Search Results (67)

Background/Objectives: Pediatric sleep-disordered breathing (SDB) is influenced by craniofacial morphology and host susceptibility. Evidence integrating cephalometric airway features with targeted genetic variation in symptomatic skeletal Class II children remains limited. We explored whether children with skeletal Class II mandibular retrognathia and SDB symptoms harbor selected genetic variants and whether carriers show distinct cephalometric airway characteristics. Methods: This cross-sectional study included 48 children with skeletal Class II malocclusion, mandibular retrognathia, and snoring/mouth-breathing symptoms. Craniofacial and airway parameters were assessed on lateral cephalograms. SDB burden was evaluated by a baseline home sleep study (respiratory event index, REI). Targeted sequencing screened TNFRSF1A, PSTPIP1, SLC6A4 (5HTT), ACE, APOE, IRS1, and additionally PHOX2B and PMP22. Exploratory group comparisons used Student’s t-test. Results: Variants were identified in 13/48 participants (27%) in TNFRSF1A, PSTPIP1, SLC6A4, ACE, APOE, and IRS1; none were detected in PHOX2B or PMP22. C3–H was higher in variant carriers (39.90 ± 6.40 vs. 36.48 ± 3.95 mm; p < 0.05). HH1 (perpendicular distance from the hyoid bone to the C3–RGN line) was higher but not significant (16.99 ± 7.58 vs. 14.61 ± 5.25 mm; p > 0.05). Conclusions: In this clinically screened pediatric skeletal Class II cohort with SDB symptoms, selected genetic variants co-occurred with specific hyoid–cervical cephalometric features. Given the cross-sectional design, absence of a control group, and small number of carriers, findings are exploratory and require replication in larger, controlled cohorts with standardized phenotyping. Full article

Background: Antegrade continence enemas (ACEs) are administered by appendicostomy or cecostomy to manage bowel conditions. Cecostomies utilize buttons while appendicostomies utilize the appendix for colonic flushing. This study evaluates the outcomes and overall burden of these procedures in a mixed urban–rural population, highlighting unique social determinants of health (SDoH) and access factors. Methods: A retrospective cohort analysis of 31 pediatric patients was conducted at a tertiary academic hospital where 8 underwent a Malone-type ACE (MACE) and 23 underwent a laparoscopic cecostomy (LC) between 2014 and 2024. Results: Age at surgery was significantly higher in the MACE group versus the LC group (14.6 vs. 8.1 years). Patients who underwent MACE had longer hospital stays than patients who underwent LC (7.5 vs. 4.5 days, p = 0.014) and significantly higher 30-day readmissions (5 vs. 2, p = 0.001). Granulation tissue was significant in LC (82.6%) compared to MACE (13.5%, p = 0.001). Moreover, need for surgical revision occurred more in the MACE group (25%). Analysis of SDoH revealed that most of the cohort lived in areas with low childhood opportunity and high socioeconomic deprivation, particularly those undergoing MACE. Financially, MACE was associated with substantially higher total, direct, and indirect costs than LC, with the difference in total cost reaching statistical significance. Conclusions: In this setting,10-year complication rates were low. This reflects the development of a new dedicated longitudinal bowel management program in mid-Missouri. Functional outcomes at the end of the 10-year period were comparable between both cohorts with the achievement of continence. These findings support tailoring surgical approaches to patient needs. Full article

Youth with neurodevelopmental disorders (NDDs) face an increased risk of trauma compared to their peers without NDDs, often leading to challenging behaviors such as self-injury, aggression, and property destruction. However, limited research exists on the behavioral profiles and treatment outcomes of youth with both NDDs and trauma. This study examines a sample of 21 youth with NDDs and trauma admitted to a specialized psychiatric unit in the Rocky Mountain region of the United States. A retrospective review of health records and admission data identified the most common target behaviors: negative vocalizations (95%), property destruction (62%), elopement (52%), and aggression (43%). Functional analyses indicated that escape was the most prevalent behavior function identified (43%), while 29% of the analyses yielded undifferentiated outcomes. Behavior analytic treatment packages incorporating differential reinforcement resulted in an average of 72% reduction from the baseline target behaviors. The average Pediatric ACEs score was 5 out of 10. The findings highlight the key behavioral patterns in this population and underscore the need for further research on effective interventions. Full article

Background/Objectives: In the present study, we hypothesized that cardiac surgery in pediatric patients with congenital heart disease (CHD) leads to profound endothelial glycocalyx degradation, measured as the increase in plasma syndecan-1 concentration, and that this endothelial damage is more pronounced in patients with cyanotic CHD. Methods: A total of 40 infants (24 with acyanotic and 16 with cyanotic CHD) were enrolled in this prospective study. A total of 39 cardiac surgeries were performed with cardiopulmonary bypass (CPB), 38 with CPB and aortic clamping, and 3 with CPB, aortic clamping, and deep hypothermic circulatory arrest. Results: Syndecan-1 concentrations increased significantly post-surgery compared to the baseline in both groups (cyanotic: 24.4 to 48.0 ng/mL, p < 0.0001; acyanotic: 28.8 to 59.8 ng/mL, p < 0.0001). However, there was no significant difference in syndecan-1 concentrations at any timepoint between children with cyanotic and those with acyanotic CHD. Baseline syndecan-1 showed no correlation with preoperative arterial oxygen saturation (r = 0.26, p = 0.102), hemoglobin (r = −0.3, p = 0.06), age (r = 0.15, p = 0.36), and weight (r = 0.13, p = 0.42). Of note, CPB time (r = 0.08, p = 0.63) and AC time (r = 0.03, p = 0.86) were not related to syndecan-1 concentrations at the end of surgery. Conclusions: Cardiac surgery leads to profound glycocalyx degradation in children with CHD detected by increased plasma syndecan-1 concentrations. Regardless of major pathophysiological differences, children with cyanotic and acyanotic CHD presented similar plasma syndecan-1 values throughout the study. Full article

Background: Galectin-10 (Gal-10), the main constituent of Charcot–Leyden crystals, is a recognized marker of eosinophilic inflammation, yet its role in nasal mucosal remodeling in Seasonal Allergic Rhinitis (SAR) remains poorly defined. Methods: Gal-10, IL-5, MUC5AC, and IFN-γ were analyzed in Nasal lavage (NL) samples from children with SAR by ELISA. Unsupervised clustering and discriminant analyses were applied. The functional effects of Gal-10 were investigated ex vivo using a 3D epithelial–mesenchymal trophic unit (EMTU) model stimulated with NL containing high, low, or depleted Gal-10 levels. EMT (epithelial–mesenchymal transition) markers (vimentin, E-cadherin, SNAIL1) and MUC5AC secretion were assessed by immunohistochemistry, Western blot, and ELISA. Results: Gal-10 levels in NL positively correlated with IL-5 and MUC5AC and inversely with IFN-γ. Clustering analysis identified distinct SAR endotypes, with Gal-10 showing the highest discriminative power. In the 3D EMTU model, high Gal-10 NL induced increased vimentin and SNAIL1 expression and enhanced MUC5AC secretion, effects attenuated after Gal-10 depletion. Conclusions: Gal-10 is associated with Th2-type inflammation, mucus hypersecretion, and early epithelial–mesenchymal transition in pediatric SAR, supporting its role as a mediator of nasal mucosal remodeling and a potential therapeutic target Full article

Introduction: Chronic Idiopathic Constipation (CIC) is a common pediatric gastrointestinal disorder (GI) characterized by persistent difficulty in defecation, with no identifiable underlying cause. Although most patients are successfully treated with medical therapies, surgical intervention is often needed for refractory disease. We evaluated the impact of Antegrade Continence Enemas (ACE) and Botulinum Toxin (BT) injection to the internal anal sphincter on laxative use, symptom resolution, and healthcare utilization. Methods: A retrospective chart review was conducted to identify patients ≤ 18 years old presenting to a pediatric surgery clinic with a chief complaint of CIC between 1 March 2014 and 1 March 2024. Patients meeting the Rome IV criteria for idiopathic constipation and fecal incontinence were included. Surgical procedures were categorized into BT injection or ACE channel creation. The primary outcome was change in daily oral laxative use at 1 year, and secondary outcomes included symptom resolution and CIC-healthcare utilization at 1 year postoperatively. Results: Of the 125 children who presented with CIC, 47 (37.6%) underwent surgery. Mean age was 6 years at the time of surgery. 17 (36.2%) had ACE channel creation, while 30 (63.8%) received BT injections. At 1 year, daily oral laxative polypharmacy decreased from 60.2% to 41.0%, p < 0.001, with a greater reduction in ACE than BT (adjusted mean difference: −1.05, 95% CI: −1.75 to 0.34, p = 0.004) after adjusting for demographics and baseline clinical factors. Overall, symptom resolution of encopresis (79.1% to 39.5%, p = 0.001), abdominal pain (88.4% to 27.9%, p < 0.001), and abdominal distension (67.4% to 27.9%, p < 0.001) was observed with no significant difference between groups at 1 year. ACE patients had significantly more postoperative outpatient CIC-related visits and no change in ED visits compared to fewer visits in BT patients. Conclusions: Both ACE and BT recipients had improvements in constipation-related symptoms and laxative use. However, ACE resulted in a significantly greater reduction in daily laxative use and more postoperative CIC-healthcare visits than BT alone. Full article

Background/Objectives: Children with single left ventricle (SLV) anatomy following Fontan palliation are at high risk for subclinical ventricular dysfunction, which may not be detected by conventional echocardiographic measures. Our objectives are as follows: (1) to assess myocardial and atrial strain profiles in pediatric Fontan patients with SLV using 2-dimensional speckle-tracking echocardiography (2D-STE), (2) to compare these findings with a healthy control group, (3) to investigate correlations with conventional echocardiographic and functional parameters. Methods: A single-center study of 66 pediatric patients, who underwent echocardiographic evaluation and a 6 min walk test (6 MWT). Conventional, 3D, and strain-based echocardiographic parameters were compared between groups. Correlations with clinical and functional indices were assessed using ANCOVA, analysis, generalized additive models, and Pearson’s correlation coefficient. Results: Fontan patients showed significantly reduced 6 MWT distances compared to controls (mean difference: 201.6 m, p < 0.0001). Post-test heart rate (HR) and oxygen saturation were significantly impaired (HR: 104.6 vs. 100.8 bpm, p = 0.0012; SaO₂: 90.3% vs. 99.8%, p < 0.0001). Fontan patients showed statistically significant differences in nearly all the 2D parameters. Three-dimensional echocardiography revealed significantly lower left ventricular (LV) ejection fraction (p = 0.0020), higher end-diastolic (p = 0.0275) and end-systolic volumes (p = 0.0125) in the study group. Global longitudinal strain (LV_GLS) was reduced in Fontan patients compared to controls (p < 0.0001), with significant differences across nearly all LV segments. Left atrial (LA) reservoir and conduit strain were markedly decreased, while contractile strain remained similar. LV_GLS was negatively correlated with IVCT (r = −0.50, p = 0.0175). The LA reservoir strain (LASr_AC) significantly correlated with MAPSE (r = 0.43, p = 0.0461). Conclusions: In pediatric Fontan patients, myocardial and atrial strain imaging reveals subclinical dysfunction despite preserved conventional ejection fraction. Full article

Background: Stress-related disorders, including PTSD, acute stress disorders, adjustment disorder, and attachment disorders, arise from complex interactions between genetic susceptibility and environmental stressors. While early environmental factors play a central role in the development of these disorders, there is growing evidence that genetic predisposition also contributes to individual differences in vulnerability and resilience. This narrative review examines current evidence on genetic predisposition and resilience mechanisms in stress-related psychopathology during developmental age. Methods: A literature search was performed using PubMed, Cochrane, MedRxiv, and Medline databases, focusing on studies published between 2010 and 2025, written in English, in the pediatric and adolescent population. Priority was given to original research articles and high-impact reviews. Studies were selected based on relevance to the genetic mechanisms underlying vulnerability and resilience to stress. 71 of 317 were selected. Two hundred forty-six articles were excluded due to a lack of relevance to the topic or because they included an adult population. Results: Polymorphisms and epigenetic modifications in genes involved in hypothalamus–pituitary–adrenal axis (FKBP5, NR3C1, ADCYAP1R1 and ACE), serotoninergic (SLC6A4 and HTR2A), noradrenergic and dopaminergic system (COMT and MAOA), BDNF, estrogen receptor and excitatory amino acid transporters are associated with increased risk of psychopathology following early trauma, but are also implicated in the development of resilience. Conclusions: Genetic factors influence both vulnerability and resilience to stress-related disorders. However, further studies based on the role of genetics are needed to advance precision and personalized medicine, which is still largely underexplored to this day in the field of stress-induced disorders. Full article

Adverse childhood experiences (ACEs) are established predictors of long-term health risks. While pediatric practices increasingly screen for social drivers of health (SDOH) and other family psycho-social stressors, routine ACEs screening is not recommended due to lack of evidence for long-term benefit and concerns over stigmatization, re-traumatization, and non-standardized follow-up protocols. We piloted routine ACEs screening in Pediatric Primary Care practices that already routinely screen for SDOH, maternal depression and intimate partner violence (IPV). This retrospective chart review (2016–2020) explored the extent to which these family psycho-social screenings could serve as a relative proxy for ACEs identification. Among 1492 participants (738 children aged 0–5 and 690 caregivers mean age 30.3 ± 6.9), ACE and SDOH screening results were significantly associated (p < 0.002), particularly with housing insecurity (p < 0.014). However, 51.7% of individuals who reported a positive ACE screen were not flagged by the SDOH measure (false negatives), indicating relatively poor sensitivity. The negative predictive value for negative SDOH screens and negative ACEs was higher at 86%. These findings suggest that SDOH screening misses over half of true positives, and therefore reliance on SDOH screening alone may underestimate ACE exposure in pediatric primary care. Full article

Pediatric thrombosis (PT) represents a rare condition that can manifest from neonatal life to adolescence, encompassing life-threatening complications. Its pathogenesis is attributed to immature hemostasis in conjunction with environmental and genetic factors, predominantly including those resulting in increased levels of plasminogen activator inhibitor 1 (PAI-1), the principal inhibitor of fibrinolysis, which is subject to upstream regulation by angiotensin-converting enzyme (ACE). Although the implication of microRNAs (miRNAs), epigenetic modulators of gene expression, has been demonstrated in adult thrombosis, evidence is lacking in the pediatric setting. Here, we investigated the involvement of two miRNA regulators of PAI-1 (SERPINE1 gene) in PT, in relation to clinical and genetic parameters that induce PAI-1 fluctuations. Following bioinformatic target-prediction, miRNA expression was assessed by quantitative real-time PCR in serum-samples of 19 pediatric patients with thrombosis (1–18 months post-incident), and 19 healthy controls. Patients were genotyped for the SERPINE1-4G/5G and ACE-I/D polymorphisms by PCR-based assays. Genotypic and thrombosis-related clinical data were analyzed in relation to miRNA-expression. Two miRNAs (miR-145-5p, miR-34a-5p) were identified to target SERPINE1 mRNA, with miR-34a additionally targeting the mRNA of ACE. The expression of miR-34a was significantly decreased in patients compared to controls (p = 0.029), while no difference was observed in miR-145 expression. Within patients, miR-34a expression demonstrated a peak 1–3 months post-thrombosis and was diminished upon treatment completion (p = 0.031), followed by a slight long-term increase. MiR-34a levels differed significantly by thrombosis site (p = 0.019), while a significant synergistic interaction between site and onset type (provoked/unprovoked) was detected (p = 0.016). Finally, an epistatic modification was observed in cerebral cases, since double homozygosity (4G/4G + D/D) led to a miR-34 decrease, with D/D carriership reversing the 4G/4G-induced upregulation of miR-34a (p = 0.006). Our findings suggest that in pediatric thrombosis, downregulation of miR-34a is indicative of impaired fibrinolytic capacity, attributed to deficient regulation of the inhibitory ACE/PAI-1 axis. Full article

Background: Optical Coherence Tomography (OCT) is a high-resolution imaging technique capable of quantifying Blood Flow at Depth (BD) and the Attenuation Coefficient (AC). However, the clinical relevance of these parameters in burn assessment remains unclear. This study investigated whether OCT-derived metrics can differentiate between superficial and deep pediatric hand burns. Method: This prospective, single-center study analyzed 73 OCT scans from 37 children with thermal hand injuries. A structured algorithm was used to evaluate AC and BD. Results: The mean AC was 1.61 mm⁻¹ (SD ± 0.48), with significantly higher values in deep burns (2.11 mm⁻¹ ± 0.53) compared to superficial burns (1.49 mm⁻¹ ± 0.38; p < 0.001), reflecting increased optical density in more severe burns. BD did not differ significantly between burn depths, although superficial burns more often showed visible capillary networks. Conclusions: This is the first study to assess both AC and BD using OCT in pediatric hand burns. AC demonstrated potential as a diagnostic marker for burn depth, whereas BD had limited utility. Image quality limitations highlight the need for technical improvements to enhance OCT’s clinical application. Full article

As the pediatric COVID-19 landscape evolves, it is essential to evaluate whether SARS-CoV-2 infection predisposes children to allergic disorders. This narrative review synthesizes current epidemiological and immunological evidence linking pediatric COVID-19 with new-onset atopy. Epidemiological data remain heterogeneous: large Korean and multinational cohorts report increased risks of asthma and allergic rhinitis following COVID-19, whereas U.S. cohorts show neutral or protective associations, highlighting geographic and methodological variability. Mechanistic insights provide biological plausibility: epithelial injury and the release of alarmin cytokines (IL-33, IL-25, TSLP) promote Th2 polarization and ILC2 expansion, while epigenetic “scars” (e.g., LMAN2 methylation changes) and hematopoietic stem cell reprogramming may sustain long-term Th2 bias. Cytokine memory involving IL-7 and IL-15 contributes to altered T- and B-cell homeostasis, whereas disrupted regulatory T-cell function may reduce tolerance thresholds. Paradoxical trade-offs exist, such as ACE2 downregulation in allergic airways, which may lower viral entry but simultaneously amplify type-2 inflammation. Together, these processes suggest that SARS-CoV-2 infection could foster a pro-allergic milieu in susceptible children. Although current evidence is inconclusive, integrating epidemiological surveillance with mechanistic studies is crucial for predicting and alleviating post-COVID allergic outcomes. Longitudinal pediatric cohorts and interventions targeting epithelial alarmins or microbiome restoration may hold promise for prevention. Full article

Background/Objectives: Enteric coating protects active pharmaceutical ingredients from gastric degradation, but conventional tablets may present swallowing difficulties in geriatric and pediatric patients. Hence, this study intended to develop pH-responsive multiparticulates, formulated into orally disintegrating tablets (ODTs), for targeted intestinal drug delivery in individuals with dysphagia. Methods: Multiparticulates were developed via sequential seal coating, drug layering, sub-coating, and enteric coating on inert cores using a fluidized bed coater (Pam Glatt, India; bottom spray). Selected enteric-coated batches were directly compressed into ODTs using microcrystalline cellulose (Avicel PH102) and mannitol (Pearlitol SD 160) as fillers, with Explotab^®, Ac-Di-Sol^®, or crospovidone M^® as superdisintegrants. Results: Multiparticulates exhibited mean diameters of 197.671–529.511 μm and span values of 0.603–0.838. Span value < 1, indicating a narrow size distribution. Electron microscopy confirmed the spherical morphology of Batches 7a and b. Enteric-coated batches (5b, 6, 7a, 7b) released ≤10% of the drug in 0.1 N HCl at 2 h. Optimized formulation ODT 7b released 7.904% of the drug under gastric conditions and 79.749% in phosphate buffer (pH 6.8) within 2.5 h, following first-order drug release kinetics. ODT 7b demonstrated hardness (2.538 ± 0.144 kg/cm²), wetting time (11.17 ± 1.051 s), friability (0.712%), and drug content (99.81 ± 1.01%) within acceptable limits. Conclusions: The pH-dependent multiparticulates provided sustained intestinal drug release and, when incorporated into ODTs, yielded a dosage form with a rapid wetting time and acceptable mechanical properties. This dosage form can offer a promising approach for improving compliance and therapeutic efficacy in patients with swallowing difficulties (dysphagia). Full article

Introduction: Human metapneumovirus (HMPV), though commonly perceived as a pediatric pathogen, significantly impacts adults, yet its role in acute respiratory tract infections (ARTIs) remains underappreciated. The COVID-19 pandemic has reshaped respiratory virus epidemiology and amplified the need for comprehensive differential diagnosis. This study aimed to comprehensively investigate the prevalence, clinical characteristics, and post-COVID-19 trends of HMPV infection in adults and to elucidate its critical role in the differential diagnosis of ARTIs by distinguishing it from other common viral pathogens. Methods: This was a retrospective, multicenter study conducted across six hospitals within the Acibadem Hospitals Group in Istanbul, Turkey. Data were collected from two periods: January 2016 to January 2020 (pre-COVID-19) and January 2021 to September 2023 (post-COVID-19), excluding the peak pandemic phase (March 2020 to May 2021). Respiratory samples (sputum, BAL, nasopharyngeal/nasal/throat swabs) were analyzed using multiplex PCR (Seegene RV12-ACE), with an expanded panel including SARS-CoV-2 in the post-COVID-19 era. Demographic data, comorbidities, symptoms, hospitalization, and ICU admission rates were collected. Results: In the post-COVID-19 period, 2197 positive viral panels were recorded, an increase from 1357 in the pre-COVID period, reflecting enhanced testing. HMPV prevalence reached 9.7% post-COVID-19, making it the fourth most common respiratory virus in adults (8.7% of 644 positive adult tests), following SARS-CoV-2 (26.4%), influenza A (21.3%), and rhinovirus (17.5%). The average age of HMPV-infected adults was 52.14 years (18–90 years); 64% were female. While 52% had no comorbidities, common underlying conditions included hypertension (24%), cancer (12%), and diabetes (10%). Weakness (34%), lower respiratory symptoms (16%), and fever (12%) were frequent. A significant proportion of HMPV patients required hospitalization (34%) and ICU admission (18%), with 40% receiving antibiotics. Despite potential severity, the mortality rate was low (2.8%). No significant difference in severity was observed between HMPV monoinfection and co-infected groups (e.g., with influenza A, rhinovirus, SARS-CoV-2, parainfluenza virus 2). Conclusion: Our findings establish HMPV as a significant and increasingly prevalent respiratory pathogen among adults in Istanbul in the post-COVID-19 era. Its non-specific clinical presentation underscores the critical importance of multiplex PCR for accurate differential diagnosis, enabling appropriate patient management and antimicrobial stewardship. While HMPV can lead to severe outcomes requiring hospitalization and ICU admission, particularly in patients with comorbidities, the overall mortality rate remains low. Given the lack of specific antiviral treatments and vaccines, sustained surveillance and continued research into targeted interventions are crucial. Full article

In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950–1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983–1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994–2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010–2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits. Full article