induced changes in the UIV are an important parameter associated with the development of PJK. LEVEL OF EVIDENCE: Level IV.

Three-dimensional pelvic incidence is much higher in (thoraco)lumbar scoliosis than in controls.

PURPOSE: The pelvic incidence (PI) is used to describe the sagittal spino-pelvic alignment. In previous studies, radiographs were used, leading to less accuracy in establishing the three-dimensional (3D) spino-pelvic parameters. The purpose of this study is to analyze the differences in the 3D sagittal spino-pelvic alignment in adolescent idiopathic scoliosis (AIS) subjects and non-scoliotic controls. METHODS: Thirty-seven female AIS patients that underwent preoperative supine low-dose computed tomography imaging of the spine, hips and pelvis as part of their general workup were included and compared to 44 non-scoliotic age-matched female controls. A previously validated computerized method was used to measure the PI in 3D, as the angle between the line orthogonal to the inclination of the sacral endplate and the line connecting the center of the sacral endplate with the hip axis. RESULTS: The PI was on average 46.8° ± 12.4° in AIS patients and 41.3° ± 11.4° in controls (p = 0.025), with a higher PI in Lenke type 5 curves (50.6° ± 16.2°) as compared to controls (p = 0.042), whereas the Lenke type 1 curves (45.9° ± 12.2°) did not differ from controls (p = 0.141). CONCLUSION: Lenke type 5 curves show a significantly higher PI than controls, whereas the Lenke type 1 curves did not differ from controls. This suggests a role of pelvic morphology and spino-pelvic alignment in the pathogenesis of idiopathic scoliosis. Further longitudinal studies should explore the exact role of the PI in the initiation and progression of different AIS types. These slides can be retrieved under Electronic Supplementary Material.

CT-based study of vertebral and intravertebral rotation in right thoracic adolescent idiopathic scoliosis.

PURPOSE: To define the longitudinal rotation axis around which individual vertebrae rotate, and to establish the various extra- and intravertebral rotation patterns in thoracic adolescent idiopathic scoliosis (AIS) patients, for better understanding of the 3D development of the rotational deformity. METHODS: Seventy high-resolution CT scans from an existing database of thoracic AIS patients (Cobb angle: 46°-109°) were included to determine the vertebral axial rotation, rotation radius, intravertebral axial rotation, and local mechanical torsion for each spinal level, using previously validated image processing techniques. RESULTS: For all levels, the longitudinal rotation axis, from which the vertebrae rotate away from the midline, was localized posterior to the spine. The axis became closer to the spine at the apex: apex, r = 11.5 ± 5.1 cm versus two levels above (radius = 15.8 ± 8.5 cm; p < 0.001) and beneath (radius = 14.2 ± 8.2 cm; p < 0.001). The vertebral axial rotation, intravertebral axial rotation, and local mechanical torsion of the vertebral bodies were largest at the apex (21.9° ± 7.4°, 8.7° ± 13.5° and 3.0° ± 2.5°) and decreased toward the neutral, junctional zones (p < 0.001). CONCLUSION: In AIS, the vertebrae rotate away around an axis that is localized posterior to the spine. The distance between this axis and the spine is minimal at the apex and increases gradually to the neutral zones. The vertebral axial rotation is accompanied by smaller amounts of intravertebral rotation and local mechanical torsion, which increases toward the apical region. The altered morphology and alignment are important for a better understanding of the 3D pathoanatomical development of AIS and better therapeutic planning for bracing and surgical intervention. These slides can be retrieved under Electronic Supplementary Material.

Club foot in association with the 22q11.2 deletion syndrome: An observational study.

The 22q11.2 Deletion Syndrome (22q11.2DS) occurs in ~1:3,000-6,000 individuals. Features less typically associated with 22q11.2DS, such as orthopedic manifestations, may be overlooked or may not lead to appropriate diagnostic testing. Club foot has a general population prevalence of ~1:1,000 and has been occasionally described in association with 22q11.2DS. Our hypothesis is that the prevalence of club foot is higher in patients with 22q11.2DS. We performed a retrospective review in two specialized 22q11.2DS centers to determine the prevalence of club foot. "True club foot" requires treatment (either conservative or surgical), therefore we only included those patients with proof of treatment. We investigated whether congenital heart disease (CHD) and/or cleft palate were associated with the presence of club foot within 22q11.2DS. The records of 1,466 patients were reviewed. Of these, 48 (3.3%) had confirmation of club foot (95% Confidence Interval: 2.4-4.3): 22 (46%) had a bilateral, 12 (25%) left, and 14 (29%) right club foot. Within our study, neither a CHD and/or a cleft palate were associated with a club foot. The prevalence of club foot in 22q11.2DS is 30 times higher than that observed in the general population. This suggests the diagnosis of club foot, especially in the face of other typically associated abnormalities of 22q11.2DS, should provoke consideration of 22q11.2DS as an underlying diagnosis, particularly in the neonatal setting.

Orthopaedic manifestations within the 22q11.2 Deletion syndrome: A systematic review.

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide phenotypic variability, including orthopaedic manifestations. The purpose of this systematic review is to increase the awareness of orthopaedic manifestations associated with 22q11.2DS. This systematic review was performed according to the PRISMA Guidelines. Original epidemiological studies on the prevalence of orthopaedic manifestations within 22q11.2DS were systematically searched for in PubMed and EMBASE. The included articles were scored according to a risk-of-bias tool, a best-evidence synthesis was performed and the prevalence data was extracted. Sixty-nine published manuscripts described 58 orthopaedic manifestations in a total of 6,055 patients. The prevalence of at least one cervical or occipital anomaly is 90.5-100% (strong evidence). Fourteen studies (n = 2,264) revealed moderate evidence for a wide scoliosis prevalence of 0.6-60%. Two studies demonstrated that 5-6.4% of all 22q11.2DS patients required surgical scoliosis correction. Fifteen studies (n = 2,115) reported a 1.1-13.3% prevalence of clubfoot with moderate evidence. Other reported orthopaedic manifestations are patellar dislocation (10-20%), juvenile rheumatic arthritis (3.75%), impaired growth and skeletal anomalies like polydactyly (1.0-3.7%), syndactyly (11-11.8%), butterfly vertebrae (11.1%) and 13 ribs (2-19%). Orthopaedic findings are important manifestations of the 22q11.2DS, both in bringing patients to diagnostic attention and in requiring surveillance and appropriate intervention. Data on these manifestations are scattered and incomprehensive. Routinely screening for cervical anomalies, scoliosis, and upper and lower limb malformations is recommended in this vulnerable group of patients.