Shriners Hospitals for Children

Between 60 and 80% of adults with osteogenesis imperfecta (OI) experience chronic pain and associated interference. Currently available pain therapies often provide marginal efficacy. Mindful self-compassion (MSC) has emerged as a promising intervention for coping with chronic pain. We conducted a single-center 8-week pilot intervention study to assess the feasibility and acceptability of a MSC program among adults with OI and co-occurring chronic pain. Individuals attended the validated MSC course consisting of 8 weekly virtual 2-h sessions. Participants completed a battery of validated questionnaires assessing pain, various aspects of well-being, and physical function at baseline and post-intervention. Participants wore the ActiGraph GT9X Link watch to measure sleep duration and sleep efficiency. Seven adults with OI and co-occurring pain participated in the MSC program. The program was feasible, as indicated by high attendance and high questionnaire completion rates. Participants reported a mean ± standard deviation(SD) of 3.5 out of 5 ± 0.4 on the Intervention Acceptability Framework. 86% (6/7) of participants found the MSC program to be acceptable. While our pilot study was not powered to show efficacy, we observed a decrease in pain interference on the PROMIS pain interference questionnaire (mean 55.9 ± 5.5 at baseline vs. 50.0 ± 7.3 at 8weeks). Implementation of the MSC program is feasible as a potential therapeutic option to address chronic pain in OI.

Vascularized composite allotransplantation (VCA) has emerged as an innovative strategy to restore form and function in patients with severe tissue defects involving anatomical regions such as the face, hand, and abdominal wall. Composite allografts are composed of diverse tissues, including skin, muscle, bone, vasculature, nerves, and mucosal surfaces, posing unique challenges in immunological management. Clinical outcomes following VCA surgeries have been encouraging; however, a comprehensive understanding of the underlying cellular interactions and molecular pathways is still predominantly derived from studies in solid organ transplantation (SOT). Recent advances in SOT have identified mitochondria as crucial therapeutic targets capable of mediating transplant rejection, mitigating ischemia-reperfusion injury (IRI), and enhancing graft longevity. Nevertheless, the explicit role and potential therapeutic applications of mitochondria within VCA remain largely unexplored. This review aims to critically examine and elucidate the significance of mitochondria in overcoming the current limitations encountered in VCA surgery. A deeper insight into mitochondrial biology could hypothetically provide clinicians and researchers with novel, targeted therapeutic strategies to improve clinical outcomes in VCA; however, these approaches require further validation in preclinical models.

IntroductionThere remains a lack of understanding of the etiology and treatment effectiveness for Adolescent idiopathic scoliosis (AIS). The objective of this study was to develop and validate a computable phenotype for patients with AIS to facilitate rapid learning through large‐scale observational research using real‐world data.Study DesignFour computable phenotype (CP) algorithms were developed and tested. The algorithms were executed against the Shriners Children's (SC) Research Data Warehouse using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) from January 1, 2016 to December 31, 2022. CPs composed of diagnosis and imaging procedure utilization codes were evaluated iteratively against a prospective registry of scoliosis patients. The highest‐performing phenotype was then evaluated through manual chart review for validation. Demographic characteristics of the patients meeting the phenotype definition were assessed.ResultsThe four alternative CPs ranged from 24 103 to 15 292 unique patients. The CP that balanced sensitivity (92.7%) and specificity (81.8%) when evaluated against a prospective registry of scoliosis patients was chosen as the final AIS CP. Among 50 patients with phenotype‐confirmed AIS, 36 (72%) had chart‐validated AIS, and 14 (28%) were identified as false positives. Of the 14 false positives, 6 cases had a diagnosis of spinal asymmetry. Among the patients meeting the phenotype definition, the average age of patients with AIS treated at SC is 13.6 years (SD = 1.64) and patients are primarily female (73.7%) and white (56.2%).ConclusionThe CP had good performance in identifying pediatric patients with AIS. Future refinements to the algorithm should include the use of x‐ray parameters or the application of natural language processing to unstructured EHR data to better distinguish AIS cases from other spinal diagnoses. This CP is a fundamental step to facilitate a learning health system environment that can rapidly develop evidence to improve pediatric patient outcomes.

ABSTRACT Background Chondrocytes, the only native cell type in cartilage, use mechanosensitive ion channels such as Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 to transduce mechanical forces into transcriptomic changes that regulate cell behavior under both physiologic and pathologic conditions. Recent work has identified and characterized the differentially expressed genes (DEGs) that are upregulated following TRPV4 or PIEZO1 activation, but the transcriptomic systems downregulated by these ion channels also represent an important aspect of the chondrocyte regulatory process that remains poorly studied. Methods Here, we utilized previously established bulk RNAsequencing libraries to analyze the transcriptomes downregulated by activation of TRPV4 and PIEZO1 through differential gene expression analysis (using DESeq2), Gene Ontology, RT-qPCR, and Weighted Gene Correlation Network Analysis (WGCNA). Results TRPV4 and PIEZO1 activations downregulated largely unique sets of DEGs, though the set of DEGs downregulated by TRPV4 exhibited a notable overlap with genes downregulated by treatment with inflammatory mediator Interleukin-1 (IL-1). The DEG set downregulated by PIEZO1 activation included genes associated with the G2/M cell cycle checkpoint, a system that checks cells for DNA damage prior to entry into mitosis, and this result was confirmed with RT-qPCR. WGCNA revealed modules of gene regulation negatively correlated with TRPV4, PIEZO1, and IL-1, outlining how these downregulated DEGs may interact to form gene regulatory networks (GRNs). Conclusion This study complements previous work in describing the full mechanosensitive transcriptome (or “mechanome”) of differential gene expression in response to activation of mechanosensitive ion channels TRPV4 and PIEZO1 Q2 and suggests potential avenues for future therapeutic treatment design.

PurposeThis study aimed to evaluate long-term functional and radiological outcomes as well as parents' perception of change and overall satisfaction following hip reconstructive surgery in children with cerebral palsy (CP).MethodsMedical charts of children between three and 18 years of age with CP who had surgery between 1993 and 2014 by the same surgeon were reviewed. The study sample consisted of 44 children (Gross Motor Function Classification System levels I-V) aged 2-18 years representing 60 hips. Mean follow-up was 8.4 years [1.8-17.5]. A final follow-up evaluation was held to obtain post-operative anteroposterior pelvic radiographs and administer patient-reported outcomes to the caregivers.ResultsCare and Comfort Hypertonicity Questionnaire scores showed that 74-79% of caregivers reported no difficulty post-surgery in terms of child's pain or discomfort during position changes, when participating in general activities, or during sleep. The Lower Extremity Parent-Rated Change Form showed that 58-76% of caregivers reported a better status in their child's overall health, leg function, activity level, and pain post-surgery. Seventy-six percent of the caregivers indicated satisfaction with the overall changes since the surgery. For the 45 hips with both pre-operative and follow-up radiological outcomes, migration percentage improved significantly (p < 0.001) by 36.7%, and there was a 62.2% increase in the number of hips that were located post-operatively compared to pre-operatively. Acetabular coverage improved significantly (p < 0.001) from non-covered to covered in 46.7% of the hips and Shenton's line improved significantly (p < 0.001) from non-intact to intact in 66.7% of the hips.ConclusionHip reconstructive surgery improved long-term functional and radiological outcomes, as well as quality of life for children and caregivers, while changes were perceived as satisfactory to the families. Evaluating pain, function, and satisfaction is important to measure the impact of hip reconstructive surgery on daily life.

Primary intracranial malignant melanoma (PIMM) is exceptionally rare and prone to misdiagnosis due to its nonspecific radiologic features. A 32-year-old female presented with a left frontal mass, initially diagnosed as meningioma on imaging. Gross total resection was performed. Histopathology revealed PIMM with an exceptionally high mitotic count (33/2mm²). Within 5 days postoperatively, she developed hydrocephalus and consciousness disturbance. Cerebrospinal fluid cytology confirmed malignant cells, and spinal MRI demonstrated diffuse leptomeningeal dissemination, indicating rapid cerebrospinal fluid spread. This case highlights the highly aggressive nature of PIMMs with elevated mitotic activity, the risk of misdiagnosis as meningioma, and the potential for surgery to precipitate devastating early leptomeningeal spread. It underscores the need for heightened preoperative suspicion and early postoperative vigilance in similar cases.

The computational complexity involved in modelling district heating (DH) networks impedes the integration of network operations into comprehensive DH system studies. We developed a flexible, accurate, and fast dynamic thermal simulation model utilising discrete event simulation (DES). This model is versatile, suitable for any tree-shaped DH network with a central heating plant and can estimate node temperatures and calculate pipe heat losses. The speed of the model is improved via using variable time steps and by incorporating two advanced techniques: lazy evaluation and a customised priority queue. To further improve the computational speed, we developed a technique to eliminate redundant sampling points. This model was tested and demonstrated excellent consistency with actual measurements. Remarkably, reducing sampling points can speed up the simulation by a factor of three without compromising the temperature accuracy. A 72-day simulation of a network with 102 pipes was completed within 0.219 s. Our findings highlight the significant potential of the DES model for large-scale dynamic network simulations and offer a promising solution for DH network simulations and system optimisation.