University Hospital and Clinics

Previous studies reported low [ 18 F] fluorodeoxyglucose ([ 18 F]FDG) PET uptake in estrogen receptor-positive breast tumours, potentially missing detection of distant metastases. This study assessed the proportion of estrogen receptor-positive hypometabolic tumours, clinical factors influencing [ 18 F]FDG uptake, and the prognostic impact. Baseline [ 18 F]FDG PET/computed tomography (CT) and [ 18 F]FDG PET/MRI exams of female patients diagnosed with estrogen receptor-positive locally advanced (cT3-4N0 or cT1-4N+), metastatic, or recurrent breast cancer between 2013-2022 were retrospectively collected. Different thresholds of maximum standardised uptake value (SUV max ) and tumour-to-background ratio (TBR; SUV max tumour/SUV max background) were applied to determine the proportion of hypometabolic [ 18 F]FDG PET exams. Logistic regression and survival analysis were performed. 119 patients underwent [ 18 F]FDG PET/CT and 31 [ 18 F]FDG PET/MRI. The proportion of hypometabolic tumours for SUV max thresholds 2.0, 2.5, 3.0, TBR of contralateral breast less than or equal to 1, and TBR of liver less than or equal to 1 was 8.4, 15.1, 21.8, 5.1, and 28.6%, respectively for [ 18 F]FDG PET/CT and 16.1, 19.4, 29.0, 6.9, and 35.5% for [ 18 F]FDG PET/MRI. Clinically tumour status (cT-status), histology type, and tumour grade were associated with the presence of a hypometabolic tumour. No PET-derived variables were associated with recurrence-free survival. A considerable proportion of estrogen receptor-positive breast tumours showed low SUV max , indicating potential suboptimal staging on [ 18 F]FDG PET. In patients with lower cT-status, lobular histology and low-grade estrogen receptor-positive tumour, [ 18 F]FDG PET may be less reliable as staging procedure. Further research is necessary to determine the optimal metabolic threshold for defining a hypometabolic tumour.

Background: Gene expression profiling in radiation-exposed blood is a valuable tool for biodosimetry and clinical research. Evaluating the blood's transcriptomic radiation response provides insight into absorbed dose, hematotoxicities, and immune reactions. However, detailed analysis using long-read RNA sequencing is currently limited in its diffusion, despite the potential additional insights that could be extracted, including novel isoform discovery and on-the-field gene expression studies, owing to its portability. Results: In this study, we utilized Oxford Nanopore Technologies' long-read RNA sequencing on human whole-blood samples from three healthy donors 6 hours after exposure to 4 Gy of X-rays. Compared to sham-irradiated (0 Gy) blood, gene-level differential expression analysis identified 117 upregulated and 66 downregulated genes, including canonical DNA damage repair and inflammatory responses. At the transcript level, 102 transcripts were significantly upregulated, and 17 were downregulated, revealing isoform-specific regulation that was not captured at the gene level. Notably, IL32, which showed no significant change at the gene level, exhibited strong upregulation of two transcript isoforms, while WDR74, ITM2B, AK2, and RPS19 displayed changes in transcript usage following irradiation. Leveraging the power of long-read RNA sequencing, we further identified 26 novel transcript isoforms, expanding the catalog of radiation-responsive transcripts. Conclusions: This is the first comprehensive study of long-read RNA-seq for transcriptomic profiling of human whole blood following ionizing radiation. These findings highlight the ability of long-read RNA sequencing to provide a more detailed view of radiation-induced transcriptomic alterations, underscoring its potential for biodosimetry and clinical applications.

Survival outcomes for infants born at 22–23 weeks’ gestation vary widely across neonatal units. This national, prospective cohort study evaluated 919 infants born at 22–23 weeks’ gestation in South Korea between 2013 and 2022, using Korean Neonatal Network data. Infants were categorized based on the level of neonatal care: 785 in lower-level centers (Group A) and 134 in higher-level centers (Group B). Survival was significantly higher in Group B (64.9%) compared to Group A (29.3%) (P < 0.0001). Early deaths occurred more frequently and earlier in Group A. Proactive care—including antenatal corticosteroids, antenatal antibiotics, and immediate surfactant administration—was more common in Group B. Antenatal corticosteroid was significantly associated with reduced risk of death (hazard ratio 0.58; 95% confidence interval, 0.49–0.69; P < 0.0001). The timing of rapid decline in survival was delayed in higher-level centers. In addition, classifying institutions into higher- and lower-level groups according to the survival of infants born at 22–23 weeks’ gestation (≥50% vs. <50%) provides a good reflection of the quality of neonatal care. These findings highlight the importance of proactive care and timely in utero transfer to higher-level units in improving survival for peri-viable infants.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-28428-1.

Abstract Background: Early-onset colorectal cancer (EOCRC) is rising for reasons not fully explained by genetics. Pediatric antibiotic prescriptions are medically ubiquitous, and nearly 1/3rd of all prescribed pedeatric antibiotics are retrospectively unnescessary. We hypothesized that brief pediatric penicillin courses ignite transient blooms of colibactin-producing (pks+) Enterobacteriaceae that seed colibactin-specific DNA damage and accelerate colon tumorigenesis. Methods: We developed an early-life exposure model (3–8 weeks) combining either corn starch, lard (HFD), or fiber-based diets with three 5-day oral penicillin pulses and colonization by a human pks+ Escherichia coli isolate (SP15), quantified bacterial dynamics (culture/qPCR), epithelial responses (RNA-seq, γH2AX), and neoplasia (AOM/DSS). We then analyzed infant metagenomes for time-locked pks+ spikes after intrapartum antibiotics (IAP) or childhood antibiotics. Results: Early-life penicillin triggered ≥100-fold, transient pks+ E. coli blooms, peaking during exposure and contracting afterward in mice across diets. In colonocytes of mice harboring pks+ E. coli, oral penicillin enriched DNA-damage response, EMT, and hyperproliferative programs and reduced homeostatic oxidative phosphorylation in a diet dependent manner. Preliminary mesenteric lymph node (MLN) flow cytometry data indicate antibiotics and pks+ (but not mutant) E. coli synergize as a critical driver of a signifcant pro-tumor TNF-rich pan-T-lymphocyte immune state across memory, effector and naive subsets that persists after AOM/DSS induction 9 weeks later. In the AOM/DSS cancer model, early-life penicillin promoted colorectal cancer in pks+-colonized HFD mice, which had increased tumor incidence, multiplicity, and burden (two-sided tests, P&amp;lt;0.05), directionally supported in the corn starch-diet mice as well (p∼0.1). Across infant cohorts, we observed congruent signals: time-locked pks+ spikes after antibiotics and higher early pks+ abundance with intrapartum penicillin exposure (p&amp;lt;0.05), consistent with transient antibiotic-induced blooms in humans. Conclusions/impact: Brief, clinically modeled penicillin courses in early life create a permissive luminal niche that blooms pks+ E. coli, perturbs epithelial programs, and accelerates colon tumorigenesis, with diet dependent effects. These data nominate precision antibiotic stewardship and colibactin-targeted interception as actionable strategies to reduce EOCRC risk, and motivate human studies pairing antibiotic timing with pks+ burden, dA-CLB, and SBS88/ID18 readouts along with first-in-human colibactin inhibitor trials. Citation Format: Max R. Van Belkum, Tamara Machado, Julia Lane, Doug P. Mortlock, Catie Shelton, Nic G. Shealy, Camila de Brito, Mariana X. Byndloss. Early-life penicillin blooms colibactin-positive Escherichia coli and drives DNA damage and tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr PR010.

Chest trauma is a common consequence of traumatic events. It may be blunt or penetrating. A low number of patients with blunt chest trauma require surgical intervention; in contrast, penetrating ones frequently require surgery and are associated with higher mortality. Chest trauma due to its anatomical location and to its potential effects on different systems must be multidisciplinary, and emergency and trauma systems should be organized and prepared to face all aspects. The present paper describes the recommendations provided by World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST), about comprehensive management of thoracic trauma.

Abstract Background Care pathways are central to organizing care. During the COVID-19 pandemic, care pathways for chronic conditions were disrupted or amended ad hoc to meet pandemic care demands. This left many patients unattended and at increased risk of complications. Protecting access to regular care is vital, with hybrid transformation of care pathways through digital integration being a possible solution. Understanding the composition of care pathways and cross-country variation is key to identifying components suitable for hybrid delivery. Methods We conducted 38 in-depth interviews with patients with type II diabetes mellitus and/or chronic heart failure, 23 with, healthcare workers (HCW) and 22 with informal care givers in Slovenia, the Netherlands and Malta, exploring patient journeys, care modifications during COVID-19, and digital care experiences. Thematic analysis informed care pathways and identified generic and country-specific sub-themes. In co-creation with HCW, informal care givers, and patients, we explored which care steps could be delivered in a hybrid way. Results Care pathways were developed for high- and low-risk conditions, with variations visualised both between and within countries. Eight generic themes emerged across all countries: care coordination, healthcare structures, patient characteristics, disease management abilities, care experiences and needs during/after COVID-19, digital/hybrid care, patient experiences, and support needs. These were divided into 40 sub-themes. The co-creation session identified opportunities to streamline care pathways by combining appointments, improving task delegation and communication, digitizing steps, as well as pre-requisites for successful patient-level implementation. Conclusions COVID-19 exposed weaknesses in regular care delivery. Hybrid transformation of care pathways, guided by multi-stakeholder input, offers a promising approach for future crises.

253 Background: Melanoma is a rare cancer accounting for approximately 1% of all skin cancers with a higher incidence in older adults with a median age of diagnosis of 66 years. We studied national mortality trends and demographic disparities in older adults with melanoma. Methods: A retrospective analysis of mortality trends among melanoma patients aged 65 years and above, diagnosed between 2000 and 2023, was conducted using the Surveillance, Epidemiology, and End Results Program (SEER) database. Variables including age, gender, race, and age-adjusted mortality rates (AAMR) were extracted and analyzed. Annual percent changes (APCs) in AAMRs with 95% confidence intervals were calculated using Joinpoint regression analysis across demographic subgroups (sex and race/ethnicity). Results: Between 2000 and 2023, 229,445 documented deaths in the US were attributed to melanoma. The overall AAMR demonstrated: initial increase from 11.6 per 100,000 in 2000 to 13.8 in 2013 (APC: 1.5%; 95% CI: 1.2% to 1.7%), followed by significant decline to 11.3 in 2017 (APC: -5.2%; 95% CI: -6.7% to -3.6%), with continued but slower decrease to 10.8 in 2023 (APC: -0.8%; 95% CI: -1.4% to -0.3%). Significant gender disparities persisted throughout the study period, with males maintaining consistently higher AAMRs than females (19.6 vs. 7.3 per 100,000). Male mortality increased from 18.0 in 2000 to peak at 22.3 in 2013, then declined substantially to 16.9 in 2023. Female mortality showed modest increase from 7.5 in 2000 to 7.7 in 2014, followed by decline to 6.2 in 2023. Pronounced racial and ethnic disparities were observed. Non-Hispanic White patients had the highest AAMR (14.6 per 100,000), followed by Hispanic or Latino patients (3.7), non-Hispanic Black or African American patients (2.1), with non-Hispanic Asian or Pacific Islander patients having the lowest rates (1.7). Conclusions: Despite overall improvements in melanoma mortality among older adults over the past two decades, significant disparities persist. Mortality remains markedly higher in men compared to women, and among non-Hispanic White patients relative to other racial and ethnic groups. The sharp decline in mortality after 2013 likely reflects the impact of advances in melanoma treatment, including immunotherapy and targeted therapies. Further studies are needed to better understand the drivers of these disparities and guide efforts to improve outcomes across all populations.