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PubMed2026

Ibuprofen versus acetaminophen for acute mild-to-moderate pain management in pediatric populations: a systematic review and meta-analysis of their efficacy.

UNLABELLED: Ibuprofen and acetaminophen are the most widely used analgesics in pediatric practice for the management of acute mild-to-moderate pain. Despite their widespread use, the comparative analgesic efficacy of these two agents in children remains a subject of ongoing debate, with existing evidence largely derived from heterogeneous clinical settings and small individual trials. Therefore, this study aimed to systematically review and meta-analyze randomized controlled trials comparing the analgesic efficacy of ibuprofen versus acetaminophen in pediatric populations with acute mild-to-moderate pain. A systematic literature search was conducted up to May 2026 in PubMed, Scopus, and Web of Science. The review was conducted and reported in accordance with the PRISMA-Children and Adolescents (PRISMA-C) 2026 reporting guideline. Eligible studies were randomized controlled trials comparing ibuprofen with acetaminophen in children and adolescents (defined as individuals aged 0 to < 18 years) with acute pain, reporting at least one extractable efficacy outcome. Continuous outcomes were synthesized as standardized mean differences (Hedges' g) using random-effects models; dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2 tool and certainty of evidence was evaluated using the GRADE framework. Eight randomized controlled trials enrolling 1325 participants were included. Three pediatric trials contributed to the primary continuous pain outcome meta-analysis (n = 196 analyzable participants), yielding a pooled SMD of - 0.28 (95% CI - 0.57 to 0.00; p = 0.052; I2 = 0%), indicating a small effect favoring ibuprofen that did not reach conventional statistical significance. Given the small number of contributing studies (k = 3), the I2 statistic should be interpreted with caution as it has limited power to detect heterogeneity in this context. For the dichotomous pain freedom outcome (2 trials, n = 114), no significant difference was observed (pooled RR 1.03, 95% CI 0.53-1.99; p = 0.93; I2 = 0%). A prespecified sensitivity analysis including an adult soft-tissue injury trial attenuated the pooled effect toward the null (SMD - 0.15, 95% CI - 0.38 to 0.09; p = 0.23; I2 = 36.6%). Narrative synthesis of additional studies generally demonstrated comparable analgesic efficacy between the two agents across postoperative and outpatient pediatric settings. The overall certainty of evidence was rated as low for both primary outcomes, primarily due to imprecision and indirectness. CONCLUSION: Current evidence from randomized controlled trials does not demonstrate a superiority of ibuprofen over acetaminophen for acute mild-to-moderate pain management in children. Both agents appear to provide clinically meaningful analgesia across heterogeneous pediatric pain settings. The clinical choice between agents should be guided by individual patient factors, including contraindications to NSAIDs, the inflammatory nature of the pain etiology, and patient-specific characteristics. The low certainty of evidence underscores the need for adequately powered, methodologically rigorous trials to definitively establish the comparative efficacy of these two analgesics in the pediatric population. WHAT IS KNOWN: • Ibuprofen and acetaminophen are the two most widely used non-opioid analgesics for acute mild-to-moderate pain in children, and both are recommended as first-line agents by major international guidelines. • Prior meta-analyses in mixed pediatric-adult populations have suggested a modest analgesic advantage of ibuprofen over acetaminophen, but pediatric-specific evidence has remained limited and methodologically heterogeneous. WHAT IS NEW: • This systematic review and meta-analysis, restricted to randomized controlled trials in pediatric populations, found that ibuprofen showed a small effect favoring pain reduction compared with acetaminophen (SMD - 0.28, p = 0.052), although this did not reach conventional statistical significance. • The analgesic advantage of ibuprofen may be more pronounced in pain etiologies with a significant inflammatory component (e.g., fractures). At the same time, both agents appear broadly equivalent in most other acute pediatric pain settings, supporting individualized analgesic selection based on clinical context and patient-specific factors.

Humans↗

PubMed2025

Genomic sequencing in diverse and underserved pediatric populations: Parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

PURPOSE: Limited evidence evaluates parents' perceptions of their child's clinical genome-scale sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap. METHODS: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure. We assessed outcomes' associations with child- and parent-related factors: child age; type of GS finding; and parent health literacy, numeracy, and education. RESULTS: A total of 1763 parents completed surveys; 83% met "underserved" criteria based on race, ethnicity, and risk factors for barriers to access. We observed high perceived understanding and personal utility and low test-related distress. Outcomes were associated with the type of GS finding; parents of children with a pathogenic or likely pathogenic finding endorsed higher personal utility and more test-related distress than those whose children had a variant of uncertain significance or normal finding. Personal utility was higher in parents who met the criteria for "underserved." CONCLUSION: Our findings shed light on correlates of parents' cognitive and emotional responses to their child's GS findings and emphasize the need for tailored support in disclosure discussions.

Humans↗

PubMed2026

Associations of Active and Passive Smoke Exposure and Hidradenitis Suppurativa in the Pediatric Population: A Case-Control Study.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory condition associated with cysts of the folliculopilosebaceous unit primarily affecting intertriginous areas. HS has been correlated with smoke exposure in the adult population, but there is a knowledge gap in understanding its effect in pediatric and adolescent patients. This study assesses correlations between active and passive smoke exposure and the development of HS in the pediatric and adolescent population. METHODS: A retrospective case-control study was conducted at Mayo Clinic (2010-2023) of patients diagnosed with HS before the age of 18 years who were age-, sex-, and race-matched to healthy controls in a 1:3 ratio, analyzed using Fisher exact for categorical variables and Kruskal-Wallis for continuous. RESULTS: One hundred and seventy-four cases and 522 controls met inclusion criteria. The prevalence of active and passive smoke exposure was significantly higher in patients with HS compared to controls (p = 0.001), with passive smoke accounting for 64.6% (N = 31/48) of smoke exposure in patients with HS. Smoke exposure was associated with a significant increase in the odds of an HS diagnosis, with an odds ratio of 4.8 (95% CI: 3.06-7.61) for passive and/or active exposure, and 1.64 (95% CI: 1.01-2.61) for passive exposure alone. Smoke exposure was associated with a later age of diagnosis than those with no smoke exposure (p < 0.001). CONCLUSION: Prevalence of active and passive smoke exposure was higher in pediatric and adolescent patients with HS compared to age, sex, and race-matched healthy controls. Smoke exposure increased the odds of having HS and was associated with a later age at diagnosis.

HS↗

PubMed2026

Feasibility of implementation, diagnostic accuracy, and end-user impact of an electronic health record (EHR)-based ureteral stent tracking tool in a pediatric population.

INTRODUCTION & OBJECTIVES: Ureteral stent tracking systems have reduced stent retention in adults, but their accuracy and impact in pediatrics have been minimally explored. With low event rates in children, such tools may yield high false positives, raising questions on balancing event prevention with provider burden. We aimed to evaluate the feasibility, diagnostic accuracy, and end-user impact of an Electronic Surveillance Tool for Evaluating Nephroureteral stent Tracking (eSTENT) at our institution. STUDY DESIGN: eSTENT, implemented in 1/2024, flags ureteral stents at risk for retention based on implant documentation, expected explant date, and explant documentation. Monthly reports are generated for stents missing explant documentation. We retrospectively evaluated the diagnostic performance of eSTENT from 1/2024-8/2025 at our pediatric hospital. A usability survey including a validated 1-7 implementation score (higher = easier implementation) was distributed to pediatric urologists and operating room nurses. RESULTS: Of 172 cases with ureteral stent placement, eSTENT flagged 28 events (16%) in 24 patients. Of these, 26 represented documentation gaps where explant had been appropriate. Two flags had no documentation of explant, representing near miss events that were identified. No retained stents occurred, consistent with high sensitivity and modest specificity. There were no flags in the last 6 months of the study period. Survey response rate was 100% for surgeons and 55% for nurses. Before eSTENT, stents were not routinely tracked. All surgeons and 93% of nurses reported no added burden, despite occasional misidentification of retained stents. Three surgeons found eSTENT beneficial, four were neutral, and free-text responses generally cited eSTENT's "fail safe" nature as positive. Nurses suggested improvements, including user support and integrated documentation reminders. The average implementation score among both groups was 6/7, indicating easy adoption. DISCUSSION: While the impact of stent tracking tools in adult literature has been positive, our study emphasizes the feasibility of broader adoption at a pediatric hospital. Integration of eSTENT may avoid the potentially devastating consequences of a retained stent. Prioritizing sensitivity over specificity appears acceptable for a "never event" in patient safety. Our study is limited by the retrospective nature of data collection and survey bias. CONCLUSIONS: Though no stents were retained in the study period, eSTENT appropriately flagged two cases without added burden to most end-users. Further optimization is warranted, but adoption in pediatric centers may enhance care reliability.

Humans↗

PubMed2026

Immunogenicity and safety of inactivated TZ84- vs. HM175-based hepatitis A vaccines in pediatric populations: A systematic review and meta-analysis.

Individual studies indicate stronger and persistent long-term immunogenicity with TZ84-based than HM175-based hepatitis A vaccines. This systematic review and meta-analysis compared immunogenicity and safety of inactivated TZ84- and HM175-based hepatitis A vaccines in children and adolescents. Studies involving adults, immunocompromised populations, non-comparative designs, non-English publications, and studies with non-extractable outcomes were excluded. MEDLINE/PubMed, Google Scholar, other electronic databases, and grey literature were searched (September-October 2025). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and meta-analyses were performed where appropriate. Seven publications arising from four randomized cohorts (total participants: 3,282) reporting seroconversion rates (SCRs), geometric mean concentrations (GMCs), long-term seroprotection, and adverse events (AEs) were identified. Pooled analyses demonstrated higher SCRs and GMCs with TZ84 than HM175-based vaccines following both one and two doses. SCRs at 1 month [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.88-4.96] and GMCs at 7 months [standardized mean difference (SMD): 0.88; 95% CI: 0.18-1.58; p = .01] both favored TZ84-based vaccines. Long-term follow-up (up to 186 months/15.5 y) showed higher reported anti-HAV antibody concentrations for TZ84-based vaccines. The AEs were comparable between vaccine types (RR: 0.95; 95% CI: 0.76-1.20; p = .69). Evidence was limited by the small number of unique randomized cohorts, geographic concentration in China, heterogeneity across studies, and reliance on surrogate immunogenicity outcomes. Overall, available evidence suggests that TZ84-based hepatitis A vaccines (HAPIBEV™/HEALIVE®) are associated with higher reported antibody responses and greater reported antibody persistence than the HM175-based vaccine (HAVRIX®) in children and adolescents, with comparable safety profiles.Registration: PROSPERO CRD420251154480.

Humans↗

PubMed2026

Chronic postsurgical pain in children: Current evidence and clinical perspectives.

The chronification of acute pain following surgery is increasingly recognized, with a reported prevalence of 10%-63%, likely reflecting the increasing number of surgical interventions performed in the pediatric population. This pain is more severe after high-risk surgeries, such as spine surgery, hernia repair, and thoracotomy. Currently, the literature reports highly variable definitions of chronic postsurgical pain (CPSP) owing to a lack of objective diagnostic parameters. The International Association for the Study of Pain defines CPSP as "chronic pain that develops or increases in intensity after surgery or a tissue injury and persists beyond three months, without other causes". This pain can be localized to the surgical field or referred to the affected nerve domain. Similarly, the reported incidence of CPSP in children is largely from low-quality studies and varies between 20% and 50% in the studied population. Its neuropathic features are strongly associated with psychological consequences, functional limitations, and adverse long-term health outcomes. Potential risk factors in the pediatric population include psychosocial behaviors, pre-existing pain, postsurgical pain intensity, and the type of surgery performed. Proposed pathophysiological mechanisms include a pro-inflammatory state after surgery, leading to altered peripheral and central sensitization, genomic factors, epigenetic modifications, and altered brain physiology associated with chronic pain. Understanding the pathophysiology helps target interventions for pre-existing pain, surgery-related pain, anxiety, and opioid-induced hyperalgesia. Preoperative protocolized analgesic strategies, cognitive behavioral therapy, and acupuncture have been tried with varied success rates, although concrete data are lacking. The literature on regional analgesia is still limited in the pediatric population and represents a potential area for further research. Furthermore, rehabilitation interventions addressing postoperative trajectories with early referral to transitional pain clinics may offer promising avenues for improving outcomes. There is a significant knowledge gap, a scarcity of available data on CPSP, and difficulties in addressing pain in the pediatric population, underscoring the need for this review.

Children↗

PubMed2025

Evolutionary adaptations of a pediatric pathogen: low-inflammatory and high-resistance phenotypes in the emerging Salmonella typhimurium monophasic variant 1,4,[5],12:i:

Salmonella enterica serovar 1,4,[5],12:i:- (S.1,4,[5],12:i:-), a monophasic variant of Salmonella typhimurium (S. typhimurium), is an emerging multidrug-resistant pathogen posing a significant threat to pediatric health. Research on this variant remains limited, and due to challenges associated with traditional identification methods, S.1,4,[5],12:i:- has often been misclassified as S. typhimurium. This study collected clinical data from 122 children infected with S.1,4,[5],12:i:- and 42 with traditional S. typhimurium in Fujian Province, China, between 2014 and 2023. Whole-genome sequencing was used for strain analysis. Our findings revealed that 77.87% of children with S.1,4,[5],12:i:- infection were aged between 1 month and 2 years. Compared with traditional S. typhimurium, children with S.1,4,[5],12:i:- exhibited milder clinical symptoms, as evidenced by lower levels of the inflammatory marker C-reactive protein (16.53 mg/L vs. 33.94 mg/L, P < 0.05) and a lower hospitalization rate (26.23% vs. 42.86%, P < 0.05). These differences may be attributed to the high carriage rate of the anti-inflammatory gene gogB in S.1,4,[5],12:i:- (95.08% vs. 16.67%, P < 0.0001). Additionally, S.1,4,[5],12:i:- exhibited a higher resistance rate to multiple antibiotics, particularly ceftriaxone, than traditional S. typhimurium (32.79% vs. 7.14%, P < 0.001). This increased resistance may be associated with the carriage of the IncHI2/IncHI2A plasmid. The S.1,4,[5],12:i:- ST34 clone prevalent in this region aligns with the global epidemic trend but exhibits greater genetic diversity. Overall, the stealthy evolutionary adaptation of low-inflammation and high-resistance provides novel insights into this variant's global dominance. These findings underscore the importance of heightened clinical awareness and targeted interventions, particularly for vulnerable pediatric populations. IMPORTANCE S.1,4,[5],12:i:- poses a growing global health threat, particularly endangering infants and young children. Characterized by increasing prevalence, multidrug resistance, and diagnostic challenges, this variant demonstrates milder inflammatory responses yet stronger antibiotic resistance than traditional S. typhimurium in pediatric infections. Crucially, we identified its unique "low-inflammation, high-resistance" evolutionary strategy associated with anti-inflammatory gene gogB and resistance plasmid IncHI2/IncHI2A. The stealthy evolutionary adaptation provides novel insights into this variant's global dominance, while offering critical guidance for improving clinical management and formulating targeted public health measures to protect vulnerable pediatric populations against this cunning pathogen.

Humans↗

PubMed2026

Incidence of acne in patients with inflammatory bowel disease treated with Janus kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: Janus kinase (JAK) inhibitors are effective oral therapies for inflammatory bowel disease (IBD). While acne is a known adverse event in dermatological cohorts, its incidence and risk factors in the IBD population are not well-defined. We aimed to determine the pooled incidence of acne in IBD patients treated with JAK inhibitors and to explore this risk across key clinical subgroups. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. MEDLINE, EMBASE, and CENTRAL were searched from inception to September 2025 for randomized controlled trials (RCTs) and observational studies reporting acne incidence in IBD patients on JAK inhibitors. Data were pooled using a random-effects generalized linear mixed-effects model. Pre-specified subgroup analyses were performed. RESULTS: A total of 50 studies (5 RCTs, 45 observational) involving 9902 IBD patients were included. The overall pooled incidence of acne was 8.6% (95% CI: 6.4%-11.6%). Acne rates were significantly higher (P < .0001) with the upadacitinib (12.2%), compared to tofacitinib (2.6%) and filgotinib (2.3%). A numerically higher incidence was observed during induction (8.6%) versus maintenance (4.2%) therapy, though this difference was not statistically significant (P = .07). The incidence was significantly higher in the pediatric population (12.2%) compared to adults (7.4%) (P = .03). In RCTs, JAK inhibitors were associated with significantly increased odds of acne compared to placebo (OR 2.43, 95% CI: 1.33-4.43, P = .019). No statistically significant difference was observed by IBD subtype. CONCLUSION: Acne is a common adverse event in IBD patients treated with JAK inhibitors. The reported incidence of acne was significantly higher with upadacitinib, in the pediatric population, and numerically higher during the induction phase of treatment.

Humans↗

PubMed2026

Genetic landscape of pediatric seizures in Southeast China: identification of a novel GLI3 frameshift variant through whole-exome sequencing.

BACKGROUND: Pediatric seizure disorders are clinically and genetically heterogeneous. Whole-exome sequencing has improved the detection of rare genetic variants in childhood epilepsy; however, data from pediatric populations in Southeast China remain limited. This study aimed to characterize the genetic landscape of pediatric seizure disorders in Southeast China and to evaluate the clinical diagnostic yield of whole-exome sequencing. MATERIALS AND METHODS: This retrospective observational study included 21 pediatric patients with seizure disorders who were recruited at the Fifth Hospital of Xiamen, Fujian, China, between January 2021 and June 2024. Clinical data were extracted from medical records. Whole-exome sequencing was performed on DNA extracted from peripheral blood. Sequence variants were annotated, filtered, and classified according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Copy-number variants were evaluated using exome-based algorithms. Descriptive statistics were used because of the limited sample size. RESULTS: WES identified three clinically relevant, likely pathogenic findings in 3 of 21 patients, corresponding to a provisional diagnostic yield of 14.3%. The remaining 62 of 65 variants were of uncertain significance (VUS). The three retained variants included a GLI3 frameshift variant (exon 2: c.90_91insCAGATGTGAGC; p.Glu31Glnfs*3) and two copy-number variants (16p13.12-16p13.11 duplication and Xp22.31 deletion) with established clinical significance. Functional analysis of all 65 variants revealed that ion channel genes and neurodevelopmental genes were the most frequently affected categories. CONCLUSION: Whole-exome sequencing identified clinically relevant genetic findings in a subset of Southeast Chinese children with seizure disorders. The novel GLI3 frameshift variant may suggest an expansion of the GLI3-associated phenotypic spectrum, but further segregation, functional validation, and larger cohort studies are needed. The high proportion of variants of uncertain significance highlights the ongoing challenges of genetic interpretation in pediatric seizure disorders.

GLI3 frameshift variant↗

PubMed2026

Clinical and molecular characterization of TCF12 variants in an Asian pediatric cohort with craniosynostosis.

BACKGROUND: Craniosynostosis is a genetically heterogeneous craniofacial disorder caused by the premature fusion of one or more cranial sutures. Pathogenic variants in TCF12, encoding a basic helix-loop-helix (bHLH) transcription factor, represent a major cause of autosomal dominant coronal craniosynostosis and are characterized by incomplete penetrance and marked phenotypic variability. However, clinical and molecular data from Asian pediatric populations remain limited. METHODS: Trio-based whole-exome sequencing was performed on ten pediatric patients with cranial deformities and their parents. The identified TCF12 variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by Sanger sequencing. Detailed clinical and radiological data were collected. In addition, a comprehensive literature review was conducted to summarize previously reported TCF12 variants and associated phenotypes. RESULTS: Ten distinct heterozygous TCF12 variants were identified in ten unrelated pediatric patients, all of which were classified as pathogenic or likely pathogenic according to ACMG criteria. Six variants were inherited, and four occurred de novo. Seven patients had imaging-confirmed craniosynostosis, predominantly involving the coronal sutures (five bilateral and one unilateral), while one patient presented with multisuture craniosynostosis (left coronal and sagittal sutures). Three patients showed cranial deformities without radiographic evidence of suture fusion. Phenotypic heterogeneity and incomplete penetrance were observed, including a mildly affected parent. Most pathogenic variants were truncating variants distributed mainly across exons 14-19 and predicted to induce loss of function, either through nonsense-mediated mRNA decay or the production of truncated proteins lacking the entire C-terminal bHLH domain. Structural modeling analysis further indicated that the bHLH-domain-located missense variant p.Arg603Trp alters the local DNA-binding conformation of TCF12 and impairs its binding affinity to the E-box DNA motif. CONCLUSIONS: This study provides additional clinical and molecular data on TCF12-related craniosynostosis in a pediatric cohort from an Asian population. Our findings support haploinsufficiency as the central pathogenic mechanism, primarily driven by truncating variants affecting the C-terminal bHLH domain. The marked clinical heterogeneity, the presence of mild or evolving phenotypes, and incomplete penetrance observed in our cohort underscore the importance of early diagnosis and longitudinal clinical surveillance in affected families.

Humans↗

PubMed2025

Monogenic disorders associated with motor speech phenotypes in children and adolescents undergoing clinical exome sequencing.

PURPOSE: Prior studies investigating the genetic architecture of pediatric motor speech disorders (MSDs) have been limited by small sample sizes and an exclusive focus on apraxia. We aimed to identify pathogenic genomic variants associated with MSDs in a large pediatric population referred for exome sequencing (ES). METHODS: We identified pediatric patients with MSDs who had clinical ES between 2012 and 2022. The rate of pathogenic/likely pathogenic (P/LP) findings considered causative of the MSD phenotype was determined and delineated by sex and neurodevelopmental comorbidity. Gene-based burden testing compared the rate of P/LP variants in each gene in MSD cases with a comparison clinical ES cohort. RESULTS: Positive diagnostic results were detected in 527 of 2004 (26.3%) patients with MSDs, with higher diagnostic rates in females and individuals with neurodevelopmental comorbidities. P/LP sequence variants were detected in 262 genes. Gene-based case-referent burden analysis revealed that 30 genes were nominally associated with MSDs, 2 of which (SETBP1 and ADCY5) survived exome-wide correction. CONCLUSION: Over 25% of patients with MSDs were found to harbor P/LP variants in 262 genes, many of which have not previously been associated with MSDs. Potential clinical implications include early implementation of intensive speech therapy for children diagnosed with monogenic causes of MSDs.

Humans↗

PubMed2026

Association between plasma homocysteine levels and P-wave dispersion in pediatric patients with hyperhomocysteinemia.

UNLABELLED: Hyperhomocysteinemia has been recognized as a cardiovascular risk factor associated with endothelial dysfunction, oxidative stress, and vascular inflammation. Experimental and clinical studies suggest that elevated homocysteine levels may also influence myocardial electrophysiology and contribute to arrhythmogenesis. However, data regarding the relationship between homocysteine levels and electrocardiographic markers of atrial conduction in pediatric populations remain limited. This study aimed to evaluate the association between plasma homocysteine levels and electrocardiographic parameters, particularly P-wave dispersion, in children. This multicenter retrospective case-control study included pediatric patients evaluated in four tertiary pediatric metabolism centers between January 2023 and December 2025. A total of 47 patients with hyperhomocysteinemia (plasma total homocysteine ≥ 15 µmol/L) and 43 age- and sex-matched controls with normal homocysteine levels were included. Controls were selected from the screened population among children with available homocysteine measurements, electrocardiographic and echocardiographic evaluations, and no confirmed inherited metabolic disease or cardiac disorder. Clinical, biochemical, and electrocardiographic parameters, including maximum P-wave duration and P-wave dispersion, were retrospectively analyzed. A total of 90 participants were included, comprising 47 children with hyperhomocysteinemia and 43 healthy controls. P-wave dispersion and maximum P-wave duration were significantly higher in the hyperhomocysteinemia group compared with controls (48.96 [19.48-100.0] vs. 38.57 [10.57-71.19] ms, p < 0.001). Plasma homocysteine levels showed a moderate positive correlation with P-wave dispersion (ρ = 0.441, p < 0.001). These differences were more pronounced in children with higher homocysteine levels and in younger age groups (< 2 years and 2-14 years). In contrast, PR interval (p = 0.790) and QTc interval (p = 0.183) did not differ significantly between groups. Vitamin B12 levels were significantly lower in the hyperhomocysteinemia group (p = 0.013), while folate levels were comparable (p = 0.974). Although sodium, potassium, and magnesium levels differed significantly between groups, all values remained within normal physiological ranges. CONCLUSIONS: Children with hyperhomocysteinemia showed increased P-wave dispersion compared with controls. These findings suggest an association between elevated homocysteine levels and altered atrial conduction parameters in children. Further prospective studies are needed to determine the clinical significance of these findings. WHAT IS KNOWN: • Hyperhomocysteinemia is associated with cardiovascular risk and endothelial dysfunction. • Elevated homocysteine levels have been linked to cardiac electrophysiological alterations in adult populations. WHAT IS NEW: • Elevated homocysteine levels are associated with increased P-wave dispersion in children, with more pronounced effects observed in younger age groups. • These findings support an association between hyperhomocysteinemia and altered atrial conduction parameters in children.

Adolescent↗

PubMed2025

Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.

BACKGROUND: Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited. METHODS: This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19 years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024. RESULTS: Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2 years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5 months) compared to lower-grade tumors (up to 57 months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico. CONCLUSION: This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region.

Humans↗

PubMed2025

Preliminary screening of urinary host protein biomarkers for Schistosomiasis haematobium: A proteome profiling study identifying candidate diagnostic targets in school-aged children.

Schistosomiasis is a major public health challenge and a globally neglected tropical disease. Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is endemic in African countries; with school-aged children ages 7-15 years being the most vulnerable population. Current diagnostic methods rely on microscopy to identify parasite eggs in urine; which is labor-intensive, requires specialized skills, and often lacks sensitivity, especially in mild infections. To address these limitations, we explored host disease-related biomarkers as a promising avenue for advancing diagnosis and detection. We recruited 135 children ages 7-15 years from Zanzibar, a known transmission hotspot, and used data-independent acquisition (DIA) proteomics combined with machine learning to identify potential host protein biomarkers in urine samples from individuals infected with Schistosoma haematobium. Proteomic analysis identified 823 common host proteins in urine samples from the infected group. Machine learning algorithms highlighted candidate discriminative proteins; which were validated using enzyme-linked immunosorbent assays (ELISA). Machine learning emphasized SYNPO2, CD276, α2M, LCAT, and hnRNPM as the most discriminating biomarkers for Schistosoma haematobium infection. ELISA validation confirmed the differential expression trends of these proteins, while machine learning further validated LCAT and α2M, underscoring their diagnostic potential. Our study focused on host-derived proteins and identified key urinary protein biomarkers associated with Schistosoma haematobium infection, and offers new insights into host-parasite interactions and potential tools for non-invasive diagnostics. While validated in African pediatric populations from transmission hotspots, this host-protein approach inherently overcomes geographic limitations of parasite-based diagnostics; which is a critical advantage for surveillance in non-endemic regions where imported cases threaten gains toward elimination. These findings lay the groundwork for developing novel diagnostic approaches that could significantly improve the detection and surveillance of schistosomiasis, particularly in high-risk populations.

Humans↗

PubMed2026

Developing Highly Effective Nanoparticle mRNA Therapeutic for Pediatric Acute Respiratory Distress Syndrome.

Sepsis-induced pediatric acute lung injury (ALI) and pediatric acute respiratory distress syndrome (PARDS) are life-threatening conditions with high mortality rates and no current cure. Most ALI/ARDS studies focus on adults, albeit the pediatric population has unique challenges often underrepresented. ALI/PARDS severely impacts pulmonary endothelial cells (ECs), causing endothelial dysfunction and vascular leakage. FOXF1 is a transcription factor critical for lung repair after injury, representing a viable target for ALI/PARDS. This study developed and tested a novel nanoparticle system for precise delivery of FOXF1 mRNA into lung ECs to reduce endothelial damage and improve lung function in mouse model of PARDS. Systemic inflammatory response was induced in neonatal mice after intraperitoneal administration of lipopolysaccharide (LPS). Specifically designed nanoparticles (NP) were used to intravenously deliver stabilized FOXF1 mRNA (FOXF1 NP) after LPS injury to restore FOXF1 expression in injured lung endothelial cells. FOXF1 NP selectively targeted pulmonary ECs without affecting other cell types or organs. FOXF1 NP treatment reduced vascular leakage, enhanced endothelial barrier function, and improved survival of neonatal mice after injury. FOXF1 NP decreased EC apoptosis by restoring the expression of BCL2, an anti-apoptotic FOXF1 target gene. Nanoparticle-based rescue of lung ECs has promise for future treatments of human ALI/PARDS.

endothelial cells↗

PubMed2026

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference = -0.02; 95% CI: -0.06 to 0.02, I2 = 0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans↗

PubMed2025

Outcome of conservative management of small renal stones in prepubertal children.

INTRODUCTION: Renal stones are relatively uncommon in the pediatric population. This study aimed to evaluate the utility of conservative management of small renal stones in prepubertal children. PATIENTS AND METHODS: A retrospective chart review was conducted for children (≤12 years old) with small renal stones (3-10 mm) from 2016 to 2023 who underwent conservative management. Management included periodic renal ultrasonography, every 6 months, in addition to good hydration. Stones were confirmed by two consecutive ultrasounds. We recorded the patient's demographics and ultrasound findings (stone side, size, laterality, location, number, and associated hydronephrosis). Surgical intervention was indicated if recurrent loin pain, recurrent UTI, or worsening hydronephrosis (obstructing stone). Nephrolithiasis was considered resolved if stones were not visualized on 2 consecutive ultrasounds. Moreover, we evaluated conservative management outcomes for those presented during infancy (<12 months) versus later. RESULTS: We included 52 patients (65renal units) who presented at a median age of 46.1months (5.3-155.1). Seventy-five percent of patients had incidental renal stones. The median stone size was 4 mm (3-10). Forty-six percent of stones were in the lower calyx. The majority (70.8 %) had no hydronephrosis at presentation. During a median follow-up of 39months, 15patients with 17units (26.2 %) were documented stone-free. Ten patients (19.2 %) had symptomatic stone events, all measured ≥4 mm. Of them, 6 patients (6 units) underwent surgical interventions, and 4 patients (4 units) experienced complications. A ROC curve analysis identified a stone size cutoff of 4 mm (sensitivity 100 % and 29 % specificity) that could be associated with symptomatic stone events. Using a multivariate Cox regression model, stone size was the only significantly associated factor with subsequent surgical intervention (p = 0.007). 19 % (10patients,12units) presented during infancy. Notably, the incidence of stone-free rate was significantly higher during infancy compared to older children (58.3 % vs 18.9 %,respectively). DISCUSSION: During a 39-month follow-up, 4 patients developed complications (2recurrent pain and 2 experienced UTI), supporting the safety of conservative management of small renal stones. This study is limited due to its retrospective design and the reliance on ultrasound as the main imaging method. To minimize that, all ultrasound images were carefully reviewed by two pediatric urologists. Moreover, renal stones were confirmed using strict criteria, which required detection in two consecutive ultrasounds. CONCLUSION: Although 26.2 % of units had spontaneously resolved nephrolithiasis, surgical intervention was only required in 11.5%of patients, all of whom had renal stones≥4 mm. Infants had higher spontaneous resolutions without complications, suggesting that conservative management may be especially effective in this subgroup.

Humans↗

PubMed2026

Methylation profiling in CNS tumor diagnostics: a single-centre real-world experience from Central Europe.

Genome-wide DNA methylation profiling has transformed neuro-oncology by providing an objective, machine learning-based taxonomy that mitigates interobserver variability and refines the histo-molecular criteria of the current WHO classification. We evaluate the real-world diagnostic performance and clinical utility of this modality in a prospective, consecutively accrued three-year cohort of 291 central nervous system (CNS) tumors across a mixed adult-pediatric population. Successful profiling was completed in 95.9% of cases. Using the Epignostix classifier, a high-confidence diagnostic match (calibrated score [CS] ≥ 0.84) was achieved in 70.3% of analyzable samples, while 26.5% returned lower-confidence scores (≥ 0.3 to < 0.84) and only 3.2% remained completely unclassifiable (CS < 0.3). When integrated into a comprehensive diagnostic framework, methylation profiling provided clinically useful results in 81.1% of cases, establishing diagnoses in 70 cases submitted for molecular subclassification and resolving diagnostic uncertainty or prompting major revisions in 149 histologically challenging tumors. Within truly ambiguous lesions, integration of methylome data dictated tumor grade modifications in 38.8% of cases (upgrading in 29.4% and downgrading in 9.4%), shifting patient risk stratification. Crucially, over half (52.7%) of the lower-confidence cases yielded meaningful clinical integration when supported by histomorphology and ancillary genetic or immunohistochemical markers, demonstrating that rigid score cutoffs should not dictate assay failure. Discrepant or misleading classifications occurred in 1.9%. Updating bioinformatic pipelines from version 11b4 to 12.8 rescued multiple ambiguous entries, increasing overall clinical utility to 84.1%. These findings demonstrate that integrating computational epigenomics with classical neuropathology enhances diagnostic precision, while highlighting the ongoing need for careful clinical-pathological correlation.

Central nervous system tumors↗