Image-based discrimination of the early stages of mesenchymal stem cell differentiation.

Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells, which can be used in cellular and tissue therapeutics. MSCs cell number can be expanded in vitro, but premature differentiation results in reduced cell number and compromised therapeutic efficacies. Current techniques fail to discriminate the "stem-like" population from early stages (12 h) of differentiated MSC population. Here, we imaged nuclear structure and actin architecture using immunofluorescence and used deep learning-based computer vision technology to discriminate the early stages (6-12 h) of MSC differentiation. Convolutional neural network models trained by nucleus and actin images have high accuracy in reporting MSC differentiation; nuclear images alone can identify early stages of differentiation. Concurrently, we show that chromatin fluidity and heterochromatin levels or localization change during early MSC differentiation. This study quantifies changes in cell architecture during early MSC differentiation and describes a novel image-based diagnostic tool that could be widely used in MSC culture, expansion and utilization.

Development of Consensus-Based Best Practice Guidelines for the Peri- and Post-operative Care of Pediatric Patients with Spinal Deformity and Programmable Implanted Devices.

STUDY DESIGN: Modified Delphi consensus study. OBJECTIVE: To develop consensus-based best practices for the care of pediatric patients who have implanted programmable devices (IPDs) and require spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Implanted programmable devices (IPDs) are often present in patients with neuromuscular or syndromic scoliosis who require spine surgery. Guidelines for monitoring and interrogating these devices during the peri-operative period are not available. METHODS: A panel was assembled consisting of 25 experts (i.e., spinal deformity surgeons, neurosurgeons, neuro-electrophysiologists, cardiologists, and otolaryngologists). Initial postulates were based on literature review and results from a prior survey. Postulates addressed the following IPDs: vagal nerve stimulators (VNS), programmable ventriculo-peritoneal shunts (VPS), intrathecal baclofen pumps (ITBP), cardiac pacemakers and implantable cardioverter-defibrillators (ICD), deep brain stimulators (DBS), and cochlear implants. Cardiologist and otolaryngologists participants responded only to postulates on cardiac pacemakers or cochlear implants, respectively. Consensus was defined as ≥80% agreement, items that did not reach consensus were revised and included in subsequent rounds. A total of three survey rounds and one virtual meeting were conducted. RESULTS: Consensus was reached on 39 total postulates across six IPD types. Postulates addressed general spine surgery considerations, use of intraoperative monitoring and cautery, use of magnetically-controlled growing rods (MCGRs), and use of an external remote controller to lengthen MCGRs. Across IPD types, consensus for the final postulates ranged from 94.4-100%. Overall, experts agreed that MCGRs can be surgically inserted and lengthened in patients with a variety of IPDs and provided guidance for the use of intraoperative monitoring and cautery, which varied between IPD types. CONCLUSION: Spinal deformity correction surgery often benefits from the use of intraoperative monitoring, monopolar and bipolar cautery, and MCGRs. Final postulates from this study can inform the peri- and post-operative practices of spinal deformity surgeons who treat patients with both scoliosis and IPDs. LEVEL OF EVIDENCE: V- Expert opinion.

The Prevalence of Hip Dysplasia on Radiographs for Adolescent Idiopathic Scoliosis.

BACKGROUND: During radiographic assessment of adolescent idiopathic scoliosis (AIS), upright images frequently capture the hip. The purpose of this study was to assess the prevalence of radiographic hip dysplasia on postero-anterior (PA) scoliosis radiographs, as defined as a lateral center edge angle (LCEA) ≤25 degrees. METHODS: All patients with upright PA scoliosis radiographs over a one-year study period at a single tertiary academic medical center (2020 to 2021) were included in the study. Radiographs containing the hip joints were annotated by 3 reviewers for left and right LCEA, and triradiate cartilage (TRC) status. Inter-rater reliability was determined among the 3 reviewers. RESULTS: Two hundred fifty patients {500 hips, 75.6% female, median age 14 [interquartile range (IQR)=3]} had PA scoliosis radiographs that captured the hip, which qualified for analysis. Seventy-four hips (14.8%) demonstrated evidence of dysplasia (LCEA ≤25 deg) in 55/250 patients (22%). The median LCEA was significantly lower in the dysplastic hip cohort (23.9 deg, IQR=4.8 deg), compared with those without dysplasia (33 deg IQR=7.3 deg; P=0.001). A higher percentage of dysplastic hip patients were female than male (72.7% vs. 27.3%). Patients with bilateral dysplasia had a similar LCEA ( 22.9 deg) [to those with unilateral dysplasia (22.9 deg left, 23.9 deg right, P=0.689)]. CONCLUSIONS: In a cohort of 250 AIS patients, 22% demonstrated evidence of hip dysplasia, as defined as an LCEA ≤2 degrees. The dysplastic patients were more likely to be female. Screening for hip symptomatology in AIS patients may be of benefit, considering the frequency of radiographic hip dysplasia in this population. LEVEL OF EVIDENCE: III. Type of Evidence: diagnostic.

Learning Morphological, Spatial, and Dynamic Models of Cellular Components.

In this chapter, we describe protocols for using the CellOrganizer software on the Jupyter Notebook platform to analyze and model cell and organelle shape and spatial arrangement. CellOrganizer is an open-source system for using microscope images to learn statistical models of the structure of cell components and how those components are organized relative to each other. Such models capture the statistical variation in the organization of cellular components by jointly modeling the distributions of their number, shape, and spatial distributions. These models can be created for different cell types or conditions and compared to reflect differences in their spatial organizations. The models are also generative, in that they can be used to synthesize new cell instances reflecting what a model learned and to provide well-structured cell geometries that can be used for biochemical simulations.

A multicenter evaluation of the time and travel burden on families with children treated for early-onset scoliosis.

PURPOSE: Patients who undergo growth-friendly (GF) treatment for early-onset scoliosis (EOS) undergo multiple clinical and surgical encounters. We sought to quantify the associated temporal and travel burden and estimate subsequent cost. METHODS: Four centers in an international study group combined data on EOS patients who underwent surgical GF treatment from 2006 to 2021. Data collected included demographics, scoliosis etiology, GF implant, encounter type, and driving distance. We applied 2022 IRS and BLS data or $0.625/mile and $208.2/day off work to calculate a relative financial burden. RESULTS: A total of 300 patients were analyzed (55% female). Etiologies were: congenital (33.3%), idiopathic (18.7%), neuromuscular (30.7%), and syndromic (17.3%). The average age at the index procedure was 5.5 years. For the 300 patients, 5899 encounters were recorded (average 18 encounters/patient). Aggregate encounter types were 2521 clinical office encounters (43%), 2045 surgical lengthening encounters (35%), 1157 magnetic lengthening encounters (20%), 149 spinal fusions (3%), and 27 spinal fusion revisions (0.5%). When comparing patients by scoliosis etiology or by GF implant type, no significant differences were noted in the total number of encounters or average travel distance. Patients traveled a median round trip distance of 158 miles/encounter between their homes and treating institutions (range 2.4-5654 miles), with a cumulative median distance of 2651 miles for the entirety of their treatment (range 29-90,552 miles), at an estimated median cost of $1656.63. The mean number of days off work was 18 (range 3-75), with an associated loss of $3643.50 in income. CONCLUSION: Patients with EOS averaged 18 encounters for GF surgical treatment. These patients and their families traveled a median distance of 158 miles/encounter, with an estimated combined mileage and loss of income of $5300.

3DCellComposer - A Versatile Pipeline Utilizing 2D Cell Segmentation Methods for 3D Cell Segmentation.

Background: Cell segmentation is crucial in bioimage informatics, as its accuracy directly impacts conclusions drawn from cellular analyses. While many approaches to 2D cell segmentation have been described, 3D cell segmentation has received much less attention. 3D segmentation faces significant challenges, including limited training data availability due to the difficulty of the task for human annotators, and inherent three-dimensional complexity. As a result, existing 3D cell segmentation methods often lack broad applicability across different imaging modalities. Results: To address this, we developed a generalizable approach for using 2D cell segmentation methods to produce accurate 3D cell segmentations. We implemented this approach in 3DCellComposer, a versatile, open-source package that allows users to choose any existing 2D segmentation model appropriate for their tissue or cell type(s) without requiring any additional training. Importantly, we have enhanced our open source CellSegmentationEvaluator quality evaluation tool to support 3D images. It provides metrics that allow selection of the best approach for a given imaging source and modality, without the need for human annotations to assess performance. Using these metrics, we demonstrated that our approach produced high-quality 3D segmentations of tissue images, and that it could outperform an existing 3D segmentation method on the cell culture images with which it was trained. Conclusions: 3DCellComposer, when paired with well-trained 2D segmentation models, provides an important alternative to acquiring human-annotated 3D images for new sample types or imaging modalities and then training 3D segmentation models using them. It is expected to be of significant value for large scale projects such as the Human BioMolecular Atlas Program.

Expanding the coverage of spatial proteomics: a machine learning approach.

MOTIVATION: Multiplexed protein imaging methods use a chosen set of markers and provide valuable information about complex tissue structure and cellular heterogeneity. However, the number of markers that can be measured in the same tissue sample is inherently limited. RESULTS: In this paper, we present an efficient method to choose a minimal predictive subset of markers that for the first time allows the prediction of full images for a much larger set of markers. We demonstrate that our approach also outperforms previous methods for predicting cell-level protein composition. Most importantly, we demonstrate that our approach can be used to select a marker set that enables prediction of a much larger set than could be measured concurrently. AVAILABILITY AND IMPLEMENTATION: All code and intermediate results are available in a Reproducible Research Archive at https://github.com/murphygroup/CODEXPanelOptimization.

Intraoperative Radiation Exposure in Adolescent Idiopathic and Neuromuscular Scoliosis.

BACKGROUND: Intraoperative imaging is often used to aid pedicle screw placement during scoliosis operations. Higher rates of cancer and death have been observed in orthopaedic surgeons and radiation technologists, including a fourfold higher rate of breast cancer in female orthopaedic surgeons. The purpose of this study was to evaluate variability in intraoperative radiation during spinal fusions for both adolescent idiopathic scoliosis (AIS) and neuromuscular scoliosis (NMS). METHODS: A retrospective review of posterior spinal fusion and segmental spinal instrumentation for scoliosis performed by pediatric orthopaedic surgeons from 2017 to 2019 at a single institution was performed. Inclusion criteria included: a diagnosis of AIS or NMS and patients between 8 and 18 years of age. Exclusion criteria included: revision surgery, use of intraoperative navigation, and patients younger than 10 at the time of scoliosis onset within the AIS cohort. Data collected included: preoperative curve, body mass index (BMI), number of levels fused, number of Ponte osteotomies, and fluoroscopy time. One-way analysis of variance tests, Bonferroni post hoc tests, independent t tests, and Pearson correlations were utilized with significance determined at the 95% confidence level ( a = 0.05). RESULTS: A total of 148 patients were included in the study. The average fluoroscopy time was 143 ± 67 seconds. Patients with NMS had higher average fluoroscopy times (193 ± 75 s) compared with patients with AIS (129 ± 58 s, P < 0.001). In patients with AIS, fluoroscopy time correlated to the patient's preoperative curve ( r = 0.182, P = 0.050). Patients with AIS with fewer than 12 levels fused had significantly less radiation exposure than those with 12 or more levels fused ( P = 0.01). When controlling for the number of levels fused, patients with AIS with higher BMIs had significantly greater fluoroscopy times ( P = 0.001). In patients with NMS, fluoroscopy time negatively correlated with BMI ( r = -0.459, P = 0.009) and positively correlated with a preoperative curve ( r = 0.475, P = 0.007). CONCLUSION: Fluoroscopy times vary greatly during adolescent spinal fusions for scoliosis. Longer fluoroscopy times are correlated with: NMS diagnosis, larger preoperative curve, BMI, and number of levels fused. Surgeons' knowledge of factors affecting fluoroscopy time will increase awareness and may be the first step in decreasing intraoperative radiation risks. LEVEL OF EVIDENCE: Level III; Therapeutic-a retrospective study.

Five Inhibitory Receptors Display Distinct Vesicular Distributions in Murine T Cells.

T cells can express multiple inhibitory receptors. Upon induction of T cell exhaustion in response to a persistent antigen, prominently in the anti-tumor immune response, many are expressed simultaneously. Key inhibitory receptors are CTLA-4, PD-1, LAG3, TIM3, and TIGIT, as investigated here. These receptors are important as central therapeutic targets in cancer immunotherapy. Inhibitory receptors are not constitutively expressed on the cell surface, but substantial fractions reside in intracellular vesicular structures. It remains unresolved to which extent the subcellular localization of different inhibitory receptors is distinct. Using quantitative imaging of subcellular distributions and plasma membrane insertion as complemented by proximity proteomics and biochemical analysis of the association of the inhibitory receptors with trafficking adaptors, the subcellular distributions of the five inhibitory receptors were discrete. The distribution of CTLA-4 was most distinct, with preferential association with lysosomal-derived vesicles and the sorting nexin 1/2/5/6 transport machinery. With a lack of evidence for the existence of specific vesicle subtypes to explain divergent inhibitory receptor distributions, we suggest that such distributions are driven by divergent trafficking through an overlapping joint set of vesicular structures. This extensive characterization of the subcellular localization of five inhibitory receptors in relation to each other lays the foundation for the molecular investigation of their trafficking and its therapeutic exploitation.

Five inhibitory receptors display distinct vesicular distributions in T cells.

T cells can express multiple inhibitory receptors. Upon induction of T cell exhaustion in response to persistent antigen, prominently in the anti-tumor immune response, many are expressed simultaneously. Key inhibitory receptors are CTLA-4, PD-1, LAG3, TIM3 and TIGIT, as investigated here. These receptors are important as central therapeutic targets in cancer immunotherapy. Inhibitory receptors are not constitutively expressed on the cell surface, but substantial fractions reside in intracellular vesicular structures. It remains unresolved to which extent the subcellular localization of different inhibitory receptors is distinct. Using quantitative imaging of subcellular distributions and plasma membrane insertion as complemented by proximity proteomics and a biochemical analysis of the association of the inhibitory receptors with trafficking adaptors, the subcellular distributions of the five inhibitory receptors were discrete. The distribution of CTLA-4 was most distinct with preferential association with lysosomal-derived vesicles and the sorting nexin 1/2/5/6 transport machinery. With a lack of evidence for the existence of specific vesicle subtypes to explain divergent inhibitory receptor distributions, we suggest that such distributions are driven by divergent trafficking through an overlapping joint set of vesicular structures. This extensive characterization of the subcellular localization of five inhibitory receptors in relation to each other lays the foundation for the molecular investigation of their trafficking and its therapeutic exploitation.

A Comparative Analysis of Revision Surgery Before or After 2 Years After Graduation From Growth-friendly Surgery for Early Onset Scoliosis.

INTRODUCTION: After discontinuation of growth-friendly (GF) surgery for early onset scoliosis, patients are termed graduates: they undergo a spinal fusion, are observed after final lengthening with GF implant maintenance, or are observed after GF implant removal. The purpose of this study was to compare the rates of and reasons for revision surgery in two cohorts of GF graduates: before or after 2 years of follow-up from graduation. METHODS: A pediatric spine registry was queried for patients who underwent GF spine surgery with a minimum of 2 years of follow-ups after graduation by clinical and/or radiographic evidence. Scoliosis etiology, graduation strategy, number of, and reasons for revision surgery were queried. RESULTS: There were 834 patients with a minimum of 2-year follow-up after graduation who were analyzed. There were 241 (29%) congenital, 271 (33%) neuromuscular, 168 (20%) syndromic, and 154 (18%) idiopathic. 803 (96%) had traditional growing rod/vertical expandable titanium rib as their GF construct and 31 (4%) had magnetically controlled growing rod. Five hundred ninety-six patients (71%) underwent spinal fusion at graduation, 208 (25%) had GF implants retained, and 30 (4%) had GF implants removed.In the entire cohort, there were 108/834 (13%) patients who underwent revision surgery. Of the revisions, 71/108 (66%) occurred as acute revisions (ARs) between 0 and 2 years from graduation (mean 0.6 y), and the most common AR indication was infection (26/71, 37%). The remaining 37/108 (34%) patients underwent delayed revision (DR) surgery >2 years (mean 3.8 y) from graduation, and the most common DR indication was implant issues (17/37, 46%).Graduation strategy affected revision rates. Of the 596 patients with spinal fusion as a graduation strategy, 98/596 (16%) underwent revision, compared with only 8/208 (4%) patients who had their GF implants retained, and 2/30 (7%) that had their GF implants removed ( P ≤ 0.001).A significantly higher percentage of the ARs had a spinal fusion as the graduation strategy (68/71, 96%) compared with 30/37 DRs, (81%, P = 0.015). In addition, the 71 patients who underwent AR undergo more revision surgeries (mean: 2, range: 1 to 7) than 37 patients who underwent DR (mean: 1, range: 1 to 2) ( P = 0.001). CONCLUSION: In this largest reported series of GF graduates to date, the overall risk of revision was 13%. Patients who undergo a revision at any time, as well as ARs in particular, are more likely to have a spinal fusion as their graduation strategy. Patients who underwent AR, on average, undergo more revision surgeries than patients who underwent DR. LEVEL OF EVIDENCE: Level III, comparative.

Definition of Tweener: Consensus Among Experts in Treating Early-onset Scoliosis.

BACKGROUND: The term "Tweener" is colloquially used to refer to early-onset scoliosis (EOS) patients whose age and development make them candidates for multiple surgical options. The purpose of this study was to establish expert consensus on a definition to formally characterize the Tweener population. METHODS: A 3-round survey of surgeons in an international EOS study group was conducted. Surgeons were provided with various patient characteristics and asked if each was part of their definition for Tweener patients. Responses were analyzed for consensus (≥70%), near-consensus (60% to 69%), and no consensus (<60%). RESULTS: Consensus was reached (89% of respondents) for including chronological age in the Tweener definition; 8 to 10 years for females and 9 to 11 years for males. Surgeons agreed for inclusion of Sanders score, particularly Sanders 2 (86.0%). Patients who have reached Sanders 4, postmenarche, or have closed triradiate cartilage should not be considered Tweeners. Bone age range of 8 years and 10 months to 10 years and 10 months for females (12 y for males) could be part of the Tweener definition. CONCLUSIONS: This study suggests that the Tweener definition could be the following: patients with open triradiate cartilage who are not postmenarche and have not reached Sanders 4, and if they have one of the following: Sanders 2 or chronological age 8 to 10 years for females (9 to 11 y for males) or bone age 8 years and 10 months to 10 years and 10 months for females (12 y for males). This definition will allow for more focused and comparative research on this population. LEVEL OF EVIDENCE: Level V-expert opinion.

Basal body organization and cell geometry during the cell cycle in Tetrahymena thermophila.

Tetrahymena thermophila possesses arrays of motile cilia that promote fluid flow for cell motility. These consist of intricately organized basal bodies (BBs) that nucleate and position cilia at the cell cortex. Tetrahymena cell geometry and spatial organization of BBs play important roles in cell size, swimming, feeding, and division. How cell geometry and BB organization are established and maintained remains poorly understood, and prior studies have been limited due to difficulties in accurate BB identification and small sample size. We therefore developed an automated image processing pipeline that segments single cells, distinguishes unique BB populations, assigns BBs into distinct ciliary rows, and distinguishes new from mature BBs. We identified unique features to describe the variation of cell shape and BB spatial organization in unsynchronized single-cell images. The results reveal asymmetries in BB distribution and ingression of the cytokinetic furrow within the cell. Moreover, we establish novel spatial and temporal waves in new BB assembly through the cell cycle. Finally, we used measurements from single cells across the cell cycle to construct a generative model that allows synthesis of movies depicting single cells progressing through the cell cycle. Our approach is expected to be of particular value for characterizing Tetrahymena mutants.

Evaluation of cell segmentation methods without reference segmentations.

Cell segmentation is a cornerstone of many bioimage informatics studies, and inaccurate segmentation introduces error in downstream analysis. Evaluating segmentation results is thus a necessary step for developing segmentation methods as well as for choosing the most appropriate method for a particular type of sample. The evaluation process has typically involved comparison of segmentations with those generated by humans, which can be expensive and subject to unknown bias. We present here an approach to evaluating cell segmentation methods without relying upon comparison to results from humans. For this, we defined a number of segmentation quality metrics that can be applied to multichannel fluorescence images. We calculated these metrics for 14 previously described segmentation methods applied to datasets from four multiplexed microscope modalities covering five tissues. Using principal component analysis to combine the metrics, we defined an overall cell segmentation quality score and ranked the segmentation methods. We found that two deep learning-based methods performed the best overall, but that results for all methods could be significantly improved by postprocessing to ensure proper matching of cell and nuclear masks. Our evaluation tool is available as open source and all code and data are available in a Reproducible Research Archive.

Improving and evaluating deep learning models of cellular organization.

MOTIVATION: Cells contain dozens of major organelles and thousands of other structures, many of which vary extensively in their number, size, shape and spatial distribution. This complexity and variation dramatically complicates the use of both traditional and deep learning methods to build accurate models of cell organization. Most cellular organelles are distinct objects with defined boundaries that do not overlap, while the pixel resolution of most imaging methods is n sufficient to resolve these boundaries. Thus while cell organization is conceptually object-based, most current methods are pixel-based. Using extensive image collections in which particular organelles were fluorescently labeled, deep learning methods can be used to build conditional autoencoder models for particular organelles. A major advance occurred with the use of a U-net approach to make multiple models all conditional upon a common reference, unlabeled image, allowing the relationships between different organelles to be at least partially inferred. RESULTS: We have developed improved Generative Adversarial Networks-based approaches for learning these models and have also developed novel criteria for evaluating how well synthetic cell images reflect the properties of real images. The first set of criteria measure how well models preserve the expected property that organelles do not overlap. We also developed a modified loss function that allows retraining of the models to minimize that overlap. The second set of criteria uses object-based modeling to compare object shape and spatial distribution between synthetic and real images. Our work provides the first demonstration that, at least for some organelles, deep learning models can capture object-level properties of cell images. AVAILABILITY AND IMPLEMENTATION: http://murphylab.cbd.cmu.edu/Software/2022_insilico. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Trends in the Utilization of Implants in Index Procedures for Early Onset Scoliosis From the Pediatric Spine Study Group.

INTRODUCTION: Because of the relative rarity of Early Onset Scoliosis (EOS) cases, patient registries were developed to combine clinical information from multiple institutions to maximize patient care and outcomes. This study examines the history and trends regarding the use of growth-friendly devices for index surgical procedures in EOS patients within the Pediatric Spine Study Group database. METHODS: All index growth-friendly implants were queried from registry inception until October 2020. EOS etiology, device/implant type, and geographic area/institution for each procedure were recorded. RESULTS: From 1994 to 2020, 2786 patients underwent index surgery at a mean age of 6.2±2.9 years. There were 908 traditional growing rods (TGR) (32.3%), 922 vertical expandable prosthetic titanium rib devices (VEPTR) (33.1%), 5 hybrid VEPTR/TGR (0.18%), and 951 magnetically controlled growing rods (MCGR) (34.2%) index implants. Fifty-six different institutions reported an index implant, and 5 accounted for 823 (30%) of the cases during the study period. Institutions in the Northeast accounted for more index implants than other regions of the United States. There was a 40% increase in index implant insertions annually when comparing 1994 (3 implants/1 center) to 2018 (234 implants/56 centers), ( P <0.001). Beginning in 2009, there was a 90.9% decrease in the number of TGR/VEPTR procedures (2009: 156 implants/32 centers; 2019: 22 implants/49 centers P =0.001), and a 479% increase in MCGR (2009: 1 implant/1 center; 2018: 197 implants/34 centers ( P =0.005). The overall number of growth-friendly index procedures performed in 2019 (150/49 centers) decreased 34.5% when compared to 2018 (234/48 centers). CONCLUSION: The number of growth-friendly implants reported in the Pediatric Spine Study Group registry as the initial surgical management of EOS increased markedly over the past 20 years. MCGR is currently the predominant type of device utilized for index surgical procedures by group members, surpassing the use of VEPTR and TGR in 2014. There was a significant decrease in index growth-friendly procedures in 2019 compared to 2018. LEVEL OF EVIDENCE: Level IV.

Contraindications to magnetically controlled growing rods: consensus among experts in treating early onset scoliosis.

PURPOSE: The purpose of this study was to describe contraindications to the magnetically controlled growing rod (MCGR) in patients with early onset scoliosis (EOS) by establishing consensus amongst expert surgeons who treat these patients frequently. METHODS: Nine pediatric spine surgeons from an international EOS study group participated in semi-structured interviews via email to identify factors that influence decision making in the use of MCGR. A 39-question survey was then developed to specify these factors as contraindications for MCGR-these included patient age and size, etiology, medical comorbidities, coronal and sagittal curve profiles, and skin and soft tissue characteristics. Pediatric spine surgeons from the EOS international study group were invited to complete the survey. A second 29-item survey was created to determine details and clarify results from the first survey. Responses were analyzed for consensus (> 70%), near consensus (60-69%), and no consensus/variability (< 60%) for MCGR contraindication. RESULTS: 56 surgeons of 173 invited (32%) completed the first survey, and 64 (37%) completed the second survey. Responders had a mean of over 15 years in practice (range 1-45) with over 6 years of experience with using MCGR (range 2-12). 71.4% of respondents agreed that patient size characteristics should be considered as contraindications, including BMI (81.3%) and spinal height (84.4%), although a specific BMI range or a specific minimum spinal height were not agreed upon. Among surgeons who agreed that skin and soft tissue problems were contraindications (78.6%), insufficient soft tissue (98%) and skin (89%) to cover MCGR were specified. Among surgeons who reported curve stiffness as a contraindication (85.9%), there was agreement that this curve stiffness should be defined by clinical evaluation (78.2%) and by traction films (72.3%). Among surgeons who reported sagittal curve characteristics as contraindications, hyperkyphosis (95.3%) and sagittal curve apex above T3 (70%) were specified. Surgeons who indicated the need for repetitive MRI as a contraindication (79.7%) agreed that image quality (72.9%) and not patient safety (13.6%) was the concern. In the entire cohort, consensus was not achieved on the following factors: patient age (57.4%), medical comorbidities (46.4%), etiology (53.6%), and coronal curve characteristics (58.9%). CONCLUSION: Surgeon consensus suggests that MCGR should be avoided in patients who have insufficient spinal height to accommodate the MCGR, have potential skin and soft tissue inadequacy, have too stiff a spinal curve, have too much kyphosis, and require repetitive MRI, particularly of the spine. Future data-driven studies using this framework are warranted to generate more specific criteria (e.g. specific degrees of kyphosis) to facilitate clinical decision making for EOS patients. LEVEL OF EVIDENCE: Level V-expert opinion.

Pelvic fixation is not always necessary in children with cerebral palsy scoliosis treated with growth-friendly instrumentation.

PURPOSE: A previous study showed that patients with neuromuscular scoliosis who underwent fusion to L5 had excellent coronal curve correction and improvement in pelvic obliquity (PO) when preoperative L5 tilt was < 15°. Our purpose was to identify indications to exclude the pelvis in children with cerebral palsy (CP) scoliosis treated with growing-friendly instrumentation. METHODS: In a retrospective cohort study, children with CP scoliosis treated with TGR, MCGR, or VEPTR with minimum 2-year follow-up were identified from a multicenter database. RESULTS: 27 patients with distal spine anchors (DSA) and 71 patients with distal pelvic anchors (DPA) placed at the index surgery were analyzed. The DSA group had a lower pre-index PO (9° vs 16°, P = 0.0001). Most recent radiographic data were similar except the DSA patients had a smaller major curve (47° vs 58°, P = 0.038). 6 (22%) DSA patients underwent extension of the instrumentation to the pelvis (DSA-EXT), most commonly at final fusion (5 patients). DSA-EXT patients had a higher pre-index L5 tilt than patients who did not require extension (DSA-NO EXT) (19° vs 10°, P = 0.009). Sub-analysis showed a lower major curve at most recent follow-up in the DSA-EXT group compared to the DPA group (33° vs 58°, P = 0.021). The DSA-EXT group had a higher number of complications per patient compared to the DSA-NO EXT group (2.3 vs 1.1, P = 0.029). CONCLUSION: Pre-index L5 tilt ≤ 10° and PO < 10° may be indications to exclude the pelvis in children with CP scoliosis treated with growth-friendly instrumentation. DSA may provide better long-term control of the major curve than DPA.

Baclofen Pump Use: Complications After Growth-friendly Instrumentation for Early-onset Scoliosis.

BACKGROUND: Patients with early-onset scoliosis (EOS) and spasticity may receive treatment with an intrathecal baclofen pump. We assessed how baclofen pumps are associated with the odds of complications and secondary interventions after growth-friendly (GF) spine surgery for EOS and analyzed infectious complications within the pump cohort. METHODS: Using a prospectively maintained, international multicenter database, we studied patients with neuromuscular EOS with baclofen pumps who underwent GF spine surgery from 2002 through 2019 (n=25). Baclofen pumps were implanted before GF instrumentation in 18 patients, during in 2 patients, and after in 5 patients. Patients with existing pumps at initial GF spine surgery were matched 1:3 with 54 patients (control group) without pumps according to treatment center, year of surgery, diagnosis, surgery type, and preoperative curve magnitude. Univariate analysis and multivariate logistic regression were performed to compare complications and secondary interventions between the 2 cohorts. RESULTS: Patients with baclofen pumps had 4.8 times the odds [95% confidence interval (CI): 1.5-16] of experiencing any complication within 1 year after initial GF spine surgery compared with controls. During mean follow-up of 6.9±4.3 years, they had 4.7 times the odds (95% CI: 1.3-16) of deep surgical site infection and 5.6 times the odds (95% CI: 1.2-26) of spinal rod removal after any complication. Differences in rates of mechanical complication, such as rod migration and breakage, were nonsignificant between the 2 groups. For the 9 patients (50%) with pumps who experienced infections, the most common microorganisms were Staphylococcus aureus (4 patients) and Pseudomonas aeruginosa (2). The pump/catheter was revised or removed, in addition to antibiotic therapy or surgical irrigation and debridement, in 2 patients. CONCLUSIONS: Among patients with neuromuscular EOS, those with baclofen pumps are much more likely to experience complications within 1 year after GF spine surgery. They are also more likely to have deep surgical site infections, with S. aureus and P. aeruginosa being the most common causative organisms, and to require spinal rod removal. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Mechanical Failure of 2 Cannulated Screw Fixation for Unstable SCFE: A Case Report.

CASE: A 13-year-old obese boy presented with an acute-on-chronic unstable left slipped capital femoral epiphysis (SCFE). He underwent in situ surgical fixation with two 6.5-mm fully threaded cannulated screws. At 6 months, he presented with mechanical failure of both screws. He underwent screw removal, revision in situ fixation, a peritrochanteric flexion and internal rotational osteotomy, and an open femoroplasty. The osteotomy healed at 6 weeks. The femoral physis took an additional year to close. CONCLUSION: This case highlights an uncommon complication of in situ pinning of SCFE, discusses revision fixation options, and suggests possible prolonged physeal closure in severe slips.