Search Results (45,349)

Bartter syndrome (BS) represents a group of rare, autosomal recessive renal tubular disorders characterized by hypokalemic hypochloremic metabolic alkalosis, secondary hyperaldosteronism, and normal to low blood pressure. The underlying pathophysiology is primarily driven by defects in critical ion transport proteins or channels localized within the thick ascending limb of the loop of Henle, leading to impaired salt reabsorption. Recent advances in molecular genetics have refined the classification of Bartter syndrome. Current evidence supports SLC12A1, KCNJ1, CLCNKB, BSND, and MAGED2 as the core disease genes within the contemporary BS spectrum, with MAGED2 causing a distinct X-linked transient antenatal form. In contrast, gain-of-function CASR variants, historically labeled “type V Bartter syndrome”, are now more appropriately described as CaSR-associated Bartter-like phenotypes within the broader spectrum of disorders of calcium homeostasis. Despite significant progress, two primary research limitations remain. First, fully elucidating genotype–phenotype correlations and overcoming diagnostic complexities continues to be highly challenging due to substantial phenotypic overlap and genetic heterogeneity. Compounding these diagnostic hurdles is the equally critical challenge of understanding mutation-driven pathogenic mechanisms to develop viable clinical interventions. This review systematically summarizes the current molecular genetic landscape of BS to address these gaps. We highlight the relationships between specific genetic variants and clinical manifestations, delve into molecular pathophysiology including protein misfolding and trafficking defects, and explore emerging therapeutic approaches such as molecular chaperones. By integrating genetic and clinical data, this work aims to provide a comprehensive framework to facilitate precise diagnosis and individualized treatment strategies, ultimately advancing precision medicine in the management of Bartter syndrome. Full article

Objectives: Primary hyperoxaluria type III (PH3) causes kidney stones in children and adults. Gas chromatography/mass spectrometry (GC/MS)-based metabolomics has been applied to study patients with primary hyperoxaluria types I and II, 2,8-dihydroxyadenine lithiasis, and xanthinuria types I to III. This study was performed to verify the usefulness of this technique for the diagnosis of PH3. Specifically, we evaluated an 8-month-old infant with recurrent kidney stones. Methods: GC/MS-based metabolomics was performed on spot urine samples using initial urease pretreatment without fractionation. Results: Metabolomics revealed increased levels of 2,4-dihydroxyglutarate and 4-hydroxyglutamate. No simultaneous elevations of these two critical biomarkers were observed in other patients, except for one case of PH3 confirmed by the identification of HOGA1 mutations. A moderate increase in 4-hydroxyglutamate has been observed only in cases of primary hyperammonemia, in which analytes such as orotate, uridine, glutamine, or proline, but not 2,4-dihydroxyglutarate, are biomarkers, thus distinguishing PH3 from primary hyperammonemia. Conclusions: GC/MS-based urine metabolomics enables the rapid screening and chemical diagnosis of PH3 and other congenital anomalies that cause urolithiasis. This technique can also be used to monitor disease progression, as patients with PH3 benefit from long-term follow-up, particularly when transitioning from childhood to adulthood. The timely identification of patients with hereditary urolithiasis is crucial. To address this, a discussion was had about the current diagnostic criteria. Full article

Background/Objectives: Pediatric intussusception, a condition where part of the intestine telescopes into an adjacent segment, predominantly affects children aged 6–18 months. Prompt diagnosis and management are crucial to prevent serious complications such as ischemia or necrosis. This systematic review aims to comprehensively evaluate and synthesize existing research on predictive and prognostic biomarkers associated with pediatric intussusception that can aid in early diagnosis, severity assessment, outcome prediction, and treatment. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science using specific MeSH and free-text terms related to intussusception, biomarkers, and the pediatric population. The review followed PRISMA guidelines, with independent screening, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. A total of 47 studies, mostly retrospective cohorts from diverse countries, with over 20,000 patients, were included. Results: The studies identified numerous biomarkers associated with disease severity, including hematological markers and indices (e.g., WBC counts and neutrophil-to-lymphocyte ratio), inflammatory markers (CRP and cytokines), biochemical markers (serum lactate, D-dimer, and electrolytes), and novel molecular markers (I-FABP, MCP-1, and transfer RNA fragments). Elevated inflammatory markers and derived ratios consistently predicted bowel necrosis, ischemia, and need for surgery. Biochemical markers like serum lactate and D-dimer correlated with ischemic severity. Emerging molecular biomarkers show promise for early, non-invasive risk stratification. However, heterogeneity in study designs, assay methods, and cutoff values currently limits immediate clinical application. Conclusions: Biomarker research offers valuable tools for improving pediatric intussusception management, with the potential to enhance early diagnosis and outcome prediction. While traditional markers are useful, novel molecular and protein biomarkers hold promise for more specific and rapid assessment. Validation through multicenter, prospective studies and standardized protocols is essential before routine implementation. Integrating biomarkers with clinical and imaging data could refine decision-making, ultimately reducing morbidity and improving prognosis in affected children. Full article

Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds for cow’s milk protein in predicting outcomes of OFCs in European children. Eligible studies focusing on CRD in European pediatric populations were identified through PubMed and Scopus databases. Our findings highlight the crucial role of Bos d 8 (casein) in the diagnostic process. Among the analyzed milk components, Bos d 8 appeared to be a promising marker for predicting positive OFC outcomes in several cohorts. However, due to significant population heterogeneity, conflicting findings exist, with some studies indicating that no single molecular component is consistently superior to whole cow’s milk specific IgE. While other molecules, such as Bos d 6 and lactoferrin, showed limited diagnostic utility, specific IgE to Bos d 8 demonstrated the highest clinical value. Although the double-blind, placebo-controlled food challenge (DBPCFC) remains the gold standard for CMPA diagnosis, the use of Bos d 8 in CRD is a key step toward risk stratification and may help reduce the need for high-risk OFCs in selected patients. Full article

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance. Full article

Background: Osteoporosis is a prevalent condition characterized by low bone mass and altered microarchitecture, increasing fracture risk. Early detection remains challenging, as conventional methods such as DXA are limited to specialized settings and often detect disease only after a fracture. Radiomics and three-dimensional (3D) imaging techniques, such as CBCT, may provide novel approaches for assessing bone quality. Methods: This pilot study analyzed 68 CBCT scans from adult patients (41 females, 27 males; mean age 57 years). Three-dimensional regions of interest (ROIs) were delineated in seven maxillofacial and mandibular sites (total 309 ROIs). Radiomic texture features were extracted and compared with corresponding T-scores from DXA measurements. Additionally, synthetic 3D reference phantoms with controlled variations in density, trabecular connectivity, and structural anisotropy were generated to evaluate the sensitivity of texture features to microarchitectural changes. Results: Several radiomic features, including GLCM-, ARM-, and Gradient-derived parameters, demonstrated consistent monotonic trends correlating with bone density and microstructural deterioration. Differences in feature values were observed across healthy, osteopenic, osteoporotic, and advanced osteoporotic states. Reference phantoms confirmed that the observed trends were attributable to structural differences rather than imaging variability. Features such as Sum Variance and Correlation exhibited potential as early indicators of microarchitectural degradation. Conclusions: Three-dimensional CBCT texture analysis may provide a non-invasive, supplementary tool for assessing bone quality and detecting early osteopenic changes. Further studies with larger cohorts are warranted to validate radiomic markers and develop predictive indices for osteoporosis screening. Full article

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I–IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I–II) or late stage (LS; CKD III–IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD. Full article

Background/Objectives: Motor competence is a key indicator of children’s developmental readiness and an important component of health and well-being education. It is conceptualized as a latent construct shaped by both individual and contextual factors. The objective of this study was to examine the influence of sex, age and class context on motor competence, with particular emphasis on skill-specific and contextual variability. Methods: Motor competence was assessed in 312 Greek primary school children aged 6–12 years (156 girls) using the Movement Assessment Battery for Children–Second Edition. Standard scores for manual dexterity, aiming–catching, and balance were analyzed using a multilevel modeling approach. Results: Balance showed the highest standard scores, while manual dexterity was the lowest-performing domain. Boys outperformed girls in aiming–catching, with a modest effect. Age effects were domain-specific, with relative age within the classroom negatively associated with manual dexterity but not with other domains. Class-level factors explained substantial variance, indicating heterogeneity across classes. Conclusions: Motor competence in primary school children is strongly domain-specific and meaningfully associated with classroom context. Manual dexterity emerges as a potential priority for curriculum development, and age-related effects appear to operate selectively across domains. Full article

Background/Objectives: The prerequisite for diagnosing celiac disease (CD) in children without duodenal biopsy is a tissue transglutaminase antibody (TGA) level exceeding 10 times the upper limit of normal levels, along with a positive confirmatory anti-endomysial antibody (EMA) test in a secondary blood sample. The aim of our study was to determine whether determination of TGA in a second blood sample could be as reliable as determination of EMA as the confirmatory test in children eligible for the no-biopsy approach. Methods: A retrospective analysis of medical data was conducted, including children under 19 years old who were diagnosed with coeliac disease at our department from January 2013 to June 2025. We examined the diagnostic process, focusing on TGA levels at the time of diagnosis. Results: Data from 185 CD patients (59.5% female, median age 8 years) were available for the analysis. 49 (26.5%) patients were diagnosed using no-biopsy approach and 46 (93.9%) of those had TGA > 10 × ULN in second blood sample as well. In the group of children diagnosed using duodenal biopsy (N = 136; 96.3% 3 Marsh), 78 (57.4%) children had initial TGA > 10 × ULN. In 34 (43.6%) of those children, secondary serology performed before introducing a diet showed that 30 (88.2%) of them had TGA > 10 × ULN. Conclusions: Our study suggests that TGA levels > 10 × ULN could serve as a reliable test for confirming the diagnosis of CD in children, eligible for the no-biopsy approach, thus making the diagnostic process more cost-effective and efficient, while maintaining accuracy. Full article

Enteroviruses represent important human pathogens, posing a substantial disease burden, particularly in children under 5 years of age. Enteroviruses are the primary causative agents of hand-foot-and-mouth disease (HFMD) and are strongly associated with acute flaccid myelitis (AFM), with severe cases potentially resulting in significant neurological complications. Inactivated vaccines against EV-A71 based on the C4 genotype are currently available. However, there are no licensed direct antiviral agents for severe cases. By focusing on viral proteins and host factors, researchers have made great strides in the creation of antiviral medications that target enteroviruses. However, several viral candidates failed to progress in clinical development due to limited efficacy or side effects. This review discusses key findings in enterovirus antiviral research, analyzes the advantages and limitations of each drug target, and highlights knowledge gaps that need to be addressed to advance further development in this field. 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/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

Although increasing numbers of young people are trying to quit e-cigarettes, personalized tools to support vaping cessation remain limited. We aimed to build a machine learning model to predict individual probability of short-term relapses and identify person-specific barriers to successful cessation. Data were taken from the “Stop Vaping Challenge” smartphone app. We included past 30-day e-cigarette users aged 15–35 years (n = 311) who completed 387 quit challenges. Feature selection minimized number of predictors while maximizing predictive ability. We built multiple GBM survival models with different sets of predictors to predict time to vaping relapse. The five-feature model yielded the best performance (C-index 0.751), thereby was selected as the final model. These five features were: self-confidence in quitting, intention to quit, average e-liquid used per week, time to first vape and mood trend during challenge. We stratified the challenges by the individual relapse risk by 7 days into low-, medium-, and high probability of quit success. This approach can inform tailored quit plans for vaping cessation. SHAP analysis demonstrated individual-level barriers to cessation, which can guide the development of personalized, predictor-centric, adaptive behavioral interventions. However, future research is needed to implement the model in real-world settings and evaluate its effectiveness and generalizability. 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