Search Results (570)

Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) in North America and the German Society of Pediatric Oncology and Hematology (GPOH) in Europe. Methods: Samples collected from NPC patients treated on the COG study ARAR0331 between 2006 and 2012 and the GPOH NPC protocol between 2003 and 2021 were retrospectively analyzed for the level of available plasma (P-EBV) or whole-blood EBV DNA (WB-EBV), both pre-treatment and post-induction chemotherapy. Patients were dichotomized into high and low groups based on the median pre-treatment EBV value. Results: Pre-treatment EBV DNA levels from 102 patients (50 and 23 P-EBV DNA from the COG and GPOH, respectively, and 29 WB-EBV from GPOH) and post-induction EBV DNA levels from 61 patients (31 and 12 P-EBV DNA from the COG and GPOH, respectively, and 18 WB-EBV DNA from GPOH) were evaluated. Patient characteristics, including age and disease stage, were not associated with high and low P-EBV values in any cohort. Disease stage correlated with high EBV levels in the WB-EBV GPOH cohort (p = 0.014). Pre-treatment P-EBV and WB-EBV levels showed no significant association with 5-year event-free survival (EFS: COG p = 0.65, GPOH P-EBV: p = 0.08, GPOH WB-EBV: p = 0.75) or 5-year overall survival (OS: COG p = 0.90, GPOH P-EBV p = 0.17, GPOH WB-EBV p = 0.19). Conclusions: Our study could not establish a significant correlation between outcome and pre-treatment EBV DNA in pediatric NPC patients from non-endemic areas. Full article

A pro-inflammatory state, characterized by elevated levels of pro-inflammatory cytokines, is frequently reported among individuals presenting with primary first-episode psychosis (FEP), particularly those with environmental risk factors such as maternal infections and early childhood traumatic experiences. These findings suggest that immune system disturbances may play a crucial role in the onset of psychotic disorders. Building on this, cytokines may contribute to the risk of FEP from the stage of neurodevelopment, where they can induce aberrant changes in neuronal growth. During early childhood, these cytokine-mediated processes may disrupt normal neuronal maturation and lead to brain alterations that increase vulnerability to primary psychotic disorders. Furthermore, pro-inflammatory cytokines exhibit strong bidirectional modulatory interactions with dopamine, a key neurotransmitter implicated in the pathogenesis and persistence of psychosis. Notably, these cytokines may also influence the clinical presentation and severity of psychosis. In addition, antipsychotic medications can partially modulate cytokine levels, and this modulation has been correlated with the efficacy of antipsychotics in treating various psychotic symptoms. Frequently reported cytokines in this context include interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ). We conducted a non-systematized literature search on Google Scholar and PubMed for studies looking at cytokines in primary psychotic disorders during FEP. In this narrative review, we provide an overview of the literature on immune dysregulation in FEP, with a particular emphasis on cytokines. Full article

Kindergarten environments combine high microbial exposure with increased immunological vulnerability, yet antibiotic resistance genes (ARGs) in kindergarten dust remain poorly characterized. This systematic review synthesized evidence on the occurrence and potential health relevance of ARGs in kindergarten dust. Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched. Four studies from China, Hong Kong, and Norway (2018–2024) met the inclusion criteria. ARGs were detected in all kindergarten dust samples, indicating that dust is a consistent reservoir of antibiotic resistance determinants. A consensus resistome (classes detected in ≥2 studies) encompassed sulfonamide, macrolide–lincosamide–streptogramin B (MLSB), tetracycline, beta-lactam, aminoglycoside, and multidrug resistance genes; beta-lactam resistance genes were the only class reported in all four studies. Clinically important ARGs associated with last-resort antibiotics, including mecA, vanA, bla_NDM, and mcr-5, were reported in three studies. Class 1 integron-integrase genes (intI1) frequently co-occurred with ARGs, suggesting potential horizontal gene transfer. Limited evidence indicated higher ARG abundance in urban and winter samples. One study reported antibiotic-resistant bacteria carrying resistance markers concordant with those in kindergarten dust in the urine of children attending the same facilities; however, this cross-sectional, single-site evidence is consistent with, but not sufficient to establish, a dust-to-child exposure pathway. The available evidence supports the plausibility that kindergarten dust may contribute to children’s exposure to ARGs and ARG-carrying bacteria, but current studies do not establish causal transmission from dust to child colonization or infection. Standardized monitoring and longitudinal studies are needed to assess health risks and guide mitigation strategies in early childhood educational settings. Full article

Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy. Full article

Background: Osteochondroma is the most common benign bone tumor in childhood. Although most lesions are asymptomatic, surgical treatment is indicated in patients with pain, mechanical symptoms, cosmetic concerns, restricted range of motion, or neurovascular compression. This study evaluated the clinical characteristics and surgical outcomes of osteochondromas in children and adolescents treated at a single tertiary pediatric surgery center. Methods: This retrospective study included 75 pediatric patients who underwent surgical excision of osteochondroma between January 2015 and January 2026. Demographic, clinical, radiological, operative, histopathological, and follow-up data were analyzed. Lesion-related variables were assessed at the level of individual exostoses. The primary outcome was surgical treatment outcome, while secondary outcomes included lesion localization, symptoms, hospital stay, postoperative complications, recurrence, and associations between clinical and morphological variables. Results: A total of 75 patients with 76 solitary osteochondromas were included. The median age was 13 years, and 64.0% of patients were male. Most lesions were located distally (73.7%), with the femur being the most common site (48.7%), followed by the tibia (22.4%). Pain was the most frequent symptom, present in 63.2% of exostoses, followed by cosmetic concern in 32.9%. Standard radiography was used in nearly all cases (98.7%). Radiographic measurements significantly underestimated lesion size compared with intraoperative measurements, with median diameters of 3.0 cm and 4.0 cm, respectively (p < 0.001). A strong positive correlation was observed between radiographic and intraoperative lesion diameter (ρ = 0.77; p < 0.001), while symptom duration showed a weak but significant correlation with lesion diameter (ρ = 0.28; p = 0.013). No significant association was found between lesion diameter and symptomatic presentation, and logistic regression did not identify age, sex, lesion location, or diameter as significant predictors of symptoms. Postoperative outcomes were favorable: 94.6% of patients had no complications, wound infection and hematoma occurred in 2.7% each, and no recurrences or reoperations were recorded during a median follow-up of 63 months. Histopathological examination confirmed osteochondroma in all cases. Conclusions: Surgical excision of symptomatic pediatric osteochondromas was associated with favorable postoperative outcomes, a low complication rate, and no observed recurrence during follow-up. Standard radiography correlates well with intraoperative findings but may underestimate true lesion size, likely due to limited visualization of the cartilaginous cap. Symptom development appears multifactorial and cannot be reliably predicted by lesion size or location alone. Full article

Background and Clinical Significance: Varicella, caused by the varicella-zoster virus (VZV), is typically a childhood disease; however, adult cases carry substantially higher morbidity and mortality. Immunocompromised individuals are particularly vulnerable to severe outcomes. Many adults in Japan lack documented varicella vaccination, representing a missed opportunity for preventing primary VZV infection. None of the patients had documented prior varicella vaccination. Case Presentation: We conducted a retrospective review of varicella cases at Hirosaki University Hospital between April 2007 and March 2025. Ten patients (eight adults and two children) were identified. Among the eight adult patients, written informed consent for publication was obtained from five patients, whose clinical courses are described in detail in this report. Four patients had underlying conditions requiring immunosuppressive therapy, and two were undergoing cancer treatment. All immunocompromised patients exhibited hepatic dysfunction, with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. All patients received antiviral therapy with valaciclovir or acyclovir, and some additionally received intravenous immunoglobulin. All five adult patients in this series recovered from varicella without long-term sequelae, although one later died from unrelated causes. We additionally note that one patient later died from cerebral embolism and pneumonia, unrelated to varicella. Conclusions: This retrospective case series illustrates the vulnerability of immunocompromised adults to severe varicella and aligns with current recommendations supporting the vaccination of susceptible high-risk adults. While antiviral therapy remains essential for clinical management, prevention through appropriate vaccination strategies—varicella vaccine for preventing primary infection in eligible individuals and RZV for preventing herpes zoster reactivation in immunocompromised adults—represent an important preventive strategy for reducing overall VZV-related morbidity and mortality. These findings reinforce the importance of preventive strategies, including vaccination and early recognition of varicella in high-risk adults. Full article

Waterborne, water-related, and foodborne infectious diseases remain preventable causes of mortality, but long-term evidence on their demographic, spatial, and premature mortality burden is limited in Costa Rica. This ecological population-based study described deaths classified under selected ICD-10 codes during 2000–2023 using official mortality and population data. Crude and age-standardized mortality rates, years of life lost (YLL), and YLL rates were estimated by time, sex, age group, and geographic area. A total of 2450 deaths were identified. Diarrhea and gastroenteritis of presumed infectious origin accounted for 1537 deaths (62.7%), followed by other bacterial intestinal infections (23.8%) and leptospirosis (7.0%). Annual crude mortality rates ranged from 1.28 per 100,000 population in 2021 to 3.03 in 2017. Mortality showed a bimodal age pattern, with the highest rate among persons aged 75 years or older and a relevant early-childhood component. A total of 57,625.5 YLL were estimated, with the largest burden among children aged 0–4 years and the highest provincial YLL rates in Limón, Puntarenas, and Guanacaste. These findings support incorporating premature mortality metrics into environmental health surveillance, although the ecological design does not identify exposure sources or causal determinants. Full article

This study aimed to investigate the prevalence of human pegivirus type 1 (HPgV-1) among healthy individuals, type 2 diabetes patients, and cancer patients in Taizhou, Jiangsu, China. A total of 2872 participants, including 2052 healthy individuals, 373 type 2 diabetes patients, and 447 cancer patients, were enrolled at Taizhou Fourth People’s Hospital between 2022 and 2024. Serum samples were collected from each participant, and HPgV-1 RNA was detected using a reverse transcription-polymerase chain reaction (RT-PCR) assay. The positive rates were compared across the three groups. The age range of healthy individuals was 5–91 years, while that of type 2 diabetes and cancer patients was 25–85 years and 34–91 years, respectively. The prevalence of HPgV-1 among healthy individuals was 15.3% (313/2052), which was significantly higher than that in type 2 diabetes patients (11.0%, 41/373, p < 0.05) and cancer patients (9.2%, 41/447, p < 0.001). In healthy individuals, the prevalence of HPgV-1 increased from childhood to young adulthood, peaking in the 19–40 years age group, followed by a decline after 40 years of age, indicating an age-related pattern. Similarly, HPgV-1 load increased from childhood to adulthood. No significant gender differences in HPgV-1 prevalence were observed across the three cohorts. In conclusion, HPgV-1 infection exhibits an age-dependent prevalence, with the lowest rate in children and adolescents and the highest in young adults (19–40 years). The significantly lower prevalence of HPgV-1 in type 2 diabetes and cancer patients raises the intriguing question of whether HPgV-1 infection may play a protective or contributory role in the pathogenesis of diabetes and cancers. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

JC polyomavirus (JCPyV) is a worldwide-distributed human virus. Primary infection with JCPyV is usually asymptomatic and followed by a lifelong persistent infection. In situations of profound immunosuppression or prolonged treatment with specific immunomodulatory drugs, such as natalizumab, viral reactivation can occur and lead to the development of JCPyV-associated diseases. Progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system, is the most common clinical manifestation of JCPyV reactivation. Less frequently, viral reactivation may be associated with granule cell neuronopathy, encephalopathy, and meningitis. However, the pathogenesis of these diseases remains a subject of debate. To date, no treatment is available for JCPyV infection. Nevertheless, some therapeutic options have been explored. Despite its ubiquity, the main mode of JCPyV transmission remains unclear. Epidemiological data suggests that primary infection may be acquired in childhood and throughout life, with the involvement of different routes of transmission. In the absence of an effective treatment, the prevention of infection is crucial in risk groups, such as immunosuppressed or natalizumab-treated patients. Therefore, until the achievement of an effective antiviral molecule or a prophylactic vaccine, prevention measures will rely on avoiding transmission, for which it is crucial to understand how transmission occurs. The present review emphasizes the current data on JCPyV transmission routes and associated diseases, including pathogenesis, diagnosis and potential treatment options, highlighting the importance of further studies. Full article

Opisthorchis viverrini (OV) is a liver fluke endemic to the Lower Mekong Basin. Infections often begin in childhood and are causally linked to cholangiocarcinoma, an often-fatal bile duct cancer. Anthelmintic treatment is the primary control strategy, but infection can recur. Therefore, additional strategies are needed. This study assessed the impact of “The Magic Glasses Opisthorchiasis” (MGO), a cartoon-based intervention, on schoolchildren’s OV-related knowledge, attitudes and practices (KAP). A cluster (school)-randomised controlled trial was conducted in Cambodia, Laos and Thailand. Clusters were randomised into either school health education only or with MGO. OV KAP was measured using a standardised questionnaire. FGDs and interviews were also conducted in intervention schools with schoolchildren, parents, and teachers. Cambodia intervention knowledge and attitude scores improved by 19.2 (p < 0.001) and 25.3 (p < 0.001) percentage points, respectively, relative to the control. Laos intervention knowledge and attitude scores improved by 19.0 (p < 0.001) and 14.2 (p < 0.001) percentage points. However, Thailand’s intervention knowledge and attitude scores declined by 23.3 (p < 0.001) and 15.8 percentage points (p < 0.001). There were no improvements in behaviour scores in any country, but parents and schoolchildren in Cambodia and Laos reported improved fish preparation practices, suggesting positive spillover effects from MGO. The findings support MGO as an effective tool for school-based health education. Full article

Background/Objectives: Probiotic and synbiotic supplementation has been proposed as a preventive strategy against respiratory tract infections (RTIs) in early childhood, although evidence in infants and young children remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of probiotic or synbiotic supplementation administered during the first 24 months of life on respiratory infection outcomes. Methods: PubMed/MEDLINE, Embase, and Scopus were systematically searched for randomized controlled trials published between January 2015 and 30 September 2025. Eligible studies included infants and children aged ≤24 months receiving oral probiotics or synbiotics compared with placebo, no intervention, or standard care. The primary outcome was the incidence of at least one upper respiratory tract infection (URTI), while the secondary outcome was the incidence of any RTI. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated according to the GRADE approach. Results: Nine randomized controlled trials were included. Probiotic or synbiotic supplementation did not significantly reduce the risk of URTI (OR 0.95, 95% CI 0.47–1.95; I² = 78%). A non-significant trend toward a reduced risk of any RTI was observed (OR 0.66, 95% CI 0.35–1.25; I² = 69%). Exploratory subgroup analyses suggested possible strain-specific effects, with signals observed for Bifidobacterium longum subsp. infantis in relation to URTI prevention and Lactiplantibacillus plantarum ATCC 202195 for reduction in any RTI. However, these findings were based on a limited number of studies and should be interpreted cautiously. No serious adverse events attributable to supplementation were reported. Conclusions: Current evidence does not support the routine use of probiotic or synbiotic supplementation for the prevention of respiratory infections in children aged ≤24 months. However, potential strain-specific benefits warrant further investigation in adequately powered randomized trials. Full article

Upper respiratory tract infections and inflammatory nasal disorders are highly prevalent in childhood and represent a major cause of morbidity and healthcare utilization. Humans are continuously exposed to airborne microorganisms, allergens, and pollutants. Although the nasal mucosa provides effective mechanical and immunological defenses, these mechanisms may be impaired by inflammation, environmental pollutants, and mucociliary dysfunction, increasing susceptibility to infection and airway inflammation. Nasal irrigation (NI) contributes to the restoration of nasal homeostasis by mechanically removing mucus, pathogens, allergens, and inflammatory mediators, while also improving mucociliary clearance (MC), mucus rheology, and epithelial barrier function. Hypertonic solutions (HS) may provide additional osmotic and decongestant effects. Current evidence suggests that NI is a safe and well-tolerated adjunctive intervention that may improve symptoms and support mucosal function in acute and chronic upper airway diseases. This narrative review provides an updated overview of NI, with particular focus on pediatric populations. This paper integrates the pathophysiological mechanisms of mucociliary dysfunction, environmental exposures, and pediatric-specific anatomical and functional characteristics into a unified framework to understand the role of NI in childhood respiratory diseases. Clinical indications, administration techniques, solution selection, safety aspects, and age-specific practical considerations are discussed, highlighting the importance of appropriate technique, caregiver education, and adherence to basic hygiene principles. Full article

Background/Objectives: Recurrent acute otitis media (AOM) in children is known to cause cumulative cochlear and vestibular injury. Whether a single fulminant episode severe enough to require surgical intervention produces an analogous long-term audiovestibular signature, and whether infection severity contributes to outcome independently of cumulative episode count, is unclear. The present study addressed this gap. Methods: In this single-centre retrospective cohort study, 65 paediatric patients who had undergone surgical treatment for acute mastoiditis—the fulminant form of AOM—between July 2001 and March 2021 were assessed a median of 11.5 years after surgery. Of these, 35 had undergone mastoidectomy with tympanostomy and 30 had undergone tympanostomy alone because their episode had not been severe enough to require mastoidectomy. Thirty-two age-matched healthy volunteers (one ear each) formed the control group, yielding 97 ears in three groups (Group TM, 35 ears; Group T, 30 ears; Group C, 32 ears). Extended high-frequency pure-tone audiometry (125–20 kHz), distortion-product otoacoustic emissions (DPOAEs), single-frequency and wideband tympanometry, ipsilateral acoustic reflex thresholds, and lateral-canal vestibulo-ocular reflex gain were measured. Results: Both operated groups showed significantly elevated audiometric thresholds in the high- and extended high-frequency ranges compared with controls (HTA: χ² = 24.25, p < 0.001), with corresponding reductions in DPOAE amplitudes (HTA: χ² = 25.04, p < 0.001). Group TM did not differ significantly from Group T at any frequency band, indicating a negligible additional contribution of mastoidectomy itself. Acoustic reflex thresholds were elevated in Group TM. Vestibulo-ocular reflex gain was within reference ranges in all groups. Conclusions: A single fulminant episode of acute middle-ear infection in childhood—whether severe enough to require mastoidectomy or treated by tympanostomy alone—was associated, more than a decade later, with significantly elevated audiometric thresholds closely resembling those reported after multiple recurrent infections, supporting an effect of infection severity independent of cumulative episode count. Long-term audiological follow-up with extended high-frequency audiometry and otoacoustic emission testing is warranted, irrespective of whether mastoidectomy was required. Full article

Background: Non-pharmaceutical interventions during the COVID-19 pandemic altered respiratory pathogen circulation, and a bacterial rebound followed once restrictions were lifted. We describe pediatric pneumococcal respiratory infections and their bacterial co-detections in the immediate post-pandemic period. Methods: We retrospectively analyzed respiratory specimens from children aged 0–18 years tested with a multiplex real-time PCR panel (Allplex Respiratory Panel, Seegene, Seoul, South Korea; seven bacterial pathogens) restricted to this predefined bacterial spectrum at a tertiary pediatric hospital in Galați, Romania, during 2022 and 2023. A total of 2546 panels were performed in 2022 and 3250 in 2023, allowing pneumococcal positivity rates to be calculated. Proportions are reported with Wilson 95% confidence intervals; associations were tested with Pearson chi-square and Fisher exact tests in SPSS v.23. Results: Children with detected Streptococcus pneumoniae rose from 100 to 415, corresponding to a rise in pneumococcal positivity from 3.9% (100/2546) to 12.8% (415/3250). Among the positive children, pneumococcus–Haemophilus influenzae co-detection increased from 33.0% to 45.1% (odds ratio 1.63, 95% CI 1.02–2.61; p = 0.029), while pneumococcus alone fell from 60.0% to 50.1%. Boys, urban residence, and early childhood predominated, and community-acquired pneumonia diagnoses rose from 61 to 214. No profile–demographic association reached significance (panel–residence 2023, p = 0.063). Conclusions: A post-pandemic rise in pediatric pneumococcal detections and increasing H. influenzae co-detection were observed, supporting syndromic multiplex PCR in rapid pediatric diagnostics and antimicrobial stewardship. Full article