Cancers

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, and the great majority of these deaths are caused by metastatic disease. Whether the immunohistochemical (IHC) phenotype of breast cancer is associated with the anatomical site of metastasis has been characterized mainly in high-income, registry-based populations, while data from ecologically stressed and medically under-served regions such as the Lower Aral Sea basin are lacking. Methods: We retrospectively reviewed 652 women diagnosed with breast cancer at the Khorezm Branch of the Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology (Uzbekistan) between 2020 and 2024, of whom 213 had metastatic disease (306 metastatic foci). Histological type was assessed on hematoxylin-eosin and van Gieson-stained sections; quantitative morphometry was performed in Fiji/ImageJ; and HER2, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 were assessed by IHC. The association between marker expression and metastatic site (liver, lung, lymph node) was tested in 187 foci with adequate tissue using the chi-square test, with significance at p < 0.05. Results: Invasive ductal carcinoma predominated. Metastatic site was significantly associated with the IHC phenotype. Liver metastases showed the highest frequency of HER2 3+ (45.7%), ER-negativity (65.2%), PR-negativity (69.6%) and high proliferation (Ki-67 [&ge;] 60%; 47.8%), whereas lymph-node metastases were more often hormone-receptor-positive (ER+ 58.7%; PR+ 52.4%) with lower HER2 3+ (22.2%); lung metastases were intermediate (all p < 0.05). The combination of HER2 3+ and Ki-67 [&ge;] 60% was associated with multi-organ spread. Morphometry corroborated these patterns: liver lesions had larger atypical cells (up to 132.8 m), a higher nuclear-to-cytoplasmic ratio (0.76 vs 0.51) and more extensive necrosis and microvascularity than lymph-node lesions. A pragmatic 5-criterion morphological score (histological type, Ki-67, HER2, ER/PR status, atypical-cell size) stratified metastatic risk into three tiers. Conclusions: In this regional cohort, the IHC phenotype of breast cancer tracked the anatomical site of metastasis, with an aggressive HER2-driven, hormone-receptor-negative profile concentrated in liver metastases and a hormone-receptor-positive profile in lymph-node metastases. These findings reproduce established organotropism patterns in a previously uncharacterized population and support phenotype-aware, site-specific surveillance together with a low-cost morphological risk score for resource-limited settings.

Objective To determine if it is possible to assess individual patient risk of the development of colorectal cancer (CRC) in people in high-risk groups due to their family history. Design/Method Retrospective observational study of prospectively collected data from consecutive patients referred for a colonoscopy. 2,478 consecutive patients were referred to a single colorectal surgical practice in Sydney, Australia between 1977 and 2018 for a colonoscopy because of a family history of CRC. Of these, 1,963 have been followed for more than 10 years and are the subject of this paper. Histopathological findings categorised as normal (N), non-advanced adenoma (NAA) or advanced neoplasia (AN) with AN proven to be the precursor to CRC. Intervention Colonoscopic screening on the basis of contemporary practice to 2006 and subsequently according to Australian National Health and Medical Research Council guidelines. Results Participants with normal or low-risk findings in the first decade remain at lower risk of CRC for 30 years from the commencement of screening. Conclusion It is possible to stratify individual patients in a high relative risk cohort into those with high or low personal risk of CRC based on colonoscopic findings in the first 10 years of surveillance. Those with no AN in the first ten years have a lower 30-year risk of developing AN than the general community. This offers the possibility of structuring surveillance programs around individual risk rather than group risk, lessening the need for multiple surveillance colonoscopies in the majority of such patients and improving the cost effectiveness of CRC screening at the population level.

Background Endometrial cancer exhibits marked molecular and immune heterogeneity that is only partially explained by established genomic biomarkers. We investigated whether T cell receptor (TCR) repertoire architecture captures complementary dimensions of antitumor immunity beyond conventional molecular classification. Methods Paired tumor and peripheral blood samples from eight patients with molecularly characterized endometrial cancer underwent TCR repertoire profiling. Diversity, clonality, and tumor blood overlap metrics were integrated with genomic variables, including tumor mutational burden (TMB), genomic instability metric (GIM), and POLE status. Principal component analysis and correlation analyses were used to identify major dimensions of repertoire organization. Composite Immune Focusing and Immune Sharing Scores were derived to summarize dominant repertoire patterns. Results The first two principal components explained 70.1% of total repertoire variance and revealed substantial heterogeneity independent of histological subtype. TMB was strongly associated with reduced repertoire diversity and increased clonal dominance, resulting in a robust association with the Immune Focusing Score ({rho} = 0.88, p = 0.004). POLE mutated tumors occupied the extreme end of this focusing continuum. In contrast, genomic instability was associated with increased tumor blood repertoire overlap and preserved diversity, reflected by a strong correlation between GIM and the Immune Sharing Score ({rho} = 0.76, p = 0.027). The two immune scores showed minimal correlation with each other ({rho} = -0.24, p = 0.57), indicating that they capture largely independent aspects of immune organization. Conclusion Integrative analysis of TCR repertoire architecture and tumor genomics identifies distinct immunogenomic states in endometrial cancer that are not fully captured by conventional molecular classification. If validated in larger cohorts, immune focusing and immune sharing metrics may provide complementary biomarkers for patient stratification and immunotherapy-oriented precision oncology

Objective: Tumor-infiltrating lymphocytes (TILs) in breast cancer are one of the most important indicators of the immune response within the tumor microenvironment. They play a particularly significant prognostic and predictive role in triple-negative and HER2-positive subtypes. However, substantial inter-observer variability has been reported in TIL scoring among pathologists, which limits its reliability in clinical practice. The aim of this study was to evaluate the agreement between artificial intelligence (AI) models and pathologists in TIL scoring and to compare this agreement using different statistical approaches, thereby assessing the potential of AI integration into pathology practice. Materials and Methods: Digitized histopathological images of breast cancer cases were included in the study. Tumor regions annotated by pathologists were evaluated for both stromal TIL percentage and the proportion of stromal tumor area within each ROI, with assessments performed independently by three pathologists and two AI models. Agreement was assessed among pathologists, between pathologists and AI, and between AI models. Statistical analyses included intraclass correlation coefficient (ICC), Cohen and Fleiss kappa, correlation tests, and Bland-Altman analysis. In addition, categorical agreement was examined using different cut-off values. Results: Inter-pathologist agreement was high, with an ICC of 0.81. In contrast, the global agreement between pathologists and AI models was lower (ICC 0.41). Pairwise comparisons of pathologist-AI agreement yielded substantially lower ICC values (0.12-0.21), although this improved to 0.53 when three pathologists were assessed jointly with a single AI model. The strongest categorical agreement was observed with dichotomized TIL scores ([&le;]10% vs. >10%), whereas multi-category classifications were associated with a marked reduction in kappa values. Spearman correlation coefficients between pathologists and AI models ranged from moderate to good ({rho} = 0.48-0.81). Agreement between the two AI models themselves was moderate, with an ICC of 0.64

Purpose: Pathogenic or likely pathogenic (P/LP) variants are increasingly identified in genes more commonly associated with adult-onset cancer predisposition, but their prevalence and relevance to children who present with cancer remain unclear. Methods: We retrospectively analyzed 1,280 consecutive pediatric patients with cancer who underwent clinical germline sequencing, using a virtual panel, from 2021 to 2024. Genes with P/LP variants were categorized as aoCPG or pediatric-onset cancer predisposition genes (poCPG) according to cancer risk before age 18 years and pediatric surveillance recommendations. Variant relevance was adjudicated using tumor diagnosis/histopathology, immunohistochemistry, and tumor molecular features and classified as primary, secondary, or indeterminate. Results: Among 1,280 patients, 197 (15.4%) harbored 211 P/LP variants across 54 genes. Sixty-six variants (31.3%) occurred in aoCPG, 87 (41.2%) in poCPG, and 58 (27.5%) were heterozygous variants in autosomal recessive genes. Among adult-onset variants, 7 (10.6%) were primary, 54 (81.8%) secondary, and 5 (7.6%) indeterminate. Among pediatric-onset variants, 77 (88.5%) were primary and 10 (11.5%) secondary. Six patients (3 adult-onset variants; 3 pediatric-onset variants) received targeted therapy informed by germline/somatic sequencing results. Conclusion: In pediatric oncology, most variants in aoCPG are secondary rather than tumor-related findings. Tumor-informed interpretation, beyond variant classification, may improve reporting, counseling, and therapeutic decision-making

OBJECTIVE: Bladder cancer (BC) is predominantly a disease of older, comorbid adults, and radical cystectomy (RC), which is the gold standard treatment, carries considerable morbidity. We sought to determine the impact of baseline dementia and frailty on the care trajectory beyond the immediate postoperative period. We hypothesized that frail patients and those with dementia undergoing RC for BC will have poorer care trajectories. METHODS AND MATERIALS: We identified Medicare beneficiaries [&ge;] 66 years old who underwent RC for BC in 2017 with 12 months of pre- and post-RC enrollment. Frailty and dementia were characterized using validated, claims-based measures. Associations between baseline frailty and dementia with postoperative care trajectory outcomes were determined using Fine-Gray competing risk models. RESULTS: We identified 3,600 beneficiaries of whom 11.6% were frail and 3.4% met criteria for dementia. Patients with dementia were more likely to be frail, comorbid, and not receive standard-of-care neoadjuvant chemotherapy. Frailty was independently associated with [&ge;] 2 transitions in care level after index discharge from RC and skilled nursing facility (SNF) admissions within 1 year of RC, exposure to intensive post-RC interventions, including dialysis and feeding tube placement, and poorer survival. Dementia remained associated with SNF admissions regardless of frailty level. CONCLUSIONS: Among a contemporary cohort of older adults undergoing RC for BC, preoperative dementia and frailty were independently associated with poorer care trajectory beyond the immediate postoperative period after RC. Our work highlights a role for preoperative geriatric assessment in identifying and optimizing patients at greatest risk.

Flow cytometry can establish T cell clonality by detecting a restricted expression pattern of the T cell receptor (TCR) {beta} constant region (TRBC), expressed in association with CD3. However, T cell neoplasms frequently lose surface expression of the CD3/TCR complex, posing a challenge to demonstrating T cell lineage and clonality. To address this challenge, here we present a 12-color flow cytometry panel, called cytoTCR, to characterize cytoplasmic expression of CD3/TCR complex components. We apply cytoTCR to 38 patient specimens with immunophenotypically abnormal T cell populations, demonstrating this approach can efficiently establish T cell lineage and clonality in challenging T cell neoplasms that have lost surface CD3 expression. While we show that natural killer (NK)-lineage neoplasms can express cytoplasmic CD3 at similar levels to T cells, we show that absent expression of cytoplasmic TCR components by mature lymphocytes can help confirm NK cell lineage. We demonstrate that cytoTCR can detect cytoplasmic TRBC-restriction in challenging cases of null-phenotype anaplastic large cell lymphoma, which lack surface expression of pan-T cell antigens. In cases of T-lymphoblastic leukemia, cytoTCR shows that cytoplasmic TRBC expression matches the expected developmental stage of the leukemia. Finally, we use cytoTCR to characterize atypical cCD3-CD7- T cells in a patient with a history of T-lymphoblastic leukemia as well as recent CAR-T therapy, showing that this atypical population is polytypic and represents CAR-T product rather than residual disease. Our study presents a broadly applicable flow cytometric approach to simultaneously assess T cell lineage and clonality in suspected T lineage populations with absent surface CD3 expression.

Introduction: Women aged 45-49 occupy a heterogeneous late-reproductive-life stage, but population research often treats them as a uniform group. This study examined correlates of Demographic and Health Survey (DHS)-defined infecund/menopausal status among Nigerian women aged 45-49. Methods: This cross-sectional secondary analysis used the 2024 Nigeria Demographic and Health Survey Women Recode dataset. Weighted descriptive statistics summarised reproductive exposure status among 3,237 women. Out of these, 3,110 women classified as either fecund or infecund/menopausal were subjected to Survey-adjusted Chi-square tests and Binary Logistic regression at p<0.05, where pregnant and postpartum amenorrhoeic women were excluded. Results: More than half of women were classified as infecund/menopausal (54.1%), while 41.5% were fecund; 3.2% were postpartum amenorrhoeic, and 1.3% were pregnant. Findings indicated that currently married/cohabiting women (AOR=4.87; 95% CI: 2.24-10.56) and formerly married women (AOR=8.30; 95% CI: 3.69-18.66) had higher odds of infecund/menopausal classification than women never in a union. Secondary education, higher education, middle-to-richest wealth quintiles, and five or more children ever born were associated with lower odds, while Northern minority ethnicity was associated with higher odds. Adding the current contraceptive method attenuated several education, wealth and parity associations; modern-method and traditional-method users had markedly lower odds than non-users. Conclusion: Late-reproductive-life exposure status among Nigerian women aged 45-49 is socially patterned, with union status showing the most stable association. DHS-defined infecund/menopausal status is a demographic exposure category rather than clinically confirmed menopause. It is therefore concluded that the cross-sectional associations should not be interpreted causally.

Background Cardiovascular-kidney-metabolic (CKM) syndrome integrates adiposity, metabolic risk, kidney dysfunction, and cardiovascular disease in a prevention-oriented framework. National estimates across 1999-2023 NHANES and future burden remain limited. Methods We analyzed US adults aged 20 years from 11 NHANES cycles, 1999-2000 through August 2021-August 2023. CKM stage 0-4 was assigned using harmonized examination, laboratory, medication, and questionnaire data. Prevalence was survey-weighted and standardized to the 2010 US Census adult population. Decade trends used survey-weighted logistic regression adjusted for age, sex, and race and ethnicity. Exploratory 2040 and 2050 projections combined NHANES prevalence models with US Census projections under population-aging-only, trend-continuation, and risk-improvement scenarios. Results Among 62,890 eligible adults, 62,888 had sufficient CKM data. In 2021-2023, age-standardized prevalence was 87.9% (95% CI, 86.5%-89.4%) for CKM stage 1 and 62.0% (95% CI, 60.1%-63.8%) for stages 2-4. Stage 2 accounted for 50.1% (95% CI, 48.2%-51.9%) and stages 3-4 for 11.9% (95% CI, 11.0%-12.7%). From 1999-2000 to 2021-2023, any CKM increased by 4.6 percentage points (95% CI, 2.4 to 6.9; P<0.001), whereas stages 2-4 changed by 2.1 percentage points (95% CI, 5.1 to 0.8; P=0.156). In adjusted decade models, any CKM increased (OR, 1.28; 95% CI, 1.19-1.38; P<0.001), while stages 2-4 showed no significant linear trend (OR, 0.95; 95% CI, 0.89-1.01; P=0.084). Excess adiposity and diabetes increased, dyslipidemia declined, and hypertension, chronic kidney disease, and clinical cardiovascular disease were stable. With population aging alone, projected stages 2-4 burden rose from 164.8 million adults in 2023 to 193.7 million in 2050; under risk improvement, it was 147.7 million. Conclusions CKM syndrome remained highly prevalent among US adults. Although later stages did not increase significantly, population aging may expand the absolute care burden unless broad risk improvement occurs.

Background: Circulating tumour DNA (ctDNA) liquid biopsy is now established across oncology for early cancer detection, minimal residual disease surveillance, and treatment monitoring. Detection thresholds for all current ctDNA assays are derived empirically through receiver operating characteristic analysis on training cohorts - a statistically valid but theoretically uninformed approach that does not specify the minimum detectable tumour fraction given assay technical characteristics, nor identify when increasing sequencing depth ceases to provide additional clinical information. Methods: We model ctDNA detection as a binary hypothesis testing problem with Binomial-distributed mutant allele counts against a sequencing error noise floor. The Neyman-Pearson lemma is applied to derive the uniformly most powerful detector and the minimum detectable tumour fraction in closed form. The sequencing assay is modelled as a binary symmetric channel and Shannon channel capacity is calculated. Empirical validation uses n=61 data points extracted from five published peer-reviewed analytical validation studies across five independent institutions in the US and EU (2018 - 2025): Yu et al. 2022, Stetson et al. 2018, Frydendahl et al. 2023, Northcott et al. 2024, and Cheng et al. 2025. Results: The minimum detectable tumour fraction is derived in closed form as f_min approximately equal to (z_alpha + z_beta) multiplied by the square root of (epsilon divided by N), where N is sequencing depth, epsilon is the platform error rate, and z_alpha, z_beta are standard normal quantiles at the specified false positive and false negative rates. Shannon channel capacity is C = 1 minus H(epsilon) bits per read, where H(epsilon) is binary entropy. Empirical validation yields 84.3% agreement for single-locus assays. Discordance for multi-locus tumour-informed assays (NeXT Personal, duplex WGS) is consistent with the single-locus model scope and identifies the principal theoretical extension required. Conclusions: This framework provides the first formal Neyman-Pearson optimality proof for ctDNA detection, a closed-form detection limit, and a platform-independent efficiency metric for NHS and regulatory standardisation. Keywords: circulating tumour DNA; liquid biopsy; Neyman-Pearson detection; Shannon channel capacity; sequencing depth; limit of detection; minimal residual disease; signal detection theory

This study aims to assess women's perceptions of artificial intelligence (AI) used in breast cancer screening in France by examining their knowledge of AI and the barriers to their participation in organized screening. The results of a survey conducted in June 2025 among a national sample of 2000 women (aged 40-75) reveal limited participation and persistent concerns among women. Nevertheless, despite a low awareness of specific AI applications, a large majority of the women surveyed are very favorable to the use of AI in breast cancer diagnosis, even considering it a lever to increase screening participation.

To explore the safety of combined use of lidocaine/prilocaine aerosol and condoms of different materials, this study conducted compatibility tests between them. By observing changes in various physical properties of condom materials after exposure to the aerosol, the compatibility of different polymer materials with the aerosol was analyzed.The results showed that within 15 minutes of exposure to the aerosol, there was no significant difference in all physical properties of natural rubber latex condoms compared with the blank control group (P>0.05), indicating they can be used together. In contrast, obvious changes in physical properties of polyurethane condoms occurred within 5 minutes of exposure (P<0.05), and their performances failed to meet industrial application standards, so combined use is strictly prohibited.This study clarifies the compatibility differences between two mainstream condom materials and lidocaine/prilocaine aerosol, providing experimental evidence and theoretical references for rational matching in clinical and daily use as well as avoiding potential safety risks.

Importance: Hereditary breast and ovarian cancer (HBOC) variant carriers benefit from risk-reducing interventions, but only if identified. The extent to which carriers are clinically recognized, and whether recognition is equitable across diverse populations, is poorly characterized in a single large U.S. cohort. Objective: To estimate P/LP HBOC carrier prevalence across genetic ancestry groups, quantify documented clinical genetic testing among carriers, and evaluate ancestry and socioeconomic disparities in testing. Design, Setting, and Participants: Cross-sectional analysis of the All of Us Research Program Controlled Tier (Curated Data Repository v8/C2024Q3R9), comprising participants with short-read whole genome sequencing and linked electronic health record (EHR) and survey data. Carriers were ascertained from research genomic data independent of clinical testing. Exposures: Genetically inferred ancestry (African [AFR], Admixed American [AMR], East Asian [EAS], European [EUR], Middle Eastern [MID], South Asian [SAS]); self-reported household income and educational attainment. Main Outcomes and Measures: (1) Carrier prevalence with Wilson 95% CIs; (2) documented clinical genetic testing (procedure codes) among carriers; (3) adjusted odds of documented testing among women, by ancestry, before and after socioeconomic adjustment, using multivariable logistic regression. Results: Among 414,830 participants, P/LP HBOC carrier prevalence was 1.42% (95% CI, 1.38-1.45) overall and similar across ancestry groups (AFR 1.24%, AMR 1.32%, EAS 1.19%, EUR 1.52%, MID 1.68%, SAS 1.33%; overlapping CIs). Among 250,071 women in the testing analysis, documented clinical genetic testing was rare: only 74 of 5,878 carriers overall (1.3%) and 59 of 3,572 European-ancestry carriers (1.7%) had a documented test, with counts below reportable thresholds in all other ancestry groups. African-ancestry women had lower adjusted odds of documented testing than European-ancestry women (Model 1 adjusted odds ratio [aOR], 0.32; 95% CI, 0.27-0.39), an association that attenuated but persisted after adjustment for income and education (Model 2 aOR, 0.48; 95% CI, 0.40-0.58; P < 0.001); Admixed American women also had reduced adjusted odds (aOR, 0.71; 95% CI, 0.61-0.84). Lower income and lower education were independently and dose-dependently associated with lower testing odds (income <$25,000 aOR, 0.46; high-school education aOR, 0.54). Conclusions and Relevance: High-risk HBOC variant carriers are present across all ancestry groups at similar frequencies, yet documented clinical genetic testing was disparate in the different ancestry groups. African-ancestry women experience a testing gap that is not fully explained by socioeconomic position, implicating structural barriers in access and referral. Population-level strategies that decouple carrier identification from current referral pathways may be required to close this gap.

Skin cancer requires early detection for improved survival rates. Most existing methods rely on deep learning based image classification, which is affected by visual similarity among lesions. Fewer studies use Gene Expression (GE) analysis, which captures molecular characteristics but lacks structural and visual details. To overcome limitations of individual modalities, this paper proposes a multimodal framework integrating dermoscopic images and GE profiles for skin cancer classification. EfficientNet and logistic regression are used for image based analysis and genomic skin lesion profiling, respectively, followed by fuzzy rule based decision systems to reduce uncertainty within individual modalities. Finally, fuzzy fusion combines predictions from both modalities using uncertainty based weighting of classifier outputs. The experimental findings show that both the image based and GE based classification models individually achieved accuracies of nearly 92%. However, the integration of prediction results through the proposed fuzzy fusion strategy further enhanced the classification performance, achieving an overall accuracy of 94.25%. The results obtained outperform contemporary methods, highlighting the effectiveness of combining complementary multimodal information compared with single modality approaches.

Background: Polygenic risk scores (PRS) for breast cancer are increasingly used for risk stratification to inform screening and prevention. However, for PRSs to be equitable and clinically useful, they need to perform well across diverse populations. While PRS performance is known to be ancestry-dependent, it is not well understood how environmental context, such as that of socioeconomic status (SES), affects PRS transferability. Here, we assess whether SES, measured via self-reported household income, modifies breast cancer PRS performance and, if so, whether socioeconomic context contributes predictive information beyond genetic risk alone. Methods: We used the US-based All of Us biobank to evaluate how SES impacts breast cancer PRS performance. First, we quantified changes in breast cancer PRS performance by modeling a commonly-cited polygenic score for breast cancer previously described by Mavaddat et al. with SES. We then reestimated the genetic effect sizes of the 3,820 variants from Mavaddat et al. in All of Us with and without income as a covariate. Because social determinants of health affect breast cancer detection and outcomes, we stratified analyses by socially defined populations on the basis of self-identified race and ethnicity. We further stratified individuals whose self-identified race is White (''White'') into three SES groups (high, middle, low) based on self-reported income and re-estimated genetic effect sizes to create SES-specific PRSs. We then applied these PRSs to White participants, the largest group in the study, and to Black or African American (''Black'') and Hispanic or Latino (''Hispanic'') participants, groups underrepresented in breast cancer research. Model discrimination between cases and controls was measured by area under the curve (AUC). Results: We analyzed 163,715 women from the All of Us biobank, which included 8,833 breast cancer cases (6,619 White, 1,178 Black, and 1,036 Hispanic), with relative income available for a subset of these cases (5,525 White, 848 Black, and 566 Hispanic). The ancestry-dependent performance of the breast cancer PRS described in Mavaddat et al. was replicated in All of Us. In Black individuals, this PRS (AUC and 95% CI: 0.576 [0.571, 0.582]) produced a similar increase in AUC as relative income (AUC: 0.573 [0.568, 0.577]) when added to an age-only model. Incorporating income with PRS, age, and genetic PCs 1-3 improved AUC by 0.007 in White Americans and 0.018 in Black Americans (both p < 10-11), while attenuating the contribution of PRS in the full model. PRS performance also varied among SES categories. Notably, PRSs with variant effect sizes that were recalibrated in low-SES White participants performed best in low-SES White participants (AUC: 0.605 [0.583, 0.628]) and Black Americans (AUC: 0.588 [0.586, 0.591]), both better than performance in high-SES White Americans (AUC: 0.579 [0.577, 0.580]) and middle-SES White Americans (AUC: 0.578 [0.569, 0.586]). Conclusion: Socioeconomic context, measured by income, significantly impacts the transferability of a PRS for breast cancer within and among groups defined by self-identified race and ethnicity. Accounting for SES improves PRS performance, most notably in Black Americans and low-SES White individuals.

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [&ge;]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

Background Pulse-field ablation (PFA) is regarded as a non-thermal ablation modality, but there is an increasing range of complications that could be due to thermal effects. Methods The hydrogel undergoes permanent colour change when a target temperature is reached allowing direct visualisation of the surface thermal footprint and depth. Comparative lesion sets using a variable loop circular catheter (VP), circular over-the-wire catheter (PS) and pentaspline catheter (FP) were performed. Protocols included single and stacked applications with variation of force, irrigation, and voltage. The hydrogel lesions were analysed en-face and by section using digital image analysis. Results All 3 PFA catheters tested had significant thermal footprints. The VP catheter had the largest mean surface footprint (156.1mm2) and thermal depth (1.31mm) compared to the other two catheters (PS 55.4mm2 & 1.1mm, FP 29.8mm2 & 1.05mm, p<0.005). Increasing irrigation showed a trend to reduce thermal footprint but did not achieve statistical significance. Increasing voltage increased thermal footprint, but increasing force had negligible effect. Stacked lesions incrementally increased thermal lesion footprint and depth in all catheters. Thermal depths of up to 2.4mm were observed. Areas of darkening and degradation of the hydrogel were observed with the VP and FP catheters, consisting of up to 47% of lesion area. No darkening was observed with the PS catheter. Conclusions There are significant thermal footprints in all the systems tested. Temperatures exceeding 60oC have been demonstrated, comparable to radiofrequency ablation, and this may explain the mechanism of injury in some reports of collateral damage during PFA.

Introduction: Stroke care is time-sensitive, yet patients in low-resource settings may reach tertiary services only after passing through multiple formal and informal care options. This study examined documented care-seeking pathways and time to presentation among stroke cases recorded at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria. Methods: A retrospective hospital record review was conducted using secondary data from the Stroke Registry, radiology department records, referral notes, and ambulance records at UNIMEDTH. The analysis included 371 stroke cases with documented time from symptom onset to UNIMEDTH presentation and reconstructable care pathways. First-contact routes were classified as hospital/biomedical, self/informal or traditional/faith-based care, and the number of documented steps defined pathway complexity before and including tertiary presentation. Frequencies and percentages described pathway patterns; median presentation times were compared using Mann-Whitney U and Kruskal-Wallis tests. Results: The median time to tertiary presentation was 24 hours (interquartile range [IQR] 9-72), and 317 patients (85.4%) presented after four hours. Only 30 patients (8.1%) presented directly to UNIMEDTH; 44 distinct care-pathway sequences were recorded. Hospital-facility first contact was documented for 81 patients (21.8%). It was associated with a median presentation time of 3 hours (IQR 2-6), compared with 48 hours (IQR 24-72) among patients whose initial contact was outside a hospital facility (U = 699.50, p < 0.001). The median time also differed across grouped first-contact categories and pathway complexity levels (both p < 0.001). Conclusion: Non-hospital or multi-step care-seeking pathways commonly preceded tertiary stroke presentations in this setting. The findings indicate that delayed tertiary arrival is partly embedded in the pathway followed after symptom onset. Interventions should combine public recognition of stroke warning signs with urgent referral linkages involving hospitals, patent medicine vendors, traditional and faith-based providers, and emergency transport systems.

Heart transplantation (HT) is the durable therapy for end-stage heart failure (HF). Despite advances in immunosuppression, cardiac allograft vasculopathy (CAV) remains a leading cause of late graft failure and mortality in the modern era. Prior studies have established donor age and immunological phenomena, such as acute cellular rejection (ACR), antibody-mediated rejection (AMR), and development of donor-specific antibodies (DSAs) as risk factors for CAV. However, it remains unclear whether acute rejection (AR) that occurs early post-HT, when individuals experience the highest degree of immunosuppression, reflects higher baseline immune activity and confers a higher risk of future CAV compared to later AR, when immunosuppression is minimized. We therefore examined whether AR occurring during pre-specified early and intermediate intervals compared to those who did not experience AR in the first post-HT year was associated with future CAV among recipients without CAV at 1 year.

Background: Olfactory dysfunction (OD) in children remains underdiagnosed and poorly characterised. Despite its known impacts on nutrition, quality of life, safety awareness, and psychosocial development, no standardised diagnostic or management pathway currently exists for paediatric OD. This study aimed to characterise global practice patterns and identify diagnostic and therapeutic challenges unique to paediatric care. Methodology/Principal: A 44-item cross-sectional online survey was distributed to a verified international network of paediatric otolaryngologists across 36 countries via a closed professional platform. The survey assessed five domains: diagnostic practices, management protocols, technology and innovation, education and training, and barriers to effective care. Regional grouping was used to facilitate meaningful statistical comparisons. Categorical variables were evaluated using chi-square tests, with odds ratios and 95% confidence intervals reported for significant findings. Results: Of 351 potential participants, 167 responded (47.6% response rate). Most respondents (83%) reported seeing children with OD, yet 95% saw fewer than ten such patients annually. Psychophysical testing was never performed by 54.8% of respondents, while 88.4% routinely ordered cross-sectional imaging. Testing frequency increased significantly with patient age (Cochran's Q p<0.001). The most common barriers to objective testing were insufficient training (44.3%), time constraints (29.9%), and funding limitations (28.1%). Multidisciplinary collaboration was negligible. Significant regional variation was observed across most practice domains. Conclusions: Paediatric OD care is characterised by functional underinvestigation, fragmented multidisciplinary collaboration, and systemic educational gaps. These findings support urgent development of standardised clinical guidelines, age-appropriate validated assessment tools, and formal interdisciplinary care pathways.