Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization.

Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance—particularly during early life—restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications—including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders—remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit.

Hydrolyzed rice formulas (HRF) are a suitable option for the nutritional management of non-breastfed children with cow’s milk allergy (CMA). Human milk oligosaccharides (HMOs) enhance gastrointestinal health, promote the growth of beneficial gut microbiota, and may reduce the incidence of infections and antibiotic use. There is currently no evidence regarding the hypoallergenicity of HRF containing HMOs. The purpose of this study is to demonstrate the hypoallergenicity of a new hydrolyzed rice protein-based formula containing two manufactured HMOs (HRF-HMO). RIGHT-HY is a multi-center randomized controlled study enrolling infants and children (60 days–3 years) with documented Immunoglobulin E-mediated CMA. Children will be randomized in a crossover fashion to double-blind placebo-controlled food challenges (DBPCFC) with HRF-HMO and an amino acid-based formula (AAF)-HMO, followed by a 7-days open challenge with HRF-HMO requiring a daily minimum intake of 240 ml. Both formulas contain 2-fucosyllactose and lacto-N-neotetraose (1.5 g/L). The primary objective is to demonstrate with 95% confidence that 90% of children with CMA do not develop allergic reactions to HRF-HMO under DBPCFC conditions. Up to 67 children will be enrolled to meet the hypoallergenicity criteria. This sample size allows for a 10% drop-out rate and occurrence of one allergic reaction. An interim analysis will be performed after 42 children have completed both food challenges to assess whether hypoallergenicity criteria have been met, in which case, the study will be stopped for success. Secondary endpoints include HRF-HMO intake and gastrointestinal tolerance during the week-long open challenge, and adverse events throughout the study. The RIGHT-HY study was approved by ethical committees of all participating sites. This study will be the first to generate robust evidence on the hypoallergenicity of this rice formula with added HMOs in children with CMA. The results of the study will be disseminated in peer-reviewed publications and presentations at scientific conferences.Study protocol registrationhttps://clinicaltrials.gov/study/NCT06633289, identifier NCT06633289.

Background: Invasive meningococcal disease (IMD) remains a rare but severe condition associated with high mortality and a significant risk of long-term sequelae. Despite global vaccination efforts, the epidemiology of Neisseria meningitidis continues to evolve, with serogroup B (MenB) representing the predominant cause of IMD in many high-income countries. Methods: This consensus document reviews current evidence on MenB epidemiology and the role of the multicomponent meningococcal serogroup B vaccine (4CMenB), with a focus on immunogenicity, strain coverage, real-world effectiveness, and remaining challenges. Results: Protein-based MenB vaccines have overcome the limitations of polysaccharide approaches, demonstrating robust immunogenicity across age groups. Real-world data confirm substantial vaccine effectiveness, particularly in infant immunization programs and outbreak settings, with significant reductions in disease incidence. For example, in England in the 3 years after vaccine introduction, MenB IMD incidence declined by 75% in immunized infants compared to unvaccinated controls. Adjusted vaccine efficacy was 52.7% after the two-dose primary series and 59.1% following the booster dose, highlighting the contribution of the booster. However, protection is influenced by antigenic variability among circulating strains, resulting in incomplete and geographically variable coverage. In addition, antibody waning over time and the limited impact on nasopharyngeal carriage reduce the potential for long-term and indirect protection. These factors highlight the need to optimize vaccination strategies, including the timing of booster doses, particularly in adolescents, and the role of vaccination in different epidemiological contexts. In this regard, it is not precisely defined whether infants who were immunized in the first year of life need a booster dose in the preschool period, especially in countries with a high incidence of MenB disease. Moreover, it is not established whether and when adolescents who were vaccinated both in infancy and during the preschool period need a booster dose. Economic considerations and variability in national immunization policies further contribute to heterogeneity in vaccine implementation. Emerging evidence suggests possible cross-protection against other meningococcal serogroups and Neisseria gonorrhoeae, although findings remain inconsistent across different risk groups and do not allow us to recommend 4CMenB vaccine beyond MenB IBD prevention. Conclusions: 4CMenB is an effective tool for preventing MenB IMD, although further studies are needed. Future strategies should prioritize age-targeted boosting and enhanced genomic surveillance to maximize impact.

Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infec-tion and a major contributor to lower respiratory tract disease, hospitalization, and intensive care admission in young infants. The burden of severe disease is greatest during the first months of life, when active infant immunization is not yet feasible or may not provide sufficiently rapid protec-tion. The recent availability of prefusion F protein–based vaccines and long-acting monoclonal antibodies has transformed the RSV prevention landscape, making protection during early in-fancy an achievable public health objective. Methods: This consensus document summarizes and critically appraises updated evidence on RSV epidemiology, disease burden, seasonality, pre-ventive strategies, and implementation challenges, with a specific focus on maternal immuniza-tion. Evidence was reviewed in relation to infant protection, transplacental antibody transfer, optimal timing of vaccination during pregnancy, integration into antenatal care, and the posi-tioning of maternal vaccination alongside infant monoclonal antibody prophylaxis. Results: RSV imposes a substantial clinical and economic burden in infancy, including among previously healthy term infants, with the most severe outcomes concentrated in the first months after birth. Post-pandemic changes in RSV circulation have reduced the predictability of seasonal patterns, challenging prevention strategies based solely on traditional RSV seasons. Maternal RSV vac-cination provides passive protection to newborns through transplacental transfer of neutralizing antibodies and has demonstrated efficacy in reducing medically attended RSV-associated lower respiratory tract infection, severe disease, and hospitalization in early infancy. However, re-al-world effectiveness depends on several factors, including gestational age at vaccination, the interval between vaccination and delivery, prematurity, maternal immune response, vaccine uptake, and local RSV epidemiology. The coexistence of maternal vaccination and infant mono-clonal antibody prophylaxis requires clear, coordinated recommendations to prevent gaps in protection and support efficient resource allocation. Conclusions: Maternal immunization is a clinically relevant strategy to protect infants against RSV during their period of greatest vulner-ability. Successful implementation will require integration into routine antenatal care, adaptation to local epidemiology, coordination with monoclonal antibody programs, and continued sur-veillance of effectiveness, safety, uptake, and equity. A flexible prevention framework combining maternal vaccination and infant monoclonal antibody prophylaxis, according to local needs and individual risk, has the potential to substantially reduce RSV-associated morbidity, hospitaliza-tions, and healthcare burden in early infancy.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab, a long-acting monoclonal antibody, provides single-dose protection during the RSV season, but the effectiveness of prophylaxis programs depends on sustained parental acceptance and high uptake. This study evaluated changes in parental knowledge, perceptions, and willingness to accept nirsevimab across two consecutive RSV seasons in Emilia-Romagna, Italy. Methods: Two multicenter cross-sectional surveys were conducted during consecutive RSV seasons, 2024–2025 and 2025–2026, using a comparable questionnaire and recruitment approach. Parents or legal guardians of infants eligible for nirsevimab completed a semi-structured questionnaire during routine counseling in neonatal units. Survey 1 included 1042 respondents and survey 2 included 867 respondents. Sociodemographic characteristics, RSV awareness, knowledge and perception of nirsevimab, willingness to accept prophylaxis, trust in healthcare providers and the healthcare system, preferred information sources, and willingness to pay were compared between seasons. Results: Willingness to administer nirsevimab remained high and stable—87.04% in survey 1 and 88.00% in survey 2. Awareness of RSV-related risks increased from 68.23% to 73.47% (p < 0.05), and correct identification of nirsevimab as an antibody increased from 65.93% to 71.74% (p < 0.01). Explicit refusal rose slightly from 2.21% to 3.81% (p < 0.05). In survey 2, acceptance was associated with higher education, awareness of RSV risks, perceived child susceptibility, confidence in efficacy, lower concern about side effects, trust in pediatricians and the healthcare system, and willingness to pay. Notably, acceptance in 2025–2026 was higher among infants born in September–December than among those born in January–March, indicating a late-season decline. Conclusions: Parental acceptance of nirsevimab remained high across two seasons. Future campaigns should address residual knowledge gaps, reinforce communication on safety and efficacy, and sustain high coverage throughout the entire RSV season, particularly among infants born in its final months.

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide and a key-model to illustrate dysregulation of innate immunity, etiologically determined by pathogenic variants in the MEFV gene, encoding pyrin, leading to uncontrolled interleukin-1β and interleukin-18 release. Despite its genetic basis, FMF shows marked clinical heterogeneity in all-aged patients, mostly in children, suggesting a role of potential environmental modifiers which are far to be exactly unraveled. Recent medical literature has increasingly illuminated the importance of gut microbiota in maintaining overall health and immune functions, and its contribution has been claimed also to explain both FMF inflammatory activity and heterogeneous disease expression. This narrative review summarizes current evidence on the interaction between gut microbiota and FMF, with a specific focus on differences between children and adults. Pediatric studies dedicated to FMF have reported intestinal dysbiosis in terms of reduced microbial diversity and depletion of short-chain fatty acid-producing bacteria, with subsequent enrichment of pro-inflammatory taxa: such alteration could modulate pyrin-inflammasome activation and contribute to systemic inflammation, disease phenotype, and response to colchicine or to other drugs specifically used in colchicine-resistant FMF. Geographic and lifestyle factors may shape intestinal microbiota composition early in life, reinforcing the relevance of gut flora and confirming its activity as a crucial tessera to determine FMF sceneries, mostly in children, and a potential target for future add-on therapeutic strategies. In addition, colchicine therapy appears to partially remodel the gut microbiome, empowering a local beneficial anti-inflammatory microbial profile.

Background: Pediatric bacterial meningitis remains an important cause of death and long-term neurological disability despite advances in vaccination, antimicrobial therapy, and supportive care. Because host inflammation contributes substantially to secondary neuronal injury, adjunctive cor-ticosteroids have been investigated as a strategy to reduce inflammation-mediated complications. This narrative review aims to critically evaluate the current evidence on corticosteroid therapy in pediatric meningitis, with particular emphasis on acute bacterial meningitis, major clinical and neurological outcomes, treatment timing, pathogen-specific effects, and the impact of changing post-vaccination epidemiology. Methods: A structured search of PubMed/MEDLINE, Scopus, and Web of Science was conducted for relevant publications available up to June 2026. Randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international guide-lines involving patients aged 0–18 years were considered. Evidence was synthesized narratively, focusing on mortality, hearing loss, neurological sequelae, long-term outcomes, safety, causative pathogen, and timing of corticosteroid administration. Results: Adjunctive dexamethasone does not consistently reduce mortality, hospital stay, intensive care utilization, or healthcare costs. Its most reproducible benefit is a reduction in sensorineural hearing loss, particularly in Haemophilus influ-enzae type b meningitis. Benefits in pneumococcal meningitis are less consistent, while evidence supporting routine use in meningococcal disease remains limited. Efficacy is greatest when dexa-methasone is administered before or with the first antibiotic dose and appears less pronounced in the post-vaccination era. In tuberculous meningitis, corticosteroids improve survival, whereas rou-tine use is not supported in viral or fungal meningitis. Conclusion: Current evidence supports a se-lective, pathogen- and context-specific approach to corticosteroid therapy in pediatric meningitis. Dexamethasone is best regarded as a neuroprotective adjunct, with hearing preservation repre-senting its most consistent clinical benefit.

INTRODUCTION:Early-life respiratory infections may disrupt lung development during critical fetal, neonatal, and infant windows, when alveolarization, airway and vascular maturation, and immune programming remain active, potentially causing effects beyond the acute illness. AREAS COVERED:This narrative review examines prenatal and postnatal respiratory infections and long-term respiratory outcomes, with emphasis on chorioamnionitis, fetal inflammatory responses, bronchopulmonary dysplasia, respiratory syncytial virus, and other pathogens. Literature was identified through targeted searches of biomedical databases and reference lists using terms related to early-life infection, lung development, bronchopulmonary dysplasia, wheeze, asthma, lung function, COPD, and respiratory mortality. Priority was given to systematic reviews, meta-analyses, longitudinal cohorts, mechanistic studies, and relevant reports. Proposed pathways include impaired alveolar and vascular growth, epithelial injury, immune dysregulation, trained immunity, airway remodeling, and reduced peak lung function. Epidemiological evidence linking early lower respiratory tract infection with recurrent wheeze, asthma, impaired lung function, COPD-like trajectories, and respiratory mortality is appraised. EXPERT OPINION:Early respiratory infections likely contribute to chronic morbidity through interactions among pathogen, timing, host susceptibility, prematurity, and environmental exposures. Causality remains difficult to establish. Newly available respiratory syncytial virus prevention strategies may clarify whether preventing severe infection improves long-term lung health. Standardized outcomes and longitudinal follow-up are essential.

Telemedicine has the potential to substantially improve the care of children and adolescents with chronic respiratory diseases, including asthma, cystic fibrosis, bronchiectasis, and chronic respiratory failure. Digital health interventions—such as remote monitoring, virtual consultations, adherence-support tools, and educational platforms—can enhance disease control, continuity of care, and access to specialized services. Despite these opportunities, the implementation of telemedicine in pediatric respiratory care remains fragmented and uneven across healthcare systems. A central barrier to progress is the marked heterogeneity of outcome measures used to evaluate telemedicine interventions. Inconsistent definitions, variable endpoints, and limited follow-up reduce comparability across studies, hinder evidence synthesis, and impede translation into clinical guidelines, reimbursement models, and policy decisions. Consequently, telemedicine is often confined to isolated pilot projects rather than embedded within standard care pathways. This narrative review issues a Call to Action for the coordinated implementation and harmonization of telemedicine in pediatric chronic respiratory diseases. We advocate for the urgent development and adoption of a Core Outcome Set (COS) to standardize outcome measurement across clinical trials and real-world evaluations. In addition, we highlight the importance of integrating implementation science, economic evaluation, ethical oversight, and equity considerations into telemedicine research and deployment. Addressing regulatory fragmentation, ensuring interoperability, and aligning accreditation with reimbursement and Health Technology Assessment requirements are essential for sustainable scale-up. Finally, we emphasize the need for international collaboration among clinicians, researchers, policymakers, payers, technology developers, and patient advocacy groups to accelerate learning and promote equitable, evidence-based digital care models. Through coordinated action, telemedicine can evolve from a promising innovation into a reliable and accessible standard of care for children with chronic respiratory diseases.

Pain and stress are frequent and clinically relevant challenges in neonatal intensive care, particularly among preterm and critically ill newborns exposed to repeated invasive procedures, mechanical ventilation, surgery, and advanced life-support interventions. Effective analgosedation is essential to reduce discomfort, attenuate physiological instability, improve tolerance of intensive care procedures, and potentially limit adverse neurodevelopmental consequences. However, neonatal pain and analgosedation management remain complex because of developmental immaturity, pharmacokinetic and pharmacodynamic variability, and the need to balance adequate analgosedation against treatment-related complications. This narrative review summarizes current evidence on analgosedation in the Neonatal Intensive Care Unit, focusing on clinical indications, pharmacological agents, non-pharmacological strategies, monitoring tools, adverse effects, and future perspectives. Opioids, benzodiazepines, dexmedetomidine, and ketamine each have specific potential benefits and limitations, requiring individualized selection, careful titration, and continuous reassessment. Non-pharmacological interventions, including oral sucrose, non-nutritive sucking, facilitated tucking, breastfeeding, skin-to-skin care, and environmental modulation, should be integrated into multimodal pain-management protocols. Validated instruments such as COMFORTneo, N-PASS, and PIPP-R support standardized assessment and guide therapeutic decisions. Future advances may derive from objective monitoring technologies, artificial intelligence, developmental pharmacology, and precision-medicine approaches. A multidisciplinary, protocol-driven, and family-centered strategy is essential to optimize neonatal comfort while minimizing avoidable drug exposure.

ABSTRACT Introduction Infectious diseases can affect the endocrine system through multiple mechanisms, including direct cytopathic effects, immune dysregulation, inflammatory pathways, and in some cases the secretion of hormone‐like substances by the pathogens themselves. While viral and bacterial infections represent the most frequent triggers, fungal and parasitic agents can also contribute, though less commonly. Methods This narrative review, based on a search in PubMed and Google Scholar, examined both paediatric and adult studies, given the limited evidence available in children. The analysis focused on the pituitary, thyroid, adrenal glands, gonads and endocrine pancreas, summarising current knowledge on the acute and long‐term endocrine consequences of infections. Results Reported outcomes range from type 1 diabetes mellitus and adrenal insufficiency to hypopituitarism, thyroiditis and hypogonadism. These complications may appear during the acute phase or emerge later as delayed sequelae, with significant implications for prognosis, quality of life and overall morbidity. The review highlights the need for increased clinical awareness, timely recognition of infection‐related endocrine dysfunctions, and structured follow‐up to prevent long‐lasting complications. Conclusion Further translational and clinical studies are warranted to clarify underlying mechanisms, identify early biomarkers and develop evidence‐based diagnostic and therapeutic strategies, ultimately improving patient care and outcomes in both paediatric and adult populations. In the future, through genomic and transcriptomic techniques, the identification of the dysregulated cellular pathways could help clarify the real ‘cause‐and‐effect’ relationship between infections and cellular dysfunction.

TANGO2-deficiency disorder (TDD) is a rare autosomal recessive condition characterised by neurodevelopmental delay, TANGO2 spells, life-threatening metabolic crises, and cardiac arrhythmias. Genotype-phenotype correlations remain poorly defined and the neurobehavioural profile of affected individuals is largely unexplored. We conducted a retrospective multicentre study of five Italian patients with genetically confirmed TDD, identified between June 2023 and May 2025. Clinical, neurophysiological, neuroimaging, genetic, and neurodevelopmental data were collected. Adaptive functioning, cognitive ability, and behavioural profiles were assessed using standardised instruments. All five patients carried biallelic TANGO2 mutations, including two previously unreported variants. Clinical severity ranged from an asymptomatic individual under preventive therapy to a fatal early-onset metabolic crisis. Marked intrafamilial variability was observed in two siblings sharing the same genotype. Systematic neurodevelopmental assessment revealed a spectrum of cognitive and adaptive outcomes, with attentional difficulties identified as a recurrent feature. No metabolic crises or TANGO2 spells were documented following initiation of B-vitamin and cofactor supplementation in surviving patients. This cohort expands the mutational and phenotypic spectrum of TDD and highlights the diagnostic value of TANGO2 testing in patients with neurodevelopmental delay or paroxysmal neurological episodes, even in the absence of metabolic crises. Early supplementation therapy may contribute to clinical stability, though prospective controlled studies are needed.

BACKGROUND:Nirsevimab prevents respiratory syncytial virus (RSV)-associated hospitalizations in infants. However, its impact on the broader epidemiology of acute respiratory infections (ARI) in hospitalized children remains unclear. METHODS:We conducted a retrospective study of ARI hospitalizations among children aged ≤5 years at a tertiary pediatric hospital in Parma, Emilia Romagna region, Italy, across 3 respiratory seasons (from September 1, 2022 to April 30, 2025), spanning the period before and after nirsevimab introduction (October 2024). All children hospitalized with ARI during the seasonal period (September-April) who tested positive for at least 1 respiratory virus by multiplex polymerase chain reaction were included. We analyzed temporal trends in ARI hospitalization rates, viral distribution and RSV-specific infection patterns. Hospitalization rates were contextualized using the resident population aged ≤5 years in Emilia Romagna. RESULTS:A total of 241 ARI hospitalizations were included, with 347 viral detections, of which 44.7% were monoinfections and 55.3% were coinfections. The incidence of ARI hospitalizations decreased in the 2024-2025 season compared with the previous 2 seasons (from 14.3 to 2.2 per 100 person-months). The overall distribution of respiratory viruses remained stable over time (P -trend = 0.4736), with RSV and rhinovirus accounting for approximately 35% and 30% of detections, respectively. The proportion of RSV monoinfections remained unchanged, whereas RSV coinfections declined significantly ( P -trend = 0.0161). CONCLUSIONS:Following nirsevimab introduction, pediatric ARI hospitalizations declined without evidence of viral replacement. The selective reduction in RSV coinfections suggests that RSV prevention may reduce infection complexity in addition to RSV-associated disease. Continued surveillance is needed to assess the long-term epidemiologic impact.

Background: Metabolic acidosis is a frequent and serious complication in critically ill neonates, particularly preterm infants, and is associated with an increased risk of mortality, intraventricular hemorrhage, and long-term neurodevelopmental impairment. Despite limited evidence, sodium bicarbonate (SB) is widely administered in neonatal intensive care units (NICUs) to correct acidosis, largely extrapolated from adult and pediatric practice. However, concerns have been raised about its potential adverse effects, including paradoxical intracellular acidosis, impaired cerebral autoregulation, and increased risk of neurological injury. Given the uncertainty regarding both its efficacy and safety, we conducted a systematic review and meta-analysis to evaluate the role of SB administration in the neonatal population. Methods: MEDLINE, Scopus, and the Cochrane Library were searched using specific medical subject headings and terms. We included all study published up to July 2025 that involved newborns treated with SB. The primary outcome was positive response to treatment, while secondary outcomes included mortality, morbidity, and long-term impairment. Results: We analyzed 10 studies (9 randomized and 1 unrandomized study, including 660 neonates). Pooled results from the randomized controlled studies showed no efficacy of SB in newborns. Data from one unrandomized study showed an increased risk for mortality (OR 13.1 p = 0.02), clinical seizures (OR 2.8, p = 0.01), and a combined outcome of death or neurological damage (OR 3.1 p < 0.01) for neonates treated with SB. Conclusions: Current evidence is insufficient to support the routine administration of SB in NICUs. Neonatologists have the responsibility to administer only drugs of proven efficacy, personalizing therapy on the basis of a pathology's etiology, in order to reduce risk and optimize benefits. In the absence of robust, statistically significant data, the indiscriminate use of SB should be discouraged in current clinical practice. PROSPERO registration number: CRD420251132502.

Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations.

Background: Dengue has expanded rapidly beyond traditional tropical and subtropical regions, driven by climate change, urbanization, population mobility, and the spread of competent Aedes vectors. Vaccination is an increasingly important component of dengue prevention, but development has been complicated by four viral serotypes, antibody-dependent enhancement, variable baseline serostatus, and the need for balanced and durable tetravalent immunity. Methods: We conducted a narrative review of PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, and relevant public health and regulatory sources. Evidence on dengue epidemiology, immunopathogenesis, licensed vaccines, advanced candidates, efficacy, immunogenicity, safety, durability, and implementation was critically evaluated. Priority was given to randomized trials, long-term follow-up studies, regulatory assessments, and surveillance data. Evidence was synthesized descriptively without formal meta-analysis or risk-of-bias assessment. Results: CYD-TDV was the first licensed dengue vaccine but is restricted to individuals with documented previous infection because seronegative recipients may experience an increased risk of severe dengue. TAK-003 provides protection against symptomatic dengue and hospitalization in both seropositive and seronegative individuals and can be administered without mandatory prevaccination screening, although efficacy varies by serotype. Butantan-DV offers a promising single-dose strategy, but broader use requires additional long-term safety, effectiveness, and serotype-specific data. Inactivated, DNA, viral-vectored, virus-like particle, and mRNA vaccines remain investigational. Conclusion: Dengue vaccination should be integrated with surveillance, vector control, clinical preparedness, and risk communication. Population-based vaccination is most appropriate in high-transmission settings, whereas selective, risk-based strategies are preferable in temperate regions. Continued pharmacovigilance and effectiveness monitoring are essential to guide safe and equitable implementation.

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality among children worldwide, with approximately one million new pediatric cases annually. The conventional treatment for drug-susceptible TB has long relied on a 6-month multidrug regimen, which is highly effective but associated with challenges in adherence, toxicity, and healthcare burden. Objectives: To evaluate whether short-course therapy is an appropriate regimen for children and young adolescents with drug-susceptible TB, with particular focus on its efficacy, safety, and applicability in different clinical contexts. Methods: A structured narrative review of the literature was conducted, including randomized controlled trials, observational studies, and international guidelines addressing treatment duration in children and young adolescents with drug-susceptible TB. Evidence was synthesized focusing on children and young adolescents <16 years with drug-susceptible TB treated with short-course regimens compared to standard therapy. Results: A shorter treatment regimen, particularly 4-month courses, has been investigated as an alternative to standard therapy in the pediatric population with drug-susceptible TB. Children often present with paucibacillary and non-severe forms of TB, providing a biological rationale for treatment shortening. Evidence from a randomized controlled trial has demonstrated that a 4-month regimen is non-inferior to the standard 6-month therapy in children and young adolescents with non-severe, drug-susceptible TB. These findings have informed recent international guideline updates, which now recommend short therapy in carefully selected patients. However, a short regimen is not appropriate for infants younger than 3 months, children with severe or complicated TB, extrapulmonary disease such as central nervous system involvement, or those with drug-resistant TB. The overall quality of evidence remains moderate, and long-term relapse data are still emerging. Conclusions: Short-course therapy represents a promising but selective strategy in pediatric drug-susceptible TB management. It offers potential advantages, including improved adherence, reduced drug toxicity, and lower healthcare costs. However, its safe implementation requires accurate patient selection, access to appropriate diagnostic tools, and structured follow-up. Careful application within clearly defined clinical criteria is essential to ensure optimal outcomes.