Search Results (547)

Multiple sclerosis (MS) and allergic diseases, traditionally considered immunologically opposing entities, may share pathogenic mechanisms rooted in immune dysregulation. While MS is predominantly mediated by Th1 and Th17 responses and allergies by Th2 responses, emerging evidence suggests overlapping immunological pathways, including the involvement of histamine, regulatory T cells, and innate lymphoid cells. This review synthesizes current knowledge on the epidemiological and immunopathological associations between MS and allergies. Epidemiological studies have yielded inconsistent results, with some suggesting a protective role for respiratory and food allergies against MS onset, while others find no significant correlation. Clinical studies indicate that food allergies in adults may be associated with increased MS inflammatory activity, whereas childhood atopy might exert a protective effect. In addition, we review hypersensitivity reactions to disease-modifying treatments for MS, detailing their immunological mechanisms, clinical presentation, and management, including desensitization protocols where applicable. Finally, we explore how treatments for allergic diseases—such as clemastine, allergen immunotherapy, montelukast, and omalizumab—may modulate MS pathophysiology, offering potential therapeutic synergies. Understanding the interplay between allergic and autoimmune processes is critical for optimizing care and developing innovative treatment approaches in MS. Full article

Purpose: The present study aims to evaluate alterations in the peripapillary retinal nerve fiber layer (RNFL) thickness in pediatric patients following surgical resection of childhood-onset craniopharyngioma (CP) and to identify tumor characteristics and other factors influencing these alterations, including changes in the lesion’s location. Design: retrospective clinical cohort study. Methods: A retrospective analysis was conducted on 73 eyes from 38 patients with CP and 64 eyes from 32 age- and sex-matched healthy controls. The mean age of the CP patients was 10.3 ± 4.2 years (range 4–17), while the control group had a mean age of 10.5 ± 3.1 years (range 4–17). Optical coherence tomography (OCT) was used to assess the peripapillary RNFL thickness in the study and control groups. RNFL thickness was analyzed in the superior, inferior, and average sectors, as well as across eight optic nerve sectors. Tumor characteristics were evaluated to determine their correlation with changes in RNFL thickness in individual sectors. Results: Postoperative thickness of peripapillary RNFL in all individual sectors was significantly reduced in the CP group compared to healthy controls. Location, tumor volume, maximum tumor diameter, calcification, ventriculoperitoneal shunt, surgery technique, total resection, presence of Rosenthal fibers, and reoperation due to progression or recurrence correlated with damage to RNFL. Conclusions: CP is associated with significant reductions in RNFL thickness, indicating the tumor’s impact on optic nerve fibers. OCT is a valuable tool for monitoring visual pathway impairment and postoperative outcomes. Correlations between RNFL thickness in individual sectors and clinical parameters may offer valuable insights for diagnosis and monitoring, underlining their potential role in predicting visual outcomes. Regular RNFL evaluation should be integrated into the long-term care of CP patients to optimize visual prognosis and detect progressive or residual damage. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article

The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article

Background: Childhood obesity is a growing global health concern, with an increasing prevalence of severe obesity among young children. This study aimed to determine the average age of severe obesity onset in Polish children and evaluate the time gap between diagnosis and referral for specialized care. Methods: This data analysis was conducted across four Polish pediatric endocrinology centers specializing in childhood obesity management (Szczecin, Cracow, Zabrze, Rzeszów) between July 2022 and November 2023. The study included 367 children and adolescents (186 boys, 181 girls) aged 0–18 years, diagnosed with severe obesity based on age-specific BMI criteria. Anthropometric measurements were performed during the patient’s inclusion into the study and based on past medical records. BMI and BMI Z-scores were calculated for all current and past measurements. Results: The median age of the study population at the moment of inclusion into the study was 13.7 ± 2.9 years (range: 2.2–18 years). The median BMI was 40.9 ± 5.1 kg/m² (range: 30.1–65.8 kg/m²), and the median BMI Z-score was 2.7 ± 0.4 (range: 2.3–6.2). Out of the 367 children included, 327 (89%) had entered puberty. An analysis of past measurements revealed that 83% of children had severe obesity at their earliest recorded BMI measurement, with n median onset age of 3.2 years. The median age of referral to specialized care was 10 ± 5.0 years, reflecting a delay of almost 7 years from diagnosis to targeted medical care. Conclusions: This study highlights a substantial delay between the onset of severe obesity and referral for specialized care, underscoring the need for earlier intervention strategies tailored to age, sex, and developmental stage. Full article

Background/Objectives: Childhood overweight/obesity status is a critical risk factor for adverse cardiometabolic outcomes. We aimed to evaluate the sex-specific associations between a maintained childhood overweight status and late-adolescent cardiometabolic risk factors using data from a Korean longitudinal study. Methods: We used data from the Korean Children-Adolescents Study, a prospective cohort of children enrolled at age 7 and followed annually from 2005 to 2020. Among participants who were followed at least once, a total of 899 children (438 boys, 461 girls) with consistent body mass index (BMI) status at ages 7–9 and 10–12 were included in the analysis. Participants were categorized into two groups on the basis of BMI: normal weight maintenance and overweight maintenance. Multivariable linear regression was used to examine the associations between BMI patterns and cardiometabolic risk factors, with adjustments for covariates. Results: Among the 899 children (mean age: 7.1 ± 0.4 years, 48.7% boys), 12.8% of boys and 5.9% of girls were classified into the overweight maintenance group. Boys in the overweight maintenance group had significantly greater BMIs, waist circumferences (WC), body fat percentages, trunk fat mass, and aspartate aminotransferase and alanine aminotransferase levels at ages 15 and 18. Girls in the same group had elevated BMI, WC, body fat percentage, trunk fat mass, and blood pressure and experienced earlier pubertal onset. Conclusions: Maintaining an overweight status during childhood is associated with adverse cardiometabolic profiles in adolescence, with sex-specific differences. These findings highlight the importance of early, sex-specific interventions to prevent long-term health risks associated with childhood obesity. Full article

Introduction: The monitoring of autonomic nervous balance during childhood remains underexplored. However, heart rate variability (HRV) is widely recognized as a biomarker of health risk across the lifespan. Juvenile idiopathic arthritis (JIA), a group of chronic inflammatory joint disorders, is associated with persistent inflammation and pain, both of which contribute to increased cardiovascular risk, commonly linked to reduced HRV. Among HRV parameters, very-low frequency (VLF) components have been associated with physiological recovery processes. This study aimed to assess HRV during sleep in patients with JIA. Methods: We studied 10 patients with JIA and 10 age-, gender-, and Tanner stage-matched healthy controls. All participants underwent polysomnographic monitoring following an adaptation night in the sleep laboratory. HRV was analyzed using standard time and frequency domain measures over 5 min epochs across all sleep stages. Frequency components were classified into low- and high-frequency bands, and time domain measures included the standard deviation of the beat-to-beat intervals. Group differences in HRV parameters were assessed using nonparametric tests for independent samples, with a significance level set at p < 0.05. Results: JIA exhibited greater sleep disruption than controls, including reduced NREM sleep, longer total sleep time, and increased wake time after sleep onset. HRV analyses in both time and frequency domains revealed significant differences between groups across all stages of sleep. In JIA patients, the standard deviation of the normal-to-normal interval during slow wave sleep (SWS) and total power across all sleep stages (p < 0.05) was reduced. In JIA patients, the standard deviation of the normal-to-normal interval during slow wave sleep and total power across all sleep stages were significantly reduced (p < 0.05). VLF power was also significantly lower in JIA patients across all sleep stages (p = 0.002), with pronounced reductions during N2 and SWS (p = 0.03 and p = 0.02, respectively). A group effect was observed for total power across all stages, mirroring the VLF findings. Additionally, group differences were detected in LF/HF ratio analyses, although values during N2, SWS, and REM sleep did not differ significantly between groups. Notably, the number of affected joints showed a moderate positive correlation with the parasympathetic HRV parameter. Conclusions: Patients with JIA exhibited sleep disruption and alterations in cardiovascular autonomic functioning during sleep. Reduced HRV across all sleep stages in these patients suggests underlying autonomic nervous dysfunction. Addressing sleep disturbances in patients with chronic pain may serve as an effective strategy for managing their cardiovascular risk. Full article

This overview explores the complex relationship between environmental factors, particularly obesity, and the timing of puberty, with a focus on how hormonal and genetic interactions are influenced by external conditions. Puberty (gonadarche) is characterised by the activation of the hypothalamic–pituitary–gonadal (HPG) axis. The onset and progression of puberty vary significantly among individuals, primarily due to genetic factors, with key genes like kisspeptin 1 (KISS1) and makorin ring finger protein 3 (MKRN3) playing a crucial role. Cohesively, this paper emphasises that environmental factors, particularly obesity and exposure to endocrine-disrupting chemicals (EDCs), have become significant influences on the timing of puberty. Childhood obesity has risen significantly in recent decades and the age of pubertal onset has declined over the same period. Obesity greatly disrupts hormone regulation in pre-pubertal children. Leptin accelerates the onset of puberty in girls but not in boys. The underlying mechanism is proposed to be the increase in Kiss1/GnRH signalling. On the contrary, excess leptin in boys suppresses testosterone production by increasing oestrogen conversion. Low adiponectin in obese girls may contribute to earlier puberty due to a reduced inhibition of Kiss1/GnRH signalling. Low adiponectin in boys is linked to delayed puberty due to its role in maintaining insulin sensitivity and testosterone production. Hyperinsulinemia influences pubertal timing through central and peripheral mechanisms. Insulin acting synergistically with leptin promotes the earlier onset of puberty in girls but not in boys. The effects of exposure to certain EDCs—mostly obesogenic chemicals that mimic the action of natural hormones—on the timing of puberty remain unclear; hence, further research on this topic is needed. Addressing and preventing obesity in children could potentially mitigate these alterations in pubertal timing. Full article

Objective: Epilepsy, a common neurological disorder marked by recurrent seizures often starting in childhood, has a complex etiology. Advances in high-throughput sequencing now confirm that 70–80% of cases have a genetic basis. Accordingly, this study aims to evaluate the clinical relevance of genetic variations detected through epilepsy panels and whole exome sequencing (WES) in pediatric-onset epilepsy patients. Methods: For this study, we enrolled a cohort of pediatric patients involving 205 subjects with a preliminary diagnosis of epilepsy. Targeted next-generation sequencing panels for epilepsy and whole exome sequencing was performed using the NextSeq 500 platform. The results were analyzed with the QIAGEN Clinical Insight bioinformatic platform and were further confirmed and approved by the Human Genome Mutation Database and ClinVar databases. Results: In this study, an epilepsy panel was conducted in 138 patients, and whole exome sequencing was performed in 67 patients. No clinically relevant variants were identified in 29 (21.0%) patients who underwent the epilepsy panel and 27 (40.3%) patients who underwent WES. Variants were detected in 128 different genes in the epilepsy panel group and in 54 different genes in the WES group, with the frequency of these variants limited to one or two patients. Significance: In both the epilepsy panel and WES groups, variants in sodium channel proteins, specifically in the SCN1A, SCN8A, and SCN9A genes, were found to have a high frequency. Collectively, these findings suggest that sodium channel proteins may play an important role in epilepsy. Full article

Background/Objectives: Compulsive rituals in Obsessive–Compulsive Disorder (OCD) are characterized by a specific motor structure, built upon the fragmentation of action flow, obtained through act repetitions and the intrusion of non-functional acts. No study to date has adopted a hierarchical analysis to subtype OCD according to specific behavioral patterns, nor has a possible association between motor profiles and psychopathology been investigated. Methods: This study involved 31 OCD patients (11 female, 35%) and 31 healthy controls (11 female, 35%). The participants were asked to provide videotapes of their behaviors (OCD compulsions for patients and corresponding normal behaviors for healthy controls). BORIS software version 2.84.1 was adopted to analyze the recorded videos. Psychopathology was assessed through the Yale–Brown Obsessive–Compulsive Scale, the Childhood Trauma Questionnaire, the Frankfurt Complaint Questionnaire, and the Social and Occupational Functioning Assessment Scale. Results: Hierarchical analysis revealed three behavioral clusters based on motor profile: Cluster 1 included OCD compulsions structurally characterized by act repetitions (“iterative” rituals); Cluster 2 was represented by OCD compulsions mainly built upon non-functional acts (“idiosyncratic” rituals); and Cluster 3 comprised routinized and normative behaviors, without behavioral ritualization (no act repetitions and few non-functional acts). No significant differences were found in age, age at onset, and OCD severity between “iterative” and “idiosyncratic” rituals. However, patients with “iterative” rituals showed both more severe pre-psychotic symptoms and childhood trauma experiences than patients with “idiosyncratic” rituals. Conclusions: These findings may have significant clinical implications as they hint at a relationship between specific behavioral patterns of OCD compulsions and different underlying psychopathologies and/or vulnerabilities. Full article

Parainfluenza virus (PIV) infections contribute to the overall childhood morbidity from acute respiratory illness, yet virus-specific epidemiologic data are lacking across many regions globally. Here, we describe the clinical manifestations, seasonality, and meteorologic associations with PIV infections in Ecuadorian children. Between July 2018 and July 2023, we documented demographic and clinical information from children younger than 5 years seen in a single public health clinic with signs and symptoms consistent with an acute respiratory infection. Nasopharyngeal swabs collected at study enrollment underwent multiplex polymerase chain reaction-based diagnostic testing (Biofire FilmArray v. 1.7™). Regional meteorological data from the same period were provided by Ecuador’s Instituto Nacional de Meteorologia e Hidrologia. Parainfluenza viruses were detected in 9% of the 1251 enrolled subjects. PIVs were most frequently detected between March and July, with no change in seasonality following SARS-CoV-2 pandemic onset. Clinical manifestations of PIV infections included non-specific upper respiratory illness (82%), laryngotracheitis (3%), and bronchiolitis (11%). Events of PIV detection were negatively associated with ambient temperature and rainfall. Our findings highlight the contribution that PIVs play in the morbidity associated with pediatric medically attended outpatient respiratory tract infection and provide new insights into the seasonal epidemiology of PIV infections in coastal Ecuador. Full article

This report provides a concise selective representative overview of the predictor factors for progression in Idiopathic Scoliosis (IS). The Cobb angle method, rib hump deformity, imaging and advanced techniques for assessing skeletal maturity serve as key elements in evaluating prognostic factors for IS progression based on the patient’s age at diagnosis—particularly in Infantile Idiopathic Scoliosis (IIS), Juvenile Idiopathic Scoliosis (JIS), and Adolescent Idiopathic Scoliosis (AIS). The commonly used approaches for determining skeletal maturity include the assessment of the iliac apophysis and scoliosis curve deterioration, the Sanders skeletal maturity staging system, the distal radius and ulna (DRU) classification for predicting growth spurts and curve progression in IS, as well as the ossification of vertebral epiphyseal rings, the humeral head, and the calcaneal apophysis. Prognostic factors influencing IS progression are further discussed in relation to the patient’s age at onset—whether in infancy, childhood, or adolescence—as well as in both untreated and braced AIS patients. Additionally, the apical convex rib–vertebra angle in AIS is explored as an indicator of progression. Predictors for curve progression at skeletal maturity are outlined, along with various models for forecasting IS deterioration. Lastly, the Rib and Segmental Rib Index, a rib cage deformity parameter, is introduced as a predictor of scoliosis progression. In conclusion, this concise and selective overview of predictor factors for progression in IS highlights the current understanding of IS progression factors. It also introduces the Rib and Segmental Rib Index—a rib cage deformity parameter—as a predictor of IS progression. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder that often persists into adulthood, leading to various adverse outcomes. Its underlying pathology is multifactorial, involving neurotransmitter imbalances, gut microbiota alterations, and oxidative and inflammatory dysregulation. Diet, a key environmental modifier of gut ecology, is consistently poorer in individuals with ADHD, with multiple nutrients implicated in its pathophysiology. This review examines the role of specific nutrients such as omega-3 fatty acids, key micronutrients, and potentially harmful dietary components, as well as broader dietary patterns, particularly the Western diet and Mediterranean diet (MedDiet), in relation to ADHD symptoms. It also evaluates both whole-diet and supplement-based clinical interventions, supporting the growing recognition of nutrition as a safe and relatively affordable modifiable factor in ADHD management. Additionally, the biological mechanisms linking diet to ADHD are reviewed, highlighting strong evidence for the involvement of gut dysbiosis and inflammatory processes. Despite the well-documented antioxidant, anti-inflammatory, and microbiome benefits of the MedDiet, direct research investigating its role in ADHD remains limited. Most whole-diet approaches to date have focused on elimination diets, leaving a significant gap in understanding the potential role of the MedDiet in ADHD management. Therefore, this review outlines preliminary evidence supporting the MedDiet and its key components as modulators of ADHD-related biological pathways, indicating its potential as a therapeutic approach. However, further research is required to rigorously evaluate its clinical efficacy. Finally, the limitations of observational and interventional nutritional research in ADHD are discussed, along with recommendations for future research directions. Full article

Background: N-glycosylation is a post-translational modification involving the attachment of oligosaccharides to proteins and is known to influence immunoglobulin G (IgG) effector functions and even antigen binding. IgG contains an evolutionarily conserved N-glycosylation site in its fragment crystallizable (Fc) region, while during V-D-J recombination and somatic hypermutation processes it can also obtain N-glycosylation sites in its antigen binding fragment (Fab). Our previous study demonstrated altered IgG N-glycosylation in children at type 1 diabetes (T1D) onset, with the most prominent changes involving sialylated glycans, hypothesized to mainly come from the Fab region, however, the analytical method used could not distinguish between Fc and Fab. Methods: IgG was isolated from plasma from 118 children with T1D and 98 healthy controls from the Danish Registry of Childhood and Adolescent Diabetes. Isolated IgG was cleaved into Fc and Fab fragments using IdeS enzyme. N-glycans were enzymatically released from each fragment, fluorescently labelled with procainamide, and analyzed separately using the UPLC-MS method. Structural annotation of resulting chromatograms was performed using MS/MS. Results: T1D related N-glycosylation changes were more pronounced in the Fab glycans compared to Fc glycans, with five Fab glycans (Man5, Man7, FA2BG1S1, A2G2S2, FA2BG2S1) being significantly altered compared to only one in the Fc region (FA2[3]BG1). Comparing Fc and Fab glycosylation overall reveals stark differences in the types of glycans on each region, with a more diverse and complex repertoire being present in the Fab region. Conclusions: These findings suggest that N-glycosylation changes in early onset T1D predominantly originate from the Fab region, underscoring their potential role in modulating (auto)immunity and highlighting distinct glycosylation patterns between Fc and Fab. Full article