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Studies have shown a positive correlation between higher physical activity (PA) and health benefits. However, device-based assessment of PA and sedentary time (ST) in people with adolescent idiopathic scoliosis (AIS) has not been deeply investigated. Analysis and comparison of weekend and weekdays PA and ST using multiple accelerometers in people with AIS with different curvature severity compared to healthy controls. 24 participants with AIS divided into 2 groups of 12 with Cobb angles 40°, along with 12 age and BMI matched healthy controls. Daily PA and ST during four consecutive days were measured using four tri-axial accelerometers. Clinical functional assessment was performed using the scoliosis research society (SRS-22) questionnaire. The combined weekend and weekdays average daily step count was found to be 22% and 29% lower in the AIS groups with Cobb angle 40°, respectively, compared to the controls. The average ST was also reported to be 5% and 7% higher in the AIS groups with Cobb angle 40°, respectively, compared to the controls. The reported differences were significant in the AIS group with higher Cobb angle (p[less than or equal to]0.05). No significant differences in PA or ST were reported between the AIS groups based on curvature severity. Decreased PA and increased ST observed in patients with AIS may have long term health implications and may play a role in the disease process. The device-based assessment of PA to understand potential benefits in clinical practice is recommended.

Background Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL). Methods In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors. Results We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells. Conclusions Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria. Clinical trials Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007 . Registered August 26, 2013. MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540 . Registered April 23, 2013. Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027 . Registered October 31, 2014. Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145 . Registered August 17, 2006. A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283 . Registered May 18, 2012.

Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine. Human development provides a roadmap for advancing pluripotent stem cell-based regenerative therapies. Here the authors mapped human skeletogenesis using RNA sequencing on 5 cell types from a single foetal stage as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation.

Background Acetabular protrusio is an uncommon finding in hip arthritis. Several reconstructive approaches have been used; however the best approach remains undefined. Questions/purposes Our purposes in this study were to (1) describe the THA survivorship for protrusio as a function of the acetabular component, (2) evaluate survivorship of the cup as a function of restoration of radiographic hip mechanics and offset, and (3) report the long-term clinical results. Methods One hundred twenty-seven patients (162 hips) undergoing primary THA with acetabular protrusio were retrospectively reviewed. The mean age of the patients at surgery was 66 ± 13 years, and the mean followup was 10 ± 6 years (range, 2–25 years).The cup fixation was uncemented in 107 (83 with bone graft) and cemented in 55 hips (14 with bone graft). Preoperative and postoperative radiographs were reviewed for restoration of hip mechanics and offset. Results The THA survival from aseptic cup revision at 15 years was 89% (95% CI, 75%–96%) for uncemented compared with 85% (95% CI, 68%–94%) for cemented cups. The risk of aseptic cup revision significantly increased by 24% (hazards ratio, 1.24; 95% CI, 1.02–1.5) for every 1 mm medial or lateral distance away from the native hip center of rotation to the prosthetic head center. Harris hip scores were improved by mean of 27 ± 20 points (n = 123) with a higher postoperative score for uncemented bone grafted compared with solely cemented cups (81 ± 16 versus 71 ± 20 points). Conclusions Restoring hip center of rotation using an uncemented cup with or without bone graft was associated with increased durability in our series. There was a 24% increase in the risk of aseptic cup revision for every 1 mm medial or lateral distance away from the native hip center to the prosthetic head center. Level of Evidence Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Vibrational characteristics of bone are directly dependent on its physical properties. In this study, a vibrational method for bone evaluation is introduced. We propose a new type of quantitative vibro-acoustic method based on the acoustic radiation force of ultrasound for bone characterization in persons with fracture. Using this method, we excited the clavicle or ulna by an ultrasound radiation force pulse which induces vibrations in the bone, resulting in an acoustic wave that is measured by a hydrophone placed on the skin. The acoustic signals were used for wave velocity estimation based on a cross-correlation technique. To further separate different vibration characteristics, we adopted a variational mode decomposition technique to decompose the received signal into an ensemble of band-limited intrinsic mode functions, allowing analysis of the acoustic signals by their constitutive components. This prospective study included 15 patients: 12 with clavicle fractures and three with ulna fractures. Contralateral intact bones were used as controls. Statistical analysis demonstrated that fractured bones can be differentiated from intact ones with a detection probability of 80%. Additionally, we introduce a “healing factor” to quantify the bone healing progress which successfully tracked the progress of healing in 80% of the clavicle fractures in the study.

Artificial intelligence (AI) is increasingly shaping pediatric spine care, leveraging its rapid advancements in healthcare to improve efficiency, accuracy, and disease understanding. Moreover, machine learning and deep learning excel at detecting complex patterns. This holds promise in processing spinal deformity data, with the potential to surpass traditional statistical methods in predictive accuracy. Challenges persist, however, including unclear clinical implementation guidelines, limited model transparency, and ethical concerns surrounding data privacy and bias. Small sample sizes and the need for larger, diverse datasets further complicate integration. In order to realize AI’s transformative potential in pediatric spine care, these critical obstacles must be addressed for effective and ethical clinical adoption. This review examines the role of AI through applications such as image sorting, surgical outcome prediction, forecasting of spinal curve progression, and vertebral volumetric analysis using deep reasoning. It also explores possible intraoperative contributions from AI, including robotics and optimized screw trajectory planning, and the potential of large language models in clinical practice.

Anterior vertebral body tethering (VBT) is a non-fusion, minimally invasive, growth-modulating procedure with some early positive clinical outcomes reported in pediatric patients with idiopathic scoliosis (IS). VBT offers potential health-related quality of life (HRQoL) benefits over spinal fusion in allowing patients to retain a greater range of motion after surgery. We conducted an early cost-utility analysis (CUA) to compare VBT with fusion as a first-choice surgical treatment for skeletally immature patients (age >10 years) with moderate to severe IS, who have failed nonoperative management, from a US integrated healthcare delivery system perspective. The CUA uses a Markov state transition model, capturing a 15-year period following index surgery. Transition probabilities, including revision risk and subsequent fusion, were based on published surgical outcomes and an ongoing VBT observational study (NCT02897453). Patients were assigned utilities derived from published patient-reported outcomes (PROs; SRS-22r mapped to EQ-5D) following fusion and the above VBT study. Index and revision procedure costs were included. Probabilistic (PSA) and deterministic sensitivity analyses (DSA) were performed. VBT was associated with higher costs but also higher quality-adjusted life years (QALYs) than fusion (incremental costs: $45,546; QALYs gained: 0.54). The subsequent incremental cost-effectiveness ratio for VBT vs fusion was $84,391/QALY gained. Mean PSA results were similar to the base case, indicating that results were generally robust to uncertainty. The DSA indicated that results were most sensitive to variations in utility values. This is the first CUA comparing VBT with fusion in pediatric patients with IS and suggests that VBT may be a cost-effective alternative to fusion in the US, given recommended willingness-to-pay thresholds ($100,000-$150,000). The results rely on HRQoL benefits for VBT compared with fusion. For improved model accuracy, further analyses with longer-term PROs for VBT, and comparative effectiveness studies, would be needed.

Background Developmental dysplasia of the hip (DDH) is a leading cause of total hip arthroplasty (THA) in younger patients. It is unknown how the hospital costs of THA in patients with DDH compare with patients with degenerative arthritis. Questions/purposes We undertook this study to determine (1) the hospital cost and length of stay associated with primary THA in patients with dysplasia compared with nondysplastic control subjects; (2) the hospital cost and length of stay of THA in severely dysplastic hips compared with mildly dysplastic hips; and (3) perioperative complications in patients with DDH compared with patients without dysplasia. Methods This matched-cohort study included 354 patients undergoing primary THA for DDH and 1029 age-, sex-, and calendar year-matched patients undergoing THA for primary osteoarthritis between 2000 and 2008. DDH severity was measured by the Crowe classification. An institutional database was used to calculate the cost of care. Using line item details (date, type, frequency, and billed charge) for every procedure or service billed at our institution for each patient, bottom-up microcosting valuation techniques were used to generate standardized inflation-adjusted estimates of the cost of each service or procedure in constant dollars. Generalized linear random effects models were used to compare length of stay and costs during hospitalization and the 90-day period after surgery. Query of a longitudinal institutional database was used to identify documented complications. Results Patients with DDH undergoing primary THA incurred higher hospital costs than patients with primary osteoarthritis (USD 16,949 versus USD 16,485, p = 0.012). Operating room costs (USD 3471 versus USD 3417, p = 0.0085) and implant costs (USD 3896 versus USD 3493, p < 0.001) were higher in the DDH group compared with the osteoarthritis group. Length of stay was not different between the two groups (4 versus 4 days, p = 0.46). Crowe 4 hips had higher hospital costs than Crowe 1 hips (USD 21,246 versus USD 16,345, p < 0.001) with an associated longer length of stay (5 days versus 4 days, p = 0.0011) and higher implant costs (USD 4380 versus USD 3788, p = 0.0012). There was no detectible difference in 90-day complications in the case group compared with patients undergoing THA for osteoarthritis. Conclusions Hospital cost of primary THA is approximately USD 450 higher in patients with DDH compared with osteoarthritis. Increased severity of dysplasia (Crowe classification) was associated with higher costs. Level of Evidence Level IV, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence.

Study Design Prospective Cohort Study. Objective The present study aims to determine if the racial representation of patients enrolled in a large prospective scoliosis registry is reflective of the general United States population. Further, we studied whether there was an association between race, pre-operative parameters, outcomes and loss to follow-up. Methods Prospectively collected data for patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) was reviewed, including self-reported race/ethnicity. The U.S. pediatric population and U.S. patients enrolled in the prospective registry were compared. The data obtained was analyzed for variations between races, for pre-operative variables and follow-up. Results Of the 2210 included patients in the registry 66% of patients reported as White, while 52% of the 2018 U.S. pediatric population reported as White. 15% of the registry reported as Hispanic/Latino compared to 22% of the U.S. pediatric population, 13% Black compared to 14% of the U.S. pediatric population, and 4% Asian compared to 5% of the U.S. pediatric population. Asian and White patients had statistically significant higher 2-year follow-up in all but one of six enrollment sites (P < 0.001). Native American, Other, and Hispanic/Latino patients had the highest BMIs. Native American and Black patients had the highest pre-op thoracic Cobb angles. Pre-op ages of Black, Hispanic, and Native American patients were statistically lower (P < 0.01). Conclusion This study demonstrates the association between race and patient follow-up and pre-operative factors in patients who underwent surgery for AIS. Black, Native American, and Hispanic populations were underrepresented both at pre-op and follow-up when compared to their relative proportion in the U.S. pediatric population.

Study designAssessment of screw pattern, implant density (ID), and optimization of 3D correction through computer-based biomechanical models.ObjectiveTo investigate how screw pattern and ID affect intraoperative 3D correction of thoracic curves in adolescent idiopathic scoliosis, and how different correction objectives impact the optimal screw pattern.Summary of background dataScrew pattern, ID, correction objectives and surgical strategies for posterior fusion of AIS are highly variable among experienced surgeons. The “optimal” instrumentation remains not well defined.Methods10 patient-specific multibody models of representative adolescent idiopathic scoliosis Lenke 1A cases were built and used to compare alternative virtual correction surgeries. Five screw patterns and IDs (average: 1.6 screws/instrumented level, range: 1.2–2) were simulated, considering concave rod rotation, en bloc derotation, and compression/distraction as primary correction maneuvers. 3D correction descriptors were quantified in the coronal, sagittal and transverse planes. An objective function weighting the contribution of intraoperative 3D correction and mobility allowed rating of the outcomes of the virtual surgeries. Based on surgeon-dependent correction objectives, the optimal result among the simulated constructs was identified.ResultsLow-density (ID ≤ 1.4) constructs provided equivalent 3D correction compared to higher (ID ≥ 1.8) densities (average differences ranging between 2° and 3°). The optimal screw pattern varied from case to case, falling within the low-density screw category in 14% of considered scenarios, 73% in the mid-density (1.4 < ID < 1.8) and 13% in the high-density. The optimal screw pattern was unique in five cases; multiple optima were found in other cases depending on the considered correction objectives.ConclusionsLow-density screw patterns provided equivalent intraoperative 3D correction to higher-density patterns. Simulated surgeon’s choice of correction objectives had the greatest impact on the selection of the optimal construct for 3D correction, while screw density and ID had a limited impact.Level of evidenceN/A.