Search Results (67)

Background/Objectives: The global incidence of diabetes in childhood is increasing, raising concern about its long-term effects on the developing brain. Although paediatric diabetes research has traditionally focused on microvascular and macrovascular complications, accumulating evidence indicates that the brain is also a vulnerable target. Methods: This narrative review synthesizes current knowledge on the impact of diabetes on brain health in children and adolescents, with emphasis on epidemiology, neuroimaging and cognitive outcomes, underlying mechanisms, risk and protective factors, and clinical implications. Results: In type 1 diabetes (T1D), studies consistently demonstrate subtle but measurable alterations in brain structure, including reduced growth of total, grey, and white matter volumes, alongside functional and microstructural changes. These neurobiological differences are associated with mild deficits in cognition, particularly in attention, executive function, memory, and processing speed. While clinically significant impairment affects a minority, subclinical alterations are common and may accumulate over time. Key risk factors include chronic hyperglycaemia, glycaemic variability, severe hypoglycaemia, diabetic ketoacidosis, and younger age at onset, whereas good glycaemic stability, diabetes technologies, supportive psychosocial environments, and adequate sleep appear protective. Proposed mechanisms involve oxidative stress, neuroinflammation, disrupted insulin signalling, altered cerebral metabolism, and vulnerability of the immature brain during critical developmental windows. Type 2 diabetes (T2D), increasingly diagnosed in youth, is also associated with adverse brain outcomes. Emerging data link early-onset T2D to alterations in brain structure and connectivity, poorer cognitive performance, and increased mental health burden, mediated by hyperglycaemia, insulin resistance, inflammation, and psychosocial stressors. Conclusions: Overall, childhood diabetes—both T1D and T2D—is associated with meaningful effects on brain development and function. Longitudinal and interventional studies are needed to establish causality and determine whether optimizing glycaemic control and psychosocial support can mitigate neurocognitive risk. Recognizing brain health as a potential complication of paediatric diabetes has important implications for monitoring, prevention, and clinical care. Full article

Background/Objectives: Childhood-onset Sjögren disease (cSjD) is a rare autoimmune disorder with heterogeneous manifestations and ongoing diagnostic challenges, as there are no validated paediatric criteria. Our study aims to characterise the clinical, laboratory, and imaging features of children diagnosed with cSjD at a single Romanian paediatric rheumatology centre between 2015 and 2025 and contextualise these findings within the most recent literature. Methods: A retrospective review of 15 consecutive cSjD patients was conducted, including clinical features, autoantibodies, imaging, biopsy findings, treatment, and outcomes. Results: Our cohort showed a significant female predominance (80%) and a broad age range at disease onset (3–15 years). Extraglandular manifestations were more common at presentation than glandular phenotypes (53.3% vs. 40%). Lupus-like extraglandular presentations frequently led to initial misdiagnosis as childhood-onset systemic lupus erythematosus (SLE) in our cohort. Sicca symptoms were present at diagnosis in only 3 of 15 patients (20%) and developed later during follow-up in an additional 4 patients (26.7%). Notably, the cohort included novel findings, such as an unprecedented presentation with acute exudative pericarditis complicated by cardiac tamponade. Anti-SSA antibodies and salivary gland ultrasound abnormalities were highly prevalent (86.7% and 100%, respectively). Anti-SSB antibodies were detected in seven patients (46.7%), with titres showing more variability than those of anti-SSA, ranging from just above the positivity threshold to mildly elevated levels. The association with macro-creatine kinase type I was another distinctive feature of this series. Chronic musculoskeletal pain and dryness were our patients’ most frequently reported symptoms at the last assessment, affecting up to 5/15 (33.3%) in each domain. One patient showed irreversible ocular damage during our study. Conclusions: Extraglandular presentations of cSjD are highly heterogeneous and diagnostically challenging, often occurring without glandular symptoms. Lupus-like systemic features—including facial vasculitic purpura, with or without arthralgia, and occasional pericarditis, as observed in our cohort—may contribute to frequent initial diagnostic misattribution to SLE. Early salivary gland ultrasonography, targeted autoantibody testing, and selective biopsy are essential for timely diagnosis, underscoring the urgent need for paediatric-specific validated classification criteria. Full article

Improved survival rates for paediatric cancer patients represent a major medical achievement, but they have simultaneously brought the long-term sequelae of oncological treatments into sharp focus. Cardiotoxicity stands out as one of the most serious complications, being the leading cause of non-relapse-related morbidity and mortality among childhood cancer survivors. This comprehensive review analyses the current landscape, highlighting the significant gap in evidence that hinders optimal care. This paper constitutes a comprehensive narrative and scoping review based on a critical analysis of current clinical guidelines, landmark studies, and consensus papers in paediatric cardio-oncology. Crucially, it assesses the heterogeneity and limitations of existing evidence regarding standardized surveillance protocols, primary prevention strategies, and acute/late-onset cardiovascular complication management. The review then identifies and critically discusses key areas for future research and clinical development. A critical gap in evidence persists in paediatric cardio-oncology, leading to significant variability in clinical practice and the underdiagnosis/undertreatment of cardiovascular risk factors in this vulnerable population. To bridge this gap, there is an urgent need for international collaborative research. The overarching goal is to transform paediatric cardio-oncology into a predictive and preventive speciality, ensuring that all childhood cancer survivors achieve not only extended life expectancy but also improved cardiovascular quality of life. Full article

Background: Growth impairment and poor nutritional status are recognized complications of pediatric inflammatory bowel disease (IBD), yet data specific to ulcerative colitis (UC) are limited. This systematic review aims to provide an overview of current knowledge on growth, nutritional status, and body composition in children and adolescents with UC. Methods: A systematic literature search was performed up to August 2025. Studies including patients aged 5–22 years with confirmed UC were reviewed. Results related to growth, nutritional status, and body composition were narratively synthesized to summarize findings. Results: Fifteen studies with 1575 patients with UC met inclusion criteria, comprising 5 prospective, 5 cross-sectional, and 5 retrospective designs. Although the included studies were conducted in broader IBD cohorts, only UC-specific outcomes were reported. The data were limited by sample size, heterogeneity in patient characteristics, outcome definitions, and assessment methods. The majority of patients had prolonged disease with remission or mild activity. Growth failure prevalence ranged from 7% to 36%, with weight deficits being more common than height deficits. Undernutrition affected up to 25% of patients, with variability across studies. Overweight and obesity were also observed, though most studies showed no significant differences between UC patients and controls. Only five very small studies assessed body composition, reporting inconsistent findings regarding reductions in lean body mass. Conclusions: Growth impairment and poor nutritional status can occur in children and adolescents with UC. Larger, standardized, high-quality studies focused specifically on UC are needed to better characterize its impact on growth and nutritional status, including the essential integration of body composition assessment. Full article

Objectives: To investigate the clinical value of cerebrospinal fluid (CSF) testing for biogenic amine, pterins, amino acids, and folates in paediatric onset epilepsies. Methods: Retrospective clinical and biochemical phenotyping of patients with epilepsy who underwent diagnostic CSF measurement of monoamine neurotransmitters, pterins, folates, and amino acids between 2009 and 2022. Results: The studied cohort included 123 patients with epilepsy (mean age at the procedure: 4.54 ± 3.65 years). The diagnostic yield for primary neurotransmitter disorders was 1.68% and zero for inherited amino acid and folate metabolism disorders. Patients with higher seizure frequency showed higher levels of CSF homovanillic acid (HVA) and HVA/5-hydroxyindolacetic acid (5HIAA) ratio. Lower levels of 3-O-methyldopa (3-OMD) were found in patients with co-occurring neurodevelopmental disorders, and lower levels of biopterin, 3-methoxy-4-hydroxyphenylglycol (3-MHPG) and 5-methyltetrahydrofolate (5-MTHF) in those with movement disorders. Significantly lower CSF glutamine levels were found in patients receiving antiseizure medications as polytherapy. Patients with a history of status epilepticus had significantly lower levels of CSF aspartic acid, glycine, leucine, ornithine, and valine, and higher levels of CSF serine. Conclusions: CSF analysis disclosed differences in the concentrations of various metabolites that might be related to the severity of the epilepsy, the presence of comorbid conditions, and medications. Full article

Psychotropic medication is commonly used for the treatment of mental health conditions. However, the genetic factors that influence psychotropic medication responses in children have not been thoroughly investigated. To address this gap, a systematic review and thematic analysis were conducted to examine the genetic impact of psychotropic medication response in children. The Down and Blacks and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists assessed the quality of studies and health economics, respectively. Using PRISMA reporting guidelines, 50 articles were identified with a sample size ranging from 2 to 2.9 million individuals. Most of the studies reported on ethnicity, and approximately half of the studies (24/50) were performed in North America. Five themes emerged from the thematic analysis: (1) implications of non-CYP450 polymorphisms, (2) paediatric CYP450 pharmacogenetics, (3) genetic predictors of response, (4) insights for implementation and future research and (5) phenoconversion. The thematic analysis revealed that assessment of non-CYP450 polymorphisms and psychotropic medication response, especially in those with mental health conditions such as autism, would be helpful. Epilepsy onset, risk and treatment response were associated with non-CYP450 genetic variants. Phenoconversion of substrates associated with CYP2D6 and CYP2C19 metabolisers is common in individuals with mental health conditions, and ABCB1 variants can influence psychotropic medication responses. A multidisciplinary model could also help guide clinical decision-making in cases involving complex neurodevelopmental profiles. Using the Down and Blacks checklist, the average score from the 50 studies was 17.7 points (min. 14, max. 24). The health economic evaluation of studies using the CHEERS checklist gave an average score of 33.0% (range: 21.4% to 35.7%). The study provides an important resource of information for healthcare professionals, researchers and policymakers working at the intersection of child psychiatry, pharmacogenomics and precision medicine. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Background: GSK3β is an intracellular regulatory kinase that is dysregulated in multiple tissues in Type 1 myotonic dystrophy (DM-1). Tideglusib inhibits GSK3β activity in preclinical models of DM-1 and promotes cellular maturation, normalising aberrant molecular and behavioural phenotypes. It is currently in clinical development for the treatment of paediatric and adult patients affected by congenital and juvenile-onset DM-1. Here, we summarise the development of a population pharmacokinetic model and subsequent characterisation of influential demographic and clinical factors on the systemic exposure to tideglusib. The availability of a population PK model will allow further evaluation of age-and weight-related changes in drug disposition, supporting the dose rationale and implementation of a paediatric extrapolation plan. Methods: Given the sparse pharmacokinetic sampling scheme in patients receiving tideglusib, model development was implemented in two steps. First, data from Phase I studies in healthy elderly subjects (i.e., 1832 plasma samples, n = 54) were used to describe the population pharmacokinetics of tideglusib in adults. Then, pharmacokinetic model parameter estimates obtained from healthy subjects were used as priors for the evaluation of the disposition of tideglusib in adolescent and adult DM-1 patients (51 plasma samples, n = 16), taking into account demographic and clinical baseline characteristics, as well as food intake. Secondary pharmacokinetic parameters (AUC, C_max and T_max) were derived and summarised by descriptive statistics. Results: Tideglusib pharmacokinetics was described by a two-compartment model with first-order elimination and dose-dependent bioavailability. There were no significant differences in disposition parameters between healthy subjects and DM-1 patients. Body weight was a significant covariate on clearance and volume of distribution. Median AUC_(0–12) and C_max were 1218.1 vs. 3145.7 ng/mL∙h and 513.5 vs. 1170.9 ng/mL, following once daily doses of 400 and 1000 mg tideglusib, respectively. In addition, the time of food intake post-dose or the type of meal appeared to affect the overall exposure to tideglusib. No accumulation, metabolic inhibition, or induction was observed during the treatment period. Conclusions: Even though clearance was constant over the dose range between 400 and 1000 mg, a less than proportional increase in systemic exposure appears to be caused by the dose-dependent bioavailability, which reflects the solubility properties of tideglusib. Despite large interindividual variability in the tideglusib concentration vs. time profiles, body weight was the only explanatory covariate for the observed differences. This finding suggests that the use of weight-banded or weight-normalised doses should be considered to ensure comparable exposure across the paediatric population, regardless of age or body weight. Full article

Introduction: Paediatric acute haematogenous bone and joint infections (BJIs) are serious conditions. This study aimed to analyse the characteristics of paediatric acute haematogenous osteomyelitis (AHO) and septic arthritis (SA) in Hungary, with a focus on causative pathogens, clinical outcomes, and long-term complications. Methods: A retrospective cohort study was conducted at a Hungarian tertiary referral centre between 2015 and 2022. Children aged 18 years or younger diagnosed with acute haematogenous osteomyelitis (AHO) or septic arthritis (SA) within two months of symptom onset were included. Exclusion criteria were chronic infection, post-operative infections, or wound-related infections. Complicated AHO was defined by intraosseous abscess or necrosis confirmed radiologically or intraoperatively. The primary outcome was surgical intervention beyond 30 days after diagnosis; secondary outcomes included long-term complications. Results: Forty patients were included (77.5% male, median age 8.7 years). AHO was diagnosed in 8 patients (20.0%), complicated AHO in 22 (55.0%), and SA in 10 (25.0%). MRI had the highest diagnostic sensitivity (97.0%). Pathogens were identified in 72.5% of cases; Staphylococcus aureus (S. aureus) was most common (57.5%), followed by Salmonella and Streptococcus pyogenes (5% each). Surgery was required in 90.0% of SA cases, 77.2% of complicated AHO, and 37.5% of uncomplicated AHO. Long-term complications occurred in 10%, mainly with S. aureus and complicated AHO. Conclusions: Paediatric BJIs, especially due to S. aureus, often require surgery and cause long-term sequelae. Full article

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R² = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits. Full article

This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4/84) and 19.1% in adults (13/68). The median age of CFRD diagnosis was 14 years (range 9–22 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia. Full article

Paediatric congenital enteropathies (PCEs) are a group of rare inherited diseases with a typical early onset in life. Prompt identification and treatment are crucial to avoid potentially fatal consequences. This review aims to provide a paradigmatic framework for clinical and histological identification of PCEs, with an emphasis on congenital conditions involving epithelial shape, trafficking and polarity, enteroendocrine function, immunomodulatory diseases, and extremely early onset inflammatory bowel illness. A proper classification is founded on histopathological characteristics and clinical parameters (such as consanguinity, anomalies in amniotic fluid, prenatal expression or early neonatal onset, stool appearance, persistence of symptoms despite fasting, and extra-intestinal manifestations, etc.). The increasing accessibility and convenience of genetic tests has also accelerated the identification of genes related to specific phenotypes of PCEs, improving the diagnostic and care pathway. As a “niche” pathology, PCEs are susceptible to misdiagnosis due to a limited awareness of these entities, and their identification requires extensive training and specialized facilities. The aim of our review is to emphasize the importance of an integrated approach, combining clinical, histological, and molecular analysis, to achieve a definitive diagnosis and guide the treatment. Full article

Background: Neonatal sepsis is a major cause of infant mortality, and it accounts for a significant consumption of antimicrobials in paediatrics. This is the first comprehensive study on neonatal sepsis in Hong Kong. Methods: From 2014 to 2023, all neonates admitted to a single institution with culture-proven infections from the blood and/or cerebrospinal fluid were selected and reviewed retrospectively. The infecting organisms, their antibiotic nonsusceptibility pattern, and the concordance of empirical antimicrobial therapy with the microbiological profiles were described and were further compared between infants of normal/low birth weight (≥1.5 kg) and very low/extremely low birth weight (<1.5 kg), early-onset sepsis (<72 h), and late-onset sepsis (4–28 days), the first and the second 5-year periods (2014–2018 vs. 2019–2023). Results: After contaminants were excluded, there were 118 affected neonates with 125 organisms identified. Fifty-nine were male. Thirty-four were very low/extremely low birth weight infants, and twenty-eight infants had early-onset sepsis. Patient demographics and the microbiology findings did not differ between the first 5 years and the latter 5 years. However, the incidence of neonatal sepsis was significantly lower in the latter 5 years (3.23 vs. 1.61 per 1000 live births, p < 0.001), the period that coincided with the COVID-19 pandemic. Escherichia coli was the most common Gram-negative pathogen. Streptococcus agalactiae and Streptococcus bovis group infections were more common in early-onset sepsis, while coagulase-negative Staphylococcus and non-E. coli Gram-negative pathogens were more likely to occur in late-onset sepsis. In very low/extremely low birth weight infants, the rate of cefotaxime or ceftriaxone nonsusceptibility among Gram-negative isolates was higher (p = 0.01), and concordance of empirical antimicrobial therapy was lower (p = 0.006). Conclusions: Management of neonatal sepsis remains challenging, and there is a need for optimising antimicrobial therapy, especially in preterm patients. Antepartum screening with intrapartum antibiotic prophylaxis is effective in reducing the risk of early-onset sepsis associated with S. agalactiae, while stringent infection control measures are important for the prevention of late-onset sepsis. Full article

Background: Evidence of the beneficial effects of animal-assisted interventions (AAI) on patients admitted to paediatric hospitals is growing. However, there is still little information about healthcare professionals’ knowledge of and attitudes towards AAI, both as a complement to medical treatments and as a tool for improving the workplace environment. The present study explores the perspectives of Italian paediatric hospital staff after the onset of the COVID-19 pandemic. Methods: An online questionnaire was developed and distributed to paediatric hospital personnel across Italy. The questionnaire addressed topics including AAI’ impact on the hospital environment, their role as a resource for patients and families, their effect on staff well-being, and the perception of the feasibility of AAI implementation in hospitals. Data were analysed descriptively and qualitatively. Results: A total of 44 respondents took part in the survey. Most respondents agreed that AAI could improve hospital environments and serve as a valuable resource for patients and families. However, results were more mixed about the effects of AAI on staff well-being and the feasibility of their implementation. Qualitative analysis identified recurring themes including the positive impact of AAI on emotions/general well-being, improved compliance and treatment outcomes, and reduced stress and distress. Concerns included organisational/logistical challenges, hygiene issues, and potential impact on staff workload. Notably, most participants felt that the COVID-19 pandemic had not affected their perception of AAI safety. Conclusions: Most respondents viewed AAI favourably and supported their implementation as a means of benefiting patients and caregivers. Concerns mainly related to organisational and logistical barriers highlight areas that require further exploration in future research. Full article

Background/Objectives: Children with congenital or early onset sensorineural hearing loss (SNHL) are at a greater risk of vestibular dysfunction (VD), hypothesized to occur from the close embryological relationship between the cochlear and vestibular systems. Even with increasing focus on early detection and rehabilitation through Universal Newborn Hearing Screening (UNHS) programmes in many countries, few studies have focused on the prevalence and feasibility of vestibular assessment in infant populations. The objectives of this review are to 1. identify the prevalence of VD infants with congenital or early onset (<12 months old) SNHL, 2. identify which vestibular assessment tests/protocols are conducted on this population, 3. report sensitivity and specificity values for identified vestibular assessment tests/protocols. Methods: Studies that included infants aged 0–12 months, with congenital or early onset SNHL of any laterality, degree, or configuration, and who underwent any method of vestibular assessment were included. The review adhered to the Joanna Briggs Institute (JBI) guidance and the PRISMA-ScR extension statement. Results: A total of 18 studies were included in the review. All articles reported that infants with congenital or early onset SNHL are at a greater risk of VD, particularly those with bilateral severe–profound SNHL. The cervical vestibular-evoked myogenic potentials (cVEMP) test was the most frequently identified vestibular assessment tool for this age demographic. Conclusions: Results from the included articles coincide with results from literature assessing older paediatric populations. cVEMPs have been reported to be a feasible, sensitive, and specific screening tool in infants with congenital or early onset SNHL. The prevalence of VD in infants with congenital or early onset SNHL justify further investigation on the feasibility of establishing a pathway for vestibular assessment for all infants referred by UNHS programmes. Full article