Nevin Manimala

Eur J Pediatr. 2025 Nov 17;184(12):768. doi: 10.1007/s00431-025-06598-4.

ABSTRACT

Epidemiological data on venous thromboembolism (VTE) in children and adolescents is sparse and available primarily for the USA. In Europe, the burden and management of VTE have rarely been subjects of nationwide analyses.We conducted a nationwide, retrospective, patient-level analysis of the Swiss medical statistics an administrative data collection including 1961 hospitalizations (1653 incident events) with VTE aged 19 or younger between 2004 and 2023. We estimated the disease-specific incidence rate, in-hospital case fatality rates, length of stay (LOS), and related admission to the intensive care unit (ICU). Furthermore, we evaluated therapeutic procedures.The incidence rate of incident VTE-related hospitalizations was 4.9 (95%CI 4.7; 5.2) per 100,000 children and adolescents per year. The in-hospital case fatality rate was 4.0% (95%CI 3.2; 5.0); the median LOS was 8 (Q1-Q3 4-24) days. Systemic thrombolysis, catheter-directed treatment, and inferior vena cava filters were used in less than 15% of patients. Among patients receiving systemic thrombolysis, the in-hospital case fatality rate was 19.4% (95%CI 12.6; 28.5), whereas patients managed with catheter-directed treatment had a rate of 8.0% (95%CI 3.2; 18.8). 39.3% of patients were admitted to ICU. Age- and sex-specific differences in incidence rate, proportion of hospital admissions, and in-hospital case fatality rate were observed, particularly among infants aged < 1 year and adolescents aged 15-19 years.

CONCLUSION: VTE among children and adolescents is rare with age- and sex-specific differences in incidence. Patients who underwent advanced treatment strategies presented with a substantial risk of in-hospital death despite treatment, especially evident among patients aged 0-9 years.

WHAT IS KNOWN: • Venous thromboembolism and in extension pulmonary embolism and deep vein thrombosis are rare diseases among children and adolescents.

WHAT IS NEW: • We provided national estimates for measures of occurrence of venous thromboembolism from a European country. • We analyzed the management of these patients with a focus on advanced treatment strategies, providing estimates on the in-hospital fatality rate.

PMID:41249729 | DOI:10.1007/s00431-025-06598-4

Arch Sex Behav. 2025 Nov 17. doi: 10.1007/s10508-025-03253-9. Online ahead of print.

ABSTRACT

We examined the association between sexual orientation at age 15.5 years and depressive symptoms at age 17 years and whether this association was explained by a path involving earlier pubertal timing leading to worse inhibitory control at age 15.5 years using the Avon Longitudinal Study of Parents and Children. A total number of 5,125 adolescents were included (46.65% adolescent males and 87.38% White). Age at peak height velocity was derived from multiple height assessments annually from childhood to adolescence and used as an objective measure of pubertal timing. We found that adolescents who were unsure of their sexual orientation did not differ statistically significantly from their heterosexual counterparts in either pubertal timing or depressive symptoms. Sexual minority adolescents reported both earlier pubertal timing and more depressive symptoms than heterosexual adolescents. Sexual orientation disparities in depressive symptoms could potentially be explained by earlier pubertal timing reported by sexual minority adolescents than heterosexual adolescents, but not by the indirect path through earlier pubertal timing leading to worse inhibitory control. The results were consistent across both sexes, suggesting that pubertal timing makes a small contribution to sexual orientation disparities in depressive symptoms.

PMID:41249693 | DOI:10.1007/s10508-025-03253-9

Eur Arch Otorhinolaryngol. 2025 Nov 17. doi: 10.1007/s00405-025-09760-8. Online ahead of print.

ABSTRACT

PURPOSE: Artificial intelligence (AI) has emerged as a potential tool in postoperative care, particularly for complex procedures like Endoscopic Transnasal Skull Base Surgery (ETSBS), where patient comprehension of recovery instructions is critical. This study aimed to compare the readability, understandability, and actionability of postoperative instructions generated by three AI platforms (ChatGPT, DeepSeek, and Gemini).

METHODS: Each platform was prompted to create ETSBS postoperative instructions. Readability was assessed using Flesch Kincaid Grade Level (FKGL) and Reading Ease (FKRE). The Patient Education Materials Assessment Tool for printable materials (PEMAT-P) was used to evaluate understandability and actionability. Two outputs per platform were analyzed. Statistical comparisons were conducted using Kruskal-Wallis tests and Pearson correlation coefficients.

RESULTS: Gemini had the highest FKRE score (52.18), followed by DeepSeek (46.46) and ChatGPT (39.85), though differences were not significant (p = 0.458). FKGL was lowest in Gemini (9.07), compared to DeepSeek (9.82) and ChatGPT (10.87) (p = 0.469). Understandability scores were highest in ChatGPT and DeepSeek (76.45%), while Gemini scored lower (63.30%, p = 0.005). ChatGPT showed the highest actionability (58.5%), followed by DeepSeek (51.0%) and Gemini (45.15%), with no significant difference (p = 0.645). A strong inverse correlation was found between FKRE and FKGL (r = -0.998, p = 0.000). Correlations with understandability and actionability were moderate and non-significant (p > 0.1).

CONCLUSION: While AI platforms generated similarly readable content, significant differences emerged in usability. None met optimal standards for patient education, highlighting the need for clinician review before clinical application.

PMID:41249683 | DOI:10.1007/s00405-025-09760-8

Eur Spine J. 2025 Nov 18. doi: 10.1007/s00586-025-09565-7. Online ahead of print.

ABSTRACT

PURPOSE: The aim was to study the developmental characteristics of the cartilaginous union anatomical structure at the base of odontoid process in normal children aged 1 to 6 years, analyze the factors influencing its fusion, and provide basic data for understanding its evolutionary patterns and application in clinical disease diagnosis and treatment. Additionally, the study aimed to conduct morphological staining observations of the anatomical features of the base of the odontoid process in normal children.

METHODS: A total of 140 cases of normal cervical spine CT images from children aged 1 to 6 years were collected and grouped by age, with 20 cases in the 1-year-old group and 30 cases in each of the other four groups. The original data of the cervical spine continuous CT scan images were imported into Mimics 21.0 software in DICOM format for the measurement of anatomical indexes including Transverse Diameter (TD), Sagittal Diameter (SD), Area (A), Perimeter (P), and the positional indexes including Distance from Upper Cartilage Border to Odontoid Process Base (DSB), Distance from Lower Cartilage Border to Odontoid Process Base (DIB), Distance from Left Cartilage Border to Left Transverse Process (DLT), Distance from Right Cartilage Border to Right Transverse Process (DRT). Additionally, the axis vertebra of a 3-year-old child’s cervical spine was extracted, and thin sections were prepared by hard tissue embedding and section techniques. Toluidine blue staining was performed to observe the histopathological characteristics of the cartilaginous intervertebral disc and bone tissue in the base region of the odontoid process.

RESULTS: TD, SD, A, and P values decreased gradually with increasing age. TD, A, and P values showed statistical differences between group E and the other groups (P < 0.05); SD values showed statistical differences between group E and groups A, B, and C (P < 0.05). DSB, DIB, DLT, and DRT values all increased with age. DLT values in groups A and B showed statistical differences with group E (P < 0.05); DRT values in group A showed statistical differences with groups D and E (P < 0.05). There was a high correlation between TD and SD, A and P, DLT and DRT, and a low correlation between TD and DSB, P and DLT, DRT. After staining, it was observed that the chondrocytes in the central region of the base of the odontoid process were scattered and spindle-shaped, while in the peripheral areas, chondrocytes formed oval-shaped clusters, with the cell nuclei stained blue and the matrix showing a light blue color, providing clear contrast with the intervertebral disc and bone tissue.

CONCLUSION: The ossification center of the base of odontoid process in children is in a continuous growth and change process and exhibits evident regularity. The measurement results of this study can provide anatomical data for the growth and developmental characteristics of this region. The cartilage at the base of the odontoid process in children is hyaline cartilage, with the characteristic of being relatively brittle and prone to fracture.

PMID:41249664 | DOI:10.1007/s00586-025-09565-7

J Gen Intern Med. 2025 Nov 17. doi: 10.1007/s11606-025-10042-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To validate the RECOVER Post-Acute Sequelae of SARS-CoV-2 infection (PASC) score in a cohort of patients who develop long COVID (LC) or fully recover while iteratively improving the tool’s sensitivity and specificity.

METHODS: A cross-sectional study in 130 LC patients followed at LC clinics in Baltimore, MD, USA, who met the National Academies of Sciences, Engineering, and Medicine (NASEM) 2024 LC definition, and 60 SARS-CoV-2 exposed but fully recovered individuals. LC participants were required to have at least one neuropsychiatric symptom. Participants completed comprehensive surveys and questionnaires assessing symptoms based on published methods to determine PASC score. Using the NASEM 2024 LC definition as the “true” condition, we compared evaluation metrics for the RECOVER PASC score cutoff (PASC > 12) and the presence of individual/multiple symptoms. Evaluation metrics (e.g., sensitivity, specificity, F1) were calculated based on these classifications for the overall PASC score and symptom combinations.

RESULTS: The LC cohort (n = 130) had a mean age of 47.2 years and was predominantly female (72%), White (79%), and well-educated (77% > 16 years). Controls (n = 60) were similar demographically. LC diagnosis and PASC scores were significantly associated (χ² = 102.99, P < 0.001). The PASC score showed excellent specificity (100%) and positive predictive value (PPV; 100%) albeit limited sensitivity (80%), missing 20% of participants with LC. We found that loss of smell/taste, post-exertional malaise, or lack of sexual desire or capacity demonstrated 94% sensitivity, 92% specificity, and 96% PPV, 87% NPV, and an F1 score of 0.949.

CONCLUSION: Validation of the RECOVER PASC supports its utility and highlights the need for ongoing refinement of the LC definition. We call for national efforts to develop readily implementable clinical tools for LC diagnosis.

PMID:41249654 | DOI:10.1007/s11606-025-10042-6

J Gen Intern Med. 2025 Nov 17. doi: 10.1007/s11606-025-09950-4. Online ahead of print.

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively promote weight reduction and improve glycemic control, blood pressure, and lipid profiles in individuals with overweight or obesity. This systematic review and meta-analysis evaluates the durability of these therapeutic benefits following treatment discontinuation.

METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP from inception to June 2024, to identify randomized controlled trials that assessed the effects of GLP-1RAs with a follow-up period of at least six months after treatment discontinuation. The outcomes were changes in weight, body mass index (BMI), waist circumference (WC), glycemia, blood pressure, and lipid profiles.

RESULTS: We screened 10,670 studies and ultimately identified 5 eligible studies, encompassing 719 patients. Compared to the control group, GLP-1RAs were associated with significant reductions in weight (mean difference (MD) = -5.70 kg, 95% confidence interval (CI): -9.52 to -1.88), BMI (MD = -2.94 kg/m², 95% CI: -5.60 to -0.28), WC (MD = -3.66 cm, 95% CI: -4.89 to -2.43), glycated hemoglobin A1c (HbA1c) (standardized mean difference (SMD) = -0.73, 95% CI: -1.14 to -0.32), and systolic blood pressure (SBP) (MD = -3.62 mm Hg, 95% CI: -5.51 to -1.73) after cessation of therapy. After discontinuation, there was a pronounced rebound in weight (MD = 4.13 kg, 95% CI: 1.60 to 6.65), BMI (MD = 0.84 kg/m², 95% CI: 0.37 to 1.32), WC (MD = 3.64 cm, 95% CI: 2.27 to 5.01), and HbA1c (SMD = 0.69, 95% CI: 0.50 to 0.89). From study baseline to the end of follow-up, GLP-1RAs treatment resulted in statistically significant decreases in weight (MD = -2.32 kg, 95% CI: -4.21 to -0.43) and BMI (MD = -0.82 kg/m², 95% CI: -1.47 to -0.17).

CONCLUSIONS: This meta-analysis demonstrated that although statistically significant weight reduction persists after GLP-1RAs discontinuation, the clinical significance and durability of this effect are limited. To achieve sustained therapeutic benefits, continued treatment with these agents may be necessary.

PMID:41249646 | DOI:10.1007/s11606-025-09950-4

Health Econ Rev. 2025 Nov 17;15(1):97. doi: 10.1186/s13561-025-00690-z.

NO ABSTRACT

PMID:41249635 | DOI:10.1186/s13561-025-00690-z

Ann Biomed Eng. 2025 Nov 17. doi: 10.1007/s10439-025-03890-0. Online ahead of print.

ABSTRACT

PURPOSE: Digital twin (DT) cohorts are collections of models where each member represents an individual real-world asset. DT cohorts can be used for in-silico trials, outlier detection and forecasting, and are used across engineering, industry, and increasingly in personalised medicine. To increase the scalability of DT cohorts, researchers often train emulators to be used as cheap surrogates of computationally expensive mathematical models. Frequently, each cohort member is emulated individually, without reference to other members. We propose that instead, we can treat each DT as a thread in a larger network, and that these threads can be woven together into a digital tapestry using cohort learning methods.

METHODS: We propose two statistical approaches for transferring knowledge between threads. The first method, ‘latent-feature emulators’, utilises a latent representation of individual cohort members to generate a single emulator for the entire cohort. The second method, ‘discrepancy emulators’, learns the discrepancy between a new cohort member and existing members.

RESULTS: In two cardiac DT case studies, we show that these methods can reduce computational costs by more than 50% compared to the standard approach of training individual emulators, even in small cohorts.

CONCLUSIONS: We find that by transferring information between meshes, the cohort methods improve both the computational efficiency and the accuracy of emulators when compared to the standard approach of individually emulating each cohort member. As cohort size increases, the computational savings grow further. We focus on the use of Gaussian process emulators, but the transfer methods are applicable to other surrogate approaches such as neural networks.

PMID:41249625 | DOI:10.1007/s10439-025-03890-0

Cancer Gene Ther. 2025 Nov 17. doi: 10.1038/s41417-025-00988-4. Online ahead of print.

ABSTRACT

Thyroid cancer (TC) is an endocrine malignancy characterized by metabolic abnormalities, with its incidence continually on the rise. Understanding the pathogenesis of this cancer would help develop better diagnostic and therapeutic methods. We aimed to integrate single-cell transcriptomics, bulk transcriptomics, and GWAS data to identify causal associations with thyroid cancer at the gene level. We intended to utilize single-cell atlases to identify malignant cells and their characteristics, and employed SMR to search for genetic loci causally associated with thyroid cancer. We validated the expression differences of the genes at the single-cell level and bulk level, as well as through immunohistochemistry experimental results. We investigated the tumor immune microenvironment of patients, attempting to find immune subgroups with differential proportions. Based on these subgroups, we conducted multi-machine learning modeling to predict the likelihood of disease and developed a corresponding interactive web application. HMGA2, SDCCAG8, DLG5, MT1E, RABL2B, RERE, and NDUFA12 all demonstrated to varying degrees their roles in promoting or inhibiting the occurrence and development of thyroid cancer, with HMGA2 showing consistency across all analyses. We also identified some immune subtypes significantly associated with TC and chose markers of T_cell_C8_STMN1 to construct patient diagnostic models. Through various combinations of machine learning feature selection and model construction, we ultimately built 178 diagnostic models, with the combination of glmBoost+RF having the best diagnostic performance (Average AUPR: 0.9915). The predictive web pages ( https://zclab-cnp.shinyapps.io/TC-WEB/ ) can provide convenience and reference for clinical personnel.

PMID:41249621 | DOI:10.1038/s41417-025-00988-4

J Clin Immunol. 2025 Nov 18;45(1):162. doi: 10.1007/s10875-025-01959-y.

ABSTRACT

Flow cytometric immunophenotyping of lymphocytes and dendritic cells, and functional lymphocyte mitogen response tests are used in the diagnostics of inborn errors of immunity (IEI), especially in pediatrics. These routinely used tests lack sufficient age-matched reference values in children. We established reference values for lymphocyte and dendritic cell subsets for four age groups from 68 healthy children under 12 years of age. These values were then compared to prior publicly available articles and 46 clinical samples from children with confirmed IEI diagnosis. Mitogen response results were also compared between 27 children and 177 adults. In the literature review, we found considerable variability in lymphocyte subset definitions and statistical approaches. Most IEI patients had increased transitional and naïve B, and decreased memory B cells. CHH patients had increased γδ T and DNTs. Lymphocyte stimulation via FASCIA method provides weaker stimulation results in children than in adults, which seems to result from a larger proportional count of naïve lymphocytes in children. The established reference values can be used in diagnostics of pediatric immunological conditions in laboratories that use similar analytic methods. Lower lymphocyte mitogen response results in children need to be taken into consideration when interpreting the results of lymphocyte functional tests.

PMID:41249610 | DOI:10.1007/s10875-025-01959-y