Search Results (26,983)

Background: Early detection and monitoring of enamel changes during caries lesion formation are essential for preventive management. This study aimed to evaluate time-dependent enamel demineralization using micro-computed tomography (micro-CT) and to compare its diagnostic performance with laser fluorescence and digital colorimetric image analysis. Methods: Twelve sound human permanent teeth were subjected to a gel-based lactic acid demineralization for 14 days. Assessments were performed at baseline and after 3, 7, and 14 days. Enamel mineral density (MD) and demineralization depth (DD) were measured using micro-CT. Laser fluorescence was evaluated using DIAGNOdent, while colorimetric changes were analyzed through standardized digital imaging using the CIE Lab* system, including ΔE and Whiteness Index (WI). Statistical analysis included repeated measures ANOVA and Pearson correlation (p < 0.05). Results: A significant time-dependent progression of enamel demineralization was observed. Demineralization depth increased from 0.0828 mm (3 days) to 0.234 mm (14 days) (p < 0.001), while mineral density decreased significantly over time (p < 0.001). DIAGNOdent values showed significant increases after 7 and 14 days (p = 0.002). Colorimetric analysis revealed early detectable changes, with ΔE exceeding clinically perceptible thresholds as early as day 3. WI values increased progressively, indicating enhanced enamel opacity. A weak but significant negative correlation between MD and DD was found (p = 0.04). Conclusions: Enamel demineralization progresses in a time-dependent manner and can be effectively monitored using micro-CT, laser fluorescence, and colorimetric analysis. Digital colorimetric analysis may serve as a valuable adjunctive tool in caries diagnostics. Full article

Background/Objectives: Dental caries continues to represent a major oral health concern in children, particularly in uncooperative patients, where effective sealant placement is often compromised. This study evaluated the long-term clinical performance of hydrophilic (UltraSeal XT hydro) and hydrophobic (Helioseal-F) resin-based sealants in uncooperative children aged 6–9 years, assessing retention and caries incidence over 24 months. Methods: In a split-mouth, double-blinded randomized controlled trial, 34 children (104 first permanent molars) were enrolled, with 31 participants (98 teeth) completing the study. Sealants were randomly assigned to hydrophilic or hydrophobic group, with assessments at 3, 6, 12, 18, and 24 months. Results: Complete retention declined progressively in both groups, from 59.2% to 2.0% in the hydrophilic group and from 42.9% to 0% in the hydrophobic group at 24 months, with no significant intergroup differences (p = 0.719). Caries-free rates decreased from 81.6% to 49.0% in the hydrophilic group and from 75.5% to 40.8% in the hydrophobic group (p = 0.293). Children with definitely negative behavior showed significantly lower retention at 6 and 12 months (p = 0.006 and p < 0.001) compared to those with negative behavior, although differences were not significant at 24 months. Conclusions: Overall, both sealants demonstrated comparable retention and cariostatic performance, indicating that material properties alone do not determine long-term success. Further research should focus on long-term follow-up and comparative evaluation of hydrophilic sealants in cooperative and uncooperative populations to better understand how patient behavior affects sealant performance. Full article

Background: Total hip arthroplasty (THA) for the late sequelae of childhood septic hip arthritis is technically demanding, and infection-related risk remains incompletely defined. This systematic review and meta-analysis address the research question: “In adults undergoing THA after childhood septic arthritis of the hip, what is the incidence of post-THA infection, revision, and mechanical/neurologic complications?” We systematically reviewed and meta-analyzed outcomes after THA in patients with septic hip arthritis diagnosed at ≤18 years. Methods: PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to 31 December 2025 (PRISMA). Eligible studies reported THA outcomes after childhood septic arthritis and met a Methodological Index for Non-Randomized Studies (MINORS) threshold (≥9). A random-effects meta-analysis of events per hip was performed. Results: Nine studies were included; eight contributed to the quantitative synthesis (343 hips). The pooled incidence of any post-THA infection was 1.55% (95% CI 0.38–3.48; I² = 23.8%; 5/343); when microbiology was available, no relapse due to the index organism was reported and events were classified as new infections. The pooled incidence of revision for any cause was 4.99% (95% CI 2.27–8.70; I² = 43.4%; 15/334). Non-infectious complications were clinically relevant, including intraoperative fracture (6.95%) and nerve palsy (4.84%). Evidence was limited by retrospective designs and heterogeneous reporting. Conclusions: THA after childhood septic hip arthritis demonstrates a low risk of postoperative infection, with relapse of the original pathogen appearing rare in carefully selected quiescent cases, but a clinically meaningful burden of mechanical and neurologic complications. These findings underscore the importance of careful preoperative assessment, meticulous surgical technique, and highlight the limitations of the current evidence. The protocol was registered in PROSPERO (ID: CRD420261298181). No external funding was received. Full article

Background/Objectives: Nutrition is essential to outcomes in critically ill children; however, optimal timing, route, and composition of feeding remain uncertain. Prior studies demonstrate considerable variability in study design, patient populations, and outcome measures, limiting comparability. This review synthesizes international pediatric intensive care unit (PICU) nutrition studies evaluating timing, route, and content of nutritional interventions and summarizes associated clinical outcomes and nutritional adequacy. Methods: A comprehensive scoping review was conducted using the PICOS framework. PubMed and Embase databases were searched for studies published between 2015 and 2025 enrolling critically ill children ≤21 years old admitted to PICUs. Eligible studies assessed timing (early vs. late enteral nutrition), nutritional composition, or feeding route (enteral vs. parenteral). Screening and full-text review were performed independently by two reviewers using Covidence, with discrepancies resolved by a third reviewer. Quality assessment used STROBE. The protocol was registered with PROSPERO. Results: Of 652 identified records, 30 studies met inclusion criteria. Studies were conducted primarily in the United States (27%), with additional contributions from Spain and Brazil (10% each) and several other countries. Study designs included randomized controlled trials (27%) and observational studies (73%). Interventions examined feeding route (14%), nutritional content (38%), and timing (48%). Frequently reported outcomes included feeding intolerance or adverse events, duration of mechanical ventilation, time to nutrition goals, PICU length of stay, mortality, and nutritional adequacy. Conclusions: The contemporary PICU nutrition literature demonstrates persistent heterogeneity in practice and outcomes. This review identifies ongoing gaps in timing, delivery, and adequacy of nutritional support. Full article

Background/Objectives: Elevated central adiposity (ECA) in childhood is associated with early cardiometabolic risk and hemodynamic alterations. However, evidence in Spanish schoolchildren regarding the relationship between eating behavior traits and central adiposity is limited, particularly across developmental stages. This study aimed to examine the association between Children’s Eating Behaviour Questionnaire (CEBQ) subscales and ECA, and to explore potential differences by age group. Methods: A cross-sectional study was conducted in 496 rural schoolchildren aged 6–15 years. ECA was defined using the waist-to-height ratio (WHtR) and sex-specific cut-offs validated for the Spanish pediatric population. Eating behavior was assessed with the CEBQ (Z-scores), and diet quality was measured using the KIDMED index. Multivariable logistic regression models were adjusted for sex, KIDMED score, and maternal education. Analyses were subsequently stratified by age (6–9 and 10–15 years). Results: The prevalence of ECA was 45.90%. In fully adjusted models, higher Food Responsiveness (FR) was associated with increased odds of ECA, while Satiety Responsiveness (SR) acted as a protective factor; sex also showed an independent association. After stratification, sex remained the only significant predictor in children aged 6–9 years. Among those aged 10–15 years, FR was significantly associated with ECA (p = 0.008), while Slowness in Eating (SE) showed a borderline positive association in the adjusted model (p = 0.049) and was therefore interpreted cautiously. SR and Emotional Undereating (EU) showed protective trends near significance (p = 0.081 and p = 0.082, respectively). Conclusions: The association between eating behavior traits and ECA varies by age. In older children, FR showed a robust association with ECA, whereas no behavioral predictors were observed in younger children. The protective role of SR in the global model and the emergence of behavioral predictors in older participants highlight the importance of targeted interventions during late childhood. Full article

Background/Objectives: Immunocompromised children undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic disorders face a high risk of serious, life-threatening infections caused by multidrug-resistant (MDR) bacteria. Cefiderocol is a novel siderophore cephalosporin, indicated for use in adult patients with MDR Gram-negative infections. Clinical data in immunocompromised children are limited. To report a multicenter real-life experience from the Infection Working Group of the Italian Pediatric Hematology and Oncology Association (IWG-AIEOP) on the use of cefiderocol in treating pediatric onco-hematologic patients with severe, high-risk infections. Methods: Multicenter retrospective collection of infectious episodes treated with cefiderocol, from January 2021 to December 2024, in patients 18 years or younger, after treatment for malignancies or undergoing HSCT in the AIEOP network, part of a prospective, observational study on the etiology and outcome of febrile episodes among 24 AIEOP centers (code NCT06419426). Results: Fifteen episodes of MDR, life-threatening Gram-negative infections treated with cefiderocol in 13 pediatric onco-hematologic patients were collected. There were eight males and five females, mainly affected by acute leukemia (six lymphoblastic and four myeloid, three other hematologic malignancies). The median age was 11.1 years (range 1–17.4 years), and the median weight was 37.8 kg (range 8–65). Bloodstream infection occurred in 10 of 15 episodes. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Stenotrophomonas maltophilia were isolated in 11, 3, and 1 episodes, respectively. Notably, 11 of 15 isolated pathogens carried a metallo-beta-lactamase (MBL) gene (Verona integron-encoded, VIM, n = 10; New Delhi, NDM, n = 1). All patients achieved infection resolution and were alive and infection-free 90 days after infection onset. Conclusions: Cefiderocol was well tolerated and showed encouraging, favorable clinical outcomes, without serious adverse effects. Full article

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype–phenotype correlations. Methods: We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. Results: All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. Conclusions: This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype–phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. Full article

Nephrocalcinosis, defined as the deposition of calcium salts within the renal parenchyma, represents a radiologic and pathologic endpoint shared by a broad spectrum of metabolic and monogenic disorders. Advances in genomic medicine have identified more than 30 genes involved in tubular transport, mineral and acid–base homeostasis, oxalate metabolism, mitochondrial function, ciliary signaling, and nephron development, reframing nephrocalcinosis as a heterogeneous manifestation of discrete molecular defects rather than a single disease entity. Despite this diversity, these conditions converge on common physicochemical pathways of tubular supersaturation, crystal nucleation, growth, and intrarenal retention. These processes are amplified by the intrinsic vulnerability of the renal medulla—characterized by hyperosmolality, hypoxia, and slow tubular flow—and by epithelial injury, loss of crystallization inhibitors, and impaired ciliary signaling. Distinct genotype–phenotype signatures, including age at onset, biochemical profiles, and extrarenal manifestations, provide important diagnostic clues and help differentiate major monogenic entities. The increasing availability of targeted gene panels, whole-exome sequencing, and whole-genome sequencing has substantially improved diagnostic yield, particularly in pediatric populations. Molecular diagnosis now directly informs therapeutic decision-making and long-term management, enabling a shift toward precision nephrology. This narrative review integrates genetic, mechanistic, and clinical perspectives to illustrate how molecular diagnosis reshapes the evaluation, prognosis, and treatment of nephrocalcinosis. Full article

Background/Objectives: Temporal bone surgery in children is technically challenging due to their smaller anatomical structures, developmental differences, and the closer proximity of critical neurovascular structures. The limited availability of conventional training materials and pediatric cadaveric specimens has led to greater enthusiasm for simulation-based methods. The aim of this systematic review was to identify existing otologic simulation models and evaluate their anatomical accuracy, teaching effectiveness, and supporting evidence. Methods: In accordance with PRISMA guidelines, the PubMed, Embase, Scopus, and Cochrane Library databases were searched for studies reporting simulation tools for pediatric otologic surgery. Articles describing three-dimensional printed (3DP) models, virtual reality (VR) platforms, cadaver specimens, and animal models were included. Studies focusing on children and providing educational outcomes were selected. The extracted data were synthetized and analytically discussed. Results: Thirteen studies met the inclusion criteria: nine on 3DP models and four on VR environments. No research involving cadavers or animals was identified. 3DP models exhibited consistent anatomical accuracy and notable educational advantages. Five studies used surveys for their evaluations, and three relied on expert observer assessments. The studies including validation analyses showed a high correlation between printed models and computed tomography (CT) images. VR systems supported anatomical reconstruction and segmentation tasks, as well as guided simulation exercises. However, most of the research consisted of feasibility studies with limited participant groups. Conclusions: Simulation-based training with 3DP and VR models could be ethical and accurate methods for obtaining relevant skills in pediatric otologic surgery. The reviewed data suggest that these tools may be suitable as a first-line step within an integrated, multimodal training pathway prior to direct patient contact. Full article

Lyme disease is the most common reported vector-borne disease in North America and is also highly prevalent across Europe. Although tick-borne diseases are uncommon in Singapore, there remains a risk of imported tick-borne diseases among travelers from endemic regions. We present a case series of three pediatric patients with imported Lyme disease managed at a tertiary children’s hospital in Singapore, illustrating the varied clinical presentations of Lyme disease in children. One child developed meningitis following prior antibiotic therapy for Lyme disease, although causality cannot be definitively established. This series aims to highlight key diagnostic considerations and management principles relevant to clinicians practicing in non-endemic regions. Full article

Background: RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS/mitogen-activated protein kinase (MAPK) signaling cascade. Methods: The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. Results: A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the PTPN11 gene (c.188A>G and c.922A>G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including PTPN11, LZTR1, SOS1, and RAF1, with PTPN11 being the most frequently affected gene. Males predominated (17/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. Conclusions: Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling. Full article

Metabolically-dysfunction-associated steatotic liver disease (MASLD) represents the most common chronic liver disease in the pediatric population, and its prevalence has doubled over the past decade. The etiology is multifactorial, including genomic risk factors, perinatal and developmental or behavioral factors. Still, many cases of MASLD are associated with being overweight and obesity, particularly in children who have poor dietary habits and sedentary lifestyles that contribute to excessive weight gain. Given the progressive and heterogeneous nature of MASLD, early identification of high-risk patients before the development of severe liver disease is a major clinical priority. Recent studies indicate that disorders of amino acid metabolism are closely linked to both obesity and MASLD, reflecting profound alterations in systemic metabolic homeostasis. The reported data sustain significant changes in circulating amino acid profiles, particularly elevated levels of branched-chain amino acids (BCAAs) and aromatic amino acids. These alterations are thought to reflect fundamental metabolic disturbances, including insulin resistance, compromised mitochondrial activity, and altered hepatic lipid metabolism. Consequently, alterations in amino acid metabolism have been proposed as potential biomarkers for disease progression and metabolic dysfunction in MASLD. This review aims to evaluate the correlation between the amino acid profile and histological changes in pediatric MASLD, including steatosis, steatohepatitis, and fibrosis. Full article

Background/Objectives: Inguinal hernia and hydrocele are common pediatric surgical conditions resulting from failed obliteration of the processus vaginalis during fetal development. Although prenatal exposure to fine particulate matter (PM2.5) has been linked to adverse perinatal outcomes and congenital anomalies, its role in structurally defined pediatric surgical diseases remains unclear. We examined the association between maternal PM2.5 exposure during pregnancy and the risk of inguinal hernia or hydrocele in offspring. Methods: We performed a retrospective cohort study of 1093 mother–offspring pairs delivering at a tertiary referral center (July 2016–June 2019). Monthly residential PM2.5 levels were estimated at geocoded maternal addresses using kriging interpolation from fixed-site monitoring stations. Offspring diagnosed with inguinal hernia or hydrocele through March 2024 were identified using ICD-10 codes. Perinatal characteristics were compared using t-tests and chi-square tests, and multivariable logistic regression assessed trimester-specific PM2.5 exposure and risk. Results: During follow-up, 53 offspring (4.85%) developed inguinal hernia or hydrocele. Male sex (odds ratio [OR], 24.71; 95% CI, 5.95–102.54; p < 0.001) and second-trimester PM2.5 exposure (OR, 1.07 per µg/m³; 95% CI, 1.01–1.14; p = 0.028) were independent risk factors. A dose–response pattern was observed across quartiles of second-trimester exposure; an interquartile range increase was associated with a 64% higher risk (OR, 1.64). The model showed good discrimination (AUC, 0.804). Conclusions: Elevated maternal PM2.5 exposure during the second trimester was independently associated with increased risk of inguinal hernia or hydrocele in offspring. Prenatal air pollution may contribute to persistence of the processus vaginalis and represents a potentially modifiable environmental risk factor. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive desmoplastic microenvironment; however, reproducible stromal-associated biomarkers linked to disease progression remain limited. This study therefore aimed to identify and validate a biologically relevant stromal/extracellular matrix (ECM)-associated candidate biomarker for PDAC. Methods: Three GEO bulk transcriptomic PDAC cohorts (GSE15471, GSE16515, and GSE62452) were integrated for differential expression, functional enrichment, protein–protein interaction, and hub-gene analyses. Candidates identified as a promising biomarker were further evaluated using the following: public proteomic and survival resources; head-to-head receiver operating characteristic (ROC) comparisons against COL1A1, COL3A1, and COL5A1; a progression cohort (GSE43288); and single-nucleus RNA sequencing data (GSE202051). Results: Among 206 shared differentially expressed genes, COL5A2 was the only consensus hub retained across multiple network-ranking methods. COL5A2 protein expression was found to be elevated in tumor tissue and associated with worse overall and disease-free survival. In ROC analyses, COL5A2 exhibited stable tumor-versus-non-tumor discrimination across GSE15471, GSE16515, and GSE62452 (AUC = 0.932, 0.760, and 0.782, respectively) and significantly outperformed COL3A1 in two cohorts. In GSE43288, COL5A2 expression increased along the normal–pancreatic intraepithelial neoplasia–PDAC axis and remained positively associated with ECM and cancer-associated fibroblast (CAF) signature scores after adjustment for disease group. Reanalysis of GSE202051 restricted to the original 18 untreated PDAC specimens revealed that COL5A2 expression was concentrated in fibroblast-lineage compartments, with CAFs accounting for the largest overall contribution and myCAFs demonstrating the strongest per-specimen expression enrichment. Conclusions: COL5A2 is a reproducible stromal/ECM-associated candidate biomarker linked to PDAC progression, with predominant expression in fibroblast/CAF compartments. Full article

Background: Adults with disabilities living in low-resource communities experience persistent inequities in access to healthcare, mental health services, and community participation. However, qualitative data capturing lived experiences in the Deep South remain limited. This study aimed to identify priority needs among adults with mobility disabilities residing in economically distressed communities near Birmingham, Alabama, to inform future telehealth programming. Methods: Fifteen adults (mean age = 60 ± 10 years), predominantly African American and female, completed semi-structured phone interviews exploring basic needs, neighborhood accessibility, health priorities, and perceived supports. Interviews were audio-recorded, transcribed verbatim, and analyzed using Braun and Clarke’s six-phase thematic analysis. Results: Five themes emerged: (1) seeking stability amid severe mental health strain and inadequate supports; (2) constrained food environments shaped by cost, location, and safety; (3) feeling forgotten: systemic neglect and restricted participation in community life; (4) physical health deprioritized by competing needs and structural barriers; and (5) remote support as a viable but unrealized option. Participants described how safety concerns, transportation barriers, and rising food costs constrained daily functioning, while unmet mental health needs compounded isolation. Despite widespread cardiometabolic disease, immediate needs related to mental health, food, and housing consistently superseded physical health. Mental health support was identified as the most feasible area for remote delivery, though poor awareness of available resources limited engagement with any service model. Conclusions: Findings demonstrate that disability-related disparities in low-resource communities are driven largely by structural and environmental factors rather than individual choice. Telehealth and mobile-based services may provide a feasible access strategy for mental health and supportive care in under-resourced settings, particularly when integrated with broader community supports. Addressing foundational needs is essential for advancing health equity among people with disabilities in the Southeast. Full article