Children's Medical Center

ObjectiveTo compare 3D mandibular morphometrics of neonates with Pierre Robin sequence (PRS) to age-matched controls, establish normative data, and better understand anatomic differences.DesignRetrospective case-control study.SettingTertiary pediatric medical center.PatientsTwenty-five neonates with non-syndromic PRS (mean age 15 days) with computed tomography (CT) scans of the head and mandibular distraction osteogenesis (MDO) and 25 age-matched controls (mean age 14 days) with CT scans of the head.InterventionsNone.Main Outcome MeasuresStandardized morphometric measurements, including linear distances, angles, and ratios, were generated from digital 3D reconstructions of mandibular anatomy.ResultsAsymmetry in PRS body length was significantly higher than in control mandibles (p = .006). PRS measurements larger than control measurements included intercondylar distance (p = .044), intergonial distance (p = .008), pogonion-interdental distance (p = .015), ramus height (p = .001), and ramus height to body length ratio (p < .001). PRS measurements smaller than control measurements included intercondylar angle (p < .001), body length (p < .001), and effective mandibular length (p < .001).ConclusionsIn a cohort of neonates with PRS severe enough to warrant MDO, findings indicate that micrognathia is constituted by a wide and antero-posteriorly short mandible for its height. Except for body length, PRS and control mandibles are similarly asymmetrical in other dimensions. These findings may contextualize structural abnormalities contributing to glossoptosis and airway obstruction in PRS, with implications for surgical management, although decision-making remains primarily guided by clinical severity of airway obstruction.

ZFTA-RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA-RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse and human EPN. We demonstrated that specific developmental lineage programs present in transient progenitor cells and regulated by PLAG/L family transcription factors were at risk of neoplastic transformation. Binding of this chromatin network by ZR or other PLAG/L family motifs targeting fusion oncoproteins led to persistent chromatin accessibility at oncogenic loci and oncogene expression. Cross-species analysis of mouse and human ZR EPN revealed significant cell type heterogeneity indicating incomplete neurogenic and gliogenic differentiation, with a small percentage of cycling progenitor-like or radial glial-like cells that established a putative tumour cell hierarchy. In vivo lineage tracing studies identified neoplastic clones that aggressively dominated tumour growth and established the entire EPN cellular hierarchy. These findings identify developmental epigenomic states that are critical for fusion-oncoprotein-driven transformation and show how these states continue to shape tumour progression.

Introduction: Withdrawal of life-sustaining treatment (WLST) is the most common mode of death in pediatric intensive care units (PICUs), yet data on how WLST is operationalized remain limited. Prior studies have not adequately examined variability in WLST medical management practices for children across institutions or over time. We hypothesized that substantial institutional and temporal variation exists in WLST practices related to analgesic and sedative use, vasoactive medication discontinuation, neuromuscular blockade, and post-extubation respiratory support. Methods: We performed a secondary analysis of the multicenter DONATE study (2009-2021), which included 905 pediatric patients who died following WLST defined as terminal extubation. Data were abstracted from 9 U.S. tertiary-care PICUs and included medications and interventions administered before and after extubation. Site-level differences were assessed using chi-square or Fisher’s exact tests. Logistic regression was used to assess temporal trends. Results: Of 905 patients, 75.1% died within 1 hour of WLST. Opioids were administered in 79.7% (site range 68-89%, p< 0.001; no significant temporal trend); benzodiazepines in 56.0% (site range 41-66%, p< 0.001; decrease over time OR 0.95 per year, 95% CI 0.90-0.99, p=0.04); dexmedetomidine in 15.5% (site range 4-21%, p=0.002; increase over time OR 1.16 per year, 95% CI 1.05-1.27, p=0.004). Vasoactive infusions were discontinued in 88.1% of cases (site range 59-100%, p< 0.001; increase over time OR 1.15 per year, 95% CI 1.04-1.26, p=0.007). Neuromuscular blockade was used in 5.1% of patients (site range 0-13%, p< 0.001; increase over time OR 1.23 per year, 95% CI 1.08-1.40, p=0.002). Use of any post-extubation respiratory support was rare (5.5%) with no significant site or temporal variation. Conclusions: There is substantial institutional and temporal variability in WLST practices across US PICUs. These findings highlight a need for clearer guidance to reduce variability and support consistent, high-quality end-of-life care for critically ill children.

Childhood obesity is a major global health concern associated with increased metabolic and cardiovascular risk. Although oat-derived beta-glucan has shown metabolic benefits in adults, evidence in pediatric populations remains limited. This study evaluated the effects of beta-glucan supplementation on anthropometric measures and cardiometabolic risk factors in children and adolescents with overweight and obesity. In a randomized, double-blind, placebo-controlled trial, 86 participants aged 6-17 years with overweight or obesity were assigned to receive either 3g/day of oat-derived beta-glucan or an isocaloric starch placebo for 8 weeks. Anthropometric indices, glycemic and lipid profiles, liver enzymes, dietary intake, and physical activity were assessed at baseline and post-intervention. Between-group comparisons of change scores were performed using ANCOVA, adjusting for baseline values and relevant covariates. Seventy-three participants completed the study (beta-glucan: n = 34; placebo: n = 39). After 8 weeks, the beta-glucan group showed greater reductions in body weight, BMI, BMI-for-age z-score, waist circumference, and hip circumference compared with placebo (all adjusted-p-values < 0.01). For selected biochemical outcomes, unadjusted between-group comparisons showed significantly greater reductions in fasting blood sugar (p-value = 0.04), triglycerides (p-value = 0.02), and ALT (p-value = 0.01) in the beta-glucan group. No significant differences were observed for insulin, HOMA-IR, LDL-C, HDL-C, or total cholesterol. Total energy intake decreased more substantially in the beta-glucan group than in the placebo group (p < 0.001). beta-glucan supplementation may improve body composition and selected cardiometabolic markers in children with overweight and obesity; however, the short intervention duration and modest effect sizes highlight the need for longer and more comprehensive trials. The study was registered in the Iranian Registry of Clinical Trials (IRCT20180805040703N3; registration date: January 26, 2025). The online version contains supplementary material available at 10.1007/s40200-025-01832-0.

The extracellular matrix (ECM) critically influences cell behavior, yet its properties in human endometrial lesions (HEL) and human uterine fibromas (HUF) are not well characterized. This study aimed to characterize their ECM and evaluate its impact on cell engraftment and proliferation while optimizing a decellularization protocol. HEL and HUF tissues, collected during laparoscopic surgeries, were decellularized using a novel protocol. Complete cell removal and preserved ECM microstructure were confirmed by histology, DAPI, Masson's trichrome staining and scanning electron microscopy. The decellularized scaffolds were used as a platform for three-dimensional culture of human endometrial-derived mesenchymal stem cells (hEMSCs), with HUF serving as a fibrotic control originated from the same organ system. The biological impact of the ECM was assessed via immunohistochemistry for engraftment marker matrix metalloproteinase-9 and proliferation marker antigen Kiel-67. The in vivo recellularization potential of HEL scaffolds was further evaluated in a rat model, with HEL scaffold group at two timepoints (n = 6/group) and a sham control (n = 3). Results confirmed complete decellularization with maintained ECM integrity in both HEL and HUF. In vitro evaluation indicated that hEMSCs seeded more efficiently onto HEL scaffolds (51.16 ± 28.84) compared to HUF scaffolds (6.16 ± 7.29) (p = 0.012). The in vivo peritoneal implanted HEL scaffolds demonstrated significant time-dependent host cell recruitment and remodeling compared to the sham control. In conclusion, the decellularized HEL scaffold provides a superior ECM platform for cell seeding and engraftment compared to HUF, making it a promising platform for modeling endometriosis in both in vitro and in vivo settings.