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Methylphenidate is widely prescribed for attention-deficit/hyperactivity disorder, and its use has increased substantially in recent years. Although generally considered safe within therapeutic ranges, supratherapeutic ingestion may result in various systemic adverse effects. This study aimed to evaluate the demographic and clinical characteristics of children presenting with overdose ingestion and to identify potential factors associated with symptom development. We conducted a retrospective review of patients younger than 18 years who presented to a tertiary pediatric emergency department between January 1, 2020, and December 31, 2024, due to overdose ingestion. Demographic characteristics, psychiatric history, ingested dose, mode of exposure, clinical findings, emergency department course, and factors potentially associated with adverse effects were analyzed. Thirty-two patients were included; 72% were female, and ingestion was intentional in 84%. The mean ingested dose was 5.7 mg/kg. Clinical symptoms developed in 41% of patients. The most frequent findings were tachycardia (38%), mild hypertension (34%), agitation (22%), and seizures (16%). Although most cases were mild and resolved within 12 h of observation, one toddler developed neuropsychiatric manifestations requiring close monitoring with full recovery within 48 h. No statistically significant association was observed between age, sex, gastrointestinal decontamination status, or reported ingested dose and the development of clinical symptoms (p > 0.05). Pediatric methylphenidate intoxication is generally mild, but severe neuropsychiatric and cardiovascular effects may occur. Careful clinical monitoring remains essential. Not applicable.

Gaucher disease (GD) is one of the most common lysosomal storage disorders, and has three clinical subtypes (Type 1, 2 and 3). Of the three subtypes, type 2 GD (GD2), also referred to as acute infantile neuronopathic GD is the most severe type. It is characterized by early and profound central nervous system involvement, and patients succumb to disease before two years of age due to severe neurological deterioration and associated complications. It is the rarest of the three subtypes with a reported proportion of <&#x2009;1% among all Gaucher subtypes. Furthermore, data from the Indian subcontinent on clinical profiles, molecular spectrum, and outcomes in GD2 remain scarce. The present study describes the clinical, biochemical, and molecular spectrum of GD2 cases in an Indian cohort. This is a retrospective study comprising 19 patients referred by pediatricians from across India, who were diagnosed with GD based on &#x3b2;-Glucosidase enzyme activity and GBA gene study. Plasma chitotriosidase activity and &#x3b2;-glucosidase activity were measured in plasma sample and leukocytes respectively using fluorometric enzyme assays. Molecular confirmation was performed in all 19 patients by using one of the following tests: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Sanger sequencing, targeted panel or whole exome sequencing study. The common clinical signs observed in the study cohort were hepatosplenomegaly, thrombocytopenia, oculomotor signs, failure to thrive and feeding difficulties. Molecular study revealed causative variants distributed across exons 3, 4, 5, 6, 7, 9, 10, and 11 of the GBA1 gene, with exon 10 being the most common (n&#x2009;=&#x2009;11/19). The variant c.1448T&#x2009;>&#x2009;C (p.Leu483Pro) was identified in a compound heterozygous state in majority cases (n&#x2009;=&#x2009;10/19). Furthermore, we also identified a rare recurrent missense variant c.371T&#x2009;>&#x2009;G (p.Met124Arg) in exon 4 of the GBA1 gene in 4 patients with GD2 from Gujarat, suggesting the possibility of a founder effect. Computational protein modeling and in-silico analysis predicted a destabilizing effect on GBA1 protein structure and stability. Overall, the present study represents the largest case series of type 2 Gaucher disease reported from India to date and provides important insights into its clinical and molecular spectrum in the Indian population.

With increasing recognition of children's evolving decision-making capacities, assessing decision-making capacity in pediatric clinical practice has become legally and ethically important, yet no standardized assessment approach exists. The aim of this systematic review was to identify and evaluate assessment tools for decision-making capacity in children and to examine their clinical applicability and validation in pediatric populations. We conducted a systematic search in accordance with PRISMA guidelines across major academic databases and grey&#x2011;literature sources. Two reviewers independently screened studies and extracted data using predefined criteria. We appraised validation studies using the QUADAS&#x2011;2 tool. Due to substantial heterogeneity in study designs, populations, and outcomes, a descriptive synthesis was conducted. A total of 27 peer&#x2011;reviewed studies and one guideline met the inclusion criteria. Across these studies, we identified seven tools: the MacArthur Competence Assessment Tools (MacCAT-T and MacCAT-CR), the Measure of Competency to Render Informed Treatment Decisions (MOC), the Maturtest, the University of California San Diego Brief Assessment of Capacity to Consent (UBACC), the Competency Questionnaire for Pediatric Population (CQ-Peds), and the Hopkins Competency Assessment Test (HCAT). The assessment tools demonstrated considerable heterogeneity in purpose, conceptual grounding, methodological approach, administration, time requirements, scoring procedures, and validation in child populations. The Maturtest, assessing moral maturity, and the child-adapted MacCAT-CR, assessing decision-making capacity in clinical research, are the only two identified validated assessment tools in a child population. One official WHO guideline was also identified. We identified seven assessment tools, assessing either moral maturity or decision-making capacity. The child-adapted MacCAT-CR remains the only validated instrument for assessing decision-making capacity in children, although mainly in research settings. No validated tool for routine clinical practice was identified, highlighting the need for clinically applicable, multidimensional assessment tools. PROSPERO: CRD420251052918.

Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases that include dermatomyositis, polymyositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy in both adult and juvenile populations. Interstitial lung disease (ILD) is a common and serious complication of IIM, with a highly variable clinical course ranging from indolent disease to rapidly progressive respiratory failure, often influenced by underlying myositis-specific autoantibody profiles. Despite the substantial morbidity and mortality associated with IIM-ILD in both adults and children, high-quality evidence to guide clinical management remains limited. A major barrier to progress in this field is the lack of standardized disease nomenclature and uniform diagnostic or classification criteria, which hampers cohort development, limits comparability across studies, and restricts generalizability of findings. To address this gap, we will conduct a systematic review to inform a consensus-based disease definition for adult and juvenile IIM-ILD, with detailed methodology outlined in this protocol. This review will not evaluate prognosis, treatment, or clinical outcomes, but instead focus exclusively on how IIM-ILD is defined and operationalized across studies. Following PRISMA 2020 statement and Cochrane methodology, we will search PubMed, EMBASE, Scopus, Cochrane Systematic Reviews, and Cochrane Central from inception to June 30, 2025, using a ''Peer Review of Electronic Search Strategies (PRESS)''-validated strategy. Eligible studies will include randomized controlled trials (RCTs), cohort and case-control studies, systematic reviews, meta-analyses, guidelines, and consensus statements explicitly reporting IIM-ILD definitions in human participants of all ages. Study selection will be performed in Covidence using predefined criteria. Data extraction will capture case definitions, classification criteria, diagnostic methods, ILD patterns, autoantibody profiles, and study characteristics. Quantitative synthesis will summarize the frequency and components of definitions where possible; otherwise, a structured narrative synthesis will be performed. Our systematic review protocol is the first comprehensive attempt at synthesizing the highly heterogenous disease nomenclature currently employed in adult and juvenile IIM-ILD literature. Findings will map areas of agreement and inconsistency in existing definitions, forming an evidence base for subsequent consensus processes, such as Delphi, to establish standardized nomenclature. Harmonized definitions are expected to improve research reproducibility, facilitate multicentric collaboration, and improve patient stratification in clinical practice and trials. PROSPERO ID: 1129967.

Globally, especially in the Asia Pacific region, chronic hepatitis B infection has led to an undesirable escalating morbidity and mortality with acute-on chronic liver failure, end-staged liver cirrhosis, and hepatocellular carcinoma. This has happened despite the past four decades of major scientific advances made in screening methods, vaccination strategies, highly effective low-cost anti-viral therapies, and surveillance strategies for early detection of hepatocellular carcinoma. To address this health threat, APASL has formed a Viral Elimination Taskforce to unite key opinion leaders from its member countries and regions. The ongoing shifts in hepatitis B epidemiology, socioeconomic changes, and advancements in technology are taken into consideration. With the conjoint efforts of all the members of the APASL Viral Elimination Taskforce, these clinical practice guidelines have been formulated aiming to facilitate healthcare professionals, policy-makers, and patients in making practical and cost-effective management decisions for chronic hepatitis B infection. Altogether, it provides recommendations in 13 major areas related to screening, vaccination, treatment, and HCC surveillance. The implementation of these clinical practice guidelines represents major APASL effort toward elimination of the disease burden due to chronic hepatitis B infection in Asia Pacific region.

Non-allergic rhinitis syndrome (NAR) is a chronic rhinitis characterized by the significant absence of an allergy history, negative skin prick test results, and normal serum IgE levels. Nasal cytology is a valuable diagnostic method that enables qualitative and quantitative assessment of inflammatory cells - including eosinophils, neutrophils, mast cells, and lymphocytes - in the nasal mucosa. This study aimed to evaluate the levels of nasal eosinophilia in a pediatric NAR population and to evaluate the correlation of this local inflammatory biomarker with clinical severity scales such as ARIA and PRQLQ. This prospective, cross-sectional study included 103 children aged 5-18 years: 53 with NAR and 50 healthy controls. Symptom duration and severity were classified according to ARIA 2019 criteria. The Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) was used for quality of life assessment. Nasal cytology specimens were collected by nasal swab from the middle meatus and the eosinophil percentage was calculated by counting a total of 100 cells in the area of highest cell density. A total of 103 children were enrolled: 53 NAR patients and 50 healthy controls. Median age was 10 (8-13) years in the study group and 11 (8-14) years in the control group. Family history of allergy was significantly higher in the study group (30.2%) compared to controls (12.0%) (p&#x2009;=&#x2009;0.024). Median nasal eosinophil level was 7.0 (3.5-15.5) in the study group and 0 (0-3.0) in controls; the difference was statistically significant (p&#x2009;<&#x2009;0.001). The nasal eosinophil cut-off value was determined as 3.5%. No significant difference was found between nasal eosinophil groups (<&#x2009;3.5% and &#x2265;&#x2009;3.5%) and any PRQLQ subscale or total score (p&#x2009;>&#x2009;0.05). Nasal cytology may serve as a simple, non-invasive diagnostic tool to identify NAR subtypes and to determine clinical severity in pediatric patients.

This study aimed to evaluate the determinants of postoperative complications in pediatric surgical patients and investigate whether the Systemic Immune-Inflammation Index (SII) independently predicts complication type in a predominantly acute abdominal pediatric surgical population. This retrospective study included patients aged 0 to 18 years who underwent surgical procedures between 2017 and 2024. Demographic characteristics, preoperative laboratory parameters, culture results, postoperative complications, and clinical outcomes were recorded. The primary outcome was postoperative complication class (local vs systemic). Secondary outcomes included in-hospital mortality, length of hospital stay, and readmission. Multivariable regression analyses were performed. A total of 307 pediatric patients were included; 64.17% were male. The majority underwent acute abdominal emergency surgery (89.54%). The most frequent culture growth site was the peritoneum (65.47%). Gram-negative microorganisms accounted for 94.46% of isolates, whereas Gram-positive organisms constituted 5.21%; fungal growth was observed in 1.30% of patients. Local complications were observed in 96.42% of patients, whereas systemic complications occurred in 3.58%. Overall mortality was 2.93%. Fever was significantly more common among non-survivors compared to survivors (77.78% vs 12.75%, P&#x2005;<&#x2005;.001), and systemic complications were associated with mortality (P&#x2005;=&#x2005;.040). Although SII values were higher in Gram-negative infections, SII did not independently predict complication type or mortality in this heterogeneous cohort. Gram-negative pathogens predominate in pediatric surgical infections. However, laboratory inflammatory indices, including SII, did not independently predict postoperative complication type or mortality. These findings suggest that clinical and perioperative factors play a more important role in determining outcomes in this predominantly acute abdominal pediatric surgical population.

To build on existing evidence regarding single-item measurement instruments of patient-reported bother or trouble from medical side effects in individuals with rheumatic and musculoskeletal diseases (RMDs). Further, to collect input from the OMERACT community through a structured survey that rated and ranked available options and to seek agreement to advance one or more of these measures for use as exploratory outcomes in future clinical trials. At OMERACT 2025 we presented and discussed survey results for domain match, feasibility and ranking of six candidate instruments of bother or trouble from side effects. Collaborator feedback - including comments from patients, clinicians, and researchers - was synthesized with a large-language-model (LLM) to identify key concerns and guide refinement of the instrument's relevance, clarity, and acceptability. The LLM-assisted synthesis of participant comments resulted in a new, single-item instrument designed to improve patient safety reporting from the patient's perspective. The merged and modified version of the instrument was presented at the OMERACT 2025 meeting, where 33 participants approved it as a reasonable approach to incorporate collaborator input. The proposed instrument is feasible (32 [97%]) and voting supported advancing its further assessment (30 [91%]) as an exploratory outcome measurement instrument in coming RMD trials. We developed a novel single-item instrument. This is the first known application of LLMs in refining a patient-reported outcome instrument for clinical trials. It is designed to capture the patient perspective on symptomatic treatment-related side effects in RMDs and is supported for exploratory use in trials.

Primary ciliary dyskinesia (PCD) is a rare congenital disorder marked by impaired motile ciliary function, resulting in chronic oto-sino-pulmonary infections, including Pseudomonas aeruginosa . While enhanced infection prevention and control (IPC) practices have successfully reduced P. aeruginosa prevalence and transmission in cystic fibrosis (CF), comparable IPC strategies have not been evaluated in PCD. This study aimed to characterize bacterial epidemiology across PCD Clinical Centers, hypothesizing that P. aeruginosa prevalence would be higher at centers lacking enhanced IPC measures. We performed a retrospective observational study assessing the period prevalence and chronic infection rates of P. aeruginosa and other respiratory microorganisms at three pediatric PCD Centers and one adult Center. Between-center comparisons of patients ever infected status used Fisher's exact test, with age-adjusted repeated-measures analyses conducted via Bayesian mixed-effects logistic regression. The cohort included 41 pediatric patients from Center A (Standard Precautions), 25 from Center B (clinic cohorting), and 30 from Center C (enhanced IPC based on CF Foundation Guidelines, CF-IPC). An additional 13 adult patients from Center A were included for descriptive analysis only. P. aeruginosa period prevalence at pediatric Centers A, B, and C was 37%, 32%, and 47%, respectively (p = 0.55). In contrast, pediatric Haemophilus influenzae prevalence (p=0.001) and chronic H. influenzae infection rates (p<0.0001) were significantly higher at Center A compared with Centers B and C. Age-stratified analysis across all pediatric Centers demonstrated increasing P. aeruginosa prevalence beginning around age 10, while H. influenzae prevalence declined with age. Nearly 85% of adults had a history of P. aeruginosa infection. Our findings suggest that CF- IPC protocols may not exert the same influence on bacterial epidemiology in PCD as they do in CF. P. aeruginosa may be more prevalent in PCD than previously recognized, and variations in IPC strategies were not significantly associated with differences in P. aeruginosa rates across pediatric PCD Centers.

Marginalized populations experience increased eating disorder (ED) risk and encounter significant barriers to treatment. Intersectionality provides a framework for understanding how systemic oppression contributes to inequities in EDs; however, intersectional approaches have yet to be applied to a clinical ED sample. The current study examined inequities in ED severity and treatment outcome across the intersections of race/ethnicity, sexual orientation, and socioeconomic status (SES). Adult women (N=3016; M&#x202f;=&#x202f;27.2 years) with transdiagnostic EDs presenting to affiliated treatment sites across the United States completed the Eating Disorder Examination-Questionnaire (EDE-Q) at admission and discharge. Race/ethnicity and sexual orientation were self-reported; SES was measured using the area deprivation index of participants' neighborhoods. Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) was used to estimate baseline EDE-Q global score; change in EDE-Q global score and binge eating, self-induced vomiting, laxative use, and driven exercise frequency from admission to discharge; and reason for discharge (routine or non-routine) across intersectional subgroups. In this sample of women with access to treatment, MAIHDA models predicted higher baseline levels of overall ED pathology among sexual minorities (predicted M&#x202f;=&#x202f;4.10). Few differences in ED symptom improvement were observed across intersectional subgroups, with some small yet potentially meaningful inequities. Racially/ethnically minoritized subgroups appeared slightly less likely to complete treatment (predicted percent non-routine discharge&#x202f;=&#x202f;41.50%). Future research should build on these findings by analyzing other dimensions of inequity (e.g., gender, weight status, disability status) to further characterize and address intersecting systems of oppression that disparately influence ED outcomes.

Preterm birth affects approximately 10% of U.S. births, and children born preterm face twice the lifetime risk of chronic kidney disease (CKD). Despite this, kidney health surveillance after preterm birth is uncommon. Although clinical decision support (CDS) tools are widely used in pediatric practice, none address CKD risk stratification after preterm birth. This study assessed pediatric clinician perspectives on facilitators and barriers to CDS tool use, in general and for pediatric CKD risk stratification. We conducted a qualitative descriptive study using semistructured interviews with neonatologists, general pediatricians, and pediatric nephrologists in the United States (December 2023-April 2024). Interviews were conducted by video or teleconference, digitally recorded, and professionally transcribed. Thematic analysis followed COREQ guidelines, and sampling continued until thematic saturation was confirmed. Twenty-five pediatric clinicians participated (44% neonatologists, 44% general pediatricians, and 12% nephrologists; median age 39&#xa0;years, 76% female, 52% White, 88% non-Hispanic, and 80% academic practice). Clinicians reported strong preferences for CDS tools that efficiently support workflows, integrate with the electronic health record (EHR), and provide actionable recommendations with caregiver education. Key concerns included unintended consequences such as false reassurance, over-referral to nephrology, and care burden for families with limited subspecialty access. All participants endorsed the need for a pediatric CKD risk stratification tool. Pediatric clinicians prefer EHR-integrated, evidence-based, family-centered CDS tools to guide CKD risk identification after preterm birth. These findings represent an important step toward developing a pediatric kidney disease risk stratification CDS tool.

Patients with variations exhibiting abnormal phenotypes or no significant clinical signs offer crucial insights into our genome's complexities. To help determine the pathogenicity of 13q21.1q21.32 deletion, we reported four patients in a family carrying this variation. Our study identified a family of four patients harboring a deletion of approximately 10.884 Mb spanning 13q21.1 to q21.32, despite exhibiting no apparent phenotypic manifestations. This finding, alongside evidences from existing research, suggests that the deletion of 13q21.1q21.32 is a likely benign copy number variation (CNV). The findings can be used as a reference for genetic counseling in cases of similar abnormalities encountered during future prenatal diagnosis.

To evaluate the efficacy and safety of Xiao'er Niuhuang antipyretic plaster in treating fever associated with acute upper respiratory tract infection (AURI) accompanied by wind-heat syndrome in children. A total of 464 pediatric patients diagnosed with AURI and wind-heat syndrome were enrolled. Participants were stratified into two age subgroups (1-2 years and 3-5 years) and then randomly assigned in a 3:1 ratio to receive either the Xiao'er Niuhuang antipyretic plaster or an extremely low-dose control plaster. The primary outcome was the time to onset of fever reduction. Safety assessments included monitoring of vital signs, laboratory tests (complete blood count, urinalysis, stool routine, and liver and kidney function), electrocardiogram, and local skin reactions. The median time to onset of antipyretic effect was significantly shorter in the Xiao'er Niuhuang antipyretic plaster group than in the control group (2.53 h vs 3.98 h). The complete antipyretic rates at the 4-h time point were 31.76% for the Xiao'er Niuhuang antipyretic plaster group and 17.70% for the control group; at the 8-h time point, the rates were 49.55% and 33.04%, respectively. No significant difference was observed in the incidence of adverse events between the two groups (P >0.05). No serious adverse events were reported. Xiao'er Niuhuang antipyretic plaster is an effective and safe treatment for fever in children with AURI and wind-heat syndrome.

Differences in sex development (DSD) with 46,XY karyotype are a group of rare congenital conditions affecting the structure and function of the urogenital system. Published data indicate, that despite the increasingly widespread use of genetic testing, the etiology remains unclear in approximately half of cases. To clarify the molecular causes of 46,XY DSD by performing whole-exome sequencing (WES) in a precisely phenotyped and clinically comprehensively evaluated group of patients. WES was performed in a consecutive cohort of 39 children diagnosed in our center as 46,XY DSD (aged 0.2-17.9&#x2009;years). 32 were assigned male, 6 female, and 1 was a transgender boy. All patients underwent detailed clinical, hormonal and biochemical evaluation prior to genetic testing. A genetic cause explaining DSD phenotype was identified in 8 children. Pathogenic variants were detected in 3 patients, including variants in the AR and DHX37 genes. Likely pathogenic variants were found in 5 patients, affecting the AR and HSD17B3 genes. Variants of uncertain significance (VUSs) were identified in 7 patients, involving genes with well-established relevance to DSD- NR5A1, DHX37, AR, MAMLD1, SOS2andFAM111A. Although classified as VUSs these variants represent plausible contributors to the patients' phenotypes. In the remaining children, no variants currently known or suspected to be associated with 46,XY DSD were identified. The most common confirmed etiology in the cohort was androgen insensitivity syndrome (AIS). In addition, pathogenic variants in genes not linked to DSD were identified in 7 patients, demonstrating the broader clinical utility of WES. Our findings confirm that even a broad, high-throughput method such as WES fails to establish the molecular cause of 46,XY DSD in a substantial proportion of well-phenotyped patients, while at the same time enabling the identification of pathogenic variants in genes unrelated to DSD. We observed frequent genotype-phenotype discordance: similar clinical phenotypes could be associated with different genotypes, whereas the same gene variant could present with variable clinical expression. Re-analysis of WES data after 12-24&#x2009;months should be considered in patients without a definitive diagnosis or in those who develop additional clinical features.

Early recurrence of intussusception frequently occurs within 48&#xa0;h after reduction, yet current assessments lack objective tools for accurate risk prediction. This multicenter study sought to develop and validate a predictive model for early intussusception recurrence using abdominal ultrasound imaging. We retrospectively collected data from 1,314 primary pediatric intussusception cases across three hospitals (2016-2024). Cases from center 1 were split into training (60%) and internal validation (40%) sets, and those from centers 2 and 3 composed the external test sets. An automated segmentation model (DeepLabv3 with ResNet101) was developed for lesion delineation. Radiomics and deep learning features were extracted from the segmented regions. Three classifiers (K-nearest neighbors, random forest, and extreme gradient boosting) were evaluated on the radiomics, deep learning, and fused feature sets. We integrated the fused model with clinical variables to construct a nomogram. The Dice coefficients of the segmentation model were 0.935 (seg-training) and 0.862 (seg-test). The key clinical predictors were age, onset-to-presentation time, and vomiting. After seven radiomics features and nine deep learning features were selected, we integrated the fused model with clinical variables to construct a nomogram. It showed good discrimination (internal validation area under the receiver operating characteristic curve (AUC), 0.892; external test set AUCs, 0.884 and 0.851, respectively). The results of the calibration and decision curve analyses supported its potential as a risk stratification tool. Integrating ultrasound-derived deep learning, radiomics, and clinical data shows promise for predicting recurrence of primary intussusception within 48&#xa0;h. The model may aid early risk stratification, although prospective validation in diverse populations is needed.

Epstein-Barr virus (EBV) infection is a common pediatric infectious disease. Infectious mononucleosis (IM) and hemophagocytic lymphohistiocytosis (HLH), two major complications of EBV infection, share similar clinical manifestations in the early stage. While IM is typically self-limiting, HLH is life-threatening and requires immediate intervention. Early differentiation between these two conditions is crucial for clinical decision-making; however, reliable prediction models based on readily available laboratory parameters remain scarce. This study aimed to develop and validate a machine learning prediction model using routine blood parameters obtained within 24&#xa0;h of hospital admission in children with confirmed acute EBV infection to distinguish EBV-associated IM (EBV-IM) from EBV-associated HLH (EBV-HLH). This retrospective cohort study included 4,871 pediatric patients diagnosed with either EBV-IM or EBV-HLH from two campuses of Children's Hospital of Chongqing Medical University. Demographic information and initial complete blood count (CBC) parameters within 24&#xa0;h of admission were collected. The cohort was divided into a model development group (Yuzhong Campus, n&#x2009;=&#x2009;2,848; 70% for training, 30% for internal testing) and an external validation group (Liangjiang Campus, n&#x2009;=&#x2009;2,023). Thirteen machine learning algorithms were evaluated using random search with 5-fold cross-validation for hyperparameter tuning. Shapley Additive exPlanations (SHAP) analysis was performed to interpret model predictions. EBV-HLH accounted for 12.46% (607/4,871) of the total cohort, with significantly different prevalence between the development and validation cohorts (18.29% vs. 4.25%, p&#x2009;<&#x2009;0.001). Significant differences were observed between cohorts in age and all CBC parameters except gender (p&#x2009;<&#x2009;0.05). The Random Forest (RF) model demonstrated optimal performance in the internal validation set (AUC&#x2009;=&#x2009;0.993, 95% CI: 0.990-0.996). In the external validation cohort, the RF model maintained robust discriminative ability (AUC&#x2009;=&#x2009;0.971, 95% CI: 0.949-0.992). Calibration curves indicated excellent agreement between predicted probabilities and actual risks. SHAP analysis identified WBC, PLT, LAC, and Hb as the most critical predictors of EBV-HLH. DCA demonstrated substantial clinical net benefit. A free online decision-support tool (https://wangrj1988.shinyapps.io/EBV-HLH-IM/) was developed based on the RF model to facilitate real-time risk assessment. The RF-based model using routine CBC parameters enables admission-based risk assessment of pediatric EBV-HLH with excellent generalizability, offering a cost-effective tool for diverse healthcare settings. Clinical trial number: not applicable.

Liver fibrosis is a major complication in patients with transfusion-dependent beta-thalassemia, primarily driven by iron overload and suboptimal chelation therapy. This study aimed to assess the prevalence and severity of hepatic fibrosis in children with beta-thalassemia major using non-invasive modalities and to identify associated clinical and laboratory risk factors. This cross-sectional analytical study included 82 transfusion-dependent thalassemia patients. All participants underwent clinical evaluation, hematological and biochemical investigations, and liver fibrosis assessment using transient elastography (TE) (by FibroScan) and calculation of aspartate aminotransferase (AST)/platelet ratio index (APRI) and Fibrosis 4 score (FIB-4). Based on TE, 18 patients (22%) exhibited significant hepatic fibrosis (F2-F4). Both APRI and FIB-4 scores were significantly elevated in patients with significant fibrosis. Significant fibrosis was associated with older age (p&#x2009;=&#x2009;0.019), longer disease duration (p&#x2009;=&#x2009;0.015), heterogeneous liver echotexture on ultrasound (p&#x2009;<&#x2009;0.001), poor adherence to chelation therapy (p&#x2009;<&#x2009;0.001), and elevated transaminases and serum ferritin levels (p&#x2009;<&#x2009;0.05). &#xa0;Significant hepatic fibrosis was observed in approximately one-fifth of the studied cohort of Egyptian children with beta-thalassemia major. It is strongly associated with older age, longer disease duration, iron overload, and inadequate chelation. TE, APRI, and FIB-4 are effective for early detection of hepatic fibrosis in these patients. &#x2022; Hepatic fibrosis is a well-recognized complication of transfusion-dependent beta-thalassemia major, primarily resulting from chronic iron overload. &#x2022; Liver biopsy remains the gold standard for fibrosis assessment; however, it is invasive. Non-invasive tools such as transient elastography, APRI, and FIB-4 have been increasingly used in adults, but limited data are available in pediatric populations, particularly in low- and middle-income countries. &#x2022; This study shows that significant hepatic fibrosis affects approximately one in five Egyptian children with beta-thalassemia major. &#x2022; It supports the clinical utility of FibroScan, APRI, and FIB-4 for fibrosis assessment in pediatric patients and highlights poor chelation adherence, iron overload, and longer disease duration as key modifiable risk factors.

To develop a nomogram for predicting major intra-operative hemorrhage in patients with placenta accreta spectrum (PAS) based on ultrasound features, aiming to guide clinical decision-making in hemorrhage prevention and management. This retrospective cohort study enrolled patients diagnosed with PAS who underwent pre-operative ultrasound evaluation at Fujian Maternity and Child Health Hospital. Participants were randomly allocated to training and validation cohorts in a 7:3 ratio. The training cohort was stratified into the non-major hemorrhage group (n = 77) and major hemorrhage group (n = 61). univariate and multi-variate logistic regression analyses were performed to identify independent risk factors for major intra-operative hemorrhage and to develop a nomogram, and its predictive performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves and Decision Curve Analysis (DCA). A total of 196 patients were included. Multi-variable logistic regression analysis identified four independent predictors of major intra-operative hemorrhage: placental lacunae feeder vessels , sub-placental hypervascularity/bridging vessels, intra-cervical lakes, and incomplete cervical morphology. These predictors were incorporated into a nomogram. The model demonstrated discriminative capacity with areas under the ROC curves values of 0.877 (95% confidence interval (CI) 0.819-0.935) and 0.851 (95% CI 0.754-0.948) in training and validation cohorts, respectively. A total of 1000 bootstrap-resampling confirmed model stability. Calibration curves showed good consistency between predicted and observed probabilities, and the DCA demonstrated clinical utility. This study developed and validated a nomogram for predicting intra-operative major hemorrhage in patients with PAS, which has clinically applicable performance and robustness, providing actionable perioperative decision-making.

The COVID-19 pandemic was a dynamic and often confusing period for clinical and biomedical research. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread globally, knowledge accumulated rapidly through publications that were frequently based on preliminary or sometimes conflicting evidence, yet these papers played a critical role in shaping evolving medical, research and societal responses. Early in the pandemic, diabetes emerged as one of the strongest predictors of severe COVID-19 outcomes and mortality, placing it at the centre of early risk-stratification and therapeutic frameworks and prompting urgent efforts to understand the biological basis of these associations. As the pandemic progressed, reports of new-onset diabetes following COVID-19 infection raised the possibility of a bidirectional relationship between SARS-CoV-2 infection and diabetes. In this review, we provide a post-pandemic reappraisal of the clinical and experimental literature examining the intersection of COVID-19 and diabetes. We summarise proposed pathophysiological mechanisms, including the effects of SARS-CoV-2 infection in the pancreas and on peripheral insulin-sensitive tissues. We review key meta-analyses assessing the association between COVID-19 and incident type 1 and type 2 diabetes and highlight strengths and weaknesses of the epidemiologic studies underpinning these findings. We highlight the highest-quality evidence from prospective cohorts, as well as relevant clinical trials and registry-based studies that emerged from this collective experience. We discuss emerging relationships between long COVID and diabetes and the effect of vaccination on diabetes risk following SARS-CoV-2 infection. Finally, we identify critical knowledge gaps and outline priorities for ongoing and future studies needed to resolve remaining uncertainties.