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.

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.

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.