Immunoglobulin A (IgA) deficiency is the most common primary antibody deficiency and contributes to recurrent respiratory tract infections (rRTIs) in children, with prevalence rates in this group ranging from 1:4 to 1:65. Previous studies in healthy humans and animals suggest that the gut microbiota significantly influences IgA production. We investigated the role of the gut microbiota in IgA deficiency and its potential in promoting IgA induction in children with rRTIs. Children under 7 years of age with rRTIs were enrolled in a prospective cohort study. Serum and feces were collected for IgA level measurement using ELISA and to determine the composition of the intestinal microbiota by 16S rRNA sequencing. We included 82 children with rRTIs, 38
Paediatric septic thrombophlebitis secondary to head and neck infections is a rare but life-threatening disease. Although commonly associated with oropharyngeal infections, otogenic cases have also been described, yet paediatric literature on their disease course and thrombotic distribution remains sparse. To describe the clinical presentation, thrombotic distribution, management, and outcomes of paediatric septic thrombophlebitis secondary to primary otogenic infections. We conducted a retrospective case series of children aged 0–18 years admitted to a tertiary paediatric referral centre between 2016 and 2021 with septic thrombophlebitis following an otogenic infection. Clinical, microbiological, radiological, and treatment data were extracted from records. Ten patients (median age 4.5 years, 70
Abstract Background Although individual rare and complex diseases (RDs) affect small patient populations, together they impact an estimated 27–36 million people across the European Union. Addressing this major public health challenge has been a long-term priority for the European Union, leading to the establishment of the European Reference Networks (ERNs) in 2017. Main body ERNs are cross-border networks connecting clinical expert centres to share knowledge, improve and harmonise diagnosis and care for patients with rare and complex diseases. Since their inception, 24 ERNs have united 1,606 expert centres across 375 hospitals in all EU Member States and Norway. Their activities span multidisciplinary clinical collaboration, patient-centred governance, education and training, and the development of clinical guidelines. Over 4900 extremely rare or difficult cases have been discussed among experts without requiring the patients to travel abroad when expertise was not available in their own countries. A key factor for this success is the cross-border IT platform - known as the Clinical Patient Management System 2.0 - provided by the European Commission for medical discussions, which enables experts to share patient data, including medical images and lab results, in a secure and protected environment that is fully compliant with all relevant security and data privacy requirements. ERNs have demonstrated resilience in crises such as the COVID-19 pandemic and the war in Ukraine, providing rapid, coordinated responses to sustain care for vulnerable patient groups. The first formal evaluation in 2023 confirmed that more than 95% of member centres met quality standards, underscoring the networks’ maturity and effectiveness. Moving into the next phase, the Joint Action JARDIN (2024–2027) aims to integrate ERNs into national healthcare systems to ensure sustainability and equitable access to high-quality RD care. Conclusions ERNs exemplify European solidarity and innovation in healthcare, transforming how rare disease expertise is shared and applied across borders. Their continued integration into national systems will be pivotal to achieving a truly cohesive European Health Union that delivers improved outcomes for all patients with rare and complex diseases.
Abstract Background Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease associated with ventricular arrhythmias (VAs) and progressive right ventricular systolic dysfunction. Exercise triggers most VAs and increases phenotypic penetrance among ACM-associated pathogenic variant carriers. However, evidence on the interaction between exercise and ACM remains limited. Moreover, while metabolic dysfunction has been demonstrated in other cardiomyopathies and heart failure, data in ACM are scarce(1,2). Purpose To investigate the metabolic response of ACM-associated pathogenic variant carriers to cardiopulmonary exercise testing (CPET) using indirect calorimetry and untargeted metabolomics. Methods This cross-sectional case-control study included 20 plakophilin-2 (PKP2) pathogenic variant carriers and 10 age- and sex-matched healthy controls (35 ± 11 vs 30 ± 3 years, respectively, p=0.20; 60% males in both groups). The PKP2 group included 10 patients with a definite ACM diagnosis as per 2010 Task Force Criteria. Participants performed a CPET with incremental workload until volitional exhaustion. Fat and carbohydrate (CHO) oxidation were calculated using indirect calorimetry(3). CPET data were collected at rest, low-intensity exercise (i.e. increase in heart rate of 30 bpm from baseline), moderate-intensity exercise (i.e. reaching the ventilatory anaerobic threshold; VT1) and peak-intensity exercise. Untargeted metabolomics by mass spectrometry on dried blood spots was performed from samples collected 3 minutes after peak exercise. Metabolites significantly different in both univariate analysis (fold-change analysis with an FC >2 cut-off) and multivariate analysis (s-PLSDA) were considered of interest. Results Maximal oxygen uptake (VO2max), peak heart rate and peak power output were significantly lower in the PKP2 group than in controls, despite no difference in peak respiratory exchange ratio (Figure 1). PKP2 carriers and controls did not show differences in fat and CHO oxidation at rest, while at low intensity exercise (i.e. before VT1) fat oxidation was significantly lower (0.18 ± 0.10 g/min vs 0.32 ± 0.14 g/min, p=0.002) and CHO oxidation higher (0.80 ± 0.34 g/min vs 0.30 ± 0.26 g/min, p<0.001) in the PKP2 group than in controls, even when correcting for VO2max and body mass index (BMI). Out of 1792 detected peaks, levels of 31 metabolites were significantly different in both statistical analyses (Figure 2). Among those, metabolites involved in fatty acid metabolism (dodecenoylcarnitine; tetradecadiencarnitine; oxo-methylthiobutanoic acid) and branched-chain amino acid metabolism ([iso]leucine; methyl-ketovaleric acid) were significantly lower in PKP2 carriers after exercise. Conclusion Our results support metabolic dysfunction upon exercise in PKP2 carriers. CPET results showed impaired fat oxidation and untargeted metabolomics further suggests a shift towards a more CHO-based metabolism.Fig 1.CPET dataFor image description, please refer to the figure legend and surrounding text.Fig 2.Heatmap of metabolites of interestFor image description, please refer to the figure legend and surrounding text.
Abstract Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry is a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions.
